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Biomedical subjects

Francesco Perticone

Publications and source records attributed to Francesco Perticone.

At least 19 recordsLinked to original sources

Successful radiofrequency ablation determines atrio-ventricular remodelling and improves systo-diastolic function at tissue Doppler-imaging.

BACKGROUND: Clinical, echocardiographic results and determinants of atrial fibrillation (AF) recurrence following AF ablation during mitral valve surgery (AFAMVS) were evaluated. METHODS: Fifty-two patients undergoing radiofrequency AFAMVS between January 2003 and December 2005, underwent serial echocardiographies with tissue Doppler imaging to assess atrio-ventricular function. Recurrence of AF, hospital readmission, episodes of congestive heart failure (CHF) were recorded. Predictors for AF-recurrence were evaluated. RESULTS: At a 29.5+/-8.6 months of follow-up (100% complete), 78.8% patients were in sinus rhythm (SR). Freedom from AF-recurrence was 64.6+/-0.76%, from hospital readmission 88.9+/-0.47%, from CHF 91.6+/-0.63%. SR-patients demonstrated better freedom from hospital readmission (97.4 vs 60.6%; p=0.0003) and from CHF (100 vs 72.7%; p=0.008) during follow-up. At follow-up SR-patients demonstrated left atrial (preoperative 5.8+/-0.8 cm vs follow-up 5.1+/-0.9; p=0.013) and ventricular reverse remodelling (preoperative LVDd 5.7+/-1.1cm vs follow-up 5.2+/-1.1; p=0.048 - preoperative LVDs 4.0+/-1.4 vs follow-up 3.6+/-1.1; p=0.036). E/A ratio was normal in 73.1% (92.7% of SR-patients). TDI at the level of the left lateral annulus showed an improved left ventricular systole (Sm), and diastole (Em, E/Em) of SR-patients, compared with AF-patients (Sm 9.40+/-1.74 vs 7.72+/-1.5, p=0.0001; Em: 10.45+/-1.98 vs 7.68+/-0.72, p=0.001; E/Em: 0.07+/-0.02 vs 0.10+/-0.04, p=0.0001). Large preoperative atrial diameter (OR=5.81; p=0.002), preoperative NYHA-IV (OR=3.55; p=0.001), high diuretics at discharge (OR=1.27; p=0.03), tricuspid insufficiency at follow-up (OR=2.31; p=0.02) were independent predictors of AF-recurrence. CONCLUSIONS: Radiofrequency AFAMVS achieves 78.8% of SR recovery. Maintenance of SR improves clinic, haemodynamic and echocardiographic endpoints. Pre- and post-operative cardiac failure is the main determinant of AF-recurrence.

Aged↗

Plasma interleukin-6 levels are increased in subjects with impaired glucose tolerance but not in those with impaired fasting glucose in a cohort of Italian Caucasians.

BACKGROUND: While the relationship between impaired glucose tolerance (IGT) and circulating interleukin-6 (IL-6) is well established, there is no information whether IL-6 levels are elevated in impaired fasting glucose (IFG). METHODS: To this end, we examined the relationship between plasma IL-6 concentration and different degrees of glucose homeostasis in a cohort of 470 Italian Caucasian subjects comprising 236 normal glucose tolerant (NGT), 49 IFG, 51 IGT, and 134 type 2 diabetic subjects. RESULTS: We observed that IL-6, CRP and fibrinogen levels were higher in subjects with IGT or type 2 diabetes as compared with NGT and IFG subjects. Univariate correlations between IL-6 concentrations and metabolic variables in the whole cohort showed that IL-6 levels were positively correlated with age, BMI, waist, systolic and diastolic blood pressure, fasting plasma glucose, triglycerides, CRP, fibrinogen, and negatively correlated with insulin sensitivity, IGF-I and HDL. In a subgroup analysis including NGT, IFG and IGT (n = 336), IL-6 levels were positively correlated with age, BMI, waist, systolic and diastolic blood pressure, triglycerides, CRP, fibrinogen, fasting insulin, 2 h post-load glucose, and negatively correlated with insulin sensitivity, IGF-I and HDL. Stepwise linear regression analysis in a model including gender, age, BMI, waist, glucose tolerance status, fasting plasma glucose, 2 h post-load glucose, triglycerides, HDL, fasting insulin, and insulin sensitivity revealed that waist was the only independent variable associated with IL-6 levels accounting for 21.0% of its variation (P < 0.0001). CONCLUSIONS: These data show that IGT and type 2 diabetes, but not IFG, are associated with elevated plasma IL-6 levels.

