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)(2)D 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.