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.

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.

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.

Soluble CD40L and cardiovascular risk in asymptomatic low-grade carotid stenosis.

BACKGROUND AND PURPOSE: We investigated whether soluble CD40L (sCD40L) may predict the risk of cardiovascular (CV) events in patients with asymptomatic carotid plaques. METHODS: Forty-two patients with asymptomatic low-grade carotid stenosis (ALCS) and 21 controls without any carotid stenosis were enrolled. All subjects had at least a major cardiovascular risk factor (CRF). Plasma levels of C-reactive protein (CRP), IL-6, and sCD40L were measured. Subjects were reviewed every 12 months (median follow-up, 8 years). RESULTS: ALCS patients had higher (P<0.0001) CRP, IL-6, and sCD40L than controls. Fourteen patients experienced a CV event. Cox regression analysis showed that only high sCD40L levels (P=0.003) independently predicted cardiovascular risk. CONCLUSIONS: High levels of sCD40L may predict the risk of CV events in ALCS.

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.