Adolescent↗

Endogenous testosterone and endothelial function in postmenopausal women.

OBJECTIVE: It is well known that coronary heart disease incidence increases in women after menopause. This phenomenon was related to reduced levels of female sex hormones. Estrogen decline, however, is not the only hormonal change during the postmenopausal period and estrogen administration did not protect women from cardiovascular disease. Therefore, it is justified to explore other hormonal changes. The role of androgens is still controversial. The aim of the present study was to investigate the relationship between endogenous sex hormones and endothelial function, measuring the brachial artery flow-mediated dilation. METHODS AND RESULTS: Sixty postmenopausal women were consecutively enrolled and underwent a clinical and biochemical examination. Brachial artery flow-mediated dilation was also evaluated by ultrasound. After correction for confounding variables, testosterone was positively correlated to flow-mediated dilation (beta=0.277, P=0.03). Indeed, women in the lowest testosterone tertile had a flow-mediated dilation smaller than that in the highest tertile (P=0.02). CONCLUSIONS: This result could suggest that the development of cardiovascular disease after menopause is due not only to estrogen decline but also to androgen decline. More studies are needed to evaluate the role of androgen replacement therapy on postmenopausal women with low level of this hormone.

Age Distribution↗

Effects of growth hormone and insulin-like growth factor-1 on cardiac hypertrophy of hypertensive patients.

OBJECTIVES: Growth hormone (GH) and insulin-like growth factor-1 (IGF-1) interfere with cardiac mass (left ventricular mass; LVM) development. We investigated the role of the GH/IGF-1 axis on LVM and ventricular geometry in a group of 230 never-treated hypertensive patients. METHODS: Partition values for left ventricular hypertrophy (LVH) were 125 g/m2 for both women and men. Insulin resistance was estimated by the homeostasis model assessment (HOMA) index. RESULTS: A significant inverse correlation was observed between IGF-1 and both fasting insulin (r = -0.249; P < 0.0001) and GH (r = -0.218; P < 0.0001). Systolic blood pressure (157.3 +/- 13.6 versus 149.4 +/- 12.8 mmHg; P < 0.001), fasting insulin (17.4 +/- 8.5 versus 11.4 +/- 6.0 microU/l; P < 0.0001), HOMA (4.4 +/- 2.3 versus 2.9 +/- 1.6; P < 0.0001) and GH (1.0 +/- 1.0 versus 0.4 +/- 0.5 ng/ml; P < 0.0001) were significantly higher in patients with LVH; on the contrary, IGF-1 values (119.1 +/- 47.8 versus 160.1 +/- 75.5 ng/ml; P < 0.0001) were higher in patients without LVH. In a logistic regression analysis, the strongest independent predictors of LVH were GH [relative risk (RR) = 2.078; 95% confidence interval (CI) = 1.364-3.163], HOMA (RR = 1.345; 95% CI = 1.133-1.596), IGF-1 (RR = 0.993; 95% CI = 0.998-0.999) and systolic blood pressure (RR = 1.036; 95% CI = 1.013-1.060). IGF-1 showed an opposite trend in patients with eccentric and concentric hypertrophy. CONCLUSIONS: Present data demonstrate that the increase in LVM prevalent in human essential hypertension is directly associated with serum GH levels and inversely related to circulating IGF-1.

Adult↗

Carotid atherosclerosis associated to metabolic syndrome but not BMI in healthy menopausal women.

