Background
Methods
Study design
Component population
Pooled methodology
Iron status and other laboratory measurements
Statistical analysis
Results
Variables | Overall N = 1684 | No ID N = 786 | ID N = 898 | P value |
---|---|---|---|---|
Age (years) | 72 (61–79) | 70 (58–78) | 73 (63–79) | < 0.0001 |
Female gender | 588 (35) | 207 (26) | 381 (42) | < 0.0001 |
BMI (kg/m2) | 27 (24–30) | 30 (27–34) | 31 (27–36) | 0.011 |
Systolic BP (mm Hg) | 120 (108–139) | 118 (105–133) | 125 (110–140) | < 0.0001 |
Heart rate (bpm) | 70 (62–80) | 70 (60–80) | 70 (62–80) | 0.398 |
NYHA Class III-IV | 592 (35) | 218 (28) | 374 (42) | < 0.0001 |
LVEF (%) | 35 (27–50) | 35 (27–48) | 36 (28–53) | 0.032 |
HFPEF | 428 (25) | 182 (23) | 246 (27) | 0.046 |
Ischaemic aetiology | 738 (44) | 331 (42) | 407 (45) | 0.185 |
Hypertension | 1136 (68) | 492 (63) | 644 (72) | < 0.0001 |
Diabetes Mellitus | 639 (38) | 262 (33) | 377 (42) | < 0.0001 |
COPD | 318 (19) | 158 (20) | 160 (18) | 0.232 |
Treatment | ||||
ACE-I or ARB | 1457 (87) | 695 (89) | 762 (85) | 0.019 |
Beta blockers | 1474 (88) | 690 (88) | 784 (87) | 0.766 |
MRAs | 716 (43) | 357 (45) | 359 (40) | 0.024 |
Digoxin | 395 (23) | 184 (23) | 211 (24) | 0.966 |
Oral anticoagulation | 755 (45) | 356 (45) | 399 (44) | 0.723 |
Antiplatelet | 879 (52) | 412 (52) | 467 (52) | 0.884 |
Diuretics | 1458 (87) | 661 (84) | 797 (89) | 0.001 |
ICD | 136 (8) | 64 (8) | 72 (8) | 0.933 |
Resynchronization | 77 (5) | 35 (5) | 42 (5) | 0.826 |
Laboratory values | ||||
Haemoglobin (g/dL) | 13.0 (11.7–14.3) | 13.4 (12.0–14.7) | 12.7 (11.5–13.9) | < 0.0001 |
eGFR (ml/min/1.73 m2) | 53 (37–71) | 56 (38–75) | 52 (36–68) | 0.032 |
Ferritin (ng/mL) | 155 (72–276) | 276 (172–435) | 76 (43–141) | < 0.0001 |
Transferrin (mg/dL) | 261 (224–313) | 245 (213–288) | 276 (239–330) | < 0.0001 |
Serum iron (ug/dL) | 73 (51–99) | 90 (71–116) | 59 (44–79) | < 0.0001 |
TSAT (%) | 20 (15–28) | 26 (22–34) | 16 (12–19) | < 0.0001 |
NTproBNP (ng/L) | 1355 (536–3171) | 1111 (488–2747) | 1584 (609–3597) | < 0.0001 |
Sodium (mmol/L) | 140 (138–142) | 140 (138–142) | 140 (138–142) | 0.011 |
Variables | Univariate OR | P value | Multivariate OR | P value |
---|---|---|---|---|
Age (per 5 years) | 1.09 (1.05–1.13) | < 0.001 | ||
Female sex | 2.05 (1.67–2.53) | 0.396 | 1.62 (1.29–2.03) | < 0.001 |
Hypertension | 1.50 (1.23–1.85) | < 0.001 | ||
Diabetes Mellitus | 1.44 (1.18–1.76) | < 0.001 | ||
COPD | 0.86 (0.67–1.10) | 0.223 | ||
HFPEF | 1.25 (1.00–1.56) | 0.047 | ||
Ischaemic aetiology | 1.15 (0.94–1.39) | 0.175 | ||
NYHA class III-IV | 1.84 (1.50–2.26) | < 0.001 | 1.50 (1.20–1.88) | < 0.001 |
