Depression as a Risk Factor for the Initial Presentation of Twelve Cardiac, Cerebrovascular, and Peripheral Arterial Diseases: Data Linkage Study of 1.9 Million Women and Men

Abstract

Background: Depression is associated with coronary heart disease and stroke, but associations with a range of pathologically diverse cardiovascular diseases are not well understood. We examine the risk of 12 cardiovascular diseases according to depression status (history or new onset).

Methods: Cohort study of 1,937,360 adult men and women, free from cardiovascular disease at baseline, using linked UK electronic health records between 1997 and 2010. The exposures were new-onset depression (a new GP diagnosis of depression and/or prescription for antidepressants during a one-year baseline), and history of GP-diagnosed depression before baseline. The primary endpoint was initial presentation of 12 cardiovascular diseases after baseline. We used disease-specific Cox proportional hazards models with multiple imputation adjusting for cardiovascular risk factors (age, sex, socioeconomic status, smoking, blood pressure, diabetes, cholesterol).

Results: Over a median [IQR] 6.9 [2.1-10.5] years of follow-up, 18.9% had a history of depression and 94,432 incident cardiovascular events occurred. After adjustment for cardiovascular risk factors, history of depression was associated with: stable angina (Hazard Ratio = 1.38, 95%CI 1.32-1.45), unstable angina (1.70, 1.60-1.82), myocardial infarction (1.21, 1.16-1.27), unheralded coronary death (1.23, 1.14-1.32), heart failure (1.18, 1.13-1.24), cardiac arrest (1.14, 1.03-1.26), transient ischemic attack (1.31, 1.25-1.38), ischemic stroke (1.26, 1.18-1.34), subarachnoid haemorrhage (1.17, 1.01-1.35), intracerebral haemorrhage (1.30, 1.17-1.45), peripheral arterial disease (1.24, 1.18-1.30), and abdominal aortic aneurysm (1.12,1.01-1.24). New onset depression developed in 2.9% of people, among whom 63,761 cardiovascular events occurred. New onset depression was similarly associated with each of the 12 diseases, with no evidence of stronger associations compared to history of depression. The strength of association between depression and these cardiovascular diseases did not differ between women and men.

Conclusion: Depression was prospectively associated with cardiac, cerebrovascular, and peripheral diseases, with no evidence of disease specificity. Further research is needed in understanding the specific pathophysiology of heart and vascular disease triggered by depression in healthy populations.

Fig 1. Cohort diagrams.

(A) History of depression cohort (B) New onset depression cohort.

Fig 2. Hazard ratios (HR) and 95% confidence interval (95%CI) for the association of history of depression with 12 cardiovascular diseases, adjusted for age, gender, smoking, systolic blood pressure, diabetes, cholesterol, and socio-economic status (94,432 events in 1,937,360 men and women).

Abbreviations: CHD, coronary heart disease; SCD, sudden cardiac death. Vertical dotted line indicates the HRs for total cardiovascular diseases: HR = 1.28 (95%CI 1.26–1.30).

Fig 3. Hazard ratios (HR) and 95% confidence intervals (95%CI) by gender for the association of history of depression with 12 cardiovascular diseases, adjusted for age, smoking, systolic blood pressure, diabetes, cholesterol, and socio-economic status (94,432 events in 958,329 men and 979,031 women).

P-values for interaction between gender and history of depression: stable angina p = 0.618, unstable angina p = 0.174, myocardial infarction p = 0.210, unheralded coronary death p = 0.478, heart failure p = 0.101, cardiac arrest/sudden cardiac death p = 0.972, transient ischaemic attack p = 0.632, ischaemic stroke p = 0.113, subarachnoid haemorrhage p = 0.683, intracerebral haemorrhage p = 0.612, peripheral arterial disease p = 0.265, abdominal aortic aneurysm p = 0.303. Abbreviation: SCD; sudden cardiac death.

Fig 4. Hazard ratios (HR) and 95% confidence interval (95%CI) for the association of new onset depression with 12 cardiovascular diseases, adjusted for age, gender, smoking, systolic blood pressure, diabetes, cholesterol, and socio-economic status (63,761 events in 1,356,578 men and women).

Abbreviations: CHD; coronary heart disease, SCD; sudden cardiac death. Vertical dotted line indicates the HRs for total cardiovascular diseases: HR = 1.30 (95%CI 1.24–1.35).