Vitamin D status and 12-year mortality risk after myocardial infarction

Abstract

Abstract Introduction Vitamin D deficiency has been associated with an increased risk of cardiovascular disease (CVD) mortality in healthy populations. Whether this association is also present in patients with established CVD is not yet clear. Purpose We examined the association of serum 25-hydroxyvitamin D [25(OH)D] as an indicator of vitamin D status with 12-year risk of CVD and all-cause mortality in post-myocardial infarction (MI) patients. Methods A prospective analysis was carried out in 4,479 Dutch patients from the Alpha Omega Cohort (aged 60-80 y) who had an MI ≤10 y prior to study enrolment. Non-fasting venous blood was sampled at baseline (2002-2006) for the assessment of 25(OH)D using LC-MS/MS. Patients were followed for cause-specific mortality through December 2018. Hazard ratios (HRs) for CVD and all-cause mortality were obtained in sex-specific 25(OH)D tertiles using Cox regression models, adjusted for age, education, physical activity, smoking status, alcohol intake, adherence to dietary guidelines (i.e. 2015 Dutch Healthy Diet index [DHD15]), prevalent diabetes and kidney function (eGFR). Restricted cubic splines (RCS) analysis was performed for continuous associations, using median 25(OH)D as the reference. Results Patients were 69.0 ± 5.6 y old, 78% was male, 17% were current smokers, 18% had diabetes and 8% used vitamin-D containing supplements. A total of 2,091 deaths occurred during a median follow-up period of 12.4 y (49,529 person-years), including 924 from CVD as a primary or contributing cause. Median 25(OH)D was 21.3 ng/mL, and tertile cut-offs were 18.3 and 26.2 ng/mL for males and 15.2 and 22.0 ng/mL for females. Of the cohort, 44% were vitamin D deficient (<20 ng/mL). Lower risks of CVD mortality were observed in the mid tertile (HR: 0.76, 95%CI:0.65-0.88) and upper tertile (HR: 0.67, 95%CI:0.57-0.79) of 25(OH)D, compared to the lower tertile. RCS showed a roughly linear association (P-non-linearity = 0.08), with a 11% lower risk of CVD mortality per 5 ng/mL-increment in 25(OH)D (HR: 0.89, 95%CI: 0.86-0.93). Inverse associations were more pronounced in patients with a higher calcium intake (>845 g/d; 0.87, 95%CI:0.96-0.98; per 5 ng/mL) and in patients who were more physically active (HR: 0.88, 95%CI: 0.83-0.93; per 5 ng/mL). Exclusion of 378 vitamin D supplement users did not materially change the associations. For all-cause mortality, multivariable HRs were 0.74 (95%CI: 0.67-0.82) in the mid tertile, and 0.65 (95%CI: 0.58-0.73) in the upper tertile, compared to the lower tertile. Conclusion A low vitamin D serum concentration is related to a higher risk of recurrent CVD and all-cause mortality in patients with coronary artery disease. Causality remains to be determined preferably in a clinical trial to evaluate the effect of oral suppletion of vitamin D on recurrent CVD and mortality risk in these patients.