Table 5. Associations of the risk score and epigenetic clock with all-cause and cause-specific mortality in the ESTHER study.
| Outcome | Mortality score*/epigenetic clock† | HR (95% CI) | ||
|---|---|---|---|---|
| Model 1‡ | Model 2§ | Model 3|| | ||
| All-cause mortality | 0 | Ref. | Ref. | Ref. |
| 1 | 2.04 (1.11–3.75) | 2.02 (1.10–3.72) | 2.15 (1.09–4.21) | |
| 2–5 | 3.18 (1.81–5.59) | 3.07 (1.74–5.41) | 3.31 (1.75–6.28) | |
| >5 | 7.64 (4.21–13.85) | 7.18 (3.92–13.15) | 6.96 (3.46–14.01) | |
| Hannum Δage (per 5 years) | 1.27 (1.10–1.46) | 1.09 (0.94–1.27) | 1.08 (0.92–1.27) | |
| Cancer mortality | 0–1 | Ref. | Ref. | Ref. |
| 2–5 | 1.24 (0.72–2.11) | 1.19 (0.69–2.04) | 1.16 (0.65–2.06) | |
| >5 | 3.12 (1.69–5.78) | 2.89 (1.53–5.46) | 2.33 (1.12–4.84) | |
| Hannum Δage (per 5 years) | 1.25 (0.98–1.59) | 1.13 (0.87–1.46) | 1.15 (0.88–1.51) | |
| CVD mortality | 0–1 | Ref. | Ref. | Ref. |
| 2–5 | 3.41 (1.82–6.40) | 3.28 (1.74–6.18) | 3.85 (1.87–7.89) | |
| >5 | 7.19 (3.54–14.62) | 6.63 (3.19–13.78) | 8.47 (3.54–20.28) | |
| Hannum Δage (per 5 years) | 1.34 (1.05–1.71) | 1.12 (0.87–1.45) | 1.12 (0.85–1.48) | |
CI, confidence interval; HR, hazard ratio; Ref., reference category.
*Score was based on methylation of 10 CpGs (cg01612140, cg05575921, cg06126421, cg08362785, cg10321156, cg14975410, cg19572487, cg23665802, cg24704287 and cg25983901) using their respective first quartile values (cg08362785: using its highest quartile) among the ESTHER participants as the cutoff points to define aberrant methylation. Score 0–10 refer to simultaneously aberrant methylation at 0–10 CpGs.
†The epigenetic clock estimated by the difference between DNA methylation age calculated according to Hannum's algorithm and chronological age.
‡Model 1: adjusted for age and sex.
§Model 2: similar to model 1, additionally adjusted for the epigenetic clock/risk score.
||Model 3: similar to model 2, additionally adjusted for smoking status, body mass index, physical activity, alcohol consumption, systolic blood pressure, total cholesterol, hypertension and prevalent cardiovascular disease, diabetes and cancer at baseline.