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Saturday, September 26, 2015

Dosing Blood Pressure Control Medicines at Bed Time Reduces the risk of Stroke and T2 Diabetes Mellitus

Posted by Dr Prahallad Panda on 9:12 PM Comments

We all prescribe medications for control of Hypertension. Most common among those are the ACE (Angiotensin Converting Enzyme) inhibitors, ARBs (Angiotensin Receptor Blocker) and Third generation β-Blocker like Nebivolol. But, seldom we advise the patients which is the preferred time to take these groups of medications. Most of the patients, conventionally, take these medicines after awakening, in the morning.
It has been observed that most susceptible people get heart attack towards dawn or early morning. One of the factors can possibly be due to the fact that blood pressure starts rising from 03 to 04 AM and gradually rises till 12 Noon.
Normally, there is a fall of systolic blood pressure more than 10% of mean day time BP reaching the zenith from 12 Mid-Night to 03-04 AM, regulated by circadian rhythm. This phenomenon is called as “Dipping.”
Alterations in these intrinsic circadian rhythms can result in the absence of the nocturnal BP decline (non-dipping). This altered pattern is commonly seen in patients with essential hypertension, several forms of secondary hypertension and disorders of the autonomic nervous system.
The clinical relevance of this phenomenon lies in the fact that non-dipping has been associated with increased frequency of hypertensive target organ damage (brain, heart and kidney), as well as cerebrovascular and cardiovascular events in hypertensive patients.
Circadian rhythms typically originate in “master oscillators” located in the suprachiasmatic nuclei (SCN) of the anterior hypothalamus. How this hypothalamic rhythm is translated into changes in blood pressure is not entirely known, but the autonomic nervous system is suspected to play a role; sympathetic activity is also modulated by hypothalamic centers, and follows a circadian pattern similar to that of blood pressure.
Patients are categorized, usually based on systolic blood pressure, as extreme dippers (night–day blood pressure ratio ≤ 0.8), dippers (0.8 < ratio ≤ 0.9), non-dippers (0.9 < ratio ≤ 1.0) and reverse dippers or risers (ratio > 1.0). Reverse dipper are particularly in the risk of developing end organ damages.
A new research article published in The Diabetologia by Ramón C. Hermida, Diana E. Ayala, Artemio Mojón and José R. Fernández of University of Vigo, Campus Universitario, Vigo, Pontevedra 36310, Spain, titled as”Bedtime ingestion of hypertension medications reduces the risk of new-onset type 2 diabetes: a randomised controlled trial” has concluded that in hypertensive patients without diabetes, ingestion of 1 BP-lowering medications at bedtime, mainly those modulating or blocking the effects of angiotensin-II, compared with ingestion of all such medications upon awakening, results in improved ambulatory BP (ABP) control (significant further decrease of asleep BP) and reduced risk of new-onset diabetes.
Renin angiotensin pathway or RAAS.
Renin angiotensin pathway or RAAS. (Photo credit: Wikipedia)
Drugs that target angiotensin include angiotensin receptor blockers (ARBs), ACE inhibitors and beta blockers. These medications act through blockade of the RAAS (Rennin-Angiotensin-Aldosterone System) in kidney that causes blood vessels to constrict and blood pressure to rise. 
Angiotensin, Aldosterone and adrenaline also contribute to increased glucose (sugar) release from the liver and decreased insulin sensitivity. These factors can lead to Type 2 diabetes.
 The researchers conducted a prospective, randomised, open-label, blinded endpoint trial of 2,012 hypertensive patients without diabetes, 976 men and 1,036 women, 52.7±13.6 years of age. Patients were randomised, using a computer-generated allocation table, to ingest all their prescribed hypertension medications upon awakening or the entire daily dose of 1 of them at bedtime.
During a median follow-up of 5.9 years, 171 participants developed type 2 diabetes. Patients in the bedtime, compared with the morning-treatment group, showed a significantly lower asleep mean BP and a greater sleep-time relative BP decline.
In the bedtime treated group, there was a lower-prevalence of a phenomenon known as 'non-dipping' -- in which patients' night time BP falls by less than 10% compared to daytime BP. Non-dipping occurred in 32% of bedtime-treated patients and 52% of those getting their treatment in the morning.
There was also a 57% decrease in the risk of developing new-onset type 2 diabetes in the bedtime-treated group after adjustment for the potential confounders of fasting glucose, waist circumference, mean asleep systolic BP, dipping classification and chronic kidney disease.
Specifically, the odds of type 2 diabetes dropped 61 percent for people taking angiotensin receptor blockers at bedtime compared to morning. For those on ACE inhibitors at night, the odds went down 69 percent. People on beta blockers reduced their odds of the blood sugar disease by 65 percent when they took their medicine at night, the researchers reported.
All three classes of medication were associated with a reduced risk of type 2 diabetes when taken at bedtime as the effect will be much more on liver/kidney in comparison to the waning effect at night when taken in the morning.
Let us remember to advise our hypertensive patients to take their anti-hypertensive medications at bed time, especially ARBs, ACE-Inhibitors and Nebovolol for better effect and delaying development of T2DM.

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