Table 2.
Multivariable Cox analysis for the occurrence of composite cardiovascular outcome, including all strokes, hemorrhagic stroke, ischemic stroke, myocardial infarction, all-cause death, based on changes of presence and severity of proteinuria.
| Number of events | Event rate (%) | Incidence rate (per 1000 person years) |
Unadjusted | Multivariable adjusted (1) | Multivariable adjusted (2) | ||||
|---|---|---|---|---|---|---|---|---|---|
| HR (95% CI) | p-value | HR (95% CI) | p-value | HR (95% CI) | p-value | ||||
| Composite outcome | 143,041 | 8.37 | 5.89 | ||||||
| Normal: 0 → 0 | 136,261 | 8.18 | 5.75 | 1 (reference) | 1 (reference) | 1 (reference) | |||
| Improved: | |||||||||
| +1 → 0 | 1,697 | 13.08 | 9.40 | 1.63 (1.55, 1.71) | < 0.001 | 1.19 (1.14, 1.25) | < 0.001 | 1.19 (1.13, 1.24) | < 0.001 |
| + 2 → 0 | 647 | 16.57 | 12.11 | 2.11 (1.95, 2.27) | < 0.001 | 1.50 (1.38, 1.62) | < 0.001 | 1.47 (1.36, 1.59) | < 0.001 |
| + 2 → +1 | 160 | 21.89 | 16.42 | 2.89 (2.48, 3.38) | < 0.001 | 1.72 (1.47, 2.01) | < 0.001 | 1.70 (1.45, 1.98) | < 0.001 |
| + 3 ~ 4 → 0 | 170 | 21.91 | 16.48 | 2.89 (2.48, 3.35) | < 0.001 | 1.97 (1.69, 2.29) | < 0.001 | 1.94 (1.67, 2.26) | < 0.001 |
| + 3 ~ 4 → +1 | 50 | 28.25 | 22.31 | 4.04 (3.06, 5.33) | < 0.001 | 1.90 (1.44, 2.51) | < 0.001 | 1.86 (1.41, 2.46) | < 0.001 |
| + 3 ~ 4 → +2 | 59 | 29.80 | 23.39 | 4.18 (3.24, 5.39) | < 0.001 | 2.26 (1.75, 2.92) | < 0.001 | 2.24 (1.73, 2.84) | < 0.001 |
| Progressed | |||||||||
| 0 → +1 | 2,072 | 14.60 | 10.57 | 1.84 (1.76, 1.92) | < 0.001 | 1.37 (1.31, 1.43) | < 0.001 | 1.37 (1.31, 1.43) | < 0.001 |
| 0 → +2 | 882 | 19.25 | 14.29 | 2.50 (2.34, 2.68) | < 0.001 | 1.64 (1.54, 1.76) | < 0.001 | 1.62 (1.51, 1.73) | < 0.001 |
| 0 → +3 ~ 4 | 201 | 20.92 | 15.75 | 2.78 (2.42, 3.19) | < 0.001 | 2.04 (1.78, 2.34) | < 0.001 | 2.03 (1.77, 2.33) | < 0.001 |
| + 1 → +2 | 174 | 22.17 | 16.70 | 2.93 (2.53, 3.40) | < 0.001 | 1.54 (1.33, 1.79) | < 0.001 | 1.52 (1.31, 1.77) | < 0.001 |
| + 1 → +3 ~ 4 | 61 | 31.28 | 24.86 | 4.52 (3.52, 5.81) | < 0.001 | 2.49 (1.94, 3.20) | < 0.001 | 2.46 (1.91, 3.16) | < 0.001 |
