Table 3.
Multivariable Cox regression models assessing the risk CHIP and mosaic loss of the Y chromosome in men on various cardiovascular-related endpoints
| Characteristic | N | Event N | HR1 | 95% CI1 | P value |
|---|---|---|---|---|---|
| Time to incident CVD | |||||
| No CH | 14 812 | 9464 | Ref. | — | — |
| Both | 341 | 254 | 0.994 | 0.877-1.127 | 0.926 |
| CHIP only | 1032 | 735 | 1.083 | 1.004-1.168 | 0.040 |
| LOY only | 6193 | 4343 | 0.993 | 0.957-1.031 | 0.717 |
| CHIP × LOY | — | — | 0.916 | 0.798-1.050 | 0.208 |
| RERI (95% CI) = –0.091 (–0.214, 0.031) | |||||
| AP (95% CI) = –0.094 (–0.107, –0.082) | |||||
| SI (95% CI) = 0.916 (0.798-1.034) | |||||
| Time to incident CAD | |||||
| No CH | 14 812 | 2920 | Ref. | — | — |
| Both | 341 | 80 | 0.918 | 0.734-1.147 | 0.452 |
| CHIP only | 1032 | 256 | 1.106 | 0.973-1.258 | 0.124 |
| LOY only | 6193 | 1467 | 1.016 | 0.953-1.084 | 0.619 |
| CHIP × LOY | — | — | 0.796 | 0.622-1.019 | 0.070 |
| RERI (95% CI) = –0.229 (–0.439 to –0.019) | |||||
| AP (95% CI) = –0.258 (–0.323 to –0.194) | |||||
| SI (95% CI) = 0.796 (0.596-0.996) | |||||
| Time to CV death | |||||
| No CH | 14 812 | 305 | — | — | |
| Both | 341 | 10 | 0.998 | 0.530-1.880 | 0.995 |
| CHIP only | 1032 | 30 | 1.151 | 0.789-1.677 | 0.466 |
| LOY only | 6193 | 173 | 1.046 | 0.864-1.267 | 0.642 |
| CHIP × LOY | — | — | 0.360 | 0.445-1.823 | 0.771 |
| RERI (95% CI) = –0.105 (–0.724 to 0.513) | |||||
| AP (95% CI) = –0.101 (–0.179 to –0.041) | |||||
| SI (95% CI) = 0.900 (0.307-1.494) | |||||
| Time to CAD death | |||||
| No CH | 14 812 | 159 | Ref. | — | — |
| Both | 341 | 4 | 0.807 | 0.298-2.188 | 0.674 |
| CHIP only | 1032 | 12 | 0.902 | 0.500-1.625 | 0.730 |
| LOY only | 6193 | 96 | 1.166 | 0.898-1.512 | 0.249 |
| CHIP × LOY | — | — | 0.775 | 0.254-2.367 | 0.654 |
| RERI (95% CI) = –0.230 (–1.094 to 0.633) | |||||
| AP (95% CI) = –0.306 (–0.709 to 0.098) | |||||
| SI (95% CI) = 0.775 (–0.249 to 1.800) | |||||
| Time to any death | |||||
| No CH | 14 812 | 3402 | Ref. | — | — |
| Both | 341 | 136 | 1.307 | 1.099-1.553 | 0.002 |
| CHIP only | 1032 | 367 | 1.342 | 1.205-1.496 | <0.001 |
| LOY only | 6193 | 1859 | 1.080 | 1.019-1.145 | 0.010 |
| CHIP × LOY | — | — | 0.907 | 0.750-1.097 | 0.315 |
| RERI (95% CI) = –0.111 (–0.306 to 0.083) | |||||
| AP (95% CI) = –0.086 (–0.098 to –0.075) | |||||
| SI (95% CI) = 0.907 (0.786-1.028) | |||||
Models adjusted for age at baseline, smoking status, chemotherapy, radiotherapy, prevalent CVD, number of days between date of recruitment and date of cancer diagnosis, and genotyping principal components 1-10.
AP, attributable proportion; CAD, coronary artery disease; CH, clonal hematopoiesis; CHIP, clonal hematopoiesis of indeterminate potential; CI, confidence interval; CVD, cardiovascular disease; HR, hazard ratio; LOY, mosaic loss of the Y chromosome; mCA, mosaic chromosomal alteration; Ref., referent category; RERI, relative excess risk due to interaction; SI, synergy index.