Baseline characteristics
Thirty patients were lost to follow-up. A total of 466 patients with AHF were included in the final analysis. After a median follow-up of 34 months, 196 (42.1%) deaths occurred, and 158 (33.9%) patients died of cardiovascular causes. At baseline, patients who died were older than survivors and were more often female. Notably, patients who died had more severe clinical symptoms, lower systolic or diastolic blood pressure, lower serum albumin, lower LVEF and higher proBNP (Table 1).
Table 1
Baseline characteristics of the enrolled patients.
Variables | All (n = 466) | Deaths (n = 196) | Survivors (n = 270) | P value |
Age(years) | 61.8 (25.0) | 65.0 (15.5) | 59.5 (29.9) | 0.019 |
Male, % | 314 (67.4%) | 111 (56.6%) | 203 (75.2%) | < 0.001 |
Diabetes,% | 118 (25.3%) | 51 (26.0%) | 67 (24.8%) | 0.768 |
Hypertension, % | 244 (52.4%) | 97 (49.5%) | 147 (54.4%) | 0.290 |
Ischemic heart failure, % | 125 (26.8%) | 53 (27.0%) | 72 (26.7%) | 0.928 |
NYHA | | | | 0.041 |
II | 57 (21.1%) | 24 (12.2%) | 81 (17.4%) | |
III | 138 (51.1%) | 108 (55.1%) | 246 (52.8%) | |
IV | 75 (27.8%) | 64 (32.7%) | 139 (29.8%) | |
Heart rate, beats/min | 85.5 (20.9) | 85.1 (21.4) | 85.7 (20.6) | 0.731 |
Systolic blood pressure (mmHg) | 127 (22.6) | 124 (19.9) | 129 (24.2) | 0.020 |
Diastolic blood pressure (mmHg) | 78.5 (15.2) | 76.0 (12.2) | 80.4 (16.8) | 0.002 |
Potassium (mmol/L) | 3.99 (0.51) | 3.99 (0.51) | 3.99 (0.50) | 0.912 |
Sodium (mmol/L) | 140 (3.9) | 139 (4.2) | 140 (3.7) | 0.086 |
Albumin (g/L) | 3.66 (0.48) | 3.60 (0.49) | 3.71 (0.47) | 0.025 |
Creatinine (mg/dL) | 1.16 (0.65) | 1.21 (0.61) | 1.12 (0.68) | 0.131 |
Uric acid (mg/dL) | 8.13 (2.83) | 8.41(3.06) | 7.93 (2.64) | 0.070 |
ALT (U/L) | 27(17–46) | 26(15–50) | 27(18–44) | 0.550 |
AST (U/L) | 28(22–42) | 28(22–48) | 28(22–39) | 0.162 |
INR | 1.20 (0.28) | 1.22 (0.26) | 1.18 (0.30) | 0.142 |
Total bilirubin (mg/dL) | 1.23 (1.03) | 1.28 (1.00) | 1.19 (1.04) | 0.348 |
proBNP (ng/L) | 2254 (1269–5835) | 2873 (1572–7373) | 1779 (1087–4601) | < 0.001 |
LVEF (%) | 41.6 (14.4) | 39.8 (13.8) | 44.0 (14.9) | < 0.001 |
Body mass index (kg/M2 ) | 24.2 (5.7) | 23.6 (5.7) | 24.6 (5.8) | 0.068 |
Antisterone, % | 415 (89.1%) | 177 (90.3%) | 238 (88.1%) | 0.451 |
ACEI/ARB, % | 365 (78.3%) | 151 (77.0%) | 214 (79.3%) | 0.566 |
Beta-blocker, % | 373 (80.0%) | 151 (77.0%) | 222 (82.2%) | 0.167 |
Aspirin, % | 198 (42.5%) | 85 (43.4%) | 113 (41.9%) | 0.744 |
MELD | 8.5(7.2–10.9) | 8.9(7.4–11.9) | 8.3(7.1–10.2) | 0.004 |
MELD_XI | 11.3(9.4–13.8) | 11.8(9.4–15.2) | 11.0(9.4–13.2) | 0.008 |
MELD_albumin | 12.3(9.6–15.2) | 13.1(10.6–16.4) | 11.6(9.0-14.6) | < 0.001 |
MELD_sodium | 8.6(6.5–12.4) | 9.4(6.9–14.0) | 8.3(6.3–11.0) | 0.004 |
Data are presented as mean (SD) or median (interquartile range), or n (%). proBNP, N-terminal pro-brain natriuretic peptide; NYHA, New York Heart Association functional; ALT, alanine aminotransferase; AST, aspartate aminotransaminase; LVEF, left ventricular ejection fraction; ACEI, angiotensin converting enzyme inhibitors; ARB, angiotensin receptor blocker. |
