Endothelial dysfunction: its clinical value and methods of assessment.

Endothelial dysfunction (ED) is a systemic disorder characterized by reduced production of nitric oxide. This pathologic condition, which impairs vascular homeostasis, leads to the loss of protective properties of endothelial cells and is related to the pathogenesis of cardiovascular diseases. ED may affect every vascular bed, accounting for several clinical implications, particularly when the coronary bed is affected. Although the reliability of ED as a cardiovascular disease surrogate is still debated, many methods for its assessment have been proposed. In this review, we underline the clinical value of ED in the cardiovascular field and summarize the principal methods currently available for its assessment.

Report on Non-fatal events cardio-cerebro-vascular to ten years in a Southern Italy cohort.

BACKGROUND: Data relating to non-fatal cardiovascular events are poor but these data are essential to organize targeted interventions on the territory and to understand their effectiveness. METHODS: We calculated the rates of morbidity from cardiovascular events covering the period 1998/99-2008/09, in a cohort of 1200 persons (600 men and 600 women) aged 25 to 74 years. Data were standardized using the European standard population. RESULTS: The incidence of events to ten years of non-fatal myocardial infarc.ion was 2.2% in men and of 1.8% in women. PCI interventions to ten year have been 3.3% in men and 3.4% in women, the interventions of aorto-coronary bypass have been 2.4% and 0.5% for men and women respectively. While all major cardiovascular events have been more frequent in men, in women there was a higher incidence of stroke (1.6% vs 0.9%). CONCLUSION: Although by comparison with other European countries Italy is among the countries considered at low-risk of coronary heart disease, in Campania cardiovascular diseases reach higher rates than the rest of the country. Our results are in keeping with the literature data and confirm that cardiovascular diseases are a major public health problem. Local analysis are useful in providing additional information for planning prevention interventions targeted to its own territory.

The safety of statins in children.

UNLABELLED: Current American Academy of Pediatrics Guidelines recommended that statins should be considered as a first-line agent in children as early as 8 years of age. The aim of our work is to assess the safety of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors in children with hypercholesterolaemia. CONCLUSION: Controlled studies in children show that statin monotherapy is efficacious, well tolerated and safe in the short-time. Unfortunately, these studies have relatively short-term follow-up periods, and therefore, long-term safety remains unclear.

[Ten year cardio-cerebro-vascular mortality and morbidity in a Southern Italy cohort: the VIP Project data]. / Mortalità e morbilità cardio-cerebro-vascolare a dieci anni (1998/99 - 2008/09) in una coorte di popolazione adulta dell'Italia meridionale: i dati del Progetto VIP.

RATIONALE: In Italy the mortality data were obtained almost exclusively from the data RENCAM (Name Causes of Death Register), while there are few prospective surveys. In order to assess whether there are particular epidemiological conditions in the geographical area of Mercato S. Severino, in Southern Italy, we have studied, and reassessed at ten years (1998/99 - 2008/09), a cohort of adult general population in a project of cardiovascular epidemiology and prevention. MATERIALS AND METHODS: We calculated the rates of mortality and morbidity from cardiovascular events covering the period 1998/99 - 2008/09, in a cohort of 1200 persons (600 men and 600 women) aged 25 to 74 years. Data were standardized using the European standard population. RESULTS: Mortality from cardiovascular causes was 46.5% in men and 48.7% in women; it was mainly concentrated in the age group 65-74 years where it occurred on 62.9% of deaths in men and 66.7% in women. Regarding morbidity, the incidence of events to ten years of non-fatal myocardial infarction was 2.2% in men and of 1.8% in women. PTCA interventions to ten year have been 3.3% in men and 3.4% in women, the interventions of aorto-coronary bypass have been 2.4% and 0.5% for men and women respectively. While all major cardiovascular events have been more frequent in men, in women there was a higher incidence of stroke (1.6% vs 0.9%). CONCLUSIONS: Although by comparison with other European countries Italy is among the countries considered at low-risk of coronary heart disease, in Campania cardiovascular diseases reach higher rates than the rest of the country. Our results are in line with the literature data and confirm that cardiovascular diseases are a major public health problem. Local analysis to propose means to provide useful information for planning prevention interventions targeted to their own territory.

