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Association Between Depressive Symptoms and Incident Cardiovascular Diseases
Quick Takes
- Depressive symptoms are associated with CVD incidence, including at symptom levels lower than the threshold indicative of a depressive disorder.
- The lack of ability to adjust for hypertension, lipids, and lifestyle variables limits the ability to understand the strength of the association.
- There is no evidence that depression per se is causal. It is associated with poor compliance with evidence-based treatments and lifestyle that markedly reduces risk of atherosclerotic CVD and events.
Study Questions:
Is there an association between depressive symptoms and cardiovascular disease (CVD) incidence across the spectrum of lower mood?
Methods:
A pooled analysis was conducted in two large epidemiologic studies of individual-participant data. The Emerging Risk Factors Collaboration (ERFC; multicountry and site study of 162,036 participants with surveys, 1960-2008; follow-up to March 2020) and the UK Biobank (401,219 participants with surveys, 2006-2010; follow-up to March 2020). Participants recorded self-reported depressive symptoms and had no CVD history at baseline. Depressive symptoms were also scored with validated instruments. ERFC used the Center for Epidemiological Studies Depression (CES-D) scale; range 0-60; ≥16 indicates possible depressive disorder. The UK Biobank recorded the two-item Patient Health Questionnaire 2 (PHQ-2); range, 0-6; ≥3 indicates possible depressive disorder. Primary outcomes were incident fatal or nonfatal coronary heart disease (CHD), stroke, and CVD (composite of the two). Hazard ratios (HRs) per 1-standard deviation (SD) higher log CES-D or PHQ-2 adjusted for age, sex, smoking, and diabetes were reported.
Results:
Among 162,036 participants from the ERFC (73% were women; baseline age, 63 ± 9 years), 5,078 CHD and 3,932 stroke events were recorded (median follow-up, 9.5 years). Associations with CHD, stroke, and CVD were log linear. The HR per 1-SD higher depression score for CHD was 1.07 (95% confidence interval [CI], 1.03-1.11); stroke, 1.05 (95% CI, 1.01-1.10); and CVD, 1.06 (95% CI, 1.04-1.08). The corresponding incidence rates per 10,000 person-years of follow-up in the highest versus the lowest quintile of CES-D score (geometric mean CES-D score, 19 vs. 1) were 36.3 versus 29.0 for CHD events, 28.0 versus 24.7 for stroke events, and 62.8 versus 53.5 for CVD events. Among 401,219 participants from the UK Biobank (55% were women, mean age at baseline, 56 ± 8 years), 4,607 CHD and 3,253 stroke events were recorded (median follow-up, 8.1 years). The HR per 1-SD higher depression score for CHD was 1.11 (95% CI, 1.08-1.14); stroke, 1.10 (95% CI, 1.06-1.14); and CVD, 1.10 (95% CI, 1.08-1.13). The corresponding incidence rates per 10,000 person-years of follow-up among individuals with PHQ-2 scores of 4 or higher versus 0 were 20.9 versus 14.2 for CHD events, 15.3 versus 10.2 for stroke events, and 36.2 versus 24.5 for CVD events. The magnitude and statistical significance of the HRs were not materially changed after adjustment for additional risk factors.
Conclusions:
In a pooled analysis of 563,255 participants in 22 cohorts, baseline depressive symptoms were associated with CVD incidence, including at symptom levels lower than the threshold indicative of a depressive disorder. However, the magnitude of associations was modest.
Perspective:
The study supports the long-held view that depression is strongly linked to atherosclerotic CVD events and CV risk factors, but not necessarily as an independent risk factor. The two very large (>1/2 million elderly) cohort studies cover 50 years with long-term follow-up, but the inability to adjust for hypertension and lipids seriously weakens the usefulness of the data. There is enough support for routine screening for depressive symptoms and depression in adults with and without CVD. Both correlate with CV events and mortality that are strongly tied to poor compliance with adverse lifestyle and the evidence-based treatments.
Clinical Topics: Cardiovascular Care Team, Dyslipidemia, Prevention, Lipid Metabolism, Hypertension
Keywords: Atherosclerosis, Coronary Disease, Depression, Hypertension, Incidence, Life Style, Lipids, Primary Prevention, Risk Factors, Stroke, Vascular Diseases
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