Vivianne Presta

Effect of resveratrol on blood pressure: A systematic review and meta-analysis of randomized, controlled, clinical trials

ABSTRACT Introduction: Results of previous clinical trials evaluating the effect of resveratrol supplementation on blood pressure (BP) are controversial. Purpose: We aimed to assess the impact of resveratrol on BP through systematic review of literature and meta-analysis of available randomized, controlled clinical trials (RCTs). Methods: Literature search included SCOPUS, PubMed-Medline, ISI Web of Science and Google Scholar databases up to 17th October 2017 to identify RCTs investigating the impact of resveratrol on BP. Two review authors independently extracted data on study characteristics, methods and outcomes. Overall, the impact of resveratrol on BP was reported in 17 trials. Results: Administration of resveratrol did not significantly affect neither systolic BP [weighted mean difference (WMD): −2.5 95% CI:(-5.5, 0.6) mmHg; p=0.116; I2=62.1%], nor diastolic BP [WMD: −0.5 95% CI:(-2.2, 1.3) mmHg; p=0.613; I2=50.8], nor mean BP [MAP; WMD: −1.3 95% CI:(-2.8, 0.1) mmHg; p=0.070; I2=39.5%] nor pulse pressure [PP; WMD: −0.9 95% CI:(-3.1, 1.4) mmHg; p=0.449; I2=19.2%]. However, significant WMDs were detected in subsets of studies categorized according to high resveratrol daily dosage (≥300 mg/day) and presence of diabetes. Meta-regression analysis revealed a positive association between systolic BP-lowering resveratrol activity (slope: 1.99; 95% CI: 0.05, 3.93; two-tailed p= 0.04) and Body Mass Index (BMI) at baseline, while no association was detected neither between baseline BMI and MAP-lowering resveratrol activity (slope: 1.35; 95% CI: −0.22, 2.91; two-tailed p= 0.09) nor between baseline BMI and PP-lowering resveratrol activity (slope: 1.03; 95% CI: −1.33, 3.39; two-tailed p= 0.39). Resveratrol was fairly well-tolerated and no serious adverse events occurred among most of the eligible trials. Conclusion: The favourable effect of resveratrol emerging from the current meta-analysis suggests the possible use of this nutraceutical as active compound in order to promote cardiovascular health, mostly when used in high daily dose (≥300 mg/day) and in diabetic patients.

Adding markers of organ damage to risk score models improves cardiovascular risk assessment: Prospective analysis of a large cohort of adult outpatients

INTRODUCTION Global cardiovascular (CV) risk stratification is recommended in all outpatients. Risk score charts, however, do not include markers of organ damage (OD). AIM To evaluate the potential added value of including different markers of subclinical OD to US Framingham, European SCORE and Italian Cuore risk score calculators. METHODS We prospectively evaluated adult outpatients, who underwent blood pressure (BP) assessment and global CV risk stratification. The following OD markers were considered: 1) cardiac OD: electrocardiographic) or echocardiographic left ventricular (LV) hypertrophy; 2) vascular OD: carotid atherosclerotic plaque; 3) renal OD: reduced estimated glomerular filtration rate or creatinine clearance. Different risk score calculators were applied for comparisons. RESULTS We included an overall population sample of 1979 outpatients (44.0% female, age 57.2±13.0years, BMI 26,6±4,4kg/m2, clinic systolic/diastolic BP 145.4±18.3/85.8±10.7mmHg), among whom 117 (5.9%) presented cardiac, 161 (8.1%) vascular, and 117 (5.9%) renal OD. US Framingham, European SCORE and Italian Cuore risk scores were all significantly raised in patients with than in those without OD. A trend toward increase for US Framingham CVD death, European ESC and Italian Cuore scores was observed according to degree of all markers of OD. Among these, reduced ClCr and eGFR showed high sensitivity and specificity to identify high risk individuals. CONCLUSIONS Presence of cardiac, vascular or renal OD is associated with higher risk scores, independently by the types of calculators, age and gender classes. OD detection should be included in CV risk stratification in order to improve diagnostic, prognostic and therapeutic processes.