[Chronic kidney disease prevalence and trends (1998-2008) in an area of southern Italy. The data of the VIP project]. / Prevalenza e trend (1998-2008) dell'insufficienza renale cronica in un'area dell'Italia meridionale: i dati del progetto VIP.

Chronic kidney disease (CKD) is a common disorder whose prevalence is increasing worldwide. In Italy the prevalence of CKD, especially the early stages, is still not exactly known. Our study examines the prevalence and trends in ten years (1200 subjects in 1998-1999 and 1200 subjects in 2008-2009) of the estimated glomerular filtration rate (eGFR) in a population of southern Italy. We analyzed, within the VIP project, the prevalence of CKD (eGFR <60) in our area and its relationship to diabetes and hypertension as well as the trend between the years 1998-1999 and 2008-2009. The estimate of the GFR was obtained with the Cockcroft-Gault formula corrected for body surface area. The prevalence of CKD, stratified by the population of Campania, was about 5.9% in males and 3.9% in females in the years 1998-1999; ten years later (2008-2009) it had increased to 6.2% in males and 4.5% in females. The differences between males and females and between the two decades are not statistically significant although the trend shows a clear increase in subjects affected by CKD among both sexes. Among the male population the prevalence of CKD in persons with hypertension or diabetes, in those with both diseases, and in those free from these diseases was 11.2%, 12%, 13.8% and 6.3% (p=0.018), respectively. The same groups among females showed a CKD prevalence of 8%, 9.2%, 9.7% and 4.4%, respectively (p=0.042). Our work provides a picture of the prevalence of CKD in an area of southern Italy. It highlights the increase in CKD and calls upon a greater use of renal function tests in clinical practice, so that individuals at increased risk of developing cardiovascular complications may be detected as early as possible.

Hyperuricemia as an independent risk factor for major cardiovascular events: a 10-year cohort study from Southern Italy.

AIMS: To date, whether hyperuricemia may represent a marker or an independent risk factor for cardiovascular disease remains unclear. This study aimed at assessing the role of hyperuricemia in the onset of major cardiovascular events (MACE). METHODS: Baseline clinical data were collected through a 1998/1999 longitudinal survey as part of the larger Valle dell'Irno Prevenzione Project. Ten years later, MACE incidence was evaluated. RESULTS: A total of 1175 patients (50% men, aged 25-74 years) completed the study. At least one MACE was reported by 135 patients, whose mean uric acid values were significantly higher compared with patients without events (6.0 ±â€Š4.8 and 4.6 ±â€Š4.0 mg/dl, respectively; P < 0.01). Patients with uric acid values of at least 6 mg/dl (prevalence of 14.6%) had significantly lower levels of high-density lipoprotein cholesterol and increased values of BMI, blood pressure (BP), cholesterol, triglycerides, white blood cells, complement component 3 (C3) and creatinine. After subgrouping patients in tertiles and considering the first one as reference [odds ratio (OR): 1], the OR (95% confidence interval) was 1.44 (0.7-2.9) in the second and 2.2 (1.3-3.5) in the third tertile, respectively. Confounder-adjusted stepwise linear regression revealed uric acid, age, creatinine, glucose and systolic BP as independent predictors of MACE. Diastolic BP and creatinine were independently correlated with uric acid in the entire population, diastolic BP only in men and BMI, creatinine, age and C3 in women. CONCLUSION: Hyperuricemia was shown to be a strong independent risk factor for MACE and should be included in cardiovascular prevention strategies. Whether hypouricemic drugs can decrease cardiovascular disease risk warrants further studies.

Trends of Prevalence of Uncontrolled Risk Factors for Cerebrocardiovascular Disease: Southern Italy from 1988/9 to 2008/9.

The aim of this study was to determine the trends of cardiovascular risk factor prevalence between 1988/9 and 2008/9 in the 25-74-year-old population in an area of Southern Italy. We compared three cross-sectional studies conducted in random population samples, in 1988/9, 1998/9, and 2008/9 in Salerno, Italy. The methodology of data collection (lipid profile, systolic and diastolic blood pressure, glycaemia, and smoking) and conducting tests which the population underwent during the three phases was standardized and comparable. Prevalence of diabetes, hypertension, hypercholesterolemia, and smoking was calculated and standardized for age. A total of 3491 subjects were included. From 1988/9 to 2008/9, in males, the prevalence of all four risk factors was reduced. In women, there was a clear reduction of hypertension, a similar prevalence of hypercholesterolemia, and an increase of smoking and diabetes. In the area of Salerno, our data confirm that the global prevalence of the major risk factors is decreasing in men, but their absolute values are still far from optimization. In women, diabetes and smoking showed a negative trend, therefore requiring targeted interventions. These data are now used as a base for executive targeted programs to improve prevention of cardiovascular disease in our community.

