Background
Methods
Study population: the Heart ‘OMics’ in AGEing (HOMAGE) initiative and the high-risk myocardial infarction database initiative
Renal function analyses and estimation of GFR and CrCl
CKD-EPI
MDRD4
CG-BSA
Outcomes
Statistical methods
Results
Population characteristics and renal function stage classification
Variables | Population-based | Cardiovascular risk | Heart failure | Post-myocardial infarction | P value |
---|---|---|---|---|---|
Number of patients | 2644 | 20,895 | 1801 | 28,771 | <0.001 |
Demographic | |||||
Age, years | 66.4 ± 14.1 | 66.7 ± 9.4 | 73.7 ± 10.4 | 65 ± 11.5 | <0.001 |
Male sex, n (%) | 1359 (51.4) | 14,083 (67.4) | 1093 (60.7) | 20,189 (70.2) | <0.001 |
Smokers, n (%) | 400 (15.1) | 5994 (28.8) | 185 (10.7) | 18,235 (63.4) | <0.001 |
Clinical and echocardiographic | |||||
Hypertension, n (%) | 1397 (53.1) | 17,892 (85.6) | 861 (47.8) | 15,570 (54.1) | <0.001 |
Diabetes, n (%) | 334 (12.7) | 5164 (24.7) | 541 (30.1) | 7386 (25.7) | <0.001 |
SBP, mmHg | 136 ± 18 | 159 ± 21 | 133 ± 24 | 122 ± 17 | <0.001 |
Heart rate, bpm | 67 ± 12 | 71 ± 13 | 75 ± 15 | 76 ± 13 | <0.001 |
LVEF, %a | 67 ± 8 | 56 ± 13 | 41 ± 15 | 34 ± 9 | <0.001 |
Height, m | 1.67 ± 8.9 | 1.69 ± 9.5 | 1.66 ± 9.7 | 1.69 ± 9.4 | <0.001 |
Weight, kg | 73.8 ± 13.9 | 80.7 ± 15.8 | 76.4 ± 18.2 | 79.1 ± 15.5 | <0.001 |
Laboratory | |||||
Hemoglobin, g/dLa | 13.9 ± 1.3 | 13.4 ± 1.9 | 13.2 ± 1.8 | 13.3 ± 1.7 | <0.001 |
Creatinine, mg/dL | 0.96 ± 0.24 | 1.12 ± 0.25 | 1.24 ± 0.53 | 1.12 ± 0.32 | <0.001 |
MDRD4, mL/min/1.73 m2 | 77.1 ± 18.2 | 66.8 ± 15.3 | 63.3 ± 24.4 | 71.05 ± 39.61 | <0.001 |
CKD-EPI, mL/min/1.73 m2 | 74.6 ± 17.0 | 65.2 ± 15.4 | 59.3 ± 21.9 | 67.93 ± 20.75 | <0.001 |
CG-BSA, mL/min/1.73 m2 | 71.1 ± 20.6 | 64.6 ± 17.8 | 57.2 ± 25.5 | 68.32 ± 32.89 | <0.001 |
Follow-up and events | |||||
Follow-up, years | 4.2 (3.6–4.9) | 5.0 (3.3–5.9) | 2.6 (1.2–3.5) | 1.0 (0.2–1.9) | <0.001 |
CVM, n (%) | 52 (2.0) | 785 (3.8) | 283 (15.7) | 4400 (15.3) | <0.001 |
Formula | MDRD4 | CKD-EPI | CG-BSA | P value | |||
---|---|---|---|---|---|---|---|
RF stage | Patients, n (%) | Events, n (%) | Patients, n (%) | Events, n (%) | Patients, n (%) | Events, n (%) | |
Population-based | |||||||
Stage 1: ≥ 90 | 521 (19.7) | 9 (1.7) | 425 (16.1) | 3 (0.7) | 429 (16.2) | 4 (0.9) | <0.001 |