| + 2 → +3 ~ 4 | 72 | 27.48 | 21.83 | 3.92 (3.11, 4.94) | < 0.001 | 2.38 (1.89, 2.99) | < 0.001 | 2.30 (1.83, 2.90) | < 0.001 |
| Persistent | |||||||||
| + 1 → +1 | 312 | 20.95 | 15.55 | 2.74 (2.45, 3.06) | < 0.001 | 1.61 (1.44, 1.80) | < 0.001 | 1.59 (1.42, 1.78) | < 0.001 |
| + 2 → +2 | 184 | 26.82 | 20.65 | 3.68 (3.18, 4.25) | < 0.001 | 2.01 (1.73, 2.31) | < 0.001 | 2.01 (1.73, 2.32) | < 0.001 |
| + 3 ~ 4 → +3 ~ 4 | 39 | 32.77 | 26.86 | 4.77 (3.49, 6.53) | < 0.001 | 2.91 (2.12, 3.96) | < 0.001 | 2.81 (2.06, 3.85) | < 0.001 |
| All strokes | 17,852 | 1.04 | 0.73 | ||||||
| Normal: 0 → 0 | 17,184 | 1.03 | 0.72 | 1 (reference) | 1 (reference) | 1 (reference) | |||
| Improved: | |||||||||
| +1 → 0 | 170 | 1.30 | 0.93 | 1.57 (1.38, 1.78) | < 0.001 | 1.11 (0.98, 1.26) | 0.108 | 1.10 (0.97, 1.25) | 0.136 |
| + 2 → 0 | 53 | 1.35 | 0.97 | 2.18 (1.79, 2.66) | < 0.001 | 1.46 (1.20, 1.79) | < 0.001 | 1.43 (1.17, 1.74) | < 0.001 |
| + 2 → +1 | 15 | 2.05 | 1.52 | 2.55 (1.67, 3.92) | < 0.001 | 1.49 (1.03, 1.96) | 0.037 | 1.45 (1.04, 1.87) | 0.009 |
| + 3 ~ 4 → 0 | 17 | 2.16 | 1.61 | 2.77 (1.86, 4.13) | < 0.001 | 1.76 (1.18, 2.63) | 0.005 | 1.72 (1.15, 2.57) | 0.008 |
| + 3 ~ 4 → +1 | 4 | 2.25 | 1.76 | 2.13 (0.80, 5.67) | 0.132 | 1.01 (0.38, 2.70) | 0.979 | 0.99 (0.37, 2.63) | 0.977 |
| + 3 ~ 4 → +2 | 11 | 5.39 | 4.24 | 1.41 (0.46, 4.38) | 0.550 | 0.76 (0.25, 2.37) | 0.641 | 0.74 (0.24, 2.28) | 0.595 |
| Progressed | |||||||||
| 0 → +1 | 214 | 1.50 | 1.07 | 1.50 (1.32, 1.70) | < 0.001 | 1.09 (0.96, 1.23) | 0.199 | 1.08 (0.95, 1.22) | 0.247 |
| 0 → +2 | 68 | 1.48 | 1.08 | 2.23 (1.86, 2.68) | < 0.001 | 1.43 (1.19, 1.72) | < 0.001 | 1.40 (1.17, 1.69) | < 0.001 |
| 0 → +3 ~ 4 | 17 | 1.76 | 1.31 | 1.68 (1.06, 2.66) | 0.029 | 1.19 (1.02, 1.36) | 0.045 | 1.18 (1.03, 1.33) | 0.048 |
| + 1 → +2 | 23 | 2.92 | 2.17 | 2.16 (1.38, 3.39) | < 0.001 | 1.14 (1.03, 1.25) | 0.027 | 1.12 (1.03, 1.21) | 0.036 |
| + 1 → +3 ~ 4 | 6 | 3.03 | 2.36 | 3.39 (1.62, 7.11) | 0.001 | 1.83 (1.12, 2.53) | 0.011 | 1.78 (1.05, 2.52) | 0.013 |
