Robust interventional studies needed to establish causality, directionality
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Stress disorders triggered by life events or trauma have a marked deleterious impact on the cardiovascular system, especially in the short term, suggests a Swedish population-based cohort study of more than 1.6 million people.

Previous studies have had limited power to detect associations and have seldom explored conditions other than PTSD, noted the investigators, led by Huan Song, PhD. In addition, little is known about how genetic predisposition to cardiovascular disease may influence the association.

Results of the new study, reported online in the BMJ, showed that with a median follow-up of about 6.5 years, relative to unaffected siblings, patients who had PTSD, acute stress reaction, adjustment disorder, or another stress reaction had a 64% higher risk of developing a cardiovascular disease during the first year post diagnosis, and a 29% higher risk thereafter.

In the first year, risk was most elevated for heart failure – nearly seven times higher for the patients than for their siblings. In addition, overall risk was increased to a significantly greater extent for cardiovascular diseases with early onset, starting before age 50 years, than for those with later onset, according to Dr. Song of the Center of Public Health Sciences at the University of Iceland, Reykjavík, and the Karolinska Institutet in Stockholm. Findings were essentially the same when patients were instead compared with age- and sex-matched individuals from the general population.

“Stress-related disorders are robustly associated with multiple types of cardiovascular disease, independently of familial background, history of somatic/psychiatric diseases, and psychiatric comorbidity,” Dr. Song and her coinvestigators wrote. “These findings call for enhanced clinical awareness and, if verified, monitoring or early intervention among patients with recently diagnosed stress related disorders.”

Study details

In their population-based cohort study of the Swedish National Patient Register, the investigators identified 136,637 patients with new-onset, stress-related disorders diagnosed between 1987 and 2013. They compared these patients with 171,314 unaffected full siblings and with 1,366,370 unaffected matched people from the general population. Median follow-up was 6.2 years, 6.9 years, and 6.5 years, respectively.

Results showed that the crude incidence rate of any cardiovascular disease was 10.5 per 1,000 person years among the patients with stress-related disorders, 8.4 per 1,000 person years among their unaffected siblings, and 6.9 per 1,000 person years among the matched unaffected individuals from the general population.

Compared with unaffected siblings, patients with stress-related disorders had a 60% elevated risk for developing any cardiovascular disease during the first year after diagnosis. Risk in this window was most elevated for heart failure (hazard ratio, 6.95); cerebrovascular disease other than ischemic and hemorrhagic stroke and arachnoidal bleeding (HR, 5.64), conduction disorders (HR, 5.00), and cardiac arrest (HR, 3.37).

Risk of any cardiovascular disease associated with stress-related disorders was still elevated but to a lesser extent after the first year post diagnosis (HR, 1.29). During this period, risk was most elevated for arterial thrombosis/embolus (HR, 2.02), hemorrhagic stroke (HR, 1.56), and fatal cerebrovascular events (HR, 1.56).

In analyses looking at age of onset of the cardiovascular disease, stress-related disorders showed stronger association with early-onset disease (occurring before age 50 years) than with later-onset disease (HR, 1.40 vs. 1.24; P = .002).

Fatal cardiovascular disease was the only category for which the associations were modified by presence of psychiatric comorbidity. Here, presence of such comorbidity amplified the risk conferred by the stress-related disorder.

Findings were much the same when patients were compared with matched individuals from the general population. Risk for any cardiovascular disease was again elevated substantially in the first year post diagnosis by 71%, and to 36% thereafter.

The authors reported that they had no relevant conflicts of interest. The study was supported by the Icelandic Research Fund, an ERC Consolidator Grant, the Karolinska Institutet, and the Swedish Research Council.

SOURCE: Song H et al. BMJ. 2019 Apr 10. doi: 10.1136/bmj.l1255.

Body

The current study cannot rule out the possibility of reverse causation, whereby cardiovascular disease, which typically manifests slowly, may predispose individuals to stress-related disorders.

In fact, the association may be bidirectional.

“[T]he ultimate test of an underlying unidirectional relation between acute stress induced psychiatric disorders and cardiovascular disease will be through intervention studies to treat these disorders,” Simon L. Bacon, PhD, maintained in an editorial. A reduction in cardiovascular risk after effective treatment of the stress disorders would provide confirmation.

“Psychiatric intervention studies have so far been disappointing in relation to reductions in cardiovascular disease events ... although some people suggest that the null findings had more to do with the limitations of the interventions than a true failure of the hypothesis,” Dr. Bacon observed. “In the future, well-designed studies evaluating more appropriate interventions ... will be critical not only to confirm the inferences of the new study but also to provide real benefits to patients.”

Dr. Bacon is a professor at the Montreal Behavioural Medicine Centre, and department of health, kinesiology, and applied physiology at Concordia University, also in Montreal.

