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DPP-4 drugs for diabetes may protect kidneys too
SAN DIEGO – Dipeptidyl peptidase–4 (DPP-4) inhibitors appear to delay the progression of chronic kidney disease (CKD) in patients with type 2 diabetes mellitus (T2DM), a new study has found. Researchers also found that all-cause long-term mortality dropped by an astonishing 78% in patients who took the drugs for an average of more than 3 years.
While the reasons for the impressive mortality results are a mystery, “these medications could have a beneficial effect on the kidneys, and it begins to show after 3 years,” said lead author Mariana Garcia-Touza, MD, of the Kansas City (Missouri) Department of Veterans Affairs Medical Center, in an interview. She presented the results at the meeting, sponsored by the American Society of Nephrology.
DPP-4 inhibitor drugs have been available for more than a decade in the United States. The medications, which include sitagliptin (Januvia) and linagliptin (Tradjenta), are used to treat patients with T2DM who are inadequately controlled by first-line treatments.
The drugs have critics. As UpToDate notes, they’re expensive and their effect on glucose levels is “modest.” In addition, UpToDate says, “some of the DPP-4 inhibitors have been associated with an increased risk of heart failure resulting in hospitalization.”
The authors of the new study sought to understand whether the drugs affect kidney function. As Dr. Garcia-Touza noted, metformin, which is processed in part by the kidneys, is considered harmful to certain patients with kidney disease. However, DPP-4 inhibitors are cleared through the liver. In fact, research has suggested the drugs may actually benefit the liver (Med Sci Monit. 2014 Sep 17;20:1662-7).
For the new study, researchers retrospectively analyzed 20,424 patients with T2DM in the VA system who took DPP-4 inhibitors (average age, 68 years) and compared them with a matched group of 52,118 patients with T2DM who didn’t take the drugs, tracking all patients for a mean of over 3 years.
T2DM control improved slightly in the DPP-4 group but remained worse than the non–DPP-4 group. However, “a significant reduction in progression of CKD was seen” in the DPP-4 group, she said.
The number of patients with creatinine levels above 1.5 mg/dL, 3 mg/dL, and 6 mg/dL was reduced by 7%, 41%, and 47%, respectively, in the DPP-4 group, compared with the other group (P less than .01). And the time to end-stage renal disease (creatinine above 6 mg/dL) was delayed by 144 days in the DPP-4 group (P less than .01).
All-cause mortality also fell by 78% in the DPP-4 group (P less than .0001). “Despite having worse glucose control [than the non–DPP-4 group], these patients have better overall mortality,” Dr. Garcia-Touza said.
The drugs may reduce the burden on the kidneys by decreasing inflammation, she said.
Could DPP-4 drugs be beneficial to patients with CKD even if they don’t have T2DM? Dr. Garcia-Touza wasn’t sure. However, she had a theory about why these kidney benefits didn’t show up in previous research. “My impression is that they didn’t go far enough [in time]. That was the main difference.”
Going forward, Dr. Garcia-Touza said her team plans to study the effects of the drugs on retinopathy and diabetic neuropathy.
The study was funded by the Midwest Biomedical Research Foundation and the VA. The study authors reported no relevant disclosures.
SOURCE: Garcia-Tourza M et al. Kidney Week 2018, Abstract TH-OR035.
SAN DIEGO – Dipeptidyl peptidase–4 (DPP-4) inhibitors appear to delay the progression of chronic kidney disease (CKD) in patients with type 2 diabetes mellitus (T2DM), a new study has found. Researchers also found that all-cause long-term mortality dropped by an astonishing 78% in patients who took the drugs for an average of more than 3 years.
While the reasons for the impressive mortality results are a mystery, “these medications could have a beneficial effect on the kidneys, and it begins to show after 3 years,” said lead author Mariana Garcia-Touza, MD, of the Kansas City (Missouri) Department of Veterans Affairs Medical Center, in an interview. She presented the results at the meeting, sponsored by the American Society of Nephrology.
DPP-4 inhibitor drugs have been available for more than a decade in the United States. The medications, which include sitagliptin (Januvia) and linagliptin (Tradjenta), are used to treat patients with T2DM who are inadequately controlled by first-line treatments.
The drugs have critics. As UpToDate notes, they’re expensive and their effect on glucose levels is “modest.” In addition, UpToDate says, “some of the DPP-4 inhibitors have been associated with an increased risk of heart failure resulting in hospitalization.”
The authors of the new study sought to understand whether the drugs affect kidney function. As Dr. Garcia-Touza noted, metformin, which is processed in part by the kidneys, is considered harmful to certain patients with kidney disease. However, DPP-4 inhibitors are cleared through the liver. In fact, research has suggested the drugs may actually benefit the liver (Med Sci Monit. 2014 Sep 17;20:1662-7).