Stage 2: 60–89 | 1688 (63.8) | 26 (1.5) | 1701 (64.3) | 29 (1.7) | 1410 (53.3) | 17 (1.2) | <0.001 |
Stage 3a: 45–59 | 353 (13.3) | 11 (3.1) | 395 (14.9) | 12 (3.0) | 602 (22.8) | 17 (2.8) | <0.001 |
Stage 3b/4/5: < 45 | 83 (3.1) | 6 (7.2) | 123 (4.7) | 8 (6.5) | 203 (7.7) | 14 (6.9) | <0.001 |
Cardiovascular risk | |||||||
Stage 1: ≥ 90 | 1223 (5.9) | 27 (2.2) | 1165 (5.6) | 20 (1.7) | 1727 (8.3) | 28 (1.6) | <0.001 |
Stage 2: 60–89 | 12,992 (62.2) | 388 (3.0) | 11,956 (57.2) | 335 (2.8) | 10,284 (49.2) | 253 (2.4) | <0.001 |
Stage 3a: 45–59 | 5325 (25.5) | 242 (4.5) | 5845 (28.0) | 261 (4.5) | 6277 (30.0) | 293 (4.7) | <0.001 |
Stage 3b/4/5: < 45 | 1355 (6.5) | 128 (9.4) | 1929 (9.2) | 169 (8.8) | 2607 (12.5) | 211 (8.1) | <0.001 |
Heart failure | |||||||
Stage 1: ≥ 90 | 229 (12.7) | 18 (7.8) | 165 (9.2) | 7 (4.2) | 179 (9.9) | 4 (2.2) | <0.001 |
Stage 2: 60–89 | 738 (41.0) | 77 (10.4) | 685 (38.0) | 70 (10.2) | 533 (29.6) | 45 (8.4) | <0.001 |
Stage 3a: 45–59 | 405 (22.5) | 71 (17.5) | 428 (23.8) | 63 (14.7) | 443 (24.6) | 62 (14.0) | <0.001 |
Stage 3b/4/5: < 45 | 429 (23.8) | 117 (27.3) | 523 (29.0) | 143 (27.3) | 646 (35.9) | 172 (26.6) | <0.001 |
Post-myocardial infarction | |||||||
Stage 1: ≥ 90 | 4277 (15.3) | 405 (9.5) | 4210 (15.1) | 351 (8.3) | 4315 (15.8) | 337 (7.8) | <0.001 |
Stage 2: 60–89 | 14,328 (51.4) | 1670 (11.7) | 13,400 (48.1) | 1515 (11.3) | 11,746 (43.1) | 1197 (10.2) | <0.001 |
Stage 3a: 45–59 | 6261 (22.5) | 1247 (19.9) | 6453 (23.1) | 1228 (19.0) | 6746 (24.8) | 1219 (18.1) | <0.001 |
Stage 3b: 30–45 | 2622 (9.4) | 793 (30.2) | 3174 (11.4) | 924 (29.1) | 3744 (13.7) | 1090 (29.1) | <0.001 |
Stage 4/5: < 30 | 388 (1.5) | 162 (41.8) | 639 (2.4) | 259 (40.5) | 682 (2.6) | 280 (41.1) | <0.001 |
Mortality prediction and accuracy
Variables | Univariable: HR (95% CI) | P value | Adjusted: HR (95% CI) | P value |
---|---|---|---|---|
Population-based | ||||
MDRD4 | ||||
Categorical | 0.001 | 0.046 | ||
Stage 1: ≥ 90 | Reference | Reference | ||
Stage 2: 60–89 | 0.818 (0.382–1.751) | 0.605 | 0.799 (0.370–1.726) | 0.568 |
Stage 3a: 45–59 | 1.908 (0.790–4.609) | 0.151 | 1.423 (0.563–3.597) | 0.456 |
Stage 3b/4/5: < 45 | 4.624 (1.644–13.008) | 0.004 | 3.004 (0.976–9.247) | 0.055 |
CKD-EPI | ||||
Categorical | <0.001 | 0.019 | ||
Stage 1: ≥ 90 | Reference | Reference | ||
Stage 2: 60–89 | 2.471 (0.752–8.117) | 0.136 | 2.007 (0.607–6.640) | 0.254 |
