Targeting Nocturnal Hypertension in Type 2 Diabetes Mellitus

Abstract

During the past decades, several studies in different populations have suggested that nighttime blood pressure (BP) is a stronger predictor of cardiovascular (CV) events than daytime BP. [1][2][3][4][5] Indeed, a recent meta-analysis concluded that nighttime BP is superior to daytime BP in predicting CV events and total mortality in both patients and general populations. 6 Consequently, treatment strategies to target nighttime BP have come into focus.Bedtime administration (BA) of different classes of antihypertensive drugs has been shown to reduce nighttime BP, although results are not unequivocal. 7 Moreover, a recent prospective study concluded that BA of ≥1 antihypertensive drugs resulted in a significantly lower relative risk of total events and major CV events.8 Consequently, the American Diabetes Association now recommends administering ≥1 antihypertensive drugs at bedtime. 9Diabetes mellitus is a condition in which CV risk is markedly increased. 10 The predictive role of nighttime BP has also been established in patients with diabetes mellitus.3 Nocturnal hypertension is more frequent in diabetic compared with that in nondiabetic patients, in part, because of autonomic dysfunction. Only a few studies have investigated the effect of BA of antihypertensive drugs in diabetes mellitus, 11,12 and these studies applied BA irrespective of the level of nighttime BP.Hence, it was our aim to conduct a randomized crossover study on the effect of change of administration time of oncedaily antihypertensive drugs in a population of patients with type 2 diabetes mellitus and nocturnal hypertension, defined as nighttime systolic BP (SBP) ≥120 mm Hg. Our primary end point was changes in ambulatory BP parameters, with specific focus on nighttime BP. MethodsThe study was approved by the Central Denmark Region Committees on Health Research Ethics and the Danish Data Protection Agency. All patients provided informed consent. The study was registered at ClinicalTrials.gov with ID NCT01158625. Study PopulationInclusion criteria included (1) type 2 diabetes mellitus, (2) antihypertensive treatment including ≥1 once-daily renin-angiotensin system Abstract-Several studies in different populations have suggested that nighttime blood pressure (BP) is a stronger predictor of cardiovascular events than daytime BP. Consequently, treatment strategies to target nighttime BP have come into focus. The aim of the present study was to investigate the effect of change of administration time of antihypertensive drugs. We included 41 patients with type 2 diabetes mellitus and nocturnal hypertension (nighttime systolic BP >120 mm Hg) in an open-label, crossover study. Patients were randomized to 8 weeks of either morning or bedtime administration of all of the individual's once-daily antihypertensive drugs, followed by 8 weeks of switched dosing regimen. Bedtime administration of antihypertensive drugs resulted in a significant reduction in nighttime (7.5 mm Hg; P<0.001) and 24-hour (3.1 mm Hg; P=0.014) systolic BP, with a nonsignificant reduct...

Effect of bedtime administration of blood-pressure lowering agents on ambulatory blood pressure monitoring results: A meta-analysis

“…Compelling evidence is now available, showing that nocturnal BP is superior to daytime BP in predicting outcomes [7]. Subsequent www.cardiologyjournal.org studies in different populations and hypertensive patients corroborated the fact that a diminished nocturnal fall in BP was associated with poor CV outcomes and superior to daytime BP in predicting CV events and total mortality [12]. It was found that for every increase of 10 mm Hg in mean SBP at night, the risk of death increased by 21% [7].…”

“…Hermida et al [13] found that each 5-mm Hg decrease in mean sleep-time SBP was associated with a 14% reduction in the risk for CV events during follow-up (p < 0.001) among patients with chronic kidney disease and hypertension. Rossen et al [12] found levels of C-reactive protein were significantly lower with bedtime administration among patients with type 2 diabetes mellitus and nocturnal hypertension (p = 0.017), which may indicate an effect on low-grade inflammation.…”

“…The activity of the sympathetic nervous system determines the circadian variation of BP. Nocturnal hypertension is more common in patients with diabetes mellitus, sleep disturbance, depression and anxiety disorder, and cerebrovascular diseases accompanied by elevated sympathetic nervous activity during sleep [10,12,23]. Bankir et al [24] proposed a pressure natriuresis mechanism hypothesis that the relative increase in BP observed during the night is in favor of a compensatory rise in sodium excretion and the maintenance of sodium balance.…”

“…In Kario's trial [14], 11 (5%) patients in the bedtime administration group and 18 (7.9%) in the morning administration group did not complete the study. In Rossen's trial [12], all patients met the criteria of compliance. No withdrawal was reported in the left trials.…”

“…Decreasing nighttime BP and bedtime administration of antihypertensive drugs have already been taken into account for the treatment strategy aiming to improve BP management, but no clear consensus has been reached on the BP-lowering effect of this strategy. Recent researches have documented that ingesting at least one antihypertensive medication at bedtime, compared with treatment with all medications upon awakening, showed a significant reduction in the 24-h mean systolic BP (SBP)/diastolic BP (DBP) and the reduction was much more prominent during nighttime, decreasing the prevalence of nondipping [8,11,12], however, the similar 24-h mean SBP/DBP reduction for both treatment times was also reported [13][14][15]. Therefore, we conducted this meta-analysis to investigate the effects of bedtime administration of BP-lowering agents on ambulatory BP monitoring (ABPM) results.…”