Stefano Omboni

In their study, Padwal and coworkers tested whether long-term (20 years) home blood pressure telemonitoring (BPT) plus pharmacist case management was more cost-effective than usual care in a cohort of high-risk Canadian patients with a recent non-disabling cerebrovascular disease. 1 Authors ran a cost-utility analysis using a Markov decision model applied to a previously published BPT study in a large population of adults with uncontrolled BP followed in a primary care setting under a pharmacist-physician collaborative practice agreement and modified it in order to fit the post-stroke and Canadian context. 2 The baseline characteristics of the cohort were based on a randomized controlled study performed in patients with a recent minor cerebrovascular event. 3 Achieved BP, risk of future cardiovascular (CV) events, attendant consequences on quality-adjusted life years (QALY), and Canadian dollar ($) costs were modeled. BPT was assumed to occur intensively for 3 months, then quarterly. In the base case analysis, the BPT intervention resulted in total costs per patient of 21 640$ and 8.83 QALY, whereas corresponding values for usual care were 23 020$ and 8.00. Home BPT and pharmacist case management resulted in an incremental 0.83 QALY and cost savings of 1929$ compared to usual care. Some sensitivity analyses were run in order to evaluate different scenarios, confirming the intervention dominance even in case the systolic blood pressure (SBP) efficacy was reduced or BPT costs were increased. The authors concluded that the intervention was dominant, achieving improved health at a reduced cost. In the past, few randomized controlled studies based on BPT in hypertensive patients have concluded that the use of technologies may only modestly increase healthcare costs compared to usual care and that the BPT is a cost-effective strategy. Unfortunately, most of these studies suffered from methodological flaws in the economic analysis, were based on a relatively small sample of subjects , short observation periods, and were often performed in mixed populations, including both low-and high-risk patients for which the cost-benefit of the intervention may substantially vary. Evidence on long-term economic benefits of BPT is substantially lacking. In a systematic review of randomized controlled studies that we performed a few years ago, 4 including 6 studies (8 comparisons), the use of BPT was associated with lower medical costs, a finding confirmed in more recent studies 5-7 supporting the cost-effectiveness of this intervention. However, medical costs were offset by those of the equipment and technologies, which contributed to the increase in the overall healthcare costs. The total expenditure was approximately 660 Euros larger in the BPT group than in the usual care group, with a substantial heterogeneity across the studies and a rather broad oscillation of costs (from 640 to 1035 Euros) (Figure). The incremental cost-effectiveness ratio for the healthcare expenditure averaged to nearly 400 Euros for SBP and to nearly 800 Euros for diastolic blood pressure (DBP) over a median follow-up period of 4 years, which means 100-200 Euros per person per year per 1 mmHg of BP reduction. However, when only medical costs were considered, the mean incremental cost-effectiveness ratio dropped to approximately 30 Euros for SBP and 25 Euros for DBP, namely an economically worthwhile intervention. Few of the economic studies published so far specifically evaluated the cost-benefit of pharmacist case management plus BPT. 8-10 These randomized studies were set in outpatient primary care clinics staffed with clinical pharmacy specialists and evaluated direct costs of the intervention on a relatively short time interval (6-12 months).

Community pharmacists play a crucial role in hypertension management and their intervention, mainly including education, medication monitoring, and reviewing, blood pressure (BP) measurement and cardiovascular risk factors tracking, have proved to enhance BP control and adherence to antihypertensive treatment. A multidisciplinary collaborative approach with the referring physician and a patient-centered model of care have been proved to be particularly effective for improving control of hypertension and promoting patients' health. The inclusion of telehealth in such model (the so-called telepharmacy) may expand the reach of the pharmacist's intervention and provide pharmacy operations and patient care at a distance with further benefits for hypertensive patients and their managing physicians. Very few randomized controlled studies have evaluated the clinical efficacy of the implementation of telepharmacy services in the management of hypertension, with the strongest evidence limited to physician-pharmacist collaborative interventions based on home BP telemonitoring plus patient education on lifestyle, drug therapy, and cardiovascular risk factors control. The results of these trials documented a benefit of telehealth mainly in terms of improvement of BP control consequent to antihypertensive medication intensification and optimization. Although promising, these results need to be corroborated through larger, prospective, and long-term studies, which should also evaluate additional long-term benefits of telepharmacy services in hypertension management.

Telepharmacy is devised to provide pharmacy operations and patient care at a distance and to expand access to healthcare, enhance patients' safety and improve patient outcomes. A variety of technologies, models of care and interventions are used to develop and provide telepharmacy services, serving diversified populations with different pathological conditions, including cardiovascular diseases. Unfortunately, very few randomized controlled studies have evaluated the clinical efficacy of the implementation of tele-pharmacy services in the management of various cardiovascular conditions, with the strongest evidence being limited to telemonitoring studies in the areas of hypertension and diabetes. Although the clinical efficacy of telepharmacy, and its cost effectiveness, are far from being fully proved, the inclusion of tele-pharmacy services in healthcare models may offer the unique opportunity to increase access to screening and improve care of cardiovascular conditions.

Hypertension and kidney disease often coexist, further increasing the risk of future car-diovascular events. Treatment of hypertensive adults with an angiotensin converting enzyme inhibi-tor in case of concomitant kidney disease may slow disease progression. The third-generation liphophilic angiotensin converting enzyme inhibitor zofenopril, administered alone or combined with a thiazide diuretic, has proved to be effective in lowering blood pressure in hypertensive patients and to reduce the risk of fatal and non-fatal events in post-acute myocardial infarction and heart failure. In almost three-hundred hypertensive patients with kidney impairment zofenopril administered for 12 weeks showed a similar blood pressure-lowering effect irrespective of the stage of the disease, with larger effects in combination with a thiazide diuretic, particularly in patients with slightly or moderately impaired kidney function. In animal models, zofenopril produced a significant and long-lasting inhibition of kidney angiotensin converting enzyme inhibitor and prevented kidney morphological and functional alterations following kidney ischemia-reperfusion injury. Treatment of hypertensive patients for 18 weeks with a combination of zofenopril 30 mg and hy-drochlorothiazide 12.5 mg resulted in a reduction in albumin creatinine ratio of 8.4 mg/g (49.6% reduction from baseline values) and no changes in glomerular filtration rate, variations in line with those obtained in the control group treated with a combination of irbesartan 150 mg and hydro-chlorothiazide 12.5 mg. Thus, some preliminary evidence exists to support that relatively long-term treatment with the angiotensin converting enzyme inhibitor zofenopril alone or combined with hy-drochlorothiazide is effective in controlling blood pressure and may confer some kidney protection due to ACE inhibition properties.

