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The VASOTENS Registry is an international telehealth-based repository of 24-hour ambulatory blood pressure monitorings (ABPM) obtained through an oscillometric upper-arm BP monitor allowing combined estimation of some vascular biomarkers. The present paper reports the results obtained in 1200 participants according to different categories of CV risk. Individual readings were averaged for each recording and 24-hour mean of brachial and aortic systolic (SBP) and diastolic blood pressure (DBP), pulse wave velocity (PWV), and augmentation index (AIx) obtained. Peripheral and central BP, PWVand AIx values were increased in older participants (SBP only) and in case of hypertension (SBP and DBP). BP was lower and PWVand AIx higher in females. PWV was increased and BP unchanged in case of metabolic syndrome. Our results suggest that ambulatory pulse wave analysis in a daily life setting may help evaluate vascular health of individuals at risk for CV disease.

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 randomized 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 = 0.66; and 95% confidence interval, CI = 0.44-0.98; p = .039). After accounting for treatment with amlodipine, the risk of cardiovascular events was significantly reduced with zofenopril compared to placebo (HR = 0.78; 95% CI = 0.63-0.97; p = .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 = 0.76; 95% CI = 0.61-0.94); p = .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.

Objective. To compare the efficacy and safety of the angiotensin II antagonist olmesartan medoxomil (O) and the ACE inhibitor ramipril (R) in elderly patients with essential arterial hypertension. Methods. After a 2-week placebo wash-out 1102 treated or untreated elderly hypertensive patients aged 65–89 years (office sitting diastolic blood pressure, DBP, 90–109mmHg and/or office sitting systolic blood pressure, SBP, 140–179mmHg) were randomized double-blind to 12-week treatment with O 10mg or R 2.5mg oncedaily. After the first 2 and 6 weeks doses could be doubled in non-normalized [blood pressure (BP)

The objective of the study was to compare the efficacy and safety of frovatriptan and almotriptan in women with menstrually related migraine (IHS Classification of Headache disorders) enrolled in a multicenter, randomized, double-blind, cross-over study. Patients received frovatriptan 2.5 mg or almotriptan 12.5 mg in a randomized sequence: after treating 3 episodes of migraine in no more than 3 months with the first treatment, the patient was switched to the other treatment. 67 of the 96 female patients of the intention-to-treat population of the main study had regular menstrual cycles and were thus included in this subgroup analysis. 77 migraine attacks classified as related to menses were treated with frovatriptan and 78 with almotriptan. Rate of pain relief at 2 and 4 h was 36 and 53 % for frovatriptan and 41 and 50 % for almotriptan (p = NS between treatments). Rate of pain free at 2 and 4 h was 19 and 47 % with frovatriptan and 29 and 54 % for almotriptan (p = NS). At 24 h, 62 % of frovatriptan-treated and 67 % of almotriptan-treated patients had pain relief, while 60 versus 67 % were pain free (p = NS). Recurrence at 24 h was significantly (p

This article offers instructions and recommendations on how to perform blood pressure measurements in the doctor's office, in the patient's home and in ambulatory conditions over 24 hours. Great attention is paid to some of the general aspects of blood pressure measurement, including the accuracy of blood pressure measuring devices, the importance of a 'white coat effect', and the need for patient education. This article also deals with a number of practical details, such as the importance of patient's relaxation and position, arm position and support, arm selection and cuff selection and application. Recommendations are provided on the observer's position and performance, and on the need to pay attention to specific factors affecting the blood pressure measurement in different patient populations, namely in children, elderly and obese people, pregnant women, patients with arrhythmias and patients on treatment. This article then separately focuses on the characteristics of auscultatory and automated measurements, the latter performed either in the office, at home or over 24 hours in ambulatory settings. Home blood pressure monitoring (HBPM) is becoming increasingly important in the diagnosis and management of arterial hypertension. The importance of HBPM in cardiovascular prevention, related to a deeper involvement of patients in their long-term management, and the wide diffusion of this approach in populations, is not always accompanied by adequate knowledge of how to make proper use of this technique, which emphasizes the need for more precise recommendations. This article summarizes the available evidence and provides recommendations on the use of home blood pressure monitoring in clinical practice and in research. It updates the previous recommendations on the same topic issued in 2000. The main topics addressed include the methodology of HBPM, focusing on measurement conditions and procedures, ranging from patient/subject position, to arm selection, arm position and support, cuff selection and application and data reporting, diagnostic and therapeutic thresholds, clinical applications in hypertension (with specific reference to special populations) and its applications in research. Special attention is given to device validation and selection as well as to patient education and to the need of HBPM to be guided by the physician in charge. The final section deals with the problems related to the implementation of these recommendations in clinical practice. Finally, the methodology and clinical impact of 24-hour ambulatory blood pressure monitoring are also addressed in detail, focusing on the parameters that can be derived from the analysis of 24-hour blood pressure recordings applied both to the diagnostic and prognostic evaluation of hypertensive patients and to the assessment of the effectiveness of antihypertensive treatment in controlling blood pressure through the day and night. Instructions to users on how to properly perform HBPM are provided as an appendix. © 2008 Adis Data Information BV. All rights reserved.

Background The role of vascular risk factors in glaucoma is still being debated. To assess the importance of vascular risk factors in patients with primary open-angle glaucoma (POAG), data from the medical history of 2,879 POAG patients and 973 age-matched controls were collected and analyzed. Methods Design: observational survey. Setting: 35 Italian academic centers. Study population: POAG patients and age-matched controls. In order to reduce bias consecutive patients were included. Observation procedures: data concerning vascular risk factors were collected for all patients with a detailed questionnaire. A complete ophthalmological examination with assessment of intraocular pressure (IOP), visual field, optic disc, and systemic blood pressure was performed. Main outcome measures: the ESH-ESC (European Society of Hypertension-European Society of Cardiology) guidelines were used to calculate the level of cardiovascular risk. Crude and adjusted estimates of the odds ratios (OR) were calculated for all cardiovascular risk factors in POAG and controls. Results The study included 2,879 POAG patients and 973 controls. POAG cases had a significantly higher systolic and diastolic blood pressure (p=0.001) and systolic perfusion pressure (p=0.02) as compared with controls. Also mean IOP was significantly higher in the POAG group (p=0.01), while diastolic perfusion pressure was not significantly different in the two groups. Myopia was more prevalent in the POAG group (23 vs 18%, p=0.005) as well as a positive family history for glaucoma (26 vs 12%, p= 0.004). POAG patients tended to have a higher cardiovascular risk than controls: 63% of glaucoma cases vs 55% of controls (OR: 1.38, p=0.005) had a “high” or “very high” cardiovascular risk. Conclusions The level of cardiovascular risk was significantly higher in glaucoma patients than in controls.

