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Real-world data favor invasive strategy for NSTEMI with CKD
Most patients with advanced chronic kidney disease (CKD) and non–ST-elevation myocardial infarction (NSTEMI) fare better with coronary angiography with and without revascularization than with medical therapy, a large nationwide study suggests.
“Invasive management was associated with lower mortality, major adverse cardiovascular events (MACE), and need for revascularization, with a minimal increased risk of in-hospital, postprocedural acute kidney injury (AKI) requiring dialysis and major bleeding,” said lead researcher Ankur Kalra, MD, Cleveland Clinic.
Also, similar post-discharge safety outcomes were seen at 6 months, he said in an online presentation of “key abstracts” released in advance of next month’s Transcatheter Cardiovascular Therapeutics (TCT) 2021 hybrid meeting.
Advanced CKD is an independent predictor of mortality and morbidity in patients with NSTEMI. In CKD, however, current guidelines lack evidence on the efficacy and safety of invasive versus medical management, he noted.
A rare randomized clinical trial in this high-risk population, ISCHEMIA-CKD, recently found no benefit and an increase in stroke with initial invasive management compared with optimal medical therapy.
Session co-moderator Ziad A. Ali, MD, DPhil, St. Francis Hospital & Heart Center, New York, said the current study is “incredibly clinically impactful and answers a question that’s very difficult to answer because these patients aren’t randomized in randomized controlled trials, and there’s a general avoidance, which we’ve now coined ‘renalism,’ like racism, where people don’t really want to touch these patients.”
He questioned, however, how the authors reconcile the results of ISCHEMIA-CKD, a “small but meaningful randomized controlled trial,” with their findings from a large dataset. “Perhaps this is all selection bias, even though the numbers are very large.”
Dr. Kalra replied that ISCHEMIA-CKD examined stable ischemic heart disease, whereas they looked at NSTEMI. “Even though it may fall under the same rubric, I truly believe it is a different set of patients – they are at a heightened risk for future cardiovascular events and have had an acute coronary event.”
For the study, ICD-10 coding data from 2016-2018 in the Nationwide Readmission Database was used to identify NSTEMI patients with CKD stages 3, 4, 5, and end-stage renal disease (ESRD). A total of 141,052 patients were available for in-hospital outcomes and 133,642 patients for post-discharge outcomes.
In-hospital and 6-month mortality – the study’s primary outcome – favored invasive management across all CKD stages and ESRD but did not achieve statistical significance for CKD stage 5. The number needed to treat (NNT) for CKD stages 3, 4, 5, and ESRD were 26, 56, 48, and 18, respectively.
Six-month MACE, including mortality, MI, stroke, and heart failure readmission, was significantly better in all groups with invasive management.
Kaplan-Meier curves for mortality showed similar benefits with an invasive strategy across CKD stages, again barring stage 5 disease.
With regard to in-hospital safety, stroke rates were not significantly different between the two treatment strategies across all groups.
Rates of AKI requiring dialysis, however, were lower with medical versus invasive management for CKD stage 3 (0.43% vs. 0.6%; hazard ratio, 1.39; P = .016), stage 4 (1.2% vs. 2.0%; HR 1.87; P < .001), and stage 5 (3.7% vs. 4.3%; HR 1.17; P = .527). The number needed to harm (NNH) was 588 for CKD 3 and 125 for CKD 4.
Major bleeding, defined as requiring transfusion, was lower with medical management for all CKD stages but not for ESRD. The rates are as follows:
- CKD stage 3: 2.5% vs. 2.8% (HR, 1.11; P = .078; NNH = 333)
- CKD stage 4: 2.9% vs. 4.0% (HR, 1.42; P < .001; NNH = 91)
- CKD stage 5: 2.2% vs. 4.7% (HR, 2.17; P = .008; NNH = 40)
- ESRD: 3.4% vs. 3.3% (HR, 0.97; P = .709)
“The risk of AKI requiring dialysis and bleeding, as has been shown previously in other studies, was high, but the number needed to harm was also high,” observed Dr. Kalra.
A separate analysis showed no difference in rates of AKI requiring dialysis among patients with CKD stages 3 and 4 who underwent angiography without revascularization and their peers who were medically managed.
Rates of the composite safety outcome of vascular complications, major bleeding, AKI, or stroke readmission at 6 months were not significantly different for invasive versus medical management for CKD stage 3 (both 3.3%), stage 4 (4.5% and 4.2%), stage 5 (3.9% vs. 4.3%), and ESRD (2.3% vs. 2.1%).
Besides the inherent limitations of observational studies and potential for selection bias, Dr. Kalra pointed out that the analysis relied on coding data for exact glomerular filtration rates and lacked information on contrast use, crystalloids before the procedure, and nephrotoxic medication use before or during admission. Out-of-hospital mortality was also not available in the database.
Co-moderator Allen Jeremias, MD, also with St. Francis Hospital & Heart Center, said one of the study’s strengths was that it included all comers, unlike randomized trials that typically exclude the highest risk patients.
“So, when we do these trials it’s very difficult to find the right balance, whereas this is a real-world analysis including everybody, and I think the benefits are clearly demonstrated,” he said. “So I think I’m bullish on doing complex [percutaneous coronary intervention] PCI in this patient population.”
Dr. Kalra reports having no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Most patients with advanced chronic kidney disease (CKD) and non–ST-elevation myocardial infarction (NSTEMI) fare better with coronary angiography with and without revascularization than with medical therapy, a large nationwide study suggests.
“Invasive management was associated with lower mortality, major adverse cardiovascular events (MACE), and need for revascularization, with a minimal increased risk of in-hospital, postprocedural acute kidney injury (AKI) requiring dialysis and major bleeding,” said lead researcher Ankur Kalra, MD, Cleveland Clinic.
Also, similar post-discharge safety outcomes were seen at 6 months, he said in an online presentation of “key abstracts” released in advance of next month’s Transcatheter Cardiovascular Therapeutics (TCT) 2021 hybrid meeting.
Advanced CKD is an independent predictor of mortality and morbidity in patients with NSTEMI. In CKD, however, current guidelines lack evidence on the efficacy and safety of invasive versus medical management, he noted.
A rare randomized clinical trial in this high-risk population, ISCHEMIA-CKD, recently found no benefit and an increase in stroke with initial invasive management compared with optimal medical therapy.
Session co-moderator Ziad A. Ali, MD, DPhil, St. Francis Hospital & Heart Center, New York, said the current study is “incredibly clinically impactful and answers a question that’s very difficult to answer because these patients aren’t randomized in randomized controlled trials, and there’s a general avoidance, which we’ve now coined ‘renalism,’ like racism, where people don’t really want to touch these patients.”
He questioned, however, how the authors reconcile the results of ISCHEMIA-CKD, a “small but meaningful randomized controlled trial,” with their findings from a large dataset. “Perhaps this is all selection bias, even though the numbers are very large.”
Dr. Kalra replied that ISCHEMIA-CKD examined stable ischemic heart disease, whereas they looked at NSTEMI. “Even though it may fall under the same rubric, I truly believe it is a different set of patients – they are at a heightened risk for future cardiovascular events and have had an acute coronary event.”
For the study, ICD-10 coding data from 2016-2018 in the Nationwide Readmission Database was used to identify NSTEMI patients with CKD stages 3, 4, 5, and end-stage renal disease (ESRD). A total of 141,052 patients were available for in-hospital outcomes and 133,642 patients for post-discharge outcomes.
In-hospital and 6-month mortality – the study’s primary outcome – favored invasive management across all CKD stages and ESRD but did not achieve statistical significance for CKD stage 5. The number needed to treat (NNT) for CKD stages 3, 4, 5, and ESRD were 26, 56, 48, and 18, respectively.
Six-month MACE, including mortality, MI, stroke, and heart failure readmission, was significantly better in all groups with invasive management.
Kaplan-Meier curves for mortality showed similar benefits with an invasive strategy across CKD stages, again barring stage 5 disease.
With regard to in-hospital safety, stroke rates were not significantly different between the two treatment strategies across all groups.
Rates of AKI requiring dialysis, however, were lower with medical versus invasive management for CKD stage 3 (0.43% vs. 0.6%; hazard ratio, 1.39; P = .016), stage 4 (1.2% vs. 2.0%; HR 1.87; P < .001), and stage 5 (3.7% vs. 4.3%; HR 1.17; P = .527). The number needed to harm (NNH) was 588 for CKD 3 and 125 for CKD 4.
Major bleeding, defined as requiring transfusion, was lower with medical management for all CKD stages but not for ESRD. The rates are as follows:
- CKD stage 3: 2.5% vs. 2.8% (HR, 1.11; P = .078; NNH = 333)
- CKD stage 4: 2.9% vs. 4.0% (HR, 1.42; P < .001; NNH = 91)
- CKD stage 5: 2.2% vs. 4.7% (HR, 2.17; P = .008; NNH = 40)
- ESRD: 3.4% vs. 3.3% (HR, 0.97; P = .709)
“The risk of AKI requiring dialysis and bleeding, as has been shown previously in other studies, was high, but the number needed to harm was also high,” observed Dr. Kalra.
A separate analysis showed no difference in rates of AKI requiring dialysis among patients with CKD stages 3 and 4 who underwent angiography without revascularization and their peers who were medically managed.
Rates of the composite safety outcome of vascular complications, major bleeding, AKI, or stroke readmission at 6 months were not significantly different for invasive versus medical management for CKD stage 3 (both 3.3%), stage 4 (4.5% and 4.2%), stage 5 (3.9% vs. 4.3%), and ESRD (2.3% vs. 2.1%).
Besides the inherent limitations of observational studies and potential for selection bias, Dr. Kalra pointed out that the analysis relied on coding data for exact glomerular filtration rates and lacked information on contrast use, crystalloids before the procedure, and nephrotoxic medication use before or during admission. Out-of-hospital mortality was also not available in the database.
Co-moderator Allen Jeremias, MD, also with St. Francis Hospital & Heart Center, said one of the study’s strengths was that it included all comers, unlike randomized trials that typically exclude the highest risk patients.
“So, when we do these trials it’s very difficult to find the right balance, whereas this is a real-world analysis including everybody, and I think the benefits are clearly demonstrated,” he said. “So I think I’m bullish on doing complex [percutaneous coronary intervention] PCI in this patient population.”
Dr. Kalra reports having no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Most patients with advanced chronic kidney disease (CKD) and non–ST-elevation myocardial infarction (NSTEMI) fare better with coronary angiography with and without revascularization than with medical therapy, a large nationwide study suggests.
“Invasive management was associated with lower mortality, major adverse cardiovascular events (MACE), and need for revascularization, with a minimal increased risk of in-hospital, postprocedural acute kidney injury (AKI) requiring dialysis and major bleeding,” said lead researcher Ankur Kalra, MD, Cleveland Clinic.
Also, similar post-discharge safety outcomes were seen at 6 months, he said in an online presentation of “key abstracts” released in advance of next month’s Transcatheter Cardiovascular Therapeutics (TCT) 2021 hybrid meeting.
Advanced CKD is an independent predictor of mortality and morbidity in patients with NSTEMI. In CKD, however, current guidelines lack evidence on the efficacy and safety of invasive versus medical management, he noted.
A rare randomized clinical trial in this high-risk population, ISCHEMIA-CKD, recently found no benefit and an increase in stroke with initial invasive management compared with optimal medical therapy.
Session co-moderator Ziad A. Ali, MD, DPhil, St. Francis Hospital & Heart Center, New York, said the current study is “incredibly clinically impactful and answers a question that’s very difficult to answer because these patients aren’t randomized in randomized controlled trials, and there’s a general avoidance, which we’ve now coined ‘renalism,’ like racism, where people don’t really want to touch these patients.”
He questioned, however, how the authors reconcile the results of ISCHEMIA-CKD, a “small but meaningful randomized controlled trial,” with their findings from a large dataset. “Perhaps this is all selection bias, even though the numbers are very large.”
Dr. Kalra replied that ISCHEMIA-CKD examined stable ischemic heart disease, whereas they looked at NSTEMI. “Even though it may fall under the same rubric, I truly believe it is a different set of patients – they are at a heightened risk for future cardiovascular events and have had an acute coronary event.”
For the study, ICD-10 coding data from 2016-2018 in the Nationwide Readmission Database was used to identify NSTEMI patients with CKD stages 3, 4, 5, and end-stage renal disease (ESRD). A total of 141,052 patients were available for in-hospital outcomes and 133,642 patients for post-discharge outcomes.
In-hospital and 6-month mortality – the study’s primary outcome – favored invasive management across all CKD stages and ESRD but did not achieve statistical significance for CKD stage 5. The number needed to treat (NNT) for CKD stages 3, 4, 5, and ESRD were 26, 56, 48, and 18, respectively.
Six-month MACE, including mortality, MI, stroke, and heart failure readmission, was significantly better in all groups with invasive management.
Kaplan-Meier curves for mortality showed similar benefits with an invasive strategy across CKD stages, again barring stage 5 disease.
With regard to in-hospital safety, stroke rates were not significantly different between the two treatment strategies across all groups.
Rates of AKI requiring dialysis, however, were lower with medical versus invasive management for CKD stage 3 (0.43% vs. 0.6%; hazard ratio, 1.39; P = .016), stage 4 (1.2% vs. 2.0%; HR 1.87; P < .001), and stage 5 (3.7% vs. 4.3%; HR 1.17; P = .527). The number needed to harm (NNH) was 588 for CKD 3 and 125 for CKD 4.
Major bleeding, defined as requiring transfusion, was lower with medical management for all CKD stages but not for ESRD. The rates are as follows:
- CKD stage 3: 2.5% vs. 2.8% (HR, 1.11; P = .078; NNH = 333)
- CKD stage 4: 2.9% vs. 4.0% (HR, 1.42; P < .001; NNH = 91)
- CKD stage 5: 2.2% vs. 4.7% (HR, 2.17; P = .008; NNH = 40)
- ESRD: 3.4% vs. 3.3% (HR, 0.97; P = .709)
“The risk of AKI requiring dialysis and bleeding, as has been shown previously in other studies, was high, but the number needed to harm was also high,” observed Dr. Kalra.
A separate analysis showed no difference in rates of AKI requiring dialysis among patients with CKD stages 3 and 4 who underwent angiography without revascularization and their peers who were medically managed.
Rates of the composite safety outcome of vascular complications, major bleeding, AKI, or stroke readmission at 6 months were not significantly different for invasive versus medical management for CKD stage 3 (both 3.3%), stage 4 (4.5% and 4.2%), stage 5 (3.9% vs. 4.3%), and ESRD (2.3% vs. 2.1%).
Besides the inherent limitations of observational studies and potential for selection bias, Dr. Kalra pointed out that the analysis relied on coding data for exact glomerular filtration rates and lacked information on contrast use, crystalloids before the procedure, and nephrotoxic medication use before or during admission. Out-of-hospital mortality was also not available in the database.
Co-moderator Allen Jeremias, MD, also with St. Francis Hospital & Heart Center, said one of the study’s strengths was that it included all comers, unlike randomized trials that typically exclude the highest risk patients.
“So, when we do these trials it’s very difficult to find the right balance, whereas this is a real-world analysis including everybody, and I think the benefits are clearly demonstrated,” he said. “So I think I’m bullish on doing complex [percutaneous coronary intervention] PCI in this patient population.”
Dr. Kalra reports having no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Fluoroquinolones linked to sudden death risk for those on hemodialysis
, a large observational study suggests.
However, in many cases, the absolute risk is relatively small, and the antimicrobial benefits of a fluoroquinolone may outweigh the potential cardiac risks, the researchers say.
“Pathogen-directed treatment of respiratory infections is of the utmost importance. Respiratory fluoroquinolones should be prescribed whenever an amoxicillin-based antibiotic offers suboptimal antimicrobial coverage and clinicians should consider electrocardiographic monitoring,” first author Magdalene M. Assimon, PharmD, PhD, University of North Carolina, Chapel Hill, told this news organization.
The study was published online Oct. 20 in JAMA Cardiology (doi: 10.1001/jamacardio.2021.4234).
Nearly twofold increased risk
The QT interval-prolonging potential of fluoroquinolone antibiotics are well known. However, evidence linking respiratory fluoroquinolones to adverse cardiac outcomes in the hemodialysis population is limited.
These new observational findings are based on a total of 626,322 antibiotic treatment episodes among 264,968 adults (mean age, 61 years; 51% men) receiving in-center hemodialysis – with respiratory fluoroquinolone making up 40.2% of treatment episodes and amoxicillin-based antibiotic treatment episodes making up 59.8%.
The rate of SCD within 5 days of outpatient initiation of a study antibiotic was 105.7 per 100,000 people prescribed a respiratory fluoroquinolone (levofloxacin or moxifloxacin) versus with 40.0 per 100,000 prescribed amoxicillin or amoxicillin with clavulanic acid (weighted hazard ratio: 1.95; 95% confidence interval, 1.57-2.41).
The authors estimate that one additional SCD would occur during a 5-day follow-up period for every 2,273 respiratory fluoroquinolone treatment episodes. Consistent associations were seen when follow-up was extended to 7, 10, and 14 days.
“Our data suggest that curtailing respiratory fluoroquinolone prescribing may be one actionable strategy to mitigate SCD risk in the hemodialysis population. However, the associated absolute risk reduction would be relatively small,” wrote the authors.
They noted that the rate of SCD in the hemodialysis population exceeds that of the general population by more than 20-fold. Most patients undergoing hemodialysis have a least one risk factor for drug-induced QT interval prolongation.
In the current study, nearly 20% of hemodialysis patients prescribed a respiratory fluoroquinolone were taking other medications with known risk for torsades de pointes.
“Our results emphasize the importance of performing a thorough medication review and considering pharmacodynamic drug interactions before prescribing new drug therapies for any condition,” Dr. Assimon and colleagues advised.
They suggest that clinicians consider electrocardiographic monitoring before and during fluoroquinolone therapy in hemodialysis patients, especially in high-risk individuals.
Valuable study
Reached for comment, Ankur Shah, MD, of the division of kidney diseases and hypertension, Brown University, Providence, R.I., called the analysis “valuable” and said the results are “consistent with the known association of cardiac arrhythmias with respiratory fluoroquinolone use in the general population, postulated to be due to increased risk of torsades de pointes from QTc prolongation. This abnormal heart rhythm can lead to sudden cardiac death.
