Vitamin D and Cardiovascular Disease: Can Novel Measures of Vitamin D Status Improve Risk Prediction and Address the Vitamin D Racial Paradox?

Abstract

Purpose of review: To provide a state-of-the-art update on some emerging measures of vitamin D status and discuss how assessment of these key vitamin D metabolites might improve prognostication of risk for cardiovascular disease (CVD) outcomes.

Recent findings: Vitamin D deficiency is a highly prevalent condition and relatively easy to treat with supplementation and/or modest sunlight exposure. A substantial body of experimental and epidemiological evidence suggest that vitamin D deficiency is a risk factor for CVD. Most epidemiologic studies to date have focused on total 25-hydroxyvitamin D [25(OH)D] concentrations, which is the established marker of vitamin D stores. However, there is emerging evidence that other novel markers of vitamin D metabolism may better characterize 'true' vitamin D status. Some key novel measures include bioavailable 25(OH)D, free 25(OH)D, 1-25 dihydroxyvitamin D, 24,25-dihydroxyvitamin D3 [24,25(OH)₂D3], and ratio of 24,25(OH)₂D3 to 25(OH)D [the vitamin D metabolic ratio]. Utilization of these biomarkers may enhance understanding of the association between vitamin D and CVD risk, and may provide explanation for the observation that 25(OH)D is a stronger CVD risk factor in whites than blacks.

Summary: Novel measures of vitamin D status could potentially change clinical practice regarding how patients are currently screened for vitamin D status and defined as vitamin D deficient or not. However, whether measuring any of these alternate markers of vitamin D status can provide further insight regarding CVD risk beyond the traditionally measured 25(OH)D concentrations is uncertain at this time. This is an area where further research is strongly needed.

Keywords: Biomarker; Cardiovascular Risk Factor; Vitamin D.

Figure 1. Vitamin D Metabolism Pathway

Vitamin D can be obtained in the form of D3 from conversion of 7-dehydrocholestrol in the skin after exposure to UVB or in dietary forms of D2 or D3. D2 and D3 are then hydroxylated to 25-hydroxyvitamin D in the liver. 25(OH)D circulates as the predominant storage form, with the majority bound to vitamin D binding protein (VDBP). Subsequently, the 25(OH)D is hydroxylated by the 1α hydroxylase in the kidney, converting it to the active 1,25(OH)₂D. 1,25(OH)₂D then circulates and binds to the vitamin D receptor (VDR) in various tissue cells including cardiovascular tissues which triggers cellular activity. Both 25(OH)D and 1,25(OH)₂D can be catabolized with 24-hydroxylase activity and ultimately excreted by the kidneys.