Methylation-Based Biological Age and Hypertension Prevalence and Incidence

Hypertension is common in older individuals and is a major risk factor for cardiovascular disease. Blood DNA methylation profiles have been used to derive metrics of biological age that capture age-related physiological change, disease risk, and mortality. The relationships between hypertension and DNA methylation-based biological age metrics have yet to be carefully described.

Among 4419 women enrolled in the prospective Sister Study cohort, DNA methylation data generated from whole blood samples collected at baseline were used to calculate 3 biological age metrics (PhenoAgeAccel, GrimAgeAccel, DunedinPACE). Women were classified as hypertensive at baseline if they had high blood pressure (systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg) or reported current use of antihypertensive medication. New incident cases of hypertension during follow-up were identified via self-report on annual health questionnaires.

All 3 DNA methylation metrics of biological age were positively associated with prevalent hypertension at baseline (per 1-SD increase; PhenoAgeAccel, adjusted odds ratio, 1.16 [95% CI, 1.05-1.28]; GrimAgeAccel, adjusted odds ratio, 1.28 [95% CI, 1.14-1.45]; DunedinPACE, adjusted odds ratio, 1.16 [95% CI, 1.03-1.30]). Among 2610 women who were normotensive at baseline, women with higher biological age were more likely to be diagnosed with incident hypertension (per 1-SD increase; PhenoAgeAccel, adjusted hazard ratio, 1.09 [95% CI, 0.97-1.23]; GrimAgeAccel, adjusted hazard ratio, 1.16 [95% CI, 0.99-1.36]; DunedinPACE, adjusted hazard ratio, 1.16 [95% CI, 1.01-1.33]).

Methylation-based biological age metrics increase before a hypertension diagnosis and appear to remain elevated in the years after clinical diagnosis and treatment.