| + 2 → +3 ~ 4 | 8 | 2.99 | 2.27 | 2.10 (1.04, 3.25) | 0.007 | 1.27 (1.03, 1.50) | 0.046 | 1.22 (1.02, 1.41) | 0.022 |
| Persistent | |||||||||
| + 1 → +1 | 52 | 2.74 | 2.00 | 2.12 (1.53, 2.95) | < 0.001 | 1.25 (1.01, 1.50) | 0.019 | 1.22 (1.04, 1.39) | 0.023 |
| + 2 → +2 | 26 | 2.75 | 2.04 | 2.25 (1.40, 3.62) | < 0.001 | 1.27 (1.07, 1.48) | 0.036 | 1.25 (1.05, 1.46) | 0.037 |
| + 3 ~ 4 → +3 ~ 4 | 9 | 3.28 | 2.59 | 2.41 (1.05, 3.87) | 0.013 | 1.46 (1.06, 1.87) | 0.012 | 1.40 (1.05, 1.77) | 0.026 |
| Hemorrhagic stroke | 1,051 | 0.06 | 0.04 | ||||||
| Normal: 0 → 0 | 1,016 | 0.06 | 0.04 | 1 (reference) | 1 (reference) | 1 (reference) | |||
| Improved: | |||||||||
| +1 → 0 | 11 | 0.08 | 0.06 | 1.43 (1.10, 1.87) | 0.008 | 1.15 (0.88, 1.50) | 0.304 | 1.14 (0.88, 1.49) | 0.327 |
| + 2 → 0 | 3 | 0.08 | 0.05 | 2.01 (1.34, 3.03) | < 0.001 | 1.56 (1.04, 2.36) | 0.033 | 1.54 (1.02, 2.32) | 0.040 |
| + 2 → +1 | 4 | 0.55 | 0.40 | 1.91 (0.72, 5.09) | 0.195 | 1.33 (0.50, 3.55) | 0.570 | 1.30 (0.49, 3.48) | 0.597 |
| + 3 ~ 4 → 0 | 2 | 0.21 | 0.15 | 1.81 (0.68, 4.82) | 0.236 | 1.37 (0.51, 3.65) | 0.530 | 1.35 (0.51, 3.59) | 0.552 |
| + 3 ~ 4 → +1 | 0 | - | - | - | - | - | - | - | - |
| + 3 ~ 4 → +2 | 0 | - | - | - | - | - | - | - | - |
| Progressed | |||||||||
| 0 → +1 | 7 | 0.05 | 0.03 | 1.58 (1.24, 2.01) | < 0.001 | 1.29 (1.01, 1.64) | 0.042 | 1.28 (1.01, 1.63) | 0.047 |
| 0 → +2 | 3 | 0.07 | 0.05 | 1.66 (1.10, 2.53) | 0.017 | 1.25 (0.82, 1.90) | 0.295 | 1.23 (0.81, 1.88) | 0.327 |
| 0 → +3 ~ 4 | 2 | 0.21 | 0.15 | 1.47 (0.55, 3.91) | 0.442 | 1.20 (0.45, 3.19) | 0.722 | 1.18 (0.44, 3.15) | 0.738 |
| + 1 → +2 | 0 | - | - | - | - | - | - | - | - |
| + 1 → +3 ~ 4 | 0 | - | - | - | - | - | - | - | - |
| + 2 → +3 ~ 4 | 0 | - | - | - | - | - | - | - | - |
| Persistent | |||||||||
| + 1 → +1 | 2 | 0.13 | 0.10 | 1.86 (0.93, 3.72) | 0.080 | 1.28 (0.64, 2.57) | 0.482 | 1.27 (0.63, 2.53) | 0.507 |
| + 2 → +2 | 1 | 0.14 | 0.11 | 1.56 (0.50, 4.84) | 0.442 | 1.05 (0.34, 3.27) | 0.928 | 1.05 (0.34, 3.25) | 0.935 |
| + 3 ~ 4 → +3 ~ 4 | 0 | - | - | - | - | - | - | - | - |
| Ischemic stroke | 22,441 | 1.31 | 0.92 | ||||||
