Association Between Long-Term Blood Pressure Patterns and Onset of Stroke: A Nested Case–Control Study of a Randomized Clinical Trial

Elevated blood pressure (BP) and its variability are established stroke risk factors; however, whether long-term BP patterns are associated with stroke onset in patients with type 2 diabetes remains unclear. As a post hoc analysis, we conducted a nested case–control study among 2535 patients in the Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes (JPAD) trial. During follow-up, 117 patients developed cerebral infarction (CI), and 35 developed intracerebral hemorrhage (ICH). Controls for these cases were matched for sex, aspirin allocation, age, and diabetes duration. Systolic, diastolic, and mean BP values were collected at baseline, annually during the trial, and every two years after the completion of the trial. Sequential BP levels and coefficient of variations (CVs) were compared between cases and controls. In both CI and ICH subsets, the median intervals from the most recent BP measurement to stroke onset were similar between cases and controls (CI: 300 vs. 288 days, p = 0.46; ICH: 481 vs. 448 days, p = 0.76). The most recent BP measurements before stroke were similar between cases and controls for both CI (systolic BP, 135 vs. 133 mmHg, p = 0.15; diastolic BP, 74 vs. 74 mmHg, p = 0.85) and ICH (systolic BP, 137 vs. 134 mmHg, p = 0.40; diastolic BP, 75 vs. 72 mmHg, p = 0.17). CVs were also comparable. Among patients with type 2 diabetes enrolled in a clinical trial, we found no clear evidence of an association between long-term BP patterns and subsequent stroke onset, suggesting that other factors triggering stroke onset warrant investigation.