In the last three decades, ischemic heart disease, stroke, and diabetes became leading causes of mortality and years of life lost (YLL), although with some divergences among countries in the ratio of observed and expected YLLs which is based on sociodemographic indexes. 1 Worldwide, the morbidity and mortality burden associated to cardio-metabolic risk appears to be largely influenced by a rise in blood pressure (BP) levels, body mass index, glucose, and cholesterol. These risk factors are responsible of more than 60% of global death from cardiovascular disease (CVD), chronic kidney disease (CKD), and diabetes, with the high BP having the largest effect. 2 In 2013, high systolic blood pressure (SBP) accounted for 10.4 million deaths and 208.1 million Disability-Adjusted Life Years. 3 People with hypertension (BP ≥140/90 mm Hg or those receiving BP-lowering drugs) have a higher lifetime risk of overall CVD at 30 years of age (63.3% vs 46.1% of those with normal BP) and tend to develop CVD 5.0 years earlier. 4 Even among individuals without known vascular Summary Elevated blood pressure (BP) is a major determinant of morbidity and mortality burden related to cardio-metabolic risk. Current guidelines indicate that controlling and lowering BP promotes cardiovascular (CV) risk reduction. Among antihypertensive agents, angiotensin receptor blockers (ARBs) are characterized by an efficacy profile equivalent to other antihypertensive agents and are provided with excellent tolera-bility and low discontinuation rates during chronic treatments. Moreover, CV outcomes are reduced by ARBs. Olmesartan is a long-lasting ARB which proved to achieve a comparable or more effective action in lowering BP when compared to other ARBs. Olmesartan, in fact, displayed a larger and more sustained antihyperten-sive effect over the 24 hours, with a buffering effect on short-term BP variability. These are important features which differentiate olmesartan from the other principles of the same class and that may help to control the increased CV risk in the presence of high BP variability. Olmesartan shows similar benefits as other ARBs in terms of all-cause and CV mortality, and a favorable tolerability profile. Combination of ol-mesartan with long-lasting calcium-channel blockers and thiazide diuretics represents a rational and effective therapy. Thus, ARBs, including olmesartan, represent one of the most effective and safe treatments for patients with arterial hypertension. K E Y W O R D S ambulatory blood pressure, angiotensin receptor blockers, arterial hypertension, blood pressure, blood pressure variability, olmesartan

Purpose: Hypertension guidelines recommend measuring blood pressure (BP) on both arms, since an abnormal inter-arm difference (IAD) in BP is associated with an increased risk of vascu-lar abnormalities and cardiovascular (CV) disease. We tested whether an automatic oscillometric BP monitor allowing simultaneous both arm BP measurement might be effective for screening of subjects with potential vascular disease. Materials and methods: 220 consecutive subjects from an unselected sample of individuals of a small Italian community were screened using an automated upper-arm electronic BP monitor (Microlife WatchBP Office). Seated BP was measured in triplicate at 1 min interval. Demographic and clinical data were collected prior to any BP measurement. An average IAD difference >20 mmHg for systolic (S) and/or >10 mmHg for diastolic (D) BP was considered abnormal. Results: In 9 subjects (4.1%) an abnormal IAD was found, with lower BPs measured in the non-dominant arm (147 ± 28/78 ± 9 vs. 154 ± 15/92 ± 11 mmHg dominant, p<.01). Subjects with a significant IAD were significantly older (71 ± 8 vs. 57 ± 15 years, p¼.005), had a greater body mass index (BMI: 32 ± 7 vs. 25 ± 4 kg/m 2 , p¼.0001), higher BP levels (154 ± 15/92 ± 11 vs. 133 ± 18/ 80 ± 10 mmHg, p¼.001) and were more likely to report obesity (56 vs. 13%, p¼.001), a history of hypertension (67 vs. 35%, p¼.044) or cardiovascular disease (33 vs. 10%, p¼.034) than subjects with normal IAD. In a multivariate analysis, a higher BMI [odds ratio (95% confidence interval): 1.29 (1.11, 1.51)] and SBP [1.06 (1.01, 1.10)] were significantly associated with a larger risk of an abnormal IAD (p¼.001 and p¼.012, respectively). Conclusions: An abnormal IAD in BP is associated with a larger prevalence of CV risk factors and CV disease. Our study confirms that simultaneous both arm BP measurement must always be accomplished in subjects at risk for or with established CV disease. ARTICLE HISTORY

Blood pressure lowering by all classes of anti-hypertensive drugs is accompanied by significant reductions of stroke and major cardiovascular (CV) events. Drugs acting on the renin-angiotensin-aldosterone system, such as angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), showed similar benefit on major CV events to other antihypertensive medications. In real-world practice, ARBs reduced by 10% the incidence of CV mortality, non-fatal myocardial infarction, non-fatal stroke and provided superior protection against CV events than ACEIs in high-risk patients. Despite similar antihyper-tensive properties and a favourable safety profile for both ACEIs and ARBs, evidence indicates that patients treated with ARBs have lower rates of withdrawal for adverse events and greater persistence to therapy than those treated with ACEIs. Among ARBs, olmesartan is one of the latest generation compounds introduced in clinical practice for treating hypertension: head-to-head comparative trials suggest that the efficacy of olmesartan is superior to that of commonly prescribed ACEIs (ramipril and perindopril). The drug, administered as a monotherapy or in combination with a dihy-dropyridine calcium channel blocker or a thi-azide diuretic, has proved to be effective in maintaining blood pressure stability over 24 h, with a favourable safety profile and low dis-continuation rates. These properties are pivotal for considering olmesartan as a useful antihy-pertensive agent especially for high-risk patients (e.g. elderly, diabetics, patients with metabolic syndrome). Funding: Article preparation and open access fee were funded by Menarini International Operations Luxembourg S.A. (M.I.O.L.)

BACKGROUND:
In the Survival of Myocardial Infarction Long-Term Evaluation (SMILE) studies, early administration of zofenopril after acute myocardial infarction (AMI) was prognostically beneficial as compared to placebo and other angiotensin-converting enzyme inhibitors (ACEIs), such as lisinopril and ramipril. Here, we investigated whether zofenopril efficacy could be affected by a concomitant use of thiazide diuretics (TDs).
METHODS:
This was a post hoc analysis of pooled individual patient data from the SMILE studies. Patients treated with other diuretics than TDs were excluded. The primary study endpoint was the 1-year combined occurrence of death or hospitalization for CV causes, with or without TD.
RESULTS:
Among 2,995 patients, 263 (8.8%) were treated with a combination including a TD (TD+), whereas 2,732 (91.2%) were not treated with any diuretic (TD-). Proportions of subjects who were treated with TD were equally distributed (p=0.774) within the placebo, zofenopril, and other ACEIs groups. The 1-year risk of major cardiovascular events was similar in TD+ (18.3%) and TD- (16.8%) patients (hazard ratio [HR] 1.04; 95% CI 0.74-1.45; p=0.838). After stratifying per concomitant treatment and TD, the 1-year risk of CV events was significantly lower with zofenopril than with placebo (HR 0.70; 95% CI 0.55-0.88; p=0.002) and other ACEIs (HR 0.58; 95% CI 0.46-0.74; p=0.0001). Treatment with ACEIs and TD as concomitant therapy was associated with a larger blood pressure (BP) reduction (p=0.0001 for systolic BP and p=0.045 for diastolic BP).
CONCLUSION:
In post AMI patients, zofenopril maintained its positive impact on prognosis compared to placebo or other ACEIs, regardless concomitant TD administration. In this setting, TD shows advantages in managing the most difficult hypertensive patients.