BACKGROUND: Obesity and the metabolic syndrome (MS) frequently coexist. Both are apparently associated to cardiovascular disease. However, the contribution of obesity to cardiovascular risk, independent of the presence of the metabolic syndrome, remains controversial. The purpose of this study was to investigate whether the subclinical carotid atherosclerosis prevalence is different in obese postmenopausal women with and without the metabolic syndrome. METHODS: On the basis of consecutive recruitment, 313 postmenopausal women underwent a clinical, biochemical and ultrasound characterization. Women affected by cardiovascular disease or diabetes were excluded from the study. RESULTS: Among enrolled women the metabolic syndrome and body mass index (BMI) resulted strongly associated, but only metabolic syndrome was associated with carotid atherosclerosis, a well-known marker of cardiovascular disease. Similarly, increases in BMI unit (normal to overweight to obese) were not associated with carotid atherosclerosis whereas metabolic status (normal to metabolic syndrome) conferred an approximate three-fold adjusted odds of carotid atherosclerosis. CONCLUSIONS: The metabolic syndrome but not obesity is associated to carotid atherosclerosis in postmenopausal women. Although it remains prudent to recommend weight loss in overweight and obese women, evaluation and control of metabolic risk factors should be considered the main goal to prevent cardiovascular and cerebrovascular disease.

Aged↗

Carotid artery intima-media thickness is associated with insulin-mediated glucose disposal in nondiabetic normotensive offspring of type 2 diabetic patients.

The aim of this study was to investigate whether insulin resistance is independently associated with early manifestations of atherosclerosis. To this end, 176 normotensive offspring of type 2 diabetic patients were subjected to euglycemic hyperinsulinemic clamp to assess insulin sensitivity. Early atherosclerosis was studied by ultrasonography of the common carotid artery. Of the total 176 subjects, 145 were glucose tolerant, 18 had impaired fasting glucose, and 13 had impaired glucose tolerance. Univariate correlations showed that age, body mass index, waist, blood pressure, 2-h postchallenge glucose, fasting insulin, triglycerides, interleukin-6, fibrinogen, and white blood cell count were significantly correlated with carotid intima-media thickness (IMT), whereas HDL cholesterol and glucose disposal showed a negative correlation. A stepwise multivariate regression analysis including sex, age, waist circumference, smoking status, systolic blood pressure, diastolic blood pressure, triglyceride, HDL cholesterol, 2-h postchallenge glucose, plasma IL-6, fibrinogen, white blood cell count, insulin-stimulated glucose disposal, and fasting insulin showed that the four variables that remained significantly associated with carotid IMT were waist circumference, insulin-stimulated glucose disposal, white blood cell count, and diastolic blood pressure, accounting for 33.7% of its variation. These findings support the concept that insulin sensitivity, rather than plasma insulin levels, is associated with early atherosclerosis in nondiabetic normotensive offspring of type 2 diabetic patients.

Adult↗

Uric acid and endothelial dysfunction in essential hypertension.

Recent epidemiologic and experimental evidence suggests that serum uric acid (UA) is an independent risk factor for cardiovascular and renal diseases. However, endothelial dysfunction is an early predictor of cardiovascular events, particularly in hypertensive patients. For assessment of the association between UA and endothelial function, 217 (108 men, 109 women; aged 48.0 +/- 10.6 yr) white never-treated hypertensive patients were studied. All patients underwent the following procedures: BP measurements, laboratory tests (C-reactive protein [CRP], insulin resistance by homeostasis model assessment, serum creatinine, and UA), and endothelial function evaluated by intra-arterial infusion of acetylcholine (ACh). Serum creatinine, CRP, and maximal vasodilatory response to ACh were related to the UA (all P < 0.0001). In the multiple regression analysis, serum UA ranked as the third correlate of peak of forearm blood flow predictor, after homeostasis model assessment and CRP. The data show an independent link between UA and endothelial function, also in a statistical model that included CRP. In conclusion, the data demonstrate an inverse and significant relationship between UA and ACh-stimulated vasodilation in patients with uncomplicated, untreated essential hypertension, independent of traditional cardiovascular risk factors. Probably, the chronic inflammation that was documented in these patients may be considered the mechanistic link between serum UA and vascular damage.

