Andrea Ferrucci

Angiotensin-Converting Enzyme Inhibitors, Angiotensin II Receptor Blockers and Diabetes: A Meta-Analysis of Placebo-Controlled Clinical Trials

BACKGROUND To determine whether the administration of angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) on top of standard cardiovascular (CV) therapies may reduce the incidence of new onset diabetes (NOD) in placebo-controlled clinical trials. The effects of these drugs on CV and non-CV mortality were also tested. METHODS We performed a meta-analysis of all randomized clinical trials (11 trials, n = 84,363 patients, aged 64.2 ± 5.86 years), published until 14 March 2010, in which ACE inhibitors or ARBs were compared with placebo and NOD incidence, CV, and non-CV mortality were reported. RESULTS Over an average follow-up of 4.0 ± 1.0 years, there were 1,284/15,142 (8.5%) cases of NOD in active-treated and 1,411/15,130 (9.3%) cases in placebo-treated patients in the ACE inhibitor trials, and 2,330/18,756 (12.4%) cases in active-treated and 2,669/18,800 (14.2%) cases in placebo-treated patients in the ARB trials. Overall, active therapy reduced NOD compared to placebo (odds ratio (OR) 95%, confidence interval (CI): 0.8 (0.8-0.9); P < 0.01). Both ACE inhibitors (OR 95%, CI: 0.8 (0.7-1.0); P = 0.07) and ARBs (OR 95%, CI: 0.8 (0.8-0.9); P < 0.01) reduced NOD as compared to placebo. Active treatment reduced CV mortality (OR 95%, CI: 0.9 (0.8-1.0); P < 0.01) and had a favorable impact on non-CV mortality (OR 95%, CI: 0.7 (0.9-1.0); P = 0.2) as compared to placebo. CONCLUSIONS Our findings demonstrated that ACE inhibitors or ARBs should be preferred in patients with clinical conditions that may increase risk of NOD, since these drugs reduced NOD incidence. In addition, these drugs have favorable effects on CV and non-CV mortality in high CV risk patients.

Blood pressure control in Italy: Analysis of clinical data from 2005-2011 surveys on hypertension

Introduction: Blood pressure (BP) control is poorly achieved in hypertensive patients, worldwide. Aim: We evaluated clinic BP levels and the rate of BP control in hypertensive patients included in observational studies and clinical surveys published between 2005 and 2011 in Italy. Methods: We reviewed the medical literature to identify observational studies and clinical surveys on hypertension between January 2005 and June 2011, which clearly reported information on clinic BP levels, rates of BP control, proportions of treated and untreated patients, who were followed in different clinical settings (mostly in general practice, and also in outpatient clinics and hypertension centres). Results: The overall sample included 158 876 hypertensive patients (94 907 women, mean age 56.6 ± 9.6 years, BMI 27.2 ± 4.2 kg/m2, known duration of hypertension 90.2 ± 12.4 months). In the selected studies, average SBP and DBP levels were 145.7 ± 15.9 and 87.5 ± 9.7 mmHg, respectively; BP levels were higher in patients followed in hypertension centres (n = 10 724, 6.7%; 146.5 ± 17.3/88.5 ± 10.3 mmHg) than in those followed by general practitioners (n = 148 152, 93.3%; 143.5 ± 13.9/84.8 ± 8.9 mmHg; P < 0.01). More than half of the patients were treated (n = 91 318, 57.5%); among treated hypertensive patients, only 31 727 (37.0%) had controlled BP levels. Conclusion: The present analysis confirmed inadequate control of BP in Italy, independently of the clinical setting. Although some improvement was noted compared with a similar analysis performed between 1995 and 2005, these findings highlight the need for a more effective clinical management of hypertension.

Reduced levels of N-terminal-proatrial natriuretic peptide in hypertensive patients with metabolic syndrome and their relationship with left ventricular mass.