BACKGROUND:
Oxidative stress is increased in hyperuricemic patients with acute myocardial infarction (AMI). Use of sulfhydryl ACE-inhibitors (ACEIs), such as zofenopril or captopril, plus xanthine oxidase inhibitors (XOIs), may potentially result in enhanced antioxidant effects and improved survival.
OBJECTIVE:
We verified the benefit of such combination in a randomly stratified sample of 525 of the 3630 post-AMI patients of the four randomized prospective SMILE (Survival of Myocardial Infarction Long-term Evaluation) studies.
METHODS:
One hundred sixty-five (31.4%) patients were treated with XOIs (79 under zofenopril, 86 placebo, lisinopril or ramipril), whereas 360 were not (192 zofenopril, 168 placebo or other ACEIs). In these four groups, we separately estimated the 1-year combined risk of major cardiovascular events (MACE, death or hospitalization for cardiovascular causes).

RESULTS:
MACE occurred in 10.1% of patients receiving zofenopril + XOIs, in 18.6% receiving placebo or other ACEIs + XOIs, in 13.5% receiving zofenopril without XOIs and in 22.0% receiving placebo or other ACEIs, but no XOIs (p = 0.034 across groups). Rate of survival free from MACE was significantly larger under treatment with zofenopril + XOIs than with other ACEIs with no XOIs [hazard ratio: 2.29 (1.06-4.91), p = 0.034]. A non-significant trend for superiority of zofenopril + XOIs combination was observed vs. zofenopril alone [1.19 (0.54-2.64), p = 0.669] or vs. placebo or other ACEIs + XOIs [1.82 (0.78-4.26), p = 0.169].
CONCLUSIONS:
Our retrospective analysis suggests an improved survival free from MACE in post-AMI patients treated with a combination of an urate lowering drug with antioxidant activity and an ACEI, with best effects observed with zofenopril.

Zofenopril is a lipophilic, sulfhydryl group-containing angiotensin-converting enzyme (ACE)-inhibitor, characterized by wide tissue distribution, long duration of action, and pleiotropic effects on endothelial dysfunction. Its clinical efficacy and safety have been described in the four randomized controlled trials of the SMILE program, which globally enrolled more than 3600 patients in post-acute myocardial infarction (AMI) setting. The SMILE-4 study specifically selected patients with left ventricular dysfunction at admission, and compared the effects of zofenopril or ramipril in combination with acetylsalicylic acid (ASA). Zofenopril demonstrated its superiority over ramipril in reducing the combined occurrence of death or hospitalization for cardiovascular causes both in the overall population included in the original study and in subgroups of patients at highest risk, namely hypertensive and diabetic subjects. The effects of the early treatment with zofenopril were sustained over time, and, after 5 years of follow-up, zofenopril increased the survival likelihood and reduced the hospitalization rate. Compared to ramipril, zofenopril was cost-effective with a number to treat of 13 and an incremental cost-effectiveness ratio (ICER) of 2125.45 euros for any additional event prevented. Furthermore, in real-world settings, zofenopril decreased the risk of death in patients with heart failure, particularly in men, and in subjects older than 76 years or with ejection fraction lower than 54%. These results support the early use of zofenopril immediately after AMI, even in the presence of comorbidities, and its maintenance over time to reduce the risk of heart failure.

Blood pressure telemonitoring (BPT) is a telehealth strategy that allows remote data transmission of blood pressure and additional information on patients' health status from their dwellings or from a community setting to the doctor's office or the hospital. There is sufficiently strong evidence from several randomized controlled trials that the regular and prolonged use of BPT combined with telecounseling and case management under the supervision of a team of healthcare professionals is associated with a significant blood pressure reduction compared with usual care, particularly in cases of patients at high risk. However, most current evidence is based on studies of relatively short duration (<12 months), and in the few studies that have investigated longer-term outcomes, no evidence of better or sustained effect could be provided. In addition, no definition of the optimal BPT-based healthcare delivery model could be derived from the studies performed so far, because of the heterogeneity of interventions, technologies, and study designs. BPT can also be provided in the context of "mobile health" (m-health) wireless solutions, together with educational support, medication reminders, and teleconsultation. When BPT is integrated in an m-health solution, it has the potential to promote patient's self-management, as a complement to the doctor's intervention, and encourage greater participation in medical decision-making. In conclusion, BPT has a potential key role in the management of patients with hypertension, since it seems to improve the quality of delivered care and allow for more effective prevention of the cardiovascular consequences of hypertension.

Cardiovascular events in hypertensives are associated with elevated average blood pressure (BP) and higher short-term BP variability (V), but little is known on treatment effects on BPV and on how to assess changes in short-term BPV. Aim of our study was to address the methodology of short-term BPV assessment and its reduction by Lercanidipine (L) or Enalapril (E) and their combination, through analysis of 24-hour ambulatory BP recordings from two studies including subjects of different age. Study-1: 64 middle-age hypertensives (52.9 ± 9.5 yrs) received L and E s.i.d. at 10 mg (L10, E10) or 20 mg doses (L20, E20) for 8 weeks. Study-2: 66 elderly hypertensives (65.5 ± 4.7 yrs) received placebo, L10, E20 and L10 + E20 s.i.d. for 4 weeks. In middle-age subjects, both L and E decreased mean BP and, at the highest dose, also short-term BPV. In elderly subjects, L10 alone or in combination with E20 reduced BPV. Treatment-induced reductions in BP levels and BPV were uncorrelated. Different methods for short-term BPV assessment did not always provide superimposable results in the elderly. Our study supports a better reduction of BPV by L in the elderly and by E + L combination at any age, suggesting BPV reduction to be independent from reduction in average BP.

Objective: In the four SMILE (Survival of Myocardial Infarction Long-Term Evaluation) studies, early administration of zofenopril in acute myocardial infarction (AMI) showed beneficial effects as compared to placebo and other angiotensin converting enzyme inhibitors (ACEIs). This study investigated whether the concomitant administration of the dihydropyridine calcium channel-blocker amlodipine may improve zofenopril efficacy to prevent cardiovascular events in post-AMI patients. Methods: This was a post-hoc analysis of pooled individual patient data from the four large random-ized SMILE studies. The primary endpoint was the 1-year combined occurrence of death or hospitalization for cardiovascular causes. Results: In total, 3488 patients were considered, 303 (8.7%) treated with concomitant amlodipine. Baseline systolic blood pressure and prevalence of metabolic syndrome were higher in amlodipine treated patients. The 1-year occurrence of major cardiovascular outcomes was significantly reduced in patients receiving concomitant treatment with amlodipine (hazard ratio, HR ¼ 0.66; and 95% confidence interval, CI ¼ 0.44–0.98; p ¼ .039). After accounting for treatment with amlodipine, the risk of cardiovascular events was significantly reduced with zofenopril compared to placebo (HR ¼ 0.78; 95% CI ¼ 0.63–0.97; p ¼ .026]. Among ACEI-treated patients, the zofenopril plus amlodipine combination reduced the risk of cardiovascular events by 38%, compared to the combination of other ACEIs plus amlodipine [HR ¼ 0.76; 95% CI ¼ 0.61–0.94); p ¼ .013). The prognostic benefit of concomitant treatment with zofenopril plus amlodipine was independent from blood pressure lowering. Conclusions: Zofenopril had a positive impact on prognosis in post-AMI patients, compared to other ACEIs. Concomitant administration of amlodipine may help to reduce the risk of cardiovascular events at 1 year.

