Preclinical atherosclerosis and metabolic syndrome increase cardio- and cerebrovascular events rate: a 20-year follow up.

BACKGROUND: Intima-media thickness (IMT) is a validated marker of preclinical atherosclerosis and a predictor of cardiovascular events. PATIENTS: We studied a population of 529 asymptomatic patients (age 62 ± 12.8 years), divided into two groups of subjects with and without Metabolic Syndrome (MetS). METHODS: All patients, at baseline, have had a carotid ultrasound evaluation and classified in two subgroups: the first one without atherosclerotic lesions and the second one with preclinical atherosclerosis (increased IMT or asymptomatic carotid plaque). Cardiovascular endpoints were investigated in a 20-years follow-up. RESULTS: There were 242 cardiovascular events: 144 among patients with MetS and 98 among in healthy controls (57.4% vs. 35.2%; P < 0.0001). 63 events occurred in patients with normal carotid arteries, while 179 events occurred in patients with preclinical atherosclerosis (31.8% vs. 54.1%; P < 0.0001). Of the 144 total events occurred in patients with MetS, 36 happened in the subgroup with normal carotid arteries and 108 in the subgroup with preclinical atherosclerosis (45% vs. 63.15%; P = 0.009). 98 events occurred in patients without MetS, of which 27 in the subgroup with normal carotid arteries and 71 in the subgroup with preclinical atherosclerosis (22.88% vs. 44.37%; P = 0.0003). In addition, considering the 63 total events occurred in patients without atherosclerotic lesions, 36 events were recorded in the subgroup with MetS and 27 events in the subgroup without MetS (45% vs. 22.88%; P = 0.0019). Finally, in 179 total events recorded in patients with preclinical carotid atherosclerosis, 108 happened in the subgroup with MetS and 71 happened in the subgroup without MetS (63.15% vs. 44.37%; P = 0.0009). The Kaplan-Meier function showed an improved survival in patients without atherosclerotic lesions compared with patients with carotid ultrasound alterations (P = 0.01, HR: 0.7366, CI: 0.5479 to 0.9904). CONCLUSIONS: Preclinical atherosclerosis leads to an increased risk of cardiovascular events, especially if it is associated with MetS.

Xioglican Cream in Italian Patients with Chronic Venous Disease: A Post-Marketing Study Investigating Effects on Clinical and Cutaneous Signs and Symptoms.

INTRODUCTION: The progression of chronic venous disease (CVD) is characterized by edema of the legs and/or venous ulcers of the lower limbs in association with cutaneous signs and/or skin alterations, such as hyperpigmentation, corona phlebectatica, telangiectasia, eczematous dermatitis, lipodermatosclerosis, atrophie blanche, cellulitis, and induration. Xioglican cream is a galactosaminoglycan polysulfate and hyaluronic acid-containing medical device with strong hydrophilic, moisturizing, and soothing properties. This post-marketing observational study evaluated topical Xioglican cream in the amelioration of skin manifestations and clinical signs and symptoms in patients with CVD treated in routine clinical practice. METHODS: Adult patients (18-75 years) with a clinical diagnosis of C2-C3 CVD according to Clinical, Etiology, Anatomy, and Pathophysiology (CEAP) classification who received 12 weeks of treatment with Xioglican (applied up to 3 times daily), according to investigator decision (and consistent with conventional clinical practice and established standard of care), were enrolled from two study sites in Italy. A range of endpoints were used to evaluate efficacy, safety, effect on patient quality of life (QoL), and patient satisfaction with topical application of Xioglican cream in the physiological restoration of skin signs and symptoms. RESULTS: In patients with CVD (n = 30), Xioglican cream reduced CVD-related skin manifestations and associated symptoms, with significant reductions in leg circumference [mean ± standard deviation (SD): - 3.21 ± 3.39 cm for left and - 2.92 ± 2.70 cm for right legs, both p < 0.0001] and local edema (- 5.52 ± 7.94 cm, p = 0.0034) and significant improvement in Venous Clinical Severity Scores (mean 0.52 ± 1.94 decrease from baseline, p = 0.1952) observed after 12 weeks. Skin burning, pain, aching or tiredness, and QoL were also significantly improved. There was no change in CEAP classification. Globally, 92.0% of patients were "Very satisfied" or "Satisfied" with the product. CONCLUSIONS: Topical treatment with Xioglican cream improves the signs, symptoms, and QoL of patients with CVD class C2-C3.

