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

Damien Gruson,Sylvie A Ahn,Claudia Zierold,Fabrizio Bonelli,Douglas M Hawkins,Michel F Rousseau,Frank Blocki,Benjamin Ferracin,Claudio Passino

doi:10.1371/journal.pone.0135427

Abstract

ObjectivesVitamin 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)2D), 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.MethodsWe 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.ResultsSerum levels of 1,25(OH)2D 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)2D to PTH(1–84) ratio and the (1,25(OH)2D)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)2D and the 1,25(OH)2D to PTH(1–84) ratios to be strongly predictive of outcomes.Conclusions1,25(OH)2D and its ratios to PTH(1–84) strongly and independently predict cardiovascular mortality in chronic HF.

Highlights

Cardiovascular (CV) diseases remain a leading cause of death around the world [1]
There is a growing body of evidence supporting the role of vitamin D and parathyroid hormone (PTH) in cardiac remodeling and worsening heart failure (HF) [14,15,16,17]
Because 1,25(OH)2D and PTH(1–84) are physiologically interrelated (23), we examined the ratio of these two hormones and found them to be significantly related to HF severity: New York Heart Association (NYHA) class II ratio = 1.14, NYHA class III ratio = 0.47, and NYHA class IV ratio = 0.38 (p

Summary

Introduction

Cardiovascular (CV) diseases remain a leading cause of death around the world [1]. Among CV diseases, heart failure (HF) represents a major health concern because of increasing prevalence worldwide with major human, societal and economic impacts [2,3,4,5,6,7]. PTH together with aldosterone and fibroblast growth factor 23 (FGF-23), may be part of a vicious and deleterious cycle which compromises CV function [18]. Elevated levels of FGF-23 and PTH were observed in patients with CV disorders and HF, and have been related to adverse CV events [14;15;19,20,21]

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Results

Conclusion