Two recent identically designed trials (one Italian and one European multinational) have compared the head-to-head efficacy and safety of the angiotensin II receptor blocker olmesartan medoxomil and the angiotensin converting enzyme inhibitor ramipril, in elderly patients with essential hypertension. The aim of the present study was to assess the antihypertensive efficacy of olmesartan and ramipril in elderly patients with hypertension, with or without metabolic syndrome, by performing a pooled analysis of data from the two head-to-head trials. After a 2-week, placebo wash-out, 1,453 treated or untreated elderly hypertensive patients aged 65–89 years [with sitting office diastolic blood pressure (DBP) 90–109 mmHg and/or sitting office systolic BP (SBP) 140–179 mmHg] were randomized to 12-weeks of double-blind treatment with olmesartan 10 mg or ramipril 2.5 mg once daily. Treatment could be up-titrated to 20 and 40 mg for olmesartan, and 5 and 10 mg for ramipril, after the first 2 and 6 weeks, respectively, in patients with inadequately controlled BP (BP ≥140/90 mmHg for non-diabetics and ≥130/80 mmHg for diabetics). Office BP was measured at randomization and after 2, 6 and 12 weeks of treatment. 24-h ambulatory BP recordings were obtained at randomization and after 12 weeks. Of the 1,426 patients in the intent-to-treat analysis, 735 (51.5 %) had metabolic syndrome (olmesartan, n = 372; ramipril, n = 363). After 12 weeks of treatment, baseline-adjusted office BP reductions were greater (p

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. Objective: We recently launched an investigator-initiated, international, multicenter, observational, prospective study, the Vascular health Assessment Of The Hypertensive patients (VASOTENS) Registry, aimed at (1) evaluating non-invasive 24-hour ABP and arterial stiffness estimates (through 24-hour pulse wave analysis, PWA) in hypertensive subjects undergoing ambulatory blood pressure monitoring (ABPM) for clinical reasons; (2) assessing the changes in estimates following treatment; (3) weighing the impact of 24-hour PWA on target organ damage and cardiovascular prognosis; (4) assessing the relationship between arterial stiffness, BP absolute mean level and variability, and prognosis; and (5) validating the use of a 24-hour PWA electronic health (e-health) solution for hypertension screening. Methods: Approximately 2000 subjects, referred to 20 hypertension clinics for routine diagnostic evaluation and follow-up of hypertension of any severity or stage, will be recruited. Data collection will include ABPM, performed with a device allowing simultaneous non-invasive assessment of 24-hour CAP and arterial stiffness (BPLab), and clinical data (including cardiovascular outcomes). As recommended by current guidelines, each patient will be followed-up with visits occurring at regular intervals (ideally every 6 months, and not less than once a year depending on disease severity). A Web-based telemedicine platform (THOLOMEUS) will be used for data collection. The use of the telemedicine system will allow standardized and centralized data collection, data validation by experts and counseling to remote centers, setup and maintenance of the Registry, and prompt data analysis. Results: First follow-up results are expected to be available in the next 2 years. Conclusions: The results of the VASOTENS Registry will help define the normalcy thresholds for current and future indices derived from 24-hour PWA, according to outcome data, and will also provide supporting evidence for the inclusion of this type of evaluation in hypertension management. Trial registration: Clinicaltrials.gov NCT02577835; https://clinicaltrials.gov/ct2/show/NCT02577835 (Archived by WebCite at http://www.Webcitation.org/6hzZBKY2Q) [JMIR Res Protoc 2016;5(2):e137]

The early use of triptan in combination with a nonsteroidal anti-inflammatory drug after headache onset may improve the efficacy of acute migraine treatment. In this retrospective analysis of a randomized, double-blind, parallel group study, we assessed the efficacy of early or late intake of frovatriptan 2.5 mg + dexketoprofen 25 or 37.5 mg (FroDex 25 and FroDex 37.5) vs. frovatriptan 2.5 mg alone (Frova) in the acute treatment of migraine attacks. In this double-blind, randomized parallel group study 314 subjects with acute migraine with or without aura were randomly assigned to Frova, FroDex 25, or FroDex 37.5. Pain free (PF) at 2-h (primary endpoint), PF at 4-h and pain relief (PR) at 2 and 4-h, speed of onset at 60, 90, 120 and 240-min, and sustained pain free (SPF) at 24-h were compared across study groups according to early (≤1-h; n = 220) or late (>1-h; n = 59) intake. PF rates at 2 and 4-h were significantly larger with FroDex 37.5 vs. Frova (early intake, n = 71 FroDex 37.5 and n = 75 Frova: 49 vs. 32 % and 68 vs. 52 %, p < 0.05; late intake, n = 20 Frodex 37.5, and n = 18 Frova: 55 vs. 17 %, p < 0.05 and 85 vs. 28 %, p < 0.01). Also with FroDex 25, in the early intake group (n = 74) PF episodes were significantly higher than Frova. PR at 2 and 4-h was significantly better under FroDex 37.5 than Frova (95 % vs. 50 %, p < 0.001, 100 % vs. 72 %, p < 0.05) in the late intake group (n = 21). SPF episodes at 24-h after early dosing were 25 % (Frova), 45 % (FroDex 25) and 41 % (FroDex 37.5, p < 0.05 combinations vs. monotherapy), whereas they were not significantly different with late intake. All treatments were equally well tolerated. FroDex was similarly effective regardless of intake timing from headache onset.

The present paper provides an update of previous recommendations on Home Blood Pressure Monitoring from the European Society of Hypertension (ESH) Working Group on Blood Pressure Monitoring and Cardiovascular Variability sequentially published in years 2000, 2008 and 2010. This update has taken into account new evidence in this field, including a recent statement by the American Heart association, as well as technological developments, which have occurred over the past 20 years. The present document has been developed by the same ESH Working Group with inputs from an international team of experts, and has been endorsed by the ESH. ispartof: JOURNAL OF HYPERTENSION vol:39 issue:9 pages:1742-1767 ispartof: location:Netherlands status: published

BACKGROUND: In SMILE-4 (the Survival of Myocardial Infarction Long-term Evaluation 4 study), zofenopril + acetylsalicylic acid (ASA) was superior to ramipril + ASA in reducing the occurrence of major cardiovascular events in patients with left ventricular dysfunction following acute myocardial infarction. The present post hoc analysis was performed to compare the cost-effectiveness of zofenopril and ramipril. METHODS: In total, 771 patients with left ventricular dysfunction and acute myocardial infarction were randomized in a double-blind manner to receive zofenopril 60 mg/day (n = 389) or ramipril 10 mg/day (n = 382) + ASA 100 mg/day and were followed up for one year. The primary study endpoint was the one-year combined occurrence of death or hospitalization for cardiovascular causes. The economic analysis was based on evaluation of cost of medications and hospitalizations and was applied to the intention-to-treat population (n = 716). Cost data were drawn from the National Health Service databases of the European countries participating in the study. The incremental cost-effectiveness ratio was used to quantify the cost per event prevented with zofenopril versus ramipril. RESULTS: Zofenopril significantly (P = 0.028) reduced the risk of the primary study endpoint by 30% as compared with ramipril (95% confidence interval, 4%-49%). The number needed to treat to prevent a major cardiovascular event with zofenopril was 13 less than with ramipril. The cost of drug therapies was higher with zofenopril (328.78 Euros per patient per year, n = 365) than with ramipril (165.12 Euros per patient per year, n = 351). The cost related to the occurrence of major cardiovascular events requiring hospitalization averaged 4983.64 Euros for zofenopril and 4850.01 Euros for ramipril. The incremental cost-effectiveness ratio for zofenopril versus ramipril was 2125.45 Euros per event prevented (worst and best case scenario in the sensitivity analysis was 3590.09 and 3243.96 Euros, respectively). CONCLUSION: Zofenopril is a viable and cost-effective treatment for managing patients with left ventricular dysfunction after acute myocardial infarction.

The extensive use of angiotensin-converting enzyme inhibitors (ACEIs) as antihypertensive agents and the huge amount of data collected in clinical trials and post-marketing studies has allowed the extending of the indication of ACEIs beyond blood pressure control. Current guidelines recommend ACEIs in symptomatic patients with heart failure with reduced ejection fraction to decrease the risk of heart failure hospitalization, and also in patients after acute myocardial infarction (AMI) with ST-elevation with or without post-AMI ventricular dysfunction. Analyzing the association between the choice of an ACEI after AMI with the risk of mortality and re-infarction, a class effect, rather than the superiority of some agents, has been described. The focus of this review is centered on the role of ACEIs in addition to and beyond blood pressure control. It summarizes clinical evidence on the use of these agents in cardiovascular diseases, with a specific interest in the experience with zofenopril, which presents a peculiar pharmacological profile that may contribute to additional clinical benefits in some identifiable populations of patients. Indeed, the presence of a sulfhydryl group in its structure confers on zofenopril high anti-oxidant and anti-ischemic properties involving the activation of the H2S system, resulting in a cardioprotective effect. The efficacy and safety of zofenopril have been extensively evaluated and proved in the Survival of Myocardial Infarction Long-Term Evaluation (SMILE) program in numerous clinical settings. The pharmacological features and ancillary characteristics of zofenopril with potent cardioprotective effects seem to differentiate it from other ACEIs and to confer further benefits to patients.

