Behaviour of the plasma concentration of gelatinases and their tissue inhibitors in subjects with venous leg ulcers.

Venous leg ulcers are common in subjects with chronic venous insufficiency. The increased intraluminal pressure causes alteration of the skin microcirculation, leukocyte activation and release of proteolytic enzymes leading to ulceration. An impaired expression and activity of matrix metalloproteases (MMPs) and their tissue inhibitors (TIMPs) might influence extracellular matrix degradation and deposition in chronic venous ulcers with the failure of the healing process. Our aim was to evaluate plasma concentration of gelatinases (MMP-2 and MMP-9) and their inhibitors (TIMP-1 and TIMP-2) in subjects with venous leg ulcers before and after the compression therapy. We enrolled 36 subjects (12 men and 24 women, mean age 67.38 ± 12.7 yrs) with non-infected venous leg ulcers (CEAP C6), which underwent a color Duplex scan examination of the veins and arteries of the inferior limbs and were treated with a multi-layer bandaging system. The ulcer healing was obtained in 23 subjects only (9 men and 14 women). We evaluated, on fasting venous blood, the plasma levels of MMP-2, MMP-9, TIMP-1 and TIMP-2 using ELISA kit, before and after the treatment. We observed a significant increase in plasma concentration of gelatinases and their inhibitors and in MMP-2/TIMP-2 ratio in subjects with leg ulcers in comparison with normal controls. In subjects with healed ulcers we found a decrease in MMP-9 and TIMP-1 levels and in MMP-2/TIMP-2 ratio compared to the baseline values, although higher levels of all the examined parameters in comparison with normal controls. In conclusion, plasma MMPs profile is impaired in subjects with venous leg ulcers and it improves after the healing, persisting anyway altered in respect to healthy controls.

Prevalence of metabolic syndrome: a comparative analysis in an unselected sample of mediterranean subjects.

AIM: The metabolic syndrome (MS) is associated with increased cardiovascular and cerebrovascular risk. This study aimed to compare the difference of the three established diagnostic criteria of MS, developed by Adult Treatment Panel III (ATP III), American Heart Association (AHA) and National Heart Lung and Blood Institute (NHLBI), and International Diabetes Federation (IDF), with regard to the prevalence of the syndrome and the ability to correctly identify individuals with cardiovascular or cerebrovascular disease or subclinical atherosclerosis. METHODS: We studied 947 consecutive patients underwent clinical evaluation between the 1997-2002. The project design included a medical assessment, biochemical analyses and the ecocolordoppler examination of carotid arteries. RESULTS: The MS prevalence was 37% in ATPIII subjects, 36% in AHA/NHLBI subjects and 43% in IDF subjects. Excluding patients with diabetes (N.=259), the MS prevalence ranged from 32% (ATPIII and AHA/NHLBI subjects) and 40% (IDF subjects). By most criteria, MS-positive subjects had significant incidence of carotid atherosclerosis (P<0.05) and cardiovascular events (P<0.05) than MS-negative subjects, but not cerebrovascular events. Finally, patients with MS had higher serum levels of fibrinogen (P<0.04). CONCLUSION: Subclinical atherosclerosis and cardiovascular events were increased in presence of the MS, irrespective of the several definitions.

Prediction of vascular events in subjects with subclinical atherosclerosis and the metabolic syndrome: the role of markers of inflammation.

