Prognostic Value of Serum Parathyroid Hormone Level in Acute Decompensated Heart Failure

Abstract

Background: Secondary hyperparathyroidism develops as a compensatory response to chronic heart failure (HF) and renal failure. The role of parathyroid hormone (PTH) level in acute decompensated HF remains unclear. The aim of this study was therefore to investigate the relationships among mortality, renal function, and serum PTH level in acute decompensated HF patients.

Methods and Results: A total of 266 consecutive patients admitted for acute decompensated HF without acute coronary syndrome (78±12 years; 48% male) were enrolled. Demographic, clinical, and laboratory characteristics were obtained on admission. During 1-year follow-up, 65 patients (24%) died. Serum PTH level on admission was within the normal range (10–65 pg/ml) in 108 patients (41%), of whom 39 (15%) had low-normal PTH (10–40 pg/ml). On Kaplan-Meier analysis all-cause mortality was significantly higher in patients with low-normal PTH than in those with high-normal (40–65 pg/ml) or high (>65 pg/ml) PTH (log-rank test). On univariate and multivariate Cox regression analysis, low-normal PTH was significantly associated with increased all-cause mortality (unadjusted HR, 2.88; 95% CI: 1.69–4.91; P<0.001; adjusted HR, 3.84; 95% CI: 1.54–9.57; P=0.004).

Conclusions: In patients with acute decompensated HF resulting in hospitalization, low-normal PTH on admission is associated with increased all-cause mortality, regardless of renal function. (Circ J 2014; 78: 2704–2710)

The origin of heart failure (HF) is rooted in inappropriate neurohormonal activation, which includes the hypothalamic-pituitary-adrenal (HPA) axis, the adrenergic nervous system, and the renin-angiotensin-aldosterone system (RAAS).^1,2 The secondary aldosteronism associated with chronic HF contributes to increased fecal and urinary Ca²⁺ excretion and consequent secondary hyperparathyroidism,^3,4 which also develops as a result of renal failure. Recent studies showed that secondary hyperparathyroidism is associated with development and progression of HF.^5,6

Editorial p 2631

As a consequence of the considerable worldwide growth in the number of HF patients, hospitalizations for acute decompensated HF have been increasing for many years.⁷ Acute decompensated HF resulting in hospitalization may be associated with cardiac and renal injuries, which contribute to the progression of HF. Therefore, hospitalized HF should be identified as a specific entity or risk factor that is different from chronic stable HF. Although elevated parathyroid hormone (PTH) has been reported to have prognostic value in the community⁸ and outpatient HF,^9,10 the prognostic value of PTH level in acute decompensated HF has not been evaluated. In addition, in acute decompensated HF patients, an association between renal dysfunction and increased mortality has been reported^11,12 and cystatin C has been shown as a reliable glomerular filtration rate marker compared with glomerular filtration rate estimates, including creatinine and creatinine-based formulae, with independent prognostic value.¹⁰

This study was conducted to assess the prognostic impact of PTH level in patients admitted with acute decompensated HF in comparison with that of other conventional risk factors, including renal function.

Methods

Subjects

All patients presenting with symptoms, signs, and diagnostic findings of acute HF according to current European Society of Cardiology guidelines and requiring hospitalization were eligible. The diagnosis of HF had to be confirmed during the hospital stay. Consecutive patients were enrolled between June 2009 and November 2012 at the Cardiology Department of Ise Red Cross Hospital, Mie, Japan, which is a tertiary care hospital. The follow-up period ended in October 2013. Patients with new-onset acute HF and those with exacerbation of chronic HF were included and enrolled once during the study period. We excluded patients with symptoms and/or electrocardiography signs suggestive of acute coronary syndrome; those with myocarditis, cardiac tamponade, aortic dissection, sepsis, or non-cardiovascular factors as the main cause of symptoms; those undergoing chronic renal replacement therapy, or cancer chemotherapy, and those who did not agree to the protocol. The local ethics committee approved the study, and all patients provided informed consent. Patient follow-up was conducted during regular outpatient visits or via telephone calls and letters to the patients’ homes or respective physicians. The study endpoint was all-cause mortality. In-hospital death was considered to be cardiovascular unless a specific non-cardiovascular cause was present.

