Giuliano Tocci

Blood pressure control in Italy: Results of recent surveys on hypertension

Background Blood pressure (BP) control is reported to be poor in hypertensive patients worldwide. Objective BP levels, the rate of BP control, prevalence of risk factors and total cardiovascular risk were assessed in a large cohort of hypertensive patients, derived from recent surveys performed in Italy. Methods Fifteen studies on hypertension, performed in different clinical settings (general population, general clinical practice, specialist outpatient clinics and hypertension centres) over the past decade were considered. Results The overall sample included 52 715 hypertensive patients (26 315 men and 26 410 women, mean age 57.3 ± 6.9 years). Despite the high percentage of patients on stable antihypertensive treatment (n = 36 556, 69%), mean systolic and diastolic BP levels were 147.8 ± 8.5 and 89.5 ± 5.2 mmHg, respectively. On the basis of the nature of the study (population surveys or clinical referrals), systolic BP levels were consistently higher than the normality threshold in both settings (142.6 ± 12.4/84.8 ± 3.7 mmHg and 150.4 ± 4.6/91.9 ± 4.1 mmHg, respectively). The BP stratification could be assessed in 40 829 individuals: 4.5% had optimal, 9.2% normal and 8.3% high-normal BP levels, however, the large majority were in grade 1 (39%) or grades 2–3 (32.6%) hypertension. In the overall sample, 55.9% of hypertensive patients had hypercholesterolemia, 28.7% were smokers, 36.4% were overweight or obese and 15.0% had diabetes mellitus. Cardiovascular risk stratification was assessed in 37 813 hypertensives: 23.2% had low, 33.9% moderate, 30.2% high and 12.7% very high added risk. Conclusion Our analysis demonstrates the persistence of poor BP control and high prevalence of risk factors, supporting the need for more effective, comprehensive and urgent actions to improve the clinical management of hypertension.

Antihypertensive Treatment and Development of Heart Failure in Hypertension: A Bayesian Network Meta-analysis of Studies in Patients With Hypertension and High Cardiovascular Risk

BACKGROUND It is still debated whether there are differences among the various antihypertensive strategies in heart failure prevention. We performed a network meta-analysis of recent trials in hypertension aimed at investigating this issue. METHODS Randomized, controlled trials published from 1997 through 2009 in peer-reviewed journals indexed in the PubMed and EMBASE databases were selected. Selected trials included patients with hypertension or a high-risk population with a predominance of patients with hypertension. RESULTS A total of 223,313 patients were enrolled in the selected studies. Network meta-analysis showed that diuretics (odds ratio [OR], 0.59; 95% credibility interval [CrI], 0.47-0.73), angiotensin-converting enzyme (ACE) inhibitors (OR, 0.71; 95% CrI, 0.59-0.85) and angiotensin II receptor blockers (ARBs) (OR, 0.76; 95% CrI, 0.62-0.90) represented the most efficient classes of drugs to reduce the heart failure onset compared with placebo. On the one hand, a diuretic-based therapy represented the best treatment because it was significantly more efficient than that based on ACE inhibitors (OR, 0.83; 95% CrI, 0.69-0.99) and ARBs (OR, 0.78; 95% CrI, 0.63-0.97). On the other hand, diuretics (OR, 0.71; 95% CrI, 0.60-0.86), ARBs (OR, 0.91; 95% CrI, 0.78-1.07), and ACE inhibitors (OR, 0.86; 95% CrI, 0.75-1.00) were superior to calcium channel blockers, which were among the least effective first-line agents in heart failure prevention, together with β-blockers and α-blockers. CONCLUSIONS Diuretics represented the most effective class of drugs in preventing heart failure, followed by renin-angiotensin system inhibitors. Thus, our findings support the use of these agents as first-line antihypertensive strategy to prevent heart failure in patients with hypertension at risk to develop heart failure. Calcium channel blockers and β-blockers were found to be less effective in heart failure prevention.

