Table 3.
Association of Anemia and Hemoglobin with the Composite Outcome
| Univariable analysis | Multivariable analysis* | |||
|---|---|---|---|---|
| HR (95% CI) | P value | HR (95% CI) | P value | |
| Total cohort (n=4339) | ||||
| Hemoglobin (per 1g/L increase) | 0.982 (0.979–0.986) | <0.001 | 0.990 (0.986–0.994) | <0.001 |
| Anemia (vs no) | 2.152 (1.852–2.499) | <0.001 | 1.509 (1.283–1.775) | <0.001 |
| Medically treated MR (n=3365) | ||||
| Hemoglobin (per 1g/L increase) | 0.984 (0.981–0.988) | <0.001 | 0.989 (0.985–0.993) | <0.001 |
| Anemia (vs no) | 1.898 (1.627–2.213) | <0.001 | 1.500 (1.269–1.773) | <0.001 |
| MVI (n=974)† | ||||
| Hemoglobin (per 1g/L increase) | 0.989 (0.973–1.006) | 0.200 | 1.007 (0.987–1.028) | 0.488 |
| Anemia (vs no) | 2.137 (1.097–4.162) | 0.026 | 1.439 (0.704–2.941) | 0.318 |
| Heart failure (n=3148) | ||||
| Hemoglobin (per 1g/L increase) | 0.982 (0.978–0.985) | <0.001 | 0.991 (0.987–0.995) | <0.001 |
| Anemia (vs no) | 2.191 (1.862–2.580) | <0.001 | 1.472 (1.232–1.758) | <0.001 |
| No heart failure (n=1191) | ||||
| Hemoglobin (per 1g/L increase) | 0.983 (0.975–0.992) | <0.001 | 0.983 (0.972–0.993) | 0.001 |
| Anemia (vs no) | 2.009 (1.378–2.931) | <0.001 | 1.609 (1.059–2.443) | 0.026 |
| NYHA I (n=1249) | ||||
| Hemoglobin (per 1g/L increase) | 0.983 (0.974–0.992) | <0.001 | 0.983 (0.973–0.993) | 0.001 |
| Anemia (vs no) | 2.077 (1.439–2.999) | <0.001 | 1.610 (1.073–2.415) | 0.021 |
| NYHA II–IV (n=3090) | ||||
| Hemoglobin (per 1g/L increase) | 0.982 (0.978–0.986) | <0.001 | 0.991 (0.986–0.995) | <0.001 |
| Anemia (vs no) | 2.184 (1.853–2.573) | <0.001 | 1.474 (1.232–1.762) | <0.001 |
| LA≥55mm (n=753) | ||||
| Hemoglobin (per 1g/L increase) | 0.987 (0.980–0.994) | <0.001 | 0.994 (0.985–1.003) | 0.167 |
| Anemia (vs no) | 2.007 (1.449–2.781) | <0.001 | 1.428 (0.987–2.067) | 0.059 |
| LA<55mm (n=3586) | ||||
| Hemoglobin (per 1g/L increase) | 0.981 (0.977–0.985) | <0.001 | 0.989 (0.984–0.993) | <0.001 |
| Anemia (vs no) | 2.189 (1.850–2.591) | <0.001 | 1.500 (1.248–1.802) | <0.001 |
| LVEF>60% (n=1151) | ||||
| Hemoglobin (per 1g/L increase) | 0.976 (0.967–0.984) | <0.001 | 0.997 (0.986–1.009) | 0.656 |
| Anemia (vs no) | 2.990 (1.998–4.473) | <0.001 | 1.415 (0.893–2.242) | 0.140 |
| LVEF≤60% (n=3188) | ||||
| Hemoglobin (per 1g/L increase) | 0.983 (0.980–0.987) | <0.001 | 0.988 (0.984–0.993) | <0.001 |
| Anemia (vs no) | 1.965 (1.672–2.309) | <0.001 | 1.513 (1.270–1.804) | <0.001 |
| NT-proBNP≥2034‡ (n=1411) | ||||
| Hemoglobin (per 1g/L increase) | 0.986 (0.981–0.990) | <0.001 | 0.990 (0.985–0.995) | <0.001 |
| Anemia (vs no) | 1.859 (1.520–2.274) | <0.001 | 1.573 (1.262–1.960) | <0.001 |
| NT-proBNP<2034 (n=1408) | ||||
| Hemoglobin (per 1g/L increase) | 0.993 (0.983–1.002) | 0.135 | 0.995 (0.984–1.006) | 0.402 |
| Anemia (vs no) | 1.269 (0.847–1.901) | 0.249 | 1.022 (0.655–1.595) | 0.923 |
| Isolated MR (n=2677) | ||||
| Hemoglobin (per 1g/L increase) | 0.979 (0.974–0.984) | <0.001 | 0.985 (0.979–0.991) | <0.001 |
| Anemia (vs no) | 2.369 (1.930–2.908) | <0.001 | 1.566 (1.248–1.965) | <0.001 |
| MR+TR (n=1662) | ||||
| Hemoglobin (per 1g/L increase) | 0.987 (0.982–0.992) | <0.001 | 0.994 (0.989–1.000) | 0.049 |
| Anemia (vs no) | 1.841 (1.478–2.292) | <0.001 | 1.421 (1.120–1.802) | 0.004 |
| Moderate MR (n=2692) | ||||
| Hemoglobin (per 1g/L increase) | 0.984 (0.980–0.988) | <0.001 | 0.991 (0.986–0.996) | <0.001 |
| Anemia (vs no) | 1.951 (1.623–2.346) | <0.001 | 1.402 (1.148–1.713) | <0.001 |
| Severe MR (n=1647) | ||||
| Hemoglobin (per 1g/L increase) | 0.979 (0.973–0.985) | <0.001 | 0.986 (0.979–0.993) | <0.001 |
| Anemia (vs no) | 2.598 (2.005–3.366) | <0.001 | 1.820 (1.373–2.412) | <0.001 |
| Primary VHD (n=1692) | ||||
| Hemoglobin (per 1g/L increase) | 0.977 (0.971–0.982) | <0.001 | 0.990 (0.983–0.997) | 0.007 |
| Anemia (vs no) | 2.894 (2.208–3.794) | <0.001 | 1.596 (1.192–2.138) | 0.002 |
| Secondary VHD (n=2519) | ||||
| Hemoglobin (per 1g/L increase) | 0.986 (0.982–0.990) | <0.001 | 0.991 (0.985–0.996) | <0.001 |
| Anemia (vs no) | 1.789 (1.487–2.152) | <0.001 | 1.438 (1.173–1.763) | <0.001 |
Notes: *Adjusted for age, sex, BMI, smoking status, hypertension, hyperlipidemia, diabetes, coronary artery disease, cardiomyopathy, atrial fibrillation or flutter, chronic lung disease, chronic kidney disease, NYHA functional class (I–II/III–IV), creatinine, albumin, LA, LVEDD, LVEF, TR, pulmonary hypertension, severity of MR, and MVI. MVI, NYHA functional class, and TR were not adjusted in corresponding subgroup analyses. †Chronic kidney disease were not adjusted in patients undergoing MVI because no event occurred in patients with chronic kidney disease. ‡The median level of NT-proBNP was used for the subgroup analysis.
Abbreviations: MR, mitral regurgitation; MVI: mitral valve intervention; NYHA, New York Heart Association; LVEF, left ventricular ejection fraction; TR, tricuspid regurgitation; VHD, valvular heart disease; BMI, body mass index; LA, left atrial end-diastolic dimension; LVEDD, left ventricular end-diastolic dimension; HR, hazard ratio; CI: confidence interval.