Asymptomatic carotid lesions add to cardiovascular risk prediction.

AIM: To show that subclinical atherosclerosis (subclinical-ATS) of carotid arteries [intima-media thickness (IMT) or asymptomatic carotid plaque (ACP)], may provide additional information for risk stratification, in asymptomatic patients, aged greater than 45 years, with a cluster of risk factors (RFs). METHODS AND RESULTS: We studied 558 asymptomatic patients (235 males). RFs for atherosclerosis were assessed and the 10-year-risk was calculated according to the Italian risk score. Doppler ultrasound of carotid arteries identified the presence of IMT greater than 0.9 mm in 183 patients and ACP in 147 patients. One hundred and fifty-three patients developed cerebrovascular or cardiovascular (CV) events in the follow-up: 67 developed acute myocardial infarction, 39 developed angina, 25 had a stroke or transient ischemic attack, six died for CV events, and 16 underwent percutaneous or surgical revascularization. The incidence reflected the different risk profiles (4, 14, and 20%, respectively). However, in patients with baseline subclinical-ATS the incidence of events increased to 35, 46, and 63%, respectively. In the multivariate analysis the incidence of events was significantly influenced by the presence of asymptomatic carotid lesions in each risk category. CONCLUSION: In our experience, the incidence of CV events is enhanced in patients with subclinical-ATS. Increased IMT and ACP predict CV events and improve the risk stratification of asymptomatic patients aged greater than 45 years and with a cluster of RFs, in a long-term follow-up.

Impact of preclinical carotid atherosclerosis on global cardiovascular risk stratification and events in a 10-year follow-up: comparison between the algorithms of the Framingham Heart Study, the European SCORE and the Italian 'Progetto Cuore'.

BACKGROUND: The aim of the study was to compare three widely used algorithms for stratification of the global cardiovascular risk (GCVR): the Framingham Heart Study (FHS) score, the European systemic coronary risk estimation (SCORE) and the Italian 'Progetto Cuore' (heart project) score. It was also investigated how preclinical carotid atherosclerosis (pre-ATS) might influence the incidence and improve the risk prediction of cerebrovascular and cardiovascular events. METHODS: Subjects (n = 358) without previous history of cardiovascular disease (CVD) were recruited and the GCVR was calculated for each patient. An ultrasound evaluation of the carotid arteries was also performed. RESULTS: According to SCORE, the recruited population had globally a low risk of cardiovascular mortality and the risk equation estimated a GCVR of 2% in spite of the in spite of the observed rate of 0.8% (95% CI -0.001 to 0.02) of fatal events. The FHS and the 'Progetto Cuore' risk equations, regarding a 10-year risk of fatal and nonfatal events, predicted a low GCVR of 31 and 30%, an intermediate risk of 64 and 66%, and a high risk of 5 and 4% of the population respectively. They also estimated a general GCVR of 6.9 and 6.4% respectively versus an observed event rate 27.7 (95% CI 23.0 to 32.0). The discriminative power, calculated with the area under the receiving operator curve (AUROC), was 0.53 for SCORE, 0.54 for FHS and 0.55 for Progetto Cuore. Based on the ultrasound evaluation of carotid arteries, a first clinical event at 10-year follow-up was reported in 3% of subjects with normal ultrasound examination, 32% with intima-media thickening (IMT) and 62% with asymptomatic carotid plaque (ACP). CONCLUSION: The present study has evaluated for the first time the prediction of GCVR in an asymptomatic population, comparing three different risk scores. Carotid pre-ATS was related to the major cardiovascular risk factors (RFs) and was independently associated with a major incidence of cerebro- and cardiovascular events, therefore enhancing the predictive value of the three different risk scores.