Systolic BP (per 10 mmHg) | 1.11 (1.06–1.16) | < 0.001 | 1.09 (1.04–1.14) | < 0.001 |
Heart rate (per 10 bpm) | 1.03 (0.97–1.10) | 0.379 | ||
BMI (1 kg/m2) | 1.03 (1.01–1.04) | 0.008 | 1.03 (1.00–1.05) | 0.018 |
ACE-I or ARB | 0.71 (0.53–0.95) | 0.021 | ||
Beta blockers | 0.96 (0.72–1.28) | 0.781 | ||
Diuretics | 1.50 (1.13–1.98) | 0.005 | ||
MRAs | 0.81 (0.66–0.98) | 0.028 | ||
Digoxin | 1.00 (0.80–1.26) | 0.988 | ||
Oral anticoagulants | 0.96 (0.79–1.17) | 0.690 | ||
Antiplatelet | 0.99 (0.82–1.20) | 0.921 | ||
ICD | 1.02 (0.71–1.44) | 0.94 | ||
Haemoglobin (per 1 g/dL) | 0.82 (0.78–0.87) | < 0.001 | 0.87 (0.82–0.92) | < 0.001 |
Log NT-proBNP (per 1 SD) | 1.20 (1.09–1.33) | < 0.001 | 1.12 (0.99–1.25) | 0.051 |
Sodium (per 5 mmol/L) | 1.17 (1.02–1.34) | 0.030 | ||
eGFR (per 5 ml/min/1.73m2) | 0.98 (0.96–0.99) | 0.016 |
Iron deficiency and mortality
Variables | Univariate HR | P value | Multivariate HR | P value |
---|---|---|---|---|
Age (per 5 years) | 1.36 (1.30–1.42) | < 0.001 | 1.21 (1.16–1.27) | < 0.001 |
Female sex | 1.08 (0.90–1.30) | 0.39 | 0.65 (0.54–0.79) | < 0.001 |
Hypertension | 1.35 (1.12–1.63) | 0.002 | ||
Diabetes Mellitus | 1.51 (1.27–1.80) | < 0.001 | 1.30 (1.08–1.55) | 0.005 |
COPD | 1.63 (1.33–1.99) | < 0.001 | ||
HFPEF | 1.11 (0.90–1.36) | 0.34 | ||
Ischaemic aetiology | 1.09 (0.92–1.30) | 0.33 | ||
NYHA class III-IV | 3.14 (2.63–3.74) | < 0.001 | 1.85 (1.53–2.24) | < 0.001 |
Systolic BP (per 10 mmHg) | 0.97 (0.93–1.01) | 0.112 | ||
Heart rate (per 10 bpm) | 1.09 (1.03–1.16) | 0.004 | ||
BMI (1 kg/m2) | 0.96 (0.95–0.98) | < 0.001 | ||
ACE-I or ARB | 0.37 (0.29–0.46) | < 0.001 | 0.70 (0.55–0.89) | 0.004 |
Beta blockers | 0.41 (0.33–0.51) | < 0.001 | 0.59 (0.47–0.74) | < 0.001 |
Diuretics | 2.46 (1.77–3.42) | < 0.001 | 1.66 (1.19–2.31) | 0.005 |
MRAs | 0.97 (0.82–1.16) | 0.77 | ||
Digoxin | 1.26 (1.05–1.52) | 0.015 | ||
ICD | 0.72 (0.52–0.98) | 0.039 | ||
Iron deficiency | 1.32 (1.11–1.57) | 0.002 | 1.09 (0.91–1.31) | 0.337 |
Haemoglobin (per 1 g/dL) | 0.78 (0.75–0.82) | < 0.001 | 0.90 (0.85–0.95) | < 0.001 |
Log NT-proBNP (per 1 SD) | 1.93 (1.76–2.11) | < 0.001 | 1.49 (1.34–1.66) | < 0.001 |
Sodium (per 5 mmol/L) | 0.78 (0.69–0.88) | < 0.001 | 0.96 (0.94–0.99) | 0.003 |
eGFR (per 5 ml/min/1.73m2) | 0.89 (0.87–0.91) | < 0.001 |
Iron deficiency and hospitalizations due to heart failure
Variables | Univariate HR | P value | Multivariate HR | P value |
---|---|---|---|---|
Age (per 5 years) | 1.23 (1.18–1.29) | < 0.001 | 1.11 (1.05–1.17) | < 0.001 |
Female sex | 1.50 (1.25–1.83) | < 0.001 | ||
Hypertension | 1.47 (1.19–1.81) | < 0.001 | ||
Diabetes Mellitus | 1.46 (1.20–1.77) | < 0.001 | 1.26 (1.03–1.54) | 0.026 |