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Body

The current study cannot rule out the possibility of reverse causation, whereby cardiovascular disease, which typically manifests slowly, may predispose individuals to stress-related disorders.

In fact, the association may be bidirectional.

“[T]he ultimate test of an underlying unidirectional relation between acute stress induced psychiatric disorders and cardiovascular disease will be through intervention studies to treat these disorders,” Simon L. Bacon, PhD, maintained in an editorial. A reduction in cardiovascular risk after effective treatment of the stress disorders would provide confirmation.

“Psychiatric intervention studies have so far been disappointing in relation to reductions in cardiovascular disease events ... although some people suggest that the null findings had more to do with the limitations of the interventions than a true failure of the hypothesis,” Dr. Bacon observed. “In the future, well-designed studies evaluating more appropriate interventions ... will be critical not only to confirm the inferences of the new study but also to provide real benefits to patients.”

Dr. Bacon is a professor at the Montreal Behavioural Medicine Centre, and department of health, kinesiology, and applied physiology at Concordia University, also in Montreal.

Body

The current study cannot rule out the possibility of reverse causation, whereby cardiovascular disease, which typically manifests slowly, may predispose individuals to stress-related disorders.

In fact, the association may be bidirectional.

“[T]he ultimate test of an underlying unidirectional relation between acute stress induced psychiatric disorders and cardiovascular disease will be through intervention studies to treat these disorders,” Simon L. Bacon, PhD, maintained in an editorial. A reduction in cardiovascular risk after effective treatment of the stress disorders would provide confirmation.

“Psychiatric intervention studies have so far been disappointing in relation to reductions in cardiovascular disease events ... although some people suggest that the null findings had more to do with the limitations of the interventions than a true failure of the hypothesis,” Dr. Bacon observed. “In the future, well-designed studies evaluating more appropriate interventions ... will be critical not only to confirm the inferences of the new study but also to provide real benefits to patients.”

Dr. Bacon is a professor at the Montreal Behavioural Medicine Centre, and department of health, kinesiology, and applied physiology at Concordia University, also in Montreal.

Title
Robust interventional studies needed to establish causality, directionality
Robust interventional studies needed to establish causality, directionality

Stress disorders triggered by life events or trauma have a marked deleterious impact on the cardiovascular system, especially in the short term, suggests a Swedish population-based cohort study of more than 1.6 million people.

Previous studies have had limited power to detect associations and have seldom explored conditions other than PTSD, noted the investigators, led by Huan Song, PhD. In addition, little is known about how genetic predisposition to cardiovascular disease may influence the association.

Results of the new study, reported online in the BMJ, showed that with a median follow-up of about 6.5 years, relative to unaffected siblings, patients who had PTSD, acute stress reaction, adjustment disorder, or another stress reaction had a 64% higher risk of developing a cardiovascular disease during the first year post diagnosis, and a 29% higher risk thereafter.

In the first year, risk was most elevated for heart failure – nearly seven times higher for the patients than for their siblings. In addition, overall risk was increased to a significantly greater extent for cardiovascular diseases with early onset, starting before age 50 years, than for those with later onset, according to Dr. Song of the Center of Public Health Sciences at the University of Iceland, Reykjavík, and the Karolinska Institutet in Stockholm. Findings were essentially the same when patients were instead compared with age- and sex-matched individuals from the general population.

“Stress-related disorders are robustly associated with multiple types of cardiovascular disease, independently of familial background, history of somatic/psychiatric diseases, and psychiatric comorbidity,” Dr. Song and her coinvestigators wrote. “These findings call for enhanced clinical awareness and, if verified, monitoring or early intervention among patients with recently diagnosed stress related disorders.”

Study details

In their population-based cohort study of the Swedish National Patient Register, the investigators identified 136,637 patients with new-onset, stress-related disorders diagnosed between 1987 and 2013. They compared these patients with 171,314 unaffected full siblings and with 1,366,370 unaffected matched people from the general population. Median follow-up was 6.2 years, 6.9 years, and 6.5 years, respectively.

Results showed that the crude incidence rate of any cardiovascular disease was 10.5 per 1,000 person years among the patients with stress-related disorders, 8.4 per 1,000 person years among their unaffected siblings, and 6.9 per 1,000 person years among the matched unaffected individuals from the general population.

Compared with unaffected siblings, patients with stress-related disorders had a 60% elevated risk for developing any cardiovascular disease during the first year after diagnosis. Risk in this window was most elevated for heart failure (hazard ratio, 6.95); cerebrovascular disease other than ischemic and hemorrhagic stroke and arachnoidal bleeding (HR, 5.64), conduction disorders (HR, 5.00), and cardiac arrest (HR, 3.37).

