The prevalence of hypertension in patients with chronic kidney disease (CKD) is extremely high, escalating with diminishing renal function. Typically, the diagnosis of hypertension and the clinical decisions regarding treatment are based solely on daytime clinic blood pressure (BP) measurements. Yet, correlation between BP level and target organ damage, cardiovascular disease (CVD) risk, and long-term prognosis is greater for ambulatory (ABPM) than clinic measurements. Consistent result of numerous studies show the elevated risk and incidence of end-organ injury and fatal and non-fatal CVD events are significantly associated with blunted nighttime BP decline (non-dipper pattern), and also that CVD events are better predicted by the asleep BP mean than either the awake or 24h BP means. The prevalence of abnormally high asleep BP and nondipping is extensive in patients with CKD, significantly increasing with advancing stage of severity. Indeed, elevated asleep BP is the major criterion for diagnosing hypertension and/or inadequate therapeutic ambulatory BP control in CKD. Endogenous circadian rhythms are known to explain statistically and clinically significant ingestion-time differences in the efficacy, duration of action, safety, and/or effects on the 24h BP pattern of at least six different classes of hypertension medications and their combinations. The renin-angiotensin-aldosterone system, which is highly circadian rhythmic, activates during the second half of nighttime sleep. Accordingly, bedtime versus morning ingestion of the full daily dose of the angiotensin-converting enzyme inhibitors benazepril, captopril, enalapril, lisinopril, perindopril, quinapril, ramipril, spirapril, trandolapril, and zofenopril better reduces asleep BP, with the additional benefit, independent of drug terminal half-life, of converting the 24h BP profile into a more normal dipper pattern. Therapeutic restoration of normal physiologic BP reduction during nighttime sleep, a novel therapeutic target best achieved by the ingestion of the entire daily dose of ≥1 hypertension medications at bedtime, has been identified in a recent outcome trial as the most significant independent predictor of decreased CVD risk, both in patients with and without CKD. Collectively, recent findings indicate around-the-clock ambulatory BP monitoring must be conducted on patients with CKD to accurately diagnose hypertension and assess CVD risk, and that the associated hypertension ought to be managed by a bedtime therapeutic strategy, preferably including a medication that blocks the renin-angiotensin-aldosterone system.

Chronotherapy of Hypertension with ACEIs and CKD: A New Solution to an Old Problem

PORTALUPPI, Francesco
2014

Abstract

The prevalence of hypertension in patients with chronic kidney disease (CKD) is extremely high, escalating with diminishing renal function. Typically, the diagnosis of hypertension and the clinical decisions regarding treatment are based solely on daytime clinic blood pressure (BP) measurements. Yet, correlation between BP level and target organ damage, cardiovascular disease (CVD) risk, and long-term prognosis is greater for ambulatory (ABPM) than clinic measurements. Consistent result of numerous studies show the elevated risk and incidence of end-organ injury and fatal and non-fatal CVD events are significantly associated with blunted nighttime BP decline (non-dipper pattern), and also that CVD events are better predicted by the asleep BP mean than either the awake or 24h BP means. The prevalence of abnormally high asleep BP and nondipping is extensive in patients with CKD, significantly increasing with advancing stage of severity. Indeed, elevated asleep BP is the major criterion for diagnosing hypertension and/or inadequate therapeutic ambulatory BP control in CKD. Endogenous circadian rhythms are known to explain statistically and clinically significant ingestion-time differences in the efficacy, duration of action, safety, and/or effects on the 24h BP pattern of at least six different classes of hypertension medications and their combinations. The renin-angiotensin-aldosterone system, which is highly circadian rhythmic, activates during the second half of nighttime sleep. Accordingly, bedtime versus morning ingestion of the full daily dose of the angiotensin-converting enzyme inhibitors benazepril, captopril, enalapril, lisinopril, perindopril, quinapril, ramipril, spirapril, trandolapril, and zofenopril better reduces asleep BP, with the additional benefit, independent of drug terminal half-life, of converting the 24h BP profile into a more normal dipper pattern. Therapeutic restoration of normal physiologic BP reduction during nighttime sleep, a novel therapeutic target best achieved by the ingestion of the entire daily dose of ≥1 hypertension medications at bedtime, has been identified in a recent outcome trial as the most significant independent predictor of decreased CVD risk, both in patients with and without CKD. Collectively, recent findings indicate around-the-clock ambulatory BP monitoring must be conducted on patients with CKD to accurately diagnose hypertension and assess CVD risk, and that the associated hypertension ought to be managed by a bedtime therapeutic strategy, preferably including a medication that blocks the renin-angiotensin-aldosterone system.
2014
9781629484228
chronic kidney disease; angiotensin-converting enzyme inhibitors; chronotherapy; arterial hypertension; cardiovascular risk; ambulatory blood pressure monitoring; asleep blood pressure
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/1904212
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