Parameters of Mineral Metabolism predict Midterm Clinical Outcome in End-Stage Heart Failure Patients

Figures & data

Table I. Characteristics of patients who reached and did not reach the primary endpoint.¹

	Primary endpoint not reached n = 203	Primary endpoint reached n = 102	P-value
Age (years)	56.5 ± 0.7	54.2 ± 1.3	0.368
Gender (%males)	81.3	76.5	0.366
Weight (kg)	80.9 ± 0.9	73.1 ± 1.4	< 0.001
Height (cm)	175 ± 1	174 ± 1	0.289
Time on waiting list (days)	275 ± 47	230 ± 82	0.633
Urgent/high urgent listing (%)	5.4	35.4	0.001
LVEF (%)	30.1 ± 0.7	29.4 ± 1.2	0.558
LVEDD (mm)	70.0 ± 0.85	68.8 ± 1.6	0.460
Cardiac index (l/min/m^2)	1.98 ± 0.03	2.01 ± 0.06	0.693
Glomerular filtration rate (ml/min/1.73m^2)	56.0 ± 19.6	60.9 ± 26.0	0.094
Diagnosis
Dilated cardiomyopathy (%)	38.4	56.9	0.003
Ischemic heart disease (%)	49.8	33.3	0.004
Others (%)	11.8	9.8	0.374
Concomitant diagnoses
Previous thoracic surgery (%)	84.7	68.6	0.002
Diabetes mellitus (%)	27.2	24.8	0.306
Chronic kidney disease stage > III (%)	8.4	8.8	0.531
Medication
Potassium sparing diuretics (%)	68.7	64.3	0.265
Loop diuretics (%)	94.0	96.9	0.216
Thiazid diuretics (%)	32.3	28.6	0.301
ACE inhibitors (%)	78.1	72.1	0.163
ß-blockers (%)	89.1	84.7	0.182
Antiarrhythmics (%)	31.2	42.2	0.165
Inotropes (%)	7.4	19.2	0.004

¹Continuous variables are given as mean ± SEM; the primary endpoint was a composite of the need of mechanical circulatory support, transplantation, or death.

Table II. Biochemical parameters of in- and outpatients (mean ± SEM).

	Outpatients N = 259	Inpatients N = 46	P value
Glomerular filtration rate (ml/min/m^2)	56.1 ± 1.4	65.6 ± 3.6	0.016
Sodium (mmol/l)	138.2 ± 0.2	136.9 ± 0.6	0.052
Magnesium (mmol/l)	0.90 ± 0.01	0.87 ± 0.02	0.402
Calcium (mmol/l)	2.30 ± 0.02	2.27 ± 0.02	0.147
Inorganic phosphate (mmol/l)	1.16 ± 0.02	1.08 ± 0.06	0.07
NTproBNP (pmol/l)	470 ± 73	430 ± 51	0.582
Parathyroid hormone (pmol/l)	8.63 ± 0.42	3.66 ± 2.97	< 0.001
25(OH)D (nmol/l)	34.3 ± 2.5	23.5 ± 4.5	0.018
1,25(OH)2D (pmol/l)	65.8 ± 2.6	44.2 ± 3.3	< 0.001
FGF-23 (RU/ml)	755 ± 175	608 ± 214	0.595
C-reactive protein (mg/dl)	1.10 ± 0.12	2.47 ± 0.64	0.042
TNF-α (pg/ml)	10.8 ± 0.4	11.9 ± 0.9	0.258
TIMP-1 (ng/ml)	163 ± 4	169 ± 13	0.638

Abbreviations: NTproBNP, n-terminal propeptide of brain natriuretic peptide; 25(OH)D, 25-hydroxyvitamin D; 1,25(OH)₂D, 1,25-dihydroxyvitamin D; FGF-23, fibroblast growth factor-23; TNF, tumor necrosis factor; TIMP, tissue inhibitor of metalloproteinases.

Table III. Biochemical parameters of the study cohort by clinical outcome (mean ± SEM).

	Event-free Survivors n = 203	MCS implantation N = 17	Transplanted n = 58	Non Survivors N = 27	P value
Sodium (mmol/l)	138.6 ± 0.3	136.1 ± 0.9	137.1 ± 0.5	135.7 ± 0.8	< 0.001
Magnesium (mmol/l)	0.90 ± 0.01	0.92 ± 0.04	0.81 ± 0.01	0.86 ± 0.03	< 0.001
Calcium (mmol/l)	2.31 ± 0.02	2.29 ± 0.04	2.29 ± 0.02	2.21 ± 0.08	0.023
Inorganic phosphate (mmol/l)	1.15 ± 0.02	1.12 ± 0.08	1.28 ± 0.03	1.10 ± 0.06	0.001
NTproBNP (pmol/l)	450 ± 53	390 ± 104	410 ± 49	676 ± 130	0.166
Parathyroid hormone (pmol/l)	8.93 ± 0.42	6.83 ± 1.26	5.88 ± 0.74	9.66 ± 1.89	0.001
25(OH)D (nmol/l)	34.5 ± 2.5	22.8 ± 2.5	25.8 ± 3.0	33.8 ± 4.5	0.077
1,25(OH)2D (pmol/l)	69.8 ± 2.8	46.8 ± 9.0	47.5 ± 2.3	47.8 ± 6.8	< 0.001
FGF-23 (RU/ml)	564 ± 120	2088 ± 1627	492 ± 150	2416 ± 1245	< 0.001
C-reactive protein (mg/dl)	0.80 ± 0.08	2.76 ± 1.29	2.10 ± 0.41	3.28 ± 0.98	< 0.001
TNF-α (pg/ml)	10.6 ± 0.4	11.3 ± 1.7	11.8 ± 0.9	13.4 ± 1.3	0.048
Creatinine (µmol/l)	132 ± 4	131 ± 15	115 ± 5	148 ± 9	0.002
Bilirubin (µmol/l)	15.4 ± 0.9	16.8 ± 2.9	13.9 ± 1.2	18.1 ± 0.34	0.343
MMP-9 (ng/ml)	521 ± 21	399 ± 72	551 ± 38	597 ± 80	0.255
TIMP-1 (ng/ml)	154 ± 4	339 ± 152	158 ± 8	235 ± 20	< 0.001

Abbreviations: NTproBNP, n-terminal propeptide of brain natriuretic peptide; 25(OH)D, 25-hydroxyvitamin D; 1,25(OH)₂D, 1,25-dihydroxyvitamin D; FGF-23, fibroblast growth factor-23; TNF, tumor necrosis factor; MMP, matrix metalloproteinases;

TIMP, tissue inhibitor of metalloproteinases.

Table IV. Logistic regression analysis of independent predictors of the primary endpoint.¹

	Univariate analysis HR 95%CI	Multivariate analysis HR 95% CI	P value
Sodium (< 138 mmol/l)	3.116 (1.880–5.166)	1.947 (1.240–3.058)	0.004
Magnesium (< 0.87 mmol/l)	3.228 (1.951–5.341)	1.988 (1.255–3.150)	0.003
PTH (< 6.1 pmol/l)	2.540 (1.550–4.151)	1.992 (1.268–3.128)	0.003
1,25(OH)2D (< 58.7 pmol/l)	3.791 (2.268–6.338)	1.950 (1.213–3.137)	0.006
FGF-23 (> 204 RU/ml)	2.643 (1.597–4.375)	1.948 (1.216–3.122)	0.006

¹The primary endpoint was a composite of the need of mechanical circulatory support, transplantation, or death. Additional parameters that were included in the multivariate analysis (but did not show statistical significance) are glomerular filtration rate, serum Ca, serum PO₄, C-reactive protein, tissue inhibitor of metalloproteinases, and the logarithmic transformed propeptide of brain natriuretic peptide.

Table V. Logistic regression analysis of parameters of mineral metabolism as predictors of a composite endpoint of mechanical circulatory support or death.

	Univariate analysis HR 95%CI	Multivariate analysis HR 95% CI	P value
Sodium (< 138 mmol/l)	2.878 (1.477–5.607)	2.114 (1.063–4.207)	0.033
Magnesium (< 0.87 mmol/l)	2.170 (1.168–4.029)	2.038 (1.089–3.815)	0.026
PTH (< 6.1 pmol/l)	1.642 (0.899–3.000)	1.701 (0.904–3.201)	0.100
1,25(OH)2D (< 58.7 pmol/l)	2.813 (1.466–5.398)	1.682 (0.843–3.355)	0.140
FGF-23 (> 204 RU/ml)	2.947 (1.513–5.742)	2.447 (1.191–5.026)	0.015

Figure 1. Kaplan-Meier estimates of the incidence of the Primary Endpoint broken down by the 5 score groups of deranged mineral metabolism. The primary endpoint was a composite of the need of mechanical circulatory support, transplantation, or death. Log rank test P < 0.001 between groups.