Objective: To evaluate the impact of olmesartan alone or combined with one to three antihypertensive drugs on 24-h blood pressure variability (BPV) and on distribution of BP reduction in a pooled individual data analysis of 10 doubleblind, randomized, ambulatory BP monitoring (ABPM) studies. Methods: ABPMs were performed before and after 6-12 weeks of treatment with placebo (n=119), active control monotherapy [n=1195, angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), dihydropyridine calcium channel blockers (DCCBs)] olmesartan monotherapy (n=1410), active control dual combination [n=79, DCCBRthiazide diuretic (TD)], olmesartan dual combination (n=637, DCCB or TD), and triple combination therapy (n=102, DCCBRTD). 24-h BPV was calculated as unweighted or weighted SD of the mean BP, and average real variability. BP control was assessed by smoothness index and treatment-on-variability index. Results: The greatest effect on 24-h systolic BPV/diastolic BPV was observed under olmesartan triple [-2.6/-1.9;-1.9/-1.3;-1.4/-1.3mmHg] and active control dual combination [-1.8/-1.4;-1.9/-1.5; 1.2/1.1 mmHg]. Smoothness indexes and treatment-on-variability indexes were significantly (P=0.0001) higher under olmesartan dual (1.53/1.22, 1.67/1.29, 2.05/1.59), olmesartan triple (2.47/1.85, 2.80/2.06, 3.64/2.67), or active control dual combination (1.70/1.26, 1.85/1.33, 2.29/1.65) than under monotherapies (control: 0.86/0.73, 0.80/0.65, 1.01/0.82; olmesartan: 1.02/0.86, 0.95/0.78, 1.23/1.00). They were also greater in patients receiving high-dose olmesartan monotherapy or high-dose olmesartan dual combination than in the corresponding low-dose group. Conclusion: Olmesartan plus a DCCB and/or a TD produces a larger, more sustained, and smoother BP reduction than placebo and monotherapies, a desirable feature for a more effective prevention of the cardiovascular consequences of uncontrolled hypertension. Keywords: Ambulatory blood pressure monitoring, arterial hypertension, blood pressure, blood pressure variability, olmesartan, smoothness index, treatment-on-variability index. sTrough-To-peak Ratio.

BACKGROUND The analysis of ambulatory blood pressure monitorings (ABPMs) performed in 639 Italian pharmacies in the context of a telehealth-based service allowed to evaluate the level of blood pressure (BP) control in the community. METHODS Twenty-four-hour ABPMs were performed by a clinically validated, automated, upper-arm BP monitor. Recordings were uploaded on a certified web-based telemedicine platform (www.tholomeus.net) and remote medical reporting provided. In each subject, an automatic BP measurement was obtained in the pharmacy and clinical information collected before starting the ABPM. RESULTS A total of 20,773 subjects (mean age 57 ± 15 years; 54% females; 28% receiving antihypertensive medications, 31% with any cardiovascular [CV] risk factor) provided valid ABPMs. BP control was poor, but better in ambulatory conditions (24-hour BP CONCLUSIONS A telemedicine-based service provided to community pharmacies may facilitate access to ABPM, thus favoring a more accurate hypertension screening and detection. It may also help describe the occurrence of different 24-hour BP phenotypes and personalize the physician’s intervention.

Introduction Masked uncontrolled hypertension (MUCH) carries an increased risk of cardiovascular (CV) complications and can be identified through combined use of office (O) and ambulatory (A) blood pressure (BP) monitoring (M) in treated patients. However, it is still debated whether the information carried by ABPM should be considered for MUCH management. Aim of the MASked-unconTrolled hypERtension management based on OBP or on ambulatory blood pressure measurement (MASTER) Study is to assess the impact on outcome of MUCH management based on OBPM or ABPM. Methods and analysis MASTER is a 4-year prospective, randomised, open-label, blinded-endpoint investigation. A total of 1240 treated hypertensive patients from about 40 secondary care clinical centres worldwide will be included -upon confirming presence of MUCH (repeated on treatment OBP

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. 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.

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 (

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.

Office blood pressure measurement has been the basis for hypertension evaluation for almost a century. However, the evaluation of blood pressure out of the office using ambulatory or self-home monitoring is now strongly recommended for the accurate diagnosis in many, if not all, cases with suspected hypertension. Moreover, there is evidence that the variability of blood pressure might offer prognostic information that is independent of the average blood pressure level. Recently, advancement in technology has provided noninvasive evaluation of central (aortic) blood pressure, which might have attributes that are additive to the conventional brachial blood pressure measurement. This position statement, developed by international experts, deals with key research and practical issues in regard to peripheral blood pressure measurement (office, home, and ambulatory), blood pressure variability, and central blood pressure measurement. The objective is to present current achievements, identify gaps in knowledge and issues concerning clinical application, and present relevant research questions and directions to investigators and manufacturers for future research and development (primary goal).

Background Self-monitoring of blood pressure (BP) appears to reduce BP in hypertension but important questions remain regarding effective implementation and which groups may benefit most. This individual patient data (IPD) meta-analysis was performed to better understand the effectiveness of BP self-monitoring to lower BP and control hypertension. Methods and findings Medline, Embase, and the Cochrane Library were searched for randomised trials comparing self-monitoring to no self-monitoring in hypertensive patients (9June 2016). Two reviewers independently assessed articles for eligibility and the authors of eligible trials were approached requesting IPD. Of 2,846 articles in the initial search, 36 were eligible. IPD were provided from 25 trials, including 1 unpublished study. Data for the primary outcomes-change in mean clinic or ambulatory BP and proportion controlled below target at 12 months-were available from 15/19 possible studies (97,138/8,292 [86%] of randomised participants). Overall, self-monitoring was associated with reduced clinic systolic blood pressure (9sBP) compared to usual care at 12 months (-3.2 mmHg, [95% CI -4.9, -1.6 mmHg]). However, this effect was strongly influenced by the intensity of co-intervention ranging from no effect with self-monitoring alone (-1.0 mmHg [-3.3, 1.2]), to a 6.1 mmHg (-9.0, -3.2) reduction when monitoring was combined with intensive support. Self-monitoring was most effective in those with fewer antihypertensive medications and higher baseline sBP up to 170 mmHg. No differences in efficacy were seen by sex or by most comorbidities. Ambulatory BP data at 12 months were available from 4 trials (91,478 patients), which assessed selfmonitoring with little or no co-intervention. There was no association between self-monitoring and either lower clinic or ambulatory sBP in this group (9clinic -0.2 mmHg [-2.2, 1.8]; ambulatory 1.1 mmHg [-0.3, 2.5]). Results for diastolic blood pressure (9dBP) were similar. The main limitation of this work was that significant heterogeneity remained. This was at least in part due to different inclusion criteria, self-monitoring regimes, and target BPs in included studies. Conclusions Self-monitoring alone is not associated with lower BP or better control, but in conjunction with co-interventions (9including systematic medication titration by doctors, pharmacists, or patients; education; or lifestyle counselling) leads to clinically significant BP reduction which persists for at least 12 months. The implementation of self-monitoring in hypertension should be accompanied by such co-interventions., This research was funded by the Institute for Health Research School for Primary Care Research (NIHR SPCR number 112) and via an NIHR Professorship for RM (NIHR-RP-02-12-015). JS holds a Medical Research Council (MRC) Strategic Skills Postdoctoral Fellowship (MR/K022032/1). FDRH is part funded as Director of the National Institute for Health Research (NIHR) School for Primary Care Research (SPCR), Theme Leader of the NIHR Oxford Biomedical Research Centre (BRC), and Director of the NIHR Collaboration for Leadership in Applied Health Research and Care (CLAHRC) Oxford. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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

