MAJOR DEPRESSION AND CARDIOVASCULAR RISK: MARKER, MEDIATOR, OR CAUSAL FACTOR?

Abstract

DOI: https://doi.org/10.46296/gt.v9i17.0342

Abstract

Major depression is a common disorder worldwide, associated with substantial disability burden, and it frequently coexists with cardiovascular disease (CVD) (1,2). Recent epidemiologic evidence indicates that depression is linked to a modest yet consistent increase in the risk of cardiovascular events (myocardial infarction and stroke) and cardiovascular mortality, even after adjustment for traditional risk factors; meta-analyses have estimated a relative increase of ~20–30% in incident coronary heart disease risk and up to ~40% in total cardiovascular events among individuals with depression (3,5,9,10). Large multicountry studies support this association: for instance, across 21 countries (PURE), depressive symptoms were associated with higher CVD incidence (adjusted hazard ratio, HR, ≈1.14) and mortality (HR ≈1.17) over 7 years of follow-up (4), while two large Chinese cohorts (~539,000 adults) showed that depression was associated with higher cardiovascular mortality (HR 1.22–1.32) and all-cause mortality (~1.3), with a more pronounced effect in men than in women (6). In patients with established CVD, depression predicts worse prognosis (e.g., ~60–80% higher mortality risk at 2–5 years after myocardial infarction compared with non-depressed patients) (13). Plausible pathways include chronic low-grade inflammation, autonomic dysfunction (reduced heart rate variability), endothelial dysfunction, and adverse health behaviors (smoking, physical inactivity, poor medication adherence) that commonly accompany depression. Whether depression acts merely as a risk marker or contributes causally to CVD remains debated; current evidence suggests a mixed role. Genetic approaches using Mendelian randomization support a small but significant causal effect of genetic liability to depression on ischemic heart disease (odds ratio, OR, ~1.15), with no clear evidence of reverse causality (3). Nevertheless, clinical trials treating depression in cardiovascular populations have not demonstrated clear reductions in hard cardiovascular endpoints, underscoring the multifactorial nature of the relationship. Overall, major depression can be considered an emerging cardiovascular risk factor of moderate magnitude, relevant for comprehensive risk assessment and management, while further research is needed to clarify causal mechanisms and identify effective interventions that translate into improved cardiovascular outcomes.

Keywords: Major Depressive Disorder, Cardiovascular Diseases, Myocardial Infarction, Stroke, Mortality and Inflammation.