Chronotherapy improves blood pressure control and reduces vascular risk in CKD

Abstract

In patients with chronic kidney disease (CKD), the prevalence of increased blood pressure during sleep and blunted sleep-time-relative blood pressure decline (a nondipper pattern) is very high and increases substantially with disease severity. Elevated blood pressure during sleep is the major criterion for the diagnoses of hypertension and inadequate therapeutic ambulatory blood pressure control in these patients. Substantial, clinically meaningful ingestion-time-dependent differences in the safety, efficacy, duration of action and/or effects on the 24 h blood pressure pattern of six different classes of hypertension medications and their combinations have been substantiated. For example, bedtime ingestion of angiotensin-converting-enzyme inhibitors and angiotensin-receptor blockers is more effective than morning ingestion in reducing blood pressure during sleep and converting the 24 h blood pressure profile into a dipper pattern. We have identified a progressive reduction in blood pressure during sleep--a novel therapeutic target best achieved by ingestion of one or more hypertension medications at bedtime--as the most significant predictor of decreased cardiovascular risk in patients with and without CKD. Recent findings suggest that in patients with CKD, ambulatory blood pressure monitoring should be used for the diagnosis of hypertension and assessment of cardiovascular disease risk, and that therapeutic strategies given at bedtime rather than on awakening are preferable for the management of hypertension.

The Circadian Clock in the Regulation of Renal Rhythms

“…The aim of chronotherapy is to administer medicines at certain times of the day to maximize efficacy and reduce side effects. Many hypertension medications are usually taken in the morning, however convincing evidence concerning the effects of chronotherapy shows the benefit of taking at least one hypertension medication at night (for an excellent review, see (Hermida et al 2013)). The MAPEC study followed over 2000 hypertensive patients over the course of a median of 5.6 years (Hermida et al 2010).…”

Circadian Rhythms in Anesthesia and Critical Care Medicine

“…Administration of blood pressure lowering drugs at bedtime could therefore lead to significant improvement is this clinical setting. 80,86 …”

Clock genes in hypertension

“…In mammals, mounting evidence has demonstrated that the circadian clock regulates a multitude of physiological functions including but not limited to: metabolism, immune response, renal function, sleep-wake cycles, and blood pressure [3, 4]. Interestingly, it has been shown that deregulation of the circadian clock can also be attributed to certain pathological states, including hypertension [5]. The purpose of this review is to examine the role of the circadian clock genes in the regulation of blood pressure and their potential role in hypertension from insights gathered through the use of rodent models.…”