The pharmacist may play a relevant role in primary and secondary prevention of cardiovascular diseases, mainly through patient education and counselling, drug safety management, medication review, monitoring and reconciliation, detection and control of specific cardiovascular risk factors (eg, blood pressure, blood glucose, serum lipids) and clinical outcomes. Systematic reviews of randomised controlled and observational studies have documented an improved control of hypertension, dyslipidaemia or diabetes, smoking cessation and reduced hospitalisation in patients with heart failure, following a pharmacist’s intervention. Limited proof for effectiveness is available for humanistic (patient satisfaction, adherence and knowledge) and economic outcomes. A multidisciplinary approach, including medical input plus a pharmacist, specialist nurse or both, and a greater involvement of community rather than hospital pharmacists, seems to represent the most efficient and modern healthcare delivery model. However, further welldesigned research is demanded in order to quantitatively and qualitatively evaluate the impact of pharmacist’s
interventions on cardiovascular disease and to identify specific areas of impact of collaborative practice. Such research should particularly focus on the demonstration of a sensitivity to community pharmacist’s intervention. Since pharmacy services are easily accessible and widely
distributed in the community setting, a maximum benefit should be expected from interventions provided in this context.

Purpose: The four SMILE studies demonstrated that early administration of zofenopril following acute myocardial infarction is prognostically beneficial compared to placebo or other angioten-sin-converting enzyme (ACE) inhibitors. In the present retrospective pooled analysis of individual SMILE studies, we evaluated the efficacy of zofenopril on cardiovascular (CV) outcomes in 1880 hypertensive and 1662 normotensive patients. Materials and methods: Four hundred and forty-nine hypertensives and 486 normotensives were treated with placebo, 980 and 786 with zofenopril 30–60 mg daily, 252 and 259 with lisino-pril 5–10 mg daily, 199 and 131 with ramipril 10 mg daily, for 6 to 48 weeks. Results: The 1-year risk of death or hospitalization for CV causes was significantly reduced with zofenopril and lisinopril vs. placebo in both hypertensive (HR: 0.65; 95%CI: 0.48–0.86; p ¼ .003 and .60, .36–.99; p ¼ .049, respectively) and normotensive patients (0.56, 0.42–0.75; p ¼ .0001 and .51, .28–.90; p ¼ .020), whereas this was not the case for ramipril (hypertensives: 1.02, 0.69–1.52; p ¼ .918; normotensives: 0.91, 0.59–1.41; p ¼ .670). Zofenopril significantly reduced the risk of CV outcomes vs. the other two ACE-inhibitors pooled together in hypertensive (0.76; 0.58–0.99; p ¼ .045), but not in normotensive patients (0.77; 0.55–1.10; p ¼ .150). Conclusions: In cardiac patients of the SMILE studies with arterial hypertension treatment with the ACE-inhibitor zofenopril was beneficial in reducing the 1-year risk of CV events as compared to placebo and ramipril. An efficacy similar to that of zofenopril was observed with lisinopril.

Background: The metabolic syndrome (MS) is a clustering of different cardiovascular (CV) risk factors, which further enhances the risk of death and CV complications in post-acute myocardial infarction (AMI) patients. In the present meta-analysis of individual data of the four randomized, prospective SMILE studies, we evaluated the efficacy of zofenopril vs. lisinopril, ramipril, and placebo on 1-year CV morbidity and mortality, according to the presence (+) or absence (of of the MS. Methods: 2203 (63.2%) of the 3488 patients were classified as MS+, 1285 (36.8%) as MS-. Five hundred two MS+ and 380 MS-were treated with placebo, 1134 and 608 with zofenopril 30–60 mg/die, 340 and 175 with lisinopril 5–10 mg/die, and 227 and 122 with ramipril 10 mg/die. Treatment was continued for 6 to 48 weeks. Results: The 1-year risk of a major CV event was similar (P = 0.420) in MS+ (18.1%) and MS-(18.0%) patients [HR and 95% confidence interval: 0.92 (0.76–1.12)]. After accounting for MS+/MS-, the 1-year risk of CV events vs. placebo was significantly lower under zofenopril [0.79 (0.63–0.97); P = 0.028] and lisinopril [0.65 (0.47–0.89); P = 0.007], but larger under ramipril [2.57 (1.94–3.93); P = 0.0001]. Treatment with zofe-nopril was associated with a statistically significant (P = 0.0001) reduction in CV risk as compared with the other angiotensin-converting enzyme inhibitors [MS+: 0.52 (0.42–0.66); MS-: 0.52 (0.38–0.73)]. Conclusions: In post-AMI patients with MS, zofenopril treatment is associated with a clinically relevant reduction in long-term CV morbidity and mortality, compared with placebo, with an efficacy similar to lisi-nopril, but better than ramipril.

