Plasma Levels of Intact Parathyroid Hormone and Congestion Burden in Heart Failure: Clinical Correlations and Prognostic Role

Abstract

Circulating parathyroid hormone (PTH) concentrations increase in heart failure (HF) and are related to disease severity. The relationship between PTH and congestion is still a matter of debate. The objective of this analysis was to evaluate the role of PTH as a marker of congestion and prognosis in HF. We enrolled 228 patients with HF. Intact PTH concentrations and HYDRA score (constituted by: B-type natriuretic peptide, blood urea nitrogen−creatinine ratio, estimated plasma volume status, and hydration status) were evaluated. The study endpoint was all-cause mortality. PTH levels were higher in acute compared with chronic HF and in patients with clinical signs of congestion (i.e., peripheral oedema and orthopnea). PTH concentrations significantly correlated with NYHA class and HYDRA score. At multivariate analysis of HYDRA score, estimated glomerular filtration rate (eGFR), and corrected serum calcium were independently determinants of PTH variability. Fifty patients (22%) died after a median follow-up of 408 days (interquartile range: 283−573). Using univariate Cox regression analysis, PTH concentrations were associated with mortality (hazard ratio [HR]: 1.003, optimal cut-off: >249 pg/mL—area under-the-curve = 0.64). Using multivariate Cox regression analysis, PTH was no longer associated with death, whereas HYDRA score, left ventricular ejection fraction, and eGFR acted as independent predictors for mortality (HR: 1.96, 0.97, and 0.98, respectively). Our study demonstrated that intact PTH was related to clinical and subclinical markers of congestion. However, intact PTH did not act as an independent determinant of all-cause death in HF patients.

Keywords: BIVA; BNP; HYDRA score; PTH; congestion; heart failure; prognosis.

Figure 1

(A) Differences in parathyroid hormone (PTH) plasma concentrations between patients with acute (AHF) and chronic heart failure (CHF). (B) Relationship between PTH plasma concentrations and NYHA functional class (NYHA II: n = 100, NYHA III: n = 68, NYHA IV: n = 60). Data are expressed as mean ± standard error of mean.

Figure 2

Relationship between intact parathyroid hormone (PTH) plasma concentrations and peripheral oedema (“no” peripheral oedema: n = 170, “yes” peripheral oedema: n = 58) (A) or orthopnoea (“no” orthopnoea: n = 171, “yes” orthopnoea: n = 57) (B). Data are expressed as mean ± standard error of mean.

Figure 3

(A) Relationship between congestion degree as assessed by the HYDRA score (multiparametric approach: from 0 to 4) and parathyroid hormone (PTH) plasma concentrations in patients with chronic (CHF) and acute (AHF) heart failure. (B) Relationship between congestion degree as assessed by the HYDRA score (HYDRA “0”, n = 45, HYDRA “1”: n = 65, HYDRA “2”: n = 44, HYDRA “3”: n = 50, and HYDRA “4”: n = 24) and renal function (as assessed by means of estimated glomerular filtration rate [eGFR] calculated with Cockroft–Gault formula). Data are expressed as mean ± standard error of mean.

Figure 4

ROC curve for PTH as predictor of all-cause death. AUC: area-under-the curve; PTH: parathyroid hormone.