none 8 si Combinations between an angiotensin converting enzyme (ACE) inhibitor or an angiotensin 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 ≥1 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 office and ambulatory BPs after 18–24 weeks. In the ZODIAC study a larger reduction in high sensitivity C reactive protein (hs-CRP) was observed under zofenopril (−0.52 vs. +0.97 mg/dL under irbesartan, p = 0.001), suggesting a potential protective effect against the development of atherosclerosis. In the ZENITH study the rate of carotid plaque regression was significantly larger under zofenopril (32% vs. 16%; p = 0.047). In the diabetic patients of the ZAMES study, no adverse effects of treatments on blood glucose and lipids as well as an improvement of renal function were observed. In patients with isolated systolic hypertension of the ZEUS study, a slight and similar improvement in renal function and small reductions in pulse wave velocity (PWV), augmentation index (AI), and central systolic BP were documented with both treatments. Thus, the fixed combination of zofenopril and HCTZ may have a relevant place in the treatment of high-risk or monotherapy-treated uncontrolled hypertensive patients requiring a more prompt, intensive, and sustained BP reduction, in line with the recommendations of current guidelines. none Omboni, Stefano; Malacco, Ettore; Napoli, Claudio; Modesti, Pietro Amedeo; Manolis, Athanasios; Parati, Gianfranco; Agabiti-Rosei, Enrico; Borghi, Claudio Omboni, Stefano; Malacco, Ettore; Napoli, Claudio; Modesti, Pietro Amedeo; Manolis, Athanasios; Parati, Gianfranco; Agabiti-Rosei, Enrico; Borghi, Claudio

Given the increasing use of ambulatory blood pressure monitoring (ABPM) in both clinical practice and hypertension research, a group of scientists, participating in the European Society of Hypertension Working Group on blood pressure monitoring and cardiovascular variability, in year 2013 published a comprehensive position paper dealing with all aspects of the technique, based on the available scientific evidence for ABPM. The present work represents an updated schematic summary of the most important aspects related to the use of ABPM in daily practice, and is aimed at providing recommendations for proper use of this technique in a clinical setting by both specialists and practicing physicians. The present article details the requirements and the methodological issues to be addressed for using ABPM in clinical practice, The clinical indications for ABPM suggested by the available studies, among which white-coat phenomena, masked hypertension, and nocturnal hypertension, are outlined in detail, and the place of home measurement of blood pressure in relation to ABPM is discussed. The role of ABPM in pharmacological, epidemiological, and clinical research is also briefly mentioned. Finally, the implementation of ABPM in practice is considered in relation to the situation of different countries with regard to the reimbursement and the availability of ABPM in primary care practices, hospital clinics, and pharmacies. ispartof: Journal of Hypertension vol:32 issue:7 pages:1359-1366 ispartof: location:Netherlands status: published

Introduction. The accuracy of impedance cardiography for cardiac index assessment is matter of debate, with available studies reporting inconsistent results. Our study aimed at evaluating the agreement between measurements of cardiac index provided by a new-generation thoracic electrical bioimpedance device (Hotman System) and an invasive approach based on thermodilution in humans. Methods. Cardiac index was assessed simultaneously with thoracic electrical bioimpedance and conventional thermodilution through comparison of five consecutive measurements in 51 cardiac patients, hospitalized in an intensive care unit (mean± SD age: 60 ± 11 years; 68% males). The agreement between cardiac index values measured by both methods was assessed by the Bland-Altman approach, adjusted for repeated measures. The repeatability coefficient and the intraclass correlation coefficient were used to assess reproducibility of replicates. Results. Average (± SD) cardiac index was 3.05 ± 0.91 l/min/m2 with Hotman System and 3.14 ± 1.12 l/min/m2 with thermodilution. The bias of precision was-0.09 ± 0.41. The coefficients of repeatability and intraclass correlation coefficients were high and similar for the two techniques (0.95 l/min/m 2 and 0.91 for Hotman System vs 0.78 l/min/m2 and 0.90 for thermodilution). Conclusions. Cardiac index values yielded by Hotman system compares favorably with that obtained with thermodilution in cardiac patients. © 2014 Scandinavian Foundation for Cardiovascular Research.

Objective: To systematically review data from randomized controlled studies on the effectiveness of home blood pressure telemonitoring (HBPT) versus usual care with respect to improvement of BP control, healthcare resources utilization and costs, patient's quality of life and adverse events. Methods: Electronic databases were searched for publications in English. The benefit and relative risk (RR) were estimated applying a random-effect model. Results: Twenty-three randomized controlled trials with a high level of heterogeneity were selected (7037 patients). Compared to usual care, HBPT improved office SBP by 4.71 mmHg [95% confidence interval (CI): 6.18, 3.24; P < 0.001] and DBP by 2.45mmHg (3.33, 1.57; P < 0.001). A larger proportion of patients achieved office BP normalization (

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 57-14 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

Over the last decades, 2 main techniques for measuring blood pressure (BP) out of the physician’s office have gained increasing importance in the clinical approach to arterial hypertension, both being supported by recent international hypertension management guidelines.1,2 These techniques are home BP monitoring (HBPM) and 24-hour ambulatory BP monitoring (ABPM). Their diffusion in clinical practice has been favored by a number of factors, including on one side technical progress and wider availability of accurate HBPM and ABPM devices and on the other side the increasing awareness of the limitations of office BP (Table 1).3,4 Office BP is in fact characterized by a random error affecting casual BP readings and by a systematic error related to the patient’s alerting reaction to the measurement procedure and setting, known as “white coat effect.”1,3 Both ABPM and HBPM are devoid of these limitations and, thus, provide more stable and reproducible information on BP values,5 which is also of greater prognostic relevance6–21 (Table 2). Furthermore, office BP readings are unable to collect information on BP during a subject’s usual activities and over a long period of time,22 an important limitation in everyday management of hypertensive subjects that can be overcome by out-of-office BP monitoring. View this table: Table 1. Comparison of Main Features of 3 Main Methods of BP Measurement View this table: Table 2. Home BP Measurements and Outcome ABPM was initially confined to specialized hypertension centers because of its relatively high cost, but over the years its availability has steadily increased. HBPM, on the other hand, has been used rather reluctantly by physicians in routine management of hypertensive patients. Although its potential usefulness in clinical practice was acknowledged many years ago,23 its application has been limited until the end of last century by the need to use auscultatory measurements, an approach …

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

Morning blood pressure (BP) surge has been reported to be a prognostic factor for cardiovascular events. Its determinants are still poorly defined, however. In particular, it is not clear whether ethnic differences play a role in determining morning surge (MS) size. Aim of our study was to explore whether differences exist in the size of MS between Japanese and Western European hypertensive patients. We included 2887 untreated hypertensive patients (age 62.3±8.8 years) from a European ambulatory BP monitoring database and 811 hypertensive patients from a Japanese database (Jichi Medical School Ambulatory Blood Pressure Monitoring WAVE1, age 72.3±9.8 years) following the same inclusion criteria. Their 24-hour ambulatory BP monitoring recordings were analyzed focusing on MS. Sleep-trough MS was defined as the difference between mean systolic BP during the 2 hours after awakening and mean systolic BP during the 1-hour night period that included the lowest sleep BP level. The sleep-trough MS was higher in Japanese than in European hypertensive patients after adjusting for age and 24-hour mean BP levels (40.1 [95% confidence interval 39.0–41.2] versus 23.0 [22.4–23.5] mm Hg; P

