Sleep-Time Blood Pressure as a Therapeutic Target for Cardiovascular Risk Reduction in Type 2 Diabetes

Abstract

Independent studies have found that elevated sleep-time blood pressure (BP) is a better predictor of cardiovascular risk than the awake or 24-h BP means in patients without as well as with diabetes. However, the impact of the alteration over time of ambulatory BP on cardiovascular risk has never been investigated. We evaluated in a subgroup cohort of MAPEC (Monitorización Ambulatoria para Predicción de Eventos Cardiovasculares, i.e., ambulatory blood pressure monitoring for prediction of cardiovascular events) with diabetes whether reduced cardiovascular risk is more related to the progressive decrease of awake vs. asleep BP. We studied 607 patients with type 2 diabetes during a median 5.4 years follow-up. Those with hypertension at baseline (74%) were randomized to ingest all their prescribed hypertension medications upon awakening or ≥1 of them at bedtime. BP was measured for 48 h at baseline, and again annually in all patients, or more frequently (quarterly) after adjustments in treatment. Using baseline data, when asleep BP was adjusted by awake mean, only the former was a significant predictor of outcome in a Cox proportional-hazard model adjusted for sex, age, anemia, and chronic kidney disease. Analyses of changes in BP during follow-up revealed a 20% cardiovascular risk reduction for each 5 mm Hg decrease in asleep systolic BP mean (P < 0.001), independently of changes in clinic or any other ambulatory BP parameter. Sleep-time BP is the most significant independent prognostic marker of cardiovascular events in diabetes. Most important, decreasing sleep-time BP, a novel therapeutic target requiring proper patient evaluation by ambulatory monitoring, was the most significant independent predictor of event-free survival in diabetes.