Table 2.
Association of log-transformed interleukin-6, interleukin-18 and high-sensitivity C-reactive protein with incident cardiovascular disease events and death after Visit 5
| Event | IL-6 | IL-18 | hs-CRP | |||
|---|---|---|---|---|---|---|
| HR (95% CI) | P-value | HR (95% CI) | P-value | HR (95% CI) | P-value | |
| CHD (638/5672, 11.25%) | ||||||
| Model 1 | 1.81 (1.63–2.02) | <0.001 | 1.29 (1.11–1.50) | 0.001 | 1.30 (1.21–1.40) | <0.001 |
| Model 2 | 1.53 (1.36–1.74) | <0.001 | 1.12 (0.96–1.31) | 0.158 | 1.20 (1.11–1.29) | <0.001 |
| Model 3a | 1.53 (1.35–1.73) | <0.001 | 1.05 (0.90–1.24) | 0.519 | 1.08 (1.00–1.18) | 0.061 |
| Model 4a | 1.44 (1.25–1.66) | <0.001 | 1.08 (0.92–1.26) | 0.363 | 1.20 (1.11–1.29) | <0.001 |
| Model 5 | 1.24 (1.07–1.44) | 0.003 | 1.08 (0.92–1.27) | 0.331 | — | — |
| Ischaemic stroke (232/5672, 4.09%) | ||||||
| Model 1 | 1.36 (1.12–1.65) | 0.002 | 1.26 (0.98–1.62) | 0.067 | 1.17 (1.04–1.32) | 0.011 |
| Model 2 | 1.15 (0.93–1.43) | 0.191 | 1.06 (0.82–1.37) | 0.645 | 1.04 (0.92–1.19) | 0.512 |
| Model 3a | 1.15 (0.93–1.42) | 0.208 | 1.04 (0.80–1.35) | 0.763 | 1.01 (0.87–1.16) | 0.929 |
| Model 4a | 1.15 (0.90–1.46) | 0.260 | 1.05 (0.81–1.36) | 0.700 | 1.04 (0.91–1.18) | 0.543 |
| Model 5 | 1.03 (0.81–1.31) | 0.800 | 1.06 (0.82–1.37) | 0.661 | — | — |
| HF hospitalization (785/5672, 13.84%) | ||||||
| Model 1 | 2.10 (1.91–2.31) | <0.001 | 1.36 (1.19–1.56) | <0.001 | 1.35 (1.27–1.44) | <0.001 |
| Model 2 | 1.82 (1.64–2.02) | <0.001 | 1.19 (1.03–1.37) | 0.017 | 1.23 (1.15–1.32) | <0.001 |
| Model 3a | 1.81 (1.62–2.01) | <0.001 | 1.09 (0.94–1.25) | 0.247 | 1.06 (0.98–1.14) | 0.145 |
| Model 4a | 1.75 (1.55–1.97) | <0.001 | 1.14 (0.99–1.31) | 0.080 | 1.22 (1.14–1.31) | <0.001 |
| Model 5 | 1.37 (1.20–1.56) | <0.001 | 1.16 (1.00–1.34) | 0.043 | — | — |
| HFpEF (518/5672, 9.13%) | ||||||
| Model 1 | 2.00 (1.78–2.25) | <0.001 | 1.42 (1.21–1.68) | <0.001 | 1.37 (1.27–1.48) | <0.001 |
| Model 2 | 1.71 (1.50–1.96) | <0.001 | 1.28 (1.07–1.52) | 0.006 | 1.24 (1.14–1.35) | <0.001 |
| Model 3a | 1.69 (1.47–1.93) | <0.001 | 1.19 (1.00–1.42) | 0.049 | 1.09 (1.00–1.20) | 0.055 |
| Model 4a | 1.60 (1.38–1.87) | <0.001 | 1.22 (1.03–1.45) | 0.024 | 1.23 (1.13–1.34) | <0.001 |
| Model 5 | 1.35 (1.15–1.59) | <0.001 | 1.23 (1.03–1.46) | 0.019 | — | — |
|
HFrEF
(376/5672, 6.63%) |
||||||
| Model 1 | 1.99 (1.73–2.28) | <0.001 | 1.29 (1.06–1.57) | 0.011 | 1.36 (1.24–1.49) | <0.001 |
| Model 2 | 1.79 (1.53–2.09) | <0.001 | 1.13 (0.93–1.39) | 0.226 | 1.27 (1.16–1.40) | <0.001 |
| Model 3a | 1.78 (1.53–2.08) | <0.001 | 1.03 (0.84–1.26) | 0.771 | 1.11 (1.00–1.23) | 0.061 |
| Model 4a | 1.66 (1.39–1.98) | <0.001 | 1.07 (0.87–1.31) | 0.512 | 1.27 (1.15–1.40) | <0.001 |