For the new study, researchers retrospectively analyzed 20,424 patients with T2DM in the VA system who took DPP-4 inhibitors (average age, 68 years) and compared them with a matched group of 52,118 patients with T2DM who didn’t take the drugs, tracking all patients for a mean of over 3 years.
T2DM control improved slightly in the DPP-4 group but remained worse than the non–DPP-4 group. However, “a significant reduction in progression of CKD was seen” in the DPP-4 group, she said.
The number of patients with creatinine levels above 1.5 mg/dL, 3 mg/dL, and 6 mg/dL was reduced by 7%, 41%, and 47%, respectively, in the DPP-4 group, compared with the other group (P less than .01). And the time to end-stage renal disease (creatinine above 6 mg/dL) was delayed by 144 days in the DPP-4 group (P less than .01).
All-cause mortality also fell by 78% in the DPP-4 group (P less than .0001). “Despite having worse glucose control [than the non–DPP-4 group], these patients have better overall mortality,” Dr. Garcia-Touza said.
The drugs may reduce the burden on the kidneys by decreasing inflammation, she said.
Could DPP-4 drugs be beneficial to patients with CKD even if they don’t have T2DM? Dr. Garcia-Touza wasn’t sure. However, she had a theory about why these kidney benefits didn’t show up in previous research. “My impression is that they didn’t go far enough [in time]. That was the main difference.”
Going forward, Dr. Garcia-Touza said her team plans to study the effects of the drugs on retinopathy and diabetic neuropathy.
The study was funded by the Midwest Biomedical Research Foundation and the VA. The study authors reported no relevant disclosures.
SOURCE: Garcia-Tourza M et al. Kidney Week 2018, Abstract TH-OR035.
SAN DIEGO – Dipeptidyl peptidase–4 (DPP-4) inhibitors appear to delay the progression of chronic kidney disease (CKD) in patients with type 2 diabetes mellitus (T2DM), a new study has found. Researchers also found that all-cause long-term mortality dropped by an astonishing 78% in patients who took the drugs for an average of more than 3 years.
While the reasons for the impressive mortality results are a mystery, “these medications could have a beneficial effect on the kidneys, and it begins to show after 3 years,” said lead author Mariana Garcia-Touza, MD, of the Kansas City (Missouri) Department of Veterans Affairs Medical Center, in an interview. She presented the results at the meeting, sponsored by the American Society of Nephrology.
DPP-4 inhibitor drugs have been available for more than a decade in the United States. The medications, which include sitagliptin (Januvia) and linagliptin (Tradjenta), are used to treat patients with T2DM who are inadequately controlled by first-line treatments.
The drugs have critics. As UpToDate notes, they’re expensive and their effect on glucose levels is “modest.” In addition, UpToDate says, “some of the DPP-4 inhibitors have been associated with an increased risk of heart failure resulting in hospitalization.”
The authors of the new study sought to understand whether the drugs affect kidney function. As Dr. Garcia-Touza noted, metformin, which is processed in part by the kidneys, is considered harmful to certain patients with kidney disease. However, DPP-4 inhibitors are cleared through the liver. In fact, research has suggested the drugs may actually benefit the liver (Med Sci Monit. 2014 Sep 17;20:1662-7).
For the new study, researchers retrospectively analyzed 20,424 patients with T2DM in the VA system who took DPP-4 inhibitors (average age, 68 years) and compared them with a matched group of 52,118 patients with T2DM who didn’t take the drugs, tracking all patients for a mean of over 3 years.
T2DM control improved slightly in the DPP-4 group but remained worse than the non–DPP-4 group. However, “a significant reduction in progression of CKD was seen” in the DPP-4 group, she said.
The number of patients with creatinine levels above 1.5 mg/dL, 3 mg/dL, and 6 mg/dL was reduced by 7%, 41%, and 47%, respectively, in the DPP-4 group, compared with the other group (P less than .01). And the time to end-stage renal disease (creatinine above 6 mg/dL) was delayed by 144 days in the DPP-4 group (P less than .01).
All-cause mortality also fell by 78% in the DPP-4 group (P less than .0001). “Despite having worse glucose control [than the non–DPP-4 group], these patients have better overall mortality,” Dr. Garcia-Touza said.
The drugs may reduce the burden on the kidneys by decreasing inflammation, she said.
Could DPP-4 drugs be beneficial to patients with CKD even if they don’t have T2DM? Dr. Garcia-Touza wasn’t sure. However, she had a theory about why these kidney benefits didn’t show up in previous research. “My impression is that they didn’t go far enough [in time]. That was the main difference.”
Going forward, Dr. Garcia-Touza said her team plans to study the effects of the drugs on retinopathy and diabetic neuropathy.
