The interplay between antihypertensive medication and lifestyle with cardiovascular outcomes in patients with hypertension: the PURE-China study

OBJECTIVE: Although antihypertensive medication is central to hypertension management, substantial residual risks persist. This study evaluated the associations of healthy lifestyle behaviors with all-cause mortality and cardiovascular disease (CVD) among individuals with hypertension, and assessed whether favorable lifestyles provided additional benefits beyond antihypertensive medication. From the perspective of predictive, preventive, and personalized medicine (PPPM/3PM), we assumed that comprehensive lifestyle assessment could refine risk stratification and help identify priority targets. METHODS: This study included 16,314 participants with hypertension from the Prospective Urban Rural Epidemiology (PURE)-China study. A healthy lifestyle score (0-6, higher scores indicating healthier behaviors) was constructed based on six lifestyle behaviors. Antihypertensive medication use was defined as regular intake at least once per week. Cox frailty models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: During a median follow-up of 11.9 years, 1,423 deaths and 2,418 CVD events occurred. Compared with the high score group (5-6), participants in the low score group (0-2) had higher risks of all-cause mortality (HR: 1.77, 95% CI 1.42-2.20) and CVD (HR: 1.56, 95% CI 1.28-1.89). Diet emerged as the strongest lifestyle predictor based on explained relative risk ( CONCLUSIONS: Among individuals with hypertension, healthier lifestyles were associated with lower risks of all-cause mortality and CVD, independent of antihypertensive medication. Integrating lifestyle assessment into hypertension management may reduce risk in line with the PPPM/3PM framework. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13167-026-00444-9.