2017 Position Paper of the Italian Society for Cardiovascular Prevention (SIPREC) for an Updated Clinical Management of Hypercholesterolemia and Cardiovascular Risk: Executive Document

The benefits achieved by implementing cardiovascular prevention strategies in terms of reduced incidence of atherosclerotic diseases and mortality are accepted, worldwide. In particular, the clinical management of hypercholesterolemia has a fundamental role for all preventive strategies, both in primary and secondary prevention, at each stage of cardiovascular risk. Since the net clinical benefit of lipid-lowering therapy largely depends on baseline individual cardiovascular risk profile, the assessment of individual risk is essential to establish type and intensity of both preventive and therapeutic strategies. Thus, the real challenge in a setting of clinical practice is not only to identify whom to treat among individuals at low-to-moderate risk, but mostly how much and how long to treat high or very-high risk patients. This manuscript, which reflects concepts and positions that have been published in a more extensive document of the Italian Society for Cardiovascular Prevention (SIPREC), deals with the diagnostic and therapeutic management of patients with dyslipidaemia, with an evidence-based approach adapted and updated from recent guidelines of the European Society of Cardiology and very recent results of randomized clinical trials. The purpose is to suggest a multidimensional and integrated actions aimed at eliminating or minimizing the impact of cardiovascular diseases and their related disabilities and mortality in patients with hypercholesterolemia.

Prevalence and clinical outcomes of white-coat and masked hypertension: Analysis of a large ambulatory blood pressure database

The aim of this study was to analyze prevalence and clinical outcomes of the following clinical conditions: normotension (NT; clinic BP < 140/90 mm Hg; 24‐hour BP < 130/80 mm Hg), white‐coat hypertension (WCHT; clinic BP ≥ 140 and/or ≥90 mm Hg; 24‐hour BP < 130/80 mm Hg), masked hypertension (MHT; clinic BP < 140/90 mm Hg; 24‐hour BP ≥ 130 and/or ≥80 mm Hg), and sustained hypertension (SHT; clinic BP ≥ 140 and/or ≥90 mm Hg; 24‐hour BP ≥ 130 and/or ≥80 mm Hg) in a large cohort of adult untreated individuals. Systematic research throughout the medical database of Regione Lazio (Italy) was performed to estimate incidence of myocardial infarction (MI), stroke, and hospitalizations for HT and heart failure (HF). Among a total study sample of 2209 outpatients, 377 (17.1%) had NT, 351 (15.9%) had WCHT, 149 (6.7%) had MHT, and 1332 had (60.3%) SHT. During an average follow‐up of 120.1 ± 73.9 months, WCHT was associated with increased risk of hospitalization for HT (OR 95% CI: 1.927 [1.233‐3.013]; P = .04) and HF (OR 95% CI: 3.449 [1.321‐9.007]; P = .011). MHT was associated with an increased risk of MI (OR 95% CI: 5.062 [2.218‐11.550]; P < .001), hospitalization for HT (OR 95% CI: 2.553 [1.446‐4.508]; P = .001), and for HF (OR 95% CI: 4.214 [1.449‐12.249]; P = .008). These effects remained statistically significant event after corrections for confounding factors including age, BMI, gender, smoking, dyslipidaemia, diabetes, and presence of antihypertensive therapies.

Favourable impact of statin use on diastolic blood pressure levels: Analysis of a large database of 24-hour ambulatory blood pressure monitoring

Introduction: Assumption of lipid-lowering drugs, mostly statins, is recommended at bed-time and evidence demonstrated a strong and independent correlation between night-time blood pressure (BP) and increased risk of cardiovascular events. Aim: To evaluate the effects of statins on night-time BP levels. Methods: We analysed data derived from a large cohort of adult individuals, who consecutively underwent home, clinic and ambulatory BP monitoring at our Unit. All BP measurements were performed and BP thresholds were set according to recommendations from European guidelines. Study population was stratified according to statin use. Results: We included an overall sample of 5634 adult individuals (women 48.9%, age 60.5 ± 11.6 years, BMI 27.0 ± 4.6 kg/m2, clinic BP 144.3 ± 18.4/90.9 ± 12.4 mmHg, 24-h BP 130.7 ± 13.4/79.0 ± 9.7 mmHg), among whom 17.3% received and 82.7% did not received statins. Treated outpatients were older, had higher BMI and prevalence of risk factors and comorbidities than those who were untreated (P < 0.001 for all). Patients treated with statins showed lower DBP levels at all BP measurements, including night-time (67.3 ± 9.4 vs. 70.9 ± 9.7 mmHg; P < 0.001) periods, than those observed in untreated patients. Also, statin use resulted an independent factor associated with 24-h [odds ratio (95% confidence interval): 1.513(1.295–1.767); P < 0.001] and night-time [odds ratio (95% confidence interval): 1.357(1.161–1.587); P < 0.001] BP control, even after adjusting for age, sex, BMI, diabetes, number of antihypertensive drugs (model 1) or presence/absence of antihypertensive treatment (model 2). Conclusion: Statin use was associated with significantly lower DBP levels. These effects were independently observed, even after correction for cardiovascular risk factors and comorbidities, as well as number of antihypertensive drugs.