Blood pressure (BP) values and thresholds are dependent on the setting in which BP is measured. When patients are categorized according to office and ambulatory or home BP, different combinations may result, with different prognostic significance. There is little doubt that patients with uncontrolled hypertension in the office and out-of-office have a worse prognosis than patients with controlled hypertension. Studies mainly performed in the general population, involving untreated or treated subjects, indicate that the incidence of cardiovascular events is not significantly different between individuals with white-coat hypertension and true normo-tension, whereas the outcome is worse in those with masked hypertension. 1–3 Thus, each BP elevation carries an increase in risk which adds to that of other BP elevations, in a sort of " continuum " from normotension to sustained hyperten-sion, passing through white-coat hypertension and masked hypertension. Such risk may vary in treated vs. untreated patients and in younger vs. older hypertensives. 4,5 It is thus important to identify patients with masked hypertension or white-coat hypertension because failure to do so may result in significant misdiagnosis and mismanagement of hyper-tension, with increase in patients' cardiovascular risk. In this issue of the American Journal of Hypertension, Pierdomenico and coworkers present results of a prospective study aiming at evaluating the impact of different BP phenotypes on long-term cardiovascular prognosis in elderly treated hypertensive patients. 6 All patients were seen at an initial visit, where both clinic and ambulatory BPs were collected , together with clinical information. The occurrence of fatal or nonfatal cardiovascular events was recorded during a follow-up visit taking place after an average of 9.1 years. Patients with masked uncontrolled hypertension (MUCH, office BP <140/90 mm Hg + 24-hour average systolic BP ≥130 and/or diastolic BP ≥80 mm Hg) had a 60% larger risk of cardiovascular events than controlled hypertensives (CH, office BP <140/90 mm Hg + 24-hour average BP <130/80 mm Hg), a figure only marginally lower than the 81% increased risk observed in sustained uncontrolled hypertensives (SUCH, office systolic BP ≥140 and/or diastolic BP ≥90 mm Hg + 24-hour average systolic BP ≥130 and/or diastolic BP ≥80 mm Hg). Conversely, the cardiovascular risk of white-coat uncontrolled hypertensives (WCUCH, office systolic BP ≥140 and/or diastolic BP ≥90 mm Hg + 24-hour average BP <130/80 mm Hg) was only slightly and not significantly increased as compared to controlled hypertensives (+9%). The results of this study are quite unique because of the large sample of patients studied (1,191), the length of the follow up , the event rate (3.63/100 patient-years) and the lack of such relevant data in the elderly. The only comparable study available so far in the literature is the SHEAF (Self measurement of blood pressure at Home in the Elderly: Assessment and Follow-up) Study which evaluated 4,939 treated hyper-tensives, aged 60 years or older, followed in general practices. 7 At variance from the study of Pierdomenico et al., the SHEAF Study was based on home BP monitoring (HBPM), had a shorter mean follow-up (3.2 years) and consequently a lower overall rate of cardiovascular morbidity and mortality (event rate 2.22/100 patient-years). The prevalence of CH (14%), MUCH (9%), and WCUCH (13%) was smaller and that of SUCH (63%) larger than that showed in the study by Pierdomenico et al. (23% CH, 12% MUCH, 19% WCUCH, 46% SUCH). However, in the SHEAF Study as in the study presented in this issue of the journal, when compared to CH, the relative risk of cardiovascular events was larger in SUCH (1.96) and MUCH (2.06) than in WCUCH patients (1.18). Unfortunately, in the study by Pierdomenico and coworkers, all information on predictors of fatal and nonfatal events were collected only at baseline. No data on variations in patients' health status and treatment during the follow-up is available. Thus, we cannot exclude that some patients belonging to a BP category may have shifted to another in the course of the study, this modifying the initial grade of cardiovascu-lar risk. Additionally, some patients were followed-up in the hospital and managed by the team of the study investigators, whereas others were only seen by their family doctors. Thus, the intensity and efficacy of hypertension management may have not been comparable across patients. Finally, the average 24-hour BP level was used to categorize patients, and thus we do not know whether the prognostic impact of the different BP phenotypes may have changed by categorizing

Purpose of the Review This review article will summarize available data on mobile applications for the management of hypertension, by highlighting their potential for clinical use, the current limitations and the yet pending issues to be addressed in future studies. Recent Findings The number of available applications related to arterial hypertension and their usage by smartphone owners is constantly increasing. However, most applications lack standardization and scientific validation, and security flaws could be an important, yet still underrated, issue. Small studies showed that treatment strategies based on telemonitoring of home blood pressure with mobile applications could improve blood pressure control, but there are no data on strong outcomes and the high heterogeneity of available studies severely limits the possibility of reaching a definitive conclusion on the impact of such strategies. Summary Smartphone applications for arterial hypertension represent a great chance to improve management of this condition. Results from small studies are promising, but there is a strong need for large, long-term, well-designed clinical trials, before these potential solutions might be reliably applied in real-life patients' care.

Combinations between an angiotensin converting enzyme (ACE) inhibitor or an angio-tensin II receptor blocker (ARB) and hydrochlorothiazide (HCTZ) are among the recommended treatments for hypertensive patients uncontrolled by monotherapy. Four randomized, double-blind, parallel group studies with a similar design, including 1469 hypertensive patients uncontrolled by a previous monotherapy and with C1 cardiovascular risk factor, compared the efficacy of a combination of a sulfhydryl ACE inhibitor (zofenopril at 30 or 60 mg) or an ARB (irbesartan at 150 or 300 mg) plus HCTZ 12.5 mg. The extent of blood pressure (BP)-lowering was assessed in the office and over 24 h. Pleiotropic features of the treatments were evaluated by studying their effect on systemic inflammation, organ damage, arterial stiffness, and metabolic biochemical parameters. Both treatments similarly reduced Enhanced content To view enhanced content for this article go to

Purpose: The four SMILE studies demonstrated that early administration of zofenopril following acute myocardial infarction is prognostically beneficial compared to placebo or other angioten-sin-converting enzyme (ACE) inhibitors. In the present retrospective pooled analysis of individual SMILE studies, we evaluated the efficacy of zofenopril on cardiovascular (CV) outcomes in 1880 hypertensive and 1662 normotensive patients. Materials and methods: Four hundred and forty-nine hypertensives and 486 normotensives were treated with placebo, 980 and 786 with zofenopril 30–60 mg daily, 252 and 259 with lisino-pril 5–10 mg daily, 199 and 131 with ramipril 10 mg daily, for 6 to 48 weeks. Results: The 1-year risk of death or hospitalization for CV causes was significantly reduced with zofenopril and lisinopril vs. placebo in both hypertensive (HR: 0.65; 95%CI: 0.48–0.86; p ¼ .003 and .60, .36–.99; p ¼ .049, respectively) and normotensive patients (0.56, 0.42–0.75; p ¼ .0001 and .51, .28–.90; p ¼ .020), whereas this was not the case for ramipril (hypertensives: 1.02, 0.69–1.52; p ¼ .918; normotensives: 0.91, 0.59–1.41; p ¼ .670). Zofenopril significantly reduced the risk of CV outcomes vs. the other two ACE-inhibitors pooled together in hypertensive (0.76; 0.58–0.99; p ¼ .045), but not in normotensive patients (0.77; 0.55–1.10; p ¼ .150). Conclusions: In cardiac patients of the SMILE studies with arterial hypertension treatment with the ACE-inhibitor zofenopril was beneficial in reducing the 1-year risk of CV events as compared to placebo and ramipril. An efficacy similar to that of zofenopril was observed with lisinopril.

In the Survival of Myocardial Infarction Long-term Evaluation (SMILE) 1, 3, and 4 studies, early administration of zofenopril in acute myocardial infarction showed to be prognostically beneficial versus placebo or ramipril. The SMILE-2 showed that both zofenopril and lisinopril are safe and showed no significant differences in the incidence of major cardiovascular (CV) complications. In this pooled analysis of individual data of the SMILE studies, we evaluated whether the superior efficacy of zofenopril is maintained also in patients with $1 CV risk factor (CV+, n = 2962) as compared to CV2 (n = 668). The primary study end point was set to 1-year combined occurrence of death or hospitalization for CV causes. The risk of CV events was significantly reduced with zofenopril versus placebo either in the CV+ (237%; hazard ratio: 0.63; 95% confidence interval: 0.51–0.78; P = 0.0001) or in the CV2 group (255%; hazard ratio: 0.45; 0.26–0.78; P = 0.004). Also, the other angiotensin-converting enzyme inhibitors reduced the risk of major CV outcomes, though the reduction was not statistically significant versus placebo (CV+: 0.78; 0.58–1.05; P = 0.107; CV2: 0.71; 0.36–1.41; P = 0.334). The benefit was larger in patients treated with zofenopril than other angiotensin-converting enzyme inhibitors, with a statistically significant difference for CV+ (0.79; 0.63–0.99; P = 0.039) versus CV2 (0.62; 0.37–1.06; P = 0.081). In conclusion, zofenopril administered to patients after acute myocardial infarction has a positive impact on prognosis, regardless of the patient's CV risk profile.