This paper aims to provide practical indications to healthcare professionals and manufacturers of ambulatory blood pressure monitoring (ABPM) devices on the characteristics and minimum required contents of a standard ABPM report to be used in the clinical practice. Such indications will help make ABPM reports more easily interpretable and independent from the ABPM device and software used. The first important and unavoidable step of ABPM reporting is a quality assessment: if a recording does not meet the minimum requirements for quality criteria, the reporting physician should advise the patient to repeat the test and should not further proceed to a diagnostic evaluation and interpretation of the recording. A basic clinical report must contain the list of each single reading, the graphical display of individual readings and hourly average values, the mean, minimum and maximum values, and SDs of blood pressure and heart rate values for the 24 h, daytime and night-time, day-night differences, and blood pressure loads. The final medical report should be prepared in a quite logically structured way, considering the following: (i) a judgment on the overall quality of the 24 h recording; (ii) an indication of whether average 24 h, daytime and night-time systolic, and diastolic blood pressure values are within or above the normal limits; and (iii) a description of the 24 h pattern of blood pressure fluctuations. A final general statement on the normotensive or hypertensive status and on the degree of blood pressure control in case of treated patients should also be provided.

Objectives The International Nifedipine GITS Study Intervention as a Goal in Hypertension Treatment (INSIGHT) showed, by means of office blood pressure measurements, that long-term treatment with nifedipine GITS is as effective as diuretics in preventing cardiovascular and cerebrovascular complications. However, since office blood pressure measurements reflect to a limited extent blood pressure outside the office, a side-arm INSIGHT study in which patients underwent both office measurement and 24 h ambulatory blood pressure monitoring was also performed. Design and methods The study had a randomized, double-blind, parallel group design. After 4 weeks of placebo, mild-to-moderate essential hypertensive patients were randomized to nifedipine GITS 30 mg or amiloride 2.5 + hydrochlorothiazide 5 mg for 3.1 years. Dose titration was performed by dose doubling and addition of atenolol 25–50 mg or enalapril 5–10 mg, or other drugs when needed. Analysis was carried out by intention-to-treat and included computation of 24 h, day and night ambulatory blood pressure and heart rate values. Additional analyses included computation of the trough-to-peak ratio and the smoothness index (the ratio between the average of the 24-hourly blood pressure reductions after treatment and its standard deviation). Results A total of 151 patients were recruited and 149 were valid for analysis: 78 patients had 24 h ambulatory recordings both at baseline and during treatment and 134 during treatment. Office, 24 h and day and night blood pressures were all significantly and similarly reduced by both treatments. Office and ambulatory heart rate was left unchanged by diuretics, while it was slightly reduced by nifedipine. Median trough-to-peak ratios were always > 0.5 and superimposable between the two treatment groups. Similarly, smoothness indices of systolic and diastolic blood pressures were comparably high for nifedipine and diuretics, thus demonstrating a similar well-balanced antihypertensive response to both drugs. No significant differences were observed between the two treatment groups in the number of cardiovascular events (17 in the nifedipine-based and 26 in the diuretics-based treatment group). Conclusions In the INSIGHT study, the long-term antihypertensive effect on 24 h blood pressure and the cardiovascular protection of nifedipine was similar to that of diuretics.

Background: the SMILE studies proved the prognostic benefit of zofenopril vs. placebo or other ACE-inhibitors (ACEIs) in post-acute myocardial infarction (AMI). In this retrospective pooled analysis of these studies we assessed whether the zofenopril effect is influenced by gender. Methods the four double-blind, randomized, parallel-group SMILE studies, compared the efficacy and safety of 6–48 week treatment with zofenopril 60 mg/day with that of placebo, lisinopril 10 mg/day or ramipril 10 mg/day in 3630 AMI patients. This pooled analysis compared treatment efficacy (1-year combined occurrence of death or hospitalization for CV causes) in 2733 men and 897 women. Results women were older than men, had a higher prevalence of diabetes and of other major CV risk factors. The risk of a major CV event was significantly larger for women (23% vs. 17% men, pConclusions post-AMI women are at higher risk of CV complications than men, particularly when living in Mediterranean countries. Their response to ACE-inhibition varies according to the type of drug and is usually better in men.

Background Baseline data from the European Lacidipine Study on Atherosclerosis (ELSA) have shown that carotid intima-media thickness (IMT) is not related to diastolic blood pressure (BP), but that it is related to clinic systolic (S) or pulse pressure (PP) and more so to their 24 h average values. The aim of the present study was to determine whether IMT independently relates to additional information obtained through ambulatory BP, in particular to SBP or PP variability. Methods and results In 1663 hypertensive patients, after a wash-out period from antihypertensive treatment (mean age 56.2 +/- 7.65 years), IMT was assessed from 12 different carotid sites. Ambulatory BP measurements were performed every 15 min (day) and every 20 min (night). IMT values were positively related to 24 h, day and night average SBP and PP. There was some relationship of IMT with day-night or clinic-day SBP and PP differences. The most important finding, however, was that IMT values were related with 24 h SBP or PP standard deviation (P < 0.001), a measure of overall SBP or PP variability. The relationship was seen also by multiple regression analysis, the standard deviation for SBP or PP only following age and 24 h average SBP or PP in accounting for IMT values. Conclusions This is the first demonstration from a large database that not only average 24 h PP and SBP values, but also 24 h BP fluctuations, are associated with, and possibly determinants of, the alterations of large artery structure in hypertension. (C) 2001 Lippincott Williams & Wilkins.

Background and aims The Hypertension Optimal Treatment (HOT) study showed that when antihypertensive treatment reduces diastolic blood pressure well below 90 mmHg, there can be a further reduction of cardiovascular events, particularly myocardial infarction, with no evidence of a J-shaped curve at lower pressures. Office measurement however, gives no information about blood pressure outside the office. This paper describes a HOT substudy in which patients underwent both office measurement and 24 h ambulatory blood pressure monitoring. Methods The mean age of the substudy population was 62 +/- 7 years. Substudy patients were treated for a median period of 2 years. All received the dihydropyridine calcium antagonist felodipine, while some also received an ACE-inhibitor, a beta-blocker or a diuretic. Average 24 h, day and night ambulatory blood pressure values were computed at baseline (n = 277) and during treatment (n = 347): 112 patients had been randomized to a target office diastolic blood pressure less than or equal to 90 mmHg, 117 to less than or equal to 85 mmHg and 118 to less than or equal to 80 mmHg. Additional analyses included computation of: (1) trough-to-peak ratio and (2) the smoothness index (the ratio between the average of the 24 hourly blood pressure reductions after treatment and its standard deviation). Results Taking the subgroup as a whole, baseline 24 h average blood pressures (146 +/- 18/90 +/- 10 mmHg) were significantly and markedly lower than office blood pressures (170 +/- 14/105 +/- 3 mmHg, P

Ambulatory blood pressure monitoring (ABPM) is being used increasingly in both clinical practice and hypertension research. Although there are many guidelines that emphasize the indications for ABPM, there is no comprehensive guideline dealing with all aspects of the technique. It was agreed at a consensus meeting on ABPM in Milan in 2011 that the 34 attendees should prepare a comprehensive position paper on the scientific evidence for ABPM.This position paper considers the historical background, the advantages and limitations of ABPM, the threshold levels for practice, and the cost-effectiveness of the technique. It examines the need for selecting an appropriate device, the accuracy of devices, the additional information and indices that ABPM devices may provide, and the software requirements.At a practical level, the paper details the requirements for using ABPM in clinical practice, editing considerations, the number of measurements required, and the circumstances, such as obesity and arrhythmias, when particular care needs to be taken when using ABPM.The clinical indications for ABPM, among which white-coat phenomena, masked hypertension, and nocturnal hypertension appear to be prominent, are outlined in detail along with special considerations that apply in certain clinical circumstances, such as childhood, the elderly and pregnancy, and in cardiovascular illness, examples being stroke and chronic renal disease, and the place of home measurement of blood pressure in relation to ABPM is appraised.The role of ABPM in research circumstances, such as pharmacological trials and in the prediction of outcome in epidemiological studies is examined and finally the implementation of ABPM in practice is considered in relation to the issue of reimbursement in different countries, the provision of the technique by primary care practices, hospital clinics and pharmacies, and the growing role of registries of ABPM in many countries. ispartof: Journal of Hypertension vol:31 issue:9 pages:1731-68 ispartof: location:Netherlands status: published

