Zofenopril plus hydrochlorothiazide fixed combination in the treatment of hypertension and associated clinical conditions.

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

Does ABPM replace office blood pressure measurement in the clinical evaluation of patients?

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Cepstral Analysis for Scoring the Quality of Electrocardiograms for Heart Rate Variability

Mobile-health solutions based on heart rate variability often require electrocardiogram (ECG) recordings by inexperienced operators or real-time automatic analyses of long-term recordings by wearable devices in free-moving individuals. In this context, it is useful to associate a quality index with the ECG, scoring the adequacy of the recording for heart rate variability to identify noise or arrhythmias. Therefore, this work aims to propose and validate a computational method for assessing the adequacy of single-lead ECGs for heart rate variability analysis that may run in real time on wearable systems with low computational power. The method quantifies the ECG pseudo-periodic structure employing cepstral analysis. The cepstrum (spectrum of log-spectrum) is estimated on a running ECG window of 10 s before and after "liftering" (filtering in the cepstral domain) to remove slower noise components. The ECG periodicity generates a dominant peak in the liftered cepstrum at the "quefrency" of the mean cardiac interval. The Cepstral Quality Index (CQI) is the ratio between the cepstral-peak power and the total power of the unliftered cepstrum. Noises and arrhythmias reduce the relative power of the cepstral peak decreasing CQI. We analyzed a public dataset of 6072 single-lead ECGs manually classified in normal rhythm or inadequate for heart rate variability analysis because of noise or atrial fibrillation, and the CQI = 47% cut-off identified the inadequate recordings with 79% sensitivity and 85% specificity. We showed that the performance is independent of the lead considering a public dataset of 1,000 12-lead recordings with quality classified as "acceptable" or "unacceptable" by visual inspection. Thus, the cepstrum describes the ECG periodic structure effectively and concisely and CQI appears to be a robust score of the adequacy of ECG recording for heart rate variability analysis, evaluable in real-time on wearable devices

Morning blood pressure surge: pathophysiology, clinical relevance and therapeutic aspects

Morning hours are the period of the day characterized by the highest incidence of major cardiovascular events including myocardial infarction, sudden death or stroke. They are also characterized by important neurohormonal changes, in particular, the activation of sympathetic nervous system which usually leads to a rapid increase in blood pressure (BP), known as morning blood pressure surge (MBPS). It was hypothesized that excessive MBPS may be causally involved in the pathogenesis of cardiovascular events occurring in the morning by inducing hemodynamic stress. A number of studies support an independent relationship of MBPS with organ damage, cerebrovascular complications and mortality, although some heterogeneity exists in the available evidence. This may be due to ethnic differences, methodological issues and the confounding relationship of MBPS with other features of 24-hour BP profile, such as nocturnal dipping or BP variability. Several studies are also available dealing with treatment effects on MBPS and indicating the importance of long-acting antihypertensive drugs in this regard. This paper provides an overview of pathophysiologic, methodological, prognostic and therapeutic aspects related to MBPS

Day and Night Changes of Cardiovascular Complexity: A Multi-Fractal Multi-Scale Analysis

Recently, a multifractal-multiscale approach to detrended fluctuation analysis (DFA) was proposed to evaluate the cardiovascular fractal dynamics providing a surface of self-similarity coefficients alpha(q,tau), function of the scale tau, and moment order q. We hypothesize that this versatile DFA approach may reflect the cardiocirculatory adaptations in complexity and nonlinearity occurring during the day/night cycle. Our aim is, therefore, to quantify how alpha(q, tau) surfaces of cardiovascular series differ between daytime and night-time. We estimated alpha(q,tau) with -5 <= q <= 5 and 8 <= tau <= 2048 s for heart rate and blood pressure beat-to-beat series over periods of few hours during daytime wake and night-time sleep in 14 healthy participants. From the alpha(q,tau) surfaces, we estimated short-term (<16 s) and long-term (from 16 to 512 s) multifractal coefficients. Generating phase-shuffled surrogate series, we evaluated short-term and long-term indices of nonlinearity for each q. We found a long-term night/day modulation of alpha(q,tau) between 128 and 256 s affecting heart rate and blood pressure similarly, and multifractal short-term modulations at q < 0 for the heart rate and at q > 0 for the blood pressure. Consistent nonlinearity appeared at the shorter scales at night excluding q = 2. Long-term circadian modulations of the heart rate DFA were previously associated with the cardiac vulnerability period and our results may improve the risk stratification indicating the more relevant alpha(q,tau) area reflecting this rhythm. Furthermore, nonlinear components in the nocturnal alpha(q,tau) at q not equal 2 suggest that DFA may effectively integrate the linear spectral information with complexity-domain information, possibly improving the monitoring of cardiac interventions and protocols of rehabilitation medicine