Risk of any cardiovascular disease associated with stress-related disorders was still elevated but to a lesser extent after the first year post diagnosis (HR, 1.29). During this period, risk was most elevated for arterial thrombosis/embolus (HR, 2.02), hemorrhagic stroke (HR, 1.56), and fatal cerebrovascular events (HR, 1.56).

In analyses looking at age of onset of the cardiovascular disease, stress-related disorders showed stronger association with early-onset disease (occurring before age 50 years) than with later-onset disease (HR, 1.40 vs. 1.24; P = .002).

Fatal cardiovascular disease was the only category for which the associations were modified by presence of psychiatric comorbidity. Here, presence of such comorbidity amplified the risk conferred by the stress-related disorder.

Findings were much the same when patients were compared with matched individuals from the general population. Risk for any cardiovascular disease was again elevated substantially in the first year post diagnosis by 71%, and to 36% thereafter.

The authors reported that they had no relevant conflicts of interest. The study was supported by the Icelandic Research Fund, an ERC Consolidator Grant, the Karolinska Institutet, and the Swedish Research Council.

SOURCE: Song H et al. BMJ. 2019 Apr 10. doi: 10.1136/bmj.l1255.

Stress disorders triggered by life events or trauma have a marked deleterious impact on the cardiovascular system, especially in the short term, suggests a Swedish population-based cohort study of more than 1.6 million people.

Previous studies have had limited power to detect associations and have seldom explored conditions other than PTSD, noted the investigators, led by Huan Song, PhD. In addition, little is known about how genetic predisposition to cardiovascular disease may influence the association.

Results of the new study, reported online in the BMJ, showed that with a median follow-up of about 6.5 years, relative to unaffected siblings, patients who had PTSD, acute stress reaction, adjustment disorder, or another stress reaction had a 64% higher risk of developing a cardiovascular disease during the first year post diagnosis, and a 29% higher risk thereafter.

In the first year, risk was most elevated for heart failure – nearly seven times higher for the patients than for their siblings. In addition, overall risk was increased to a significantly greater extent for cardiovascular diseases with early onset, starting before age 50 years, than for those with later onset, according to Dr. Song of the Center of Public Health Sciences at the University of Iceland, Reykjavík, and the Karolinska Institutet in Stockholm. Findings were essentially the same when patients were instead compared with age- and sex-matched individuals from the general population.

“Stress-related disorders are robustly associated with multiple types of cardiovascular disease, independently of familial background, history of somatic/psychiatric diseases, and psychiatric comorbidity,” Dr. Song and her coinvestigators wrote. “These findings call for enhanced clinical awareness and, if verified, monitoring or early intervention among patients with recently diagnosed stress related disorders.”

Study details

In their population-based cohort study of the Swedish National Patient Register, the investigators identified 136,637 patients with new-onset, stress-related disorders diagnosed between 1987 and 2013. They compared these patients with 171,314 unaffected full siblings and with 1,366,370 unaffected matched people from the general population. Median follow-up was 6.2 years, 6.9 years, and 6.5 years, respectively.

Results showed that the crude incidence rate of any cardiovascular disease was 10.5 per 1,000 person years among the patients with stress-related disorders, 8.4 per 1,000 person years among their unaffected siblings, and 6.9 per 1,000 person years among the matched unaffected individuals from the general population.

Compared with unaffected siblings, patients with stress-related disorders had a 60% elevated risk for developing any cardiovascular disease during the first year after diagnosis. Risk in this window was most elevated for heart failure (hazard ratio, 6.95); cerebrovascular disease other than ischemic and hemorrhagic stroke and arachnoidal bleeding (HR, 5.64), conduction disorders (HR, 5.00), and cardiac arrest (HR, 3.37).

Risk of any cardiovascular disease associated with stress-related disorders was still elevated but to a lesser extent after the first year post diagnosis (HR, 1.29). During this period, risk was most elevated for arterial thrombosis/embolus (HR, 2.02), hemorrhagic stroke (HR, 1.56), and fatal cerebrovascular events (HR, 1.56).

In analyses looking at age of onset of the cardiovascular disease, stress-related disorders showed stronger association with early-onset disease (occurring before age 50 years) than with later-onset disease (HR, 1.40 vs. 1.24; P = .002).

Fatal cardiovascular disease was the only category for which the associations were modified by presence of psychiatric comorbidity. Here, presence of such comorbidity amplified the risk conferred by the stress-related disorder.

Findings were much the same when patients were compared with matched individuals from the general population. Risk for any cardiovascular disease was again elevated substantially in the first year post diagnosis by 71%, and to 36% thereafter.

The authors reported that they had no relevant conflicts of interest. The study was supported by the Icelandic Research Fund, an ERC Consolidator Grant, the Karolinska Institutet, and the Swedish Research Council.

SOURCE: Song H et al. BMJ. 2019 Apr 10. doi: 10.1136/bmj.l1255.

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