Objectives The metabolic syndrome (MS) is associated with left ventricular hypertrophy (LVH). Previous evidence has shown that LVH is favoured by low levels of atrial natriuretic peptide (ANP), independently from blood pressure (BP), in hypertension. Although levels of natriuretic peptides are known to be lower in obesity, plasma ANP levels have not yet been assessed in MS. We aimed to assess the ANP levels and their relationship with left ventricular mass (LVM) in patients affected by MS. Methods One hundred and twenty-eight essential hypertensive patients were included in the study: 51 with MS and 77 without MS. Clinical, echocardiographical and biochemical parameters, and levels of both N-terminal (NT)-proANP and alphaANP were assessed. Results Hypertensive patients affected by MS had higher LVM and increased frequency of LVH. NT-proANP levels were significantly lower in MS, independent of waist circumference (WC). Log(NT-proANP) levels were significantly inversely related to left ventricular mass index (LVMI) (β = −0.360, P < 0.001) and LVM/height2.7 (β = −0.370, P < 0.001) in the whole hypertensive population by multiple linear regression analysis. The relationship of log(NT-proANP) with LVM was more enhanced in patients with MS. Conclusions The present study demonstrates that levels of NT-proANP are significantly reduced in hypertensive patients affected by MS, and they are significantly inversely related to the increased LVM observed in these patients. Our findings, while supporting previous experimental and clinical evidence of the antihypertrophic role of ANP in hypertension, may help to identify one of the possible mechanisms directly underlying LVH in MS.

Independent association of ECG abnormalities with microalbuminuria and renal damage in hypertensive patients without overt cardiovascular disease : data from Italy-Developing Education and awareness on MicroAlbuminuria in patients with hypertensive Disease study

Objectives Renal abnormalities are strongly associated with cardiac damage in essential hypertension. Detection of preclinical cardiac and renal abnormalities is a key clinical step in hypertension management. This study investigated the relationship between ECG abnormalities and microalbuminuria (MAU) in hypertensive patients without overt cardiovascular disease. This relationship, in fact, has never been extensively studied. Methods The study population was that of Italy-Developing Education and awareness on MicroAlbuminuria in patients with hypertensive Disease, a large observational study including 4121 hypertensive patients in Italy. Patients with overt cardiovascular diseases were excluded from the present analysis. ECGs were centrally read and urinary albumin/creatinine ratio was carefully assessed. Chronic kidney disease was defined by the presence of albuminuria or by a reduction of glomerular filtration rate. Results The presence of ECG abnormalities was significantly and directly associated with chronic kidney disease [odds ratio (OR) 1.66, 95% confidence interval (CI) 1.32–2.07, P < 0.001], particularly with MAU (OR 1.81, 95% CI 1.39–2.36, P < 0.001). Main selected ECG abnormalities were also significantly associated with MAU [rhythm abnormalities (OR 2.94, 95% CI 1.77–4.88, P < 0.001), intraventricular conduction defects (OR 1.95, 95% CI 1.32–2.87, P < 0.01), ventricular repolarization alterations (OR 1.84, 95% CI 1.26–2.70, P < 0.01) and left-axis deviation (OR 1.87, 95% CI 1.26–2.79, P < 0.01)]. After adjustment for confounders, an abnormal ECG and all the main ECG abnormalities remained significantly associated with MAU. Conclusion This is the first large and systematic analysis of the relationship between detailed ECG abnormalities and MAU/chronic kidney disease in hypertensive patients without overt cardiovascular diseases. We report a significant and independent relationship between the presence of ECG abnormalities and renal damage in a preclinical stage of hypertension. Identification of ECG abnormalities in hypertension should prompt physicians to careful detection for renal damage, also in order to achieve an accurate risk stratification.