Agreement Of Measurements
Figure 3A presents the estimates of the MELD score and its 3 modifications using the four formulas. The median (interquartile) values of the MELD, MELD_XI, MELD_albumin and MELD_sodium scores were 7.2 (8.5–10.9), 11.3 (9.4–13.8), 12.3 (9.6–15.2) and 8.6 (6.5–12.4), respectively. The MELD_XI and MELD_albumin scores were significantly higher than the MELD score (all P value < 0.001), and the MELD_sodium score was similar to the MELD score. Pairwise Spearman correlation test was performed among the MELD score and its 3 modifications. MELD correlated better with MELD_XI (r value = 0.94, P < 0.001) than the 2 other modified MELD scores (r value for MELD_albumin = 0.67, P < 0.001; r value for MELD_sodium = 0.72, P < 0.001) (Fig. 3B).
Impact of MELD score and its 3 modifications on mortality
Table 2 shows the main predictors of all-cause mortality by univariate Cox regression analysis. Baseline age, sex, NYHA class, LVEF, proBNP, systolic blood pressure and diastolic blood pressure (P values < 0.05) were considered potential risk factors for long-term all-cause mortality in patients with AHF. After further adjusting all risk factors at baseline, standardized hazard ratios (HRs) with 95% confidence intervals (CIs) expressing the risk of all-cause mortality were 1.22 (1.06–1.40), 1.20 (1.04–1.39), 1.21 (1.05–1.41) and 1.23 (1.06–1.42) for the MELD, MELD_ XI, MELD_albumin and MELD_sodium scores, respectively, and the corresponding hazard ratios for cardiovascular mortality were 1.30 (1.12–1.50), 1.28 (1.10–1.49), 1.27 (1.07–1.49) and 1.34 (1.14–1.57), respectively (Table 3).
Table 2
Univariate analysis of predictors for all-cause mortality.
| HR(95%CI) | P value |
Age(years) | 1.00(1.00, 1.01) | 0.016 |
Male, % | 0.55(0.41, 0.73) | < 0.001 |
Diabetes,% | 1.01(0.74, 1.39) | 0.936 |
Hypertension, % | 0.87(0.66, 1.15) | 0.327 |
Ischemic heart failure, % | 1.12(0.82, 1.54) | 0.483 |
NYHA | | |
II | 1.00 | |
III | 1.63(1.05, 2.54) | 0.031 |
IV | 2.01(1.25, 3.21) | 0.004 |
Heart rate (beats/min) | 1.00(0.99, 1.00) | 0.521 |
Systolic blood pressure (mmHg) | 0.99(0.99, 1.00) | 0.023 |
Diastolic blood pressure (mmHg) | 0.98(0.97, 0.99) | 0.001 |
Potassium (mmol/L) | 1.08(0.81, 1.42) | 0.612 |
Uric acid (mg/dL) | 1.05(0.99, 1.10) | 0.057 |
ALT (U/L) | 1.00(1.00, 1.00) | 0.598 |
AST (U/L) | 1.00(1.00, 1.00) | 0.659 |
proBNP (ng/L) | 1.00(1.00, 1.00) | < 0.001 |
LVEF (%) | 0.98(0.97, 0.99) | 0.001 |
Body mass index (kg/M2 ) | 0.98(0.95, 1.00) | 0.082 |
Antisterone, % | 1.13(0.70, 1.81) | 0.622 |
ACEI/ARB, % | 0.94(0.67, 1.31) | 0.699 |
Beta-blocker, % | 0.79(0.57, 1.10) | 0.163 |
Aspirin, % | 1.08(0.82, 1.44) | 0.583 |
NYHA, New York Heart Association functional class; ALT, alanine aminotransferase; AST, aspartate aminotransaminase; LVEF, left ventricular ejection fraction; ACEI, angiotensin converting enzyme inhibitors; ARB, angiotensin receptor blocker. |
Table 3
Standardized hazard ratios (95% confidence intervals) of mortality.
| Unadjusted | | Model 1 | | Model 2 |
| HR(95%CI) | P value | | HR(95%CI) | P value | | HR(95%CI) | P value |
All cause mortality | | | | | | | |
MELD | 1.23(1.10–1.38) | < 0.001 | | 1.31(1.16–1.47) | < 0.001 | | 1.22(1.06–1.40) | 0.006 |
MELD_XI | 1.21(1.08–1.36) | 0.002 | | 1.28(1.14–1.45) | < 0.001 | | 1.20(1.04–1.39) | 0.012 |
MELD_albumin | 1.27(1.13–1.42) | < 0.001 | | 1.31(1.16–1.47) | < 0.001 | | 1.21(1.05–1.41) | 0.011 |
MELD_sodium | 1.29(1.14–1.46) | < 0.001 | | 1.36(1.19–1.54) | < 0.001 | | 1.23(1.06–1.42) | 0.006 |
Cardiovascular mortality | | | | | | | |
MELD | 1.31(1.17–1.48) | < 0.001 | | 1.39(1.23–1.56) | < 0.001 | | 1.30(1.12–1.50) | 0.001 |
MELD_XI | 1.29(1.14–1.46) | < 0.001 | | 1.36(1.20–1.53) | < 0.001 | | 1.28(1.10–1.49) | 0.002 |
MELD_albumin | 1.31(1.15–1.48) | < 0.001 | | 1.35(1.18–1.53) | < 0.001 | | 1.27(1.07–1.49) | 0.005 |
MELD_sodium | 1.41(1.23–1.60) | < 0.001 | | 1.48(1.29–1.69) | < 0.001 | | 1.34(1.14–1.57) | < 0.001 |
Model 1 was adjusted for age and sex |
Model2 was adjusted age, sex, NYHA class, LVEF, proBNP, systolic blood pressure, diastolic blood pressure. |
Prognostic Accuracy
The predictive accuracy of the MELD, MELD_XI, MELD_albumin and MELD_sodium scores was compared using time-dependent ROC curves. If we considered the entire follow-up period, the MELD_albumin score showed the best prognostic accuracy for all-cause and cardiovascular mortality in nearly the entire follow-up period. The quantified AUCs with a four-year cut-off for all-cause mortality outcome were 0.580 (0.509–0.650) for the MELD score, 0.544 (0.476–0.614) for the MELD_XI score, 0.658 (0.591–0.728) for the MELD_albumin score, and 0.590 (0.519–0.661) for the MELD_sodium score. The MELD_albumin score was significantly better than the MELD and the 2 other modified MELD scores for predicting 4-year all-cause mortality risk (all P value < 0.05, Fig. 4).
The quantified AUCs with a four-year cut-off for cardiovascular mortality outcome were 0.617 (0.545–0.689) for the MELD score, 0.580 (0.508–0.652) for the MELD_XI score, 0.663 (0.593–0.734) for the MELD_albumin score, and 0.625 (0.553–0.697) for the MELD_sodium score. The MELD_albumin score was significantly better than the MELD_XI score for predicting the 4-year risk of cardiovascular mortality (P value = 0.009, Fig. 5). However, MELD_albumin showed no significant better than the MELD and MELD_sodium score in predicting 4-year cardiovascular mortality risk.