Chronobiology international
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Multicenter Study
Circadian pattern of ambulatory blood pressure in hypertensive patients with and without type 2 diabetes.
There is strong association between diabetes and increased risk of end-organ damage, stroke, and cardiovascular disease (CVD) morbidity and mortality. Non-dipping (<10% decline in the asleep relative to awake blood pressure [BP] mean), as determined by ambulatory BP monitoring (ABPM), is frequent in diabetes and consistently associated with increased CVD risk. The reported prevalence of non-dipping in diabetes is highly variable, probably due to differences in the study groups (normotensive subjects, untreated hypertensives, treated hypertensives), relatively small sample sizes, reliance only on a single, low-reproducibility, 24-h ABPM evaluation per participant, and definition of daytime and nighttime periods by arbitrary selected fixed clock-hour spans. ⋯ Most important, prevalence of the riser BP pattern, associated with highest CVD risk among all possible BP patterns, was more than twice as prevalent in diabetes. Patients with diabetes also presented significantly elevated ambulatory PP, reflecting increased arterial stiffness and enhanced CVD risk. These collective findings indicate that diabetes should be included among the clinical conditions for which ABPM is recommended for proper CVD risk assessment.
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Randomized Controlled Trial
Role of time-of-day of hypertension treatment on the J-shaped relationship between blood pressure and cardiovascular risk.
Several previous studies found that too great a reduction of clinic blood pressure (BP) by treatment increased cardiovascular disease (CVD) risk, whereas moderate reduction decreased it. Thus, it has been suggested that the relationship between BP and CVD events is J-shaped, with CVD risk decreasing as BP is lowered, and then rising as BP is further decreased. Correlation between BP level and CVD risk, however, is stronger for ambulatory BP monitoring (ABPM) than clinical BP measurements. ⋯ There was no single major event, i.e., CVD death, myocardial infarction, or stroke, in patients who achieved an asleep systolic BP mean <103 mm Hg. Our findings indicate that bedtime hypertension treatment is not associated with a J-shaped relationship between achieved BP and CVD risk. The decreased CVD risk associated with the progressive reduction in asleep BP, more feasible by bedtime than morning hypertension treatment, has clinical implications, in particular, the need to consider the proper timing of hypertension medications, in conjunction with ABPM for proper assessment of BP control, as an improved and potentially safer means of reducing CVD risk of hypertensive patients.
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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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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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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.