“Notably, the population receiving respiratory fluoroquinolones had a higher incidence of cardiac disease at baseline, but the risk persisted after adjustment for this increased burden of comorbidity,” Dr. Shah said in an interview. He was not involved in the current research.
Dr. Shah cautioned that observational data such as these should be considered more “hypothesis-generating than practice-changing, as there may be unrecognized confounders or differences in the population that received the respiratory fluoroquinolones.
“A prospective randomized trial would provide a definitive answer, but in the interim, caution should be taken in using respiratory fluoroquinolones when local bacterial resistance patterns or patient-specific data offer another option,” Dr. Shah concluded.
Dr. Assimon reported receiving grants from the Renal Research Institute (a subsidiary of Fresenius Medical Care), honoraria from the International Society of Nephrology for serving as a statistical reviewer for Kidney International Reports, and honoraria from the American Society of Nephrology for serving as an editorial fellow for the Journal of the American Society of Nephrology. Dr. Shah has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, a large observational study suggests.
However, in many cases, the absolute risk is relatively small, and the antimicrobial benefits of a fluoroquinolone may outweigh the potential cardiac risks, the researchers say.
“Pathogen-directed treatment of respiratory infections is of the utmost importance. Respiratory fluoroquinolones should be prescribed whenever an amoxicillin-based antibiotic offers suboptimal antimicrobial coverage and clinicians should consider electrocardiographic monitoring,” first author Magdalene M. Assimon, PharmD, PhD, University of North Carolina, Chapel Hill, told this news organization.
The study was published online Oct. 20 in JAMA Cardiology (doi: 10.1001/jamacardio.2021.4234).
Nearly twofold increased risk
The QT interval-prolonging potential of fluoroquinolone antibiotics are well known. However, evidence linking respiratory fluoroquinolones to adverse cardiac outcomes in the hemodialysis population is limited.
These new observational findings are based on a total of 626,322 antibiotic treatment episodes among 264,968 adults (mean age, 61 years; 51% men) receiving in-center hemodialysis – with respiratory fluoroquinolone making up 40.2% of treatment episodes and amoxicillin-based antibiotic treatment episodes making up 59.8%.
The rate of SCD within 5 days of outpatient initiation of a study antibiotic was 105.7 per 100,000 people prescribed a respiratory fluoroquinolone (levofloxacin or moxifloxacin) versus with 40.0 per 100,000 prescribed amoxicillin or amoxicillin with clavulanic acid (weighted hazard ratio: 1.95; 95% confidence interval, 1.57-2.41).
The authors estimate that one additional SCD would occur during a 5-day follow-up period for every 2,273 respiratory fluoroquinolone treatment episodes. Consistent associations were seen when follow-up was extended to 7, 10, and 14 days.
“Our data suggest that curtailing respiratory fluoroquinolone prescribing may be one actionable strategy to mitigate SCD risk in the hemodialysis population. However, the associated absolute risk reduction would be relatively small,” wrote the authors.
They noted that the rate of SCD in the hemodialysis population exceeds that of the general population by more than 20-fold. Most patients undergoing hemodialysis have a least one risk factor for drug-induced QT interval prolongation.
In the current study, nearly 20% of hemodialysis patients prescribed a respiratory fluoroquinolone were taking other medications with known risk for torsades de pointes.
“Our results emphasize the importance of performing a thorough medication review and considering pharmacodynamic drug interactions before prescribing new drug therapies for any condition,” Dr. Assimon and colleagues advised.
They suggest that clinicians consider electrocardiographic monitoring before and during fluoroquinolone therapy in hemodialysis patients, especially in high-risk individuals.
Valuable study
Reached for comment, Ankur Shah, MD, of the division of kidney diseases and hypertension, Brown University, Providence, R.I., called the analysis “valuable” and said the results are “consistent with the known association of cardiac arrhythmias with respiratory fluoroquinolone use in the general population, postulated to be due to increased risk of torsades de pointes from QTc prolongation. This abnormal heart rhythm can lead to sudden cardiac death.
“Notably, the population receiving respiratory fluoroquinolones had a higher incidence of cardiac disease at baseline, but the risk persisted after adjustment for this increased burden of comorbidity,” Dr. Shah said in an interview. He was not involved in the current research.
Dr. Shah cautioned that observational data such as these should be considered more “hypothesis-generating than practice-changing, as there may be unrecognized confounders or differences in the population that received the respiratory fluoroquinolones.
“A prospective randomized trial would provide a definitive answer, but in the interim, caution should be taken in using respiratory fluoroquinolones when local bacterial resistance patterns or patient-specific data offer another option,” Dr. Shah concluded.
Dr. Assimon reported receiving grants from the Renal Research Institute (a subsidiary of Fresenius Medical Care), honoraria from the International Society of Nephrology for serving as a statistical reviewer for Kidney International Reports, and honoraria from the American Society of Nephrology for serving as an editorial fellow for the Journal of the American Society of Nephrology. Dr. Shah has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, a large observational study suggests.
However, in many cases, the absolute risk is relatively small, and the antimicrobial benefits of a fluoroquinolone may outweigh the potential cardiac risks, the researchers say.
“Pathogen-directed treatment of respiratory infections is of the utmost importance. Respiratory fluoroquinolones should be prescribed whenever an amoxicillin-based antibiotic offers suboptimal antimicrobial coverage and clinicians should consider electrocardiographic monitoring,” first author Magdalene M. Assimon, PharmD, PhD, University of North Carolina, Chapel Hill, told this news organization.
The study was published online Oct. 20 in JAMA Cardiology (doi: 10.1001/jamacardio.2021.4234).
Nearly twofold increased risk
The QT interval-prolonging potential of fluoroquinolone antibiotics are well known. However, evidence linking respiratory fluoroquinolones to adverse cardiac outcomes in the hemodialysis population is limited.
These new observational findings are based on a total of 626,322 antibiotic treatment episodes among 264,968 adults (mean age, 61 years; 51% men) receiving in-center hemodialysis – with respiratory fluoroquinolone making up 40.2% of treatment episodes and amoxicillin-based antibiotic treatment episodes making up 59.8%.
The rate of SCD within 5 days of outpatient initiation of a study antibiotic was 105.7 per 100,000 people prescribed a respiratory fluoroquinolone (levofloxacin or moxifloxacin) versus with 40.0 per 100,000 prescribed amoxicillin or amoxicillin with clavulanic acid (weighted hazard ratio: 1.95; 95% confidence interval, 1.57-2.41).
The authors estimate that one additional SCD would occur during a 5-day follow-up period for every 2,273 respiratory fluoroquinolone treatment episodes. Consistent associations were seen when follow-up was extended to 7, 10, and 14 days.
“Our data suggest that curtailing respiratory fluoroquinolone prescribing may be one actionable strategy to mitigate SCD risk in the hemodialysis population. However, the associated absolute risk reduction would be relatively small,” wrote the authors.
They noted that the rate of SCD in the hemodialysis population exceeds that of the general population by more than 20-fold. Most patients undergoing hemodialysis have a least one risk factor for drug-induced QT interval prolongation.
In the current study, nearly 20% of hemodialysis patients prescribed a respiratory fluoroquinolone were taking other medications with known risk for torsades de pointes.
“Our results emphasize the importance of performing a thorough medication review and considering pharmacodynamic drug interactions before prescribing new drug therapies for any condition,” Dr. Assimon and colleagues advised.
They suggest that clinicians consider electrocardiographic monitoring before and during fluoroquinolone therapy in hemodialysis patients, especially in high-risk individuals.
Valuable study
Reached for comment, Ankur Shah, MD, of the division of kidney diseases and hypertension, Brown University, Providence, R.I., called the analysis “valuable” and said the results are “consistent with the known association of cardiac arrhythmias with respiratory fluoroquinolone use in the general population, postulated to be due to increased risk of torsades de pointes from QTc prolongation. This abnormal heart rhythm can lead to sudden cardiac death.
“Notably, the population receiving respiratory fluoroquinolones had a higher incidence of cardiac disease at baseline, but the risk persisted after adjustment for this increased burden of comorbidity,” Dr. Shah said in an interview. He was not involved in the current research.
Dr. Shah cautioned that observational data such as these should be considered more “hypothesis-generating than practice-changing, as there may be unrecognized confounders or differences in the population that received the respiratory fluoroquinolones.
“A prospective randomized trial would provide a definitive answer, but in the interim, caution should be taken in using respiratory fluoroquinolones when local bacterial resistance patterns or patient-specific data offer another option,” Dr. Shah concluded.
Dr. Assimon reported receiving grants from the Renal Research Institute (a subsidiary of Fresenius Medical Care), honoraria from the International Society of Nephrology for serving as a statistical reviewer for Kidney International Reports, and honoraria from the American Society of Nephrology for serving as an editorial fellow for the Journal of the American Society of Nephrology. Dr. Shah has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Antithrombotic therapy not warranted in COVID-19 outpatients
Antithrombotic therapy in clinically stable, nonhospitalized COVID-19 patients does not offer protection against adverse cardiovascular or pulmonary events, new randomized clinical trial results suggest.
Antithrombotic therapy has proven useful in acutely ill inpatients with COVID-19, but in this study, treatment with aspirin or apixaban (Eliquis) did not reduce the rate of all-cause mortality, symptomatic venous or arterial thromboembolism, myocardial infarction, stroke, or hospitalization for cardiovascular or pulmonary causes in patients ill with COVID-19 but who were not hospitalized.
“Among symptomatic, clinically stable outpatients with COVID-19, treatment with aspirin or apixaban compared with placebo did not reduce the rate of a composite clinical outcome,” the authors conclude. “However, the study was terminated after enrollment of 9% of participants because of a primary event rate lower than anticipated.”
The study, which was led by Jean M. Connors, MD, Brigham and Women’s Hospital, Boston, was published online October 11 in JAMA.
The ACTIV-4B Outpatient Thrombosis Prevention Trial was a randomized, adaptive, double-blind, placebo-controlled trial that sought to compare anticoagulant and antiplatelet therapy among 7,000 symptomatic but clinically stable outpatients with COVID-19.
The trial was conducted at 52 sites in the U.S. between Sept. 2020 and June 2021, with final follow-up this past August 5, and involved minimal face-to-face interactions with study participants.
Patients were randomized in a 1:1:1:1 ratio to aspirin (81 mg orally once daily; n = 164 patients), prophylactic-dose apixaban (2.5 mg orally twice daily; n = 165), therapeutic-dose apixaban (5 mg orally twice daily; n = 164), or placebo (n = 164) for 45 days.
The primary endpoint was a composite of all-cause mortality, symptomatic venous or arterial thromboembolism, myocardial infarction, stroke, or hospitalization for cardiovascular or pulmonary cause.
The trial was terminated early this past June by the independent data monitoring committee because of lower than anticipated event rates. At the time, just 657 symptomatic outpatients with COVID-19 had been enrolled.
The median age of the study participants was 54 years (Interquartile Range [IQR] 46-59); 59% were women.
The median time from diagnosis to randomization was 7 days, and the median time from randomization to initiation of study medications was 3 days.
The trial’s primary efficacy and safety analyses were restricted to patients who received at least one dose of trial medication, for a final number of 558 patients.
Among these patients, the primary endpoint occurred in 1 patient (0.7%) in the aspirin group, 1 patient (0.7%) in the 2.5 mg apixaban group, 2 patients (1.4%) in the 5-mg apixaban group, and 1 patient (0.7%) in the placebo group.
The researchers found that the absolute risk reductions compared with placebo for the primary outcome were 0.0% (95% confidence interval not calculable) in the aspirin group, 0.7% (95% confidence interval, -2.1% to 4.1%) in the prophylactic-dose apixaban group, and 1.4% (95% CI, -1.5% to 5%) in the therapeutic-dose apixaban group.
No major bleeding events were reported.
The absolute risk differences compared with placebo for clinically relevant nonmajor bleeding events were 2% (95% CI, -2.7% to 6.8%) in the aspirin group, 4.5% (95% CI, -0.7% to 10.2%) in the prophylactic-dose apixaban group, and 6.9% (95% CI, 1.4% to 12.9%) in the therapeutic-dose apixaban group.
Safety and efficacy results were similar in all randomly assigned patients.
The researchers speculated that a combination of two demographic shifts over time may have led to the lower than anticipated rate of events in ACTIV-4B.
“First, the threshold for hospital admission has markedly declined since the beginning of the pandemic, such that hospitalization is no longer limited almost exclusively to those with severe pulmonary distress likely to require mechanical ventilation,” they write. “As a result, the severity of illness among individuals with COVID-19 and destined for outpatient care has declined.”
“Second, at least within the U.S., where the trial was conducted, individuals currently being infected with SARS-CoV-2 tend to be younger and have fewer comorbidities when compared with individuals with incident infection at the onset of the pandemic,” they add.
Further, COVID-19 testing was quite limited early in the pandemic, they note, “and it is possible that the anticipated event rates based on data from registries available at that time were overestimated because the denominator (that is, the number of infected individuals overall) was essentially unknown.”
Robust evidence
“The ACTIV-4B trial is the first randomized trial to generate robust evidence about the effects of antithrombotic therapy in outpatients with COVID-19,” Otavio Berwanger, MD, PhD, director of the Academic Research Organization, Hospital Israelita Albert Einstein, Sao Paulo-SP, Brazil, told this news organization.
“It should be noted that this was a well-designed trial with low risk of bias. On the other hand, the main limitation is the low number of events and, consequently, the limited statistical power,” said Dr. Berwanger, who wrote an accompanying editorial.
The ACTIV-4B trial has immediate implications for clinical practice, he added.
“In this sense, considering the neutral results for major cardiopulmonary outcomes, the use of aspirin or apixaban for the management of outpatients with COVID-19 should not be recommended.”
ACTIV-4B also provides useful information for the steering committees of other ongoing trials of antithrombotic therapy for patients with COVID-19 who are not hospitalized, Dr. Berwanger added.
“In this sense, probably issues like statistical power, outcome choices, recruitment feasibility, and even futility would need to be revisited. And finally, lessons learned from the implementation of an innovative, pragmatic, and decentralized trial design represent an important legacy for future trials in cardiovascular diseases and other common conditions,” he said.
The study was funded by the National Institutes of Health, and the National Heart, Lung, and Blood Institute. Dr. Connors reports financial relationships with Bristol-Myers Squibb, Pfizer, Abbott, Alnylam, Takeda, Roche, and Sanofi. Dr. Berwanger reports financial relationships with AstraZeneca, Amgen, Servier, Bristol-Myers Squibb, Bayer, Novartis, Pfizer, and Boehringer Ingelheim.
A version of this article first appeared on Medscape.com.
Antithrombotic therapy in clinically stable, nonhospitalized COVID-19 patients does not offer protection against adverse cardiovascular or pulmonary events, new randomized clinical trial results suggest.
Antithrombotic therapy has proven useful in acutely ill inpatients with COVID-19, but in this study, treatment with aspirin or apixaban (Eliquis) did not reduce the rate of all-cause mortality, symptomatic venous or arterial thromboembolism, myocardial infarction, stroke, or hospitalization for cardiovascular or pulmonary causes in patients ill with COVID-19 but who were not hospitalized.
“Among symptomatic, clinically stable outpatients with COVID-19, treatment with aspirin or apixaban compared with placebo did not reduce the rate of a composite clinical outcome,” the authors conclude. “However, the study was terminated after enrollment of 9% of participants because of a primary event rate lower than anticipated.”
The study, which was led by Jean M. Connors, MD, Brigham and Women’s Hospital, Boston, was published online October 11 in JAMA.
The ACTIV-4B Outpatient Thrombosis Prevention Trial was a randomized, adaptive, double-blind, placebo-controlled trial that sought to compare anticoagulant and antiplatelet therapy among 7,000 symptomatic but clinically stable outpatients with COVID-19.
The trial was conducted at 52 sites in the U.S. between Sept. 2020 and June 2021, with final follow-up this past August 5, and involved minimal face-to-face interactions with study participants.
Patients were randomized in a 1:1:1:1 ratio to aspirin (81 mg orally once daily; n = 164 patients), prophylactic-dose apixaban (2.5 mg orally twice daily; n = 165), therapeutic-dose apixaban (5 mg orally twice daily; n = 164), or placebo (n = 164) for 45 days.
The primary endpoint was a composite of all-cause mortality, symptomatic venous or arterial thromboembolism, myocardial infarction, stroke, or hospitalization for cardiovascular or pulmonary cause.
The trial was terminated early this past June by the independent data monitoring committee because of lower than anticipated event rates. At the time, just 657 symptomatic outpatients with COVID-19 had been enrolled.
The median age of the study participants was 54 years (Interquartile Range [IQR] 46-59); 59% were women.
The median time from diagnosis to randomization was 7 days, and the median time from randomization to initiation of study medications was 3 days.
The trial’s primary efficacy and safety analyses were restricted to patients who received at least one dose of trial medication, for a final number of 558 patients.
Among these patients, the primary endpoint occurred in 1 patient (0.7%) in the aspirin group, 1 patient (0.7%) in the 2.5 mg apixaban group, 2 patients (1.4%) in the 5-mg apixaban group, and 1 patient (0.7%) in the placebo group.
The researchers found that the absolute risk reductions compared with placebo for the primary outcome were 0.0% (95% confidence interval not calculable) in the aspirin group, 0.7% (95% confidence interval, -2.1% to 4.1%) in the prophylactic-dose apixaban group, and 1.4% (95% CI, -1.5% to 5%) in the therapeutic-dose apixaban group.
No major bleeding events were reported.
The absolute risk differences compared with placebo for clinically relevant nonmajor bleeding events were 2% (95% CI, -2.7% to 6.8%) in the aspirin group, 4.5% (95% CI, -0.7% to 10.2%) in the prophylactic-dose apixaban group, and 6.9% (95% CI, 1.4% to 12.9%) in the therapeutic-dose apixaban group.
Safety and efficacy results were similar in all randomly assigned patients.
The researchers speculated that a combination of two demographic shifts over time may have led to the lower than anticipated rate of events in ACTIV-4B.