The study was funded by the Midwest Biomedical Research Foundation and the VA. The study authors reported no relevant disclosures.
SOURCE: Garcia-Tourza M et al. Kidney Week 2018, Abstract TH-OR035.
REPORTING FROM KIDNEY WEEK 2018
Key clinical point: Dipeptidyl peptidase–4 (DPP-4) inhibitors may delay progression of chronic kidney disease in patients with type 2 diabetes mellitus (T2DM) and may dramatically reduce all-cause mortality.
Major finding: Compared with those who didn’t take the drugs, patients with T2DM who took DPP-4 inhibitors were much less likely to progress to creatinine levels above 1.5 mg/dL, 3 mg/dL, and 6 mg/dL (reduction of 7%, 41%, and 47%, respectively; P less than .01). All-cause mortality in the DPP-4 group fell by 78% (P less than .0001).
Study details: A retrospective study of 20,424 patients with T2DM in the Department of Veterans Affairs system who took DPP-4 inhibitors for mean of more than 3 years and a matched group of 52,118 patients with T2DM who didn’t take the drugs.
Disclosures: The study was funded by the Midwest Biomedical Research Foundation and the VA. The study authors reported no relevant disclosures.
Source: Garcia-Tourza M et al. Kidney Week 2018, Abstract TH-OR035.
Gastric Banding vs Metformin
Gastric banding was just as successful as metformin alone in stabilizing prediabetes or new-onset type 2 diabetes in the Beta Cell Restoration through Fat Mitigation study (BetaFat), an NIH-supported study.
The study is part of the Restoring Insulin Secretion (RISE) study, a set of 3 clinical trials designed to find ways to reverse or slow the loss of insulin production and release in people at risk for type 2 diabetes.
In this study, 44 patients were randomly assigned to have a gastric banding procedure, and 44 were taking metformin. After 2 years, people in the gastric banding group had lost an average of 23 lb , vs 4 lb in the metformin group. Insulin sensitivity improved similarly in both groups, as did function of insulin-producing cells. Both groups showed small improvements in blood glucose levels.
Gastric banding was just as successful as metformin alone in stabilizing prediabetes or new-onset type 2 diabetes in the Beta Cell Restoration through Fat Mitigation study (BetaFat), an NIH-supported study.
The study is part of the Restoring Insulin Secretion (RISE) study, a set of 3 clinical trials designed to find ways to reverse or slow the loss of insulin production and release in people at risk for type 2 diabetes.
In this study, 44 patients were randomly assigned to have a gastric banding procedure, and 44 were taking metformin. After 2 years, people in the gastric banding group had lost an average of 23 lb , vs 4 lb in the metformin group. Insulin sensitivity improved similarly in both groups, as did function of insulin-producing cells. Both groups showed small improvements in blood glucose levels.
Gastric banding was just as successful as metformin alone in stabilizing prediabetes or new-onset type 2 diabetes in the Beta Cell Restoration through Fat Mitigation study (BetaFat), an NIH-supported study.
The study is part of the Restoring Insulin Secretion (RISE) study, a set of 3 clinical trials designed to find ways to reverse or slow the loss of insulin production and release in people at risk for type 2 diabetes.
In this study, 44 patients were randomly assigned to have a gastric banding procedure, and 44 were taking metformin. After 2 years, people in the gastric banding group had lost an average of 23 lb , vs 4 lb in the metformin group. Insulin sensitivity improved similarly in both groups, as did function of insulin-producing cells. Both groups showed small improvements in blood glucose levels.
Dulaglutide meets primary endpoint in REWIND
Eli Lilly has announced top line results from REWIND, a multicenter, randomized, double-blind, placebo-controlled trial designed to study dulaglutide (Trulicity). The cardiovascular outcomes trial, which had a median follow-up period of more than 5 years, evaluated cardiovascular outcomes in nearly 10,000 patients with type 2 diabetes.
The primary endpoint of REWIND was time until the first occurrence of a major adverse cardiovascular event. Patients who received dulaglutide had a significantly reduced incidence of these events, compared with placebo, meeting the primary trial endpoint. No specific results were announced.
REWIND was distinct in that it had limited participation from people with established cardiovascular disease, which allowed dulaglutide’s effect to be measured in a broad population of people with type 2 diabetes, Eli Lilly said in their press release.
Dulaglutide is a GLP-1 receptor agonist, and trial participants received a 1.5-mg dose once a week.
Full results of the REWIND trial will be presented at the annual scientific sessions of the American Diabetes Association in June 2019.
Eli Lilly has announced top line results from REWIND, a multicenter, randomized, double-blind, placebo-controlled trial designed to study dulaglutide (Trulicity). The cardiovascular outcomes trial, which had a median follow-up period of more than 5 years, evaluated cardiovascular outcomes in nearly 10,000 patients with type 2 diabetes.
