Dataset Information

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

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.

SUBMITTER: Gruson D

PROVIDER: S-EPMC4550259 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Gruson Damien D Ferracin Benjamin B Ahn Sylvie A SA Zierold Claudia C Blocki Frank F Hawkins Douglas M DM Bonelli Fabrizio F Rousseau Michel F MF

PloS one 20150826 8

<h4>Objectives</h4>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 ...[more]

PMID: 26308451

Similar Datasets

Project description:BackgroundSecondary hyperparathyroidism (SHPT) is a common complication of chronic kidney disease (CKD) leading high mortality and even long-term morbidity. SHPT is manifested by elevation of parathyroid hormone (PTH) and accurate determining the level of serum PTH is very essential for early diagnosis of SHPT secondary to CKD. It is very important to match the values obtained for intact parathormone (iPTH) and 1- 84 PTH with the minimized measurement bias.ObjectivesThe present study aimed to first determine the agreement value between the iPTH and 1- 84 PTH measures in patients with hyperparathyroidism secondary to endstage renal disease under chronic hemodialysis. Then, we attempted to determine the best cutoff values for these two measurements for detecting SHPT in such patients.Patients and methodsThis cross-sectional study was conducted on hemodialysis patients. The value of study biomarkers including iPTH and 1- 84 PTH was assessed.ResultsA strong positive association was revealed between the two indicators of iPTH and 1-84 PTH (r = 0.800, P < 0.001). The linear association between these two parameters is independent to baseline characteristics including gender, age, body mass index, and medical history. Among all biochemical elements, the value of 1-84 PTH was only associated with serum calcium level negatively (r = -0.267, P = 0.027) and alkaline phosphatase positively (r = 0.359, P = 0.003). Considering iPTH as the reference and according to the area under the ROC curve (AUC), 1-84 PTH had high value to predict hyperparathyroidism (AUC = 0.926, P < 0.001). The best cutoff point for 1-84 PTH to discriminate hyperparathyroidism from normal condition was 60 yielding a sensitivity of 92.3% and a specificity of 79.1%. Among other baseline laboratory parameters, only alkaline phosphatase had an acceptable value for diagnosing hyperparathyroidism (AUC = 0.731, P = 0.001).ConclusionsThe measurement of both iPTH and 1-84 PTH is valuable for predicting hyperparathyroidism secondary to CKD, but according to lower cost and comparableeffectiveness of iPTH measurement, this assay may be comparable to 1-84 PTH to predict this consequence.

Project description:Hypocalcemia and hyperphosphatemia are encountered in idiopathic hypoparathyroidism (IHP) and pseudohypoparathyroidism type Ib (PHP1B). In contrast to PHP1B, which is caused by resistance toward parathyroid hormone (PTH), the genetic defects leading to IHP impair production of this important regulator of mineral ion homeostasis. So far, only five PTH mutations were shown to cause IHP, each of which is located in the hormone's pre-pro leader segment and thus impair hormone secretion. In three siblings affected by IHP, we now identified a homozygous arginine-to-cysteine mutation at position 25 (R25C) of the mature PTH(1-84) polypeptide; heterozygous family members are healthy. Depending on the assay used for evaluating these patients, plasma PTH levels were either low or profoundly elevated, thus leading to ambiguities regarding the underlying diagnosis, namely IHP or PHP1B. Consistent with increased PTH levels, recombinant [Cys25]PTH(1-84) and wild-type PTH(1-84) were secreted equally well by transfected COS-7 cells. However, synthetic [Cys25]PTH(1-34) was found to have a lower binding affinity for the PTH receptor type-1 (PTH1R) than PTH(1-34) and consequently a lower efficiency for stimulating cAMP formation in cells expressing this receptor. Consistent with these in vitro findings, long-term infusion of [Cys25]PTH(1-34) resulted only in minimal calcemic and phosphaturic responses, despite readily detectable levels of [Cys25]PTH(1-34) in plasma. The mineral ion abnormalities observed in the three IHP patients are thus most likely caused by the inherited homozygous missense PTH mutation, which reduces bioactivity of the secreted hormone. Based on these findings, screening for PTH(1-84) mutations should be considered when clinical and laboratory findings are consistent with PHP1B, but GNAS methylation changes have been excluded. Differentiating between IHP and PHP1B has considerable implications for genetic counseling, therapy, and long-term outcome because treatment of IHP patients with inappropriately high doses of active vitamin D and calcium can contribute to development of nephrocalcinosis and chronic kidney disease.

Dataset Information

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

Objectives

Methods

Results

Conclusions

Publications

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

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