Association of phenotypic age acceleration with the risk of all-cause and cardiovascular disease-related mortality in patients with hypertension

Objective To investigate the associations between phenotypic age acceleration (PhenoAgeAccel) and all-cause/cardiovascular disease (CVD)-related mortality in hypertensive patients. Methods We analyzed data from 14 352 hypertensive adults (≥20 years) in the National Health and Nutrition Examination Survey 1999–2010. PhenoAge was calculated using chronological age and nine biomarkers (albumin, creatinine, glucose, C-reactive protein, lymphocyte%, mean cell volume, red blood cell distribution width, alkaline phosphatase, and white blood cell count). PhenoAgeAccel was derived as residuals from linear regression of PhenoAge on chronological age. Participants were stratified by PhenoAge [<46.6792 (792–64.774 (T1–T2), ≥64.774 (≥T2)] and PhenoAgeAccel [<−4.3382 (382–0.9896 (T1–T2), ≥0.9896 (≥T2)] tertiles. Cox proportional hazards models assessed mortality risks. Results Increased all-cause mortality was observed in hypertensive patients with PhenoAge in T1–T2 group [hazards ratio = 4.38, 95% confidence interval (CI): 3.79–5.06] and greater than or equal to T2 (hazards ratio = 14.22, 95% CI: 12.32–16.43). Significant association between PhenoAgeAccel greater than or equal to T2 and increased risk of all-cause mortality in hypertensive patients (hazards ratio = 1.41, 95% CI: 1.29–1.55) was identified. PhenoAge of T1–T2 (hazards ratio = 5.15, 95% CI: 3.86–6.86) and greater than or equal to T2 (hazards ratio = 20.20, 95% CI: 14.98–27.26) were related to increased CVD-related mortality in hypertensive patients. Increased risk of CVD-related mortality was identified in hypertensive patients with PhenoAgeAccel greater than or equal to T2 (hazards ratio = 1.35, 95% CI: 1.17–1.56). Conclusion Elevated PhenoAge and PhenoAgeAccel significantly predict higher all-cause and CVD mortality in hypertension, supporting clinical risk stratification.