Hypovitaminosis D and cardiovascular disease
Vitamin D has been linked to a number of physiologic processes affecting vascular function, atherosclerosis, and blood pressure regulation,2 and also indirectly in the development of various risk factors of cardiovascular disease; it is possible that vitamin D deficiency exerts its effects on mortality through the de novo development and/or through the accelerated progression of CVD.
Low serum 25(OH)D levels have been associated with significantly increased cardiovascular mortality24,25 and fatal strokes26 in general population-based studies and higher non- fatal cardiovascular event rates in peritoneal dialysis patients.27 Trends toward higher cardiovascular mortality associated with lower 25(OH)D levels were seen in studies using population-based data from NHANES III28 and data on non-dialysis dependent CKD patients from the same cohort.29
The lack of statistical significance in these studies may have been the result of the lower cause-specific event rates characteristic of this cohort. Other studies explored associations between 25(OH)D levels and the incidence or prevalence of CVD. Associations between low 25(OH)D levels and prevalent cardiovascular and peripheral vascular disease were shown in two cross sectional studies based on data from various stages of NHANES.30,31 Lower 25(OH)D levels were also associated with prevalent CVD in diabetic patients with chronic kidney disease, independent of the level of kidney function.32
The association of 25(OH)D levels with incident cardiovascular disease was examined in longitudinal studies. A study based on the Multiethnic Study of Atherosclerosis cohort detected an association between lower 25(OH)D levels and incident coronary artery calcification, especially in patients with CKD.33 Another study examined 18,225 men without preexisting CVD enrolled in the Health Professionals Follow-up Study and found that lower 25(OH)D levels were associated with a significantly increased risk of myocardial infarctions.34
In summary, there seems to be a robust link between low 25(OH)D levels and both incident and prevalent CVD. This could be because of a direct effect of low vitamin D levels on vascular biology or because of the impact of hypovitamin osis D on more proximal causes of CV such as hypertension or diabetes mellitus; alternatively, a combination of these could also be responsible for the observed associations. (See Figure below.)