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 136 637 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 reactions, from 1987 to 2013; 171 314 unaffected full siblings of these patients; and 1 366 370 matched unexposed people from the general population.

MAIN OUTCOME MEASURES Primary diagnosis of incident cardiovascular disease-any or specific subtypes (ischaemic heart disease, cerebrovascular disease, emboli/thrombosis, hypertensive diseases, heart failure, arrhythmia/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 cardiovascular 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, history of somatic/psychiatric diseases, and psychiatric comorbidity.