Abstract

Background: The effect of lowering diastolic blood pressure (DBP) on the risk for ischemic cardiovascular disease (CVD) is usually only assessed with a single timepoint at baseline. This has led to a lack of explanation for the U- or J-shaped association between DBP and the risk for ischemic CVD among hypertensive patients. Methods: We studied a cohort of 7074 hypertensive patients (42.9% men) aged 35-79 years (mean age=56.5 years) at baseline in 1980-1989, with annually repeated blood pressure measurements. Time-dependent DBP trajectories were assessed by group-based trajectory analysis, adjusted by sex, age, and antihypertensive medication use. Hazard ratios (HRs) and 95% confidence intervals (95%CIs) of ischemic CVD, composed of ischemic stroke and myocardial infarction, according to DBP trajectories were estimated by competing risk analysis. For references, we examined the same approaches mentioned above were used for systolic blood pressure. Findings: For 24.1 years, there were 799 incident cases of ischemic CVD. Eight DBP trajectories were identified. We found a U-shaped association between DBP trajectories and a risk for ischemic CVD. The HRs (95%CI) of ischemic CVD with reference to a moderately-stable trajectory were 2.0 (1.8-2.2) for a very-low-stable, 1.4 (1.3-1.6) for low-decreasing, 1.6 (1.3-1.5) for low-stable, 1.4 (1.3-1.5) for moderately-decreasing, 1.5 (1.4-1.7) for high-decreasing, 1.2 (1.1-1.4) for high-stable, and 1.4 (1.2-1.62) for very-high-stable. This U-shaped association was more pronounced in antihypertensive medication users than in non-users. No such association was observed for SBP trajectories. Interpretation: We found a U-shaped association between DBP trajectory and ischemic CVD in hypertensive patients in a time-dependent analysis, which cannot be detected by single timepoint analysis. Changes in DBP among hypertensive patients should be carefully documented for preventing ischemic CVD. Funding Statement: Ministry of Health, Labor and Welfare of Japan. Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: This study was approved by the ethics committees of Osaka University and Osaka Center for Cancer and Cardiovascular Disease Prevention, and was performed in accordance with the Declaration of Helsinki.

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