Adult↗

The E23K variant of KCNJ11 encoding the pancreatic beta-cell adenosine 5'-triphosphate-sensitive potassium channel subunit Kir6.2 is associated with an increased risk of secondary failure to sulfonylurea in patients with type 2 diabetes.

CONTEXT: Several studies suggest that genetic factors may play a role in the different responses to antidiabetic therapy; however, conclusive evidence is still lacking. OBJECTIVE: The objective of the study was to investigate whether diabetic patients carrying the E23K variant in KCNJ11 are at increased risk for secondary sulfonylurea failure. DESIGN: Secondary sulfonylurea failure was defined as fasting plasma glucose greater than 300 mg/dl despite sulfonylurea-metformin combined therapy and appropriate diet, in the absence of other conditions causing hyperglycemia. SETTING: The study was conducted in an ambulatory care facility. PATIENTS: A total of 525 Caucasian type 2 diabetic patients were enrolled in the study. INTERVENTION: Sulfonylurea treatment was followed by sulfonylurea-metformin combined therapy and then insulin treatment. MAIN OUTCOME MEASURE: Secondary failure was the main outcome measure. RESULTS: Of the diabetic patients enrolled in the study, 38.5% were E23E homozygous, 51.4% were E23K heterozygous, and 10.1% were K23K homozygous. The frequency of carriers of the K allele was 58 and 66.8% among patients treated with oral therapy or secondary sulfonylurea failure, respectively (odds ratio, 1.45; 95% confidence interval, 1.01-2.09; P = 0.04). Adjustment for age, gender, fasting glycemia, glycosylated hemoglobin, age at diagnosis, and duration of diabetes in a logistic regression analysis did not change this association (odds ratio, 1.69; 95% confidence interval, 1.02-2.78; P = 0.04). Islets isolated from carriers of the K allele showed no differences in glucose-stimulated insulin secretion and a tendency toward reduced response upon glibenclamide stimulation (P = 0.09). After 24-h exposure to high (16.7 mmol/liter) glucose concentration, impairment of glibenclamide-induced insulin release was significantly (P = 0.01) worse with the E23K variant. CONCLUSIONS: These data suggest that the E23K variant in KCNJ11 may influence the variability in the response of patients to sulfonylureas, thus representing an example of pharmacogenetics in type 2 diabetes.

Adult↗

Effect of interaction between left ventricular dysfunction and endothelial function in hypertension.

Hypertension, one of the most important risk factors for cardiovascular diseases, is associated with both left ventricular hypertrophy and endothelial dysfunction. Both have been recently recognized as independent predictors of clinical events in different groups of patients. In fact, a dysfunctioning endothelium loses its antiatherosclerotic and antithrombotic action, and, therefore, promotes the atherosclerotic process. Similarly, cardiac hypertrophy is recognized as a powerful and independent risk factor for cardiovascular morbidity and mortality because it predisposes to arrhythmias and maximizes the consequences of acute myocardial ischemia. Recently, an evident interaction has been demonstrated between endothelial dysfunction and left ventricular mass. In particular, the coexistence of both left ventricular hypertrophy and endothelial dysfunction almost doubles the risk for future vascular events in hypertensives. Thus, in hypertensive patients, it is clinically useful to choose an aggressive therapeutic strategy--to reduce left ventricular mass and to improve endothelial function.

Coronary Artery Disease↗

The prognostic value of big endothelin-1 in more than 2,300 patients with heart failure enrolled in the Valsartan Heart Failure Trial (Val-HeFT).

