Abstract
Serum 25-hydroxyvitamin D (25(OH)D) levels have been found to be inversely associated with both prevalent and incident cardiovascular disease (CVD) risk factors; dyslipidemia, hypertension and diabetes mellitus. This review looks for evidence of a causal association between low 25(OH)D levels and increased CVD risk. We evaluated journal articles in light of Hill’s criteria for causality in a biological system. The results of our assessment are as follows. Strength of association: many randomized controlled trials (RCTs), prospective and cross-sectional studies found statistically significant inverse associations between 25(OH)D levels and CVD risk factors. Consistency of observed association: most studies found statistically significant inverse associations between 25(OH)D levels and CVD risk factors in various populations, locations and circumstances. Temporality of association: many RCTs and prospective studies found statistically significant inverse associations between 25(OH)D levels and CVD risk factors. Biological gradient (dose-response curve): most studies assessing 25(OH)D levels and CVD risk found an inverse association exhibiting a linear biological gradient. Plausibility of biology: several plausible cellular-level causative mechanisms and biological pathways may lead from a low 25(OH)D level to increased risk for CVD with mediators, such as dyslipidemia, hypertension and diabetes mellitus. Experimental evidence: some well-designed RCTs found increased CVD risk factors with decreasing 25(OH)D levels. Analogy: the association between serum 25(OH)D levels and CVD risk is analogous to that between 25(OH)D levels and the risk of overall cancer, periodontal disease, multiple sclerosis and breast cancer. Conclusion: all relevant Hill criteria for a causal association in a biological system are satisfied to indicate a low 25(OH)D level as a CVD risk factor.
Highlights
Cardiovascular disease (CVD) is the leading cause of death in the United States and has been since the early 1900s [1]
Results from a study performed by Rezai and colleagues [14] found that there was an association between serum 25(OH)D levels and left ventricular end-diastolic volumes for men of all ethnicities
This may mean that disparities in the prevalence of low vitamin D status among ethnicities may cause the disparities among ethnicities in the prevalence of CVD
Summary
Cardiovascular disease (CVD) is the leading cause of death in the United States and has been since the early 1900s [1]. Almost half of the decline can be attributed to decreasing CVD risk factors, including hypertension (HTN), smoking and dyslipidemia [2]. Multiple pathways may exist between a low serum 25(OH)D level and increased CVD risk. The. primary causes of low serum 25(OH)D levels are strict sun protection and inadequate dietary or supplemental vitamin D intake [40]. Results from epidemiological studies suggest that if a low serum 25(OH)D level is a primary risk factor for CVD and corrected, all-cause mortality could decrease significantly, both in the United States [43] and worldwide [44]
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