Table 1.
Baseline characteristics according to duration of heart failure
| Characteristic | HF 0–1 year (n = 2523) | HF > 1–2 years (n = 1178) | HF > 2–5 years (n = 2054) | HF > 5 years (n = 2644) | P‐value for trend (P trend) |
|---|---|---|---|---|---|
| Age, years | 61.0 ± 12.1 | 62.4 ± 11.8 | 64.5 ± 10.9 | 66.5 ± 10.1 | <0.001 |
| Age ≥70 years, no. (%) | 651 (25.8) | 344 (29.2) | 713 (34.7) | 1090 (41.2) | <0.001 |
| Female sex, no. (%) | 622 (24.7) | 253 (21.5) | 422 (20.5) | 535 (20.2) | <0.001 |
| Race or ethnic group, no. (%) | <0.001 | ||||
| White | 1353 (53.6) | 711 (60.4) | 1403 (68.3) | 2077 (78.6) | |
| Black | 127 (5.0) | 74 (6.3) | 100 (4.9) | 127 (4.8) | |
| Asian | 718 (28.5) | 256 (21.7) | 312 (15.2) | 223 (8.4) | |
| Other | 325 (12.9) | 137 (11.6) | 239 (11.6) | 217 (8.2) | |
| Region, no. (%) | <0.001 | ||||
| North America | 110 (4.4) | 53 (4.5) | 119 (5.8) | 320 (12.1) | |
| Latin America | 475 (18.8) | 209 (17.7) | 366 (17.8) | 383 (14.5) | |
| Western Europe and other | 509 (20.2) | 250 (21.2) | 474 (23.1) | 818 (30.9) | |
| Central Europe | 715 (28.3) | 414 (35.1) | 793 (38.6) | 904 (34.2) | |
| Asia Pacific | 714 (28.3) | 252 (21.4) | 302 (14.7) | 219 (8.3) | |
| Systolic BP, mmHg | 121 ± 15 | 122 ± 16 | 122 ± 15 | 120 ± 15 | 0.014 |
| Heart rate, b.p.m. | 73 ± 12 | 73 ± 12 | 73 ± 12 | 71 ± 12 | <0.001 |
| BMI, kg/m2 | 27.3 ± 5.5 | 27.7 ± 5.4 | 28.5 ± 5.6 | 29.0 ± 5.4 | <0.001 |
| BMI classification | <0.001 | ||||
| Obesity (BMI ≥ 30) | 690 (27.4) | 343 (29.2) | 685 (33.4) | 1001 (37.9) | |
| Overweight (BMI 25–29.9) | 929 (36.9) | 452 (38.4) | 818 (39.8) | 1050 (39.8) | |
| Normal weight (BMI 18.5–24.9) | 814 (32.3) | 352 (29.9) | 526 (25.6) | 576 (21.8) | |
| Underweight (BMI < 18.5) | 87 (3.5) | 29 (2.5) | 24 (1.2) | 13 (0.5) | |
| Haemoglobin, g/L | 137.7 ± 16.2 | 138.8 ± 16.4 | 140.4 ± 15.8 | 140.4 ± 15.6 | <0.001 |
| Serum creatinine, mg/dL | 1.06 ± 0.3 | 1.10 ± 0.3 | 1.14 ± 0.3 | 1.19 ± 0.3 | <0.001 |
| eGFR, mL/min/1.73 m2 | 72.6 ± 21.8 | 69.8 ± 20.1 | 66.7 ± 18.7 | 62.9 ± 18.2 | <0.001 |
| Clinical HF features | |||||
| Ischaemic cardiomyopathy, no. (%) | 1329 (52.7) | 699 (59.3) | 1295 (63.1) | 1713 (64.8) | <0.001 |
| LVEF, % | 29.3 ± 6.0 | 29.7 ± 6.3 | 29.7 ± 6.3 | 29.3 ± 6.3 | 0.438 |
| Median BNP (IQR), pg/mL | 242 (139–468) | 268 (159–502) | 261 (161–483) | 247 (157–441) | 0.326 |
| Median NT‐proBNP (IQR), pg/mL | 1550 (845–3183) | 1838 (1008–3521) | 1648 (889–3368) | 1570 (888–3016) | 0.948 |
