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Chronotherapy improves blood pressure control and reduces vascular risk in CKD

  • Review Article
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From Nature Reviews Nephrology

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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.

Key Points

  • 24 h variations in blood pressure are the result of rest–activity alterations in behaviour, environmental phenomena and endogenous 24 h rhythms in neural, endocrine, endothelial and haemodynamic variables

  • A blunted sleep-time-relative blood pressure decline is significantly associated with an increased risk of end-organ injury and cardiovascular events

  • In patients with chronic kidney disease (CKD), the prevalence of increased blood pressure during sleep and the nondipper profile is very high and increases substantially with disease severity

  • Ingestion of one or more hypertension medications at bedtime is significantly associated with lower asleep systolic and diastolic blood pressure means and attenuated prevalence of the nondipper profile in patients with CKD

  • In patients with hypertension, including those with CKD, a progressive reduction of blood pressure during sleep is the most significant predictor of decreased cardiovascular disease risk

  • We recommend ambulatory blood pressure monitoring in patients with CKD to ensure accurate diagnosis of hypertension, assess cardiovascular disease risk and establish the optimal therapeutic strategy to reduce this risk

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Figure 1: Exogenous and endogenous determinants of the circadian blood pressure rhythm.
Figure 2: Blood pressure patterns in patients with CKD enrolled in the Hygia project.
Figure 3: Effect of timing of hypertension treatment regimen on blood pressure pattern in patients with CKD.

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Acknowledgements

The authors' research is supported by unrestricted grants from the Ministerio de Ciencia e Innovación (SAF2009-7028-FEDER), the Consellería de Economía e Industria, Xunta de Galicia (INCITE07-PXI-322003ES, INCITE08-E1R-322063ES, INCITE09-E2R-322099ES, IN845B-2010/114 and 09CSA018322PR), the European Research Development Fund, the Consellería de Cultura, Educación e Ordenación Universitaria, Xunta de Galicia (CN2012/251 & CN2012/260) and Vicerrectorado de Investigación, University of Vigo (awarded to R. C. Hermida, D. E. Ayala, A. Mojón and J. R. Fernández).

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R. Hermida, D. E. Ayala and M. H. Smolensky researched the data for the article and wrote the manuscript. All authors made a substantial contribution to discussions of the content and reviewed and/or edited the article before submission.

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Correspondence to Ramón C. Hermida.

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Hermida, R., Ayala, D., Smolensky, M. et al. Chronotherapy improves blood pressure control and reduces vascular risk in CKD. Nat Rev Nephrol 9, 358–368 (2013). https://doi.org/10.1038/nrneph.2013.79

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