Transradial versus transfemoral approach in patients undergoing percutaneous coronary intervention for acute coronary syndrome. A meta-analysis and trial sequential analysis of randomized controlled trials.

BACKGROUND: Transfemoral approach (TFA) remains the most common vascular access for percutaneous coronary intervention (PCI) in many countries. However, in the last years several randomized trials compared transradial approach (TRA) with TFA in patients with acute coronary syndrome (ACS), but only few studies were powered to estimate rare events. The aim of the current study was to clarify whether TRA is superior to TFA approach in patients with ACS undergoing percutaneous coronary intervention. A meta-analysis, meta-regression and trial sequential analysis of safety and efficacy of TRA in ACS setting was performed. METHODS AND RESULTS: Medline, the Cochrane Library, Scopus, scientific session abstracts and relevant websites were searched. Data concerning the study design, patient characteristics, risk of bias, and outcomes were extracted. The primary endpoint was death. Secondary endpoints were: major bleeding and vascular complications. Outcomes were assessed within 30 days. Eleven randomized trials involving 9,202 patients were included. Compared with TFA, TRA significantly reduced the risk of death (odds ratio [OR] 0.70; 95% confidence interval [CI], 0.53-0.94; p = 0.016), but this finding was not confirmed in trial sequential analysis, indicating that sufficient evidence had not been yet reached. Furthermore, TRA compared with TFA reduced the risk of major bleeding (OR 0.60; 95% CI, 0.41-0.88; p = 0.008) and vascular complications (OR 0.35; 95% CI, 0.28-0.46; p<0.001); these findings were supported by trial sequential analyses. CONCLUSIONS: In patients with ACS undergoing PCI, a lower risk of death was observed with TRA. Nevertheless, the association between mortality and TRA in ACS setting should be interpreted with caution because it is based on insufficient evidence. However, because of the clinical relevance associated with major bleeding and vascular complications reduction, TRA should be recommended as first-choice vascular access in patients with ACS undergoing cardiac catheterization.

Reperfusion correlates and clinical outcomes of right ventricular dysfunction in patients with inferior ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention.

We evaluated the relation between reperfusion indexes and right ventricular (RV) dysfunction in patients with inferior ST-segment elevation myocardial infarction (STEMI). We included patients with inferior STEMI undergoing percutaneous coronary intervention and right coronary artery as infarct-related artery. Myocardial reperfusion was evaluated by Thrombolysis In Myocardial Infarction (TIMI) flow, TIMI frame count, myocardial blush grade, and ST-segment resolution. RV dysfunction was defined as tricuspid annular plane systolic excursion≤16 mm in M-mode imaging. RV dysfunction was present in 58 of 141 patients (41.1%) and was more frequent in patients achieving suboptimal postprocedural TIMI flow grade (66.7% vs 36.7%, grades 0 to 2 vs 3, p=0.01), TIMI frame count (63.2% vs 37.7%, ≥40 vs <40 frames, p=0.04), and myocardial blush grade (33.3% vs 56.2%, grade 0 or 1 vs 2 or 3, p=0.001). RV dysfunction rates did not differ according to ST-segment resolution. Patients with RV dysfunction had increased rates of cardiac death (13.2% vs 2.6%, p=0.03), reinfarction (24.5% vs 10.3%, p=0.03), and stent thrombosis (22.6% vs 6.4%, p=0.01) at 2-year follow-up. Postprocedural TIMI flow grade 3 (odds ratio 0.25, 95% confidence interval 0.09 to 0.68, p=0.007) was the only reperfusion correlate of RV dysfunction at multivariate analysis. In an independent cohort of 84 patients with STEMI, postprocedural TIMI flow grade 3 had a limited sensitivity (52%), with a high specificity (74.5%) and negative predictive value (71%) for excluding RV dysfunction. In conclusion, in patients with inferior STEMI undergoing coronary revascularization, RV dysfunction is associated with a worse long-term prognosis. Postprocedural TIMI flow grade may be a useful tool to predict RV dysfunction.

