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Non-linear Mendelian randomization analyses support a role for vitamin D deficiency in cardiovascular disease risk

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Date: 5 December 2021
Journal: European Heart Journal , Volume 43 , Issue 18 , Pages 1731 - 1739
Topic: PREVENTIVE CARDIOLOGY, Risk Factors and Prevention, BASIC SCIENCE
Authors: A. Zhou , J. Selvanayagam , E. Hyppönen

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AbstractAims

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.

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About the contributors

Ang Zhou

Role: Author

Joseph B Selvanayagam

Role: Author

Elina Hyppönen

Role: Author