24-Hour ambulatory blood pressure control with triple-therapy amlodipine, valsartan and hydrochlorothiazide in patients with moderate to severe hypertension

To determine the effectiveness and safety of once-daily combination therapy with amlodipine, valsartan and hydrochlorothiazide for reducing ambulatory blood pressure (ABP) in patients with moderate to severe hypertension, a multicenter, double-blind study was performed (N=2271) that included ABP monitoring in a 283-patient subset. After a single-blind, placebo run-in period, patients were randomized to receive amlodipine/valsartan/hydrochlorothiazide (10/320/25 mg), valsartan/hydrochlorothiazide (320/25 mg), amlodipine/valsartan (10/320 mg) or amlodipine/hydrochlorothiazide (10/25 mg) each morning for 8 weeks. Efficacy assessments included change from baseline in 24-h, daytime and night time mean ambulatory systolic BP (SBP) and diastolic BP (DBP). Statistically significant and clinically relevant reductions from baseline in all these parameters occurred in all treatment groups (P<0.0001, all comparisons versus baseline). At week 8, least squares mean reductions from baseline in 24-h, daytime and night time mean ambulatory SBP/DBP were 30.3/19.7, 31.2/20.5 and 28.0/17.8 mm Hg, respectively, with amlodipine/valsartan/hydrochlorothiazide; corresponding reductions with dual therapies ranged from 18.8–24.1/11.7–15.5, 19.0–25.1/12.0–16.0 and 18.3–22.6/11.1–14.3 mm Hg (P⩽0.01, all comparisons of triple versus dual therapy). Treatment with amlodipine/valsartan/hydrochlorothiazide maintained full 24-h effectiveness, including during the morning hours; all hourly mean ambulatory SBP and mean ambulatory DBP measurements were ⩽130/85 mm Hg at end point. Amlodipine/valsartan/hydrochlorothiazide combination therapy was well tolerated. Once-daily treatment with amlodipine/valsartan/hydrochlorothiazide (10/320/25 mg) reduces ABP to a significantly greater extent than component-based dual therapy and maintains its effectiveness over the entire 24-h dosing period

Circadian clock and vascular disease.

Cardiovascular functions, including blood pressure and vascular functions, show diurnal oscillation. Circadian variations have been clearly shown in the occurrence of cardiovascular events such as acute myocardial infarction. Circadian rhythm strongly influences human biology and pathology. The identification and characterization of mammalian clock genes revealed that they are expressed almost everywhere throughout the body in a circadian manner. In contrast to the central clock in the suprachiasmatic nucleus (SCN), the clock in each tissue or cell is designated as a peripheral clock. It is now accepted that peripheral clocks have their own roles specific to each peripheral organ by regulating the expression of clock-controlled genes (CCGs), although the oscillation mechanisms of the peripheral clock are similar to that of the SCN. However, little was known about how the peripheral clock in the vasculature contributes to the process of cardiovascular disorders. The biological clock allows each organ or cell to anticipate and prepare for changes in external stimuli. Recent evidence obtained using genetically engineered mice with disrupted circadian rhythm showed a novel function of the internal clock in the pathogenesis of endothelial dysfunction, hypertension and hemostasis. Loss of synchronization between the central and peripheral clock also contributes to the pathogenesis of cardiovascular diseases, as restoration of clock homeostasis could prevent disease progression. Identification of CCGs in each organ, as well as discovery of tools to manipulate the phase of each biological clock, will be of great help in establishing a novel chronotherapeutic approach to the prevention and treatment of cardiovascular disorders

Is ambulatory blood pressure monitoring cost-effective in the routine surveillance of treated hypertensive patients in primary care?

Achieving target levels of office and/or ambulatory blood pressure readings among treated hypertensive patients is an important aspect of cardiovascular disease prevention. Although office blood pressure measurement is simple and convenient, ambulatory blood pressure monitoring is especially useful for identifying patients with 'white coat' hypertension, in whom falsely raised office blood pressure recordings often lead to unnecessary return visits and additional treatment. Office and ambulatory blood pressure control was compared in 374 treated hypertensive patients in a single general practice, and the costs of performing annual ambulatory blood pressure measurements were compared with potential clinical savings. Ambulatory blood pressure monitoring detected 115 (31%) patients who fulfilled the British Hypertension Society target for ambulatory but not office blood pressure, i.e. white coat hypertension, and 21 patients apparently controlled by office but not ambulatory blood pressure criteria. In economic modelling, the capital, maintenance and user costs of ambulatory blood pressure monitoring (13,790 Pounds per year) were partly offset by fewer follow-up visits and second-line treatments in the group with white coat hypertension (there were modelled savings of 10,178 Pounds). Thus, ambulatory blood pressure monitoring identified a much larger number of treated hypertensive patients with adequate blood pressure control at an extra net cost of 3612 Pounds per year