Insufficient Vitamin D Levels Associated with Higher Risk of Cardiovascular Disease

by | May 12, 2022 | 2022, Cardiovascular Health, Vitamin D - Heart

Written by Taylor Woosley, Staff Writer. Analysis of a prospective cohort study with data collected from around 267, 980 subjects, using Mendelian randomization framework, resulted in a non-linear association between 25(OH)D levels and CVD risk. Every 10 nmol/L increase in serum 25(OH)D levels was associated with 1.6% lower odds of CVD. 

cardiovascular healthCardiovascular disease (CVD) is the leading cause of mortality worldwide 1. CVD revolves around atherosclerosis, a chronic inflammation of the blood vessel wall, which can lead to ischemic stroke, hypertension, and dyslipidemia 2. Several risk factors for CVD include age, male sex, obesity, hypertension, and diabetes 3.

Vitamin D has long been reported to play a role in cardiovascular health, with vitamin D receptors being in almost all tissues, including the heart and blood vessels 4. Vitamin D, also known as 25(OH)D, is a common deficiency worldwide, with a prevalence of 28.9% of the United States being deficient 5. It is a fat-soluble vitamin with hormone-like properties that plays a critical role in bone metabolism and growth 6. Vitamin D exerts an immunomodulatory role by promoting the development of an anti-inflammatory environment 7.

In this study, Zhou et al. conducted an analysis using data for the UK Biobank (a large prospective cohort study with over 500,000 participants, aged 37-73 years) to employ a non-linear Mendelian randomization approach to observe the association of vitamin D levels with CVD incidence. Primary outcome measures included cardiovascular disease occurrence, with secondary outcome measures being blood pressure and cardiovascular imaging phenotypes. Final genetic analyses were selected among individuals (n=267,980) with information regarding serum 25(OH)D levels. BP was measured at the baseline assessment, along with cardiac-imaging phenotypes. Phenotypic associations of serum 25(OH)D levels with cardiovascular factors were assessed by fitting logistic or linear regression models, while adjusting for covariates such as demographic and lifestyle aspects. Likelihood ratio test was used to compare model fit between the fractional polynomial model and the linear model, taking p < 0.05 to indicate a non-linear association. After comparing participants serum 25(OH)D levels and occurrence of CVD, the main findings are as follows:

  • The average 25(OH)D serum level of participants was 50.0 nmol/L, with 11.4% (n=32,868) having concentrations < 25 nmol/L.
  • Every 10 nmol/L increase in serum 25(OH)D levels was associated with 1.6% lower odds of CVD [(OR): 0.98, 95% CI: 0.98-0.99, Plinear = 0.0001, Pnon-linear=0.48].
  • Additionally, non-linear associations were noted for systolic blood pressure and diastolic blood pressure (Pnon-linear ≤ 1.8E-04).
  • Using MR analyses, a non-linear association was observed between 25(OH)D and CVD risk. The L-shaped association indicated the highest CVD risk pertained to the lowest 25(OH)D concentrations, levelling off around 50 nmol/L.
  • Regarding blood pressure, similar curved associations were observed for 25(OH)D levels with systolic blood pressure (Pnon-linear=0.03) and diastolic blood pressure (Pnon-linear=0.07). Individuals with 25(OH)D levels of 25 nmol/L were estimated to have 0.70 mmHg (95% CI: 0.15-1.26) and 0.25 mmHg (95%CI: -0.02 to 0.51) higher blood pressure compared to those with 50 nmol/L.

Observational findings using MR framework confirm an L-shaped association, with higher levels of serum 25(OH)D resulting in an overall lower risk of CVD, along with lower blood pressure. Study limitations include the use of data pertaining to one ethnic group and the use of the UK Biobank which is not an exact representation of the UK population, possibly interfering with the accuracy of the non-linear MR analysis. Further research should explore the potential associations between a broader variety of race, sex, and age to better understand the potential cardioprotective benefits of vitamin D.

Source: Zhou, Ang, Joseph B. Selvanayagam, and Elina Hyppönen. “Non-linear Mendelian randomization analyses support a role for vitamin D deficiency in cardiovascular disease risk.” European heart journal 43, no. 18 (2022): 1731-1739.

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Posted May 12, 2022.

Taylor Woosley studied biology at Purdue University before becoming a 2016 graduate of Columbia College Chicago with a major in Writing. She currently resides in Glen Ellyn, IL.

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