Author + information
- Will Chan,
- Tai-Hing Lam,
- G. Neil Thomas,
- Chao-Qiang Jiang,
- Pak-Chung Sham,
- Mary Schooling,
- Benjamin Cowling,
- Kar-Keung Cheng,
- Karen Siu-Ling Lam and
- Hung-Fat Tse
Background: Prior cardiovascular (CV) studies on vitamin D are vastly short-termed. We investigated whether a novel multi-loci genetic risk score for lifelong-deficient vitamin D exposure infer causality to cardiac events and death under Mendelian-randomized approach.
Methods: We studied serum 25-hydroxyvitamin D in 5772 subjects in a prospective clinical cohort including mainly high-risk subjects with known CV disease and/or diabetes mellitus using validated enzyme immunoassay (Abott/IDS). Subjects were genotyped by high-throughput Exome chip analysis. 12 pre-specified candidate SNPs involved along vitamin D mechanistic pathways (biosynthesis/activation/receptor) from prior GWAS were studied. We constructed a 12-point genetic risk score (GRS) based on 6 SNPs confirmed associated with serum 25-hydroxyvitamin D level (rs2282679, rs4588, rs7041, rs1155563, rs1993116, rs2060793, all P<0.05). Study endpoints were acute coronary syndrome (ACS)/ myocardial infarction (MI), ischemic stroke, congestive heart failure (CHF), peripheral vascular disease (PVD), CV death, and combined CV endpoints.
Results: After 58.4±27.8 months follow-up, incident events of ACS, MI, CHF, ischemic stroke, PVD and CV death were respectively 99 (1.7%), 191 (3.3%), 431 (7.5%), 98 (1.7%), 24 (0.4%) and 47 (0.7%). Total combined CV event was 660 (11.4%). Vitamin D GRS was inversely associated with incident combined CV events (OR=0.96, 95%CI 0.92-0.99, P=0.009). Kaplan-Meier analysis showed that lifelong vitamin D exposure as indicated by GRS was associated with improved survival from combined CV events (log-rank=12.9, P=0.012). Adjusted for potential confounders, GRS was independently predictive of reduced combined CV events (HR 0.96, 95%CI 0.93-0.99, P=0.011, Figure). Mendelian-randomization analysis showed that lifelong vitamin D exposure protects against risk of combined CV events (OR=0.89, 95%CI 0.81 – 0.97, P=0.009).
Conclusions: Lifelong vitamin D exposure protects against risk of incident combined CV events in this high-risk population.
Room 147 A
Sunday, March 19, 2017, 9:17 a.m.-9:27 a.m.
Session Title: Highlighted Original Research: Prevention and the Year in Review
Abstract Category: 32. Prevention: Clinical
Presentation Number: 911-14
- 2017 American College of Cardiology Foundation