BACKGROUND: Endothelin is elevated in heart failure and contributes to neurohormonal activation, hemodynamic deterioration, and cardiovascular remodeling. Here, we examined its prognostic value in a large population of patients with chronic heart failure. METHODS AND RESULTS: Big endothelin-1 (Big ET-1) and 4 other neurohormones were measured at study entry in 2359 patients enrolled in the Valsartan Heart Failure Trial (Val-HeFT) and their concentrations related to outcome over a median follow-up of 23 months. Baseline concentration of Big ET-1 (median 0.80 pmol/L) was proportional to severity of disease (New York Heart Association class, left ventricular structure and function). High circulating concentrations of brain natriuretic peptide (BNP), creatinine and bilirubin, advanced New York Heart Association class, elevated body mass index, and the presence of atrial fibrillation were independently associated to higher concentrations of Big ET-1. Big ET-1 (ranking second just behind BNP among neurohormonal factors) was an independent predictor of outcome defined as all-cause mortality (hazard ratio 1.49, 95% CI 1.20-1.84, P = .0003) or the combined endpoint of mortality and morbidity (hazard ratio 1.43, 95% CI 1.20-1.69, P < .0001) and provided incremental prognostic value compared with BNP. CONCLUSIONS: In a large population of patients with symptomatic heart failure, the circulating concentration of Big ET-1, a precursor of the paracrine and bioactive peptide ET-1, was an independent marker of mortality and morbidity. In this setting, BNP remained the strongest neurohormonal prognostic factor.

Aged↗

Serum ionized magnesium levels in relation to metabolic syndrome in type 2 diabetic patients.

OBJECTIVE: To evaluate circulating serum ionized magnesium (i-Mg) concentrations in patients with type 2 diabetes mellitus, and to investigate its relationship with the components of the metabolic syndrome. DESIGN: cross-sectional study. SETTING: Outpatients' service for diabetic patients at the University Hospital of Messina, Italy. SUBJECTS: 290 patients with type 2 diabetes mellitus. MEASURES OF OUTCOME: Serum i-Mg was measured by ion selective electrode. Age, gender, body mass index (BMI), waist circumference, blood pressure, fasting glucose, HbA1c, HDL cholesterol, triglycerides, and urinary albumin excretion rate (UAER) were considered in the analyses. Patients with hypomagnesemia, defined as serum i-Mg <0.46 mmol/l, were compared with those having normal serum i-Mg levels, and variables proven to be associated with low i-Mg levels in the univariate analysis were entered in a multivariable logistic regression model to obtain a deconfounded estimate of the association between metabolic parameters and hypomagnesemia. RESULTS: In univariate analysis, serum i-Mg levels were significantly reduced in patients with low HDL cholesterol, high triglycerides values, high waist circumference, high blood pressure, microalbuminuria and clinical proteinuria. Hypomagnesemia was highly prevalent in our study population (N = 143, 49.3%). After adjusting for potential confounders, plasma triglycerides (OR = 4.71; 95% CI = 2.56-8.67), waist circumference (OR = 2.21; 95% CI = 1.21-4.04), microalbuminuria (OR = 2.43; 95% CI = 1.16-5.08) and clinical proteinuria (OR = 2.04; 95% CI = 1.02-5.68) were independently associated with hypomagnesemia. CONCLUSIONS: Hypomagnesemia is highly prevalent in diabetic outpatients. High plasma triglycerides, waist circumference and albuminuria are independent correlates of hypomagnesemia.

Albuminuria↗

Inflammation as a mediator of the link between mild to moderate renal insufficiency and endothelial dysfunction in essential hypertension.

The relationship among inflammation (plasma high-sensitivity C-reactive protein [CRP]), endothelial function (hemodynamic response to acetylcholine [ACh] in the forearm), and renal function (serum creatinine and GFR [Modification of Diet in Renal Disease formula]) was investigated in 264 never-treated individuals with uncomplicated essential hypertension and serum creatinine within the normal range. Multiple regression models of renal function (creatinine) were constructed in sequence including Framingham risk factors as well the hemodynamic response to ACh and plasma CRP. The inclusion of endothelial function into a model based on Framingham risk factors added highly significant (P < 0.001) power to this model (+5%). Of note, in an alternative model that included CRP (instead of endothelial function), the creatinine variance explained by this factor was two times higher (+10%) than that associated with endothelial function in the first model. In the full model that included both endothelial function and CRP, CRP maintained a much stronger independent link with the outcome measure than endothelial function. In individuals with untreated, uncomplicated essential hypertension, multivariate modeling indicated that inflammation is a crucial mechanism mediating the endothelial-renal function link. The proatherogenic potential of inflammation associated with subtle impairment in renal function may contribute to the cardiovascular risk of essential hypertension.

