Non-linear Mendelian randomization analyses support a role for vitamin D deficiency in cardiovascular disease risk. (5th December 2021)

• Record Type: Journal Article
• Authors: Zhou, Ang; Selvanayagam, Joseph B; Hyppönen, Elina
• Is Part Of: European heart journal. Volume 43:Number 18(2022)
• Page Start: 1731
• Page End: 1739
• Publication Date: 2021-12-05
• Subjects: Non-linear Mendelian randomization -- Vitamin D -- Serum 25-hydroxyvitamin Dconcentration -- Cardiovascular diseases -- Systolic blood pressure -- Diastolic blood pressure -- Cardiac-imaging phenotypes; Cardiology -- Periodicals; Heart -- Diseases -- Periodicals; 616.12005
• DOI: 10.1093/eurheartj/ehab809
• Languages: English
• ISSNs: 0195-668X

Abstract

Abstract: Aims: Low vitamin D status is associated with a higher risk for cardiovascular diseases (CVDs). Although most existing linear Mendelian randomization (MR) studies reported a null effect of vitamin D on CVD risk, a non-linear effect cannot be excluded. Our aim was to apply the non-linear MR design to investigate the association of serum 25-hydroxyvitamin D [25(OH)D] concentration with CVD risk. Methods and results: The non-linear MR analysis was conducted in the UK Biobank with 44 519 CVD cases and 251 269 controls. Blood pressure (BP) and cardiac-imaging-derived phenotypes were included as secondary outcomes. Serum 25(OH)D concentration was instrumented using 35 confirmed genome-wide significant variants. We also estimated the potential reduction in CVD incidence attributable to correction of low vitamin D status. There was a L-shaped association between genetically predicted serum 25(OH)D and CVD risk ( P non-linear = 0.007), where CVD risk initially decreased steeply with increasing concentrations and levelled off at around 50 nmol/L. A similar association was seen for systolic ( P non-linear = 0.03) and diastolic ( P non-linear = 0.07) BP. No evidence of association was seen for cardiac-imaging phenotypes ( P = 0.05 for all). Correction of serum 25(OH)D level below 50 nmol/L was predicted to result in a 4.4% reduction in CVD incidence (95% confidence interval: 1.8– 7.3%). Conclusion: Vitamin D deficiency can increase the risk of CVD. Burden of CVD could be reduced by population-wide correction of low vitamin D status. Graphical Abstract: