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Blood pressure (BP) is one of the most dynamic physiologic variables that is routinely measured in clinical practice and is characterized by continuous and significant changes beat-to-beat, over 24 h, day-to-day, and visit-to-visit. Under physiological conditions, these BP variations largely represent a response to environmental stimulations and challenges of daily life aimed at maintaining so-called cardiovascular "homeostasis". However, sustained increases in blood pressure variability (BPV) may also reflect alterations in cardiovascular regulatory mechanisms or underlying pathological conditions and may represent a source of damage to the cardiovascular system. The clinical significance and prognostic implications of these BP variations have been demonstrated by a series of clinical and population studies conducted in recent years, in which increasing BPV has been associated with a higher risk of subclinical organ damage, cardiovascular events, and cardiovascular and all-cause mortality, independent of elevated average BP values. This paper will review the available evidence on the current definitions, classification, and mechanisms responsible for different types of BPV by focusing on their relevance to cardiovascular homeostasis and cardiovascular disease.

During blood pressure (BP) measurement, the recommended positioning of the cuff bladder center is directly above the brachial artery. We investigated the relevance of incorrect cuff positioning during (1) auscultatory measurement with an appropriate or improperly small cuff and (2) oscillometric measurement with a wide-range cuff designed to guarantee accurate measurements regardless of position. In subjects with wide BP and arm circumference ranges, (1) auscultatory BP was repeatedly measured with a properly positioned cuff (reference) and, simultaneously, with an identical cuff placed on the other arm in either a correct or an incorrect position (test). The measurements were performed with a properly sized (N=57) or an improperly small cuff (N=33). (2) Auscultatory measurements obtained with a properly positioned and sized cuff were compared with oscillometric measurements obtained with a specially designed wide-range cuff (Omron IntelliWrap) placed on the contralateral arm either in a correct or an incorrect position. Auscultatory BP measures were unaffected by incorrect positioning of a properly sized cuff, whereas with undercuffing, BP was overestimated with the cuff displaced by 90° laterally (systolic/diastolic BP differences: 4.9±4.6/4.0±4.6 mm Hg, P<0.01) or by 180° (3.9±5.4/4.2±5.1 mm Hg, P<0.01) in relation to the correct position. Incorrect placement of the oscillometric cuff had no significant effect on the accuracy of the measurements (difference with correct position <1.5 mm Hg). Incorrect cuff positioning introduces a systematic overestimation of auscultatory BP when the cuff is too small in relation to arm circumference but not when it is correctly sized. No systematic error was observed with oscillometric measurements obtained with a specially designed wide-range cuff.

This previously unpublished, preplanned analysis investigated the efficacy of the olmesartan/amlodipine combination at different doses on 24-h blood pressure (BP) control, as well as assessed trough estimation of trough-to-peak ratio (TPR) and smoothness index (SI). Ambulatory BP monitoring was performed in patients with moderate-to-severe hypertension whose BP was inadequately controlled after 8 weeks' treatment with amlodipine 5 mg. Patients were randomized to continue with amlodipine 5 mg or to receive olmesartan/amlodipine 10/5, 20/5 or 40/5 mg for 8 weeks (Period II). Patients not achieving BP control were uptitrated to a more powerful regimen for another 8 weeks (Period III). During Period II, each olmesartan/amlodipine combination reduced 24-h systolic and diastolic BP (SBP/DBP), as well as morning and early morning SBP/DBP, significantly more than amlodipine 5 mg (P<0.001 for all). TPRs were higher in each olmesartan/amlodipine group than with amlodipine 5 mg, and SI values showed dose-related increases; olmesartan/amlodipine 40/5 mg produced a significantly higher SI for SBP and DBP (1.55 and 1.33, respectively) than amlodipine 5 mg (0.96 and 0.77, respectively, P<0.0001 for each). During Period III, uptitrated patients showed further BP reductions, which were largest in those on olmesartan/amlodipine 40/10 mg. SI values increased in uptitrated patients and were highest with olmesartan/amlodipine 40/10 mg (SBP 1.62/DBP 1.41). The olmesartan/amlodipine combination effectively reduces BP over 24 h, including the morning hours, in a dose-related manner. Compared with amlodipine alone, the olmesartan/amlodipine combination has a better 24-h coverage (TPR) and a dose-related improvement in BP lowering homogeneity (SI).

Evidence has consistently supported the association of obstructive sleep apnea syndrome (OSAS) with an increased prevalence of hypertension. It has also been shown that the severity of OSAS is directly correlated with the degree of blood pressure (BP) elevation and that hypertension occurring in subjects with OSAS is more likely to be severe, resistant to antihypertensive treatment and associated with alterations in day-to-night BP changes. Proposed mechanisms for the pathogenesis of OSAS-related hypertension include the activation of the sympathetic nervous system, alterations in autonomic cardiovascular (CV) modulation, the activation of the renin-angiotensin-aldosterone system, endothelial dysfunction, systemic and vascular inflammation, oxidative stress, metabolic abnormalities, arterial stiffness and alterations in cardiac function and structure. Given the adverse prognostic implications of OSAS-related hypertension for CV morbidity and mortality, the confirmation of resistant hypertension by using ambulatory BP monitoring (ABPM) and the identification of alterations in day-to-night BP changes is of the utmost importance to implement more aggressive strategies for achieving BP control. In turn, the proper identification and implementation of specific treatment strategies for OSAS (that is, continuous positive airway pressure) in subjects with resistant hypertension may promote BP control and optimize CV protection. The present paper will review the evidence supporting the association of OSAS with resistant hypertension and the proposed mechanisms for this association. It will also address the role of ABPM in the confirmation of resistant hypertension in subjects with OSAS and whether the proper identification and management of OSAS in subjects with resistant hypertension will improve BP control.

Observational studies have shown that 24-h and morning ambulatory blood pressure (BP) control is low. This large-scale, practice-based study evaluated the effects of telmisartan 40 or 80 mg alone or in combination with hydrochlorothiazide (HCTZ) 12.5 mg on these BP parameters over 8 weeks; treatment was adjusted if clinic BP remained ≥140/90 mm Hg. A total of 863 patients were evaluated (baseline mean clinic BP, morning and 24-h ambulatory BP: 155±15/93±10 mm Hg, 137±15/83±11 mm Hg, 133±14/79±10 mm Hg, respectively; 68% were previously treated at baseline). Telmisartan with/without HCTZ significantly reduced the mean morning ambulatory BP (-8.2/-4.9 mm Hg), daytime ambulatory BP (-8.0/-4.7 mm Hg), 24-h ambulatory BP (-7.9/-4.7 mm Hg) and clinic BP (-22.3/-13.2 mm Hg) (all P<0.001) in previously untreated and in treated patients who switched to telmisartan and telmisartan/HCTZ. After treatment with telmisartan with/without HCTZ, the morning ambulatory BP control increased from 36.5 to 64.4%; daytime ambulatory BP control increased from 40.8 to 67.6%; 53.0% of patients achieved 24-h ambulatory BP <125/80 mm Hg and 62% achieved <130/80 mm Hg targets. Only 0.8% (7/863) reported an adverse event. In summary, telmisartan and telmisartan/HCTZ increased smooth 24-h BP control in daily management of hypertension.

Self-monitoring of blood pressure by patients at home (home blood pressure monitoring (HBPM)) is being increasingly used in many countries and is well accepted by hypertensive patients. Current hypertension guidelines have endorsed the use of HBPM in clinical practice as a useful adjunct to conventional office measurements. Recently, a detailed consensus document on HBPM was published by the European Society of Hypertension Working Group on Blood Pressure Monitoring. However, in daily practice, briefer documents summarizing the essential recommendations are needed. It is also accepted that the successful implementation of clinical guidelines in routine patient care is dependent on their acceptance by involvement of practising physicians. The present document, which provides concise and updated guidelines on the use of HBPM for practising physicians, was therefore prepared by including the comments and feedback of general practitioners.

Early combination therapy is increasingly recommended in hypertension management because of increased risk of adverse effects with high-dose monotherapy. However, this risk is not necessarily increased for high doses of angiotensin receptor blockers (ARB). ValTop study compared efficacy and safety of high vs. conventional dose of valsartan in hypertensive patients. ValTop was a controlled, randomized, double-blind trial. Of 6035 screened subjects, 4004 mild-to-moderate hypertensive patients (mean seated diastolic blood pressure (MSDBP) 90-109 mm Hg) started 4-week open-label treatment with valsartan 160 mg. Of them, 3776 were randomized to receive valsartan 160 mg (N=1900) or 320 mg (N=1876) o.d. for 4 weeks. In 28-week open-label extension study, all participating patients (N=642) received valsartan 320 mg. Valsartan 160 mg reduced MSDBP by 10.0 mm Hg in the initial open-label phase. Further BP reductions in the double-blind phase were significantly (P<0.0001) greater in the 320 mg group than in the 160 mg group for MSDBP (1.6 ± 0.18 mm Hg vs. 0.5 ± 0.18 mm Hg) and mean seated systolic BP (3.3 ± 0.31 mm Hg vs. 0.7 ± 0.31 mm Hg). The size of the additional effect of the 320 mg dose on BP was similar in subjects controlled or not by the initial 160 mg dose. Adverse event (AE) rates were similar in both treatment groups, drug-related AEs occurring in <5% of subjects in each phase. High-dose valsartan is safe and effective in uncomplicated mild-to-moderate hypertension independently of the initial response to a moderate dose. High-dose ARB monotherapy may thus be a viable option in hypertension management.