Multiscale Sample Entropy of Cardiovascular Signals: Does the Choice between Fixed- or Varying-Tolerance among Scales Influence Its Evaluation and Interpretation?

Multiscale entropy (MSE) quantifies the cardiovascular complexity evaluating Sample Entropy (SampEn) on coarse-grained series at increasing scales τ. Two approaches exist, one using a fixed tolerance r at all scales (MSEFT), the other a varying tolerance r(τ) adjusted following the standard-deviation changes after coarse graining (MSEVT). The aim of this study is to clarify how the choice between MSEFT and MSEVT influences quantification and interpretation of cardiovascular MSE, and whether it affects some signals more than others. To achieve this aim, we considered 2-h long beat-by-beat recordings of inter-beat intervals and of systolic and diastolic blood pressures in male (N = 42) and female (N = 42) healthy volunteers. We compared MSE estimated with fixed and varying tolerances, and evaluated whether the choice between MSEFT and MSEVT estimators influence quantification and interpretation of sex-related differences. We found substantial discrepancies between MSEFT and MSEVT results, related to the degree of correlation among samples and more important for heart rate than for blood pressure; moreover the choice between MSEFT and MSEVT may influence the interpretation of gender differences for MSE of heart rate. We conclude that studies on cardiovascular complexity should carefully choose between fixed- or varying-tolerance estimators, particularly when evaluating MSE of heart rate

Clinical Study Blood Pressure Response to Zofenopril or Irbesartan Each Combined with Hydrochlorothiazide in High-Risk Hypertensives Uncontrolled by Monotherapy: A Randomized, Double-Blind, Controlled, Parallel Group, Noninferiority Trial

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%; = 0.778) and 24-hour BP response (zofenopril: 85% versus irbesartan: 84%; = 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

Nocturnal Arrhythmias and Heart-Rate Swings in Patients With Obstructive Sleep Apnea Syndrome Treated With Beta Blockers

Background: The higher cardiovascular variability and the increased prevalence of arrhythmias in patients with obstructive sleep apneas may contribute to their higher rate of fatal events during sleep. In this regard, the use of beta blockers (BB) is debated because they may induce bradyarrhythmias and alter the pattern of heart rate changes induced by apneas. Thus, the aim of our study is to quantify peri-apneic heart-rate swings and prevalence of nocturnal bradyarrhythmias in BB-treated and BB-naive patients with obstructive sleep apnea. Methods and Results: Our real-life, retrospective, cohort study analyzed data from patients with obstructive sleep apnea after a basal cardiorespiratory polysomnography. Among 228 eligible participants, we enrolled 78 BB-treated and 88 BB-naive patients excluding those treated with antiarrhythmic drugs or pacemakers, or with uninterpretable ECG traces during polysomnography. In each patient, type and frequency of arrhythmias were identified and peri-apneic changes of RR intervals were evaluated for each apnea. BB-treated patients were older and with more comorbidities than BB-naive patients, but had similar obstructive sleep apnea severity, similar frequency of arrhythmic episodes, and similar prevalence of bradyarrhythmias. Apnea-induced heart-rate swings, unadjusted for age, showed lower RR interval changes in BB-treated (133.5 +/- 63.8 ms) than BB-naive patients (171.3 +/- 87.7 ms, P=0.01), lower RR interval increases during apneas (58.5 +/- 28.5 versus 74.6 +/- 40.2 ms, P=0.01), and lower RR interval decreases after apneas (75.0 +/- 42.4 versus 96.7 +/- 55.5 ms, P0.05). Conclusions: BB appear to be safe in patients with obstructive sleep apnea because they are not associated with worse episodes of nocturnal bradyarrhythmias and even seem protective in terms of apnea-induced changes of heart rate