Introduction
Materials and methods
Study population
Clinical evaluation and follow-up
Laboratory measurements
Statistical analysis
Results
Patient characteristics
Characteristic | Total (n= 287) | ADHF (n= 154) | No ADHF (n= 133) | P-value |
---|---|---|---|---|
Age (years)
a
| 74 ± 12 | 78 ± 9 | 68 ± 13 | < 0.0001 |
Male sex (% of patients) | 52 | 51 | 53 | 0.906 |
BMI (kg/m2)
a
| 26.1 ± 6.2 | 26.6 ± 5.9 | 25.5 ± 6.5 | 0.124 |
Medical conditions (% of patients)
| ||||
Heart failure | 24 | 40 | 7 | < 0.0001 |
Coronary artery disease | 28 | 38 | 16 | < 0.0001 |
Chronic obstructive pulmonary disease | 34 | 27 | 42 | 0.006 |
Diabetes | 18 | 24 | 11 | 0.005 |
Hypertension | 68 | 78 | 56 | < 0.0001 |
Hyperlipidemia | 29 | 33 | 25 | 0.165 |
Chronic kidney disease | 28 | 44 | 11 | < 0.0001 |
Initial clinical findings
| ||||
Heart rate (bpm)
a
| 93 ± 23 | 93 ± 25 | 92 ± 19 | 0.495 |
Systolic pressure (mm Hg)
a
| 138 ± 26 | 135 ± 27 | 140 ± 25 | 0.098 |
NYHA functional class (% of patients) | ||||
II | 20 | 10 | 32 | < 0.0001 |
III | 40 | 45 | 35 | 0.109 |
IV | 40 | 45 | 33 | 0.034 |
Edema | 42 | 57 | 26 | < 0.0001 |
Rales | 54 | 64 | 43 | < 0.0001 |
Medication at admission
| ||||
Beta-blockers | 39 | 57 | 17 | < 0.0001 |
ACE-Inhibitors/AT-receptor-blockers | 49 | 62 | 34 | < 0.0001 |
Diuretics | 52 | 64 | 39 | < 0.0001 |
Laboratory findings
| ||||
eGFR - ml/min/1.73m2
b
| 67 (44 to 89) | 54 (36 to 73) | 80 (63 to 112) | < 0.0001 |
BNP (pmol/l)
b
| 349 (89 to 1,121) | 976 (467 to 1,925) | 81 (39 to 181) | < 0.0001 |
NT-proBNP (pmol/l)
b
| 1,656 (314 to 6,105) | 5,757 (1,924 to 13,243) | 300 (76 to 974) | < 0.0001 |
Copeptin (pmol/l)
b
| 21 (8 to 52) | 34 (13 to 71) | 11 (6 to 31) | < 0.0001 |
Copeptin levels and prognostic value of Copeptin on short-term outcome
All patients | ADHF | No ADHF | ||||
---|---|---|---|---|---|---|
Characteristic | HR for 30-day mortality |
P -value
| HR for 30-day mortality |
P -value
| HR for 30-day mortality |
P -value
|
Age (yr) | 1.05 (1.01 to 1.10) | 0.012 | 1.03 (0.98 to 1.09) | 0.230 | 1.06 (0.99 to 1.13) | 0.1 |
Male sex | 1.55 (0.73 to 3.27) | 0.255 | 1.59 (0.66 to 3.84) | 0.300 | 1.51 (0.36 to 6.33) | 0.57 |
BMI | 0.99 (0.93 to 1.05) | 0.68 | 1.01 (0.94 to 1.08) | 0.830 | 0.91 (0.80 to 1.04) | 0.18 |
Medical conditions (% of patients) | ||||||
Heart failure | 1.40 (0.64 to 3.08) | 0.4 | 1.13 (0.48 to 2.69) | 0.780 | 0.05 (0.00 to 7228) | 0.61 |
Coronary artery disease | 0.52 (0.20 to 1.35) | 0.18 | 0.47 (0.17 to 1.29) | 0.140 | 0.04 (0.00 to 127) | 0.43 |
Chronic obstructive pulmonary disease | 0.47 (0.33 to 1.68) | 0.48 | 1.12 (0.44 to 2.89) | 0.810 | 0.46 (0.09 to 2.26) | 0.34 |
Diabetes | 0.72 (0.25 to 2.06) | 0.53 | 0.50 (0.15 to 1.70) | 0.270 | 1.16 (0.14 to 9.40) | 0.89 |
Hypertension | 0.77 (0.36 to 1.62) | 0.49 | 0.52 (0.21 to 1.28) | 0.150 | 0.80 (0.20 to 3.20) | 0.75 |
