Association of Serum 25-Hydroxyvitamin D Concentrations With All-Cause and Cause-Specific Mortality Among Adult Patients With Existing Cardiovascular Disease

Abstract

Background: Vitamin D insufficiency and deficiency are common in patients with cardiovascular disease (CVD). We aimed to prospectively examine the associations of serum 25-hydroxyvitamin D [25(OH)D] concentrations with all-cause and cause-specific mortality among adult patients with existing CVD. Methods: We included 37,079 patients with CVD from the UK Biobank study, a prospective cohort of half a million participants aged 40-69 years. We defined patients with CVD as those who suffered coronary heart disease, atrial fibrillation, heart failure, or stroke. The associations of serum 25(OH)D concentration with all-cause and cause-specific mortality were examined by using multivariable Cox regression models and competing risk analyses. Results: Among 37,079 patients with CVD at baseline, 57.5% were subjected to vitamin D deficiency (i.e., 25[OH]D <50 nmol/L). During a median follow-up of 11.7 years, 6,319 total deaths occurred, including 2,161 deaths from CVD, 2,230 deaths from cancer, 623 deaths from respiratory disease, and 1,305 other-cause deaths. We observed non-linear inverse associations for all-cause, cancer, respiratory disease, and other-cause mortality (P-non-linearity <0.01) and approximately linear inverse associations for CVD mortality (P-non-linearity = 0.074). Among CVD patients with vitamin D deficiency, per 10 nmol/L increment in serum 25(OH)D concentrations was associated with an 12% reduced risk for all-cause mortality and 9% reduced risk for CVD mortality. Conclusion: Among patients with existing CVD, increasing levels in serum 25(OH)D were independently associated with a decreased risk of all-cause and cause-specific mortality. These findings suggest that elevated serum 25(OH)D concentration benefits CVD patients with vitamin D deficiency.

Keywords: UK Biobank; cardiovascular disease; cohort study; mortality; vitamin D.

Figure 1

Dose-response curves for serum 25(OH)D concentrations and all-cause and cardiovascular mortality. Hazard ratios (blue lines) and 95% confidence intervals (light blue shade) were adjusted for age (continuous), sex (male, female), and ethnicity (White, mixed, Asian, Black, Chinese, others, or unknown), education (college or university, vocational qualification, upper secondary, lower secondary, others, or unknown), Townsend deprivation index (in quintiles), household income (<18,000, 18,000–30,999, 31,000–51,999, 52,000–1,00,000, >1,00,000 £, or unknown), smoking status (never smoker, former smoker, current smoker, or unknown), alcohol consumption (0, 0.1–4.9, 5.0–14.9, 15.0–19.9, 20.0–29.9, ≥30.0 g/day, or unknown), physical activity (inactive group, insufficient group, active group, or unknown), healthy diet score (in quintiles), and BMI (<18.5, 18.5–22.9, 23.0–24.9, 25.0–29.9, 30.0–34.9, or ≥35.0 kg/m²), eGFRcr-cys (<30.0, 30.0–60.0, 60.0–90.0, ≥90.0 ml min⁻¹ per 1.73 m²), C-reactive protein (in quintiles), antihypertensive medication use (yes, no), cholesterol lowering medication use (yes, no), diabetes medication use (none, only oral medication, only insulin, or insulin and oral medication), history of cancer, diabetes, hypertension, and duration of CVD (<1.0, 1.0–4.9, 5.0–9.9, or ≥10.0 years). BMI, body mass index; CVD, cardiovascular disease; eGFRcr-cys, estimated glomerular filtration rate (creatinine–cystatin C equation).