TABLE 2.

Mediation analysis of epigenetic age acceleration on the associations of DASH score with all-cause mortality¹

	Indirect association
	HR (95% CI)	P	Proportion mediated, %
All, n = 1995
DunedinPoAm	0.981 (0.963–0.996)	0.038	22.1
GrimAA	0.964 (0.945–0.981)	0.001	45.1
PhenoAA	0.982 (0.966–0.995)	0.025	22.9
Never smoker, n = 1149
DunedinPoAm	0.995 (0.975–1.012)	0.505	14.9
GrimAA	0.989 (0.971–1.004)	0.204	0.0
PhenoAA	0.986 (0.966–1.000)	0.133	96.5
Ever smoker, n = 846
DunedinPoAm	0.925 (0.880–0.963)	0.004	31.3
GrimAA	0.890 (0.843–0.932)	<0.001	46.8
PhenoAA	0.971 (0.943–0.994)	0.049	10.3

Abbreviations: DASH, Dietary Approaches to Stop Hypertension; DunedinPoAm, Dunedin Pace of Aging Methylation; GrimAA, DNA methylation GrimAge Acceleration; HR, hazard ratio; PhenoAA, DNA methylation PhenoAge Acceleration.

¹An ever-smoker was defined as a current or former smoker. HRs per 1-SD increase of the DASH score in standardized z-score and P values were derived from mixed-effect Cox proportional hazard models. A linear mixed-effect model was estimated for epigenetic age acceleration (mediator), conditional on the DASH score (exposure) and covariates. A mixed-effect Cox proportional hazard model was estimated for all-cause mortality (outcome), conditional on the DASH score, epigenetic age acceleration, and covariates to estimate the indirect (mediation) effect. The proportion of mediation was calculated as the ratio of an indirect effect to the sum of both direct and indirect effects. Models were adjusted for age, sex, smoking status, physical activity score, alcohol consumption, energy intake, BMI, systolic blood pressure, hypertension medications, total and HDL cholesterol, type 2 diabetes, and history of cardiovascular disease and cancer. For a stratified analysis on smoking status, the same covariates were used as in the models, except for smoking status.