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

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

doi:10.1371/journal.pone.0135427

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

PLoS One. 2015 Aug 26;10(8):e0135427. doi: 10.1371/journal.pone.0135427. eCollection 2015.

Authors

Damien Gruson¹, Benjamin Ferracin², Sylvie A Ahn³, Claudia Zierold⁴, Frank Blocki⁴, Douglas M Hawkins⁵, Fabrizio Bonelli⁴, Michel F Rousseau³

Affiliations

¹ Pôle de recherche en Endocrinologie, Diabète et Nutrition, Institut de Recherche Expérimentale et Clinique, Cliniques Universitaires St-Luc and Université Catholique de Louvain, Brussels, Belgium; Department of Laboratory Medicine, Cliniques Universitaires St-Luc and Université Catholique de Louvain, Brussels, Belgium.
² Pôle de recherche en Endocrinologie, Diabète et Nutrition, Institut de Recherche Expérimentale et Clinique, Cliniques Universitaires St-Luc and Université Catholique de Louvain, Brussels, Belgium.
³ Division of Cardiology, Cliniques Universitaires St-Luc and Pôle de recherche cardiovasculaire, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Brussels, Belgium.
⁴ DiaSorin Inc, 1951 Northwestern Avenue, Stillwater, Minnesota, 55082, United States of America.
⁵ School of Statistics, University of Minnesota, Minneapolis, Minnesota, 55455, United States of America.

Abstract

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)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.

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)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.

Conclusions: 1,25(OH)2D and its ratios to PTH(1-84) strongly and independently predict cardiovascular mortality in chronic HF.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Aged, 80 and over
Chronic Disease / mortality
Female
Heart Failure / blood*
Heart Failure / diagnosis*
Heart Failure / mortality
Humans
Male
Middle Aged
Parathyroid Hormone / blood*
Prognosis
Vitamin D / analogs & derivatives*
Vitamin D / blood
Young Adult

Substances

Parathyroid Hormone
Vitamin D
1,25-dihydroxyvitamin D

Grants and funding

DiaSorin Inc., funder, provided support in the form of salaries for authors Claudia Zierold, Frank Blocki, and Fabrizio Bonelli, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.