Stage 3a: 45–59 | 4.968 (1.400–17.635) | 0.013 | 3.122 (0.851–11.456) | 0.086 |
Stage 3b/4/5: < 45 | 11.207 (2.967–42.335) | <0.001 | 6.426 (1.610–25.652) | 0.008 |
CG-BSA | ||||
Categorical | <0.001 | <0.001 | ||
Stage 1: ≥ 90 | Reference | Reference | ||
Stage 2: 60–89 | 1.367 (0.459–4.070) | 0.574 | 1.078 (0.360–3.230) | 0.894 |
Stage 3a: 45–59 | 3.658 (1.226–10.915) | 0.020 | 2.393 (0.787–7.275) | 0.124 |
Stage 3b/4/5: < 45 | 9.562 (3.131–29.199) | <0.001 | 5.347 (1.665–17.170) | 0.005 |
Cardiovascular risk | ||||
MDRD4 | ||||
Categorical | <0.001 | <0.001 | ||
Stage 1: ≥ 90 | Reference | Reference | ||
Stage 2: 60–89 | 1.008 (0.682–1.489) | 0.969 | 1.096 (0.740–1.624) | 0.647 |
Stage 3a: 45–59 | 1.682 (1.130–2.504) | 0.010 | 1.924 (1.285–2.881) | 0.001 |
Stage 3b/4/5: < 45 | 4.308 (2.844–6.526) | <0.001 | 5.138 (3.361–7.857) | <0.001 |
CKD-EPI | ||||
Categorical | <0.001 | <0.001 | ||
Stage 1: ≥ 90 | Reference | Reference | ||
Stage 2: 60–89 | 1.292 (0.823–2.029) | 0.266 | 1.391 (0.884–2.190) | 0.154 |
Stage 3a: 45–59 | 2.263 (1.436–3.566) | <0.001 | 2.543 (1.605–4.029) | <0.001 |
Stage 3b/4/5: < 45 | 5.397 (3.393–8.583) | <0.001 | 6.292 (3.923–10.091) | <0.001 |
CG-BSA | ||||
Categorical | <0.001 | <0.001 | ||
Stage 1: ≥ 90 | Reference | Reference | ||
Stage 2: 60–89 | 1.347 (0.911–1.990) | 0.135 | 1.504 (1.009–2.241) | 0.045 |
Stage 3a: 45–59 | 2.927 (1.986–4.315) | <0.001 | 3.416 (2.290–5.094) | <0.001 |
Stage 3b/4/5: < 45 | 6.277 (4.227–9.322) | <0.001 | 7.520 (4.981–11.353) | <0.001 |
Heart failure | ||||
MDRD4 | ||||
Categorical | <0.001 | <0.001 | ||
Stage 1: ≥ 90 | Reference | Reference | ||
Stage 2: 60–89 | 1.076 (0.643–1.800) | 0.781 | 1.016 (0.605–1.706) | 0.952 |
Stage 3a: 45–59 | 1.791 (1.066–3.007) | 0.028 | 1.517 (0.896–2.569) | 0.121 |
Stage 3b/4/5: < 45 | 3.298 (2.007–5.420) | <0.001 | 2.824 (1.704–4.680) | <0.001 |
CKD-EPI | ||||
Categorical | <0.001 | <0.001 | ||
Stage 1: ≥ 90 | Reference | Reference | ||
Stage 2: 60–89 | 2.194 (1.008–4.774) | 0.048 | 2.248 (1.030–4.906) | 0.042 |
Stage 3a: 45–59 | 2.997 (1.372–6.549) | 0.006 | 2.871 (1.306–6.310) | 0.009 |
Stage 3b/4/5: < 45 | 6.557 (3.070–14.006) | <0.001 | 5.784 (2.692–12.430) | <0.001 |
CG-BSA | ||||
Categorical | <0.001 | <0.001 | ||
Stage 1: ≥ 90 | Reference | Reference | ||