Older age and markers of inflammation are strong predictors of clinical events in women with asymptomatic carotid lesions.

OBJECTIVE: Limited information exists regarding the association between markers of inflammation, such as high-sensitivity C-reactive protein (hs-CRP) and fibrinogen, and adverse events in postmenopausal women with subclinical atherosclerosis. Therefore, we investigated the prognostic impact of traditional risk factors and inflammation on adverse cardiac events in women with asymptomatic carotid lesions. DESIGN: We studied 250 postmenopausal women who were free of cardiovascular disease. Traditional cardiovascular risk factors were investigated, and laboratory analysis included measurement of plasma lipids, fibrinogen, and hs-CRP. The early phases of carotid atherosclerosis were assessed by B-mode ultrasonography. Women were asked about symptoms or a previous history of coronary artery disease and were followed for a period of 5 years. RESULTS: We found that the increment in age (in quintiles) was significantly associated with higher incidence of current smokers (P = 0.0286), hypertension (P = 0.0230), family history of coronary artery disease (P = 0.0216), dyslipidemia (P = 0.0330), and higher levels of fibrinogen (P = 0.0158). Moreover, older women had a higher prevalence of carotid lesions (P < 0.0001). After the follow-up, cardio- and cerebrovascular events were registered in 22% of the women. Using multivariate analysis, we observed that older age (odds ratio [OR], 1.7; 95% CI, 1.3-2.2; P < 0.0001), fibrinogen (OR, 1.6; 95% CI, 1.2-2.0; P < 0.0001), the presence of carotid lesions (OR, 2.0; 95% CI, 1.4-3.0; P = 0.0002), and hs-CRP (OR, 1.3; 95% CI, 1.2-2.0; P = 0.0175) were predictors of adverse events during the follow-up. CONCLUSIONS: Adverse events occurred more frequently in women with higher levels of fibrinogen and hs-CRP. The significance of these results requires confirmation in other studies, but they may have important implications for screening subjects at risk for cardiovascular disease and identifying candidates for anti-inflammatory therapy.

Endothelial dysfunction and carotid lesions are strong predictors of clinical events in patients with early stages of atherosclerosis: a 24-month follow-up study.

BACKGROUND: The purpose of this study was to investigate whether the vasodilator response to brachial artery and the presence of carotid lesions may have a prognostic significance in patients with early stages of atherosclerosis. METHODS AND RESULTS: Vascular echography was performed to analyze flow-mediated vasodilatation (FMD) at the brachial artery and intima-media thickness (IMT) of carotid arteries in 84 asymptomatic patients. At baseline, we evaluated all the established traditional cardiovascular risk factors. Transient ischemic attack, stroke, effort or unstable angina, acute myocardial infarction, peripheral arterial disease and cerebrovascular and cardiovascular death served as outcome variables over a follow-up period of 24 months. Brachial FMD was correlated inversely with carotid IMT (P=0.003), systolic blood pressure (P=0.0001) and age (P=0.0001). IMT was positively correlated with systolic blood pressure (P=0.0001), waist circumference (P=0.004) and age (P=0.01). At the end of the follow-up cardiovascular and cerebrovascular events were registered in 29% of the patients and in a multivariate analysis, including all the variables evaluated at baseline, male sex [odds ratio (OR) 1.6, P=0.005], the presence of baseline carotid lesions (OR 3.5, P=0.02) and FMD below the median (OR 3.2, P=0.03) were the only variables predictive of clinical events. CONCLUSION: In this study, endothelial dysfunction and carotid lesions significantly increased the risk of vascular events in asymptomatic patients with early stages of atherosclerosis. Assessment of systemic vasoreactivity and carotid IMT evaluation may provide, in this category of patients, important prognostic information in addition to that derived from traditional established cardiovascular risk factors.

Prediction of cerebrovascular and cardiovascular events in patients with subclinical carotid atherosclerosis: the role of C-reactive protein.