| Median NT‐proBNP (IQR), pg/mL if AF on ECG | 1992 (1115–3700) | 2249 (1220–4038) | 1919 (1174–3908) | 2015 (1209–3833) | 0.754 |
| Median NT‐proBNP (IQR), pg/mL if no AF on ECG | 1450 (804–3021) | 1765 (961–3360) | 1512 (831–3137) | 1428 (790–2798) | 0.255 |
| NYHA class, no. (%) | <0.001 | ||||
| I | 151 (6.0) | 56 (4.8) | 84 (4.1) | 98 (3.7) | |
| II | 1924 (76.3) | 819 (69.5) | 1376 (67.0) | 1800 (68.1) | |
| III | 435 (17.2) | 281 (23.9) | 576 (28.0) | 726 (27.5) | |
| IV | 10 (0.4) | 16 (1.4) | 15 (0.7) | 19 (0.7) | |
| Missing data | 3 (0.1) | 6 (0.5) | 3 (0.2) | 1 (0.0) | |
| KCCQ‐CSS (baseline) | 79.3 ± 18.2 | 75.6 ± 19.4 | 74.8 ± 19.3 | 74.0 ± 19.9 | <0.001 |
| Symptoms and signs, no. (%) | |||||
| Effort dyspnoea | 2115 (84.0) | 1000 (85.3) | 1798 (87.7) | 2294 (86.8) | 0.001 |
| Rest dyspnoea | 65 (2.6) | 31 (2.6) | 106 (5.2) | 107 (4.0) | <0.001 |
| Fatigue | 1234 (49.0) | 603 (51.5) | 1118 (54.5) | 1388 (52.5) | 0.003 |
| Orthopnoea | 182 (7.2) | 89 (7.6) | 139 (6.8) | 198 (7.5) | 0.903 |
| Paroxysmal nocturnal dyspnoea | 100 (4.0) | 57 (4.9) | 125 (6.1) | 117 (4.4) | 0.210 |
| Rales | 169 (6.8) | 96 (8.2) | 196 (9.6) | 202 (7.6) | 0.091 |
| Oedema | 432 (17.2) | 241 (20.6) | 450 (21.9) | 625 (23.6) | <0.001 |
| Jugular venous distention | 238 (9.5) | 120 (10.2) | 209 (10.2) | 251 (9.5) | 0.932 |
| 3rd heart sound | 271 (10.8) | 121 (10.3) | 198 (9.7) | 206 (7.8) | <0.001 |
| Median biomarkers (IQR) | |||||
| Gal‐3, ng/mL | 16.03 (13.16–20.15) | 17.41 (14.64–20.81) | 16.69 (13.41–21.21) | 17.48 (14.32–21.97) | 0.001 |
| GDF‐15, ng/L | 1473 (1005–2126) | 1828 (1284–2552) | 1554 (1100–2184) | 1772 (1281–2644) | <0.001 |
| KIM‐1, pg/mL | 128 (84–180) | 146 (104–221) | 125 (82–192) | 128 (88–192) | 0.629 |
| MMP‐2, ng/mL | 132.64 (114.50–155.69) | 137.64 (115.52–160.86) | 133.03 (114.53–153.67) | 136.03 (118.59–156.69) | 0.350 |
| MMP‐9, ng/mL | 57.57 (38.37–120.61) | 62.26 (40.18–124.52) | 71.73 (39.16–137.39) | 63.67 (38.16–128.26) | 0.599 |
| sST2, ng/mL | 30 (25–40) | 32 (26–42) | 32 (25–41) | 33 (27–42) | 0.003 |
| TIMP1, ng/mL | 121 (101–146) | 127 (107–152) | 124 (106–151) | 126 (105–154) | 0.059 |
| hsTnT, μg/L | 0.014 (0.009–0.022) | 0.0175 (0.012–0.028) | 0.017 (0.01–0.024) | 0.018 (0.012–0.027) | <0.001 |
| Medical history, no. (%) | |||||
| Hypertension | 1646 (65.2) | 825 (70.0) | 1527 (74.3) | 1942 (73.5) | <0.001 |
| Diabetes | 765 (30.3) | 388 (32.9) | 718 (35.0) | 1036 (39.2) | <0.001 |
| Atrial fibrillation (history) | 696 (27.6) | 410 (34.8) | 804 (39.1) | 1181 (44.7) | <0.001 |
| Atrial fibrillation (ECG) | 481 (19.1) | 271 (23.0) | 559 (27.2) | 725 (27.4) | <0.001 |