COPD | 1.76 (1.41–2.19) | < 0.001 | 1.63 (1.28–2.07) | < 0.001 |
HFPEF | 1.60 (1.30–1.97) | < 0.001 | 1.67 (1.31–2.18) | < 0.001 |
Ischaemic aetiology | 1.14 (0.95–1.38) | 0.166 | 1.40 (1.12–1.73) | 0.003 |
NYHA class III-IV | 2.55 (2.10–3.09) | < 0.001 | 1.64 (1.33–2.03) | < 0.001 |
Systolic BP (per 10 mmHg) | 0.97 (0.93–1.01) | 0.123 | ||
Heart rate (per 10 bpm) | 1.09 (1.03–1.16) | 0.005 | ||
BMI (per 1 kg/m2) | 0.99 (0.97–1.01) | 0.21 | ||
ACE-I or ARB | 0.47 (0.37–0.61) | < 0.001 | ||
Beta blockers | 0.46 (0.36–0.58) | < 0.001 | 0.71 (0.54–0.93) | 0.013 |
Diuretics | 3.47 (2.28–5.28) | < 0.001 | 2.53 (1.64–3.91) | < 0.001 |
MRAs | 1.10 (0.91–1.33) | 0.327 | ||
Digoxin | 1.13 (0.91–1.40) | 0.263 | ||
ICD | 0.91 (0.66–1.27) | 0.581 | ||
Iron deficiency | 1.21 (1.00–1.47) | 0.047 | 0.96 (0.78–1.17) | 0.677 |
Haemoglobin (per 1 g/dL) | 0.84 (0.80–0.89) | < 0.001 | ||
Log NT-proBNP (per 1 SD) | 2.00 (1.87–2.15) | < 0.001 | 1.49 (1.32–1.68) | < 0.001 |
Sodium (per 5 mmol/L) | 0.93 (0.81–1.07) | 0.328 | ||
eGFR (per 5 ml/min/1.73m2) | 0.95 (0.93–0.97) | < 0.001 |
Iron deficiency and hospitalizations due to any cause
Variables | Univariate HR | P value | Multivariate HR | P value |
---|---|---|---|---|
Age (per 5 years) | 1.17 (1.13–1.20) | < 0.001 | 1.06 (1.02–1.09) | 0.001 |
Female sex | 1.29 (1.12–1.45) | < 0.001 | ||
Hypertension | 1.42 (1.22–1.65) | < 0.001 | ||
Diabetes Mellitus | 1.46 (1.27–1.68) | < 0.001 | 1.23 (1.06–1.42) | 0.006 |
COPD | 1.56 (1.32–1.84) | < 0.001 | 1.44 (1.21–1.71) | < 0.001 |
HFPEF | 1.40 (1.20–1.63) | < 0.001 | 1.44 (1.21–1.73) | < 0.001 |
Ischaemic aetiology | 1.16 (1.01–1.33) | 0.032 | 1.32 (1.14–1.54) | < 0.001 |
NYHA class III-IV | 2.03 (1.77–2.34) | < 0.001 | 1.40 (1.20–1.64) | < 0.001 |
Systolic BP (per 10 mmHg) | 1.01 (0.98–1.04) | 0.522 | ||
Heart rate (per 10 bpm) | 1.13 (1.08–1.19) | < 0.001 | 1.07 (1.02–1.12) | 0.006 |
BMI (per 1 kg/m2) | 0.99 (0.97–0.99) | 0.033 | ||
ACE-I or ARB | 0.50 (0.41–0.61) | < 0.001 | 0.80 (0.65–0.98) | 0.030 |
Beta blockers | 0.51 (0.43–0.62) | < 0.001 | 0.69 (0.57–0.86) | 0.001 |
Diuretics | 1.70 (1.36–2.12) | < 0.001 | 1.31 (1.04–1.65) | 0.022 |
MRAs | 0.95 (0.83–1.09) | 0.488 | ||
Digoxin | 1.01 (0.86–1.18) | 0.940 | ||
ICD | 0.88 (0.69–1.12) | 0.284 | ||
Iron deficiency | 1.21 (1.05–1.39) | 0.007 | 0.99 (0.86–1.14) | 0.857 |
Haemoglobin (per 1 g/dL) | 0.85 (0.81–0.88) | < 0.001 | 0.94 (0.90–0.98) | 0.002 |
LogNT-proBNP (per 1 SD) | 1.53 (1.42–1.64) | < 0.001 | 1.31 (1.20–1.42) | < 0.001 |
Sodium (per 5 mmol/L) | 0.89 (0.80–0.98) | 0.023 | ||
eGFR (per 5 ml/min/1.73m2) | 0.95 (0.94–0.96) | < 0.001 |