| Normal: 0 → 0 | 21,424 | 1.28 | 0.90 | 1 (reference) | 1 (reference) | 1 (reference) | |||
| Improved: | |||||||||
| +1 → 0 | 238 | 1.83 | 1.30 | 1.60 (1.39, 1.85) | < 0.001 | 1.10 (0.95, 1.26) | 0.211 | 1.09 (0.94, 1.25) | 0.252 |
| + 2 → 0 | 99 | 2.52 | 1.82 | 2.23 (1.79, 2.77) | < 0.001 | 1.44 (1.15, 1.79) | 0.001 | 1.40 (1.12, 1.74) | 0.003 |
| + 2 → +1 | 39 | 5.33 | 4.01 | 2.90 (1.85, 4.55) | < 0.001 | 1.60 (1.02, 2.51) | 0.041 | 1.56 (0.99, 2.45) | 0.053 |
| + 3 ~ 4 → 0 | 21 | 2.67 | 1.99 | 2.89 (1.86, 4.48) | < 0.001 | 1.75 (1.13, 2.72) | 0.012 | 1.71 (1.10, 2.65) | 0.016 |
| + 3 ~ 4 → +1 | 12 | 6.74 | 5.38 | 2.67 (1.00, 7.11) | 0.050 | 1.17 (0.44, 3.11) | 0.757 | 1.14 (0.43, 3.03) | 0.800 |
| + 3 ~ 4 → +2 | 13 | 6.37 | 5.06 | 1.77 (0.57, 5.50) | 0.321 | 0.91 (0.29, 2.81) | 0.865 | 0.88 (0.28, 2.71) | 0.817 |
| Progressed | |||||||||
| 0 → +1 | 302 | 2.12 | 1.52 | 1.48 (1.28, 1.70) | < 0.001 | 1.03 (0.90, 1.19) | 0.663 | 1.02 (0.89, 1.18) | 0.748 |
| 0 → +2 | 132 | 2.87 | 2.11 | 2.41 (1.98, 2.94) | < 0.001 | 1.48 (1.21, 1.80) | < 0.001 | 1.44 (1.19, 1.76) | < 0.001 |
| 0 → +3 ~ 4 | 28 | 2.90 | 2.17 | 1.75 (1.05, 2.90) | 0.030 | 1.20 (0.72, 1.99) | 0.488 | 1.19 (0.72, 1.97) | 0.507 |
| + 1 → +2 | 30 | 3.81 | 2.86 | 2.28 (1.40, 3.72) | 0.001 | 1.13 (0.69, 1.84) | 0.636 | 1.11 (0.68, 1.81) | 0.690 |
| + 1 → +3 ~ 4 | 9 | 4.55 | 3.60 | 4.25 (2.03, 8.92) | < 0.001 | 2.19 (1.04, 4.59) | 0.038 | 2.13 (1.01, 4.47) | 0.046 |
| + 2 → +3 ~ 4 | 10 | 3.73 | 2.86 | 2.19 (0.91, 5.26) | 0.080 | 1.26 (0.53, 3.03) | 0.603 | 1.21 (0.50, 2.90) | 0.677 |
| Persistent | |||||||||
| + 1 → +1 | 50 | 3.34 | 2.46 | 2.14 (1.49, 3.08) | < 0.001 | 1.20 (1.03, 1.33) | 0.027 | 1.18 (1.02, 1.34) | 0.037 |
| + 2 → +2 | 25 | 3.60 | 2.73 | 2.49 (1.50, 4.13) | < 0.001 | 1.30 (1.02, 1.58) | 0.031 | 1.30 (1.02, 1.58) | 0.030 |
| + 3 ~ 4 → +3 ~ 4 | 9 | 7.38 | 5.94 | 2.52 (1.01, 4.02) | 0.033 | 1.34 (1.03, 1.63) | 0.022 | 1.33 (1.03, 1.62) | 0.018 |
| Myocardial infarction | 9,285 | 0.54 | 0.38 | ||||||
| Normal: 0 → 0 | 8,937 | 0.54 | 0.37 | 1 (reference) | 1 (reference) | 1 (reference) | |||