Acetylcholine↗

Variants of the interleukin-10 promoter gene are associated with obesity and insulin resistance but not type 2 diabetes in caucasian italian subjects.

Interleukin (IL)-10 is a major anti-inflammatory cytokine that has been associated with obesity and type 2 diabetes. The three polymorphisms -1082G/A, -819C/T, and -592C/A in the IL10 promoter were reported to influence IL10 transcription. We investigated whether these polymorphisms were associated with type 2 diabetes and related traits in a cohort of Italian Caucasians comprising 551 type 2 diabetic and 1,131 control subjects. The -819C/T and -592C/A polymorphisms were in perfect linkage disequilibrium (r(2) = 1.0). The -1082G/A polymorphism was not associated with type 2 diabetes or related traits. Although the -592C/A polymorphism was not associated with type 2 diabetes, nondiabetic homozygous carriers of the A allele showed increased BMI and insulin resistance and lower plasma IL-10 levels compared with the other genotypes. In the nondiabetic group, the ATA haplotype was associated with an increased risk for obesity (odds ratio 1.28 [95% CI 1.02-1.60]; P = 0.02). The ATA/ATA composite genotype was associated with an increased risk for obesity (1.96 [1.16-3.31]; P = 0.01) and insulin resistance (1.99 [1.12-3.53]; P = 0.01). This study suggests that polymorphisms and haplotypes of the IL10 promoter may be associated with obesity and insulin resistance in a large sample of Italian Caucasians.

Adult↗

Plasma interleukin-6 levels are independently associated with insulin secretion in a cohort of Italian-Caucasian nondiabetic subjects.

We have investigated the relationships between plasma interleukin-6 (IL-6) levels and insulin sensitivity and insulin secretion in a cohort of Italian-Caucasian glucose-tolerant subjects. Insulin sensitivity was assessed by euglycemic-hyperinsulinemic clamp, and first-phase insulin secretion was measured by intravenous glucose tolerance test. Fasting plasma IL-6 concentration was negatively correlated with the rate of insulin-stimulated glucose disposal (M) (P = 0.001). The correlation remained statistically significant, while attenuated, after adjusting for sex, age, and BMI (P < 0.03); after an additional adjustment for free fatty acids (FFAs), a further attenuation was observed, but statistical significance was maintained (P < 0.044). Fasting plasma IL-6 concentration was positively correlated with first-phase insulin secretion assessed as acute insulin response (AIR) (P = 0.001). The correlation remained significant after adjusting for sex, age, and BMI (P = 0.003). To estimate the independent contribution of plasma IL-6 levels to AIR, we carried out forward stepwise linear regression analysis in a model that included sex, age, BMI, waist-to-hip ratio, FFAs, and insulin-stimulated glucose disposal. Only insulin sensitivity and plasma IL-6 concentration were independently associated with AIR, accounting, respectively, for 19.0 and 5.2% of its variation. These data indicate that IL-6 is associated in a reciprocal manner with the two pathophysiological components of type 2 diabetes, i.e., insulin resistance and insulin secretion.

Adult↗

HEARTFAID: A knowledge based platform of services for supporting medical-clinical management of heart failure within elderly population.