Trend in prevalence of uncontrolled total serum cholesterol for cardio-cerebro-vascular disease in a mediterranean area, 1988/89-2008/09.

AIM: To examine trends of uncontrolled total serum cholesterol, treatment and control in a Mediterranean region (Campania). METHODS: We considered and compared the data collected as part of "Montecorvino Rovella Project" 1988-1989 and cross-sectional data from the two phases of the "VIP Project-Valle dell'Irno Prevenzione": 1998-1999 (1(st) phase) and 2008-2009 (2(nd) phase), in the 35-74-year-old-population. RESULTS: Data show a reduction of mean cholesterolemia in the last twenty years of 7.3 mg/dL for men and unchanged values for women. In the three surveys the mean values for serum cholesterol are in men: 205.2 ± 47.1 mg/dL (1988/89), 200 ± 38.9 mg/dL (1998/99) and 197.9 ± 40.2 mg/dL (2008/09); in the women: 203.1 ± 42.5 mg/dL (1988/89), 198.9 ± 37.9 mg/dL (1998/99) and 203.3 ± 39.3 mg/dL (2008/09). Prevalence of uncontrolled high cholesterol ≥ 240 mg/dL for men decreased from 20.8% (1988/89) to 14.3% (1998/99) and 13.9% (2008/9), P = 0.002; for women the values decreased from 19.9% (1988/89), to 18.2% (1998/99) and 18.1% (2008/09), P = 0.007. Is statistically increased the number of patients treated and those treated to target. CONCLUSION: Encouraging increases in awareness, treatment, and control of hypercholesterolemia occurred from 1988 through 2008. Nevertheless, control of hypercholesterolemia remains poor.

Effects of physical activity on endothelial progenitor cells (EPCs).

Physical activity has a therapeutic role in cardiovascular disease (CVD), through its beneficial effects on endothelial function and cardiovascular system. Circulating endothelial progenitor cells (EPCs) are bone marrow (BM) derived cells that represent a novel therapeutic target in CVD patients, because of their ability to home to sites of ischemic injury and repair the damaged vessels. Several studies show that physical activity results in a significant increase in circulating EPCs, and, in particular, there are some evidence of the beneficial exercise-induced effects on EPCs activity in CVD settings, including coronary artery disease (CAD), heart failure (HF), and peripheral artery disease (PAD). The aim of this paper is to review the current evidence about the beneficial effects of physical exercise on endothelial function and EPCs levels and activity in both healthy subjects and patients with CVD.

[Management of hypercholesterolemia in children: needs and concerns]. / Il trattamento dell'ipercolesterolemia nei bambini: necessità e preoccupazioni.

In childhood, cholesterol values are closely related to the genetic heritage of the young patient. Among familial hypercholesterolemia, it is essential to identify the monogenic and multigenic forms. In monogenic forms, heterozygotes respond poorly or partially to changes in diet and lifestyle, making pharmacological therapy necessary; in homozygote patients plasmapheresis is required, and liver transplantation is the only intervention that can impact permanently on the development of cardiovascular lesions in adulthood. Conversely, multigenic forms or familial hypercholesterolemia secondary to other diseases respond to changes in diet and lifestyle as well as to pharmacological treatment. It remains unclear how early pharmacological intervention should be implemented. In particular, the presence in children of typical histological lesions of athero- sclerosis and their interaction with cardiovascular disease in adulthood justify a prompt, although cautious, intervention. In fact, cholesterol is necessary for normal development of the organism, provided that percentile values are in the normal range according to age and sex. Two methods of intervention are identified: a population strategy that should be implemented on a large scale for advice about diet and optimal level of physical activity; and an individual strategy, in which diet advice should be followed by pharmacological treatment. Pharmacological therapy may be administered even in children over the age of 8-10 years, if necessary. In younger patients, therapeutic interventions should be restricted to children with LDL cholesterol levels >500 mg/dl. Although statins have only been studied in populations affected by severe familial hypercholesterolemia in the short term, they seem to be the most effective agents in children owing to their efficacy and limited side effects.