Stage 2: 60–89 | 3.243 (1.164–9.031) | 0.024 | 3.457 (1.240–9.642) | 0.018 |
Stage 3a: 45–59 | 5.266 (1.915–14.485) | 0.001 | 5.078 (1.838–14.024) | 0.002 |
Stage 3b/4/5: < 45 | 12.388 (4.595–33.398) | <0.001 | 11.006 (4.066–29.793) | <0.001 |
Post-myocardial infarction | ||||
MDRD4 | ||||
Categorical | <0.001 | <0.001 | ||
Stage 1: ≥ 90 | Reference | Reference | ||
Stage 2: 60–89 | 1.243 (1.115–1.385) | <0.001 | 1.296 (1.162–1.446) | <0.001 |
Stage 3a: 45–59 | 2.253 (2.014–2.521) | <0.001 | 2.251 (2.009–2.523) | <0.001 |
Stage 3b: 30–45 | 3.692 (3.276–4.162) | <0.001 | 3.509 (3.104–3.967) | <0.001 |
Stage 4/5: < 30 | 5.509 (4.591–6.610) | <0.001 | 5.076 (4.208–6.123) | <0.001 |
CKD-EPI | ||||
Categorical | <0.001 | <0.001 | ||
Stage 1: ≥ 90 | Reference | Reference | ||
Stage 2: 60–89 | 1.363 (1.214–1.531) | <0.001 | 1.427 (1.269–1.603) | <0.001 |
Stage 3a: 45–59 | 2.430 (2.158–2.736) | <0.001 | 2.442 (2.165–2.754) | <0.001 |
Stage 3b: 30–45 | 3.976 (3.516–4.497) | <0.001 | 3.852 (3.396–4.368) | <0.001 |
Stage 4/5: < 30 | 6.098 (5.193–7.160) | <0.001 | 5.765 (4.887–6.800) | <0.001 |
CG-BSA | ||||
Categorical | <0.001 | <0.001 | ||
Stage 1: ≥ 90 | Reference | Reference | ||
Stage 2: 60–89 | 1.302 (1.154–1.470) | <0.001 | 1.369 (1.213–1.546) | <0.001 |
Stage 3a: 45–59 | 2.447 (2.169–2.761) | <0.001 | 2.523 (2,234–2.849) | <0.001 |
Stage 3b: 30–45 | 4.230 (3.744–4.780) | <0.001 | 4.239 (3.745–4.799) | <0.001 |
Stage 4/5: < 30 | 6.536 (5.578–7.659) | <0.001 | 6.639 (5.649–7.802) | <0.001 |
Discrimination, calibration, and reclassification improvement analysis
Cohorts | Model comparison (A vs. B) | C-index A% | C-index B% | ΔC-index% | P value | IDI% (95% CI) | P value | NRI% (95% CI) | P value |
---|---|---|---|---|---|---|---|---|---|
Population | Model vs. MDRD4 | 72.8 | 75.7 | 2.9 (−0.3 to 6.1) | 0.072 | 0.5 (−0.1 to 4.3) | 0.16 | 16.7 (−2.0 to 44.1) | 0.072 |
Model vs. CKD-EPI | 72.8 | 75.2 | 2.4 (−1.6 to 6.4) | 0.23 | 0.6 (0.1 to 4.8) | 0.016 | 23.4 (−0.9 to 44.4) | 0.054 | |
Model vs. CG-BSA | 72.8 | 77.3 | 4.5 (−0.7 to 9.7) | 0.087 | 1.0 (0.2 to 5.7) | 0.020 | 39.1 (4.6 to 51.2) | 0.020 | |
MDRD4 vs. CKD-EPI | 75.7 | 75.2 | 0.5 (−2.4 to 3.4) | 0.74 | 0.2 (0.0 to 0.8) | 0.026 | 23.2 (−10.7 to 36.8) | 0.20 | |
MDRD4 vs. CG-BSA | 75.7 | 77.3 | 1.6 (−2.8 to 6.1) | 0.48 | 0.5 (0.0 to 2.1) | 0.045 | 27.4 (−6.8 to 47.9) | 0.13 | |