Achievement of multiple therapeutic targets for cardiovascular disease prevention: Retrospective analysis of real practice in Italy

Pharmacological therapy in patients at high cardiovascular (CV) risk should be tailored to achieve recommended therapeutic targets.

Time Trend Analysis of Hypertension Prevalence, Awareness, Treatment and Control in Italy: Novel Insights from Recent National Surveys in the General Population

Essential hypertension is the most common risk factor in the general population and it is has been related to a markedly higher risk of having major cardiovascular events, including myocardial infarction, stroke, congestive heart failure and cardiovascular death, in the following 10 years compared to normotension [1]. On the other hand, it has been demonstrated that lowering high blood pressure (BP) levels to less than 140/90 mmHg is paralleled by a substantial reduction of cardiovascular risk, improved cardiovascular prognosis and event-free survival [2]. Hypertension, in fact, is deeply involved in the pathogenesis of atherosclerotic diseases, promoting development and progression asymptomatic structural and functional remodelling of heart and vessels towards acute cardiovascular events or death [3]. For these reasons, and in view of the large prevalence of high BP in the general population [4], preventive strategies aimed at controlling non-communicable diseases, particularly hypertension, represent a fundamental aspect of health care policies at both national and world levels. Indeed, the World Health Organization (WHO) recommended a 25% relative reduction of the prevalence of hypertension among the public health targets to be achieved within 2020 in order to reduce the global burden of diseases [5]. Systematic and periodic assessments of hypertension prevalence, awareness, treatment and control are available in various countries around the world [6–9]. These reports have been used not only for epidemiological purposes, but mostly for planning educational and therapeutic interventions aimed at ameliorating the BP control rates and reducing the incidence of hypertension-related cardiovascular diseases at various levels or settings. Over the last few years, such analyses were made available also in Italy, thus confirming a high prevalence of hypertension in the general adult population, with relatively low rates of awareness and control [10–14]. Among these surveys, the analysis provided by the National Institute of Health represents the first and most inclusive assessment of hypertension prevalence and control in the general population in our Country [13, 14]. In this issue of high blood pressure and cardiovascular prevention, Di Lonardo and colleagues [15] reported an updated analysis of this large database, which included data from three large epidemiological surveys: the risk factors and life expectancy (RIFLE) study [16], the Osservatorio Epidemiologico Cardiovascolare (OEC) [17] and the Osservatorio Epidemiologico Cardiovascolare/Health Examination Surveys (OEC/HES) [18]. What is relevant from this analysis is the very long observational period, which covered three main intervals (which covered 1978–1987, 1998–2002 and 2008–2012 periods, respectively), as well as the large population sample (which included about 70,000, 9712 and 9111 adult individuals, respectively). Although participants included in these surveys may not represent the whole Italian population, as properly acknowledged by the authors, the main findings of this analysis offered some interesting aspects to be discussed on hypertension status in the general adult population in Italy. As shown in Fig. 1, hypertension prevalence had a substantial decrease, whereas awareness and control & Giuliano Tocci giuliano.tocci@uniroma1.it

Tp–Te interval predicts heart rate reduction after fingolimod administration in patients with multiple sclerosis

