Unspecified stress disorders and risk of arterial and venous thromboembolic disease in the Danish population

•Unspecified reaction to severe stress is associated with cardiovascular diseases.•Incidence of 7 cardiovascular events/conditions is 1.3–1.9 times that in the general population.•Results are consistent with those observed for posttraumatic stress disorder.•This disorder category may represent subsyndromal stress disorders. Posttraumatic stress disorder is a well-documented risk factor for cardiovascular disease. Whether non-specific stress-related psychopathology also increases risk is less well known. In a cohort of adult Danish-born residents of Denmark with an incident diagnosis of unspecified reaction to severe stress (“unspecified stress reaction”) between 1995 and 2011 (N = 24,534), we assessed incidence of seven arterial and venous cardiovascular events/conditions between 1996 and 2013. We calculated standardized incidence ratios (SIRs) comparing incidence of each outcome among the cohort to expected incidence based on sex-, age-, and calendar-time-specific national rates. We conducted stratified analyses by demographic characteristics, comorbidities, and length of follow-up time. Incidence over the study period ranged from 1.1% for provoked VTE to 5.7% for stroke, adjusting for competing risk of death. Unspecified stress reaction was associated with all outcomes (SIRs ranging from 1.3, 95% confidence interval (CI): 1.1–1.4 for atrial fibrillation/flutter to 1.9, 95% CI: 1.7–2.2 for unprovoked VTE and 1.9, 95% CI: 1.6–2.3 for provoked VTE). Associations persisted, but were attenuated, when restricting to persons without alcohol use disorder and to persons without physical health comorbidities. Unspecified stress reaction has less precise criteria than other stress-related diagnoses, and we could not adjust for some potential confounders. Our results augment literature on stress disorders and cardiovascular disease by highlighting the additional importance of unspecified stress disorders. Further research on this diagnostic category, which may represent subsyndromal psychopathology, is warranted. These findings support considering persons with non-specific stress-related psychopathology in treatment and tertiary prevention activities.