PracticeUpdate Cardiology June 2019

EDITOR’S PICKS 8

Stress-Related Disorders Associated With Risk of Cardiovascular Disease

COMMENT By Viola Vaccarino MD, PhD T he link between depression and risk of cardiovascular disease (CVD) has been established by numerous stud- ies, but prospective data on posttraumatic stress disorder (PTSD) and other psychiatric conditions remain limited. In this large, Swedish population study, investigators examined the association between a diagnosis of a “stress-related disorder,” including PTSD, acute stress reaction, or adjustment disor- der, and a subsequent diagnosis of CVD over a follow-up of almost 30 years. The authors utilized data from the Swedish National Patient Register linked to other national databases. Using an elegant design, they compared approximately 130,000 individuals with such psychiatric diagnoses in the database (over about 25 years) with siblings without these disorders, as well as with unrelated people from the general population. In both types of comparisons, they found a consistent association between having a stress-related disorder and future CVD events of var- ious subtypes, with an increase in risk between 30% and 70%. The associations were strongest in the first year after a diag- nosis of a stress-induced psychiatric disorder, especially in the first few months. Associations were also stronger in those who were young at baseline (particularly if <30 years old), and those with early-onset CVD (occurring before age 50). The controlled design in a population-based sample is an important strength of this study, and its large size allowed the authors to examine relatively rare psychiatric diagnoses in relation to specific subtypes of CVD. However, reliance on diag- nostic codes in clinical databases for the definition of health conditions can be problematic, especially for psychiatric dis- orders, which tend to be systematically underdiagnosed. This problem, and the fact that the association with CVD occurred mostly within a short time after the psychiatric diagnosis, raises the potential for reverse causation, such that the acute stress disorder could be a consequence of cardiac problems rather than a cause, especially since the exact time of onset was not known. In addition, CVD diagnostic codes could have been overused in persons with stress-induced disorders, such as PTSD, who tend to report more physical symptoms. Such concern should be less, however, for acute severe cardiac conditions, such as myocardial infarction and cardiac arrest. Nonetheless, these data are an important addition to our understanding of the link between psychological stress and CVD. This study suggests that the time immediately after the diagnosis of a psychiatric disorder induced by acute stress or trauma is a vulnerable time for CVD risk. It also highlights an observation largely overlooked before, which is that stress may affect CVD risk primarily in younger people and may affect development of early-onset CVD. Studies that have focused on older populations and that have used long-term follow-up durations may have missed important early risks associated with stress-related psychiatric disorders.

British Medical Journal Take-home message

• Data from the SwedishNational Patient Register were analyzed to evaluate the association between stress-related disorders and the risk of cardiovascular disease. Data of individuals affected by post-traumatic stress disorder, acute stress reac- tion, adjustment disorder, and other stress reactions and their unaffected siblings were analyzed. The hazard ratio for any cardiovascular disease in the affected individual compared with the sibling was 1.64 in the first year after diagnosis of the stress-related disorder, and the hazard ratio for heart failure in this time period was 6.95. After the first year, the hazard ratios in the affected individual compared with the sibling ranged from 1.12 for arrhythmia to 2.02 for artery thrombosis/embolus. • Stress-related disorders have a significant association with many types of cardiovascular disease. Abstract OBJECTIVE To assess the association between stress related disorders and subsequent risk of cardiovascular disease. DESIGN Population based, sibling controlled cohort study. SETTING Population of Sweden. PARTICIPANTS 136637 patients in the Swedish National Patient Register with stress related disorders, including post-traumatic stress disorder (PTSD), acute stress reaction, adjustment disorder, and other stress reac- tions, from 1987 to 2013; 171 314 unaffected full siblings of these patients; and 1 366370 matched unexposed people from the general population. MAIN OUTCOME MEASURES Primary diagnosis of incident cardiovascular dis- ease—any or specific subtypes (ischaemic heart disease, cerebrovascular disease, emboli/thrombosis, hypertensive diseases, heart failure, arrhyth- mia/conduction disorder, and fatal cardiovascular disease)—and 16 individual diagnoses of cardiovascular disease. Hazard ratios for cardiovascular disease were derived from Cox models, after controlling for multiple confounders. RESULTS During up to 27 years of follow-up, the crude incidence rate of any cardiovascular disease was 10.5, 8.4, and 6.9 per 1000 person years among exposed patients, their unaffected full siblings, and the matched unexposed individuals, respectively. In sibling based comparisons, the hazard ratio for any cardiovascular disease was 1.64 (95% confidence interval 1.45 to 1.84), with the highest subtype specific hazard ratio observed for heart failure (6.95, 1.88 to 25.68), during the first year after the diagnosis of any stress related disorder. Beyond one year, the hazard ratios became lower (overall 1.29, 1.24 to 1.34), ranging from 1.12 (1.04 to 1.21) for arrhythmia to 2.02 (1.45 to 2.82) for artery thrombosis/embolus. Stress related disorders were more strongly associated with early onset cardiovascular diseases (hazard ratio 1.40 (1.32 to 1.49) for attained age <50) than later onset ones (1.24 (1.18 to 1.30) for attained age ≥50; P for difference=0.002). Except for fatal cardio- vascular diseases, these associations were not modified by the presence of psychiatric comorbidity. Analyses within the population matched cohort yielded similar results (hazard ratio 1.71 (1.59 to 1.83) for any cardiovascular disease during the first year of follow-up and 1.36 (1.33 to 1.39) thereafter). CONCLUSION Stress related disorders are robustly associated with multiple types of cardiovascular disease, independently of familial background, his- tory of somatic/psychiatric diseases, and psychiatric comorbidity. Stress Related Disorders and Risk of Cardiovascular Disease: Population Based, Sibling Controlled Cohort Study. BMJ 2019 Apr 10;365(xx)l1255, H Song, F Fang, FK Arnberg, et al. www.practiceupdate.com/c/82357

Dr. Vaccarino is the Wilton Looney Chair of Cardiovascular Research and Professor and Chair of the Department of Epidemiology at the Rollins School of Public Health, Emory University in Atlanta, Georgia.

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