BACKGROUND: Several studies have suggested that inflammation and infection may be important for accelerated progression of atherosclerosis, but few data are available on subjects with early stages of atherosclerosis. METHODS AND RESULTS: We included, in a prospective 5-year follow-up study, 150 patients with subclinical carotid atherosclerosis, evaluating at baseline all established traditional cardiovascular risk factors (eg, older age, male sex, obesity, hypertension, diabetes, smoking, family history of coronary artery disease, and dyslipidemia); 2 markers of inflammation, fibrinogen, and high-sensitivity C-reactive protein (CRP); and the seropositivity to Helicobacter pylori, Chlamydia pneumoniae, and cytomegalovirus. After follow-up, cardiovascular and cerebrovascular events were registered in the 19% of patients, and the increment in CRP levels (in quintiles) was significantly associated with ischemic stroke (P = 0.0253), acute myocardial infarction (P = 0.0055), cardiovascular or cerebrovascular death (P = 0.0145), and the presence of any event (P = 0.0064). Most traditional cardiovascular risk factors (eg, older age, hypertension, diabetes, and dyslipidemia) were significantly associated with the events but only in the unadjusted analysis; in fact, at logistic regression analysis, among all baseline variables, only elevated CRP levels showed a predictive role (odds ratio, 7.0; 95% confidence interval, 2.2-18.4; P = 0.0247). CONCLUSIONS: Our findings suggest that elevated CRP concentrations may significantly influence the occurrence of cerebrovascular and cardiovascular events in patients with baseline subclinical carotid atherosclerosis. Notably, null findings were obtained by viral and bacteria titers, suggesting a greater role of inflammation (and not of infection) in the progression of atherosclerosis in our cohort. However, further studies are needed to evaluate the therapeutic implications in this category of patients.

Peripheral atherosclerosis is associated with the occurrence of restenosis after percutaneous coronary intervention.

INTRODUCTION: The aim of our study was to evaluate, in patients with proven coronary artery disease (CAD) and treated with elective percutaneous coronary intervention (PCI), whether the coexistence of asymptomatic carotid and femoral atherosclerotic lesions would provide prognostic information in terms of occurrence of restenosis. METHODS: We studied 104 patients with CAD (M/F=77/27), mean age 60.5+/-9 years. All patients were treated with elective PCI. After PCI the suspicion of restenosis was confirmed by coronary angiography. All patients underwent ultrasound duplex scan of carotid and femoral-popliteal-tibial axis to detect atherosclerotic lesions. According to ultrasound results, patients were classified as normal, with increased intima-media thickness (IMT) or with asymptomatic plaque (AP). If carotid and femoral lesions coexisted (together with coronary ones) patients were considered to have multifocal atherosclerosis. RESULTS: About 90% of the patients had carotid lesions: 40% had carotid IMT and 50% AP. Femoral lesions were found in 72% of the population and in 41% there was an increased IMT and in 21% an increased AP. Prevalence of restenosis after PCI was 12.5%. Patients with restenosis had a significantly higher prevalence of asymptomatic carotid and/or femoral lesions than those without restenosis. The occurrence of restenosis was independently associated with the detection of carotid, femoral and multifocal atherosclerosis. CONCLUSION: The detection of carotid and/or peripheral atherosclerotic lesions in patients with CAD who underwent PCI may be a marker of increased risk. We believe that investigating these areas, by echo-Doppler duplex scanning, may be a cost-effective strategy in the work-up before elective PCI. It may allow identification of high-risk subgroups of patients, and enable the planning of patient-tailored therapeutic strategies and follow-up.

Markers of inflammation and infection influence the outcome of patients with baseline asymptomatic carotid lesions: a 5-year follow-up study.