“First, the threshold for hospital admission has markedly declined since the beginning of the pandemic, such that hospitalization is no longer limited almost exclusively to those with severe pulmonary distress likely to require mechanical ventilation,” they write. “As a result, the severity of illness among individuals with COVID-19 and destined for outpatient care has declined.”
“Second, at least within the U.S., where the trial was conducted, individuals currently being infected with SARS-CoV-2 tend to be younger and have fewer comorbidities when compared with individuals with incident infection at the onset of the pandemic,” they add.
Further, COVID-19 testing was quite limited early in the pandemic, they note, “and it is possible that the anticipated event rates based on data from registries available at that time were overestimated because the denominator (that is, the number of infected individuals overall) was essentially unknown.”
Robust evidence
“The ACTIV-4B trial is the first randomized trial to generate robust evidence about the effects of antithrombotic therapy in outpatients with COVID-19,” Otavio Berwanger, MD, PhD, director of the Academic Research Organization, Hospital Israelita Albert Einstein, Sao Paulo-SP, Brazil, told this news organization.
“It should be noted that this was a well-designed trial with low risk of bias. On the other hand, the main limitation is the low number of events and, consequently, the limited statistical power,” said Dr. Berwanger, who wrote an accompanying editorial.
The ACTIV-4B trial has immediate implications for clinical practice, he added.
“In this sense, considering the neutral results for major cardiopulmonary outcomes, the use of aspirin or apixaban for the management of outpatients with COVID-19 should not be recommended.”
ACTIV-4B also provides useful information for the steering committees of other ongoing trials of antithrombotic therapy for patients with COVID-19 who are not hospitalized, Dr. Berwanger added.
“In this sense, probably issues like statistical power, outcome choices, recruitment feasibility, and even futility would need to be revisited. And finally, lessons learned from the implementation of an innovative, pragmatic, and decentralized trial design represent an important legacy for future trials in cardiovascular diseases and other common conditions,” he said.
The study was funded by the National Institutes of Health, and the National Heart, Lung, and Blood Institute. Dr. Connors reports financial relationships with Bristol-Myers Squibb, Pfizer, Abbott, Alnylam, Takeda, Roche, and Sanofi. Dr. Berwanger reports financial relationships with AstraZeneca, Amgen, Servier, Bristol-Myers Squibb, Bayer, Novartis, Pfizer, and Boehringer Ingelheim.
A version of this article first appeared on Medscape.com.
Antithrombotic therapy in clinically stable, nonhospitalized COVID-19 patients does not offer protection against adverse cardiovascular or pulmonary events, new randomized clinical trial results suggest.
Antithrombotic therapy has proven useful in acutely ill inpatients with COVID-19, but in this study, treatment with aspirin or apixaban (Eliquis) did not reduce the rate of all-cause mortality, symptomatic venous or arterial thromboembolism, myocardial infarction, stroke, or hospitalization for cardiovascular or pulmonary causes in patients ill with COVID-19 but who were not hospitalized.
“Among symptomatic, clinically stable outpatients with COVID-19, treatment with aspirin or apixaban compared with placebo did not reduce the rate of a composite clinical outcome,” the authors conclude. “However, the study was terminated after enrollment of 9% of participants because of a primary event rate lower than anticipated.”
The study, which was led by Jean M. Connors, MD, Brigham and Women’s Hospital, Boston, was published online October 11 in JAMA.
The ACTIV-4B Outpatient Thrombosis Prevention Trial was a randomized, adaptive, double-blind, placebo-controlled trial that sought to compare anticoagulant and antiplatelet therapy among 7,000 symptomatic but clinically stable outpatients with COVID-19.
The trial was conducted at 52 sites in the U.S. between Sept. 2020 and June 2021, with final follow-up this past August 5, and involved minimal face-to-face interactions with study participants.
Patients were randomized in a 1:1:1:1 ratio to aspirin (81 mg orally once daily; n = 164 patients), prophylactic-dose apixaban (2.5 mg orally twice daily; n = 165), therapeutic-dose apixaban (5 mg orally twice daily; n = 164), or placebo (n = 164) for 45 days.
The primary endpoint was a composite of all-cause mortality, symptomatic venous or arterial thromboembolism, myocardial infarction, stroke, or hospitalization for cardiovascular or pulmonary cause.
The trial was terminated early this past June by the independent data monitoring committee because of lower than anticipated event rates. At the time, just 657 symptomatic outpatients with COVID-19 had been enrolled.
The median age of the study participants was 54 years (Interquartile Range [IQR] 46-59); 59% were women.
The median time from diagnosis to randomization was 7 days, and the median time from randomization to initiation of study medications was 3 days.
The trial’s primary efficacy and safety analyses were restricted to patients who received at least one dose of trial medication, for a final number of 558 patients.
Among these patients, the primary endpoint occurred in 1 patient (0.7%) in the aspirin group, 1 patient (0.7%) in the 2.5 mg apixaban group, 2 patients (1.4%) in the 5-mg apixaban group, and 1 patient (0.7%) in the placebo group.
The researchers found that the absolute risk reductions compared with placebo for the primary outcome were 0.0% (95% confidence interval not calculable) in the aspirin group, 0.7% (95% confidence interval, -2.1% to 4.1%) in the prophylactic-dose apixaban group, and 1.4% (95% CI, -1.5% to 5%) in the therapeutic-dose apixaban group.
No major bleeding events were reported.
The absolute risk differences compared with placebo for clinically relevant nonmajor bleeding events were 2% (95% CI, -2.7% to 6.8%) in the aspirin group, 4.5% (95% CI, -0.7% to 10.2%) in the prophylactic-dose apixaban group, and 6.9% (95% CI, 1.4% to 12.9%) in the therapeutic-dose apixaban group.
Safety and efficacy results were similar in all randomly assigned patients.
The researchers speculated that a combination of two demographic shifts over time may have led to the lower than anticipated rate of events in ACTIV-4B.
“First, the threshold for hospital admission has markedly declined since the beginning of the pandemic, such that hospitalization is no longer limited almost exclusively to those with severe pulmonary distress likely to require mechanical ventilation,” they write. “As a result, the severity of illness among individuals with COVID-19 and destined for outpatient care has declined.”
“Second, at least within the U.S., where the trial was conducted, individuals currently being infected with SARS-CoV-2 tend to be younger and have fewer comorbidities when compared with individuals with incident infection at the onset of the pandemic,” they add.
Further, COVID-19 testing was quite limited early in the pandemic, they note, “and it is possible that the anticipated event rates based on data from registries available at that time were overestimated because the denominator (that is, the number of infected individuals overall) was essentially unknown.”
Robust evidence
“The ACTIV-4B trial is the first randomized trial to generate robust evidence about the effects of antithrombotic therapy in outpatients with COVID-19,” Otavio Berwanger, MD, PhD, director of the Academic Research Organization, Hospital Israelita Albert Einstein, Sao Paulo-SP, Brazil, told this news organization.
“It should be noted that this was a well-designed trial with low risk of bias. On the other hand, the main limitation is the low number of events and, consequently, the limited statistical power,” said Dr. Berwanger, who wrote an accompanying editorial.
The ACTIV-4B trial has immediate implications for clinical practice, he added.
“In this sense, considering the neutral results for major cardiopulmonary outcomes, the use of aspirin or apixaban for the management of outpatients with COVID-19 should not be recommended.”
ACTIV-4B also provides useful information for the steering committees of other ongoing trials of antithrombotic therapy for patients with COVID-19 who are not hospitalized, Dr. Berwanger added.
“In this sense, probably issues like statistical power, outcome choices, recruitment feasibility, and even futility would need to be revisited. And finally, lessons learned from the implementation of an innovative, pragmatic, and decentralized trial design represent an important legacy for future trials in cardiovascular diseases and other common conditions,” he said.
The study was funded by the National Institutes of Health, and the National Heart, Lung, and Blood Institute. Dr. Connors reports financial relationships with Bristol-Myers Squibb, Pfizer, Abbott, Alnylam, Takeda, Roche, and Sanofi. Dr. Berwanger reports financial relationships with AstraZeneca, Amgen, Servier, Bristol-Myers Squibb, Bayer, Novartis, Pfizer, and Boehringer Ingelheim.
A version of this article first appeared on Medscape.com.
USPSTF statement on aspirin: poor messaging at best
: “The USPSTF concludes with moderate certainty that initiating aspirin use for the primary prevention of CVD events in adults age 60 years or older has no net benefit.” I take no issue with the data and appreciate the efforts of the researchers, but at a minimum the public statement is incomplete. At most, it’s dangerously poor messaging.
As physicians, we understand how best to apply this information, but most laypeople, some at significant cardiovascular risk, closed their medicine cabinets this morning and left their aspirin bottle unopened on the shelf. Some of these patients have never spent an hour in the hospital for cardiac-related issues, but they have mitigated their risk for myocardial infarction by purposely poisoning their platelets daily with 81 mg of aspirin. And they should continue to do so.
Don’t forget the calcium score
Take, for instance, my patient Jack, who is typical of many patients I’ve seen throughout the years. Jack is 68 years old and has never had a cardiac event or a gastrointestinal bleed. His daily routine includes a walk, a statin, and a baby aspirin because his CT coronary artery calcium (CAC) score was 10,000 at age 58.
He first visited me 10 years ago because his father died of a myocardial infarction in his late 50s. Jack’s left ventricular ejection fraction is normal and his stress ECG shows 1-mm ST-segment depression at 8 minutes on a Bruce protocol stress test, without angina. Because Jack is well-educated and keeps up with the latest cardiology recommendations, he is precisely the type of patient who may be harmed by this new USPSTF statement by stopping his aspirin.
In October 2020, an analysis from the DALLAS Heart Study showed that persons with a CAC score greater than 100 had a higher cumulative incidence of bleeding and of atherosclerotic cardiovascular disease (ASCVD) events compared with those with no coronary calcium. After adjustment for clinical risk factors, the association between CAC and bleeding was attenuated and no longer statistically significant, whereas the relationship between CAC and ASCVD remained.
I asked one of the investigators, Amit Khera, MD, MSc, from UT Southwestern Medical Center, about the latest recommendations. He emphasized that both the American College of Cardiology/American Heart Association prevention guidelines and the USPSTF statement say that aspirin could still be considered among patients who are at higher risk for cardiovascular events. The USPSTF delineated this as a 10-year ASCVD risk greater than 10%.
Dr. Khera, who was an author of the 2019 guidelines, explained that the guideline committee purposely did not make specific recommendations as to what demarcated higher risk because the data were not clear at that time. Since then, a couple of papers, including the Dallas Heart Study analysis published in JAMA Cardiology, showed that patients at low bleeding risk with a calcium score above 100 may get a net benefit from aspirin. “Thus, in my patients who have a high calcium score and low bleeding risk, I do discuss the option to start or continue aspirin,” he said.
One size does not fit all
I watched ABC World News Tonight on Tuesday, October 12, and was immediately troubled about the coverage of the USPSTF statement. With viewership for the “Big Three” networks in the millions, the message to discontinue aspirin may have unintended consequences for many at-risk patients. The blood-thinning effects of a single dose of aspirin last about 10 days; it will be interesting to see if the rates of myocardial infarction increase over time. This could have been avoided with a better-worded statement – I’m concerned that the lack of nuance could spell big trouble for some.
In JAMA Cardiology, Dr. Khera and colleagues wrote that, “Aspirin use is not a one-size-fits-all therapy.” All physicians likely agree with that opinion. The USPSTF statement should have included the point that if you have a high CT coronary artery calcium score and a low bleeding risk, aspirin still fits very well even if you haven’t experienced a cardiac event. At a minimum, the USPSTF statement should have included the suggestion for patients to consult their physician for advice before discontinuing aspirin therapy.
I hope patients like Jack get the right message.
Melissa Walton-Shirley, MD, is a native Kentuckian who retired from full-time invasive cardiology.
A version of this article first appeared on Medscape.com.
: “The USPSTF concludes with moderate certainty that initiating aspirin use for the primary prevention of CVD events in adults age 60 years or older has no net benefit.” I take no issue with the data and appreciate the efforts of the researchers, but at a minimum the public statement is incomplete. At most, it’s dangerously poor messaging.
As physicians, we understand how best to apply this information, but most laypeople, some at significant cardiovascular risk, closed their medicine cabinets this morning and left their aspirin bottle unopened on the shelf. Some of these patients have never spent an hour in the hospital for cardiac-related issues, but they have mitigated their risk for myocardial infarction by purposely poisoning their platelets daily with 81 mg of aspirin. And they should continue to do so.
Don’t forget the calcium score
Take, for instance, my patient Jack, who is typical of many patients I’ve seen throughout the years. Jack is 68 years old and has never had a cardiac event or a gastrointestinal bleed. His daily routine includes a walk, a statin, and a baby aspirin because his CT coronary artery calcium (CAC) score was 10,000 at age 58.
He first visited me 10 years ago because his father died of a myocardial infarction in his late 50s. Jack’s left ventricular ejection fraction is normal and his stress ECG shows 1-mm ST-segment depression at 8 minutes on a Bruce protocol stress test, without angina. Because Jack is well-educated and keeps up with the latest cardiology recommendations, he is precisely the type of patient who may be harmed by this new USPSTF statement by stopping his aspirin.
In October 2020, an analysis from the DALLAS Heart Study showed that persons with a CAC score greater than 100 had a higher cumulative incidence of bleeding and of atherosclerotic cardiovascular disease (ASCVD) events compared with those with no coronary calcium. After adjustment for clinical risk factors, the association between CAC and bleeding was attenuated and no longer statistically significant, whereas the relationship between CAC and ASCVD remained.
I asked one of the investigators, Amit Khera, MD, MSc, from UT Southwestern Medical Center, about the latest recommendations. He emphasized that both the American College of Cardiology/American Heart Association prevention guidelines and the USPSTF statement say that aspirin could still be considered among patients who are at higher risk for cardiovascular events. The USPSTF delineated this as a 10-year ASCVD risk greater than 10%.
Dr. Khera, who was an author of the 2019 guidelines, explained that the guideline committee purposely did not make specific recommendations as to what demarcated higher risk because the data were not clear at that time. Since then, a couple of papers, including the Dallas Heart Study analysis published in JAMA Cardiology, showed that patients at low bleeding risk with a calcium score above 100 may get a net benefit from aspirin. “Thus, in my patients who have a high calcium score and low bleeding risk, I do discuss the option to start or continue aspirin,” he said.
One size does not fit all
I watched ABC World News Tonight on Tuesday, October 12, and was immediately troubled about the coverage of the USPSTF statement. With viewership for the “Big Three” networks in the millions, the message to discontinue aspirin may have unintended consequences for many at-risk patients. The blood-thinning effects of a single dose of aspirin last about 10 days; it will be interesting to see if the rates of myocardial infarction increase over time. This could have been avoided with a better-worded statement – I’m concerned that the lack of nuance could spell big trouble for some.
In JAMA Cardiology, Dr. Khera and colleagues wrote that, “Aspirin use is not a one-size-fits-all therapy.” All physicians likely agree with that opinion. The USPSTF statement should have included the point that if you have a high CT coronary artery calcium score and a low bleeding risk, aspirin still fits very well even if you haven’t experienced a cardiac event. At a minimum, the USPSTF statement should have included the suggestion for patients to consult their physician for advice before discontinuing aspirin therapy.
I hope patients like Jack get the right message.
Melissa Walton-Shirley, MD, is a native Kentuckian who retired from full-time invasive cardiology.
A version of this article first appeared on Medscape.com.
: “The USPSTF concludes with moderate certainty that initiating aspirin use for the primary prevention of CVD events in adults age 60 years or older has no net benefit.” I take no issue with the data and appreciate the efforts of the researchers, but at a minimum the public statement is incomplete. At most, it’s dangerously poor messaging.
As physicians, we understand how best to apply this information, but most laypeople, some at significant cardiovascular risk, closed their medicine cabinets this morning and left their aspirin bottle unopened on the shelf. Some of these patients have never spent an hour in the hospital for cardiac-related issues, but they have mitigated their risk for myocardial infarction by purposely poisoning their platelets daily with 81 mg of aspirin. And they should continue to do so.
Don’t forget the calcium score
Take, for instance, my patient Jack, who is typical of many patients I’ve seen throughout the years. Jack is 68 years old and has never had a cardiac event or a gastrointestinal bleed. His daily routine includes a walk, a statin, and a baby aspirin because his CT coronary artery calcium (CAC) score was 10,000 at age 58.
He first visited me 10 years ago because his father died of a myocardial infarction in his late 50s. Jack’s left ventricular ejection fraction is normal and his stress ECG shows 1-mm ST-segment depression at 8 minutes on a Bruce protocol stress test, without angina. Because Jack is well-educated and keeps up with the latest cardiology recommendations, he is precisely the type of patient who may be harmed by this new USPSTF statement by stopping his aspirin.
In October 2020, an analysis from the DALLAS Heart Study showed that persons with a CAC score greater than 100 had a higher cumulative incidence of bleeding and of atherosclerotic cardiovascular disease (ASCVD) events compared with those with no coronary calcium. After adjustment for clinical risk factors, the association between CAC and bleeding was attenuated and no longer statistically significant, whereas the relationship between CAC and ASCVD remained.
I asked one of the investigators, Amit Khera, MD, MSc, from UT Southwestern Medical Center, about the latest recommendations. He emphasized that both the American College of Cardiology/American Heart Association prevention guidelines and the USPSTF statement say that aspirin could still be considered among patients who are at higher risk for cardiovascular events. The USPSTF delineated this as a 10-year ASCVD risk greater than 10%.
Dr. Khera, who was an author of the 2019 guidelines, explained that the guideline committee purposely did not make specific recommendations as to what demarcated higher risk because the data were not clear at that time. Since then, a couple of papers, including the Dallas Heart Study analysis published in JAMA Cardiology, showed that patients at low bleeding risk with a calcium score above 100 may get a net benefit from aspirin. “Thus, in my patients who have a high calcium score and low bleeding risk, I do discuss the option to start or continue aspirin,” he said.
One size does not fit all
I watched ABC World News Tonight on Tuesday, October 12, and was immediately troubled about the coverage of the USPSTF statement. With viewership for the “Big Three” networks in the millions, the message to discontinue aspirin may have unintended consequences for many at-risk patients. The blood-thinning effects of a single dose of aspirin last about 10 days; it will be interesting to see if the rates of myocardial infarction increase over time. This could have been avoided with a better-worded statement – I’m concerned that the lack of nuance could spell big trouble for some.