Claudio Borghi,1 Ettore Ambrosioni,1 Stefano Omboni,2 Arrigo FG Cicero,1 Stefano Bacchelli,1 Daniela Degli Esposti,1 Salvatore Novo,3 Dragos Vinereanu,4 Giuseppe Ambrosio,5 Giorgio Reggiardo,6 Dario Zava7 1Unit of Internal Medicine, Policlinico S Orsola, University of Bologna, Bologna, Italy; 2Italian Institute of Telemedicine, Varese, Italy; 3Division of Cardiology, University of Palermo, Palermo, Italy; 4University and Emergency Hospital, Bucharest, Romania; 5Division of Cardiology, University of Perugia, Perugia, Italy; 6Mediservice, Milano, Italy; 7Istituto Lusofarmaco d'Italia SpA, Peschiera Borromeo, Italy Background: In SMILE-4 (the Survival of Myocardial Infarction Long-term Evaluation 4 study), zofenopril + acetylsalicylic acid (ASA) was superior to ramipril + ASA in reducing the occurrence of major cardiovascular events in patients with left ventricular dysfunction following acute myocardial infarction. The present post hoc analysis was performed to compare the cost-effectiveness of zofenopril and ramipril. Methods: In total, 771 patients with left ventricular dysfunction and acute myocardial infarction were randomized in a double-blind manner to receive zofenopril 60 mg/day (n = 389) or ramipril 10 mg/day (n = 382) + ASA 100 mg/day and were followed up for one year. The primary study endpoint was the one-year combined occurrence of death or hospitalization for cardiovascular causes. The economic analysis was based on evaluation of cost of medications and hospitalizations and was applied to the intention-to-treat population (n = 716). Cost data were drawn from the National Health Service databases of the European countries participating in the study. The incremental cost-effectiveness ratio was used to quantify the cost per event prevented with zofenopril versus ramipril. Results: Zofenopril significantly (P = 0.028) reduced the risk of the primary study endpoint by 30% as compared with ramipril (95% confidence interval, 4%–49%). The number needed to treat to prevent a major cardiovascular event with zofenopril was 13 less than with ramipril. The cost of drug therapies was higher with zofenopril (328.78 Euros per patient per year, n = 365) than with ramipril (165.12 Euros per patient per year, n = 351). The cost related to the occurrence of major cardiovascular events requiring hospitalization averaged 4983.64 Euros for zofenopril and 4850.01 Euros for ramipril. The incremental cost-effectiveness ratio for zofenopril versus ramipril was 2125.45 Euros per event prevented (worst and best case scenario in the sensitivity analysis was 3590.09 and 3243.96 Euros, respectively). Conclusion: Zofenopril is a viable and cost-effective treatment for managing patients with left ventricular dysfunction after acute myocardial infarction. Keywords: acute myocardial infarction, left ventricular dysfunction, angiotensin-converting enzyme inhibitors, zofenopril, ramipril, acetylsalicylic acid, cost-effectiveness

Background Inadequate blood pressure control and poor adherence to treatment remain among the major limitations in the management of hypertensive patients, particularly of those at high risk of cardiovascular events. Preliminary evidence suggests that home blood pressure telemonitoring (HBPT) might help increasing the chance of achieving blood pressure targets and improve patient’s therapeutic adherence. However, all these potential advantages of HBPT have not yet been fully investigated. Methods/design The purpose of this open label, parallel group, randomized, controlled study is to assess whether, in patients with high cardiovascular risk (treated or untreated essential arterial hypertension - both in the office and in ambulatory conditions over 24 h - and metabolic syndrome), long-term (48 weeks) blood pressure control is more effective when based on HBPT and on the feedback to patients by their doctor between visits, or when based exclusively on blood pressure determination during quarterly office visits (conventional management (CM)). A total of 252 patients will be enrolled and randomized to usual care (n=84) or HBPT (n=168). The primary study endpoint will be the rate of subjects achieving normal daytime ambulatory blood pressure targets ( Discussion The TELEBPMET Study will show whether HBPT is effective in improving blood pressure control and related medical and economic outcomes in hypertensive patients with metabolic syndrome. It will also provide a comprehensive understanding of the psychological determinants of medication adherence and blood pressure control of these patients. Trial registration Clinical Trials.gov: NCT01541566

An increased rate of cardiovascular and cerebrovascular events has been described during and immediately after earthquakes. In this regard, few data are available on long-term blood pressure control in hypertensive outpatients after an earthquake. We evaluated the long-term effects of the April 2009 L’Aquila earthquake on blood pressure levels, as detected by 24 h ambulatory blood pressure monitoring. Before/after (mean±s.d. 6.9±4.5/14.2±5.1 months, respectively) the earthquake, the available 24 h ambulatory blood pressure monitoring data for the same patients were extracted from our database. Quake-related daily life discomforts were evaluated through interviews. We enrolled 47 patients (25 female, age 52±14 years), divided into three groups according to antihypertensive therapy changes after versus before the earthquake: unchanged therapy (n=24), increased therapy (n=17) and reduced therapy (n=6). Compared with before the quake, in the unchanged therapy group marked increases in 24 h (P=0.004), daytime (P=0.01) and nighttime (P=0.02) systolic blood pressure were observed after the quake. Corresponding changes in 24 h (P=0.005), daytime (P=0.01) and nighttime (P=0.009) diastolic blood pressure were observed. Daily life discomforts were reported more frequently in the unchanged therapy and increased therapy groups than the reduced therapy group (P=0.025 and P=0.018, respectively). In conclusion, this study shows that patients with unchanged therapy display marked blood pressure increments up to more than 1 year after an earthquake, as well as long-term quake-related discomfort. Our data suggest that particular attention to blood pressure levels and adequate therapy modifications should be considered after an earthquake, not only early after the event but also months later.

OBJECTIVE: Cough is a typical side effect of angiotensin-converting enzyme (ACE) inhibitors, though its frequency quantitatively varies among the different compounds. Data on the incidence of cough with the lipophilic third-generation ACE inhibitor zofenopril are scanty and never systematically analyzed. The purpose of this paper is to give an overview on the epidemiology, pathophysiology, and treatment of ACE inhibitor-induced cough and to assess the incidence of cough induced by zofenopril treatment. METHODS: Published and unpublished data from randomized and postmarketing zofenopril trials were merged together and analyzed. RESULTS: Twenty-three studies including 5794 hypertensive patients and three studies including 1455 postmyocardial infarction patients exposed for a median follow-up time of 3 months to zofenopril at doses of 7.5-60 mg once-daily were analyzed. The incidence of zofenopril-induced cough was 2.6% (range 0%-4.2%): 2.4% in the hypertension trials (2.4% in the double-blind randomized studies and 2.4% in the open-label postmarketing studies) and 3.6% in the doubleblind randomized postmyocardial infarction trials. Zofenopril-induced cough was generally of a mild to moderate intensity, occurred significantly (P < 0.001) more frequently in the first 3-6 months of treatment (3.0% vs 0.2% 9-12 months), and always resolved or improved upon therapy discontinuation. Zofenopril doses of 30 mg and 60 mg resulted in significantly (P = 0.042) greater rate of cough (2.1% and 2.6%, respectively) than doses of 7.5 mg and 15 mg (0.4% and 0.7%, respectively). In direct comparison trials (enalapril and lisinopril), incidence of cough was not significantly different between zofenopril and other ACE inhibitors (2.4% vs 2.7%). CONCLUSION: Evidence from a limited number of studies indicates a relatively low incidence of zofenopril-induced cough. Large head-to-head comparison studies versus different ACE inhibitors are needed to highlight possible differences between zofenopril and other ACE inhibitors in the incidence of cough.