Laboratory Procedures

All patients underwent complete clinical and laboratory examination at the time of hospital admission. Doppler echocardiography was carried out at least once before discharge. Serum intact PTH level was measured using an electrochemiluminescence immunoassay kit (Modular Analytics E 170; Roche, Mannheim, Germany). Serum samples for PTH measurement were separated by centrifugation at 4℃ immediately after collection and stored at −70℃ until assayed. The established normal range for this assay was 10–65 pg/ml. In this study, low-normal was defined as <40 pg/ml, the geometric mean serum intact PTH level in a previous cross-sectional survey.¹³ The interassay coefficient of variation was 3.8% at 36 pg/ml, 3.8% at 90 pg/ml, and 2.7% at 189 pg/ml. The intra-assay coefficient of variation was 2.4% at 39 pg/ml, 2.3% at 92 pg/ml, and 4.3% at 190 pg/ml. B-type natriuretic peptide (BNP) and cystatin C were measured using commercial kits (Shionoria, Shionogi, Osaka, Japan and Nescauto GC Cystatin C, Alfresa Pharma, Osaka, Japan). Anemia was defined as hemoglobin <12 g/dl in women and <13 g/dl in men. Hyponatremia was defined as serum sodium <135 mmol/L. Worsening renal function was defined as an increase >0.3 mg/dl in serum creatinine, based on the maximum increase in serum creatinine from admission to any time during hospitalization.

Statistical Analysis

One-way analysis of variance (ANOVA) and Kruskal-Wallis test were used to compare 3 groups. Chi-squared test was used to compare nominally scaled variables. Logarithmic transformation was performed to achieve approximate normal distribution for PTH. All-cause mortality was used as the primary outcome endpoint. Cumulative event-free survival estimates were calculated using the Kaplan-Meier method. Log-rank test was used for comparing the curves. Associations between PTH level and outcome were determined using Cox proportional hazards analysis (both univariate and multivariate models). The basic model (model 1) was adjusted for age (per 10-year increase), gender, diabetes mellitus, smoker/ex-smoker, cystatin C (>1.2 mg/L), and systolic blood pressure (SBP; per 10-mmHg increase). Model 2 was adjusted for all components of model 1 plus use of loop diuretics before admission, corrected serum calcium (>9.0 mg/dl), and serum inorganic phosphorus (>3.5 mg/dl). Model 3 was adjusted for all components of model 1 plus dyslipidemia, serum albumin (<3.5 g/dl), and body mass index (<20 kg/m²). Model 4 was adjusted for known risk indicators for HF: all components of model 1, New York Heart Association class IV, previous hospitalization for HF, use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARB) before admission, use of β-blockers before admission, left ventricular ejection fraction (LVEF; <50%), anemia, hyponatremia, and BNP (>1,000 pg/ml). Models 5, 6, and 7 were adjusted for all components of models 2 and 3, models 2 and 4, and models 2, 3, and 4, respectively. Heterogeneity of the influence, or interaction, was evaluated in model 7. Results are provided as mean±SD or median (interquartile range), as appropriate, and hazard ratio (HR; 95% confidence interval [CI]). For all tests, P<0.05 (2-sided) was considered significant. Data were analyzed using SPSS version 19 (SPSS, Chicago, IL, USA).

Results

Demographics and All-Cause Mortality

A total of 811 potentially eligible patients were admitted during the recruitment period. Of these, 266 (33%) were eligible for the study according to the exclusion criteria explained previously. Serum PTH (mean, 84±49 pg/ml; range, 13–316 pg/ml) followed a log-normal distribution. Frequency distribution of log-transformed PTH is shown in Figure 1. During a 1-year follow-up period, 65 patients (24%) died after initial hospitalization and 11 (4.1%) were lost to follow-up, with a median duration of follow-up of 237 days (range, 158–341 days). The clinical characteristics and mortality rate according to serum PTH level on admission are listed in Table 1. Of the patients studied, 21% had a previous history of myocardial infarction, 22% had atrial fibrillation or flutter, and 23% were smokers/ex-smokers. Before admission, 53%, 25%, 41%, and 18% of patients were receiving ACEI/ARB, β-blockers, loop diuretics, and mineralocorticoid receptor antagonists, respectively. There were significant differences in dyslipidemia, diabetes mellitus, LVEF, serum albumin, hyponatremia, serum creatinine, cystatin C, in-hospital mortality, 90-day mortality, 180-day mortality, and 180-day non-cardiovascular mortality, among the 3 groups defined according to PTH level (low-normal, <40 pg/ml; high-normal, 40–65 pg/ml; high, >65 pg/ml). Of the patients aged >80 years, 67% were female, 81% had hypertension, and 17% had in-hospital death. In each of 3 groups categorized by SBP on admission (ie, >140 mmHg, 100–140 mmHg and <100 mmHg), the in-hospital death rate was 7%, 17% and 21%, respectively. With respect to in-hospital treatment, 71%, 47%, and 10% of patients received i.v. furosemide, vasodilators, and inotropic therapy. During hospital stay, 27% of patients had worsening renal function. Median in-hospital length of stay was 18 days (interquartile range, 13–27 days). Among 3 groups defined according to PTH level, there were no significant differences in in-hospital treatment, worsening renal function, or length of stay. At discharge, 83%, 49%, 83%, and 51% of patients were receiving ACEI/ARB, β-blockers, loop diuretics, and mineralocorticoid receptor antagonists, respectively.