Role of the renin-angiotensin-aldosterone system and inflammatory processes in the development and progression of diastolic dysfunction

Left ventricular diastolic dysfunction represents a frequent clinical condition and is associated with increased cardiovascular morbidity and mortality. Diastolic dysfunction is the most common cause of HF-PSF (heart failure with preserved ejection fraction). Therefore it becomes important to understand the pathophysiological mechanisms underlying diastolic dysfunction, as well as the effective therapeutic strategies able to antagonize its development and progression. Among the complex pathophysiological factors that may contribute to the development of diastolic dysfunction, the RAAS (renin-angiotensin-aldosterone system) has been shown to play a significant role. Paracrine and autocrine signals of the RAAS promote structural and functional changes in the heart largely linked to increased myocardial fibrosis. Enhanced and dysregulated activity of the RAAS also contributes to the development of volume overload and vasoconstriction with subsequent increases in left ventricular diastolic filling pressures and a higher susceptibility of developing CHF (congestive heart failure). More recently, it has also been suggested that the RAAS may play a role in triggering myocardial and vascular inflammation through the activation of different cell types and the secretion of cytokines and chemokines. RAAS-induced myocardial inflammation leads to perivascular myocardial fibrosis and to the development or progression of diastolic dysfunction. For these reasons pharmacological blockade of the RAAS has been proposed as a rational approach for the treatment of diastolic dysfunction. In fact, ACEIs (angiotensin-converting enzyme inhibitors), ARBs (angiotensin II receptor blockers) and AAs (aldosterone antagonists) have been demonstrated to delay the development and progression from pre-clinical diastolic dysfunction towards CHF, as well as to reduce the morbidity and mortality associated with this condition.

Development of heart failure in recent hypertension trials.

Background Heart failure represents a major cause of disease burden worldwide and is expected to further rise in the coming decades. Hypertension is the clinical condition most frequently associated to heart failure. Objective To systematically review the incidence of heart failure compared to coronary heart diseases and stroke in recent hypertension trials. Methods We identified 23 trials concluded within the last decade including 193 424 patients with hypertension or at ‘high’ cardiovascular risk with a predominant presence of hypertensive patients, and reported incidence of major cardiovascular events, including heart failure, coronary heart disease and stroke. Results A total of 24 837 major cardiovascular events were recorded in trials performed between 1997 and 2007, of which 7171 (28.9%) were cases of heart failure, 10 223 (41.1%) of coronary heart disease and 7443 (30.0%) of stroke. The rate of heart failure was comparable with that of stroke, accounting for 8.5 and 9.1 events per 1000 patients (P = NS), respectively. Heart failure development was more prevalent in older subjects (>65 years) [odds ratio: 3.08, confidence interval 95% (2.88–3.31); P < 0.0001], in black versus nonblack individuals [odds ratio 1.90, (1.76–2.06); P < 0.0001], in diabetic versus nondiabetic patients [odds ratio 4.91, 95% confidence interval (4.40–5.43); P < 0.0001] and in patients with ‘very high’ risk versus those with a ‘high’ risk profile [odds ratio 1.29, 95% confidence interval (1.23–1.36); P < 0.0001]. Conclusion Our analysis shows that heart failure development remains a major problem in hypertension. In recent trials on hypertension, the development of heart failure was found comparable with that of stroke: it is more prevalent in older, black, diabetic and ‘very high’ risk individuals. These findings highlight the relevance of heart failure development in hypertension and support the need for optimizing antihypertensive strategies aimed at preventing the progression to overt heart failure, thus reducing the growing burden of disease associated with hypertension.

The Caregiver Burden Inventory in evaluating the burden of caregivers of elderly demented patients: results from a multicenter study.