Association of renal damage with cardiovascular diseases is independent of individual cardiovascular risk profile in hypertension: Data from the Italy-Developing Education and awareness on MicroAlbuminuria in patients with hypertensive Disease study

Objectives In the past years, several risk charts have been created to increase the accuracy of cardiovascular risk stratification. The most widely used and validated algorithms do not included target organ damage as risk prediction. The aim of the present study was to evaluate whether preclinical renal damage is associated with cardiovascular diseases independently of individual risk profile assessed by risk charts. Methods The study population was that of Italy-Developing Education and awareness on MicroAlbuminuria in patients with hypertensive Disease, a large observational study conducted on hypertensive patients in Italy. The Framingham Risk Score (FRS), Systematic COronary Risk Estimation (SCORE) and Progetto Cuore Risk Score (Progetto Cuore RS) were computed in each eligible patient. Chronic kidney disease was defined by the presence of albuminuria or by a reduction of glomerular filtration rate. Results Study participants were categorized to have low, medium and high risk according to the tertiles of the three charts. Prevalence of total cardiovascular diseases progressively and significantly increased according to the degrees of risk assessed by the three charts, the highest prevalence being in participants with a high-risk profile (both high and medium vs. low risk <0.01 for FRS, SCORE and Progetto Cuore RS). The presence of chronic kidney disease was associated with total cardiovascular diseases, independently of FRS (odds ratio 1.64, 95% confidence interval 1.33–2.02, P < 0.001), SCORE (odds ratio 1.55, 95% confidence interval 1.21–1.98, P < 0.001) and Progetto Cuore RS (odds ratio 1.59, 95% confidence interval 1.22–2.07, P < 0.001). Moreover, inclusion of renal damage in the logistic model significantly increased the accuracy of the FRS (P < 0.05), SCORE (P < 0.01) and Progetto Cuore RS (P < 0.01) to identify patients with overt cardiovascular diseases. Conclusion Identification of patients with preclinical renal damage should be encouraged in the hypertension cardiovascular risk stratification setting in order to achieve a more accurate individual risk computation. The presence of renal damage could improve cardiovascular risk prediction over the widely used risk stratification charts.

Do diabetes, metabolic syndrome or their association equally affect biventricular function? A tissue Doppler study

Metabolic syndrome (MetS) and type 2 diabetes (T2DM) have been associated with an impairment of left (LV) and right ventricular (RV) function as well as an increased risk of heart failure (HF). However, it remains unclear whether these clinical entities or their associations promote a similar derangement of biventricular function. Overall, 345 patients without overt cardiovascular disease consecutively underwent routine blood chemistry including high-sensitivity C reactive protein (hs-CRP) and echocardiographical examination with conventional and tissue Doppler imaging (TDI) of both ventricles. According to the ATP III criteria and fasting glucose levels, the study population was stratified into four groups: (1) healthy controls (n=120); (2) MetS without T2DM (n=84); (3) T2DM without MetS (n=49); and (4) MetS+T2DM (n=92). The Myocardial performance index (MPI) of the RV and LV was obtained with a multi-segmental approach using TDI. Patients with MetS and T2DM exhibited a similar impairment of biventricular function compared with healthy controls, whereas a further decline was observed in patients having both MetS and T2DM. In addition to MetS markers, hs-CRP exhibited the strongest association with the MPI of both ventricles. Regression analyses indicated that individual MetS markers were inferior to MetS in identifying subtle cardiac dysfunction. Independent associations of MetS and T2DM with biventricular dysfunction were comparable, and the coexistence of MetS and T2DM exhibited the highest risk for biventricular dysfunction. Our findings emphasize the importance of MetS as an equivalent of T2DM and support a synergic effect of these clinical conditions on cardiac organ damage requiring more aggressive therapeutic strategies to prevent HF.

Management of hypertension and stroke prevention: results of the Italian cardiologist survey

Objective: To provide an overview of current habits, priorities, perceptions and knowledge of cardiologists with regard to hypertension and stroke prevention in outpatient practice.