CKD-EPI vs. CG-BSA | 75.2 | 77.3 | 2.1 (−0.1 to 4.4) | 0.067 | 0.4 (−0.2 to 1.6) | 0.14 | 31.3 (−13.9 to 48.1) | 0.17 | |
CV risk | Model vs. MDRD4 | 58.9 | 66.2 | 7.3 (5.2 to 9.5) | <0.001 | 0.9 (0.6 to 1.6) | <0.001 | 18.5 (13.0 to 24.3) | <0.001 |
Model vs. CKD-EPI | 58.9 | 67.5 | 8.6 (6.4 to 10.9) | <0.001 | 1.1 (0.7 to 1.7) | <0.001 | 20.3 (15.3 to 25.8) | <0.001 | |
Model vs. CG-BSA | 58.9 | 70.2 | 11.3 (8.9 to 13.7) | <0.001 | 1.5 (1.0 to 2.4) | <0.001 | 27.3 (21.4 to 32.6) | <0.001 | |
MDRD4 vs. CKD-EPI | 66.2 | 67.5 | 1.3 (0.8 to 1.8) | <0.001 | 0.1 (0.1 to 0.2) | 0.006 | 23.0 (16.7 to 29.5) | <0.001 | |
MDRD4 vs. CG-BSA | 66.2 | 70.2 | 4.0 (2.7 to 5.3) | <0.001 | 0.6 (0.3 to 0.9) | <0.001 | 22.8 (16.8 to 29.1) | <0.001 | |
CKD-EPI vs. CG-BSA | 67.5 | 70.2 | 2.7 (1.7 to 3.7) | <0.001 | 0.4 (0.2 to 0.7) | <0.001 | 21.1 (14.6 to 27.6) | <0.001 | |
Heart failure | Model vs. MDRD4 | 70.7 | 75.0 | 4.2 (1.9 to 6.5) | <0.001 | 2.7 (1.2 to 4.8) | <0.001 | 24.6 (15.9 to 34.1) | <0.001 |
Model vs. CKD-EPI | 70.7 | 75.5 | 4.7 (2.3 to 7.1) | <0.001 | 3.0 (1.5 to 5.2) | <0.001 | 25.5 (15.5 to 34.1) | <0.001 | |
Model vs. CG-BSA | 70.7 | 77.0 | 6.3 (3.6 to 8.9) | <0.001 | 4.4 (2.6 to 7.2) | <0.001 | 29.6 (20.1 to 39.9) | <0.001 | |
MDRD4 vs. CKD-EPI | 75.0 | 75.5 | 0.5 (0.2 to 0.8) | 0.003 | 0.3 (0.1 to 0.5) | 0.006 | 12.7 (1.6 to 23.8) | 0.024 | |
MDRD4 vs. CG-BSA | 75.0 | 77.0 | 2.1 (1.1 to 3.0) | <0.001 | 1.7 (0.8 to 2.7) | <0.001 | 24.9 (14.7 to 34.7) | <0.001 | |
CKD-EPI vs. CG-BSA | 75.5 | 77.0 | 1.6 (0.8 to 2.4) | <0.001 | 1.4 (0.6 to 2.3) | <0.001 | 26.5 (14.4 to 34.5) | <0.001 | |
Post-MI | Model vs. MDRD4 | 61.7 | 66.5 | 4.9 (4.2 to 5.6) | <0.001 | 3.4 (2.9 to 3.9) | <0.001 | 21.1 (19.4 to 22.8) | <0.001 |
Model vs. CKD-EPI | 61.7 | 67.3 | 5.6 (4.9 to 6.4) | <0.001 | 3.8 (3.4 to 4.4) | <0.001 | 22.4 (20.6 to 24.0) | <0.001 | |
Model vs. CG-BSA | 61.7 | 68.8 | 7.1 (6.3 to 7.9) | <0.001 | 4.9 (4.3 to 5.6) | <0.001 | 24.9 (23.0 to 26.5) | <0.001 | |
MDRD4 vs. CKD-EPI | 66.5 | 67.3 | 0.8 (0.6 to 0.9) | <0.001 | 0.5 (0.4 to 0.6) | <0.001 | 16.4 (13.6 to 20.0) | <0.001 | |
MDRD4 vs. CG-BSA | 66.6 | 68.8 | 2.3 (1.9 to 2.6) | <0.001 | 1.6 (1.3 to 1.9) | <0.001 | 20.9 (18.9 to 23.1) | <0.001 | |
CKD-EPI vs. CG-BSA | 67.3 | 68.8 | 1.5 (1.3 to 1.8) | <0.001 | 1.1 (0.9 to 1.4) | <0.001 | 16.6 (13.8 to 20.4) | <0.001 |