In JAMA Cardiology, Dr. Khera and colleagues wrote that, “Aspirin use is not a one-size-fits-all therapy.” All physicians likely agree with that opinion. The USPSTF statement should have included the point that if you have a high CT coronary artery calcium score and a low bleeding risk, aspirin still fits very well even if you haven’t experienced a cardiac event. At a minimum, the USPSTF statement should have included the suggestion for patients to consult their physician for advice before discontinuing aspirin therapy.
I hope patients like Jack get the right message.
Melissa Walton-Shirley, MD, is a native Kentuckian who retired from full-time invasive cardiology.
A version of this article first appeared on Medscape.com.
Broken heart syndrome: on the rise, especially in women 50-74
As a pediatric kidney doctor, Elaine S. Kamil, MD, is used to long hours helping children and teens with a variety of issues, some very serious, and also makes time to give back to her specialty.
In late 2013, she was in Washington, D.C., planning a meeting of the American Society of Nephrology. When the organizers decided at the last minute that another session was needed, she stayed late, putting it together. Then she hopped on a plane and returned home to Los Angeles on a Saturday night.
Right after midnight, Dr. Kamil knew something was wrong.
“I had really severe chest pain,” she says. “I have reflux, and I know what that feels like. This was much more intense. It really hurt.” She debated: “Should I wake up my husband?”
Soon, the pain got so bad, she had to.
At the hospital, an electrocardiogram was slightly abnormal, as was a blood test that measures damage to the heart. Next, she got an angiogram, an imaging technique to visualize the heart. Once doctors looked at the image on the screen during the angiogram, they knew the diagnosis: Broken heart syndrome, known medically as takotsubo cardiomyopathy or stress-induced cardiomyopathy. As the name suggests, it’s triggered by extreme stress or loss.
The telltale clue to the diagnosis is the appearance of the walls of the heart’s left ventricle, its main pumping chamber. When the condition is present, the left ventricle changes shape, developing a narrow neck and a round bottom, resembling an octopus pot called takotsubo used by fishermen in Japan, where the condition was first recognized in 1990.
Like most who are affected, Dr. Kamil, now 74, is fine now. She is still actively working, as a researcher and professor emerita at Cedars-Sinai Medical Center and a health sciences clinical professor of pediatrics at UCLA. But she focuses more now on stress reduction.
Study: condition on the rise
New research from Cedars-Sinai suggests that broken heart syndrome, while still not common, is not as rare as once thought. And it’s on the rise, especially among middle-age and older women.
This ‘’middle” group – women ages 50 to 74 – had the greatest rate of increase over the years studied, 2006-2017, says Susan Cheng, MD, lead author of the study, published in the Journal of the American Heart Association. She is the director of the Institute for Research on Healthy Aging at the Smidt Heart Institute at Cedars-Sinai Medical Center.
Dr. Cheng and her team used national hospital inpatient data collected from more than 135,000 men and women diagnosed with the condition during the 12 years of the study. More than 88% of all cases were women, especially in those age 50 or older. When the researchers looked more closely, they found the diagnosis has been increasing at least 6 to 10 times more rapidly for women in the 50-to-74 age group than in any other group.
For every case of the condition in younger women, or in men of all age groups, the researchers found an additional 10 cases for middle-aged women and six additional cases for older women. For example, while the syndrome occurred in 15 younger women per million per year, it occurred in 128 middle aged women per year.
The age groups found most at risk was surprising, says Dr. Cheng, who expected the risk would be highest in the oldest age group of women, those over 75.
While doctors are more aware of the condition now, “it’s not just the increased recognition,” she says. “There is something going on” driving the continual increase. It probably has something to do with environmental changes, she says.
Hormones and hormonal differences between men and women aren’t the whole story either, she says. Her team will study it further, hoping eventually to find who might be more likely to get the condition by talking to those who have had it and collecting clues. “There probably is some underlying genetic predisposition,” she says.
“The neural hormones that drive the flight-or-fight response (such as adrenaline) are definitely elevated,” she says. “The brain and the heart are talking to each other.”
Experts say these surging stress hormones essentially “stun” the heart, affecting how it functions. The question is, what makes women particularly more susceptible to being excessively triggered when exposed to stress? That is unclear, Dr. Cheng says.
While the condition is a frightening experience, ‘’the overall prognosis is much better than having a garden-variety heart attack,” she says.
But researchers are still figuring out long-term outcomes, and she can’t tell patients if they are likely to have another episode.
Research findings reflected in practice
Other cardiologists say they are not surprised by the new findings.
“I think it’s very consistent with what I am seeing clinically,” says Tracy Stevens, MD, a cardiologist at Saint Luke’s Mid America Heart Institute in Kansas City, MO. In the last 5 years, she has diagnosed at least 100 cases, she says. The increase is partly but not entirely due to increased awareness by doctors of the condition, she agrees.
If a postmenopausal woman comes to the hospital with chest pain, the condition is more likely now than in the past to be suspected, says Dr. Stevens, who’s also the medical director of the Muriel I. Kauffman Women’s Heart Center at Saint Luke’s. The octopus pot-like image is hard to miss.
“What we see at the base of the left ventricle is, it is squeezing like crazy, it is ballooning.”
“We probably see at least five to ten a month,” says Kevin Bybee, MD, an associate professor of medicine at the University of Missouri-Kansas City School of Medicine.
The increase in numbers found by the Los Angeles researchers may not even capture the true picture of how many people have gotten this condition, he says. He suspects some women whose deaths are blamed on sudden cardiac death might actually have had broken heart syndrome.
“I have always wondered how many don’t make it to the hospital.”
Dr. Bybee, who’s also medical director of cardiovascular services at St. Luke’s South in Overland Park, KS, became interested in the syndrome during his fellowship at Mayo Clinic when he diagnosed three patients in just 2 months. He and his team published the case histories of seven patients in 2004. Since then, many more reports have been published.
Researchers from Texas used the same national database as the Cedars researchers to look at cases from 2005 to 2014, and also found an increase. But study co-author Abhijeet Dhoble, MD, a cardiologist and associate professor of medicine at UT Health Science Center and Memorial Hermann-Texas Medical Center in Houston, believes more recognition explains most of the increase.
And the pandemic is now playing a role in driving up cases, he says.
“In the last 2 years, we have been noticing increasing numbers of cases, probably due to the pandemic,” he says.
Profiles of cases
Over the years, Dr. Bybee has collected information on what is happening before the heart begins to go haywire.
“Fifteen to twenty percent of the time, there is no obvious trigger,” he says.
Other times, a stressful emotional event, such as the death of a spouse or a severe car accident, can trigger it.
One patient with an extreme fear of public speaking had to give a talk in front of a large group when she was new to a job. Another woman lost money at a casino before it happened, Dr. Bybee says. Yet another patient took her dog out for a walk in the woods, and the dog got caught in a raccoon trap.
Fierce arguments as well as surprise parties have triggered the condition, Dr. Bybee says. Physical problems such as asthma or sepsis, a life-threatening complication of an infection, can also trigger broken heart.
“It’s challenging because this is unpredictable,” he says.
Treatments and recovery
The condition is rarely fatal, say experts from Harvard and Mayo Clinic, but some can have complications such as heart failure.
There are no standard guidelines for treatment, Dr. Dhoble, of Memorial Hermann, says. “We give medications to keep blood pressures in the optimal range.” Doctors may also prescribe lipid-lowering medicines and blood thinner medications. “Most patients recover within 3 to 7 days.”
“Usually within a month, their [heart] function returns to normal,” Dr. Stevens says.
Getting one’s full energy back can take longer, as Dr. Kamil found. “It was about 6 months before I was up to speed.”
Survivors talk
Looking back, Dr. Kamil realizes now how much stress she was under before her episode.
“I took care of chronically ill kids,” she says, and worried about them. “I’m kind of a mother hen.”
Besides patient care and her cross-county meeting planning, she was flying back and forth to Florida to tend to her mother, who had chronic health problems. She was also managing that year’s annual media prize at a San Diego university that she and her husband established after the death of their adult son several years before.
“I was busy with that, and it is a bittersweet experience,” she says.
She is trying to take her cardiologist’s advice to slow down.
“I used to be notorious for saying, ‘I need to get one more thing done,’” she says.
Joanie Simpson says she, too, has slowed down. She was diagnosed with broken heart in 2016, after a cascade of stressful events. Her son was facing back surgery, her son-in-law had lost his job, and her tiny Yorkshire terrier Meha died. And she and her husband, Benny, had issues with their rental property.
Now 66 and retired in Camp Wood, Texas, she has learned to enjoy life and worry a little less. Music is one way.
“We’re Parrotheads,” she says, referencing the nickname given to fans of singer Jimmy Buffett. “We listen to Buffett and to ’60s, ’70s, ’80s music. We dance around the house. We aren’t big tavern goers, so we dance around the living room and hope we don’t fall over the coffee table. So far, so good.”
They have plans to buy a small pontoon boat and go fishing. Benny especially loves that idea, she says, laughing, as he finds it’s the only time she stops talking.
Reducing the what-ifs
Patients have a common question and worry: What if it happens again?
“I definitely worried more about it in the beginning,” Dr. Kamil says. “Could I have permanent heart damage? Will I be a cardiac cripple?” Her worry has eased.
If you suspect the condition, ‘’get yourself to a provider who knows about it,” she says.
Cardiologists are very likely to suspect the condition, Dr. Bybee says, as are doctors working in a large-volume emergency department.
Dr. Stevens, of St. Luke’s, is straightforward, telling her patients what is known and what is not about the condition. She recommends her patients go to cardiac rehab.
“It gives them that confidence to know what they can do,” she says.
She also gives lifestyle advice, suggesting patients get a home blood pressure cuff and use it. She suggests paying attention to good nutrition and exercise and not lifting anything so heavy that grunting is necessary.
Focus on protecting heart health, Dr. Cheng tells patients. She encourages them to find the stress reduction plan that works for them. Most important, she tells patients to understand that it is not their fault.
A version of this article first appeared on WebMD.com.
As a pediatric kidney doctor, Elaine S. Kamil, MD, is used to long hours helping children and teens with a variety of issues, some very serious, and also makes time to give back to her specialty.
In late 2013, she was in Washington, D.C., planning a meeting of the American Society of Nephrology. When the organizers decided at the last minute that another session was needed, she stayed late, putting it together. Then she hopped on a plane and returned home to Los Angeles on a Saturday night.
Right after midnight, Dr. Kamil knew something was wrong.
“I had really severe chest pain,” she says. “I have reflux, and I know what that feels like. This was much more intense. It really hurt.” She debated: “Should I wake up my husband?”
Soon, the pain got so bad, she had to.
At the hospital, an electrocardiogram was slightly abnormal, as was a blood test that measures damage to the heart. Next, she got an angiogram, an imaging technique to visualize the heart. Once doctors looked at the image on the screen during the angiogram, they knew the diagnosis: Broken heart syndrome, known medically as takotsubo cardiomyopathy or stress-induced cardiomyopathy. As the name suggests, it’s triggered by extreme stress or loss.
The telltale clue to the diagnosis is the appearance of the walls of the heart’s left ventricle, its main pumping chamber. When the condition is present, the left ventricle changes shape, developing a narrow neck and a round bottom, resembling an octopus pot called takotsubo used by fishermen in Japan, where the condition was first recognized in 1990.
Like most who are affected, Dr. Kamil, now 74, is fine now. She is still actively working, as a researcher and professor emerita at Cedars-Sinai Medical Center and a health sciences clinical professor of pediatrics at UCLA. But she focuses more now on stress reduction.
Study: condition on the rise
New research from Cedars-Sinai suggests that broken heart syndrome, while still not common, is not as rare as once thought. And it’s on the rise, especially among middle-age and older women.
This ‘’middle” group – women ages 50 to 74 – had the greatest rate of increase over the years studied, 2006-2017, says Susan Cheng, MD, lead author of the study, published in the Journal of the American Heart Association. She is the director of the Institute for Research on Healthy Aging at the Smidt Heart Institute at Cedars-Sinai Medical Center.
Dr. Cheng and her team used national hospital inpatient data collected from more than 135,000 men and women diagnosed with the condition during the 12 years of the study. More than 88% of all cases were women, especially in those age 50 or older. When the researchers looked more closely, they found the diagnosis has been increasing at least 6 to 10 times more rapidly for women in the 50-to-74 age group than in any other group.
For every case of the condition in younger women, or in men of all age groups, the researchers found an additional 10 cases for middle-aged women and six additional cases for older women. For example, while the syndrome occurred in 15 younger women per million per year, it occurred in 128 middle aged women per year.
The age groups found most at risk was surprising, says Dr. Cheng, who expected the risk would be highest in the oldest age group of women, those over 75.
While doctors are more aware of the condition now, “it’s not just the increased recognition,” she says. “There is something going on” driving the continual increase. It probably has something to do with environmental changes, she says.
Hormones and hormonal differences between men and women aren’t the whole story either, she says. Her team will study it further, hoping eventually to find who might be more likely to get the condition by talking to those who have had it and collecting clues. “There probably is some underlying genetic predisposition,” she says.
“The neural hormones that drive the flight-or-fight response (such as adrenaline) are definitely elevated,” she says. “The brain and the heart are talking to each other.”
Experts say these surging stress hormones essentially “stun” the heart, affecting how it functions. The question is, what makes women particularly more susceptible to being excessively triggered when exposed to stress? That is unclear, Dr. Cheng says.
While the condition is a frightening experience, ‘’the overall prognosis is much better than having a garden-variety heart attack,” she says.
But researchers are still figuring out long-term outcomes, and she can’t tell patients if they are likely to have another episode.
Research findings reflected in practice
Other cardiologists say they are not surprised by the new findings.
“I think it’s very consistent with what I am seeing clinically,” says Tracy Stevens, MD, a cardiologist at Saint Luke’s Mid America Heart Institute in Kansas City, MO. In the last 5 years, she has diagnosed at least 100 cases, she says. The increase is partly but not entirely due to increased awareness by doctors of the condition, she agrees.
If a postmenopausal woman comes to the hospital with chest pain, the condition is more likely now than in the past to be suspected, says Dr. Stevens, who’s also the medical director of the Muriel I. Kauffman Women’s Heart Center at Saint Luke’s. The octopus pot-like image is hard to miss.
“What we see at the base of the left ventricle is, it is squeezing like crazy, it is ballooning.”
“We probably see at least five to ten a month,” says Kevin Bybee, MD, an associate professor of medicine at the University of Missouri-Kansas City School of Medicine.
The increase in numbers found by the Los Angeles researchers may not even capture the true picture of how many people have gotten this condition, he says. He suspects some women whose deaths are blamed on sudden cardiac death might actually have had broken heart syndrome.
“I have always wondered how many don’t make it to the hospital.”
Dr. Bybee, who’s also medical director of cardiovascular services at St. Luke’s South in Overland Park, KS, became interested in the syndrome during his fellowship at Mayo Clinic when he diagnosed three patients in just 2 months. He and his team published the case histories of seven patients in 2004. Since then, many more reports have been published.
Researchers from Texas used the same national database as the Cedars researchers to look at cases from 2005 to 2014, and also found an increase. But study co-author Abhijeet Dhoble, MD, a cardiologist and associate professor of medicine at UT Health Science Center and Memorial Hermann-Texas Medical Center in Houston, believes more recognition explains most of the increase.
And the pandemic is now playing a role in driving up cases, he says.
“In the last 2 years, we have been noticing increasing numbers of cases, probably due to the pandemic,” he says.
Profiles of cases
Over the years, Dr. Bybee has collected information on what is happening before the heart begins to go haywire.
“Fifteen to twenty percent of the time, there is no obvious trigger,” he says.
Other times, a stressful emotional event, such as the death of a spouse or a severe car accident, can trigger it.
One patient with an extreme fear of public speaking had to give a talk in front of a large group when she was new to a job. Another woman lost money at a casino before it happened, Dr. Bybee says. Yet another patient took her dog out for a walk in the woods, and the dog got caught in a raccoon trap.
Fierce arguments as well as surprise parties have triggered the condition, Dr. Bybee says. Physical problems such as asthma or sepsis, a life-threatening complication of an infection, can also trigger broken heart.
“It’s challenging because this is unpredictable,” he says.
Treatments and recovery
The condition is rarely fatal, say experts from Harvard and Mayo Clinic, but some can have complications such as heart failure.
There are no standard guidelines for treatment, Dr. Dhoble, of Memorial Hermann, says. “We give medications to keep blood pressures in the optimal range.” Doctors may also prescribe lipid-lowering medicines and blood thinner medications. “Most patients recover within 3 to 7 days.”
“Usually within a month, their [heart] function returns to normal,” Dr. Stevens says.
Getting one’s full energy back can take longer, as Dr. Kamil found. “It was about 6 months before I was up to speed.”
Survivors talk
Looking back, Dr. Kamil realizes now how much stress she was under before her episode.
“I took care of chronically ill kids,” she says, and worried about them. “I’m kind of a mother hen.”
Besides patient care and her cross-county meeting planning, she was flying back and forth to Florida to tend to her mother, who had chronic health problems. She was also managing that year’s annual media prize at a San Diego university that she and her husband established after the death of their adult son several years before.
“I was busy with that, and it is a bittersweet experience,” she says.
She is trying to take her cardiologist’s advice to slow down.
“I used to be notorious for saying, ‘I need to get one more thing done,’” she says.
Joanie Simpson says she, too, has slowed down. She was diagnosed with broken heart in 2016, after a cascade of stressful events. Her son was facing back surgery, her son-in-law had lost his job, and her tiny Yorkshire terrier Meha died. And she and her husband, Benny, had issues with their rental property.
Now 66 and retired in Camp Wood, Texas, she has learned to enjoy life and worry a little less. Music is one way.
“We’re Parrotheads,” she says, referencing the nickname given to fans of singer Jimmy Buffett. “We listen to Buffett and to ’60s, ’70s, ’80s music. We dance around the house. We aren’t big tavern goers, so we dance around the living room and hope we don’t fall over the coffee table. So far, so good.”
