Sleep-time blood pressure as a therapeutic target for reducing the risk of developing diabetes

Abstract

Independent studies have found that elevated sleep-time blood pressure (BP) is a better predictor of cardiovascular disease (CVD) risk than the awake or 24h BP means in patients without as well as with diabetes (DM). Additionally, asleep BP has been identified as an independent prognostic marker for new-onset DM. However, the potential reduction in the risk of DM associated with decreasing an elevated asleep BP mean has never before been investigated. We prospectively evaluated whether reduced risk of new-onset DM is more related to the progressive decrease of clinic, awake, or asleep BP. We investigated 2656 subjects without DM, 1292 men/1364 women, 50.6 14.3 years of age, with baseline ambulatory BP ranging from normotension to sustained hypertension. At baseline and annually (or more frequently if hypertension treatment was adjusted based on ABPM) thereafter, ambulatory BP and physical activity (wrist actigraphy) were simultaneously monitored for 48h to accurately derive the awake and asleep BP means. During a 5.6-year median follow-up, 190 participants developed DM. Using baseline data, when asleep BP was adjusted by awake BP mean, only the former was a significant predictor of new-onset DM in a Cox proportional-hazard model adjusted for age, waist perimeter, glucose, and chronic kidney disease. Analyses of changes in BP during follow-up revealed a 30% reduction in the risk of developing DM for each 1-SD decrease in asleep systolic BP (SBP) mean (P<0.001), independent of changes in daytime clinic or ABPM-derived awake BP mean during follow-up. Only the increase in sleep-time relative SBP mean towards more normal dipper patterning improved the prognostic value of sleep-time SBP (adjusted hazard ratio 0.82 [95%CI: 0.70-0.96], P1⁄40.013). Sleep-time SBP mean is the most significant independent prognostic marker of new-onset DM. More important, decreasing asleep SBP and increasing sleep-time relative SBP decline, two novel therapeutic targets requiring proper patient evaluation by ABPM and more feasible by bedtime than morning hypertension treatment, were the most significant independent predictors of reduced risk of developing DM.