| Prior HF hospitalization | 1539 (61.0) | 740 (62.8) | 1285 (62.6) | 1710 (64.7) | 0.009 |
| Coronary heart disease | 1121 (44.4) | 609 (51.7) | 1199 (58.4) | 1656 (62.6) | <0.001 |
| MI | 845 (33.5) | 478 (40.6) | 940 (45.8) | 1371 (51.9) | <0.001 |
| Stroke | 149 (5.9) | 98 (8.3) | 194 (9.4) | 284 (10.7) | <0.001 |
| PAD | 98 (3.9) | 54 (4.6) | 125 (6.1) | 217 (8.2) | <0.001 |
| COPD | 244 (9.7) | 155 (13.2) | 291 (14.2) | 390 (14.8) | <0.001 |
| CKD (eGFR < 60 mL/min/1.73 m2) | 692 (27.4) | 391 (33.2) | 766 (37.3) | 1212 (45.8) | <0.001 |
| Anaemia a | 573 (23.3) | 262 (22.9) | 373 (18.8) | 484 (19.1) | <0.001 |
| Treatments at randomization, no. (%) | |||||
| Diuretic | 1981 (78.5) | 977 (82.9) | 1622 (79.0) | 2158 (81.6) | 0.040 |
| Digitalis | 751 (29.8) | 356 (30.2) | 617 (30.0) | 815 (30.8) | 0.443 |
| Beta‐blocker | 2327 (92.2) | 1092 (92.7) | 1902 (92.6) | 2490 (94.2) | 0.010 |
| MRA | 1388 (55.0) | 673 (57.1) | 1144 (55.7) | 1466 (55.4) | 0.885 |
| ICD/CRT‐D | 132 (5.2) | 112 (9.5) | 339 (16.5) | 660 (25.0) | <0.001 |
| CRT‐P/CRT‐D | 51 (2.0) | 55 (4.7) | 138 (6.7) | 330 (12.5) | <0.001 |
AF, atrial fibrillation; BMI, body mass index; BNP, B‐type natriuretic peptide; BP, blood pressure; CKD, chronic kidney disease; COPD, chronic obstructive pulmonary disease; CRT, cardiac resynchronization therapy with pacemaker (P) or defibrillator (D); ECG, electrocardiogram; eGFR, estimated glomerular filtration rate; Gal‐3, galectin‐3; GDF‐15, growth differentiation factor‐15; HF, heart failure; hsTnT, high‐sensitivity troponin‐T; ICD, implantable cardioverter‐defibrillator; IQR, inter‐quartile range; KCCQ‐CSS, Kansas City Cardiomyopathy Questionnaire clinical summary score; KIM‐1, kidney injury molecule‐1; LVEF, left ventricular ejection fraction; MI, myocardial infarction; MMP‐2, matrix metalloproteinase‐2; MMP‐9, matrix metalloproteinase‐9; MRA, mineralocorticoid receptor antagonist; NT‐proBNP, N‐terminal pro‐brain natriuretic peptide; NYHA, New York Heart Association; PAD, peripheral arterial disease; sST2, soluble suppression of tumorigenicity‐2; TIMP‐1, tissue inhibitor of matrix metalloproteinase‐1.
Anaemia: haemoglobin < 130 g/L in men and haemoglobin < 120 g/L in women.
Units: millimetres of mercury (mmHg), beats per minute (b.p.m.), kilograms per metre squared (kg/m2), grams per litre (g/L), milligrams per decilitre (mg/dL), picograms per millilitre (pg/mL), nanograms per litre (ng/L), nanograms per millilitre (ng/mL), and micrograms per litre (μg/L).