They have plans to buy a small pontoon boat and go fishing. Benny especially loves that idea, she says, laughing, as he finds it’s the only time she stops talking.
Reducing the what-ifs
Patients have a common question and worry: What if it happens again?
“I definitely worried more about it in the beginning,” Dr. Kamil says. “Could I have permanent heart damage? Will I be a cardiac cripple?” Her worry has eased.
If you suspect the condition, ‘’get yourself to a provider who knows about it,” she says.
Cardiologists are very likely to suspect the condition, Dr. Bybee says, as are doctors working in a large-volume emergency department.
Dr. Stevens, of St. Luke’s, is straightforward, telling her patients what is known and what is not about the condition. She recommends her patients go to cardiac rehab.
“It gives them that confidence to know what they can do,” she says.
She also gives lifestyle advice, suggesting patients get a home blood pressure cuff and use it. She suggests paying attention to good nutrition and exercise and not lifting anything so heavy that grunting is necessary.
Focus on protecting heart health, Dr. Cheng tells patients. She encourages them to find the stress reduction plan that works for them. Most important, she tells patients to understand that it is not their fault.
A version of this article first appeared on WebMD.com.
As a pediatric kidney doctor, Elaine S. Kamil, MD, is used to long hours helping children and teens with a variety of issues, some very serious, and also makes time to give back to her specialty.
In late 2013, she was in Washington, D.C., planning a meeting of the American Society of Nephrology. When the organizers decided at the last minute that another session was needed, she stayed late, putting it together. Then she hopped on a plane and returned home to Los Angeles on a Saturday night.
Right after midnight, Dr. Kamil knew something was wrong.
“I had really severe chest pain,” she says. “I have reflux, and I know what that feels like. This was much more intense. It really hurt.” She debated: “Should I wake up my husband?”
Soon, the pain got so bad, she had to.
At the hospital, an electrocardiogram was slightly abnormal, as was a blood test that measures damage to the heart. Next, she got an angiogram, an imaging technique to visualize the heart. Once doctors looked at the image on the screen during the angiogram, they knew the diagnosis: Broken heart syndrome, known medically as takotsubo cardiomyopathy or stress-induced cardiomyopathy. As the name suggests, it’s triggered by extreme stress or loss.
The telltale clue to the diagnosis is the appearance of the walls of the heart’s left ventricle, its main pumping chamber. When the condition is present, the left ventricle changes shape, developing a narrow neck and a round bottom, resembling an octopus pot called takotsubo used by fishermen in Japan, where the condition was first recognized in 1990.
Like most who are affected, Dr. Kamil, now 74, is fine now. She is still actively working, as a researcher and professor emerita at Cedars-Sinai Medical Center and a health sciences clinical professor of pediatrics at UCLA. But she focuses more now on stress reduction.
Study: condition on the rise
New research from Cedars-Sinai suggests that broken heart syndrome, while still not common, is not as rare as once thought. And it’s on the rise, especially among middle-age and older women.
This ‘’middle” group – women ages 50 to 74 – had the greatest rate of increase over the years studied, 2006-2017, says Susan Cheng, MD, lead author of the study, published in the Journal of the American Heart Association. She is the director of the Institute for Research on Healthy Aging at the Smidt Heart Institute at Cedars-Sinai Medical Center.
Dr. Cheng and her team used national hospital inpatient data collected from more than 135,000 men and women diagnosed with the condition during the 12 years of the study. More than 88% of all cases were women, especially in those age 50 or older. When the researchers looked more closely, they found the diagnosis has been increasing at least 6 to 10 times more rapidly for women in the 50-to-74 age group than in any other group.
For every case of the condition in younger women, or in men of all age groups, the researchers found an additional 10 cases for middle-aged women and six additional cases for older women. For example, while the syndrome occurred in 15 younger women per million per year, it occurred in 128 middle aged women per year.
The age groups found most at risk was surprising, says Dr. Cheng, who expected the risk would be highest in the oldest age group of women, those over 75.
While doctors are more aware of the condition now, “it’s not just the increased recognition,” she says. “There is something going on” driving the continual increase. It probably has something to do with environmental changes, she says.
Hormones and hormonal differences between men and women aren’t the whole story either, she says. Her team will study it further, hoping eventually to find who might be more likely to get the condition by talking to those who have had it and collecting clues. “There probably is some underlying genetic predisposition,” she says.
“The neural hormones that drive the flight-or-fight response (such as adrenaline) are definitely elevated,” she says. “The brain and the heart are talking to each other.”
Experts say these surging stress hormones essentially “stun” the heart, affecting how it functions. The question is, what makes women particularly more susceptible to being excessively triggered when exposed to stress? That is unclear, Dr. Cheng says.
While the condition is a frightening experience, ‘’the overall prognosis is much better than having a garden-variety heart attack,” she says.
But researchers are still figuring out long-term outcomes, and she can’t tell patients if they are likely to have another episode.
Research findings reflected in practice
Other cardiologists say they are not surprised by the new findings.
“I think it’s very consistent with what I am seeing clinically,” says Tracy Stevens, MD, a cardiologist at Saint Luke’s Mid America Heart Institute in Kansas City, MO. In the last 5 years, she has diagnosed at least 100 cases, she says. The increase is partly but not entirely due to increased awareness by doctors of the condition, she agrees.
If a postmenopausal woman comes to the hospital with chest pain, the condition is more likely now than in the past to be suspected, says Dr. Stevens, who’s also the medical director of the Muriel I. Kauffman Women’s Heart Center at Saint Luke’s. The octopus pot-like image is hard to miss.
“What we see at the base of the left ventricle is, it is squeezing like crazy, it is ballooning.”
“We probably see at least five to ten a month,” says Kevin Bybee, MD, an associate professor of medicine at the University of Missouri-Kansas City School of Medicine.
The increase in numbers found by the Los Angeles researchers may not even capture the true picture of how many people have gotten this condition, he says. He suspects some women whose deaths are blamed on sudden cardiac death might actually have had broken heart syndrome.
“I have always wondered how many don’t make it to the hospital.”
Dr. Bybee, who’s also medical director of cardiovascular services at St. Luke’s South in Overland Park, KS, became interested in the syndrome during his fellowship at Mayo Clinic when he diagnosed three patients in just 2 months. He and his team published the case histories of seven patients in 2004. Since then, many more reports have been published.
Researchers from Texas used the same national database as the Cedars researchers to look at cases from 2005 to 2014, and also found an increase. But study co-author Abhijeet Dhoble, MD, a cardiologist and associate professor of medicine at UT Health Science Center and Memorial Hermann-Texas Medical Center in Houston, believes more recognition explains most of the increase.
And the pandemic is now playing a role in driving up cases, he says.
“In the last 2 years, we have been noticing increasing numbers of cases, probably due to the pandemic,” he says.
Profiles of cases
Over the years, Dr. Bybee has collected information on what is happening before the heart begins to go haywire.
“Fifteen to twenty percent of the time, there is no obvious trigger,” he says.
Other times, a stressful emotional event, such as the death of a spouse or a severe car accident, can trigger it.
One patient with an extreme fear of public speaking had to give a talk in front of a large group when she was new to a job. Another woman lost money at a casino before it happened, Dr. Bybee says. Yet another patient took her dog out for a walk in the woods, and the dog got caught in a raccoon trap.
Fierce arguments as well as surprise parties have triggered the condition, Dr. Bybee says. Physical problems such as asthma or sepsis, a life-threatening complication of an infection, can also trigger broken heart.
“It’s challenging because this is unpredictable,” he says.
Treatments and recovery
The condition is rarely fatal, say experts from Harvard and Mayo Clinic, but some can have complications such as heart failure.
There are no standard guidelines for treatment, Dr. Dhoble, of Memorial Hermann, says. “We give medications to keep blood pressures in the optimal range.” Doctors may also prescribe lipid-lowering medicines and blood thinner medications. “Most patients recover within 3 to 7 days.”
“Usually within a month, their [heart] function returns to normal,” Dr. Stevens says.
Getting one’s full energy back can take longer, as Dr. Kamil found. “It was about 6 months before I was up to speed.”
Survivors talk
Looking back, Dr. Kamil realizes now how much stress she was under before her episode.
“I took care of chronically ill kids,” she says, and worried about them. “I’m kind of a mother hen.”
Besides patient care and her cross-county meeting planning, she was flying back and forth to Florida to tend to her mother, who had chronic health problems. She was also managing that year’s annual media prize at a San Diego university that she and her husband established after the death of their adult son several years before.
“I was busy with that, and it is a bittersweet experience,” she says.
She is trying to take her cardiologist’s advice to slow down.
“I used to be notorious for saying, ‘I need to get one more thing done,’” she says.
Joanie Simpson says she, too, has slowed down. She was diagnosed with broken heart in 2016, after a cascade of stressful events. Her son was facing back surgery, her son-in-law had lost his job, and her tiny Yorkshire terrier Meha died. And she and her husband, Benny, had issues with their rental property.
Now 66 and retired in Camp Wood, Texas, she has learned to enjoy life and worry a little less. Music is one way.
“We’re Parrotheads,” she says, referencing the nickname given to fans of singer Jimmy Buffett. “We listen to Buffett and to ’60s, ’70s, ’80s music. We dance around the house. We aren’t big tavern goers, so we dance around the living room and hope we don’t fall over the coffee table. So far, so good.”
They have plans to buy a small pontoon boat and go fishing. Benny especially loves that idea, she says, laughing, as he finds it’s the only time she stops talking.
Reducing the what-ifs
Patients have a common question and worry: What if it happens again?
“I definitely worried more about it in the beginning,” Dr. Kamil says. “Could I have permanent heart damage? Will I be a cardiac cripple?” Her worry has eased.
If you suspect the condition, ‘’get yourself to a provider who knows about it,” she says.
Cardiologists are very likely to suspect the condition, Dr. Bybee says, as are doctors working in a large-volume emergency department.
Dr. Stevens, of St. Luke’s, is straightforward, telling her patients what is known and what is not about the condition. She recommends her patients go to cardiac rehab.
“It gives them that confidence to know what they can do,” she says.
She also gives lifestyle advice, suggesting patients get a home blood pressure cuff and use it. She suggests paying attention to good nutrition and exercise and not lifting anything so heavy that grunting is necessary.
Focus on protecting heart health, Dr. Cheng tells patients. She encourages them to find the stress reduction plan that works for them. Most important, she tells patients to understand that it is not their fault.
A version of this article first appeared on WebMD.com.
Estimating insulin resistance may help predict stroke, death in T2D
Calculating the estimated glucose disposal rate (eGDR) as a proxy for the level of insulin resistance may be useful way to determine if someone with type 2 diabetes (T2D) is at risk for having a first stroke, Swedish researchers have found.
In a large population-based study, the lower the eGDR score went, the higher the risk for having a first stroke became.
The eGDR score was also predictive of the chance of dying from any or a cardiovascular cause, Alexander Zabala, MD, reported at the annual meeting of the European Association for the Study of Diabetes (Abstract OP 01-4).
The link between insulin resistance and an increased risk for stroke has been known for some time, and not just in people with T2D. However, the current way of determining insulin resistance is not suitable for widespread practice.
“The goal standard technique for measuring insulin resistance is the euglycemic clamp method,” said Dr. Zabala, an internal medical resident at Södersjukhuset hospital and researcher at the Karolinska Institutet in Stockholm.
“For that reason, [the eGDR], a method based on readily available clinical factors – waist circumference, hypertension, and glycosylated hemoglobin was developed,” he explained. Body mass index can also be used in place of waist circumference, he qualified.
The eGDR has already been proven to be very precise in people with type 1 diabetes, said Dr. Zabala, and could be an “excellent tool to measure insulin resistance in a large patient population.”
Investigating the link between eGDR and first stroke risk
The aim of the study he presented was to see if changes in the eGDR were associated with changes in the risk of someone with T2D experiencing a first stroke, or dying from a cardiovascular or other cause.
An observational cohort was formed by first considering data on all adult patients with T2D who were logged in the Swedish National Diabetes Registry (NDR) during 2004-2016. Then anyone with a history of stroke, or with any missing data on the clinical variables needed to calculate the eGDR, were excluded.
This resulted in an overall population of 104,697 individuals, aged a mean of 63 years, who had developed T2D at around the age of 59 years. About 44% of the study population were women. The mean eGDR for the whole population was 5.6 mg/kg per min.
The study subjects were grouped according to four eGDR levels: 24,706 were in the lowest quartile of eGDR (less than 4 mg/kg per min), signifying the highest level of insulin resistance, and 18,762 were in the upper quartile of eGDR (greater than 8 mg/kg per min), signifying the lowest level of insulin resistance. The middle two groups had an eGDR between 4 and 6 mg/kg per min (40,187), and 6 and 8 mg/kg/min (21,042).
Data from the NDR were then combined with the Swedish Cause of Death register, the Swedish In-patient Care Diagnoses registry, and the Longitudinal Database for Health Insurance and Labour Market Studies (LISA) to determine the rates of stroke, ischemic stroke, hemorrhagic stroke, all-cause mortality, and cardiovascular mortality.
Increasing insulin resistance ups risk for stroke, death
After a median follow-up of 5.6 years, 4% (4,201) of the study population had had a stroke.
“We clearly see an increased occurrence of first-time stroke in the group with the lowest eGDR, indicating worst insulin resistance, in comparison with the group with the highest eGDR, indicating less insulin resistance,” Dr. Zabala reported.
After adjustment for potential confounding factors, including age at baseline, gender, diabetes duration, among other variables, the risk for stroke was lowest in those with a high eGDR value and highest for those with a low eGDR value.
Using individuals with the lowest eGDR (less than 4 mg/kg per min) and thus greatest risk of stroke as the reference, adjusted hazard ratios (aHR) for first-time stroke were: 0.60, 0.68, and 0.77 for those with an eGDR of greater than 8, 6-8, and 4-6 mg/kg per min, respectively.
The corresponding values for risk of ischemic stroke were 0.55, 0.68, and 0.75. Regarding hemorrhagic stroke, there was no statistically significant correlation between eGDR levels and stroke occurrence. This was due to the small number of cases recorded.
As for all-cause and cardiovascular mortality, a similar pattern was seen, with higher rates of death linked to increasing insulin resistance. Adjusted hazard ratios according to increasing insulin resistance (decreasing eGDR scores) for all-cause death were 0.68, 0.75, and 0.82 and for cardiovascular mortality were 0.65, 0.75, and 0.82.
A sensitivity analysis, using BMI instead of waist circumference to calculate the eGDR, showed a similar pattern, and “interestingly, a correlation between eGDR levels and risk of hemorrhagic stroke.” Dr. Zabala said.
Limitations and take-homes
Of course, this is an observational cohort study, so no conclusions on causality can be made and there are no data on the use of anti-diabetic treatments specifically. But there are strengths such as covering almost all adults with T2D in Sweden and a relatively long-follow-up time.
The findings suggest that “eGDR, which may reflect insulin resistance may be a useful risk marker for stroke and death in people with type 2 diabetes,” said Dr. Zabala.
“You had a very large cohort, and that certainly makes your results very valid,” observed Peter Novodvorsky, MUDr. (Hons), PhD, MRCP, a consultant diabetologist in Trenčín, Slovakia.
Dr. Novodvorsky, who chaired the session, picked up on the lack of information about how many people were taking newer diabetes drugs, such as the glucagon-like peptide 1 receptor antagonists and sodium glucose-lowering transport 2 inhibitors.
“As we all know, these might have protective effects which are not necessarily related to the glucose lowering or insulin resistance-lowering” effects, so could have influenced the results. In terms of how practical the eGDR is for clinical practice, Dr. Zabala observed in a press release: “eGDR could be used to help T2D patients better understand and manage their risk of stroke and death.
“It could also be of importance in research. In this era of personalized medicine, better stratification of type 2 diabetes patients will help optimize clinical trials and further vital research into treatment, diagnosis, care and prevention.”
The research was a collaboration between the Karolinska Institutet, Gothenburg University and the Swedish National Diabetes Registry. Dr. Zabala and coauthors reported having no conflicts of interest.
Calculating the estimated glucose disposal rate (eGDR) as a proxy for the level of insulin resistance may be useful way to determine if someone with type 2 diabetes (T2D) is at risk for having a first stroke, Swedish researchers have found.
In a large population-based study, the lower the eGDR score went, the higher the risk for having a first stroke became.
The eGDR score was also predictive of the chance of dying from any or a cardiovascular cause, Alexander Zabala, MD, reported at the annual meeting of the European Association for the Study of Diabetes (Abstract OP 01-4).
The link between insulin resistance and an increased risk for stroke has been known for some time, and not just in people with T2D. However, the current way of determining insulin resistance is not suitable for widespread practice.
“The goal standard technique for measuring insulin resistance is the euglycemic clamp method,” said Dr. Zabala, an internal medical resident at Södersjukhuset hospital and researcher at the Karolinska Institutet in Stockholm.
“For that reason, [the eGDR], a method based on readily available clinical factors – waist circumference, hypertension, and glycosylated hemoglobin was developed,” he explained. Body mass index can also be used in place of waist circumference, he qualified.
The eGDR has already been proven to be very precise in people with type 1 diabetes, said Dr. Zabala, and could be an “excellent tool to measure insulin resistance in a large patient population.”
Investigating the link between eGDR and first stroke risk
The aim of the study he presented was to see if changes in the eGDR were associated with changes in the risk of someone with T2D experiencing a first stroke, or dying from a cardiovascular or other cause.
An observational cohort was formed by first considering data on all adult patients with T2D who were logged in the Swedish National Diabetes Registry (NDR) during 2004-2016. Then anyone with a history of stroke, or with any missing data on the clinical variables needed to calculate the eGDR, were excluded.
This resulted in an overall population of 104,697 individuals, aged a mean of 63 years, who had developed T2D at around the age of 59 years. About 44% of the study population were women. The mean eGDR for the whole population was 5.6 mg/kg per min.
The study subjects were grouped according to four eGDR levels: 24,706 were in the lowest quartile of eGDR (less than 4 mg/kg per min), signifying the highest level of insulin resistance, and 18,762 were in the upper quartile of eGDR (greater than 8 mg/kg per min), signifying the lowest level of insulin resistance. The middle two groups had an eGDR between 4 and 6 mg/kg per min (40,187), and 6 and 8 mg/kg/min (21,042).
