There is a renewed interest in the role of vitamin D in cardiovascular disease, largely due to observational studies suggesting a link between vitamin D deficiency and cardiovascular outcomes.  Moreover, vitamin D receptors have been found on vascular smooth muscle, and endothelial cells.  Given the vitamin D deficiency that commonly effects patients with chronic kidney disease (CKD), the purpose of this study was to examine whether supplementation with vitamin D could improve cardiac function and outcomes in patients with CKD.

The PRIMO (Paricalcitol Capsule Benefits in Renal Failure–Induced Cardiac Morbidity) trial, was an investigator-initiated, industry-sponsored, multinational, double-blind, randomized placebo-controlled trial, to test the hypothesis that 48-week treatment with paricalcitol (19-nor-1,25-[OH]₂ vitamin D₂) could reduce left ventricular mass, improve diastolic function, reduce CVD events, and improve cardiac biomarkers in patients with left ventricular hypertrophy (LVH) and CKD.  All study participants were randomly assigned to receive oral paricalcitol, 2 μg/d (n =115), or matching placebo (n = 112).  The main outcomes measures were the change in left ventricular mass index over 48 weeks as assessed by cardiovascular magnetic resonance imaging. Secondary end points included echocardiographic changes in left ventricular diastolic function.  Overall 227 patients were recruited.

Initiially, treatment with paricalcitol was seen to reduce parathyroid hormone levels within 4 weeks and maintained levels within the normal range throughout the study duration. However at 48 weeks, the change in left ventricular mass index did not differ between treatment groups (paricalcitol group, 0.34 g/m^2.7 [95% CI, −0.14 to 0.83 g/m^2.7] vs placebo group, −0.07 g/m^2.7 [95% CI, −0.55 to 0.42 g/m^2.7]). Furthermore, doppler measures of diastolic function including peak early diastolic lateral mitral annular tissue velocity (paricalcitol group, −0.01 cm/s [95% CI, −0.63 to 0.60 cm/s] vs placebo group, −0.30 cm/s [95% CI, −0.93 to 0.34 cm/s]) did not differ. However, it was noted that cardiac hospitalizations were slightly lower in the paricalcitol group as compared with the placebo group, and that increases in plasma B-type natriuretic-peptide (BNP) were less marked also.  But paricalcitol also increased serum creatinine and decreased creatinine-based measures of estimated glomerular filtration rate (eGFR), and an increase in adverse events was seen due to episodes of hypercalcaemia in the treatment group.

Conclusions:

In this multi-centre study, vitamin D supplementation in patients with CKD did not lead any structural improvements in cardiac function after 48 weeks.  Although a link seems to exist between cardiovascular disease and vitamin D levels, results from trials of vitamin D supplementation have to date been mixed.

• Thadhani R,  Appelbaum E, Pritchett Y et al.  Vitamin D Therapy and Cardiac Structure and Function in Patients With Chronic Kidney Disease.  JAMA 2012;307(7):674-684. doi:10.1001/jama.2012.120