AIM: The presence of the metabolic syndrome (MS) increases cardiovascular morbidity and mortality and we aimed to assess the outcome in subjects with the MS and subclinical atherosclerosis. METHODS: We followed-up for five years 339 Mediterranean subjects with asymptomatic carotid intima-media thickness >0.9 mm (men: 60%; age: 66±5 years), of whom 130 had the MS (men: 59%; age: 66±5 years), evaluating at baseline traditional cardiovascular risk factors (including male gender, older age, obesity, hypertension, diabetes, smoking, family history of cardiovascular diseases, dyslipidemia) and plasma levels of C-reactive protein and fibrinogen. RESULTS: Cardio- and cerebrovascular events were registered in the 29% of subjects with the MS and in the 20% of those without it and the presence of more criteria for the diagnosis of the MS was significantly associated with vascular morbidity and mortality. By multivariate analysis, including all baseline variables, independent predictive roles for the events were found for elevated markers of inflammation (OR 3.8), elevated fasting glucose (OR 2.1) and elevated triglycerides (OR 1.4). CONCLUSION: These findings confirm a worst vascular outcome in subjects with more criteria for the diagnosis of the MS and further suggest the need of future research to understand the combined role of inflammation and the MS in the progression from subclinical to clinical atherosclerosis.

Medical therapy for patients with subclinical and clinical carotid atherosclerosis.

The management of carotid artery disease includes both modifications in life style as well treatment of vascular risk factors. However, strict risk factor modification, including improved antihypertensive therapy, lipid management, smoking cessation, and antiplatelet therapy, promise for reducing the vascular event rate in patients with carotid atherosclerosis. The best medical management for stroke prevention was highlighted in clinical practice guidelines issued jointly in 2006 by the American Heart Association and the American Stroke Association, and co-sponsored by the Council on Cardiovascular Radiology and Intervention and the American Academy of Neurology. Lowering blood pressure to a target below 120/80 mm Hg by life style interventions and antihypertensive treatment. Glucose control to near-normoglycemic levels (target hemoglobin A1C ≤7%) is recommended among diabetics to reduce micro-vascular complications and, with lesser certainty, macrovascular complications. The primary objective of this review is to summarize the current evidence and standards for the advanced diagnostic and management strategies used in asymptomatic and symptomatic patients with carotid atherosclerosis.

Atrial fibrillation and mild cognitive impairment: what correlation?

AIM: Atrial fibrillation (AF), in addition to macroembolic complications, may also produce multiple cerebral ischemic areas due to microembolic phenomena and transient hypoperfusion, eventually leading to a progressive cognitive impairment and even to acclaimed vascular dementia. The aim of this study was to evaluate the prevalence of cognitive impairment in patients with AF. The reported results concern data obtained at the moment of recruitment. METHODS: The authors studied 42 patients with a history of non valvular AF (paroxysmal, persistent, recurrent or permanent) and 40 homogenous controls in sinus rhythm without previous AF. All subjects underwent anamnesis, physical examination, biochemical and instrumental tests. To investigate the cognitive status, subjects underwent the following neuropsychological rating scales: Mini Mental State Examination (MMSE), Clinical Dementia Rating Scale (CDR),Activity of Daily Living (ADL), Instrumental Activity of Daily Living (IADL) Global Deterioration Scale (GLDS), Geriatric Depression Scale (GDS) and Hachinski Ischemic Score (HIS). RESULTS: AF Patients had worse scores versus controls at GLDS (P=0.0001), HIS (P=0.001), CDR (P=0.07) and GDS (P=0.07); no significant differences were found for MMSE even after correction for age and education. AF patients treated with warfarin showed better scores at CDR (P=0.04),GLDS (P=0.03) and GDS (P=0.007), compared to those in aspirin-treatment. Corrected MMSE scores did not differ. CONCLUSIONS: The authors identified a slight cognitive impairment in the AF group; patients with paroxysmal, persistent or recurrent AF showed worse cognitive performances than permanent ones, suggesting a possible microembolic pathogenesis. Anticoagulation therapy could play a protective role, however more evidence is needed.

The predictive role of C-reactive protein in patients with hypertension and subclinical atherosclerosis.