The primary endpoint of REWIND was time until the first occurrence of a major adverse cardiovascular event. Patients who received dulaglutide had a significantly reduced incidence of these events, compared with placebo, meeting the primary trial endpoint. No specific results were announced.
REWIND was distinct in that it had limited participation from people with established cardiovascular disease, which allowed dulaglutide’s effect to be measured in a broad population of people with type 2 diabetes, Eli Lilly said in their press release.
Dulaglutide is a GLP-1 receptor agonist, and trial participants received a 1.5-mg dose once a week.
Full results of the REWIND trial will be presented at the annual scientific sessions of the American Diabetes Association in June 2019.
Eli Lilly has announced top line results from REWIND, a multicenter, randomized, double-blind, placebo-controlled trial designed to study dulaglutide (Trulicity). The cardiovascular outcomes trial, which had a median follow-up period of more than 5 years, evaluated cardiovascular outcomes in nearly 10,000 patients with type 2 diabetes.
The primary endpoint of REWIND was time until the first occurrence of a major adverse cardiovascular event. Patients who received dulaglutide had a significantly reduced incidence of these events, compared with placebo, meeting the primary trial endpoint. No specific results were announced.
REWIND was distinct in that it had limited participation from people with established cardiovascular disease, which allowed dulaglutide’s effect to be measured in a broad population of people with type 2 diabetes, Eli Lilly said in their press release.
Dulaglutide is a GLP-1 receptor agonist, and trial participants received a 1.5-mg dose once a week.
Full results of the REWIND trial will be presented at the annual scientific sessions of the American Diabetes Association in June 2019.
Sleep: The new frontier in cardiovascular prevention
MUNICH – Getting less than 6 hours of sleep nightly on a regular basis or waking up multiple times was independently associated with increased risk of subclinical atherosclerosis in the Spanish PESA study, Fernando Dominguez, MD, reported at the annual congress of the European Society of Cardiology.
Moreover, a graded response was evident in PESA (Progression of Early Subclinical Atherosclerosis): The more times an individual typically awoke per night, the greater the number of atherosclerotic carotid or femoral artery territories documented on three-dimensional vascular ultrasound, added Dr. Dominguez of the Spanish National Center for Cardiovascular Research in Madrid.
the cardiologist said.
The cross-sectional PESA study, whose principal investigator was Valentin Fuster, MD, PhD, included 3,974 middle-aged Madrid bank employees free of known heart disease or history of stroke who wore a waistband activity monitor for a week to record sleep quantity and quality. They also underwent three-dimensional vascular ultrasound and measurement of coronary artery calcium.
PESA was one of several large studies presented at the meeting that focused on deviations from normal sleep as a marker for increased risk of cardiovascular disease and/or mortality. Of note, however, PESA was the only one to use activity monitoring technology to track sleep.
“It was essential to use objectively measured sleep variables, because they showed huge disparity with patients’ self-reports on sleep questionnaires,” Dr. Dominguez explained.
Indeed, while 10.7% of PESA participants self-reported sleeping less than 6 hours per night on the Sleep Habits Questionnaire, actigraphy showed the true rate was 27.1%.
Based on actigraphic findings, subjects were divided into tertiles based upon average hours of sleep per night, ranging from less than 6 to more than 8. They were also grouped in quintiles based upon their extent of fragmented sleep.
Subjects with short sleep were significantly older and more likely to have high blood pressure, a higher body mass index, and metabolic syndrome than those who averaged 7-8 hours of sleep. Individuals in the top quintile for sleep awakening were older and had higher prevalences of smoking and hypertension than those in the lowest quintile.
In multivariate analyses adjusted for these differences as well as for physical activity, depression, obstructive sleep apnea, daily calorie consumption, alcohol intake, and other potential confounders, subjects who slept less than 6 hours per night had a 27% greater volume of noncoronary plaque than those who slept 7-8 hours. They also had 21% more vascular territories laden with subclinical atherosclerosis. The risk of subclinical noncoronary atherosclerosis was greater among women who averaged less than 6 hours of sleep per night, representing a 48% relative risk increase in plaque volume, versus 21% in men.
At the other extreme, women who slept more than 8 hours per night had an 83% increased plaque volume, while men who slept that much had no increase in risk, compared with men who slept for 7-8 hours.
Subjects in the top quintile for sleep fragmentation had 34% more vascular territories affected by atherosclerosis than those in the lowest quintile. Their noncoronary plaque burden was 23% greater as well.
