Serum 25-hydroxyvitamin D values and risk of incident cardiovascular disease: A population-based retrospective cohort study

Background: Concentrations of serum 25-hydroxyvitamin D [25(OH)D] below 20 ng/mL and above 50 ng/mL have been associated with chronic adverse events including cardiovascular disease. Objective: To conduct a comprehensive population-based study in the United States of the relationship of low and high serum 25(OH)D levels with cardiovascular disease. Methods: We identified all serum 25(OH)D measurements in adults age 18 years and older residing in Olmsted County, MN between January 1, 2005 and December 31, 2011, using the resources of the Rochester Epidemiology Project. Any new diagnosis of cardiovascular disease was the primary outcome, and time zero was 30 days after first 25(OH)D measurement. Patients were followed until their last clinical visit as an Olmsted County resident, December 31, 2014, or death. Categories of 25(OH)D values were examined using predetermined ranges of interest: <12, 12 19, 20 50 (reference range), and >50 ng/mL. Multivariable Cox proportional hazards models were adjusted for age, BMI, sex, race, smoking history, season of 25(OH)D measurement, hypertension, hyperlipidemia, socioeconomic status and Charlson comorbidity index at time of 25(OH)D measurement. Results: A total of 11,002 unique persons had a 25(OH)D measurement, with a mean (+/- SD) value of 30.0 +/- 12.9 ng/mL. Mean age was 54.3 +/- 17.2 years, and the majority were female (77.1 %) and white (87.6 %). There were 4124 new diagnoses of cardiovascular disease in this cohort after a median overall follow-up of 4.8 years (IQR 3.4-6.2). Adjusted cardiovascular disease hazard ratios (HRs) (95 % confidence interval) for 25(OH)D values <12, 12 19, and >50 ng/mL, compared to the reference range 20 50 ng/mL, were 1.28 (1.12-1.46), 1.19 (1.09-1.31), and 1.10 (0.95-1.26), respectively. Conclusion: Values of 25(OH)D <20 ng/mL were associated with development of a new diagnosis of cardiovascular disease. There was no significant association between 25(OH)D values >50 ng/mL and cardiovascular disease.