Hypertension accelerates aging: Evidence from NHANES database and Mendelian randomization analyses

Background Hypertension is thought to accelerate biological aging. However, evidence of a causal effect is lacking. This study aimed to provide evidence of a relationship between hypertension and biological aging by analyzing data from the 2005–2010 National Health and Nutrition Examination Survey (NHANES) and by Mendelian randomization (MR).Methods The association of hypertension with PhenoAge and PhenoAge acceleration was assessed by weighted multivariable-adjusted linear regression using the NHANES data. Two-sample MR was then performed using summary data from genome-wide association studies to determine causal associations of hypertension with accelerated DNA methylation (DNAm) and proxies of age, including telomere length, frailty index, and facial aging. Inverse variance weighting and complementary MR methods were used to confirm the causal relationship between hypertension and biological aging. The robustness of the results was confirmed by sensitivity analyses.Results Data for 6102 NHANES participants were analyzed. Weighted multivariable-adjusted linear regression analyses showed that hypertension increased PhenoAge (β = 12, 95% CI: 11–13, p < 0.001) and was positively associated with PhenoAge acceleration (β = 0.56, 95% CI: 0.15–0.98, p = 0.009). The MR results also suggested a potential causal association of hypertension with DNAm PhenoAge acceleration (OR 1.31, 95% CI: 1.07–1.60, p < 0.05), DNAm GrimAge acceleration (OR 1.33, 95% CI: 1.13–1.57, p < 0.05), and the frailty index (OR 1.09, 95% CI: 1.07–1.11, p < 0.05). Sensitivity analyses confirmed the robustness and reliability of these findings.Conclusion Hypertension increases PhenoAge and is correlated with PhenoAge acceleration. The potential causal association between hypertension and multiple biological indicators of aging provides clues to the relationship between hypertension and epigenetic aging.