| Improved: | |||||||||
| + 1 → 0 | 95 | 0.73 | 0.52 | 1.59 (1.40, 1.79) | < 0.001 | 1.13 (1.00, 1.27) | 0.059 | 1.12 (0.99, 1.26) | 0.077 |
| + 2 → 0 | 29 | 0.74 | 0.53 | 2.22 (1.84, 2.69) | < 0.001 | 1.46 (1.21, 1.77) | < 0.001 | 1.43 (1.18, 1.73) | < 0.001 |
| + 2 → +1 | 6 | 0.82 | 0.60 | 3.90 (2.79, 5.46) | < 0.001 | 1.94 (1.39, 2.72) | < 0.001 | 1.91 (1.36, 2.67) | < 0.001 |
| + 3 ~ 4 → 0 | 7 | 0.89 | 0.66 | 2.37 (1.56, 3.59) | < 0.001 | 1.48 (1.01, 1.95) | 0.045 | 1.45 (1.02, 1.69) | 0.041 |
| + 3 ~ 4 → +1 | 0 | - | - | - | - | - | - | - | - |
| + 3 ~ 4 → +2 | 2 | 0.98 | 0.76 | 2.69 (1.21, 5.99) | 0.015 | 1.2 (0.54, 2.68) | 0.652 | 1.16 (0.52, 2.57) | 0.724 |
| Progressed | |||||||||
| 0 → +1 | 119 | 0.84 | 0.60 | 1.76 (1.57, 1.97) | < 0.001 | 1.27 (1.13, 1.42) | < 0.001 | 1.25 (1.12, 1.40) | < 0.001 |
| 0 → +2 | 38 | 0.82 | 0.60 | 2.49 (2.11, 2.94) | < 0.001 | 1.56 (1.32, 1.85) | < 0.001 | 1.54 (1.30, 1.82) | < 0.001 |
| 0 → +3 ~ 4 | 10 | 1.04 | 0.77 | 2.64 (1.85, 3.78) | < 0.001 | 1.69 (1.18, 2.41) | 0.004 | 1.67 (1.17, 2.39) | 0.005 |
| + 1 → +2 | 12 | 1.52 | 1.13 | 2.57 (1.72, 3.83) | < 0.001 | 1.23 (1.03, 1.44) | 0.031 | 1.22 (1.02, 1.43) | 0.033 |
| + 1 → +3 ~ 4 | 1 | 0.51 | 0.39 | 4.12 (2.15, 7.93) | < 0.001 | 1.72 (0.90, 3.31) | 0.103 | 1.70 (0.89, 3.27) | 0.111 |
| + 2 → +3 ~ 4 | 0 | - | - | - | - | - | - | - | - |
| Persistent | |||||||||
| + 1 → +1 | 12 | 0.80 | 0.58 | 3.07 (2.35, 3.99) | < 0.001 | 1.60 (1.23, 2.09) | < 0.001 | 1.58 (1.21, 2.05) | < 0.001 |
| + 2 → +2 | 15 | 2.16 | 1.62 | 5.41 (4.01, 7.29) | < 0.001 | 2.58 (1.91, 3.48) | < 0.001 | 2.57 (1.90, 3.47) | < 0.001 |
| + 3 ~ 4 → +3 ~ 4 | 2 | 1.64 | 1.29 | 7.74 (4.17, 14.38) | < 0.001 | 3.48 (1.88, 6.44) | < 0.001 | 3.37 (1.82, 6.24) | < 0.001 |
| All-cause death | 109,932 | 6.43 | 4.48 | ||||||
| Normal: 0 → 0 | 104,402 | 6.26 | 4.36 | 1 (reference) | 1 (reference) | 1 (reference) | |||
| Improved: | |||||||||
| + 1 → 0 | 1,346 | 10.38 | 7.33 | 1.67 (1.58, 1.76) | < 0.001 | 1.24 (1.17, 1.30) | < 0.001 | 1.23 (1.17, 1.30) | < 0.001 |
