Cardiovascular Risk With and Without Antihypertensive Drug Treatment in the Japanese General Population: Participant-Level Meta-Analysis

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To evaluate the cardiovascular mortality risk in association with blood pressure level among people with and without antihypertensive treatment, we performed the participant-level meta-analysis that included 39 705 Japanese from 6 cohorts (58.4% women; mean age, 60.1 years; 20.4% treated). Multivariable-adjusted Cox models were used to analyze the risk of cardiovascular mortality and its subtypes among 6 blood pressure levels according to recent guidelines, optimal to Grade 3 hypertension, and the usage of antihypertensive medication at baseline. During median 10.0 years of follow-up, there were 2032 cardiovascular deaths (5.1 per 1000 person-years), of which 410 deaths were coronary heart disease, 371 were heart failure, and 903 deaths were stroke. Treated participants had significantly higher risk for cardiovascular mortality (hazard ratios, 1.50; 95% confidence intervals, 1.36–1.66), coronary heart disease (hazard ratios, 1.53; confidence intervals, 1.23–1.90), heart failure (hazard ratios, 1.39; confidence intervals, 1.09–1.76), and stroke (hazard ratios, 1.48; confidence intervals, 1.28–1.72) compared with untreated people. Among untreated participants, the risks increased linearly with an increment of blood pressure category (P≤0.011). The risk increments per blood pressure category were higher in young participants (<60 years; 22% to 79%) than those in old people (≥60 years; 7% to 15%) with significant interaction for total cardiovascular, heart failure, and stroke mortality (P≤0.026). Among treated participants, the significant linear association was also observed for cardiovascular mortality (P=0.0003), whereas no stepwise increase in stroke death was observed (P=0.19). The risks of cardiovascular mortality were ≈1.5-fold high in participants under antihypertensive medication. More attention should be paid to the residual cardiovascular risks in treated patients.

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