[OP.1A.07] SLEEP-TIME AMBULATORY BLOOD PRESSURE AS THERAPEUTIC TARGET FOR PREVENTION OF CARDIOVASCULAR EVENTS

Objective: Previous ambulatory blood pressure (BP) monitoring (ABPM) outcome investigations relied upon only a single, low-reproducible 24 h ABPM assessment per participant done at study inclusion. This approach precluded the opportunity to explore the potential reduction in cardiovascular disease (CVD) risk associated with modification of prognostic ABPM-derived parameters by hypertension therapy. The Hygia Project, a research network presently composed of 292 investigators of 40 clinical sites, was specifically designed to investigate, among other primary objectives, whether specific treatment-induced changes in ABPM-derived parameters reduce risk of CVD events. Design and method: This study involved 18,078 persons, 9,769 men/8,309 women, 59.1 ± 14.3 years of age, with baseline BP ranging, according to ABPM criteria, from normotension to hypertension. At inclusion and at every scheduled clinic visit for ABPM (at least annually) during follow-up, BP was assessed at 20-min intervals from 07:00 to 23:00 h and at 30-min intervals at night for 48 h. During ABPM, participants kept a diary listing the times of going to bed at night and awakening in the morning. The primary CVD-outcome was the composite of CVD death, myocardial infarction, coronary revascularization, heart failure, and stroke. Results: During a median 5.1-year follow-up, we documented 1,209 events for the primary CVD-outcome. Analyses of therapy-induced changes in clinic and ambulatory BP during follow-up revealed progressive decrease in sleep-time systolic BP (SBP) (adjusted for significant influential characteristics of age, sex, type 2 diabetes, chronic kidney disease, cigarette smoking, HDL-cholesterol, hypertension treatment-time, and previous CVD event) was the most significant prognostic marker of CVD event-free survival (hazard ratio 0.73 [95%CI 0.65–0.83] per SD decrease in asleep SBP mean, P < 0.001), independent of changes in office SBP (0.96 [0.87–1.06], P = 0.414) or awake SBP mean (0.92 [0.78–1.09], P = 0.326). Only the progressive increase in the sleep-time relative SBP decline was a marker of survival jointly with diminishing asleep SBP (0.87 [0.77–0.99], P = 0.035). Conclusions: Treatment-induced decrease of asleep SBP mean and increase of sleep-time SBP decline towards more normal dipper BP patterning, two novel hypertension therapeutic targets requiring proper patient evaluation by ABPM, are the most significant independent predictors of reduced CVD morbidity and mortality.