Data from the NDR were then combined with the Swedish Cause of Death register, the Swedish In-patient Care Diagnoses registry, and the Longitudinal Database for Health Insurance and Labour Market Studies (LISA) to determine the rates of stroke, ischemic stroke, hemorrhagic stroke, all-cause mortality, and cardiovascular mortality.
Increasing insulin resistance ups risk for stroke, death
After a median follow-up of 5.6 years, 4% (4,201) of the study population had had a stroke.
“We clearly see an increased occurrence of first-time stroke in the group with the lowest eGDR, indicating worst insulin resistance, in comparison with the group with the highest eGDR, indicating less insulin resistance,” Dr. Zabala reported.
After adjustment for potential confounding factors, including age at baseline, gender, diabetes duration, among other variables, the risk for stroke was lowest in those with a high eGDR value and highest for those with a low eGDR value.
Using individuals with the lowest eGDR (less than 4 mg/kg per min) and thus greatest risk of stroke as the reference, adjusted hazard ratios (aHR) for first-time stroke were: 0.60, 0.68, and 0.77 for those with an eGDR of greater than 8, 6-8, and 4-6 mg/kg per min, respectively.
The corresponding values for risk of ischemic stroke were 0.55, 0.68, and 0.75. Regarding hemorrhagic stroke, there was no statistically significant correlation between eGDR levels and stroke occurrence. This was due to the small number of cases recorded.
As for all-cause and cardiovascular mortality, a similar pattern was seen, with higher rates of death linked to increasing insulin resistance. Adjusted hazard ratios according to increasing insulin resistance (decreasing eGDR scores) for all-cause death were 0.68, 0.75, and 0.82 and for cardiovascular mortality were 0.65, 0.75, and 0.82.
A sensitivity analysis, using BMI instead of waist circumference to calculate the eGDR, showed a similar pattern, and “interestingly, a correlation between eGDR levels and risk of hemorrhagic stroke.” Dr. Zabala said.
Limitations and take-homes
Of course, this is an observational cohort study, so no conclusions on causality can be made and there are no data on the use of anti-diabetic treatments specifically. But there are strengths such as covering almost all adults with T2D in Sweden and a relatively long-follow-up time.
The findings suggest that “eGDR, which may reflect insulin resistance may be a useful risk marker for stroke and death in people with type 2 diabetes,” said Dr. Zabala.
“You had a very large cohort, and that certainly makes your results very valid,” observed Peter Novodvorsky, MUDr. (Hons), PhD, MRCP, a consultant diabetologist in Trenčín, Slovakia.
Dr. Novodvorsky, who chaired the session, picked up on the lack of information about how many people were taking newer diabetes drugs, such as the glucagon-like peptide 1 receptor antagonists and sodium glucose-lowering transport 2 inhibitors.
“As we all know, these might have protective effects which are not necessarily related to the glucose lowering or insulin resistance-lowering” effects, so could have influenced the results. In terms of how practical the eGDR is for clinical practice, Dr. Zabala observed in a press release: “eGDR could be used to help T2D patients better understand and manage their risk of stroke and death.
“It could also be of importance in research. In this era of personalized medicine, better stratification of type 2 diabetes patients will help optimize clinical trials and further vital research into treatment, diagnosis, care and prevention.”
The research was a collaboration between the Karolinska Institutet, Gothenburg University and the Swedish National Diabetes Registry. Dr. Zabala and coauthors reported having no conflicts of interest.
Calculating the estimated glucose disposal rate (eGDR) as a proxy for the level of insulin resistance may be useful way to determine if someone with type 2 diabetes (T2D) is at risk for having a first stroke, Swedish researchers have found.
In a large population-based study, the lower the eGDR score went, the higher the risk for having a first stroke became.
The eGDR score was also predictive of the chance of dying from any or a cardiovascular cause, Alexander Zabala, MD, reported at the annual meeting of the European Association for the Study of Diabetes (Abstract OP 01-4).
The link between insulin resistance and an increased risk for stroke has been known for some time, and not just in people with T2D. However, the current way of determining insulin resistance is not suitable for widespread practice.
“The goal standard technique for measuring insulin resistance is the euglycemic clamp method,” said Dr. Zabala, an internal medical resident at Södersjukhuset hospital and researcher at the Karolinska Institutet in Stockholm.
“For that reason, [the eGDR], a method based on readily available clinical factors – waist circumference, hypertension, and glycosylated hemoglobin was developed,” he explained. Body mass index can also be used in place of waist circumference, he qualified.
The eGDR has already been proven to be very precise in people with type 1 diabetes, said Dr. Zabala, and could be an “excellent tool to measure insulin resistance in a large patient population.”
Investigating the link between eGDR and first stroke risk
The aim of the study he presented was to see if changes in the eGDR were associated with changes in the risk of someone with T2D experiencing a first stroke, or dying from a cardiovascular or other cause.
An observational cohort was formed by first considering data on all adult patients with T2D who were logged in the Swedish National Diabetes Registry (NDR) during 2004-2016. Then anyone with a history of stroke, or with any missing data on the clinical variables needed to calculate the eGDR, were excluded.
This resulted in an overall population of 104,697 individuals, aged a mean of 63 years, who had developed T2D at around the age of 59 years. About 44% of the study population were women. The mean eGDR for the whole population was 5.6 mg/kg per min.
The study subjects were grouped according to four eGDR levels: 24,706 were in the lowest quartile of eGDR (less than 4 mg/kg per min), signifying the highest level of insulin resistance, and 18,762 were in the upper quartile of eGDR (greater than 8 mg/kg per min), signifying the lowest level of insulin resistance. The middle two groups had an eGDR between 4 and 6 mg/kg per min (40,187), and 6 and 8 mg/kg/min (21,042).
Data from the NDR were then combined with the Swedish Cause of Death register, the Swedish In-patient Care Diagnoses registry, and the Longitudinal Database for Health Insurance and Labour Market Studies (LISA) to determine the rates of stroke, ischemic stroke, hemorrhagic stroke, all-cause mortality, and cardiovascular mortality.
Increasing insulin resistance ups risk for stroke, death
After a median follow-up of 5.6 years, 4% (4,201) of the study population had had a stroke.
“We clearly see an increased occurrence of first-time stroke in the group with the lowest eGDR, indicating worst insulin resistance, in comparison with the group with the highest eGDR, indicating less insulin resistance,” Dr. Zabala reported.
After adjustment for potential confounding factors, including age at baseline, gender, diabetes duration, among other variables, the risk for stroke was lowest in those with a high eGDR value and highest for those with a low eGDR value.
Using individuals with the lowest eGDR (less than 4 mg/kg per min) and thus greatest risk of stroke as the reference, adjusted hazard ratios (aHR) for first-time stroke were: 0.60, 0.68, and 0.77 for those with an eGDR of greater than 8, 6-8, and 4-6 mg/kg per min, respectively.
The corresponding values for risk of ischemic stroke were 0.55, 0.68, and 0.75. Regarding hemorrhagic stroke, there was no statistically significant correlation between eGDR levels and stroke occurrence. This was due to the small number of cases recorded.
As for all-cause and cardiovascular mortality, a similar pattern was seen, with higher rates of death linked to increasing insulin resistance. Adjusted hazard ratios according to increasing insulin resistance (decreasing eGDR scores) for all-cause death were 0.68, 0.75, and 0.82 and for cardiovascular mortality were 0.65, 0.75, and 0.82.
A sensitivity analysis, using BMI instead of waist circumference to calculate the eGDR, showed a similar pattern, and “interestingly, a correlation between eGDR levels and risk of hemorrhagic stroke.” Dr. Zabala said.
Limitations and take-homes
Of course, this is an observational cohort study, so no conclusions on causality can be made and there are no data on the use of anti-diabetic treatments specifically. But there are strengths such as covering almost all adults with T2D in Sweden and a relatively long-follow-up time.
The findings suggest that “eGDR, which may reflect insulin resistance may be a useful risk marker for stroke and death in people with type 2 diabetes,” said Dr. Zabala.
“You had a very large cohort, and that certainly makes your results very valid,” observed Peter Novodvorsky, MUDr. (Hons), PhD, MRCP, a consultant diabetologist in Trenčín, Slovakia.
Dr. Novodvorsky, who chaired the session, picked up on the lack of information about how many people were taking newer diabetes drugs, such as the glucagon-like peptide 1 receptor antagonists and sodium glucose-lowering transport 2 inhibitors.
“As we all know, these might have protective effects which are not necessarily related to the glucose lowering or insulin resistance-lowering” effects, so could have influenced the results. In terms of how practical the eGDR is for clinical practice, Dr. Zabala observed in a press release: “eGDR could be used to help T2D patients better understand and manage their risk of stroke and death.
“It could also be of importance in research. In this era of personalized medicine, better stratification of type 2 diabetes patients will help optimize clinical trials and further vital research into treatment, diagnosis, care and prevention.”
The research was a collaboration between the Karolinska Institutet, Gothenburg University and the Swedish National Diabetes Registry. Dr. Zabala and coauthors reported having no conflicts of interest.
FROM EASD 2021
No benefit from lower temps for out-of-hospital cardiac arrest
The results “do not support the use of moderate therapeutic hypothermia to improve neurologic outcomes in comatose survivors of out-of-hospital cardiac arrest,” write the investigators led by Michel Le May, MD, from the University of Ottawa Heart Institute, Ontario, Canada.
The CAPITAL CHILL results were first presented at the American College of Cardiology (ACC) 2021 Scientific Sessions in May.
They have now been published online, October 19, in JAMA.
High rates of brain injury and death
Comatose survivors of OHCA have high rates of severe brain injury and death. Current guidelines recommend targeted temperature management at 32°C to 36°C for 24 hours. However, small studies have suggested a potential benefit of targeting lower body temperatures.
In the CAPITAL CHILL study of 367 OHCA patients who were comatose on admission, there were no statistically significant differences in the primary composite outcome of all-cause mortality or poor neurologic outcome at 180 days with mild-versus-moderate hypothermia.
The primary composite outcome occurred in 89 of 184 (48.4%) patients in the moderate hypothermia group and 83 of 183 (45.4%) patients in the mild hypothermia group — a risk difference of 3.0% (95% confidence interval [CI], 7.2% - 13.2%) and relative risk of 1.07 (95% CI, 0.86 - 1.33; P = .56).
There was also no significant difference when looking at the individual components of mortality (43.5% vs 41.0%) and poor neurologic outcome (Disability Rating Scale score >5: 4.9% vs 4.4%).
The baseline characteristics of patients were similar in the moderate and mild hypothermia groups. The lack of a significant difference in the primary outcome was consistent after adjusting for baseline covariates as well as across all subgroups.
The rates of secondary outcomes were also similar between the two groups, except for a longer length of stay in the intensive care unit in the moderate hypothermia group compared with the mild hypothermia group, which would likely add to overall costs.
The researchers note that the Targeted Hypothermia vs Targeted Normothermia After Out-of-Hospital Cardiac Arrest (TTM2) trial recently reported that targeted hypothermia at 33°C did not improve survival at 180 days compared with targeted normothermia at 37.5°C or less.
The CAPITAL CHILL study “adds to the spectrum of target temperature management, as it did not find any benefit of even further lowering temperatures to 31°C,” the study team says.
They caution that most patients in the trial had cardiac arrest secondary to a primary cardiac etiology and therefore the findings may not be applicable to cardiac arrest of all etiologies.
It’s also possible that the trial was underpowered to detect clinically important differences between moderate and mild hypothermia. Also, the number of patients presenting with a nonshockable rhythm was relatively small, and further study may be worthwhile in this subgroup, they say.
For now, however, the CAPITAL CHILL results provide no support for a lower target temperature of 31°C to improve outcomes in OHCA patients, Dr. Le May and colleagues conclude.
CAPITAL CHILL was an investigator-initiated study and funding was provided by the University of Ottawa Heart Institute Cardiac Arrest Program. Dr. Le May has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The results “do not support the use of moderate therapeutic hypothermia to improve neurologic outcomes in comatose survivors of out-of-hospital cardiac arrest,” write the investigators led by Michel Le May, MD, from the University of Ottawa Heart Institute, Ontario, Canada.
The CAPITAL CHILL results were first presented at the American College of Cardiology (ACC) 2021 Scientific Sessions in May.
They have now been published online, October 19, in JAMA.
High rates of brain injury and death
Comatose survivors of OHCA have high rates of severe brain injury and death. Current guidelines recommend targeted temperature management at 32°C to 36°C for 24 hours. However, small studies have suggested a potential benefit of targeting lower body temperatures.
In the CAPITAL CHILL study of 367 OHCA patients who were comatose on admission, there were no statistically significant differences in the primary composite outcome of all-cause mortality or poor neurologic outcome at 180 days with mild-versus-moderate hypothermia.
The primary composite outcome occurred in 89 of 184 (48.4%) patients in the moderate hypothermia group and 83 of 183 (45.4%) patients in the mild hypothermia group — a risk difference of 3.0% (95% confidence interval [CI], 7.2% - 13.2%) and relative risk of 1.07 (95% CI, 0.86 - 1.33; P = .56).
There was also no significant difference when looking at the individual components of mortality (43.5% vs 41.0%) and poor neurologic outcome (Disability Rating Scale score >5: 4.9% vs 4.4%).
The baseline characteristics of patients were similar in the moderate and mild hypothermia groups. The lack of a significant difference in the primary outcome was consistent after adjusting for baseline covariates as well as across all subgroups.
The rates of secondary outcomes were also similar between the two groups, except for a longer length of stay in the intensive care unit in the moderate hypothermia group compared with the mild hypothermia group, which would likely add to overall costs.
The researchers note that the Targeted Hypothermia vs Targeted Normothermia After Out-of-Hospital Cardiac Arrest (TTM2) trial recently reported that targeted hypothermia at 33°C did not improve survival at 180 days compared with targeted normothermia at 37.5°C or less.
The CAPITAL CHILL study “adds to the spectrum of target temperature management, as it did not find any benefit of even further lowering temperatures to 31°C,” the study team says.
They caution that most patients in the trial had cardiac arrest secondary to a primary cardiac etiology and therefore the findings may not be applicable to cardiac arrest of all etiologies.
It’s also possible that the trial was underpowered to detect clinically important differences between moderate and mild hypothermia. Also, the number of patients presenting with a nonshockable rhythm was relatively small, and further study may be worthwhile in this subgroup, they say.
For now, however, the CAPITAL CHILL results provide no support for a lower target temperature of 31°C to improve outcomes in OHCA patients, Dr. Le May and colleagues conclude.
CAPITAL CHILL was an investigator-initiated study and funding was provided by the University of Ottawa Heart Institute Cardiac Arrest Program. Dr. Le May has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The results “do not support the use of moderate therapeutic hypothermia to improve neurologic outcomes in comatose survivors of out-of-hospital cardiac arrest,” write the investigators led by Michel Le May, MD, from the University of Ottawa Heart Institute, Ontario, Canada.
The CAPITAL CHILL results were first presented at the American College of Cardiology (ACC) 2021 Scientific Sessions in May.
They have now been published online, October 19, in JAMA.
High rates of brain injury and death
Comatose survivors of OHCA have high rates of severe brain injury and death. Current guidelines recommend targeted temperature management at 32°C to 36°C for 24 hours. However, small studies have suggested a potential benefit of targeting lower body temperatures.
In the CAPITAL CHILL study of 367 OHCA patients who were comatose on admission, there were no statistically significant differences in the primary composite outcome of all-cause mortality or poor neurologic outcome at 180 days with mild-versus-moderate hypothermia.
The primary composite outcome occurred in 89 of 184 (48.4%) patients in the moderate hypothermia group and 83 of 183 (45.4%) patients in the mild hypothermia group — a risk difference of 3.0% (95% confidence interval [CI], 7.2% - 13.2%) and relative risk of 1.07 (95% CI, 0.86 - 1.33; P = .56).
There was also no significant difference when looking at the individual components of mortality (43.5% vs 41.0%) and poor neurologic outcome (Disability Rating Scale score >5: 4.9% vs 4.4%).
The baseline characteristics of patients were similar in the moderate and mild hypothermia groups. The lack of a significant difference in the primary outcome was consistent after adjusting for baseline covariates as well as across all subgroups.
The rates of secondary outcomes were also similar between the two groups, except for a longer length of stay in the intensive care unit in the moderate hypothermia group compared with the mild hypothermia group, which would likely add to overall costs.
The researchers note that the Targeted Hypothermia vs Targeted Normothermia After Out-of-Hospital Cardiac Arrest (TTM2) trial recently reported that targeted hypothermia at 33°C did not improve survival at 180 days compared with targeted normothermia at 37.5°C or less.
The CAPITAL CHILL study “adds to the spectrum of target temperature management, as it did not find any benefit of even further lowering temperatures to 31°C,” the study team says.
They caution that most patients in the trial had cardiac arrest secondary to a primary cardiac etiology and therefore the findings may not be applicable to cardiac arrest of all etiologies.
It’s also possible that the trial was underpowered to detect clinically important differences between moderate and mild hypothermia. Also, the number of patients presenting with a nonshockable rhythm was relatively small, and further study may be worthwhile in this subgroup, they say.
For now, however, the CAPITAL CHILL results provide no support for a lower target temperature of 31°C to improve outcomes in OHCA patients, Dr. Le May and colleagues conclude.
CAPITAL CHILL was an investigator-initiated study and funding was provided by the University of Ottawa Heart Institute Cardiac Arrest Program. Dr. Le May has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AHA: Quality of STEMI care has stalled, needs improvement
Following up on its 2007 initiative to improve care for people who have ST-segment elevation myocardial infarction (STEMI), the American Heart Association has issued a policy statement that includes a host of recommendations to further overcome barriers to optimal care for this most severe type of heart attack.
The statement recommends steps for designing what the writing committee calls “the ideal STEMI system of care” for patients who have these severe heart attacks.
The focus of the policy statement is the AHA’s Mission: Lifeline national initiative to coordinate and improve the quality of care to patients with STEMI, which was introduced in 2007. Since then, the number or participating hospitals has increased from 485 to 857, now covering more than 85% of the U.S. population, noted the new statement, published online in Circulation.