BACKGROUND AND PURPOSE: It is still in debate whether the evaluation of markers of infection and inflammation may be of importance for cerebrovascular and cardiovascular prevention, and we aimed to investigate this field in a prospective 5-year clinical follow-up study in patients with early stages of atherosclerosis. METHODS: We studied 668 subjects divided in 3 groups according to the results of carotid ultrasound examination: (1) normal subjects, if intima-media thickness (IMT) was <0.9 mm; (2) with IMT, if IMT was between 0.9 and 1.5 mm; and (3) with asymptomatic carotid plaque, if IMT was >1.5 mm. Traditional cardiovascular risk factors were investigated, and laboratory analysis included measurement of plasma lipids, fibrinogen, C-reactive protein, IgG antibodies for helicobacter pylori (HP), cytotoxic HP, cytomegalovirus, and chlamydia pneumoniae. RESULTS: Cerebrovascular or cardiovascular events were registered in 18% of patients during the follow-up, and at multivariate analysis we found that the high levels of fibrinogen (P<0.0001) and C-reactive protein (P=0.014), the seropositivity to cytotoxic HP (P=0.001) and chlamydia pneumoniae (P=0.026), the presence of IMT or asymptomatic carotid plaque (P<0.0001), and the total burden of infections (P<0.0001) were the variables predictive of the clinical events. CONCLUSIONS: Beyond traditional cardiovascular risk factors, markers of inflammation and infections seem to significantly influence the occurrence of cerebrovascular and cardiovascular events in patients with baseline asymptomatic carotid lesions.

Association of elevated fibrinogen and C-reactive protein levels with carotid lesions in patients with newly diagnosed hypertension or type II diabetes.

BACKGROUND: Inflammation may be important for accelerated progression of atherosclerosis in patients with hypertension or diabetes, but few studies included subjects with early stages of atherosclerosis such as those with asymptomatic carotid lesions. METHODS: We studied 100 patients with newly diagnosed hypertension and another 100 patients with newly diagnosed type II diabetes to evaluate in such groups the association of two markers of inflammation, fibrinogen and C-reactive protein (CRP), with carotid atherosclerosis, beyond traditional cardiovascular risk factors (e.g., older age, male gender, obesity, smoking, family history of CAD, dyslipidemia). RESULTS: We found positive correlation between the extent of carotid intima-media thickness (IMT) and levels of CRP (p <0.0001 in both groups) and fibrinogen (p <0.0001 in diabetics only). By multivariate analysis we searched, among all evaluated cardiovascular risk factors including markers of inflammation, for independent variables associated with carotid lesions (IMT >1.5 mm) and found in patients with hypertension a predictive role for elevated levels of CRP (OR 4.1, 95% CI 1.1-16.4, p = 0.0429), whereas in diabetics we found a predictive role for elevated levels of fibrinogen (OR 6.0, 95% CI 2.0-18.1, p = 0.0014) and CRP (OR 4.4, 95% CI 1.4-13.7, p = 0.0096). CONCLUSIONS: Recent studies have addressed the importance of therapeutic modulation of CRP and fibrinogen levels in high-risk patients for cardiovascular prevention; however, beyond the utility of these markers in the prediction of carotid lesions in subjects with newly diagnosed hypertension or diabetes, further studies are needed to evaluate the therapeutic implications in such patients.

Asymptomatic carotid lesions and aging: Role of hypertension and other traditional and emerging risk factors.

BACKGROUND: We evaluated the prevalence of intima-media thickening (IMT) and asymptomatic carotid plaque (ACP) in a group of subjects with or without traditional and/or emerging risk factors (RF). METHODS: There were 631 subjects (313 male and 318 female) aged between 19 and 97 years, asymptomatic for cerebro- and cardiovascular diseases. The following measurements were used: anamnesis, physical examination, height and sitting blood pressure. Biochemistry variables were also considered: total cholesterol, HDL-C, LDL-C, triglycerides, fibrinogen, high sensitive C-reactive protein, IgG antibodies for Helicobacter pylori (HP), cytotoxic HP, cytomegalovirus and Chlamydia pneumoniae. Finally, an echo color Doppler examination of the carotid arteries was performed. We subdivided the population studied in normotensive and hypertensive subjects and evaluated in each group the frequency of IMT and ACP in relation to age. RESULTS: We showed that IMT + ACP was significantly more frequent in patients >65 years in comparison with those <65 years (80.6 vs. 52.1%, p < 0.005) and in hypertensive patients in comparison to normotensive, independent of coexistence of other cardiovascular risk factors (71 vs. 48%, p < 0.005). Another interesting result of our study is a significant presence of IMT and ACP in subjects with emerging but without traditional RF than in subjects with traditional but without emerging RF. CONCLUSIONS: IMT and ACP of carotid arteries are significantly more frequent in patients >65 years vs. those <65 years and in hypertensive patients in comparison to controls. Finally, we have found that the seropositivity of infection and the presence of higher levels of marker of inflammation were correlated with carotid lesion.