BACKGROUND: Recent guidelines published by the joint European Society of Hypertension/European Society of Cardiology have suggested the inclusion of C-reactive protein (CRP) in the standard assessment of cardiovascular risk in hypertensive patients, but few data are available on the role of CRP in patients with carotid lesions. METHODS: We studied 472 patients, 236 with and 236 without hypertension, sex- and age-matched, with and without early stages of atherosclerosis (e.g. those with an asymptomatic intima-media thickness of >0.9 mm), the influence of all the other traditional cardiovascular risk factors (e.g. older age, male sex, obesity, diabetes, smoking habit, family history of coronary artery disease, dyslipidaemia) and of high-sensitivity CRP levels on cerebrovascular and cardiovascular events in a 5-year follow up. RESULTS: At the end of follow up, patients with hypertension had more events than those without (25% vs 17%, P < 0.05). Proportional hazard analysis revealed in the group of patients without hypertension the presence of baseline carotid lesions (P= 0.02) as predictor of events. In patients with hypertension, the presence of baseline carotid lesions (P= 0.04) and elevated CRP levels (P= 0.02) predicted clinical events. Patients with hypertension also showed a significant relationship between clinical events and quintiles of CRP levels (P < 0.01). CONCLUSION: Beyond the utility of high-sensitivity CRP levels in the prediction of early and late stages of atherosclerosis and subsequently on its association with clinical events, the therapeutic implications of these results remain to be evaluated by further studies.

Prognostic role of endothelial dysfunction and carotid intima-media thickness in patients undergoing coronary stent implantation.

AIM: Impaired endothelial function and increased carotid intima-media thickness are key events in the atherosclerotic process and predict future cardiovascular events in subjects with and without coronary artery disease. The purpose of this study was to investigate whether the vasodilator response to increased flow in the brachial artery and the presence of carotid lesions may have a prognostic significance for in-stent restenosis in patients undergoing coronary angioplasty. METHODS: The study population included 58 patients undergoing percutaneous coronary intervention (PCI) with stenting and at least 10 months of follow-up. All patients underwent ultrasound detection of brachial artery reactivity 30 days after PCI. Flow mediated dilatation (FMD) was investigated after 5 minutes of occlusion of the artery and nitroglycerin mediated dilation (NMD) was investigated after administration of sublingual nitrates. Vascular echography was performed to measure intima media thickness (IMT) of carotid arteries. At baseline we evaluated all the established traditional cardiovascular risk factors. We also subdivided our study cohort according to values of FMD in patients with FMD above and patients below the median value. RESULTS: Patients with FMD above the median value showed higher prevalence of hypertension (P=0.002), diabetes (P=0.02) and carotid IMT (P=0.006) than those below the median. Brachial FMD was inversely correlated (P=0.001) to carotid IMT. At the end of follow-up clinical events occurred in nine patients. In a multivariate analysis, including all the variables evaluated at baseline, carotid IMT (P=0.02), level of glycemia (P=0.001), a lower FMD (P=0.005) and presence of carotid plaque remained the only variables predictive of restenosis. CONCLUSIONS: Evaluation of FMD and carotid IMT may provide important prognostic information in patients undergoing PCI.

Markers of inflammation and prevalence of vascular disease in patients with metabolic syndrome.

AIM: The aim of this study was to determine the prevalence of carotid atherosclerosis and coronary heart disease and cerebrovascular disease in subjects with metabolic syndrome and to investigate the relationship between atherosclerosis and C-reactive protein (CRP) levels. METHODS: We studied 568 ambulatory subjects, referred to our Center for the study of atherosclerosis and cardiovascular prevention by general practitioner, for the presence of traditional cardiovascular risk factors. Subjects were divided in two groups: those with metabolic syndrome (n=163), and those with 0-2 metabolic abnormalities (n=405). All subjects underwent carotid artery ultrasound and blood tests including high sensitivity-CRP measurement. RESULTS: Prevalence of carotid lesions, previous cardiac or cerebrovascular events was higher in patients with metabolic syndrome. CRP levels were higher in patients with metabolic syndrome (0.6+/-0.23 vs 0.42+/-0.2, P<0.01). An increased relative risk for carotid atherosclerosis, coronary heart disease and cerebrovascular disease was not associated with each single component of the metabolic syndrome, but it was significantly associated with the coexistence of three or more of these. Patients with the metabolic syndrome had a higher incidence of carotid and coronary disease, if CRP levels were above 0.3 mg/dL. CONCLUSION: Patients with metabolic syndrome are at increased risk for cardiovascular events. Strategy to treat these patients is not well clarified. Life style changes are mandatory, but in very high-risk subgroups secondary prevention strategies may be advisable. These may be identified by using CRP levels as a marker.