BACKGROUND FTY720 (Fingolimod) is an immunosuppressive drug, which provides favourable effects in patients with multiple sclerosis (MS), albeit it induces heart rate (HR) and blood pressure (BP) reductions. Therefore, we tested potential factors able to predict HR response in MS patients treated with fingolimod. METHODS We analysed patients with MS followed at our Neurology Outpatient Clinic from May 2013 to June 2015. All patients underwent BP measurements and 12-lead ECG before and 6-h after drug administration. At these time intervals, conventional and new ECG indexes for cardiac damage, including Tp-Te interval, were measured. Univariate and multivariate analyses were performed to test the outcome of HR reduction more than median difference between baseline and final observations. RESULTS 69 outpatients with MS (46 males, age 35.1±9.4years, BP 119.0±12.7/73.0±9.3mmHg, HR 73.5±11.4bpm) were included. No relevant adverse reactions were reported. Fingolimod induced progressive systolic (P=0.024) and diastolic (P<0.001) BP, as well as HR (P<0.001) reductions compared to baseline. Prolonged PQ (150.4±19.5 vs. 157.0±19.5ms; P<0.001), QT (374.9±27.0 vs. 400.0±25.8ms; P<0.001), Tp-Te (1.8±0.3 vs. 1.9±0.3mm; P=0.021), and reduced QTc (414.4±24.4 vs. 404.5±24.5ms; P<0.001) intervals were also recorded at final observation. Baseline HR, QT and Tp-Te intervals provided prognostic information at univariate analysis, although Tp-Te interval resulted the best independent predictor for HR reduction at multivariate analysis [0.057 (0.005-0.660); P=0.022]. CONCLUSIONS This study firstly demonstrates that prolonged Tp-Te interval may identify those MS patients treated with fingolimod at higher risk of having significant, asymptomatic HR reduction during clinical observation.

Effects of different statin types and dosages on systolic/diastolic blood pressure: Retrospective analysis of 24-hour ambulatory blood pressure database

We previously demonstrated lower diastolic blood pressure (BP) levels under statin therapy in adult individuals who consecutively underwent 24‐hour ambulatory BP monitoring and compared their levels to untreated outpatients. Here we evaluated systolic/diastolic BP levels according to different statin types and dosages. 987 patients (47.5% female, age 66.0 ± 10.1 years, BMI 27.7 ± 4.6 kg/m2, clinic BP 146.9 ± 19.4/86.1 ± 12.1 mm Hg, 24‐hour BP 129.2 ± 14.4/74.9 ± 9.2 mm Hg) were stratified into 4 groups: 291 (29.5%) on simvastatin 10‐80 mg/d, 341 (34.5%) on atorvastatin 10‐80 mg/d, 187 (18.9%) on rosuvastatin 5‐40 mg/d, and 168 (17.0%) on other statins. There were no significant BP differences among patients treated by various statin types and dosages, except in lower clinic (P = .007) and daytime (P = .013) diastolic BP in patients treated with simvastatin and atorvastatin compared to other statins. Favorable effects of statins on systolic/diastolic BP levels seem to be independent of types or dosages, thus suggesting a potential class effect of these drugs.

Nocturnal blood pressure patterns and cardiovascular outcomes in patients with masked hypertension

Masked hypertension (MHT) is characterized by normal clinic and above normal 24‐hour ambulatory blood pressure (BP) levels. We evaluated clinical characteristics and CV outcomes of different nocturnal patterns of MHT. We analyzed data derived from a large cohort of adult individuals, who consecutively underwent home, clinic, and ambulatory BP monitoring at our Hypertension Unit between January 2007 and December 2016. MHT was defined as clinic BP <140/90 mm Hg and 24‐hour BP ≥ 130/80 mm Hg, and stratified into three groups according to dipping status: (a) dippers, (b) nondippers, and (c) reverse dippers. From an overall sample of 6695 individuals, we selected 2628 (46.2%) adult untreated individuals, among whom 153 (5.0%) had MHT. In this group, 67 (43.8%) were nondippers, 65 (42.5%) dippers, and 21 (13.7%) reverse dippers. No significant differences were found among groups regarding demographics, clinical characteristics, and prevalence of risk factors, excluding older age in reverse dippers compared to other groups (P < 0.001). Systolic BP levels were significantly higher in reverse dippers than in other groups at both 24‐hour (135.6 ± 8.5 vs 130.4 ± 6.0 vs 128.2 ± 6.8 mm Hg, respectively; P < 0.001) and nighttime periods (138.2 ± 9.1 vs 125.0 ± 6.3 vs 114.5 ± 7.7 mm Hg; P < 0.001). Reverse dipping was associated with a significantly higher risk of stroke, even after correction for age, gender, BMI, dyslipidemia, and diabetes (OR 18.660; 95% IC [1.056‐33.813]; P = 0.046). MHT with reverse dipping status was associated with higher burden of BP and relatively high risk of stroke compared to both dipping and nondipping profiles, although a limited number of CV outcomes have been recorded during the follow‐up.