An 11-study meta-analysis
Epameinondas Fountas, MD, of the Onassis Cardiac Surgery Center in Athens, presented a meta-analysis of 11 prospective studies of the relationship between daily sleep duration and cardiovascular disease morbidity and mortality published within the past 5 years, reflecting burgeoning interest in this hot-button topic. Collectively, the meta-analysis totaled 1,000,541 adults without baseline cardiovascular disease who were followed for an average of 9.3 years.
In an analysis adjusted for numerous known cardiovascular risk factors, the Greek investigators found that short sleep duration as defined by a self-reported average of less than 6 hours per night was independently associated with a statistically significant and clinically meaningful 11% increase in the risk of diagnosis of fatal or nonfatal cardiovascular disease, compared with individuals who averaged 6-8 hours nightly. Moreover, those who averaged more than 8 hours of sleep per night were also at risk: they averaged a 32% increased risk in fatal or nonfatal cardiovascular events compared to normal 6- to 8-hour sleepers. Thus, 6-8 hours of sleep per night appears to be the sweet spot in terms of cardioprotection.
“Our message to patients is simple: Sleep well, not too long, nor too short, and be active,” Dr. Fountas said.
Numerous investigators have highlighted the pathophysiologic changes related to sleep deprivation that likely boost cardiovascular risk. These include activation of the sympathetic nervous system, increased inflammation, and disrupted glucose metabolism, he noted.
Swedes weigh in
Moa Bengtsson, a combined medical/PhD student at the University of Gothenburg (Sweden), presented a prospective study of 798 men who were 50 years old in 1993, when they underwent a physical examination and completed extensive lifestyle questionnaires that included average self-reported sleep duration. Among the 759 men still available for evaluation after 21 years, or nearly 15,000 person-years of followup, those who reported sleeping an average of 5 hours or less per night back at age 50 were 93% more likely to have experienced a major cardiovascular event by age 71 -- acute MI, stroke, coronary revascularization, heart failure hospitalization, or cardiovascular death -- compared with those who averaged 7-8 hours of shut eye.
The short sleepers had a higher prevalence of obesity, diabetes, hypertension, smoking, and physical inactivity than the men who slept 7-8 hours per night. However, these and other confounders were adjusted for in the multivariate analysis.
To place sleep abnormalities in context, Ms. Bengtssen observed that short sleep in the Gothenburg men was numerically a stronger independent risk factor for future cardiovascular events than obesity, which was associated with an 82% increase in risk, or even smoking, with a 70% increase in risk.
Men who averaged either 6 hours of sleep per night or more than 8 hours were not at increased cardiovascular risk over 21 years of followup, compared with those who slept 7-8 hours.
Like the other investigators, she noted that the studies presented at the meeting, despite their extensive adjustments for potential confounders, don’t prove a direct causal relationship between short sleep and increased cardiovascular risk. An informative next step in research, albeit a challenging one, would be to show whether improved long-term sleep habits favorably alter cardiovascular risk.
All three study investigators reported having no financial conflicts regarding their research, which was conducted free of commercial support.
MUNICH – Getting less than 6 hours of sleep nightly on a regular basis or waking up multiple times was independently associated with increased risk of subclinical atherosclerosis in the Spanish PESA study, Fernando Dominguez, MD, reported at the annual congress of the European Society of Cardiology.
Moreover, a graded response was evident in PESA (Progression of Early Subclinical Atherosclerosis): The more times an individual typically awoke per night, the greater the number of atherosclerotic carotid or femoral artery territories documented on three-dimensional vascular ultrasound, added Dr. Dominguez of the Spanish National Center for Cardiovascular Research in Madrid.
the cardiologist said.
The cross-sectional PESA study, whose principal investigator was Valentin Fuster, MD, PhD, included 3,974 middle-aged Madrid bank employees free of known heart disease or history of stroke who wore a waistband activity monitor for a week to record sleep quantity and quality. They also underwent three-dimensional vascular ultrasound and measurement of coronary artery calcium.
PESA was one of several large studies presented at the meeting that focused on deviations from normal sleep as a marker for increased risk of cardiovascular disease and/or mortality. Of note, however, PESA was the only one to use activity monitoring technology to track sleep.
“It was essential to use objectively measured sleep variables, because they showed huge disparity with patients’ self-reports on sleep questionnaires,” Dr. Dominguez explained.
Indeed, while 10.7% of PESA participants self-reported sleeping less than 6 hours per night on the Sleep Habits Questionnaire, actigraphy showed the true rate was 27.1%.
Based on actigraphic findings, subjects were divided into tertiles based upon average hours of sleep per night, ranging from less than 6 to more than 8. They were also grouped in quintiles based upon their extent of fragmented sleep.
Subjects with short sleep were significantly older and more likely to have high blood pressure, a higher body mass index, and metabolic syndrome than those who averaged 7-8 hours of sleep. Individuals in the top quintile for sleep awakening were older and had higher prevalences of smoking and hypertension than those in the lowest quintile.