“Bringing STEMI referring hospitals, STEMI receiving centers and emergency medical services [EMS] together in the development of local and regional systems of care within the AHA’s Mission: Lifeline program has led to significant improvement in time to treatment and outcomes for patients with STEMI,” Alice K. Jacobs, MD, lead statement author and vice chair for clinical affairs in the department of medicine at Boston Medical Center and a professor at Boston University, said in an interview.
“Yet,” Dr. Jacobs added, “opportunities exist to further improve the coordination of care and address remaining barriers to providing ideal care. Moreover, Mission: Lifeline systems of care have been extended to other time-sensitive cardiovascular disorders including stroke and out-of-hospital cardiac arrest.”
The statement itself noted, “Although there have been significant improvements in patients with STEMI receiving guideline-recommended care, progress has slowed during the past few years.” From 2008 to 2012, a number of key quality care measures at participating hospitals had improved markedly. For example, door-in-door-out (DIDO) transfers improved from a median of 76 to 62 minutes (P < .001).
However, from 2012 to 2019, with more hospitals participating, while many key measures improved, a few either plateaued or worsened slightly. Median DIDO time, for example – again, with more hospitals participating, compared with the earlier dataset – went from 45 in 2012 to 48 in 2019, according to AHA data.
Key recommendations aim to impact and improve hospital care for patients with STEMI, Dr. Jacobs said. “In addition to avoiding patient delay at the onset of recognized symptoms of a heart attack, accessing 911 and following EMS destination protocols, the prehospital activation of the cardiac catheterization lab and providing a 911 response for interhospital transport as well as direct-to-cardiac-catheterization-lab transport bypassing the emergency department when appropriate would all impact and improve hospital care.”
Other key recommendations of the statement include:
- Increasing public awareness of heart attack signs and symptoms and the importance for calling 911.
- Addressing post-MI care, including use of evidence-based practices for cardiac rehabilitation and even getting insurance companies to encourage cardiac rehab through incentives.
- Engaging rural hospitals by leveraging telemedicine to expedite percutaneous coronary intervention (PCI) and by developing systems for treatment protocols and rapid transport among facilities.
- Tearing down financial barriers with a global reimbursement model that encompasses each stop in a patient’s journey through the care system: the referring hospital, receiving center, EMS transport and transfer, and ancillary services.
The statement also took into account improving disparities in the quality of care women with STEMI receive. “It has been reported that women with STEMI may have less typical symptoms than men and arrive later [delay longer] than men after symptom onset,” Dr. Jacobs said. “Educating the public and all members of the health-care team about issues specific to women will be helpful in improving care in women. Of note, STEMI systems of care have been shown to reduce sex and age disparities in care.”
The statement also addressed implications of the COVID-19 pandemic, stating that PCI should remain the dominant treatment for patients with classic STEMI. “Patients must be reassured that appropriate precautions have been implemented by EMS and hospital to protect them and health care workers from COVID-19 infection,” the statement noted.
Dr. Jacobs has no relevant relationships to disclose.
Following up on its 2007 initiative to improve care for people who have ST-segment elevation myocardial infarction (STEMI), the American Heart Association has issued a policy statement that includes a host of recommendations to further overcome barriers to optimal care for this most severe type of heart attack.
The statement recommends steps for designing what the writing committee calls “the ideal STEMI system of care” for patients who have these severe heart attacks.
The focus of the policy statement is the AHA’s Mission: Lifeline national initiative to coordinate and improve the quality of care to patients with STEMI, which was introduced in 2007. Since then, the number or participating hospitals has increased from 485 to 857, now covering more than 85% of the U.S. population, noted the new statement, published online in Circulation.
“Bringing STEMI referring hospitals, STEMI receiving centers and emergency medical services [EMS] together in the development of local and regional systems of care within the AHA’s Mission: Lifeline program has led to significant improvement in time to treatment and outcomes for patients with STEMI,” Alice K. Jacobs, MD, lead statement author and vice chair for clinical affairs in the department of medicine at Boston Medical Center and a professor at Boston University, said in an interview.
“Yet,” Dr. Jacobs added, “opportunities exist to further improve the coordination of care and address remaining barriers to providing ideal care. Moreover, Mission: Lifeline systems of care have been extended to other time-sensitive cardiovascular disorders including stroke and out-of-hospital cardiac arrest.”
The statement itself noted, “Although there have been significant improvements in patients with STEMI receiving guideline-recommended care, progress has slowed during the past few years.” From 2008 to 2012, a number of key quality care measures at participating hospitals had improved markedly. For example, door-in-door-out (DIDO) transfers improved from a median of 76 to 62 minutes (P < .001).
However, from 2012 to 2019, with more hospitals participating, while many key measures improved, a few either plateaued or worsened slightly. Median DIDO time, for example – again, with more hospitals participating, compared with the earlier dataset – went from 45 in 2012 to 48 in 2019, according to AHA data.
Key recommendations aim to impact and improve hospital care for patients with STEMI, Dr. Jacobs said. “In addition to avoiding patient delay at the onset of recognized symptoms of a heart attack, accessing 911 and following EMS destination protocols, the prehospital activation of the cardiac catheterization lab and providing a 911 response for interhospital transport as well as direct-to-cardiac-catheterization-lab transport bypassing the emergency department when appropriate would all impact and improve hospital care.”
Other key recommendations of the statement include:
- Increasing public awareness of heart attack signs and symptoms and the importance for calling 911.
- Addressing post-MI care, including use of evidence-based practices for cardiac rehabilitation and even getting insurance companies to encourage cardiac rehab through incentives.
- Engaging rural hospitals by leveraging telemedicine to expedite percutaneous coronary intervention (PCI) and by developing systems for treatment protocols and rapid transport among facilities.
- Tearing down financial barriers with a global reimbursement model that encompasses each stop in a patient’s journey through the care system: the referring hospital, receiving center, EMS transport and transfer, and ancillary services.
The statement also took into account improving disparities in the quality of care women with STEMI receive. “It has been reported that women with STEMI may have less typical symptoms than men and arrive later [delay longer] than men after symptom onset,” Dr. Jacobs said. “Educating the public and all members of the health-care team about issues specific to women will be helpful in improving care in women. Of note, STEMI systems of care have been shown to reduce sex and age disparities in care.”
The statement also addressed implications of the COVID-19 pandemic, stating that PCI should remain the dominant treatment for patients with classic STEMI. “Patients must be reassured that appropriate precautions have been implemented by EMS and hospital to protect them and health care workers from COVID-19 infection,” the statement noted.
Dr. Jacobs has no relevant relationships to disclose.
Following up on its 2007 initiative to improve care for people who have ST-segment elevation myocardial infarction (STEMI), the American Heart Association has issued a policy statement that includes a host of recommendations to further overcome barriers to optimal care for this most severe type of heart attack.
The statement recommends steps for designing what the writing committee calls “the ideal STEMI system of care” for patients who have these severe heart attacks.
The focus of the policy statement is the AHA’s Mission: Lifeline national initiative to coordinate and improve the quality of care to patients with STEMI, which was introduced in 2007. Since then, the number or participating hospitals has increased from 485 to 857, now covering more than 85% of the U.S. population, noted the new statement, published online in Circulation.
“Bringing STEMI referring hospitals, STEMI receiving centers and emergency medical services [EMS] together in the development of local and regional systems of care within the AHA’s Mission: Lifeline program has led to significant improvement in time to treatment and outcomes for patients with STEMI,” Alice K. Jacobs, MD, lead statement author and vice chair for clinical affairs in the department of medicine at Boston Medical Center and a professor at Boston University, said in an interview.
“Yet,” Dr. Jacobs added, “opportunities exist to further improve the coordination of care and address remaining barriers to providing ideal care. Moreover, Mission: Lifeline systems of care have been extended to other time-sensitive cardiovascular disorders including stroke and out-of-hospital cardiac arrest.”
The statement itself noted, “Although there have been significant improvements in patients with STEMI receiving guideline-recommended care, progress has slowed during the past few years.” From 2008 to 2012, a number of key quality care measures at participating hospitals had improved markedly. For example, door-in-door-out (DIDO) transfers improved from a median of 76 to 62 minutes (P < .001).
However, from 2012 to 2019, with more hospitals participating, while many key measures improved, a few either plateaued or worsened slightly. Median DIDO time, for example – again, with more hospitals participating, compared with the earlier dataset – went from 45 in 2012 to 48 in 2019, according to AHA data.
Key recommendations aim to impact and improve hospital care for patients with STEMI, Dr. Jacobs said. “In addition to avoiding patient delay at the onset of recognized symptoms of a heart attack, accessing 911 and following EMS destination protocols, the prehospital activation of the cardiac catheterization lab and providing a 911 response for interhospital transport as well as direct-to-cardiac-catheterization-lab transport bypassing the emergency department when appropriate would all impact and improve hospital care.”
Other key recommendations of the statement include:
- Increasing public awareness of heart attack signs and symptoms and the importance for calling 911.
- Addressing post-MI care, including use of evidence-based practices for cardiac rehabilitation and even getting insurance companies to encourage cardiac rehab through incentives.
- Engaging rural hospitals by leveraging telemedicine to expedite percutaneous coronary intervention (PCI) and by developing systems for treatment protocols and rapid transport among facilities.
- Tearing down financial barriers with a global reimbursement model that encompasses each stop in a patient’s journey through the care system: the referring hospital, receiving center, EMS transport and transfer, and ancillary services.
The statement also took into account improving disparities in the quality of care women with STEMI receive. “It has been reported that women with STEMI may have less typical symptoms than men and arrive later [delay longer] than men after symptom onset,” Dr. Jacobs said. “Educating the public and all members of the health-care team about issues specific to women will be helpful in improving care in women. Of note, STEMI systems of care have been shown to reduce sex and age disparities in care.”
The statement also addressed implications of the COVID-19 pandemic, stating that PCI should remain the dominant treatment for patients with classic STEMI. “Patients must be reassured that appropriate precautions have been implemented by EMS and hospital to protect them and health care workers from COVID-19 infection,” the statement noted.
Dr. Jacobs has no relevant relationships to disclose.
FROM CIRCULATION
Study points to ideal age for CAC testing in young adults
New risk equations can help determine the need for a first coronary artery calcium (CAC) scan in young adults to identify those most at risk for premature atherosclerosis, researchers say.
“To our knowledge this is the first time to derive a clinical risk equation for the initial conversion from CAC 0, which can be used actually to guide the timing of CAC testing in young adults,” Omar Dzaye, MD, MPH, PhD, Johns Hopkins University School of Medicine, Baltimore, said in an interview.
CAC is an independent predictor of adverse atherosclerotic cardiovascular disease (ASCVD), but routine screening is not recommended in low-risk groups. U.S. guidelines say CAC testing may be considered (class IIa) for risk stratification in adults 40 to 75 years at intermediate risk (estimated 10-year ASCVD risk 7.5% to 20%) when the decision to start preventive therapies is unclear.
The new sex-specific risk equations were derived from 22,346 adults 30 to 50 years of age who underwent CAC testing between 1991 and 2010 for ASCVD risk prediction at four high-volume centers in the CAC Consortium. The average age was 43.5 years, 25% were women, and 12.3% were non-White.
The participants were free of clinical ASCVD or CV symptoms at the time of scanning but had underlying traditional ASCVD risk factors (dyslipidemia in 49.6%, hypertension in 20.0%, active smokers 11.0%, and diabetes in 4.0%), an intermediate 10-year ASCVD risk (2.6%), and/or a significant family history of CHD (49.3%).
As reported in the Journal of the American College of Cardiology, 92.7% of participants had a low 10-year ASCVD risk below 5%, but 34.4% had CAC scores above 0 (median, 20 Agatston units).
Assuming a 25% testing yield (number needed to scan equals four to detect one CAC score above 0), the optimal age for a first scan in young men without risk factors was 42.3 years, and for women it was 57.6 years.
Young adults with one or more risk factors, however, would convert to CAC above 0 at least 3.3 years earlier on average. Diabetes had the strongest influence on the probability of conversion, with men and women predicted to develop incident CAC a respective 5.5 years and 7.3 years earlier on average.
The findings build on previous observations by the team showing that diabetes confers a 40% reduction in the so-called “warranty period” of a CAC score of 0, Dr. Dzaye noted. The National Lipid Association 2020 statement on CAC scoring also suggests it’s reasonable to obtain a CAC scan in people with diabetes aged 30 to 39 years.
“The predicted utility of CAC for ASCVD outcomes is similar in type 1 and type 2 diabetes; however, individuals with type 1 diabetes may actually develop CAC as young as 17 years of age,” he said. “Therefore, definitely, CAC studies in this population are required.”
In contrast, hypertension, dyslipidemia, active smoking, and a family history of CHD were individually associated with the development of CAC 3.3 to 4.3 years earlier. In general, the time to premature CAC was longer for women than for men with a given risk-factor profile.
The predicted age for a first CAC was 37.5 years for men and 48.9 years for women with an intermediate risk-factor profile (for example, smoking plus hypertension) and 33.8 years and 44.7 years, respectively, for those with a high-risk profile (for example, diabetes plus dyslipidemia).
Asked whether the risk equations can be used to guide CAC scanning in clinical practice, Dr. Dzaye said, “we very much believe that this can be used because for the process we published the internal validation, and we also did an external validation that is not published at the moment in [the] MESA [trial].”
He pointed out that study participants did not have a second CAC scan for true modeling of longitudinal CAC and do not represent the general population but, rather, a general cardiology referral population enriched with ASCVD risk factors. Future studies are needed that incorporate a more diverse population, multiple CAC scans, and genetic risk factors.
“This is helpful from a descriptive, epidemiologic point of view and helps us understand the approximate prevalence of coronary calcium greater than 0 in younger men and women, but I’m not convinced that it will or should change clinical practice,” cardiologist Philip Greenland, MD, a professor of preventive medicine and professor of medicine at Northwestern University in Chicago, said in an interview.
Dr. Greenland, who coauthored a review on CAC testing earlier this month, said CAC is the strongest tool we have to improve risk prediction beyond standard risk scores but does involve radiation exposure and some added costs. CAC testing is especially useful as a tiebreaker in older intermediate-risk patients who may be on the fence about starting primary prevention medications but could fall short among “younger, low-risk patients where, as they show here, the proportion of people who have a positive test is well below half.”
“So that means you’re going to have a very large number of people who are CAC 0, which is what we would expect in relatively younger people, but I wouldn’t be happy to try to explain that to a patient: ‘We’re not seeing coronary atherosclerosis right now, but we still want to treat your risk factors.’ That’s kind of a dissonant message,” Dr. Greenland said.
An accompanying editorial suggests “the study has filled an important clinical gap, providing highly actionable data that could help guide clinical decision making for ASCVD prevention.”
Nevertheless, Tasneem Naqvi, MD, Mayo Clinic, Scottsdale, Arizona, and Tamar Polonsky, MD, University of Chicago, question the generalizability of the results and point out that CAC screening at the authors’ recommended ages “could still miss a substantial number of young women with incident MI.”
Exposure to ionizing radiation with CAC is lower than that used in screening mammography for breast cancer but, they agree, should be considered, particularly in young women.
“Alternatively, ultrasonography avoids radiation altogether and can detect plaque earlier than the development of CAC,” write Dr. Naqvi and Dr. Polonsky. Further, the 2019 European Society of Cardiology guidelines for CV risk give ultrasound assessment of carotid artery and femoral plaque a class IIa recommendation and CAC a class IIb recommendation.
Commenting for this news organization, Roger Blumenthal, MD, director of the Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease, said the class IIb recommendation “never really made any sense because the data with coronary calcium is so much stronger than it is with carotid ultrasound.”
“Sometimes smart scientists and researchers differ, but in my strong opinion, the European Society of Cardiology in 2019 did not give it the right classification, while the group I was part of, the American Heart Association/American College of Cardiology [2019 guideline], got it right and emphasized that this is the most cost-effective and useful way to improve risk assessment.”
Dr. Blumenthal, who was not part of the study, noted that U.S. guidelines say CAC measurement is not intended as a screening test for everyone but may be used selectively as a decision aid.
“This study adds to the information about how to use that type of testing. So, I personally think it will be a highly referenced article in the next set of guidelines that the American Heart Association, American College of Cardiology, and other organizations have.”
The study was supported in part by a research grant from the National Institutes of Health National Heart, Lung, and Blood Institute. Dr. Dzaye, Dr. Blumenthal, Dr. Naqvi, and Dr. Polonsky report having no relevant financial relationships.
A version of this article appeared on Medscape.com.
New risk equations can help determine the need for a first coronary artery calcium (CAC) scan in young adults to identify those most at risk for premature atherosclerosis, researchers say.
“To our knowledge this is the first time to derive a clinical risk equation for the initial conversion from CAC 0, which can be used actually to guide the timing of CAC testing in young adults,” Omar Dzaye, MD, MPH, PhD, Johns Hopkins University School of Medicine, Baltimore, said in an interview.
CAC is an independent predictor of adverse atherosclerotic cardiovascular disease (ASCVD), but routine screening is not recommended in low-risk groups. U.S. guidelines say CAC testing may be considered (class IIa) for risk stratification in adults 40 to 75 years at intermediate risk (estimated 10-year ASCVD risk 7.5% to 20%) when the decision to start preventive therapies is unclear.
The new sex-specific risk equations were derived from 22,346 adults 30 to 50 years of age who underwent CAC testing between 1991 and 2010 for ASCVD risk prediction at four high-volume centers in the CAC Consortium. The average age was 43.5 years, 25% were women, and 12.3% were non-White.
The participants were free of clinical ASCVD or CV symptoms at the time of scanning but had underlying traditional ASCVD risk factors (dyslipidemia in 49.6%, hypertension in 20.0%, active smokers 11.0%, and diabetes in 4.0%), an intermediate 10-year ASCVD risk (2.6%), and/or a significant family history of CHD (49.3%).
As reported in the Journal of the American College of Cardiology, 92.7% of participants had a low 10-year ASCVD risk below 5%, but 34.4% had CAC scores above 0 (median, 20 Agatston units).
Assuming a 25% testing yield (number needed to scan equals four to detect one CAC score above 0), the optimal age for a first scan in young men without risk factors was 42.3 years, and for women it was 57.6 years.
