Chronobiology international
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Specific features of the 24-h blood pressure (BP) pattern are linked to progressive injury of target tissues and risk of cardiovascular disease (CVD) events. Several studies have consistently shown an association between blunted asleep BP decline and risk of fatal and nonfatal CVD events. Thus, there is growing focus on ways to properly control BP during nighttime sleep as well as during daytime activity. ⋯ Likewise, the bedtime, in comparison with morning, ingestion schedule of the angiotensin-II receptor blockers (ARBs irbesartan, olmesartan, telmisartan, and valsartan exerts greater therapeutic effect on asleep BP, plus significant increase in the sleep-time relative BP decline, with the additional benefit, independent of drug terminal half-life, of converting the 24-h BP profile into a more normal dipping pattern. This is the case also for the bedtime versus upon-awakening regimen of combination ARB-CCB, ACEI-CCB, and ARB-diuretic medications. The chronotherapy of conventional hypertension medications constitutes a new and cost-effective strategy for enhancing the control of daytime and nighttime SBP and DBP levels, normalizing the dipping status of their 24-h patterning, and potentially reducing the risk of CVD events and end-organ injury, for example, of the blood vessels and tissues of the heart, brain, kidney, and retina.
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Gestational hypertension and preeclampsia are major contributors to perinatal morbidity and mortality. The diagnosis of gestational hypertension still relies on conventional clinic blood pressure (BP) measurements and thresholds of ≥140/90 mm Hg for systolic (SBP)/diastolic (DBP) BP. However, the correlation between BP level and target organ damage, cardiovascular disease risk, and long-term prognosis is greater for ambulatory BP monitoring (ABPM) than clinic BP measurement. ⋯ Once the time-varying threshold, given, for instance, by the upper limit of a tolerance interval, is available, the hyperbaric index (HBI), as a determinant of BP excess, can be calculated as the total area of any given subject's BP above the threshold. This tolerance-hyperbaric test, where diagnosis of gestational hypertension is based on the HBI calculated with reference to a time-specified tolerance limit, has been shown to provide high sensitivity and specificity for the early identification of subsequent hypertension in pregnancy, as well as a valuable approach for prediction of pregnancy outcome. ABPM during gestation, starting preferably at the time of the first obstetric check-up following positive confirmation of pregnancy, provides sensitive endpoints for use in early risk assessment and guide for establishing prophylactic or therapeutic intervention, and should thus be regarded as the required standard for the diagnosis of hypertension in pregnancy.
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Randomized Controlled Trial
Chronotherapy with low-dose aspirin for prevention of complications in pregnancy.
Preeclampsia and gestational hypertension are major contributors to perinatal morbidity and mortality. Several studies aimed to test the effects of low-dose aspirin (ASA) in the prevention of preeclampsia concluded that the beneficial effects of such treatment outweigh adverse ones. Such benefits have not been fully corroborated by larger randomized trials usually carried out in low-risk women, testing a dose of 60 mg/d ASA presumably ingested in the morning, and including women randomized as late as at 26-32 wks of gestation. ⋯ There was no increased risk of hemorrhage, either before or after delivery, with low-dose ASA relative to placebo (HR: .57, 95% CI: .25-1.33; p = .194). Results indicate that (i) 100 mg/d ASA should be the recommended minimum dose for prevention of complications in pregnancy; (ii) ingestion of low-dose ASA should start at ≤16 wks of gestation; and (iii) low-dose ASA ingested at bedtime, but not upon awakening, significantly regulates ambulatory BP and reduces the incidence of preeclampsia, gestational hypertension, preterm delivery, and IUGR. ABPM evaluation at the first trimester of pregnancy provides sensitive endpoints for identification of women at high risk for preeclampsia who might benefit most from the cost-effective preventive intervention with timed low-dose ASA.
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Randomized Controlled Trial
Ambulatory blood pressure thresholds for diagnosis of hypertension in patients with and without type 2 diabetes based on cardiovascular outcomes.
Currently recommended ambulatory blood pressure (BP) monitoring (ABPM) thresholds for diagnosis of hypertension do not differentiate, as international guidelines do for clinic BP, uncomplicated persons at low risk from those at higher risk, e.g., patients with diabetes, for target injury and cardiovascular disease (CVD) risk. We aimed to derive diagnostic thresholds for the awake and asleep systolic (SBP) and diastolic (DBP) BP means based upon CVD outcomes (death from all causes, myocardial infarction, angina pectoris, coronary revascularization, heart failure, acute arterial occlusion of the lower extremities, thrombotic occlusion of the retinal artery, hemorrhagic stroke, ischemic stroke, and transient ischemic attack) for patients with and without diabetes. We prospectively studied 3344 subjects (1718 men/1626 women), 52.6 ± 14.5 (mean ± SD) yrs of age, 607 with type 2 diabetes, during a median follow-up of 5.6 yrs. ⋯ In terms of CVD outcome, the equivalent cutoff threshold values for patients with diabetes were 120/75 mm Hg for the awake and 105/60 mm Hg for the asleep SBP/DBP means. Outcome-based reference thresholds for the diagnosis of hypertension were 15/10 mm Hg lower for ambulatory SBP/DBP in patients with than without diabetes. This marked difference indicates the need for revision of current guidelines that propose diagnostic thresholds for ambulatory BP without differentiation between the presence/absence of diabetes.
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Randomized Controlled Trial
Cardiovascular risk of resistant hypertension: dependence on treatment-time regimen of blood pressure-lowering medications.
In resistant hypertension, ingesting one or more blood pressure (BP)-lowering medications at bedtime is associated with significant reduction of sleep-time BP, a sensitive prognostic marker of cardiovascular disease (CVD) risk. This randomized trial investigated if bedtime therapy with at least one hypertension medication exerts better BP control and CVD risk reduction than conventional, morning-time therapy with all medications. We conducted a prospective, open-label, blinded-endpoint trial on 776 patients (387 men/389 women) with resistant hypertension, 61.6 ± 11.2 (mean ± SD) yrs of age. ⋯ At the last evaluation, patients treated with the bedtime versus awakening-time-treatment regimen showed significantly lower sleep-time systolic/diastolic BP mean values (121.6/65.4 vs. 113.0/61.1 mm Hg; p < .001) and higher prevalence of controlled ambulatory BP (61% vs. 46%; p < .001). The progressive decrease in the sleep-time systolic BP mean during follow-up was the most significant predictor of event-free survival (15% risk reduction per 5 mm Hg decreased asleep systolic BP mean). Among patients with resistant hypertension, ingestion of at least one hypertension medication at bedtime, compared with all medications upon waking, resulted in improved ambulatory BP control and fewer hard and soft CVD events.