The role of chemokine CCL5/RANTES and metalloproteinase-9 as inflammatory modulators in symptomatic internal carotid artery stenosis.

Up to 80% of all ischemic strokes (IS) attributed to internal carotid athero-occlusive artery stenosis (ICAS) are related to a thromboembolic mechanism. One athero-occlusive ischemic event increases the risk for ischemia in another vascular territory, resulting from inflammation within the atherosclerotic plaque induced by cytokines. Thus, ultrasonographic characteristics of vulnerable plaques in ICAS, including plaque echolucency and ulceration might correspond to cytokine activity. The present study aimed to investigate the associations between serum cytokines and atherosclerotic plaque characteristics and the 3-year risk of a major adverse coronary and carotid ischemic event (MACCE) in symptomatic patients treated for ICAS. Plaque characteristics on ultrasonography, serum levels of C-C motif chemokine ligand 5 (CCL5)/regulated on activation, normal T-cell expressed and secreted (RANTES), metalloproteinase-9 (MMP-9), interleukin-6 (IL-6), transforming growth factor beta (TGF-ß), C-X-C motif chemokine ligand 16 (CXCL16), FAS ligand (FASL) and high sensivity C-reactive protein (hs-CRP) were analyzed in 103 symptomatic patients with ICAS prior to carotid revascularization. The incidence of MACCE: cardiovascular death (CVD), myocardial infarction (MI) and recurrent ischemic stroke (IS) were recorded prospectively for up to 5 years (median 37; IQR 21 - 40 months). Echolucent plaques, in comparison to echogenic plaques, displayed lower median levels of RANTES (P = 0.042) but higher median levels of IL-6 (P = 0.039). There was no relationship between plaque characteristics and median levels of MMP-9, TGF ß, CXCL16, FASL, or hs-CRP (P = NS). During follow-up, MACCE occurred in 15 (14.6%) patients. Univariate Cox proportional hazard analysis indicated median RANTES levels < 45.5ng/mL (hazard ratio (HR) = 3.95; 95%CI = 1.10 - 14.2; P = 0.035), MMP-9 > 0.6 µg/mL (HR 4.5; 95%CI = 1.4 - 13.9; P = 0.009), renal impairment (HR 3.48; 95%CI = 1.29 - 9.34; P = 0.013) as potential MACCE risk factors. On multivariate Cox proportional hazard analysis, MMP-9 > 0.6 µg/mL and RANTES < 45.5 ng/ml were associated with a 4.72-fold (95%CI = 1.3 - 17.0; P = 0.017) and a 3.8-fold risk increase (95%CI = 1.07 - 13.89; P = 0.038) of MACCE. Kaplan-Meier analysis showed significant differences in MACCE-free survival rates depending on RANTES and MMP-9 median levels. We conclude that serum RANTES, IL-6, and MMP-9 were associated with plaque vulnerability and predicted adverse MACCE in patients treated for ICAS.

Serum rantes, transforming growth factor-ß1 and interleukin-6 levels correlate with cardiac muscle fibrosis in patients with aortic valve stenosis.

Regulated on Activation Normal T Expressed and Secreted (RANTES) chemokine is involved in the initiation of inflammation and immune-cell recruitment. Interleukin -6 (IL-6) is used as a general index of severity of the chronic inflammatory process. Finally, transforming growth factor-ß (TGF-ß) is an immune biomarker potentially involved in the regulation of valve fibrosis and calcification. The aim of this study was to analyze selected biomarkers associated with the different stages of immune-pathogenesis in aortic stenosis. Forty consecutive patients with moderate to severe aortic stenosis (AS) and without previous myocardial infarction history were included in the study and divided into two groups. Two imaging techniques, echocardiography and magnetic resonance, were used to estimate the degree of AS and left ventricular muscle function. Inflammatory biomarker serum levels including CCL5/RANTES, IL-6, and TGF-ß1 were determined based on ELISA measurements. Mean levels of RANTES, IL-6, and TGF-ß1 did not significantly differ between both groups. A negative correlation was found between RANTES serum level and left ventricle (LV) mass as assessed by MRI (r = -0.3358, P = 0.0341). A positive correlation (r = 0.3283, P = 0.0387) was found between IL-6 serum levels and LV mass as measured by MRI. In addition, a positive correlation (r = 0.6803, P = 0.01) was seen between IL-6 serum levels and LV muscle mass with positive late gadolinium enhancement (LGE). There was a positive correlation between TGF-ß1 serum level and ejection fraction as measured by echocardiography (r = 0.3217, P = 0.043). The relationship between selected inflammatory biomarkers, LV ejection fraction, LV mass, and LV muscle mass with LGE appeared to be independent of valvular pathobiologic process severity, as we did not observe differences in IL-6, RANTES, or TGF-ß1 between groups differing in severity. On the contrary, these markers appear to be linked to myocardial function and remodeling, which may provide valuable insights into the pathobiology of AS and provide a basis for future detection strategies of AS.

Association of increased carotid intima-media thickness with the extent of coronary artery disease.

OBJECTIVE: To investigate (a) the relation between intima-media thickness (IMT) in carotid arteries and the extent of coronary artery disease (CAD); and (b) whether IMT is predictive of coronary atherosclerosis. The coexistence of severe extracranial atherosclerosis in patients with CAD was also analysed. METHODS: Coronary angiography and carotid ultrasound evaluation were performed in 558 consecutive patients (438 men), with a mean (SD) age of 58.8 (9.2) years and suspected CAD. Mean IMT was measured at both carotid arteries and expressed as the mean aggregate value. The relation between IMT and severity of CAD was determined. RESULTS: A significant correlation between mean IMT and advancing CAD (p < 0.0001) was found. Four independent predictors of CAD were found in the discriminant analysis: age (p = 0.0193), hyperlipidaemia (p < 0.0001), smoking (p = 0.0032), and IMT (p < 0.0001). A significant increase in IMT was observed among patients with one, two, and three vessel CAD. A log normal distribution of IMT values showed that if mean IMT was over 1.15 mm, patients had a 94% probability of having CAD, with sensitivity of 65% and specificity of 80% in the patients with a high risk of CAD. The number of critically stenosed extracranial arteries increased with advancing CAD. None of the patients with normal coronary arteries had severe stenosis of the extracranial arteries. Severe carotid, vertebral, or subclavian stenosis was found in 16.6% of patients with three vessel CAD. CONCLUSIONS: IMT increases with advancing CAD, patients with mean IMT over 1.15 mm have a 94% likelihood of having CAD, and the coexistence of CAD with severe stenosis of aortic arch arteries is relatively high and was found in 16.6% of patients with three vessel CAD.

[Atrial septal defect in adults--opinions, procedures and controversies]. / Ubytek w przegrodzie miedzyprzedsionkowej u doroslych--poglady, postepowanie i kontrowersje.

Atrial septal defect (ASD) accounts for 30-40% of congenital heart disease in adults diagnosed after the age of 40 and is after bicuspid aortic valve and mitral-valve prolaps the most common congenital cardiac malformation in adults. We have discussed current views on the pathological role of ASD in adults and controversies regarding its treatment. It is expected that increasing understanding of ASD pathophysiology, improved diagnostic methods and the possibility of transcatheter closure of interatrial defects will improve the treatment of patients with ASD.