Figure 1.

Distribution of log-transformed parathyroid hormone (PTH) level on admission.

Table 1. Clinical Characteristics and Mortality vs. Serum PTH on Admission

Variable	Total (n=266)	Low-normal (n=39)	High-normal (n=69)	High (n=158)	P-value
Age (years)	78±12	80±10	79±11	78±12	0.526
Male gender (%)	48	51	45	48	0.81
NYHA class IV (%)	69	62	62	75	0.089
Previous hospitalization for HF (%)	40	41	42	39	0.92
Hypertension (%)	76	69	72	79	0.32
Dyslipidemia (%)	30	15	26	35	0.045
Diabetes mellitus (%)	32	46	22	34	0.03
Body mass index (kg/m2)	22.1±4.2	21.7±5.4	21.9±3.7	22.2±4.1	0.726
SBP (mmHg)	151±35	148±33	156±34	150±36	0.371
LVEF	0.49±0.16	0.51±0.15	0.52±0.17	0.47±0.15	0.041
Serum albumin (g/dl)	3.4±0.5	3.2±0.6	3.5±0.5	3.4±0.5	0.025
Hemoglobin (g/dl)	11.8±2.5	11.2±2.3	12.1±2.4	11.9±2.5	0.205
Anemia (%)	62	72	55	63	0.222
Serum sodium (mEq/L)	140.0±4.0	138.9±5.7	139.7±4.3	140.3±3.4	0.115
Hyponatremia (%)	8	18	10	4	0.007
Corrected serum calcium (mg/dl)	9.1±0.6	9.2±0.6	9.0±0.5	9.0±0.5	0.115
Serum inorganic phosphorus (mg/dl)	3.6±0.7	3.5±0.7	3.5±0.5	3.7±0.8	0.057
Serum creatinine (mg/dl)	1.18±0.73	1.02±0.57	0.94±0.50	1.33±0.81	<0.001
Cystatin C (mg/L)	1.58±0.72	1.49±0.77	1.38±0.62	1.69±0.73	0.008
BNP (pg/ml)	798 (377–1,487)	614 (276–1,440)	677 (306–1,195)	1,019 (443–1,611)	0.065
In-hospital mortality (%)	11.3	23.1	4.3	11.4	0.013
Cardiovascular death (%)	8.6	15.4	2.9	9.5	0.072
Non-cardiovascular death (%)	2.6	7.7	1.4	1.9	0.1
90-day mortality (%)	15.8	33.3	10.1	13.9	0.004
Cardiovascular death (%)	10.5	20.5	5.8	10.1	0.056
Non-cardiovascular death (%)	5.3	12.8	4.3	3.8	0.073
180-day mortality (%), n=265	18.9	38.5	13.2	16.5	0.003
Cardiovascular death (%)	12.5	20.5	8.8	12	0.2
Non-cardiovascular death (%)	6.4	17.9	4.4	4.4	0.006

Data given as mean±SD, median (lower–upper quartile) or %. Low-normal, <40 pg/ml; high-normal, 40–65 pg/ml; high, 65<pg/ml.

BNP, B-type natriuretic peptide; HF, heart failure; LVEF, left ventricular ejection fraction; NYHA, New York Heart Association; PTH, parathyroid hormone; SBP, systolic blood pressure.

