The pivotal roles of vitamin D and calcium in skeletan metabolism are well known. It's their potential non-skeletal health effects-particularly in preventing cardiovascular disease (CVD)-that are controversial. In vitro and in vivo experimental studies have shown that vitamin D (Figure 1) and calcium (Figure 2) act independently and together to influence multiple physiologic processes that may modify CVD risk.
With more and more generally healthy people-particularly older adults-taking vitamin D and calcium supplements for bone health, a comprehensive understanding of the potential effects of these nutrients on major health outcomes such as CVD will have enormous public health impact.
Observational studies on circulating vitamin D levels and CVD risk
In people without kidney disease, studies in general populations4-7 or in patients suspected to have CVD8 also have shown an association between low 25(OH)D level and high cardiovascular mortality. The effects of vitamin D on CVD development or progression, however, cannot be determined from these studies because they included participants with both preexisting and newly developed CVD.
A few studies have examined the relationship between circulating 25(OH)D and newly developed CVD. Using a nested case-control study design, the Tromsø Heart Study found that baseline 25(OH)D levels were relatively lower in patients with newly identified myocardial infarction (MI) than in controls.9 The Health Professionals Follow-up Study reported multivariate relative risks (RRs) for coronary heart disease (CHD) of 2.09, 1.43, and 1.60, respectively, for men with baseline 25(OH)D levels of less than or equal to 15.0 ng/mL, 15.1 ng/mL to 22.5 ng/mL, and 22.6 ng/mL to 29.9 ng/mL compared with greater than or equal to 30.0 ng/mL.10 Further, the Tehran Lipid and Glucose Study showed that the odds ratio (OR) for CVD was 2.90 for participants with serum 25(OH)D less than 10 ng/mL compared with those with levels greater than or equal to 15 ng/mL.11
Among cohort studies, the Framingham Offspring Study investigated 1,739 participants during 5.4 years of follow-up and found that the multivariate RRs for CVD were 1.53 and 1.80, respectively, for individuals with 25(OH)D of 10 to less than 15 ng/mL and less than 10 ng/mL compared with greater than or equal to 15 ng/mL.12 In 27,686 patients identified from a general US healthcare database, 25(OH)D less than or equal to 15.0 ng/mL was associated with higher risk of MI (RR, 1.45), stroke (RR, 1.78), and their composite (RR, 1.79).13 However, these promising findings are counterbalanced by a lack of significant association between baseline 25(OH)D and risk of CVD in other studies.14