In multivariate analyses adjusted for these differences as well as for physical activity, depression, obstructive sleep apnea, daily calorie consumption, alcohol intake, and other potential confounders, subjects who slept less than 6 hours per night had a 27% greater volume of noncoronary plaque than those who slept 7-8 hours. They also had 21% more vascular territories laden with subclinical atherosclerosis. The risk of subclinical noncoronary atherosclerosis was greater among women who averaged less than 6 hours of sleep per night, representing a 48% relative risk increase in plaque volume, versus 21% in men.
At the other extreme, women who slept more than 8 hours per night had an 83% increased plaque volume, while men who slept that much had no increase in risk, compared with men who slept for 7-8 hours.
Subjects in the top quintile for sleep fragmentation had 34% more vascular territories affected by atherosclerosis than those in the lowest quintile. Their noncoronary plaque burden was 23% greater as well.
An 11-study meta-analysis
Epameinondas Fountas, MD, of the Onassis Cardiac Surgery Center in Athens, presented a meta-analysis of 11 prospective studies of the relationship between daily sleep duration and cardiovascular disease morbidity and mortality published within the past 5 years, reflecting burgeoning interest in this hot-button topic. Collectively, the meta-analysis totaled 1,000,541 adults without baseline cardiovascular disease who were followed for an average of 9.3 years.
In an analysis adjusted for numerous known cardiovascular risk factors, the Greek investigators found that short sleep duration as defined by a self-reported average of less than 6 hours per night was independently associated with a statistically significant and clinically meaningful 11% increase in the risk of diagnosis of fatal or nonfatal cardiovascular disease, compared with individuals who averaged 6-8 hours nightly. Moreover, those who averaged more than 8 hours of sleep per night were also at risk: they averaged a 32% increased risk in fatal or nonfatal cardiovascular events compared to normal 6- to 8-hour sleepers. Thus, 6-8 hours of sleep per night appears to be the sweet spot in terms of cardioprotection.
“Our message to patients is simple: Sleep well, not too long, nor too short, and be active,” Dr. Fountas said.
Numerous investigators have highlighted the pathophysiologic changes related to sleep deprivation that likely boost cardiovascular risk. These include activation of the sympathetic nervous system, increased inflammation, and disrupted glucose metabolism, he noted.
Swedes weigh in
Moa Bengtsson, a combined medical/PhD student at the University of Gothenburg (Sweden), presented a prospective study of 798 men who were 50 years old in 1993, when they underwent a physical examination and completed extensive lifestyle questionnaires that included average self-reported sleep duration. Among the 759 men still available for evaluation after 21 years, or nearly 15,000 person-years of followup, those who reported sleeping an average of 5 hours or less per night back at age 50 were 93% more likely to have experienced a major cardiovascular event by age 71 -- acute MI, stroke, coronary revascularization, heart failure hospitalization, or cardiovascular death -- compared with those who averaged 7-8 hours of shut eye.
The short sleepers had a higher prevalence of obesity, diabetes, hypertension, smoking, and physical inactivity than the men who slept 7-8 hours per night. However, these and other confounders were adjusted for in the multivariate analysis.
To place sleep abnormalities in context, Ms. Bengtssen observed that short sleep in the Gothenburg men was numerically a stronger independent risk factor for future cardiovascular events than obesity, which was associated with an 82% increase in risk, or even smoking, with a 70% increase in risk.
Men who averaged either 6 hours of sleep per night or more than 8 hours were not at increased cardiovascular risk over 21 years of followup, compared with those who slept 7-8 hours.
Like the other investigators, she noted that the studies presented at the meeting, despite their extensive adjustments for potential confounders, don’t prove a direct causal relationship between short sleep and increased cardiovascular risk. An informative next step in research, albeit a challenging one, would be to show whether improved long-term sleep habits favorably alter cardiovascular risk.
All three study investigators reported having no financial conflicts regarding their research, which was conducted free of commercial support.
MUNICH – Getting less than 6 hours of sleep nightly on a regular basis or waking up multiple times was independently associated with increased risk of subclinical atherosclerosis in the Spanish PESA study, Fernando Dominguez, MD, reported at the annual congress of the European Society of Cardiology.
Moreover, a graded response was evident in PESA (Progression of Early Subclinical Atherosclerosis): The more times an individual typically awoke per night, the greater the number of atherosclerotic carotid or femoral artery territories documented on three-dimensional vascular ultrasound, added Dr. Dominguez of the Spanish National Center for Cardiovascular Research in Madrid.
the cardiologist said.
The cross-sectional PESA study, whose principal investigator was Valentin Fuster, MD, PhD, included 3,974 middle-aged Madrid bank employees free of known heart disease or history of stroke who wore a waistband activity monitor for a week to record sleep quantity and quality. They also underwent three-dimensional vascular ultrasound and measurement of coronary artery calcium.
PESA was one of several large studies presented at the meeting that focused on deviations from normal sleep as a marker for increased risk of cardiovascular disease and/or mortality. Of note, however, PESA was the only one to use activity monitoring technology to track sleep.
“It was essential to use objectively measured sleep variables, because they showed huge disparity with patients’ self-reports on sleep questionnaires,” Dr. Dominguez explained.
Indeed, while 10.7% of PESA participants self-reported sleeping less than 6 hours per night on the Sleep Habits Questionnaire, actigraphy showed the true rate was 27.1%.
Based on actigraphic findings, subjects were divided into tertiles based upon average hours of sleep per night, ranging from less than 6 to more than 8. They were also grouped in quintiles based upon their extent of fragmented sleep.
Subjects with short sleep were significantly older and more likely to have high blood pressure, a higher body mass index, and metabolic syndrome than those who averaged 7-8 hours of sleep. Individuals in the top quintile for sleep awakening were older and had higher prevalences of smoking and hypertension than those in the lowest quintile.
In multivariate analyses adjusted for these differences as well as for physical activity, depression, obstructive sleep apnea, daily calorie consumption, alcohol intake, and other potential confounders, subjects who slept less than 6 hours per night had a 27% greater volume of noncoronary plaque than those who slept 7-8 hours. They also had 21% more vascular territories laden with subclinical atherosclerosis. The risk of subclinical noncoronary atherosclerosis was greater among women who averaged less than 6 hours of sleep per night, representing a 48% relative risk increase in plaque volume, versus 21% in men.
At the other extreme, women who slept more than 8 hours per night had an 83% increased plaque volume, while men who slept that much had no increase in risk, compared with men who slept for 7-8 hours.
Subjects in the top quintile for sleep fragmentation had 34% more vascular territories affected by atherosclerosis than those in the lowest quintile. Their noncoronary plaque burden was 23% greater as well.
An 11-study meta-analysis
Epameinondas Fountas, MD, of the Onassis Cardiac Surgery Center in Athens, presented a meta-analysis of 11 prospective studies of the relationship between daily sleep duration and cardiovascular disease morbidity and mortality published within the past 5 years, reflecting burgeoning interest in this hot-button topic. Collectively, the meta-analysis totaled 1,000,541 adults without baseline cardiovascular disease who were followed for an average of 9.3 years.
In an analysis adjusted for numerous known cardiovascular risk factors, the Greek investigators found that short sleep duration as defined by a self-reported average of less than 6 hours per night was independently associated with a statistically significant and clinically meaningful 11% increase in the risk of diagnosis of fatal or nonfatal cardiovascular disease, compared with individuals who averaged 6-8 hours nightly. Moreover, those who averaged more than 8 hours of sleep per night were also at risk: they averaged a 32% increased risk in fatal or nonfatal cardiovascular events compared to normal 6- to 8-hour sleepers. Thus, 6-8 hours of sleep per night appears to be the sweet spot in terms of cardioprotection.
“Our message to patients is simple: Sleep well, not too long, nor too short, and be active,” Dr. Fountas said.
Numerous investigators have highlighted the pathophysiologic changes related to sleep deprivation that likely boost cardiovascular risk. These include activation of the sympathetic nervous system, increased inflammation, and disrupted glucose metabolism, he noted.
Swedes weigh in
Moa Bengtsson, a combined medical/PhD student at the University of Gothenburg (Sweden), presented a prospective study of 798 men who were 50 years old in 1993, when they underwent a physical examination and completed extensive lifestyle questionnaires that included average self-reported sleep duration. Among the 759 men still available for evaluation after 21 years, or nearly 15,000 person-years of followup, those who reported sleeping an average of 5 hours or less per night back at age 50 were 93% more likely to have experienced a major cardiovascular event by age 71 -- acute MI, stroke, coronary revascularization, heart failure hospitalization, or cardiovascular death -- compared with those who averaged 7-8 hours of shut eye.
The short sleepers had a higher prevalence of obesity, diabetes, hypertension, smoking, and physical inactivity than the men who slept 7-8 hours per night. However, these and other confounders were adjusted for in the multivariate analysis.
To place sleep abnormalities in context, Ms. Bengtssen observed that short sleep in the Gothenburg men was numerically a stronger independent risk factor for future cardiovascular events than obesity, which was associated with an 82% increase in risk, or even smoking, with a 70% increase in risk.
Men who averaged either 6 hours of sleep per night or more than 8 hours were not at increased cardiovascular risk over 21 years of followup, compared with those who slept 7-8 hours.