Extracoronary atherosclerosis in patients with chronic ischemic heart disease: relationship with risk factors and the severity of coronary artery disease.

AIM: The aim of the present study was to investigate the prevalence of carotid and/or peripheral atherosclerotic lesions in patients with chronic ischemic heart disease (previous acute myocardial infarction [AMI] or stable angina). METHODS: We studied 248 patients (168 male and 80 female), mean age 63+/-10 years, which were investigated for traditional risk factors. Systolic blood pressure, body mass index, lipid profile, fasting glucose and plasma fibrinogen were also measured. We assessed the prevalence of atherosclerotic lesions in carotid and lower limb arteries, by ultrasound duplex scanning (UDS). RESULTS: Angina was present in 33% of the patients, a previous AMI in 67%, a previous transient ischemic attack in 4% and a previous ischemic stroke in 6% of patients. A total of 195 patients underwent coronary angiography: 1 vessel was involved in 48% of patients, 2 vessels in 33%, and 3 vessels in 19%. Detecting peripheral atherosclerotic lesions by UDS, increased intima-media thickness (IMT) or plaques in carotid arteries were found in 232 patients (94%) and carotid stenosis >70% in 13 patients (5%). In lower limb arteries, IMT or plaques were present in 202 patients (82%) and a stenosis >70% in 18 patients (7%). Severity of coronary artery disease (CAD) was correlated to extracoronary atherosclerosis: carotid and lower limb arterial atherosclerosis was detected in 73% of patients with 1 vessel, in 83% of patients with 2 vessel, in 87% of those with 3 vessel CAD. CONCLUSION: Our study suggests that in patients with CAD, it is useful to screen the peripheral circulation by non-invasive tests, such as UDS. Patients with the diagnosis of ischemic heart disease and combined extracoronary atherosclerosis need a careful follow-up and a more aggressive therapy for secondary prevention.

Carotid and peripheral atherosclerosis in patients who underwent primary percutaneous coronary intervention and outcome associated with multifocal atherosclerosis.

AIM: The aim of our study was to determine if patients with multifocal atherosclerosis have a worse prognosis than patients with atherosclerosis only in the coronary bed. METHODS: We studied 45 subjects admitted to intensive coronary care unit of the Division of Cardiology with the diagnosis of acute myocardial infarction (AMI). Traditional cardiovascular risk factors were investigated and laboratory analysis included measurement of plasma lipids, glycemia, fibrinogen and high-sensitivity-C-reactive protein (hs-CRP). Each patient underwent coronary-angiography as well as carotid and peripheral arterial ultrasound examination. A follow-up of 13+/-2 months was performed. RESULTS: We found that the severity of coronary atherosclerosis is significantly associated with the presence of carotid (P<0.05) and peripheral atherosclerosis (P<0.005). Markers of inflammation, hs-CRP (P<0.005) and fibrinogen (P<0.05), were significantly associated with multifocal atherosclerosis. We have shown that an increased number of coronary vessels with atherosclerotic stenosis is associated with a higher value of carotid (P<0.0001) and peripheral intima media thickness (P<0.0001). During 13 months of follow-up the incidence of fatal or non fatal events was 18%. The multivariate analysis showed that the variables independently associated with fatal and non fatal events were: male sex (P<0.001), family history of cardiovascular disease (P<0.005), hypertension (P<0.01), diabetes mellitus (P<0.05), higher levels of total cholesterol (P<0.05), smoking habit (P<0.05), and multifocal atherosclerosis (P<0.05). CONCLUSIONS: The ultrasound examination of carotid and peripheral atherosclerotic lesions may be useful in placing patients with AMI in a category of higher risk of cerebrovascular and cardiovascular events. Moreover, the precocious identification of patients at risk can suggest a more aggressive pharmacological treatment and a more accurate follow-up in order to avoid future events.

