Journal
EUROPEAN HEART JOURNAL
Volume 43, Issue 18, Pages 1731-+Publisher
OXFORD UNIV PRESS
DOI: 10.1093/eurheartj/ehab809
Keywords
Non-linear Mendelian randomization; Vitamin D; Serum 25-hydroxyvitamin Dconcentration; Cardiovascular diseases; Systolic blood pressure; Diastolic blood pressure; Cardiac-imaging phenotypes
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Funding
- National Health and Medical Research Council, Australia [1123603]
- National Health and Medical Research Council of Australia [1123603] Funding Source: NHMRC
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The study found a non-linear association between genetically predicted serum 25(OH)D concentration and CVD risk, with CVD risk initially decreasing steeply with increasing concentrations and leveling off at around 50 nmol/L. Correction of serum 25(OH)D level below 50 nmol/L was predicted to result in a 4.4% reduction in CVD incidence.
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 (Pnon-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 (Pnon-linear = 0.03) and diastolic (Pnon-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.
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