Hyperlipidemia | 0.37 (0.13 to 1.06) | 0.07 | 0.32 (0.10 to 1.09) | 0.070 | 0.41 (0.05 to 3.34) | 0.41 |
Chronic kidney disease | 2.89 (1.39 to 5.98) | 0.004 | 1.47 (0.62 to 3.46) | 0.380 | 9.64 (2.41 to 38.61) | 0.001 |
Initial clinical findings | ||||||
Heart rate (bpm) | 1.01 (0.99 to 1.02) | 0.45 | 1.00 (0.98 to 1.02) | 0.870 | 1.02 (0.99 to 1.05) | 0.22 |
Systolic pressure (mm Hg) | 0.97 (0.96 to 0.99) | < 0.001 | 0.98 (0.96 to 0.99) | 0.010 | 0.97 (0.94 to 1.00) | 0.02 |
NYHA functional class | 3.44 (1.74 to 6.81) | < 0.001 | 7.47 (2.28 to 24.45) | 0.001 | 1.53 (0.65 to 3.67) | 0.33 |
Edema | 1.73 (0.83 to 3.59) | 0.14 | 1.02 (0.43 to 2.42) | 0.960 | 3.00 (0.75 to 12.00) | 0.12 |
Rales | 1.40 (0.66 to 2.95) | 0.38 | 0.72 (0.30 to 1.74) | 0.460 | 4.14 (0.84 to 20.53) | 0.08 |
Medication at admission
| ||||||
Beta-blockers | 0.82 (0.38 to 1.76) | 0.61 | 0.65 (0.28 to 1.53) | 0.320 | 0.04 (0.00 to 90) | 0.41 |
ACE-Inhibitors/AT-receptor-blockers | 0.95 (0.46 to 1.96) | 0.88 | 0.51(0.22 to 1.20) | 0.120 | 1.96 (0.49 to 7.85) | 0.34 |
Diuretics | 1.76 (0.82 to 3.79) | 0.15 | 1.40 (0.54 to 3.60) | 0.490 | 1.62 (0.41 to 6.49) | 0.49 |
Laboratory findings
| ||||||
eGFR - ml/minute/1.73m2
a
| 0.11 (0.04 to 0.35) | < 0.001 | 0.18 (0.04 to 0.81) | 0.025 | 0.08 (0.01 to 0.55) | 0.011 |
BNP
a
| 2.02 (1.14 to 3.58) | 0.017 | 1.23 (0.44 to 3.41) | 0.700 | 3.66 (0.83 to 16.11) | 0.086 |
NT-proBNP
a
| 3.64 (2.02 to 6.56) | < 0.0001 | 4.57 (1.72 to 12.17) | 0.002 | 8.26 (2.34 to 29.12) | 0.001 |
Copeptin
a
| 5.28 (3.08 to 9.06) | < 0.0001 | 5.36 (2.82 to 10.19) | < 0.001 | 4.21 (1.46 to 12.14) | 0.008 |
All patients | ADHF | No ADHF | ||||
---|---|---|---|---|---|---|
Variable | HR for 30-day mortality |
P -value
| HR for 30-day mortality |
P -value
| HR for 30-day mortality |
P -value
|
Copeptin
a
| 4.58 (2.29 to 9.13) | < 0.0001 | 6.51 (2.83 to 14.95) | < 0.0001 | 1.87 (0.29 to 12.12) | 0.51 |
BNP
a
| 1.42 (0.71 to 2.86) | 0.32 | 0.76 (0.23 to 2.50) | 0.65 | 2.28 (0.49 to 10.67) | 0.3 |
NT-proBNP
a
| 3.17 (1.49 to 6.71) | 0.003 | 3.84 (1.15 to 12.89) | 0.029 | 5.32 (1.1 to 25.76) | 0.038 |
Adjusted model including NT to proBNP or Copeptin | ||||||
Copeptin
a
| 3.88 (1.94 to 7.77) | < 0.001 | 5.99 (2.55 to 14.07) | < 0.0001 | 1.23 (0.17 to 9.14) | 0.84 |
NT-proBNP
a
| 2.74 (1.27 to 5.93) | 0.01 | 2.78 (0.78 to 10.60) | 0.11 | 5.26 (1.07 to 25.79) | 0.041 |
Combined prognostic value of Copeptin and NT-proBNP
Discussion
Conclusions
Key messages
-
In patients with acute dyspnea, Copeptin levels are elevated in non-survivors compared to survivors.
-
Copeptin is a new promising prognostic marker for short-term mortality independently of natriuretic peptide levels.
-
The elevation of both Copeptin and NT-proBNP was associated with the highest rates of death at 30 days.
-
Patients with low Copeptin levels had an excellent short-term prognosis even if NT-proBNP levels were high.