The objective of this study was to evaluate patients’ satisfaction with acute treatment of migraine with frovatriptan or almotriptan by preference questionnaire. One hundred and thirty three subjects with a history of migraine with or without aura (IHS 2004 criteria), with at least one migraine attack in the preceding 6 months, were enrolled and randomized to frovatriptan 2.5 mg or almotriptan 12.5 mg, treating 1–3 attacks. The study had a multicenter, randomized, double blind, cross-over design, with treatment periods lasting

The objective of the study is to systematically review the efficacy and safety of frovatriptan (F) versus rizatriptan (R), zolmitriptan (Z) and almotriptan (A), through a pooled analysis of three individual studies. 414 subjects with a history of migraine with or without aura (IHS criteria) were randomized to F 2.5 mg or R 10 mg (study 1), F 2.5 mg or Z 2.5 mg (study 2), and F 2.5 mg or A 12.5 mg (study 3). The studies had an identical multicenter, randomized, double blind, cross-over design, with each of the two treatment periods lasting not more than 3 months. The number of pain free (PF) and pain relief (PR) episodes at 2 h, and the number of sustained pain free (SPF) and recurrent episodes within the 48 h were the efficacy endpoints. 346 patients were included in the intention-to-treat analysis. Rate of PF episodes at 2 h was 30% with F and 34% with comparators (p = NS). PR episodes at 2 h were 55% for F and 59% for comparators (p = NS). SPF episodes at 48 h were also similar between the two groups (22% F vs. 21% comparators). Rate of recurrence was significantly (p < 0.001) lower under F (27 vs. 40% comparators). Drug-related adverse events were significantly (p < 0.05) less under F, particularly cardiovascular symptoms. Our systematic analysis of individual studies suggests that F has a similar immediate efficacy, but a more sustained effect and a better tolerability than R, Z and A.

Dear Sir, We read with interest the comments of Dr. Tfelt-Hansen [1] on the two recently published randomized controlled trials comparing patients’ preference (primary end-point) and efficacy (secondary end-points) of frovatriptan with respect to rizatriptan [2] and almotriptan [3]. In both studies, frovatriptan showed similar preference and short-term efficacy outcomes (pain relief and pain free episodes at 2 h) with respect to the other two triptans. The principal concern of Dr. Tfelt-Hansen was the very early use of frovatriptan in these studies, making their results hardly comparable with those of previous randomized controlled trials [4–6], where patients waited until the headache was moderate or severe. In our studies [2, 3], patients were instructed to take one dose of study medication as early as possible after the onset of migraine and to treat at least 1 out of three attacks, but severity of headache at the time of drug intake was in the majority of patients moderate or severe. As a matter of fact, in the study by Savi et al. [2] 78% of attacks treated with frovatriptan and 74% of those treated with rizatriptan were of moderate or severe intensity. In the study by Bartolini et al. [3] 80% of overall treated attacks were of moderate or severe intensity and 97% of patients had at least one moderate or severe attack. However, these studies had a cross-over design and thus the same patient was treated with both drugs in a randomized sequence. Moreover, early treatment in our studies better reflects reality compared to the artificial design of other studies where patients usually start treatment when the attack intensity becomes moderate or severe. Thus, the results of our studies are much more consistent than those of randomized controlled studies with a parallel group design. In addition, the most significant result of our studies was a more sustained relieving effect on migraine symptoms with frovatriptan, with lower headache recurrence rates over the 48 h; these results are in line with previous reports comparing frovatriptan with placebo [7–9] or sumatriptan [10].

Background: Increasing the dose or adding a second antihypertensive agent are 2 possible therapeutic choices when blood pressure (BP) is poorly controlled with monotherapy.Objective: This study investigated the effectiveness and tolerability of barnidipine 10 or 20 mg added to losartan 50 mg versus losartan 100 mg alone in patients with mild to moderate essential hypertension whose BP was uncontrolled by losartan 50-mg monotherapy.Methods: This was a 12-week, multicenter, randomized, open-label, parallel-group study. Eligible patients (aged 30-74 years) had uncontrolled hypertension, defined as office sitting diastolic BP (DBP) 90 mm Hg and/or systolic BP (SBP) 140 mm Hg, and mean daytime DBP 85 mm Hg and/or SBP 135 mm Hg. All were being treated with losartan 50 mg at enrollment. After a 1-week run-in period while taking losartan 50 mg, patients were randomly assigned to 6 weeks of treatment with open-label barnidipine 10 mg plus losartan 50 mg or losartan 100-mg monotherapy. At the end of this period, patients with uncontrolled BP had barnidipine doubled to 20 mg and continued for an additional 6 weeks, whereas patients not achieving control on treatment with losartan 100 mg were discontinued. Office BP was measured at each visit, whereas 24-hour ambulatory BP monitoring (ABPM) was performed at randomization and at the final visit (ie, after 12 weeks of treatment, or at 6 weeks for patients not controlled on losartan 100 mg). The intent-to-treat population included all randomized patients who received at least one dose of study treatment and had valid ABPM recordings at baseline and the final visit. The primary end point was the change in daytime DBP between baseline and 12 weeks of treatment, compared between the combination treatment and monotherapy. Adverse events (AEs) were evaluated during each study visit.Results: A total of 93 patients were enrolled (age range, 30-75 years; 60% [56/93] men). After the 1-week run-in period, 68 patients were randomly assigned to 6 weeks of treatment with open-label barnidipine 10 mg plus losartan 50 mg (n = 34) or losartan 100-mg monotherapy (n = 34). A total of 53 patients were evaluable (barnidipine plus losartan, n = 28; losartan, n = 25). After 6 weeks of treatment, 18 patients in the combination treatment group (64.3%) had their dose of barnidipine doubled from 10 to 20 mg because BP was not normalized by treatment, whereas 8 patients in the losartan group (32.0%) were discontinued for the same reason. The between-treatment difference (losartan alone - combination treatment) for changes from baseline in daytime DBP was -1.7 mm Hg (95% CI, -5.8 to 2.4 mm Hg; P = NS). A similar result was observed for daytime SBP (-3.2 mm Hg; 95% CI, -8.1 to 1.7 mm Hg; P = NS). Likewise, no significant differences were found for nighttime values (mean [95% CI] DBP, 0.5 mm Hg [-3.7 to 4.7 mm Hg]; SBP, 1.5 mm Hg [-4.1 to 7.1 mm Hg]) or 24-hour values (DBP, -0.9 mm Hg [-4.8 to 2.9 mm Hg]; SBP, -1.6 mm Hg [-5.9 to 2.7 mm Hg]). Combination treatment was associated with a significantly higher rate of SBP responder patients (ie

