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The ability of glycosaminoglycans to bind to a wide number of biologically active macromolecules has already been investigated. Recent clinical trials on the possible therapeutic benefits of glycosaminoglycans must be placed in perspective, even if they appear to be particularly encouraging, especially as regards the glycosaminoglycan effects on certain coagulation factors. A multicenter, medium-term, double-blind, crossover trial was performed by several Italian Lipid Clinics to determine whether administration of a medium molecular weight glycosaminoglycan (Sulodexide) has a significant clinical effect. Patients affected by peripheral vascular disease and/or hyperlipidemia (type IIa, IIb and IV) were submitted to a 4-week wash-out period, followed by parenteral Sulodexide (S) or placebo (P) administration for 2 weeks, another 2 week wash-out period, parenteral crossover drug or P administration for 2 weeks and, finally, oral S administration for 6 months. Sulodexide lowered plasma viscosity and plasma fibrinogen in all patients. There was also a drop in triglycerides together with a rise in apo A-I and HDL-C in type IV hyperlipoproteinemics, whereas there was no significant effect on total or LDL-plasma cholesterol in type IIa and IIb patients. Moreover, there was a percent increase in peak flow and rest flow in the lower limbs of peripheral vascular disease patients. No side effects or intolerance phenomena were detected. The results indicate that Sulodexide administration may be useful in long-term treatment of patients with peripheral vascular disease and a concomitant increase in plasma triglycerides and/or fibrinogen and/or viscosity.

An increased susceptibility of platelets to aggregation induced by various agents and a higher production of active arachidonate metabolism have been described in type IIa hypercholesterolemia. This study was designed to evaluate whether changes in platelet function could be observed in hypercholesterolemic patients after synvinolin therapy. Administration of synvinolin to 12 type IIa hypercholesterolemic patients for 24 weeks had a lipid lowering effect and resulted in a marked reduction of platelet aggregation and thromboxane formation induced by collagen and arachidonate. Maximum response was achieved at 4–8 weeks and lipid lowering effects at 2 weeks. This finding indicates that platelet changes cannot be explained by a direct effect of synvinolin on platelets, and the antiplatelet response may therefore depend on platelet membrane lipid composition changes, particularly in the platelet cholesterol content of platelet membranes, following substantial reductions of total plasma cholesterol and LDL-cholesterol.

Background: The role erectile dysfunction (ED) coupled with low testosterone levels as early markers of atherosclerosis is not well understood. Objectives: To analyze the relationship between serum testosterone levels with both ED and brachial artery flow-mediated vasodilation (FMD), in a primary prevention sample of men. Methods: We enrolled 802 asymptomatic, intermediate CV risk patients, according to the Framingham Risk Score, aged 40e80 years, who underwent the ultrasound examination of FMD, the evaluation of ED and the assessment of total serum testosterone levels. Results: Testosterone levels correlated both with FMD (r ¼ 0.85; p < 0.0001) and IIEF-5 score (rs ¼ 0.65; p < 0.0001). Multivariable logistic regression analyses revealed that lower serum testosterone levels were strongly associated (p < 0.001) with severe (OR 0.78; 95% CI: 0.62e0.86), and moderate ED (OR 0.85; 95% CI: 0.72 e0.97), while impaired FMD percentages were strongly associated (p < 0.001) with severe (OR 0.68; 95% CI: 0.59e0.79), moderate (OR 0.76; 95% CI: 0.63e0.83) and mild to moderate ED (OR 0.8; 95% CI: 0.69 e0.94). Mild ED resulted statistically associated with lower FMD (OR 0.94; 95% CI: 0.82 e 1.07; p ¼ 0.03) but not with serum testosterone levels. These relations were not substantially affected by adjustments for further potential confounders including smoking status, hypertension, diabetes mellitus and body mass index. Conclusions: lower total serum testosterone levels are associated with impaired FMD and ED in this sample of intermediate CV risk men according to the Framingham Risk Score

BACKGROUND: Insulin resistance (IR), which can be quantified by HOMA index (fasting glucose X fasting insulin/22.5), is considered the "primum movens" for the development of Metabolic Syndrome. Many authors have suggested that insulin resistance could raise both incidence and mortality of coronary heart disease (CHD). IR is also associated with important predictors of cardiovascular disease, as increased concentration of LDL or triglyceride, decreased concentration of HDL, high systolic blood pressure, visceral obesity. There is accumulating evidence that chronic sub-clinical inflammation, as measured by inflammatory markers as C-reactive protein (CRP) and fibrinogen, is related with insulin resistance. AIM OF THE STUDY: To clarify if insulin resistance would predict cardiovascular disease independently of the other risk factors, such as hypertension, visceral obesity or dyslipidemia, by focusing our attention on the relation between Acute Coronary Syndrome (ACS) and high HOMA index. METHODS: We evaluated glucose and insulin levels at baseline and post-prandial phase, in order to estimate HOMA index in both the conditions; we related the data obtained with the incidence of cardiovascular events, also investigating traditional cardiovascular risk factors. The cohort included 118 patients with a clinical diagnosis of ACS and excluded those with type 1 diabetes, acute inflammatory diseases, hepatic or renal failure, disreactive disorders, autoimmunity and cancer. SUBJECTS: Subjects were followed-up for a period of 1 year, being subdivided in three groups: (1) subjects at elevated HOMA (HOMA > or = 6); (2) subjects at intermediate HOMA (HOMA or = 2); (3) subjects at low HOMA (HOMA < or = 2). We considered as end points new cardiovascular events, cerebrovascular events (both TIA and stroke), procedures of revascularization with angioplasty or surgery, cardiovascular death, sudden death. RESULTS: Patients with elevated HOMA have a higher incidence of previous cardio- and cerebrovascular events (p=0.03), myocardial infarction without ST elevation (p=0.005), unstable angina (p=0.01), asymptomatic carotid plaques (p=0.05), depressed systolic function (p=0.05); we found, also, a significant statistic correlation between HOMA index and high levels of CRP, fibrinogen, serum creatinine and TnI. Cardiovascular and cerebrovascular events were registered in 61% of patients with elevated HOMA during the follow up, despite of 25% registered in the control group: so we could consider HOMA index as a negative prognostic variable, also in virtue by the statistic correlation with the inflammatory markers, whose power of prediction is already known. CONCLUSIONS: Beyond traditional cardiovascular risk factors, insulin resistance quantified by HOMA index seems to significantly have an important prognostic role, both in primary and secondary prevention in patients with Acute Coronary Syndrome.