Objective: The Ambulatory blood pressure Registry TEleMonitoring of hypertension and cardiovascular rISk project was designed to set up an international registry including clinic blood pressure (CBP) and ambulatory blood pressure (ABP) measurements in patients attending hypertension clinics in all five continents, aiming to assess different daily life hypertension types. Methods: Cross-sectional ABP, CBP and demographic data, medical history and cardiovascular risk profile were provided from existing databases by hypertension clinics. Hypertension types were evaluated considering CBP (!140/90 mmHg) and 24-h ABP (!130/80 mmHg). Results: Overall, 14 143 patients from 27 countries across all five continents were analyzed (Europe 73%, Africa 3%, America 9%, Asia 14% and Australia 2%). Mean age was 57 AE 14 years, men 51%, treated for hypertension 46%, cardiovascular disease 14%, people with diabetes 14%, dyslipidemia 33% and smokers 19%. The prevalence of hypertension was higher by CBP than by ABP monitoring (72 vs. 60%, P < 0.0001). Sustained hypertension (elevated CBP and ABP) was detected in 49% of patients. White-coat hypertension (WCH, elevated CBP with normal ABP) was more common than masked hypertension (elevated ABP with normal CBP) (23 vs. 10%; P < 0.0001). Sustained hypertension was more common in Europe and America and in elderly, men, obese patients with cardiovascular comorbidities. WCH was less common in Australia, America and Africa, and more common in elderly, obese women. Masked hypertension was more common in Asia and in men with diabetes. Smoking was a determinant for sustained hypertension and masked hypertension. Conclusion: Our analysis showed an unbalanced distribution of WCH and masked hypertension patterns among different continents, suggesting an interplay of genetic and environmental factors, and likely also different healthcare administrative and practice patterns.

OBJECTIVE: Whether all antihypertensive drugs are equally effective in patients with metabolic syndrome is still unclear. The goal of the Zofenopril in Advanced MEtabolic Syndrome (ZAMES) study was to investigate whether treatment with the fixed-dose combination of sulphydril-containing angiotensin-converting enzyme inhibitor zofenopril plus hydrochlorothiazide is at least as effective as that with the angiotensin receptor blocker irbesartan plus hydrochlorothiazide in
patients with metabolic syndrome and essential hypertension, uncontrolled by a previous monotherapy.
METHODS: We enrolled 721 patients in a multicenter, international (Italy and Romania), randomized, double-blind, parallel group, phase III study. Following a 1-week screening withdrawal period, 482 patients (mean age 59 ± 10 years, 53% men) bearing a SBP at least 140 mmHg and/or DBP at least 90 mmHg plus metabolic syndrome (ATP-III criteria) were randomly allocated to a fixed-dose combination of zofenopril 30 mg plus hydrochlorothiazide 12.5 mg or irbesartan 150 mg plus hydrochlorothiazide 12.5 mg once daily for a cumulative period of 24 weeks. After 8 and 16 weeks, zofenopril and irbesartan doses were doubled in nonnormalized study participants. The study endpoint was the office DBP reduction at study end. In 20% of patients, an ambulatory blood pressure monitoring was performed. RESULTS: The prevalence of diabetes at baseline was significantly (P < 0.05) greater in the zofenopril plus hydrochlorothiazide group (82%) than in the irbesartan plus hydrochlorothiazide (73%) group. Baseline-adjusted DBP reductions
were superimposable (P = 0.370) with zofenopril plus hydrochlorothiazide
[n = 231; 9.8 (95% confidence interval: 11.1, 8.4) mmHg] and irbesartan plus hydrochlorothiazide [n = 235; 10.4 (11.8, 9.0) mmHg]. The same was for SBP [17.0 (19.2, 14.8) mmHg zofenopril plus hydrochlorothiazide vs. 18.8 (21.0, 16.6) mmHg irbesartan plus hydrochlorothiazide, P = 0.113]. Rate of normalized and responder patients (SBP/DBP < 140/90 mmHg or SBP reduction more than 20 mmHg or DBP reduction more than 10 mmHg) did not differ at study end (65.8% and 77.5% zofenopril plus hydrochlorothiazide vs. 67.7% and 81.5% irbesartan plus hydrochlorothiazide; P = 0.695, P = 0.301). These results were confirmed in the 69 study participants undergoing ambulatory blood pressure monitoring (35 zofenopril plus hydrochlorothiazide; 34 irbesartan plus hydrochlorothiazide), with a comparable 24-h average BP reduction [BP difference between-treatment: SBP: 0.1 (-5.7, 5.9) mmHg, P = 0.975; DBP: -0.9 (-3.8, 2.0) mmHg, P = 0.541]. Both drugs attained similar BP reductions also in the last 6 h of the dosing interval [between-treatment difference SBP: 0.1 (-7.4, 7.5) mmHg P = 0.990; DBP: -0.9 (-4.4, 2.6) mmHg, P = 0.602]. Metabolic and renal indexes were not altered.
Few patients were withdrawn for moderate adverse events (5% zofenopril plus hydrochlorothiazide; 5% irbesartan plus hydrochlorothiazide). CONCLUSION: This is the first study supporting the comparable antihypertensive and metabolic response to fixed-dose combinations of sulphydril-containing angiotensin-converting enzyme inhibitors (zofenopril) or angiotensin receptor blockers (Irbesartan) with a diuretic in patients with advanced metabolic syndrome and nonresponders to monotherapy. The results of this study can further
improve the clinical management of high cardiovascular risk patients with hypertension and metabolic syndrome, because these two drug combinations increase the number of available combinations, which may significantly improve patients' adherence in this special clinical condition that is frequently found in everyday practice.

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Background: Hypertension guidelines recommend ambulatory blood pressure (ABP), central aortic pressure (CAP), and pulse wave velocity (PWV) as parameters for estimating blood pressure (BP) control and vascular impairment. Recent advances in technology have enabled devices to combine non-invasive estimation of these parameters over the 24-hour ABP monitoring. However, currently there is limited evidence on the usefulness of such an approach for routine hypertension management.

Electronic processes and communication technologies
are more and more often employed to provide
healthcare services to caregivers and their patients. Such
solutions are currently referred as e-health, the most popular
and widely distributed being those based on telemedicine
and mobile health (m-health). A specific
application of telemedicine for hypertension management
is blood pressure telemonitoring (BPT), which allows
remote data transmission of BP and additional information
on patients’ health status from their living site or from a
community setting to the doctor’s office or the hospital.
Several randomized studies have documented a significant
BP reduction with regular BPT compared to usual care,
particularly in high risk hypertensive patients. Additional
benefits are observed when BPT is offered under the
supervision of a team of healthcare professionals, including
a community pharmacist. BPT may also be provided in the
context of m-health solutions, which commonly include
wireless diagnostic and clinical decision support tools.
M-health has the potential to promote patient’s self-management,
as a complement to the doctor’s intervention, and
encourage greater participation in medical decision making.
Current statistics show that half of smartphone owners
gather health information through their phone and 19 %
use a health app. In case of hypertensive patients the most
popular apps are those with tracking function, including
BPT. Thus, e-health, and in particular BPT and m-health,
are progressively gaining a key role in the management of
hypertensive patients, having the potential to improve the
quality of the delivered care and to more effectively prevent
cardiovascular consequences of high BP.

