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Low calcidiol levels and coronary artery calcification: true, true, and related?

There is increasing interest in the role of vitamin D in health and disease. From early articles showing associations between use of activated vitamin D and improved survival on dialysis1 to more recent analyses showing that low 25-hydroxyvitamin D (calcidiol) and 1,25-dihydroxyvitamin D (calcitriol) levels are associated with mortality in dialysis patients,2 the observational findings have been, for the most part, consistent. The associations between calcitriol use and survival have been extended to the predialysis chronic kidney disease (CKD) population,3 as have associations between low calcidiol levels and mortality.4 It is true that patients with renal disease represent an extreme population with profound deficiencies of both calcidiol and calcitriol. Low calcidiol levels associate with all-cause mortality in the general population.5 The elevated mortality risk is perhaps due to an increased hazard for cardiovascular events. Low calcidiol levels link with incident cardiovascular disease (CVD)6 and myocardial infarctions.7 Studies of vitamin D deficiency and outcomes in the general population require larger sample sizes than studies of patients with renal disease because less profound deficiency is found in the former population.

The mechanisms underlying the benefits of adequate levels of vitamin D have not been fully elucidated. Low calcidiol levels associate with diabetes8 and hypertension9 and therefore may link to CVD by predisposing people with vitamin D deficiency to two diseases that place them at high risk. Vitamin D regulates the renin-angiotensin system10 and may exert cardioprotection through this action. One of these effects may be protection against left ventricular hypertrophy. Activated vitamin D therapy prevents the progression of cardiac hypertrophy in the Dahl salt-sensitive rat model of heart failure.11 The effect …