Calcitriol, Parathyroid Hormone May Predict CV Death in Heart Failure

SAN DIEGO — Calcitriol, or 1,25-dihydroxyvitamin D (1,25[OH]₂D), and its ratio to parathyroid hormone (PTH[1-84]) are independent markers for cardiovascular (CV) death in patients with chronic heart failure, according to data presented at ENDO 2015.

The researchers also noted that patients with chronic heart failure and decreased calcitriol and a decreased ratio of calcitriol to PTH may benefit from more aggressive supplementation.

“This study is important as it identifies and provides physicians with biomarkers that strongly predict cardiovascular death in heart failure and allows them to more intensively and aggressively manage their patients,” lead study author Damien Gruson, PhD, professor and associated laboratory director in the department of laboratory medicine at Clinique Universitaires Saint Luc in Brussels, said in a press release.

“We hope that our data can contribute to the more personalized, tailored care of heart failure patients.”

Vitamin D deficiency and hyperparathyroidism are common in patients with heart failure, with data demonstrating a significant role for vitamin D and PTH in those with worsening disease, according to background information in the study abstract.

To further examine the association between 1-25(OH)₂D levels and CV death in chronic heart failure, the researchers evaluated 170 patients with chronic heart failure (women, 36; mean age, 67 years). Using a fully automated and sensitive immunoassay, they determined baseline levels of 1,25(OH)₂D. Levels of 25-hydroxyvitamin D (25[OH]D), PTH(1-84), B-type natriuretic peptide (BNP), N-terminal proBNP (NT-proBNP) and galectin-3 were also measured.

Results indicated a significant decline in serum levels of 1,25(OH)₂D according to heart failure severity. Levels were also reportedly 30.9 pg/mL in NYHA class II, 22.0 pg/mL in NYHA class III and 14.9 pg/mL in NYHA class IV (P<.001).

Additionally, a relationship between decreased ratios of 1,25(OH)₂D to PTH(1-84) and heart failure severity was noted. However, levels of 25(OH)D did not differ significantly by NYHA functional classes (P=.146).

The researchers also found that 1,25(OH)₂D and its ratio to PTH(1-84) negatively correlated with BNP, NT-proBNP and galectin-3, while 25(OH)D levels were only associated with BNP and NT-proBNP.

After 8 years, there were 106 CV deaths. Multivariable analysis indicated that 1,25(OH)₂D and the ratio of 1,25(OH)₂D to PTH(1-84) were strongly predictive of CV deaths in this patient population.

“We were surprised by the strong predictive power of 1,25(OH)₂D and its ratio to 1-84 PTH. It is noteworthy that in this study, the 1,25(OH)₂D was measured by a novel, extraction-free, fully automated assay based on a unique murine monoclonal antibody which recognizes the conformational change induced by the binding of the 1,25(OH)₂D to a recombinant fusion protein,” Dr. Gruson said.

“Our results can provide physicians with a new tool — the 1,25(OH)₂D to PTH ratio — to risk stratify heart failure patients. According to the relation between lower ratio values and increased mortality, physicians can try to modulate the ratio by increasing 1,25(OH)₂D levels with more supplementation with calcitriol/analogs or by decreasing PTH with aldosterone blockers, for example,” he added.

A larger study designed to confirm the benefit of calcitriol supplementation in patients with heart failure is planned for the future.

Reference

1. Gruson D et al. Abstract FRI-206. Presented at: The Endocrine Society’s 97th Annual Meeting & Expo (ENDO 2015); March 5-8, 2015; San Diego.