Objective: Timely detection of atrial fibrillation (AF) may effectively prevent cardiovascular consequences. However, traditional diagnostic tools are either poorly reliable (pulse palpation) or not readily accessible (ECG) in general practice. We tested whether an automatic oscillometric blood pressure (BP) monitor embedded with an algorithm for AF detection might be effective for opportunistic screening of asymptomatic AF in the community. Setting: A community-based screening campaign in an unselected population to verify the feasibility of AF screening with a Microlife WatchBP Office BP monitor with a patented AFIB algorithm. When possible AF was detected (≥2 of 3 BP measurements reporting AF), a doctor immediately performed a single-lead ECG in order to confirm or exclude the presence of the arrhythmia. The main demographic and clinical data were also collected. Participants: 220 consecutive participants from an unselected sample of individuals in a small Italian community. Primary and secondary outcome measures: Number of patients detected with AF and diagnosed risk factors for AF. Results: In 12 of 220 participants, the device detected possible AF during the BP measurement: in 4 of them (1.8%), the arrhythmia was confirmed by the ECG. Patients with AF were more likely to be older (77.0±1.2 vs 57.2±15.2 years, p=0.010), obese (50.0 vs 14.4%, p=0.048) and to suffer from a cardiovascular disease (50.0 vs 10.6%, p=0.014) than patients without AF. Participants with a positive BP AF reading and non-AF arrhythmias (n=8) did not differ in their general characteristics from participants with a negative BP AF reading and were younger than patients with AF (mean age 56.4±14.8, p=0.027; 5 of 8 participants aged <65 years). Conclusions: Opportunistic screening of AF by BP measurement is feasible to diagnose this arrhythmia in unaware participants, particularly in those older than 65 years, who are the target patient group recommended by current AF screening guidelines.

Objective: To compare a combination of a dihydropyridine
calcium-channel blocker with an angiotensin converting
enzyme inhibitor vs. monotherapy with one or the other
drug and placebo for their effects on home blood pressure
(HBP).
Methods: After a 2-week placebo wash-out, patients with
an elevated office blood pressure (BP) (diastolic 100–109
and systolic <180 mmHg) and HBP (diastolic 85 mmHg)
were randomized double-blind to a 10-week treatment
with placebo, lercanidipine, 10 or 20mg daily, enalapril,
10 or 20mg daily, or the four possible combinations. In
addition to office BP, HBP was self-measured via a
validated semiautomatic device twice in the morning and
twice in the evening during the 7 days before
randomization and at the end of treatment. Baseline and
treatment HBP values were separately averaged for each
day, morning, evening or the whole monitoring period,
excluding the first day. Day-by-day HBP variability was
defined as the SD or the variation coefficient of the daily
BP averages.
Results: Eight hundred and fifty-four patients with valid
HBP recordings at baseline and at the end of treatment
were analyzed (intention-to-treat population). From the
baseline value (147.011.6 mmHg) systolic/diastolic HBP
showed a small reduction (average baseline-adjusted
change: –1.8/–1.6 mmHg) with placebo and a more
marked significant fall with monotherapies (8.8/5.9
mmHg, P<0.001/<0.001 vs. placebo) and even more with
combination treatment (11.6/7.6 mmHg, P<0.001/
<0.001 vs. placebo and P<0.01/<0.05 vs.
monotherapy). A similar pattern was observed for each of
the days of the BP self-monitoring period as well as for
either morning or evening values, although the difference
between mono and combination treatment appeared to be
consistently significant for the morning values only. Dayby-
day systolic BP-SD was unaffected by placebo and
slightly reduced by drug treatments, with no, however,
significant changes in SBP-variation coefficient. Baseline
and end of treatment HBP values showed a limited
correlation with office BP values, this being particularly the
case for treatment-induced changes (correlation
coefficients: 0.37 for systolic and 0.45 for diastolic BP).
Conclusion: This large HBP database shows that the
lercanidipine–enalapril combination lowers HBP more
effectively than the corresponding monotherapies and
placebo, and that this greater effect is consistent between
days.

Several guidelines recommend opportunistic screening for atrial fibrillation (AF) in subjects aged ≥65 years using
pulse palpation during routine blood pressure (BP) measurement. However, this method has limited diagnostic
accuracy. A specific algorithm for AF detection during automated BP measurement was developed and implemented
in a novel oscillometric device (MicrolifeWatchBP Home-A). In 2013, theUKNational Institute for Health
and Care Excellence (NICE) recommended this device for AF screening during routine office BP measurement in
primary care in subjects ≥65 years. A review and meta-analysis of the evidence on the diagnostic accuracy of this
algorithm were performed. Six studies (n=2332) investigated the accuracy of AF detection using the Microlife
BPmonitor and estimated a pooled sensitivity at 0.98 (95% CI 0.95, 1.00) and specificity 0.92 (0.88, 0.96). Analysis
of 4 studies (n= 1126) showed more readings to improve specificity (from 0.86 to 0.91) and sensitivity (from
0.97 to 0.99). Taking 3 sequential readings with at least 2 detecting AF gave the highest diagnostic accuracy.
A single study (n=139) of paroxysmal AF screening with home BP monitoring (3316 days) showed sensitivity
99% and specificity 93%. Another study (n = 46) of AF screening with 24 h ambulatory BP monitoring showed
that AF detected in N15% of all readings has high probability of AF diagnosis requiring confirmation by 24 h electrocardiography.
AF detection with routine automated BP measurement is a reliable screening tool in the elderly,
which requires confirmation by electrocardiography. Paroxysmal AF might also be detected by routine automated
home or ambulatory BP monitoring.

In this randomized, double-blind, controlled, parallel group study (ZENITH), 434 essential hypertensives with additional cardiovascular risk factors, uncontrolled by a previous monotherapy, were treated for 18 weeks with zofenopril 30 or 60 mg plus hydrochlorothiazide (HCTZ) 12.5 mg or irbesartan 150 or 300 mg plus HCTZ. Rate of office blood pressure (BP) response (zofenopril: 68% versus irbesartan: 70%; p = 0.778) and 24-hour BP response (zofenopril: 85% versus irbesartan: 84%; p = 0.781) was similar between the two treatment groups. Cardiac and renal damage was equally reduced by both treatments, whereas the rate of carotid plaque regression was significantly larger with zofenopril. In conclusion, uncontrolled monotherapy treated hypertensives effectively respond to a combination of zofenopril or irbesartan plus a thiazide diuretic, in terms of either BP response or target organ damage progression.

