Abstract
BACKGROUND: Usual measures of blood pressure (BP) do not account for both the magnitude and duration of exposure to elevated BP over time. We aimed to demonstrate the effect of a novel time-weighted BP on cardiovascular outcomes using a post hoc analysis of two published randomized trials. HYPOTHESIS: Time-weighted blood pressure is associated with cardiovascular risk among patients with or without diabetes. METHODS: The limited-access ACCORD and SPRINT data sets were used for the current study. Time-weighted BP is obtained by dividing cumulative BP by the total follow-up time. Time-weighted BP burden above a threshold is also determined after deriving the time-weighted BP by re-zeroing the interpolated pressure values at two different hypertension thresholds (>140/90 and >130/80 mmHg). RESULTS: Eighteen thousand five hundred forty-one patients from the two clinical trials were enrolled in this study. A J-curve relation was observed between time-weighted BP and major cardiovascular events (MACE). The systolic blood pressure (SBP) burden independently predicted MACE across the two trials at different thresholds (ACCORD: SBP > 130 mmHg, HR = 1.05 [1.03-1.06]; SBP > 140 mmHg, HR = 1.06 [1.04-1.08]; SPRINT: SBP > 130 mmHg, HR = 1.04 [1.03-1.05]; SBP > 140 mmHg, HR = 1.05 [1.04-1.07]). Consistent results were found for diastolic blood pressure (DBP) burden (ACCORD: DBP > 80 mmHg, HR = 1.10 [1.06-1.15]; DBP > 90 mmHg, HR = 1.20 [1.11-1.30]. SPRINT: DBP > 80 mmHg, HR = 1.06 [1.02-1.09]; DBP > 90 mmHg, HR = 1.12 [1.06-1.18]). Significant associations were also observed for stroke, myocardial infarction, cardiovascular death, and all-cause mortality. CONCLUSION: Both time-weighted SBP and DBP independently influenced the risk of adverse cardiovascular events among patients with and without diabetes, regardless of the definition of hypertension (130/80 or <140/90 mmHg).