Background and aims: The burden perceived by caregivers of patients with dementia is a fundamental prognostic aspect in the history of the disease. The aim of this study was to demonstrate the internal consistency of the Caregiver Burden Inventory (CBI), a scale used to quantify burdens in different aspects of a caregiver’s life, and the influence of patients’ and caregivers’ characteristics on its different dimensions. Methods: In this cross-sectional study, 419 demented patients and their caregivers were evaluated in 16 geriatric centers in Italy. Cognitive status and behavioral disturbances were assessed by the Mini Mental State Examination (MMSE) and Neuropsychiatric Inventory (NPI), respectively. Activities of Daily Living (ADL) and Instrumental Activities of Daily Living (IADL) were also evaluated. Comorbidity was assessed by the Cumulative Illness Rating Scale (CIRS). The severity of dementia was evaluated by the Clinical Dementia Rating (CDR) score. Caregiver distress due to the behavioral problems of the patient was assessed by the Neuropsychiatric Inventory-Distress, a subscale of the NPI wich evaluates stress caused by each behavioral disturbance of the patient, and by the Brief Symptom Inventory wich evaluates anxiety and depression. Burden was evaluated by the CBI. Results: The CBI showed very high internal consistency (Cronbach’s alpha value >0.80). Factor analysis showed that the items clustered into four dimensions, and not five as originally proposed. Multiple regression analysis revealed that patients’ behavioral disturbances and disability were the major predictors of the time-dependent burden; the psychophysical burden was explained mainly by caregiver anxiety and depression. Conclusions: The CBI proved to be an effective multidimensional tool for evaluating the impact of burden on many aspects of caregivers’ lives.

Cardiovascular risk assessment beyond Systemic Coronary Risk Estimation: A role for organ damage markers

Background: Cardiovascular risk assessment in the clinical practice is mostly based on risk charts, such as Framingham risk score and Systemic Coronary Risk Estimation (SCORE). These enable clinicians to estimate the impact of cardiovascular risk factors and assess individual cardiovascular risk profile. Risk charts, however, do not take into account subclinical organ damage, which exerts independent influence on risk and may amplify the estimated risk profile. Inclusion of organ damage markers in the assessment may thus contribute to improve this process. Objective: Our aim was to evaluate the influence of implementation of SCORE charts with widely available indexes of organ damage, with the purpose to ameliorate individual risk assessment. Methodology: We searched www.Pubmed.gov for evidence about the predictive value of left ventricular hypertrophy (LVH), estimated glomerular filtration rate (eGFR), microalbuminuria (MAU) and metabolic syndrome on different risk profiles estimated by SCORE. Interventional and observational trials including at least 200 patients and published after 2000 were selected. Results: The presence of organ damage as well as the number of abnormal parameters indicating organ damage is associated with increased cardiovascular risk, independently of SCORE. In the area of high risk, the impact of different markers of organ damage is heterogeneous. Combined risk models of SCORE and subclinical organ damage have major impact on risk stratification and may impact on recommendation in primary prevention in all SCORE categories. Conclusion: Available evidence suggests a tangible clinical advantage of adding the evaluation of simple organ damage markers to risk charts in cardiovascular risk prediction.

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.

Right Ventricular Dysfunction in Patients with End-Stage Renal Disease

Background: While chronic dialysis treatment has been suggested to increase pulmonary pressure values, right ventricular dysfunction (RVD) is a major cause of death in patients with end-stage renal disease. We investigated the impact of different dialysis treatments on right ventricular function. Methods: We examined 220 subjects grouped as follows: healthy controls (n = 100), peritoneal dialysis (PD; n = 26), hemodialysis (HD) with radial arteriovenous fistula (AVF; n = 62), and HD with brachial AVF (n = 32). Echocardiography including tissue Doppler imaging (TDI) of the right ventricle was performed in all patients. Results: Pulmonary pressure values progressively rose from controls across the 3 dialysis groups (21.7 ± 6.8, 29.7 ± 6.7, 37.9 ± 6.7 and 40.8 ± 6.6 mm Hg, respectively; p < 0.001). TDI indices of right ventricular function were more impaired in HD patients, particularly in those with brachial AVF. RVD, assessed by TDI myocardial performance index, was higher in HD patients compared with PD patients (71.3 vs. 34.6%, p < 0.001). Moreover, the prevalence of RVD further increased in patients with brachial AVF compared with the radial access (90.6 vs. 61.3%, p < 0.001). Conclusions: Compared to DP, HD increases the risk of RVD, particularly in the presence of brachial AVF. TDI may detect early functional failure of the right ventricle in HD patients.

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.