Decreasing asleep ambulatory blood pressure reduces cardiovascular risk in chronic kidney disease

Elevated asleep blood pressure (BP) determined by ambulatory monitoring (ABPM) is a better predictor of cardiovascular (CVD) events than the awake or 24 h BP means. A limitation of all previous studies is their reliance on a single baseline ABPM profile from each participant at the time of inclusion. Thus, the potential reduction in CVD risk associated with decreasing asleep BP mean is still a matter of debate. We evaluated in patients with chronic kidney disease (CKD) whether reduced CVD risk is more related to the progressive decrease of awake, asleep, or daytime-measured clinic BP. We studied 793 patients with CKD (estimated glomerular filtration rate <60 ml/min/1.73 m2, albuminuria, or both, in at least two occasions >=3 months apart), 469 men/324 women, 57.9 ± 13.9 years of age, during a median follow-up of 5.4 years. Those with hypertension at baseline (83%) were randomized to ingest all prescribed BP-lowering 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. Changes in the hypertension therapeutic scheme during follow-up were always based on the results of the periodic evaluation by ABPM. Using baseline data, the asleep systolic BP (SBP) mean was the best predictor of outcome in a Cox proportional-hazard model adjusted for sex, age, diabetes, and albuminuria (hazard ratio 1.49, 95% confidence interval [1.30-1.71] per each 1-SD increment in the asleep SBP mean, P < 0.001). When asleep SBP mean was used jointly in the same fully adjusted Cox regression model with either clinic BP or the awake SBP mean, only asleep SBP mean significantly predicted CVD outcome. Other ABPM variables, including 48 h BP mean, morning BP surge, and standard deviation, were not statistically significant when the asleep SBP mean was simultaneously used as a predicting variable. Analyses of changes in BP during follow-up revealed a 14% CVD risk reduction for each 5 mmHg decrease in asleep SBP mean (P < 0.001), independently of changes in clinic or awake BP mean. Sleep-time SBP is the most significant independent prognostic marker of CVD events in CKD. Most important, decreasing sleep-time BP by timed hypertension therapy, a novel therapeutic target requiring proper patient evaluation by ABPM, was the most significant independent predictor of event-free survival in CKD.