SLEEP-TIME BLOOD PRESSURE AS A THERAPEUTIC TARGET FOR CARDIOVASCULAR RISK REDUCTION


Ramon C. Hermida, Ph.D., Campus Universitario, Vigo, Pontevedra, Spain

Diagnosis of hypertension and clinical decisions regarding its treatment are typically based upon clinic blood pressure (BP) measurements, occasionally supplemented by wake-time patient self-assessment. Yet, correlation between BP level and target organ damage, cardiovascular disease (CVD) risk, and long-term prognosis is greater for ambulatory BP monitoring (ABPM) than daytime in-clinic measurements. Additionally, consistent evidence of numerous studies substantiates the ABPM-determined asleep BP mean is an independent and stronger predictor of CVD risk than the awake or 24h means. Most importantly, when the asleep BP mean is adjusted by the awake mean, only the former is a significant independent predictor of CVD outcome. Hence, cost-effective adequate control of sleep-time BP is of marked clinical relevance. Endogenous circadian rhythms explain statistically and clinically significant ingestion-time differences in efficacy, duration of action, safety, and/or effects on the daily BP pattern of most hypertension medications and their combinations. For example, bedtime versus morning ingestion of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers better controls the asleep BP mean, with additional benefit, independent of medication terminal half-life, of converting the 24h BP profile into more normal dipper patterning. The MAPEC Study, first prospective randomized treatment-time investigation testing the worthiness of bedtime chronotherapy with at least one conventional hypertension medications to specifically target attenuation of asleep BP, demonstrated, relative to conventional morning therapy, significantly better reduction of CVD risk. The MAPEC Study not only documents the asleep BP mean is the most significant prognostic marker of CVD and stroke morbidity and mortality, but it also substantiates attenuation of the asleep BP mean by a bedtime hypertension treatment strategy with the entire daily dose of >1 hypertension medications significantly reduces CVD risk, both in the general hypertension population and in patients of greater vulnerability and enhanced CVD risk, i.e., those diagnosed with chronic kidney disease, diabetes, and resistant hypertension.