AIM: To evaluate if the intima-media thickening (IMT) and asymptomatic carotid plaque (ACP), as expression of carotid preclinical atherosclerosis (pre-ATS), can provide further information on the global cardiovascular risk (GCVR). METHODS: We studied 454 asymptomatic subjects, with a cluster of risk factors (RF), and evaluated the incidence of a first cardiovascular (CV) event in a five-year follow-up. The subjects at admission were subdivided in three groups of risk. RESULTS: Events occurred in 38% of subjects at high risk, in 13% and 6% of subjects at intermediate and low risk (p

BACKGROUND AND PURPOSE: Metabolic syndrome (MetS) is a cluster of cardiovascular risk factors, considered as emerging and promoting atherosclerosis. This study aimed at the evaluation of the influence of MetS on the prediction of cerebro and cardiovascular events during a 20 years follow-up period in an asymptomatic population of middle-aged subjects. METHODS: We evaluated 529 asymptomatic persons through a prospective study. Study population was divided into two subgroups: patients with and without MetS. Echo-color-Doppler was used in order to assess the presence of subclinical atherosclerosis. A 20 years follow-up study was carried out in order to estimate the incidence of cerebro and cardiovascular, fatal and non fatal, events (AMI, stroke, abdominal aortic aneurysm, TIA, angina pectoris). RESULTS: 242 cerebro and cardiovascular events were registered, 43 fatal (24 in MetS and 19 in controls) and 199 non fatal (120 with MetS and 79 without it, p < 0.0001). Free-events survival was lower in patients suffering from MetS (p < 0.0012; HR 0.6847; C.I.95%: 0.5274-0.8889). Ultrasound showed a higher prevalence of subclinical atherosclerosis in patients with MetS than in the unaffected ones (68.12% vs. 57.5% p < 0.01; OR = 1.58 with C.I.95% = 1.10-2.28, p < 0.01). CONCLUSIONS: Patients with MetS have a higher cardiovascular risk that can be explained by atherosclerotic changes: the components of MetS interact to affect vascular thickness synergistically and promote the development of subclinical atherosclerosis. So we recommend to prevent the development of MetS abnormalities and to investigate the presence of subclinical atherosclerosis by echo-color-Doppler in order to stratify more accurately the global CV risk.

Low HDL-cholesterol concentrations are associated with increased cardiovascular risk and recent evidences suggest that HDL may aggravate the atherosclerotic process promoting inflammation: HDL are anti-inflammatory in the absence of inflammation but can become proinflammatory in the presence of atherosclerosis. Yet, no data is available on the cardiovascular outcome in subjects with low HDL-cholesterol and early stages of atherosclerosis. Therefore, we included in a prospective 5-year follow-up study 150 subjects with low HDL-cholesterol concentrations and subclinical carotid atherosclerosis, as assessed by carotid colour doppler, evaluating at baseline all the established traditional cardiovascular risk factors (e.g. male gender, older age, obesity, hypertension, diabetes, smoking, family history of coronary artery disease, hypercholesterolemia), as well as levels of two markers of inflammation (C-reactive protein and fibrinogen). At the end of the follow-up we registered vascular events in the 21% of patients and we found that lower HDL-cholesterol concentrations were associated with ischemic stroke (p = .0164), peripheral arterial disease (p = .0248) and the presence of any clinical event (p = .0105). By multivariate analysis we searched, among all baseline parameters, for independent variables associated with the events and we found a predictive role for elevated fibrinogen concentrations (OR 6.3, 95% CI 2.0–19.6, p = .0016), family history of coronary artery disease (OR 4.5, 95% CI 1.7–12.8, p = .0045) and lower HDL-cholesterol levels (OR 1.4, 95% CI 1.1–1.9, p = .0278). These findings further suggest a synergistic role of low-HDL and inflammation on the atherosclerotic disease progression from subclinical lesions to clinical events. Yet, their therapeutical implications remain to be established in future studies. © 2008 Elsevier Ireland Ltd. All rights reserved.