1,25-Dihydroxyvitamin D to PTH(1-84) Ratios Strongly Predict Cardiovascular Death in Heart Failure

Objectives Vitamin D deficiency and hyperparathyroidism are common in patients with heart failure (HF). There is a growing body of evidence supporting the role of vitamin D and parathyroid hormone (PTH) in cardiac remodeling and worsening of HF. Lack of reliable automated testing of 1,25-dihydroxyvitamin D (1,25(OH)(2)D), the biologically active metabolite of vitamin D, has limited its contribution to the prognostic assessment of HF. Here, the association of 1,25(OH) 2D and PTH(1-84) levels was evaluated for prediction of cardiovascular death in chronic HF patients. Methods We conducted a single center prospective cohort including 170 chronic HF patients (females n = 36; males n = 134; NYHA II-IV; mean age: 67 years; etiology: ischemic n = 119, dilated cardiomyopathy n = 51; mean LVEF: 23%). The primary outcome was cardiovascular death. Results Serum levels of 1,25(OH)(2)D decreased markedly with increased HF severity. Medians were 33.3 pg/mL for NYHA-II patients, 23.4 pg/mL for NYHA-III, and 14.0 pg/mL for NYHA- IV patients (p<0.001). Most patients had levels of 25(OH) D below 30ng/mL, and stratification by NYHA functional class did not show significant differences (p = 0.249). The 1,25(OH)(2)D to PTH(1-84) ratio and the (1,25(OH)(2)D)(2) to PTH(1-84) ratio were found to be the most significantly related to HF severity. After a median follow-up of 4.1 years, 106 out of 170 patients reached the primary endpoint. Cox proportional hazard modeling revealed 1,25 (OH)(2)D and the 1,25(OH)(2)D to PTH(1-84) ratios to be strongly predictive of outcomes. Conclusions 1,25(OH)(2)D and its ratios to PTH(1-84) strongly and independently predict cardiovascular mortality in chronic HF.