| + 2 → 0 | 508 | 13.01 | 9.30 | 2.12 (1.94, 2.31) | < 0.001 | 1.52 (1.39, 1.66) | < 0.001 | 1.49 (1.37, 1.63) | < 0.001 |
| + 2 → +1 | 133 | 18.19 | 13.32 | 3.09 (2.61, 3.67) | < 0.001 | 1.88 (1.59, 2.23) | < 0.001 | 1.87 (1.57, 2.21) | < 0.001 |
| + 3 ~ 4 → 0 | 137 | 17.65 | 12.95 | 2.97 (2.51, 3.51) | < 0.001 | 2.07 (1.75, 2.45) | < 0.001 | 2.05 (1.74, 2.43) | < 0.001 |
| + 3 ~ 4 → +1 | 48 | 27.12 | 21.05 | 5.10 (3.84, 6.76) | < 0.001 | 2.46 (1.86, 3.27) | < 0.001 | 2.42 (1.82, 3.21) | < 0.001 |
| + 3 ~ 4 → +2 | 56 | 28.28 | 21.82 | 5.20 (4.01, 6.76) | < 0.001 | 2.88 (2.22, 3.75) | < 0.001 | 2.82 (2.17, 3.67) | < 0.001 |
| Progressed | |||||||||
| 0 → +1 | 1,698 | 11.96 | 8.51 | 1.95 (1.86, 2.04) | < 0.001 | 1.45 (1.39, 1.52) | < 0.001 | 1.45 (1.38, 1.52) | < 0.001 |
| 0 → +2 | 733 | 16.01 | 11.61 | 2.68 (2.49, 2.88) | < 0.001 | 1.73 (1.61, 1.86) | < 0.001 | 1.71 (1.59, 1.84) | < 0.001 |
| 0 → +3 ~ 4 | 177 | 18.42 | 13.61 | 3.18 (2.74, 3.68) | < 0.001 | 2.37 (2.05, 2.75) | < 0.001 | 2.37 (2.04, 2.75) | < 0.001 |
| + 1 → +2 | 148 | 18.85 | 13.84 | 3.19 (2.72, 3.75) | < 0.001 | 1.73 (1.47, 2.03) | < 0.001 | 1.71 (1.45, 2.01) | < 0.001 |
| + 1 → +3 ~ 4 | 52 | 26.67 | 20.50 | 4.93 (3.76, 6.47) | < 0.001 | 2.73 (2.08, 3.58) | < 0.001 | 2.71 (2.06, 3.55) | < 0.001 |
| + 2 → +3 ~ 4 | 57 | 21.76 | 16.31 | 3.90 (3.01, 5.06) | < 0.001 | 2.49 (1.92, 3.23) | < 0.001 | 2.43 (1.87, 3.15) | < 0.001 |
| Persistent | |||||||||
| + 1 → +1 | 251 | 16.86 | 12.21 | 2.83 (2.50, 3.20) | < 0.001 | 1.68 (1.49, 1.90) | < 0.001 | 1.67 (1.47, 1.89) | < 0.001 |
| + 2 → +2 | 152 | 22.16 | 16.51 | 3.88 (3.31, 4.55) | < 0.001 | 2.10 (1.79, 2.47) | < 0.001 | 2.11 (1.80, 2.48) | < 0.001 |
| + 3 ~ 4 → +3 ~ 4 | 34 | 28.57 | 22.38 | 5.30 (3.79, 7.41) | < 0.001 | 3.48 (2.48, 4.86) | < 0.001 | 3.45 (2.46, 4.82) | < 0.001 |
Multivariable model (1) was adjusted for age, sex, body mass index, household income, smoking status, alcohol consumption, regular exercise, and comorbidities.
The multivariable model (2) was adjusted for the variables listed above as well as the Charlson Comorbidity Index.
HR, hazard ratio, CI, confidence interval.