Young adults with one or more risk factors, however, would convert to CAC above 0 at least 3.3 years earlier on average. Diabetes had the strongest influence on the probability of conversion, with men and women predicted to develop incident CAC a respective 5.5 years and 7.3 years earlier on average.
The findings build on previous observations by the team showing that diabetes confers a 40% reduction in the so-called “warranty period” of a CAC score of 0, Dr. Dzaye noted. The National Lipid Association 2020 statement on CAC scoring also suggests it’s reasonable to obtain a CAC scan in people with diabetes aged 30 to 39 years.
“The predicted utility of CAC for ASCVD outcomes is similar in type 1 and type 2 diabetes; however, individuals with type 1 diabetes may actually develop CAC as young as 17 years of age,” he said. “Therefore, definitely, CAC studies in this population are required.”
In contrast, hypertension, dyslipidemia, active smoking, and a family history of CHD were individually associated with the development of CAC 3.3 to 4.3 years earlier. In general, the time to premature CAC was longer for women than for men with a given risk-factor profile.
The predicted age for a first CAC was 37.5 years for men and 48.9 years for women with an intermediate risk-factor profile (for example, smoking plus hypertension) and 33.8 years and 44.7 years, respectively, for those with a high-risk profile (for example, diabetes plus dyslipidemia).
Asked whether the risk equations can be used to guide CAC scanning in clinical practice, Dr. Dzaye said, “we very much believe that this can be used because for the process we published the internal validation, and we also did an external validation that is not published at the moment in [the] MESA [trial].”
He pointed out that study participants did not have a second CAC scan for true modeling of longitudinal CAC and do not represent the general population but, rather, a general cardiology referral population enriched with ASCVD risk factors. Future studies are needed that incorporate a more diverse population, multiple CAC scans, and genetic risk factors.
“This is helpful from a descriptive, epidemiologic point of view and helps us understand the approximate prevalence of coronary calcium greater than 0 in younger men and women, but I’m not convinced that it will or should change clinical practice,” cardiologist Philip Greenland, MD, a professor of preventive medicine and professor of medicine at Northwestern University in Chicago, said in an interview.
Dr. Greenland, who coauthored a review on CAC testing earlier this month, said CAC is the strongest tool we have to improve risk prediction beyond standard risk scores but does involve radiation exposure and some added costs. CAC testing is especially useful as a tiebreaker in older intermediate-risk patients who may be on the fence about starting primary prevention medications but could fall short among “younger, low-risk patients where, as they show here, the proportion of people who have a positive test is well below half.”
“So that means you’re going to have a very large number of people who are CAC 0, which is what we would expect in relatively younger people, but I wouldn’t be happy to try to explain that to a patient: ‘We’re not seeing coronary atherosclerosis right now, but we still want to treat your risk factors.’ That’s kind of a dissonant message,” Dr. Greenland said.
An accompanying editorial suggests “the study has filled an important clinical gap, providing highly actionable data that could help guide clinical decision making for ASCVD prevention.”
Nevertheless, Tasneem Naqvi, MD, Mayo Clinic, Scottsdale, Arizona, and Tamar Polonsky, MD, University of Chicago, question the generalizability of the results and point out that CAC screening at the authors’ recommended ages “could still miss a substantial number of young women with incident MI.”
Exposure to ionizing radiation with CAC is lower than that used in screening mammography for breast cancer but, they agree, should be considered, particularly in young women.
“Alternatively, ultrasonography avoids radiation altogether and can detect plaque earlier than the development of CAC,” write Dr. Naqvi and Dr. Polonsky. Further, the 2019 European Society of Cardiology guidelines for CV risk give ultrasound assessment of carotid artery and femoral plaque a class IIa recommendation and CAC a class IIb recommendation.
Commenting for this news organization, Roger Blumenthal, MD, director of the Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease, said the class IIb recommendation “never really made any sense because the data with coronary calcium is so much stronger than it is with carotid ultrasound.”
“Sometimes smart scientists and researchers differ, but in my strong opinion, the European Society of Cardiology in 2019 did not give it the right classification, while the group I was part of, the American Heart Association/American College of Cardiology [2019 guideline], got it right and emphasized that this is the most cost-effective and useful way to improve risk assessment.”
Dr. Blumenthal, who was not part of the study, noted that U.S. guidelines say CAC measurement is not intended as a screening test for everyone but may be used selectively as a decision aid.
“This study adds to the information about how to use that type of testing. So, I personally think it will be a highly referenced article in the next set of guidelines that the American Heart Association, American College of Cardiology, and other organizations have.”
The study was supported in part by a research grant from the National Institutes of Health National Heart, Lung, and Blood Institute. Dr. Dzaye, Dr. Blumenthal, Dr. Naqvi, and Dr. Polonsky report having no relevant financial relationships.
A version of this article appeared on Medscape.com.
New risk equations can help determine the need for a first coronary artery calcium (CAC) scan in young adults to identify those most at risk for premature atherosclerosis, researchers say.
“To our knowledge this is the first time to derive a clinical risk equation for the initial conversion from CAC 0, which can be used actually to guide the timing of CAC testing in young adults,” Omar Dzaye, MD, MPH, PhD, Johns Hopkins University School of Medicine, Baltimore, said in an interview.
CAC is an independent predictor of adverse atherosclerotic cardiovascular disease (ASCVD), but routine screening is not recommended in low-risk groups. U.S. guidelines say CAC testing may be considered (class IIa) for risk stratification in adults 40 to 75 years at intermediate risk (estimated 10-year ASCVD risk 7.5% to 20%) when the decision to start preventive therapies is unclear.
The new sex-specific risk equations were derived from 22,346 adults 30 to 50 years of age who underwent CAC testing between 1991 and 2010 for ASCVD risk prediction at four high-volume centers in the CAC Consortium. The average age was 43.5 years, 25% were women, and 12.3% were non-White.
The participants were free of clinical ASCVD or CV symptoms at the time of scanning but had underlying traditional ASCVD risk factors (dyslipidemia in 49.6%, hypertension in 20.0%, active smokers 11.0%, and diabetes in 4.0%), an intermediate 10-year ASCVD risk (2.6%), and/or a significant family history of CHD (49.3%).
As reported in the Journal of the American College of Cardiology, 92.7% of participants had a low 10-year ASCVD risk below 5%, but 34.4% had CAC scores above 0 (median, 20 Agatston units).
Assuming a 25% testing yield (number needed to scan equals four to detect one CAC score above 0), the optimal age for a first scan in young men without risk factors was 42.3 years, and for women it was 57.6 years.
Young adults with one or more risk factors, however, would convert to CAC above 0 at least 3.3 years earlier on average. Diabetes had the strongest influence on the probability of conversion, with men and women predicted to develop incident CAC a respective 5.5 years and 7.3 years earlier on average.
The findings build on previous observations by the team showing that diabetes confers a 40% reduction in the so-called “warranty period” of a CAC score of 0, Dr. Dzaye noted. The National Lipid Association 2020 statement on CAC scoring also suggests it’s reasonable to obtain a CAC scan in people with diabetes aged 30 to 39 years.
“The predicted utility of CAC for ASCVD outcomes is similar in type 1 and type 2 diabetes; however, individuals with type 1 diabetes may actually develop CAC as young as 17 years of age,” he said. “Therefore, definitely, CAC studies in this population are required.”
In contrast, hypertension, dyslipidemia, active smoking, and a family history of CHD were individually associated with the development of CAC 3.3 to 4.3 years earlier. In general, the time to premature CAC was longer for women than for men with a given risk-factor profile.
The predicted age for a first CAC was 37.5 years for men and 48.9 years for women with an intermediate risk-factor profile (for example, smoking plus hypertension) and 33.8 years and 44.7 years, respectively, for those with a high-risk profile (for example, diabetes plus dyslipidemia).
Asked whether the risk equations can be used to guide CAC scanning in clinical practice, Dr. Dzaye said, “we very much believe that this can be used because for the process we published the internal validation, and we also did an external validation that is not published at the moment in [the] MESA [trial].”
He pointed out that study participants did not have a second CAC scan for true modeling of longitudinal CAC and do not represent the general population but, rather, a general cardiology referral population enriched with ASCVD risk factors. Future studies are needed that incorporate a more diverse population, multiple CAC scans, and genetic risk factors.
“This is helpful from a descriptive, epidemiologic point of view and helps us understand the approximate prevalence of coronary calcium greater than 0 in younger men and women, but I’m not convinced that it will or should change clinical practice,” cardiologist Philip Greenland, MD, a professor of preventive medicine and professor of medicine at Northwestern University in Chicago, said in an interview.
Dr. Greenland, who coauthored a review on CAC testing earlier this month, said CAC is the strongest tool we have to improve risk prediction beyond standard risk scores but does involve radiation exposure and some added costs. CAC testing is especially useful as a tiebreaker in older intermediate-risk patients who may be on the fence about starting primary prevention medications but could fall short among “younger, low-risk patients where, as they show here, the proportion of people who have a positive test is well below half.”
“So that means you’re going to have a very large number of people who are CAC 0, which is what we would expect in relatively younger people, but I wouldn’t be happy to try to explain that to a patient: ‘We’re not seeing coronary atherosclerosis right now, but we still want to treat your risk factors.’ That’s kind of a dissonant message,” Dr. Greenland said.
An accompanying editorial suggests “the study has filled an important clinical gap, providing highly actionable data that could help guide clinical decision making for ASCVD prevention.”
Nevertheless, Tasneem Naqvi, MD, Mayo Clinic, Scottsdale, Arizona, and Tamar Polonsky, MD, University of Chicago, question the generalizability of the results and point out that CAC screening at the authors’ recommended ages “could still miss a substantial number of young women with incident MI.”
Exposure to ionizing radiation with CAC is lower than that used in screening mammography for breast cancer but, they agree, should be considered, particularly in young women.
“Alternatively, ultrasonography avoids radiation altogether and can detect plaque earlier than the development of CAC,” write Dr. Naqvi and Dr. Polonsky. Further, the 2019 European Society of Cardiology guidelines for CV risk give ultrasound assessment of carotid artery and femoral plaque a class IIa recommendation and CAC a class IIb recommendation.
Commenting for this news organization, Roger Blumenthal, MD, director of the Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease, said the class IIb recommendation “never really made any sense because the data with coronary calcium is so much stronger than it is with carotid ultrasound.”
“Sometimes smart scientists and researchers differ, but in my strong opinion, the European Society of Cardiology in 2019 did not give it the right classification, while the group I was part of, the American Heart Association/American College of Cardiology [2019 guideline], got it right and emphasized that this is the most cost-effective and useful way to improve risk assessment.”
Dr. Blumenthal, who was not part of the study, noted that U.S. guidelines say CAC measurement is not intended as a screening test for everyone but may be used selectively as a decision aid.
“This study adds to the information about how to use that type of testing. So, I personally think it will be a highly referenced article in the next set of guidelines that the American Heart Association, American College of Cardiology, and other organizations have.”
The study was supported in part by a research grant from the National Institutes of Health National Heart, Lung, and Blood Institute. Dr. Dzaye, Dr. Blumenthal, Dr. Naqvi, and Dr. Polonsky report having no relevant financial relationships.
A version of this article appeared on Medscape.com.
New FDA guidance aims to cut sodium in processed foods
The Food and Drug Administration has issued voluntary, short-term sodium reduction targets for food manufacturers, chain restaurants, and food service operators for processed, packaged, and prepared foods, with an eye toward reducing diet-related conditions such as heart disease and obesity.
The new targets seek to decrease average sodium intake from approximately 3,400 mg/day to 3,000 mg/day, about a 12% reduction, over the next 2.5 years, acting FDA Commissioner Janet Woodcock, MD, and Susan Mayne, PhD, director of the FDA’s Center for Food Safety and Applied Nutrition, said in joint statement.
Although this reduction keeps the average intake above the recommended limit of 2,300 mg/day for individuals 14 years and older as per the Dietary Guidelines for Americans, “we know that even these modest reductions made slowly over the next few years will substantially decrease diet-related diseases,” they added.
The FDA first proposed recommendations for reducing sodium content in draft guidance released in 2016.
Since, then a number of companies in the food industry have already made changes to sodium content in their products, “which is encouraging, but additional support across all types of foods to help consumers meet recommended sodium limits is needed,” Dr. Woodcock and Dr. Mayne said.
They emphasized that the new guidance represents short-term goals that the food industry should work to meet as soon as possible to help optimize public health.
“We will continue our discussions with the food industry as we monitor the sodium content of the food supply to evaluate progress. In the future, we plan to issue revised, subsequent targets to further lower the sodium content incrementally and continue to help reduce sodium intake,” Dr. Woodcock and Dr. Mayne said.
AHA: A good first step that does not go far enough
In a statement, the American Heart Association said the new targets will play “a critical role in helping people across the country achieve healthier levels of sodium and improved well-being overall. These targets will be an important driver to reduce sodium consumption, which can have significant health benefits and lead to lower medical costs.”
“Lowering sodium levels in the food supply would reduce risk of hypertension, heart disease, stroke, heart attack, and death in addition to saving billions of dollars in health care costs over the next decade,” the AHA said.
But the AHA also said lowering sodium intake to 3,000 mg/day is not enough.
“Lowering sodium further to 2,300 mg could prevent an estimated 450,000 cases of cardiovascular disease, gain 2 million quality-adjusted life-years, and save approximately $40 billion in health care costs over a 20-year period,” the AHA said.
The AHA is urging the FDA to “follow [this] action with additional targets to further lower the amount of sodium in the food supply and help people in America attain an appropriate sodium intake.”
A version of this article first appeared on Medscape.com.
The Food and Drug Administration has issued voluntary, short-term sodium reduction targets for food manufacturers, chain restaurants, and food service operators for processed, packaged, and prepared foods, with an eye toward reducing diet-related conditions such as heart disease and obesity.
The new targets seek to decrease average sodium intake from approximately 3,400 mg/day to 3,000 mg/day, about a 12% reduction, over the next 2.5 years, acting FDA Commissioner Janet Woodcock, MD, and Susan Mayne, PhD, director of the FDA’s Center for Food Safety and Applied Nutrition, said in joint statement.
Although this reduction keeps the average intake above the recommended limit of 2,300 mg/day for individuals 14 years and older as per the Dietary Guidelines for Americans, “we know that even these modest reductions made slowly over the next few years will substantially decrease diet-related diseases,” they added.
The FDA first proposed recommendations for reducing sodium content in draft guidance released in 2016.
Since, then a number of companies in the food industry have already made changes to sodium content in their products, “which is encouraging, but additional support across all types of foods to help consumers meet recommended sodium limits is needed,” Dr. Woodcock and Dr. Mayne said.
They emphasized that the new guidance represents short-term goals that the food industry should work to meet as soon as possible to help optimize public health.
“We will continue our discussions with the food industry as we monitor the sodium content of the food supply to evaluate progress. In the future, we plan to issue revised, subsequent targets to further lower the sodium content incrementally and continue to help reduce sodium intake,” Dr. Woodcock and Dr. Mayne said.
AHA: A good first step that does not go far enough
In a statement, the American Heart Association said the new targets will play “a critical role in helping people across the country achieve healthier levels of sodium and improved well-being overall. These targets will be an important driver to reduce sodium consumption, which can have significant health benefits and lead to lower medical costs.”
“Lowering sodium levels in the food supply would reduce risk of hypertension, heart disease, stroke, heart attack, and death in addition to saving billions of dollars in health care costs over the next decade,” the AHA said.
But the AHA also said lowering sodium intake to 3,000 mg/day is not enough.
“Lowering sodium further to 2,300 mg could prevent an estimated 450,000 cases of cardiovascular disease, gain 2 million quality-adjusted life-years, and save approximately $40 billion in health care costs over a 20-year period,” the AHA said.
The AHA is urging the FDA to “follow [this] action with additional targets to further lower the amount of sodium in the food supply and help people in America attain an appropriate sodium intake.”
A version of this article first appeared on Medscape.com.
The Food and Drug Administration has issued voluntary, short-term sodium reduction targets for food manufacturers, chain restaurants, and food service operators for processed, packaged, and prepared foods, with an eye toward reducing diet-related conditions such as heart disease and obesity.
The new targets seek to decrease average sodium intake from approximately 3,400 mg/day to 3,000 mg/day, about a 12% reduction, over the next 2.5 years, acting FDA Commissioner Janet Woodcock, MD, and Susan Mayne, PhD, director of the FDA’s Center for Food Safety and Applied Nutrition, said in joint statement.
Although this reduction keeps the average intake above the recommended limit of 2,300 mg/day for individuals 14 years and older as per the Dietary Guidelines for Americans, “we know that even these modest reductions made slowly over the next few years will substantially decrease diet-related diseases,” they added.
The FDA first proposed recommendations for reducing sodium content in draft guidance released in 2016.
Since, then a number of companies in the food industry have already made changes to sodium content in their products, “which is encouraging, but additional support across all types of foods to help consumers meet recommended sodium limits is needed,” Dr. Woodcock and Dr. Mayne said.
They emphasized that the new guidance represents short-term goals that the food industry should work to meet as soon as possible to help optimize public health.
“We will continue our discussions with the food industry as we monitor the sodium content of the food supply to evaluate progress. In the future, we plan to issue revised, subsequent targets to further lower the sodium content incrementally and continue to help reduce sodium intake,” Dr. Woodcock and Dr. Mayne said.
AHA: A good first step that does not go far enough
In a statement, the American Heart Association said the new targets will play “a critical role in helping people across the country achieve healthier levels of sodium and improved well-being overall. These targets will be an important driver to reduce sodium consumption, which can have significant health benefits and lead to lower medical costs.”
“Lowering sodium levels in the food supply would reduce risk of hypertension, heart disease, stroke, heart attack, and death in addition to saving billions of dollars in health care costs over the next decade,” the AHA said.
But the AHA also said lowering sodium intake to 3,000 mg/day is not enough.
“Lowering sodium further to 2,300 mg could prevent an estimated 450,000 cases of cardiovascular disease, gain 2 million quality-adjusted life-years, and save approximately $40 billion in health care costs over a 20-year period,” the AHA said.
The AHA is urging the FDA to “follow [this] action with additional targets to further lower the amount of sodium in the food supply and help people in America attain an appropriate sodium intake.”
A version of this article first appeared on Medscape.com.