Serum PTH Level and Mortality

The estimated survival rate in the 3 groups according to PTH level is shown in Figure 2. All-cause mortality was significantly higher in patients with low-normal PTH than in those with high-normal and high PTH (log-rank test, P<0.05 with Bonferroni correction). In univariate Cox proportional hazard regression models, the following variables were found to predict all-cause mortality: low-normal PTH (HR, 2.88; 95% CI: 1.69–4.91; P<0.001), log-transformed PTH (HR, 0.25; 95% CI: 0.09–0.72; P=0.01), age, previous hospitalization for HF, dyslipidemia, smoker/ex-smoker, use of loop diuretics before admission, body mass index, SBP, serum albumin, anemia, hyponatremia, corrected serum calcium, serum creatinine, cystatin C, and BNP. On multivariate Cox proportional hazard regression modeling, low-normal PTH was also a predictor of increased all-cause mortality after adjustment for confounders (Table 2, model 1: HR, 3.91; 95% CI: 2.2–6.95; P<0.001; model 7: HR, 3.84; 95% CI: 1.54–9.57; P=0.004), although log-transformed PTH level was a predictor of decreased all-cause mortality in models 1–6. PTH <51.3 pg/ml (first quartile) was also a predictor of outcome in model 7 (HR, 2.54; 95% CI: 1.13–5.75; P=0.025). Low-normal PTH, age (HR, 2.07; 95% CI: 1.32–3.26; P=0.002), SBP (HR, 0.83; 95% CI: 0.73–0.95; P=0.005), hyponatremia (HR, 4.59; 95% CI: 1.58–13.3; P=0.005), and cystatin C (HR, 3.89; 95% CI: 1.39–10.82; P=0.01) were shown to predict all-cause mortality in model 7. To evaluate the heterogeneity of the prognostic value of low-normal PTH on admission, subgroup analysis was performed. As listed in Table 3, there were significant interactions for age and use of β-blockers before admission in all-cause death.

Figure 2.

Kaplan-Meier curves for all-cause mortality in patients with acute decompensated heart failure according to serum parathyroid hormone level on admission. Low-normal, <40 pg/ml; high-normal, 40–65 pg/ml; high, >65 pg/ml.

Table 2. Predictors of Increased All-Cause Mortality

Model	Low-normal PTH (<40 pg/ml)		Log PTH
	HR (95% CI)	P-value	HR (95% CI)	P-value
Model 1	3.91 (2.2–6.95)	<0.001	0.17 (0.06–0.49)	0.001
Model 2	5.41 (2.5–11.68)	<0.001	0.11 (0.03–0.39)	0.001
Model 3	2.83 (1.58–5.09)	<0.001	0.28 (0.1–0.73)	0.009
Model 4	4.46 (2.41–8.26)	<0.001	0.17 (0.06–0.52)	0.002
Model 5	4.31 (1.93–9.62)	<0.001	0.17 (0.05–0.58)	0.005
Model 6	4.97 (2.14–11.56)	<0.001	0.16 (0.04–0.62)	0.008
Model 7	3.84 (1.54–9.57)	0.004	0.27 (0.06–1.14)	0.075

CI, confidence interval; HR, hazard ratio; PTH, parathyroid hormone.

Table 3. Prognostic Value of Low-Normal PTH on Admission

Stratum	HR (95% CI)	P-value	P-value for interaction
Total	2.88 (1.69–4.91)	<0.001
Age (years)
≤80	8.76 (2.94–26.15)	<0.001	0.017
>80	1.95 (1.02–3.71)	0.043
Gender
Female	3.03 (1.46–6.27)	0.003	0.925
Male	2.76 (1.26–6.07)	0.012
NYHA class IV
Absent	3.03 (1.21–7.63)	0.018	0.99
Present	2.87 (1.48–5.55)	0.002
Previous hospitalization for HF
Absent	1.79 (0.72–4.43)	0.211	0.112
Present	4.72 (2.4–9.27)	<0.001
SBP (mmHg)
≤140	3.06 (1.42–6.57)	0.004	0.818
>140	2.98 (1.41–6.3)	0.004
LVEF
≤50	3.61 (1.75–7.47)	0.001	0.308
>50	2.21 (1.00–4.91)	0.051
Hyponatremia
Absent	2.93 (1.63–5.3)	<0.001	0.425
Present	1.52 (0.41–5.68)	0.532
Cystatin C (mg/L)
≤1.2	10.04 (2.59–38.91)	0.001	0.127
>1.2	3.22 (1.69–6.13)	<0.001
BNP (pg/ml)
≤1,000	3.75 (1.76–8.02)	0.001	0.648
>1,000	2.79 (1.27–6.1)	0.01
ACEI/ARB before admission
Absent	3.02 (1.44–6.32)	0.003	0.79
Present	2.74 (1.26–5.93)	0.011
β-blockers before admission
Absent	2.16 (1.12–4.15)	0.022	0.049
Present	7.1 (2.72–18.55)	<0.001
Loop diuretics before admission
Absent	2.37 (1.08–5.2)	0.032	0.164
Present	5.46 (1.46–20.32)	<0.001

ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker. Other abbreviations as in Table 1.

Discussion

In the setting of acute decompensated HF resulting in hospitalization, low-normal PTH was associated with significantly higher all-cause mortality, even after adjusting for potential confounders, including the presence of impaired renal function (cystatin C >1.2 mg/L). Compared to the subjects in the Acute Decompensated Heart Failure Syndromes (ATTEND) registry, which is a prospective multicenter observational cohort study of patients hospitalized with HF without acute coronary syndrome in Japan,¹⁴ the present patients were elderly, female, hypertensive and with high in-hospital mortality. Length of hospital stay was similar between the present study (median, 18 days) and the ATTEND registry study (median, 21 days) but much longer than in Western countries (range of median, 4–10 days) because of differences in the health insurance system.¹⁵

PTH is secreted by the chief cells in the parathyroid gland, mainly in response to a decreased circulating ionized Ca²⁺ concentration.¹⁶ Serum PTH concentration is dependent upon the release of PTH stored in secretory granules within the parathyroid gland and by the synthesis of new PTH. Rapid PTH release from secretory granules in hypocalcemic states is modulated by the binding of Ca²⁺ to calcium-sensing receptors on chief cells, whereas long-term replenishment of PTH stores is dependent on new PTH synthesis.¹⁷ Recent experimental studies have shown that PTH has positive inotropic,¹⁸ positive chronotropic,^19,20 and vasodilator effects^19,20 on the heart. Small increases within the physiological range in PTH level reportedly improved the contractile performance of adult rat ventricular cardiomyocytes.¹⁸ Hyperparathyroidism stimulates the synthesis of renin in juxtaglomerular cells²¹ and aldosterone in zona glomerulosa cells²² by increasing intracellular Ca²⁺ level. In addition, activation of the adrenergic nervous system with a resultant elevation in circulating catecholamines facilitates intracellular Ca²⁺ overloading and a subsequent decrease in plasma Ca²⁺ level, which also provokes the parathyroid glands to release PTH,²³ potentially leading to cardiac hypertrophy and oxidative stress.^3,4,23

Recent clinical studies have suggested that secondary hyperparathyroidism is associated with HF severity, increased pulmonary capillary wedge pressure, increased BNP, decreased LVEF, and decreased cardiac index in patients with HF and that it develops as a compensatory response to HF.^5,6,9,10,24 More recent studies have reported that higher PTH in the steady state is associated with higher all-cause and cardiovascular mortality risk^8,10,25–28 and a higher risk of hospitalization for HF.^9,29

In the present study, approximately 60% of patients had abnormal increase in serum PTH (>65 pg/ml) and impaired renal function. The mean and median PTH (84 and 73 pg/ml) were higher, compared with those of outpatients with HF (62 and 49 pg/ml)⁹ and patients with chronic stable HF (46 and 40 pg/ml).⁵ Consistent with previous reports, age, SBP, hyponatremia, and presence of impaired renal function were significantly associated with mortality. The association between higher PTH and decreased mortality, however, is inconsistent with the previous observation that higher PTH, even within the normal range, predicts high mortality in the community⁸ and outpatient HF.^9,10 The present findings suggest that the prognostic value of PTH level in patients with acute decompensated HF is different from that in those with chronic HF. Sufficient PTH may be necessary for patients admitted with acute decompensated HF, although continuous high PTH and resulting oxidative stress contribute to adverse events in the setting of chronic HF.

