Cardiovascular disease and mortality risks associated with vitamin D deficiency are heightened among adults with depression in the United States

Vitamin D deficiency and depression are emerging risk factors for cardiovascular disease (CVD), sharing biological pathways including inflammation. Given this overlap, depression may magnify the cardiovascular effect of low vitamin D. Using data from adults aged ≥20 years in the 2007–2018 National Health and Nutrition Examination Survey, with prospective mortality follow-up through 2019, we investigated whether depression modifies the association between vitamin D status and cardiovascular outcomes. Vitamin D deficiency was defined as serum 25-hydroxyvitamin D < 50 nmol/L and depression as a Patient Health Questionnaire-9 score ≥10. Composite CVD outcome included self-reported heart failure, coronary heart disease, angina, heart attack, or stroke. CVD mortality was determined using ICD-10 codes. Multivariable logistic regression ( n = 11,440) and Cox proportional hazards models ( n = 11,435) were used, with product terms to assess effect modification by depression. Vitamin D deficiency was not associated with CVD overall. However, among adults with depression, deficiency was associated with higher odds of CVD (OR:2.14; 95% CI: 1.31–3.50; P interaction = 0.002). Vitamin D deficiency was also associated with increased CVD mortality; however, no significant interaction was observed by depression status (P interaction = 0.31). These findings indicate that maintaining adequate vitamin D may be especially important in individuals with depression.