HEARTFAID is a research and development project aimed at devising, developing and validating an innovative knowledge based platform of services, able to improve early diagnosis and to make more effective the medical-clinical management of heart diseases within elderly population. Chronic Heart Failure is one of the most remarkable health problems for prevalence and morbidity, especially in the developed western countries, with a strong impact in terms of social and economic effects. All these aspects are typically emphasized within the elderly population, with very frequent hospital admissions and a significant increase of medical costs. Recent studies and experiences have demonstrated that accurate heart failure management programs, based on a suitable integration of inpatient and outpatient clinical procedures, might prevent and reduce hospital admissions, improving clinical status and reducing costs. HEARTFAID aims at defining efficient and effective health care delivery organization and management models for the "optimal" management of the care in the field of cardiovascular diseases. The HEARTFAID innovative computerized system will improve the processes of diagnosis, prognosis and therapy provision, providing the following services: * electronic health record for easy and ubiquitous access to heterogeneous patients data;* integrated services for healthcare professionals, including patient telemonitoring, signal and image processing, alert and alarm system;* clinical decision support in the heart failure domain, based on pattern recognition in historical data, knowledge discovery analysis and inferences on patients' clinical data.The formalization of the pre-existing clinical knowledge and the discovery of new elicited knowledge represent the core of the HEARTFAID platform.

Aged↗

Asymmetric dimethylarginine, L-arginine, and endothelial dysfunction in essential hypertension.

OBJECTIVES: We investigated the relationship between ADMA plasma levels and endothelium-dependent vasodilation in 36 never-treated essential hypertensives and in 8 normotensive healthy subjects. BACKGROUND: It has been demonstrated that endothelium-dependent vasodilatation is impaired in essential hypertension. The potential contribution of asymmetric dimethylarginine (ADMA) to endothelial dysfunction of hypertensive humans has received poor attention. METHODS: Endothelial function was measured during intra-arterial infusion of acetylcholine (ACh), alone and during co-infusion of L-arginine, and sodium nitroprusside at increasing doses. Concentrations of ADMA and L-arginine in plasma were measured by high-performance liquid chromatography. RESULTS: Hypertensive subjects had significantly higher ADMA and L-arginine plasma concentrations than normotensive healthy controls; ACh-stimulated forearm blood flow (FBF) was significantly reduced in hypertensive subjects in comparison to normotensive control subjects (p < 0.0001). Intra-arterial coinfusion of L-arginine induced a further significant enhancement in ACh-stimulated vasodilation in hypertensive patients. In these, ADMA was strongly and inversely associated with the peak increase in FBF. In a multivariate model, only ADMA and L-arginine were independent correlates, accounting for 33.9% and 8.9% of the variability in the peak FBF response to ACh (p < 0.0001), respectively. CONCLUSIONS: The main finding in this study is that in essential hypertensives the L-arginine and endogenous inhibitor of nitric oxide synthase, ADMA, are inversely related to endothelial function.

Acetylcholine↗

Association of LDL cholesterol with carotid atherosclerosis in menopausal women affected by the metabolic syndrome.

BACKGROUND AND AIM: The metabolic syndrome is a highly prevalent condition associated with cardiovascular disease. However, the contribution of LDL to cardiovascular risk is not estimated since it is not part of ATP III criteria. METHODS AND RESULTS: This is an observational study evaluating the association between metabolic syndrome and carotid atherosclerosis, according to LDL cholesterol levels. Two hundred and sixty-five menopausal women were consecutively enrolled, they all underwent clinical examination, biochemical characterization and ultrasound evaluation. In particular, carotid atherosclerosis, a well known marker of cardiovascular disease, was evaluated. Women affected by cardiovascular disease were excluded from the study. The metabolic syndrome was found strongly associated with carotid atherosclerosis in our study population. In individuals with normal or near normal LDL, the incidence of carotid atherosclerosis was significantly lower than in subject with high LDL. A high plasma LDL concentration was independently associated with carotid atherosclerosis (p=0.026) among women with the metabolic syndrome. CONCLUSIONS: High LDL cholesterol levels are associated with carotid atherosclerosis in menopausal women with the metabolic syndrome. Although it remains prudent to recommend an integrated control of all modifiable risk factors to prevent cardiovascular disease, decreasing LDL levels should be considered a high priority.

Aged↗