Increased levels of C-reactive protein and fibrinogen influence the risk of vascular events in patients with NIDDM.

AIM: To evaluate the predictive role of hs-CRP and fibrinogen for cardio- and cerebrovascular events in a population of patients with type 2 diabetes. METHODS: We studied 156 patients with type 2 diabetes, mean age 66+10 years, and 156 sex and age matched control subjects. Patients underwent physical examination, EKG, measurement of body mass index and blood pressure. A blood sample was drawn to evaluate glycaemia, total and HDL/LDL cholesterol, triglycerides, high sensitive C-reactive protein (hs-CRP), fibrinogen. Finally, patients underwent an ecocolordoppler examination of the common carotid arteries until the bifurcation. In a follow-up of 5+/-1.2 years we evaluated the following events: transient ischemic attack, ischemic stroke, stable or unstable angina, acute myocardial infarction, critical limb ischemia and cardiovascular death. RESULTS: During the follow-up the prevalence of fatal (p<0.05) and non fatal events (p<0.0001) was higher in patients with diabetes in comparison with controls. The variables independently associated with non fatal events were: fibrinogen (p<0.0001), presence of asymptomatic carotid lesion (p<0.005), obesity (p<0.05) and plasma levels of hs-CRP (p<0.05), while fibrinogen (p<0.001) and age were (p<0.05) independently associated with fatal events. CONCLUSION: Our data show that in patients with diabetes mellitus, that in the follow-up the presence of high plasma levels of hs-CRP and fibrinogen are predictive for fatal or non fatal events.

Residual vein thrombosis and onset of post-thrombotic syndrome: influence of the 4G/5G polymorphism of plasminogen activator inhibitor-1 gene.

BACKGROUND: Plasminogen activator inhibitor-1 (PAI-1) is the most important inhibitor of plasminogen activator. The functional 4G/5G polymorphism of the gene coding for PAI-1 may affect PAI-1 plasmatic activity, influencing the imbalance between coagulation and fibrinolysis cascades. In this prospective cohort analytic study, we investigated the role of this single nucleotide polymorphism in the persistence of thrombotic lesion and the occurrence of post-thrombotic syndrome. PATIENTS/METHODS: In a group of 168 patients with post-surgical deep vein thrombosis of the legs, we analyzed the 4G/5G polymorphism in the promoter of PAI-1 gene and plasmatic PAI-1 activity. Enrolled patients were divided in two groups: patients with 4G/5G polymorphism and increased PAI-1 activity (n=85) and patients without 4G/5G polymorphism and normal PAI-1 activity (n=83). All patients were treated according to current protocols and re-examined after 3, 12 and 36 months in order to evaluate the persistence of thrombotic lesion and the occurrence of post-thrombotic syndrome. RESULTS: We found a significantly increased PAI activity in carrier of the 4G allele, who experienced much more frequently a persistence of thrombosis after 3, 12 and 36 months and/or the development of post-thrombosis syndrome, in spite of the anticoagulant treatment. CONCLUSIONS: These data not only confirm the role played by PAI-1 activity and by the 4G/5G SNP of the PAI-1 gene, but also suggest that current therapeutic protocols, recommending the administration of low weight molecular heparin and oral anticoagulant for the treatment of deep vein thrombosis, could be non sufficient for patients genetically predisposed to a less efficient clot lysis.