Like the other investigators, she noted that the studies presented at the meeting, despite their extensive adjustments for potential confounders, don’t prove a direct causal relationship between short sleep and increased cardiovascular risk. An informative next step in research, albeit a challenging one, would be to show whether improved long-term sleep habits favorably alter cardiovascular risk.
All three study investigators reported having no financial conflicts regarding their research, which was conducted free of commercial support.
REPORTING FROM THE ESC CONGRESS 2018
Canagliflozin approved for cardiovascular event risk reduction
The Food and Drug Administration has approved canagliflozin (Invokana) as a way to reduce the risk of major adverse cardiovascular events in patients with type 2 diabetes and cardiovascular disease, according to Janssen Pharmaceuticals.
The sodium–glucose cotransporter 2 inhibitor was first approved in 2013 to improve glycemic control in adults with type 2 diabetes.
FDA approval was based on results from the CANVAS (Canagliflozin Cardiovascular Assessment Study) trial, which included more than 10,000 adults with type 2 diabetes who either had cardiovascular disease or were at risk for cardiovascular disease. Overall, patients who received canagliflozin had a 14% lower risk of experiencing a major cardiovascular event over the control group, and patients with established cardiovascular disease had an 18% lower risk.
The most common adverse events associated with canagliflozin include female genital mycotic infections, urinary tract infection, and increased urination. Notably, canagliflozin also increases the risk of lower-extremity amputation, especially in those with a history of amputation.
“Americans living with type 2 diabetes are two to three times more likely to die from heart disease than adults without diabetes. With this approval, Invokana now plays an even more important role in the overall treatment mix with its demonstrated ability to reduce the risk of potentially devastating cardiovascular events,” Ralph A. DeFronzo, MD, professor and division chief of medicine and diabetes at the University of Texas, San Antonio, said in the press release.
The new indication applies to all formulations of canagliflozin.
Find the full press release on the Janssen website.
The Food and Drug Administration has approved canagliflozin (Invokana) as a way to reduce the risk of major adverse cardiovascular events in patients with type 2 diabetes and cardiovascular disease, according to Janssen Pharmaceuticals.
The sodium–glucose cotransporter 2 inhibitor was first approved in 2013 to improve glycemic control in adults with type 2 diabetes.
FDA approval was based on results from the CANVAS (Canagliflozin Cardiovascular Assessment Study) trial, which included more than 10,000 adults with type 2 diabetes who either had cardiovascular disease or were at risk for cardiovascular disease. Overall, patients who received canagliflozin had a 14% lower risk of experiencing a major cardiovascular event over the control group, and patients with established cardiovascular disease had an 18% lower risk.
The most common adverse events associated with canagliflozin include female genital mycotic infections, urinary tract infection, and increased urination. Notably, canagliflozin also increases the risk of lower-extremity amputation, especially in those with a history of amputation.
“Americans living with type 2 diabetes are two to three times more likely to die from heart disease than adults without diabetes. With this approval, Invokana now plays an even more important role in the overall treatment mix with its demonstrated ability to reduce the risk of potentially devastating cardiovascular events,” Ralph A. DeFronzo, MD, professor and division chief of medicine and diabetes at the University of Texas, San Antonio, said in the press release.
The new indication applies to all formulations of canagliflozin.
Find the full press release on the Janssen website.
The Food and Drug Administration has approved canagliflozin (Invokana) as a way to reduce the risk of major adverse cardiovascular events in patients with type 2 diabetes and cardiovascular disease, according to Janssen Pharmaceuticals.
The sodium–glucose cotransporter 2 inhibitor was first approved in 2013 to improve glycemic control in adults with type 2 diabetes.
FDA approval was based on results from the CANVAS (Canagliflozin Cardiovascular Assessment Study) trial, which included more than 10,000 adults with type 2 diabetes who either had cardiovascular disease or were at risk for cardiovascular disease. Overall, patients who received canagliflozin had a 14% lower risk of experiencing a major cardiovascular event over the control group, and patients with established cardiovascular disease had an 18% lower risk.
The most common adverse events associated with canagliflozin include female genital mycotic infections, urinary tract infection, and increased urination. Notably, canagliflozin also increases the risk of lower-extremity amputation, especially in those with a history of amputation.
“Americans living with type 2 diabetes are two to three times more likely to die from heart disease than adults without diabetes. With this approval, Invokana now plays an even more important role in the overall treatment mix with its demonstrated ability to reduce the risk of potentially devastating cardiovascular events,” Ralph A. DeFronzo, MD, professor and division chief of medicine and diabetes at the University of Texas, San Antonio, said in the press release.
The new indication applies to all formulations of canagliflozin.
Find the full press release on the Janssen website.
