Association Between Depressive Symptoms and Incident Cardiovascular Diseases

Key PointsQuestionAre depressive symptoms associated with incident cardiovascular diseases? FindingsIn a pooled analysis of individual-participant data from 563255 participants in 22 prospective cohorts, depressive symptoms (assessed by the Center for Epidemiologic Studies Depression [CES-D] scale and other validated scales) were significantly associated with incident cardiovascular disease, including scores lower than the threshold typically indicative of depressive disorders (CES-D >= 16; hazard ratio per 1-SD higher log CES-D, 1.06). MeaningDepressive symptoms, even at levels lower than what is typically indicative of potential clinical depression, were associated with risk of incident cardiovascular disease although the magnitude of the association was modest. ImportanceIt is uncertain whether depressive symptoms are independently associated with subsequent risk of cardiovascular diseases (CVDs). ObjectiveTo characterize the association between depressive symptoms and CVD incidence across the spectrum of lower mood. Design, Setting, and ParticipantsA pooled analysis of individual-participant data from the Emerging Risk Factors Collaboration (ERFC; 162036 participants; 21 cohorts; baseline surveys, 1960-2008; latest follow-up, March 2020) and the UK Biobank (401219 participants; baseline surveys, 2006-2010; latest follow-up, March 2020). Eligible participants had information about self-reported depressive symptoms and no CVD history at baseline. ExposuresDepressive symptoms were recorded using validated instruments. ERFC scores were harmonized across studies to a scale representative of the Center for Epidemiological Studies Depression (CES-D) scale (range, 0-60; >= 16 indicates possible depressive disorder). The UK Biobank recorded the 2-item Patient Health Questionnaire 2 (PHQ-2; range, 0-6; >= 3 indicates possible depressive disorder). Main Outcomes and MeasuresPrimary outcomes were incident fatal or nonfatal coronary heart disease (CHD), stroke, and CVD (composite of the 2). Hazard ratios (HRs) per 1-SD higher log CES-D or PHQ-2 adjusted for age, sex, smoking, and diabetes were reported. ResultsAmong 162036 participants from the ERFC (73%, women; mean age at baseline, 63 years [SD, 9 years]), 5078 CHD and 3932 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% 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 10000 person-years of follow-up in the highest vs the lowest quintile of CES-D score (geometric mean CES-D score, 19 vs 1) were 36.3 vs 29.0 for CHD events, 28.0 vs 24.7 for stroke events, and 62.8 vs 53.5 for CVD events. Among 401219 participants from the UK Biobank (55% were women, mean age at baseline, 56 years [SD, 8 years]), 4607 CHD and 3253 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 10000 person-years of follow-up among individuals with PHQ-2 scores of 4 or higher vs 0 were 20.9 vs 14.2 for CHD events, 15.3 vs 10.2 for stroke events, and 36.2 vs 24.5 for CVD events. The magnitude and statistical significance of the HRs were not materially changed after adjustment for additional risk factors. Conclusions and RelevanceIn a pooled analysis of 563255 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. This international study pooled individual-participant data from several long-term prospective studies to evaluate the relationship between depressive symptoms and incident cardiovascular disease.