The pathological regulation of PTH secretion in HF patients remains obscure. Fibroblast growth factor 23 (FGF23) suppresses both PTH secretion and PTH gene expression.³⁰ 1,25-hydroxyvitamin D suppresses PTH gene transcription.¹⁷ Acute hypomagnesemia stimulates PTH secretion, whereas chronic severe hypomagnesemia has a negative effect and is the exclusive cause of clinical hypoparathyroidism. A recent study identified a distinct group with low 25-hydroxyvitamin D and blunted PTH in patients with osteoporosis, and noted that magnesium deficiency (as measured by the magnesium loading test) was an important contributing factor.³¹ More recent studies have reported that type 2 diabetes mellitus patients had decreased PTH;³² incubation of human parathyroid cells with advanced glycation end-products inhibited low calcium-stimulated PTH secretion;³³ increase in PTH in response to phosphate was impaired in patients with type 2 diabetes mellitus;³⁴ and PTH secretion was impaired in patients with poorly controlled diabetes mellitus during acute stimulation.³⁵ In the present study patients with low-normal PTH had higher prevalence of malnutrition (lower prevalence of dyslipidemia and lower serum albumin) and diabetes mellitus, and higher LVEF and 180-day non-cardiovascular mortality when compared with the other subgroups. The impaired response of serum PTH may be due to magnesium deficiency and diabetes mellitus, and this might be the basis of the mechanism underlying progression of HF. It has recently been shown that hypomagnesemia is related to a higher number of comorbid diseases, low body mass index, and malnutrition.³⁶ It has been reported that non-cardiovascular mortality is higher in HF with preserved EF than with reduced EF:³⁷ there may be some overlapping between low-normal PTH and HF with preserved EF.

In the emergency department, PTH level was reportedly related to acute physiology and chronic health evaluation (APACHE II) score in critical patients including congestive HF and acute myocardial infarction, and also was higher in non-survivor patients.³⁸ Higher PTH was observed in patients with congestive HF or acute myocardial infarction compared to those with acute abdominal disorders or infections. We cannot, however, compare the present results with that previous study, because only 1 patient with congestive HF was categorized as a non-survivor in the previous study.

Study Limitations

Certain limitations must be considered when interpreting these findings. First, the current study represents an analysis of a cohort of consecutive patients admitted for acute decompensated HF without acute coronary syndrome who were evaluated and treated by investigators, which may have introduced selection bias. In fact, there were only 62 patients (23%) with cystatin C >2.0 mg/L. Some patients with both advanced renal failure and acute decompensated HF might be admitted to the Nephrology Department of Ise Red Cross Hospital. Second, this was a single-center study with a relatively small number of patients and events. It is likely that a larger study group with a greater number of events would have enabled the identification of an association between PTH level and cause of death. The size of the present sample, however, was sufficient to detect a significant association between PTH level and outcome, which was the primary aim of the study. Third, the cut-offs defining low-normal PTH were arbitrary. Further studies are necessary to define these absolute thresholds. Finally, because we did not investigate the mechanisms underlying the association between low-normal PTH and high mortality, we are unable to explain this phenomenon. We did not measure biochemical parameters of the HPA axis, adrenergic nervous system, RAAS, and the FGF23-vitamin D axis. FGF23 acts as a negative regulator of 25-hydroxyvitamin D, 1,25-hydroxyvitamin D, and PTH, which stimulates the production of 1,25-hydroxyvitamin D and FGF23.³⁹ Recent studies have shown associations between increased FGF23 and an increased risk of major cardiovascular events and mortality.⁴⁰ In addition, 25-hydroxyvitamin D deficiency is also related to higher PTH and HF risk.⁴¹ Furthermore, recent studies have found that lower 25-hydroxyvitamin D₃ was related to cardiac events in acute myocardial infarction.⁴² Further studies are required to evaluate the mechanisms behind the interplay between these biochemical parameters and PTH level in patients with both acute and chronic HF.

Conclusions

In contrast to that in the community and outpatient HF, low-normal PTH on admission was associated with increased all-cause mortality in patients with acute decompensated HF, even after adjusting for variables conventionally accepted to be associated with mortality. The compensatory response of PTH may contribute to cardiorenal protection. Further investigations are required to elucidate the pathophysiological mechanisms of PTH-related compensation in patients with acute and chronic HF.

Disclosures

Reporting Guideline: STrengthening the Reporting of OBservational studies in Epidemiology-Molecular Epidemiology (STROBE-ME). Funding: None. Conflict of Interest: None declared.

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