Preclinical carotid atherosclerosis enhances the global cardiovascular risk and increases the rate of cerebro- and cardiovascular events in a five-year follow-up.

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<0.003). Among evaluated parameters, carotid pre-ATS was a predictive marker of CV events (OR 2.7, 95% IC 1.4-5.1, p<0.0024). In subjects with GCVR<20% the prevalence of events was 8% for normal carotid ultrasound findings, 13% for increased IMT and 15% for ACP. CONCLUSIONS: In primary prevention, the IMT measurement can give further information for a better stratification of GCVR. The pre-ATS of carotid arteries should be considered a strong predictor of future CV events and should suggest a more aggressive treatment of RF.

Markers of inflammation are strong predictors of subclinical and clinical atherosclerosis in women with hypertension.

Cardiovascular diseases in women still rises and remains their leading cause of death in most developed countries; yet we have less sex-specific data in women than in men as a result of lower enrollment in clinical trials and low rates of sex-specific reporting. The aim of our study was to evaluate in hypertensive postmenopausal women the potential predictive role of markers of inflammation, for example, fibrinogen and C-reactive protein (CRP), on subclinical and clinical atherosclerosis, beyond that of the other established cardiovascular risk factors. We studied 127 asymptomatic hypertensive postmenopausal women with different degrees of carotid intima-media thickness, as examined by the eco-color-doppler ultrasonography, evaluating in a 5 years follow-up cerebrovascular and cardiovascular morbidity and mortality. We preliminarily found that both fibrinogen and CRP levels were associated with the extension of carotid atherosclerosis (P<0.0001 and P=0.0445, respectively). We also found that among all established traditional cardiovascular risk factors (including obesity, diabetes, smoking habit, family history of coronary artery disease, dyslipidemia) only older age (P=0.0162), elevated fibrinogen (P=0.0298), and CRP (P=0.0345) were independent predictors of subclinical atherosclerosis. At the end of follow-up patients clinical events were registered in the 24% of patients and multivariate analysis revealed the following predictors of events: elevated CRP levels [odds ratio (OR): 12.6], the presence of family history of coronary artery disease(OR: 8.8) and older age (OR: 1.1). Beyond the utility of CRP and fibrinogen levels in the prediction of subclinical and clinical atherosclerosis, the therapeutic implications of these results remain to be evaluated by further studies.

Prediction of cardio- and cerebro-vascular events in patients with subclinical carotid atherosclerosis and low HDL-cholesterol.

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.

Women and peripheral arterial disease: same disease, different issues.

OBJECTIVES: Atherosclerosis is a multifactorial disease and, thus, its clinical manifestations are likely to present gender-specific differences with respect to their development, course, symptom complexes and prognosis. The present study aimed to examine sex differences in peripheral arterial disease (PAD) and its clinical correlates. METHODS: PAD severity, quality of life (assessed by ST-22), cardiovascular risk factors, inflammatory profile and comorbidity were assessed in 163 men and 68 women who were consecutively diagnosed with PAD at three Italian University vascular centres. RESULTS: Compared to men, women showed a higher prevalence of critical limb ischemia (P = 0.018), but had a less impaired quality of life (assessed by ST-22), and were less likely to have a history of lower extremity revascularization. Furthermore, women tended to be older (P = 0.058), and more likely to present hypercholesterolemia (P = 0.053), diabetes mellitus (P = 0.001), body mass index > or = 30 kg/m2 (P = 0.003) and metabolic syndrome (P = 0.001). Conversely, C-reactive protein plasma levels were similar in the two groups. No gender-specific difference was observed in cardiovascular comorbidity; however, the condition showing the strongest association with coronary artery disease was diabetes mellitus in women (odds ratio = 4.96, P = 0.021), and smoking in men (odds ratio = 2.66, P = 0.008). CONCLUSION: In PAD, there are several sex differences in baseline characteristics, especially with respect to the weight and significance of cardiovascular risk factors. Knowledge of these differences may help achieve optimal gender-specific cardiovascular risk prevention.