Background Conventional calculation of mean 24-h ambulatory blood pressure (BP), SBP and DBP based on the average of all BP readings disregards the fact that a larger number of measurements is usually scheduled during the daytime than at night, an imbalance possibly leading to an overestimation of 24-h average BP. The aim of our study was to quantify this possible bias and to explore its determinants.Methods Four hundred and fifty untreated individuals were subdivided into three groups (150 individuals each) with three different ambulatory blood pressure measurement schedules for day/night: group I, four (day)/two (night) readings/h; group II, four (day)/three (night) readings/h; and group III, with BP readings every 30 min throughout 24 h. Hourly and 24-h averages were computed. The conventional 24-h averages of all SBP and DBP values were compared with the averages of hourly SBP and DBP mean values (time-weighted quantification). The difference between 24-h conventional and 24-h time-weighted BP was computed in each group and related to the degree of nocturnal BP dip and to the ratio between the number of readings of day and night.Result In the three groups, 24-h conventional and 24-h time-weighted BP values were highly correlated (r > 0.99), 24-h conventional SBP and DBP being significantly higher (P < 0.01) than the corresponding 24-h time-weighted values in groups I and II but not in group III (Bland-Altman analysis). The bias magnitude was related to the day/night ratio in number of readings and to nocturnal BP dip in groups I and II (P < 0.01) but not in group III.Conclusion The higher number of readings/h during daytime leads to an overestimation of conventional 24-h average BP, particularly in individuals with preserved nocturnal BP dipping. This can be avoided either by scheduling the same number of readings/h throughout 24 h or by performing a time-weighted quantification of 24-h BP. The clinical implications of these different approaches deserve further investigation. J Hypertens 28:459-464 (c) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

OBJECTIVE In essential hypertension, captopril attenuates forearm vasoconstriction reflexly induced by deactivation of cardiopulmonary and arterial baroreceptors, thus exerting a sympathomoderating effect. We investigated whether this is a common effect of angiotensin converting enzyme (ACE) inhibitors. METHODS AND DESIGN Cardiopulmonary and arterial baroreceptors were deactivated by progressively reducing central venous pressure (CVP) through progressively greater lower body negative pressures in eight untreated mild essential hypertensives on a moderately low-sodium diet (50 mmol/l per day). This deactivation was performed after oral administration of the non-sulphidrylic ACE inhibitor benazepril (10 mg) and placebo according to a double-blind randomized crossover experimental design. RESULTS After placebo, the reduction in CVP increased forearm vascular resistance (FVR; mean arterial pressure: plethysmographic forearm blood flow ratio). After benazepril, baseline blood pressure (beat-to-beat finger pressure) and FVR were significantly reduced whilst plasma angiotensin II was suppressed and PRA increased (both measured by radioimmunoassay). The FVR increases induced by progressive CVP reduction were less than after placebo administration, and the overall difference was statistically significant. Benazepril did not affect the reflex FVR reduction observed by increasing CVP through leg raising, nor the reflex changes in plasma norepinephrine measured by high-performance liquid chromatography accompanying the changes in FVR. CONCLUSIONS Benazepril attenuates sympathetic vasoconstriction as does captopril. This effect (which is mainly operative during an increased sympathetic drive and exerted through a reduction of adrenoceptor responsiveness) is thus likely to be a class- rather than a compound-related feature.

Zofenopril, is a highly lipophilic ACE inhibitor, characterized by long-lasting tissue penetration and sustained cardiac ACE inhibition, indicated for the treatment of hypertension and myocardial infarction. Comparative studies with different antihypertensive drug classes have demonstrated the good efficacy and tolerability of this compound in the management of the patient with mild-moderate hypertension. Zofenopril may also be combined with hydrochlorothiazide, a combination which has proved to be effective and safe as compared with monotherapy with either agent in three studies, including more than 600 patients. In addition, recent post hoc analyses in high-risk patients, such as those with the metabolic syndrome, impaired fasting glucose or diabetes, atherogenic dyslipidemia, and impaired renal function, have confirmed the superiority of zofenopril 30 mg plus hydrochlorothiazide 12.5 mg once-daily combination as compared with zofenopril monotherapy also in these high-risk populations of patients with hypertension. These data suggest the usefulness of this fixed combination in the treatment of patients with hypertension requiring more prompt, intensive, and sustained blood pressure reduction, according to guidelines recommendation. © 2009 Blackwell Publishing Ltd.

Background Electronic blood pressure monitoring devices are widely used by patients for monitoring their blood pressure at home. Few of them, however, have been validated against recognized protocols and proved to be accurate. Objective This study aimed at verifying whether the automatic electronic oscillometric blood pressure measuring device, Artsana CS 410 (Artsana S.p.A., Grandate, Como, Italy), complied with the standard of accuracy indicated by the European Society of Hypertension (ESH) International Protocol. Methods Sequential measurements of systolic and diastolic blood pressure were obtained in 33 patients (13 males, 20 females, mean age±SD 49±12 years) using the mercury sphygmomanometer (two observers) and the test device (one supervisor). A standard adult cuff was always used during the study. According to the ESH validation protocol, 99 pairs of test device and reference blood pressure measurements were obtained during the two phases of the study (three pairs of measurements for each of the 33 patients). Results The Artsana CS 410 device successfully passed phase 1 of study validation with the number of absolute differences between test and reference device never

Although standard validation protocols provide assurance of the accuracy of blood pressure monitors (BPMs), there is no guidance for the consumer as to the overall quality of a device. The PA.NET International Quality Certification Protocol, developed by the Association for Research and Development of Biomedical Technologies and for Continuing Medical Education (ARSMED), a nonprofit organization, with the support of the Italian Society of Hypertension-Italian Hypertension League, and the dabl Educational Trust denotes additional criteria of quality for BPMs that fulfilled basic validation criteria, published in full in peer-reviewed medical journals. The certification is characterized by three phases: (i) to determine that the device fulfilled standard validation criteria; (ii) to determine the technical and functional characteristics of the device (e.g. operativity, display dimension, accessory functions, memory availability, etc.) and (iii) to determine the commercial characteristics (e.g. price-quality ratio, after-sale service, guarantee, etc.). At the end of the certification process, ARSMED attributes a quality index to the device, based on a scale ranging from 1 to 100, and a quality seal with four different grades (bronze, silver, gold and diamond) according to the achieved score. The seal is identified by a unique alphanumeric code. The quality seal may be used on the packaging of the appliance or in advertising. A quality certification is released to the manufacturer and published on www.pressionearteriosa.net and www.dableducational.org. The PA.NET International Quality Certification Protocol represents the first attempt to provide health care personnel and consumers with an independent and objective assessment of BPMs based on their quality. © 2008 Wolters Kluwer Health | Lippincott Williams amp; Wilkins.

Objectives Information on the features of long-term modifications of clinic and 24-h ambulatory blood pressure (ABP) by treatment is limited. The present study aimed to address this issue. Methods Ambulatory BP monitoring and clinic BP (CBP) measurements were performed at baseline and at yearly intervals over a 4-year follow-up period in 1523 hypertensives (56.1 ± 7.6 years) randomized to treatment with lacidipine or atenolol in the European Lacidipine Study on Atherosclerosis (ELSA). Results CBP was always greater than ABP, while reductions in all BP values (greater for CBP than for ABP) were on average maintained throughout 4 years, CBP changes showing limited relationship with ABP changes (r = 0.14–0.27). BP reductions by treatment during daytime and night-time were correlated (r = 0.63–0.73). BP normalization was achieved in a greater percentage of patients for CBP (41.7%) than for ABP (25.3%), with systolic BP control being always less common than diastolic BP control. BP normalization was more frequent at single yearly visits than throughout the 4 years. Twenty-four-hour BP variability was reduced by treatment over 4 years in absolute but not in normalized units. Conclusions The present study provides the best evidence available on long-term effect of antihypertensive treatment on both ABP and CBP. On average, ABP was sustainedly reduced by treatment throughout the follow-up period, but 24-h BP was more difficult to control than CBP. In several patients, ABP control was unstable between visits, the percentage of patients under control over 4 years being much less than that of those controlled at each year. Treatment induced a reduction in absolute but not in normalized BP variability estimates. This has clinical implications because of the prognostic importance of ABP mean values and variability.