Non invasive evaluation of endothelial function in patients with Anderson-Fabry disease.

AIM: Fabry's disease is an X-linked recessive abnormality of glycosphingolipid metabolism. Increased levels of endothelial prothrombotic factors have recently been demonstrated in Fabry's disease, whereas endothelial function has not been studied using high resolution ultrasound. METHODS: We enrolled 6 patients (4 male, 2 female; mean age, 37 years) and 12 sex matched control subjects (mean age, 37 years). Patients' exclusion criteria included a prior history of cardiac disease, diabetes and treated or untreated hypertension. Patients underwent: anamnesis, physical examination, EKG, 2-dimensional echocardiography with tissue Doppler, measurement of body weight and height, blood pressure. Biochemistry variables were also considered: fasting blood sugar, total cholesterol, HDL-C, LDL-C, triglycerides, fibrinogen, C reactive protein and homocysteine. Using high resolution ultrasound, we assessed the brachial vasodilator response to reactive hyperemia (endothelium-dependent) and sublingual nitroglycerin (NTG) (endothelium-independent). Flow-mediated dilatation (FMD) was expressed as percentage change in post-stimulus diameter in comparison with the baseline. RESULTS: In baseline condition, there was no significant difference between patients and controls in the brachial artery diameter (3.5+/-0.55 vs 3.1+/-0.4). After reactive hyperemia, the FMD change was significantly higher in controls than in patients (16.5+/-6.3% vs 9.3+/-6.2%, P<0.05). After NTG, endothelium-independent vasodilation did not show a significant difference between cases and controls (15+/-7.7% vs 13.8+/-7.1%). CONCLUSIONS: Our study demonstrated the presence of endothelial dysfunction in patients with Fabry's disease in comparison to controls. We hypothesized that endothelial dysfunction may contribute to the pathogenesis of ischemic events in patients with Fabry's disease.

Relationship between endothelial dysfunction, intima media thickness and cardiovascular risk factors in asymptomatic subjects.

AIM: The aim of the study was to evaluate endothelial function and intima media thickness (IMT) in relation to cardiovascular risk factors (RF). METHODS: We enrolled 113 patients, mean age 62 +/- 12 years; patients underwent: anamnesis, physical examination, measurement of body weight and height and blood pressure. Biochemistry variables were also measured: total cholesterol, high- and low-density lipoprotein cholesterol (HDL-C and LDL-C), triglycerides and glycemia. Vascular echography was performed to analyze flow mediated vasodilatation (FMD) at the brachial artery and IMT of the carotid and femoral arteries. RESULTS: Compared with patients without RF, patients with cardiovascular RF showed an impaired FMD (p < 0.05) and higher values of mean carotid IMT (p = 0.03). Age (p < 0.005) and diabetes (p < 0.05) were directly correlated with carotid IMT, while femoral IMT is correlated with age (p < 0.005) and male gender (p < 0.02). Regarding the relationship between endothelial function cardiovascular RF, we showed an inverse linear correlation between systolic blood pressure (p < 0.005), smoking (p < 0.05) and FMD, and concerning biochemical parameters, we founded that total cholesterol (p < 0.05) and LDL-C plasma levels (p < 0.005) were inversely correlated with FMD. Finally, we showed a lower FMD in patients with carotid and femoral IMT in comparison with patients without peripheral atherosclerosis (p = 0.01). CONCLUSIONS: The present data indicate that cardiovascular RF are associated with impaired endothelial function and increased IMT, and that the presence of carotid and femoral IMT is significantly correlated with endothelial dysfunction.