Randomized controlled trials have documented that a team of health care professionals which includes a physician, a nurse and a community pharmacist may improve the benefit and adherence of anti-hypertensive therapy. If such a health care model relies on blood pressure telemonitoring, it can promote a stronger relationship between health care professionals and patients, and further improve BP control of hypertension. The major benefit of this collaborative approach is to center the patient&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s management in a tailored way, providing comprehensive and preventive care based on health information technologies. In this review, the authors summarize recent clinical studies that evaluate the role of the community pharmacist in BP measurements, and in hypertension screening and control. The authors also describe the advantages of using blood pressure telemonitoring in home and ambulatory settings to evaluate potential alternatives to primary care in hypertension management.

24-hour blood pressure variability (BPV) is a predictor of cardiovascular complications in hypertension, but its association with arterial stiffness is poorly understood. We recently showed that central aortic pressure and stiffness evaluated non-invasively over the 24-hours are increased in hypertensive patients. In the present analysis we report on the impact of 24-hour BPV on such estimates. Brachial BP was measured non-invasively over the 24-hours by an electronic, oscillometric, automated BP monitor in 661 uncomplicated, treated or untreated, hypertensive patients. Digitalized waveforms obtained during each brachial oscillometric BP measurement were stored in the device memory and analyzed by a validated transfer function algorithm (Vasotens technology) in order to obtain aortic systolic (S) BP, pulse wave velocity (PWV) and augmentation index (AI). BPV was calculated as weighted standard deviation (SD) of 24-hour SBP (average day-time and night-time SBP SD divided by the duration, in hours, of each time period). Patients were classified in two groups according to whether the 24-hour SD was below (n = 324) or above (n = 337) the median (12 mmHg) of the whole group. BPV showed a direct correlation with aortic SBP (r = 0.40 unadjusted, r = 0.33 after adjustment for age, gender, body mass index, antihypertensive treatment and 24-hour SBP; p &amp;lt; 0.001 for both), aortic PWV (r = 0.21 and r = 0.18, p &amp;lt; 0.001 for both) and aortic AI (r = 0.27, p &amp;lt; 0.001 and r = 0.10, p &amp;lt; 0.05). Aortic SBP, PWV and AI were larger in patients with high (122.6 mmHg,10.0 m/s and 25.9%) than in those with low BPV (116.0 mmHg, 9.3 m/s and 16.9%, p &amp;lt; 0.001 for all). Between-group differences were unchanged after adjustment for age, gender, body mass index, antihypertensive treatment and 24-hour SBP: the comparison was statistically significant for aortic SBP (121.6 vs. 117.0 mmHg, p &amp;lt; 0.001) and PWV (9.9 vs. 9.4 m/s, p &amp;lt; 0.001), but not for AI (22.6 vs. 20.4%, p = 0.110). In hypertensive patients 24-hour BPV shows a strong relation to aortic BP and stiffness, which is independent from the absolute 24-hour BP level.

In this paper, we present the results of a reanalysis of the data of two large randomized, double-blind, parallel group studies with a similar design, comparing the efficacy of an angiotensin-receptor blocker (olmesartan medoxomil) with that of an angiotensin-converting enzyme inhibitor (ramipril), by applying two different blood pressure targets recently recommended by hypertension guidelines for all patients, irrespective of the presence of diabetes (&amp;amp;amp;amp;amp;lt;140/90 mmHg), and for elderly hypertensive patients (&amp;amp;amp;amp;amp;lt;150/90 mmHg). The efficacy of olmesartan was not negatively affected by age, sex, hypertension type, diabetes status or other concomitant clinical conditions, or cardiovascular risk factors. In most cases, olmesartan provided better blood pressure control than ramipril. Olmesartan was significantly more effective than ramipril in male patients, in younger patients (aged 65-69 years), in those with metabolic syndrome, obesity, dyslipidemia, preserved renal function, diastolic ± systolic hypertension, and, in general, in patients with a high or very high cardiovascular risk. Interestingly, patients previously untreated or treated with two or more antihypertensive drugs showed a significantly larger response with olmesartan than with ramipril. Thus, our results confirm the good efficacy of olmesartan in elderly hypertensives even when new blood pressure targets for antihypertensive treatment are considered. Such results may be relevant for the clinical practice, providing some hint on the possible different response of elderly hypertensive patients to two different drugs acting on the renin-angiotensin system, when patients are targeted according to the blood pressure levels recommended by recent hypertension guidelines.

Automatic ambulatory blood pressure monitoring makes use of repeated cuff inflations throughout the day and night. This may interfere with the cardiovascular effects of sleep and thus alter the 24 h blood pressure profile. The possibility that intermittent automatic blood pressure measurements prevent nocturnal hypotension was examined in 17 mild or moderate essential hypertensive patients in whom blood pressure was recorded intraarterially for 48 h by the Oxford technique. During the first or the second 24 h period, blood pressure was also monitored noninvasively by the SpaceLabs (Redmond, WA) 5300 (n = 10) and by the Sandoz Pressure System SPS 1558 (Lavanchy Electronique, Prilly, Switzerland) (n = 7) devices, automatic measurements being performed at 15 min intervals during the day and at 30 min intervals during the night. Separate computer analysis of 24 h intraarterial tracings obtained in absence and in concomitance of contralateral automatic blood pressure monitoring showed th...

The AM-5600 is a new device that simultaneously monitors electrocardiogram (ECG) and noninvasive blood pressure (BP) over a 24-h period. BP readings (Korotkoff sounds and cuff air pressure) are stored into the recorder, allowing the removal of BP artifacts after a visual check. In 12 subjects with essential hypertension, we compared BP values simultaneously provided by the AM-5600 and intra-arterial recordings. At rest, noninvasive systolic BP (SBP) values were lower (5.4 +/- 4.9 mmHg) and diastolic BP (DBP) values were higher (7.3 +/- 7.3 mmHg) than were intra-arterial values. In ambulatory conditions (9 subjects), between-method discrepancies were +0.8 +/- 6.1 and +12.2 +/- 7.4 mmHg for 24-h SBP and DBP, respectively. AM-5600 underestimated 24-h intra-arterial SBP and DBP SD, but it accurately tracked intra-arterial SBP and DBP changes. Editing removed 22.1% of total readings, slightly reducing between-method discrepancies. Thus the AM-5600 provides an accurate average estimate of...

In recent years technological progress has improved the construction of ambulatory blood pressure monitoring devices. This has resulted in devices able to measure blood pressure continuously and non-invasively, and also in lighter, less noisy and more accurate intermittent blood pressure monitors. The accuracy of monitors, however, is still tested by taking blood pressure measurements at rest, and testing against intra-arterial blood pressure values, in true ambulatory conditions, is very seldom used. When evaluated by the latter approach, devices such as SpaceLabs 5300 and the Sandoz SPS 1558 recorders can be substantially inaccurate. Newer devices such as the SpaceLabs 90202 and 90207 are also somewhat inaccurate, particularly when diastolic blood pressure is considered. However, hour-to-hour changes in blood pressure obtained by the SpaceLabs 90202 and 90207 monitors are qualitatively and quantitatively similar to those obtained by invasive methods. This makes it possible to desc...