Blood pressure levels and control in Italy: comprehensive analysis of clinical data from 2000–2005 and 2005–2011 hypertension surveys

This analysis is aimed to determine blood pressure (BP) levels and BP control rates in a large population of hypertensive patients in Italy. Data were taken from two large and inclusive cross-sectional surveys, which covered two distinct and subsequent time periods (2000–2005 and 2005–2011, respectively). Observational clinical studies and surveys, which reported average systolic/diastolic clinic BP levels, proportions of treated/untreated and controlled/uncontrolled patients, and prevalence of cardiovascular risk factors in hypertensive patients followed in either outpatient clinics, hypertension centres or general practice, were considered for the analyses. The overall sample included 211 591 hypertensive patients (119 997 (56.7%) women, age 57.0±10.0 years, body mass index 26.9±4.0 kg m−2, BP levels 146.9±16.7/88.7±9.6 mm Hg). BP levels were 148.2±15.4/87.5±9.3 mm Hg in patients followed by general practitioners (n=168 313, 79.5%), 148.1±17.3/90.1±9.7 mm Hg in those followed by hypertension centres (n=28 180, 13.3%), and 142.4±17.6/86.6±9.8 mm Hg in those followed by outpatient clinics and hospital divisions (n=15 098, 7.1%). Among treated hypertensive patients (n=128 079; 60.5%), 43 008 (33.6%) were reported to have controlled BP levels. Over one decade of observation, we reported that ~60% of hypertensive patients were treated and among these only 33% achieved effective BP control. These findings highlight the need for more effective interventions to improve management of hypertension in Italy.

Prevalence and control of hypertension in the general practice in Italy: updated analysis of a large database

Systematic assessment of blood pressure (BP) control rates may help to improve the clinical management of hypertension in clinical practice. This approach had limited application in Europe over the last three decades and only recently has been implemented in some countries. The present study is aimed at evaluating hypertension prevalence and control among adult outpatients followed by a large, representative sample of general practitioners (GPs) in Italy. We retrospectively analysed the data derived from the GP Health Search-CSD database in 2013. Hypertension prevalence and control were estimated within the overall population sample and in hypertensive outpatients, respectively, according to age and gender. Hypertension diagnosis was defined according to the International Classification of Diseases 9. Clinic BP levels were measured according to the European guidelines. BP control was defined as systolic/diastolic BP <140/90 mm Hg. Data from 911 753 individuals (52.2% females) were scrutinized. Hypertension was diagnosed in 236 377 (25.9%) patients, being higher in male aged <70 years than age-matched female. Hypertension control was recorded in 60.6% of hypertensive patients, being higher in female than male individuals aged <70 years. Our current analysis demonstrates that about 26% of adult outpatients followed in the GP setting had hypertension and that about 61% had controlled BP levels. Both prevalence and control of hypertension appear to be higher when compared with the data reported from the analysis of the same database in 2005, thus confirming a positive trend in BP control in the GP clinical setting in Italy.

Global cardiovascular risk management in different Italian regions: An analysis of the evaluation of final feasible effect of control training and ultra sensitisation (EFFECTUS) educational program

BACKGROUND AND AIM The Final Evaluation Feasible Effect of Ultra Control Training and Sensitization (EFFECTUS) is an educational program, aimed at improving global CV risk stratification and management in Italy. The present study evaluates differences on clinical approach to global CV risk among physicians involved in the EFFECTUS program and stratified in three geographical macro-areas (North, Center, South) of our Country. METHODS AND RESULTS Physicians were asked to submit data already available in their medical records, covering the first 10 adult outpatients, consecutively seen in the month of May 2006. Overall, 1.078 physicians (27% females, aged 50 ± 7 years) collected data of 9.904 outpatients (46.5% females, aged 67 ± 9 years), among which 3.219 (32.5%) were residents in Northern, 3.652 (36.9%) in Central and 3.033 (30.6%) in Southern Italy. A significantly higher prevalence of major CV risk factors, including obesity, physical inactivity, hypertension and diabetes, was recorded in Southern than in other areas. Accordingly, Southern physicians more frequently prescribed antihypertensive, glucose and lipid lowering agents than other physicians, who paid significantly more attention to life-style changes in their clinical practice. CONCLUSIONS This analysis of the EFFECTUS study demonstrates a high prevalence of CV risk factors in Italy, particularly in Southern areas, and indicates some important discrepancies in the clinical management of global CV risk among physcians working in different Italian regions.