| Model 5 | 1.23 (1.02–1.48) | 0.030 | 1.13 (0.92–1.40) | 0.250 | — | — |
| Global CVD (1235/5672, 21.77%) | ||||||
| Model 1 | 1.81 (1.67–1.96) | <0.001 | 1.29 (1.16–1.44) | <0.001 | 1.29 (1.22–1.35) | <0.001 |
| Model 2 | 1.57 (1.44–1.72) | <0.001 | 1.13 (1.01–1.26) | 0.036 | 1.18 (1.12–1.25) | <0.001 |
| Model 3a | 1.57 (1.43–1.71) | <0.001 | 1.05 (0.94–1.18) | 0.367 | 1.06 (0.99–1.12) | 0.076 |
| Model 4a | 1.51 (1.37–1.67) | <0.001 | 1.08 (0.97–1.21) | 0.158 | 1.18 (1.12–1.24) | <0.001 |
| Model 5 | 1.26 (1.14–1.40) | <0.001 | 1.11 (0.99–1.24) | 0.086 | — | — |
| AF (530/5084, 10.42%) | ||||||
| Model 1 | 1.48 (1.31–1.68) | <0.001 | 1.04 (0.88–1.23) | 0.638 | 1.13 (1.04–1.22) | 0.003 |
| Model 2 | 1.37 (1.19–1.57) | <0.001 | 0.98 (0.83–1.16) | 0.825 | 1.07 (0.99–1.17) | 0.102 |
| Model 3a | 1.38 (1.20–1.58) | <0.001 | 0.93 (0.79–1.11) | 0.434 | 0.98 (0.90–1.08) | 0.726 |
| Model 4a | 1.38 (1.19–1.61) | <0.001 | 0.96 (0.81–1.14) | 0.671 | 1.08 (0.99–1.17) | 0.094 |
| Model 5 | 1.17 (0.99–1.37) | 0.059 | 0.95 (0.80–1.13) | 0.577 | — | — |
| Total mortality (1173/5672, 20.68%) | ||||||
| Model 1 | 1.77 (1.63–1.92) | <0.001 | 1.35 (1.21–1.51) | <0.001 | 1.26 (1.20–1.33) | <0.001 |
| Model 2 | 1.68 (1.54–1.83) | <0.001 | 1.24 (1.11–1.39) | <0.001 | 1.24 (1.17–1.31) | <0.001 |
| Model 3a | 1.66 (1.52–1.81) | <0.001 | 1.15 (1.02–1.29) | 0.022 | 1.09 (1.03–1.16) | 0.004 |
| Model 4a | 1.58 (1.43–1.74) | <0.001 | 1.19 (1.06–1.33) | 0.004 | 1.23 (1.16–1.30) | <0.001 |
| Model 5 | 1.39 (1.25–1.54) | <0.001 | 1.19 (1.06–1.34) | 0.003 | — | — |
Data presented as n/N and hazard ratio with 95% CI; model 1, adjusted by age, sex, and race; model 2, model 1 plus total cholesterol, HDL-C, SBP, antihypertensive medication use, diabetes, current smoking, lipid-lowering medication use, prevalent CVD, BMI, and eGFR; model 3, model 2 plus IL-18 (in IL-6 analysis) or IL-6 (in IL-18 analysis); model 4, model 2 plus log(hs-CRP). model 5: model 4 plus log(NT-proBNP) and log(hs-TnT). Global CVD includes CHD, ischaemic stroke, and HF.
For hs-CRP analysis: model 3, adjusted by model 2 plus IL-6; model 4, model 2 plus IL-18.
Abbreviations: AF, atrial fibrillation; BMI, body mass index; CHD, coronary heart disease; CI, confidence interval; CVD, cardiovascular disease; eGFR, estimated glomerular filtration rate; HDL-C, high-density lipoprotein cholesterol; HF, heart failure; HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction; hs-CRP, high-sensitivity C-reactive protein; hs-TnT, high-sensitivity troponin T; IL-6, interleukin-6; IL-18, interleukin-18; NT-proBNP, N-terminal pro–B-type natriuretic peptide; SBP, systolic blood pressure.