Cardiovascular hypertrophy: role of angiotensin II and bradykinin.

Angiotensin II can raise blood pressure rapidly by inducing direct vasoconstriction and by activating the sympathetic nervous system via central and peripheral mechanisms. In addition, this peptide may act as a growth factor to cause vascular and cardiac hypertrophy (CVH). The structural changes caused by hypertension can therefore be amplified by angiotensin II. Blockade of angiotensin II generation with angiotensin-converting enzyme (ACE) inhibitors appears to be particularly effective in preventing the development of cardiovascular hypertrophy. This beneficial effect might be related to some extent to local accumulation of bradykinin. ACE is one of the enzymes physiologically involved in bradykinin degradation. Treatment of hypertensive rats with a selective bradykinin antagonist can attenuate the blood pressure-lowering effect of ACE inhibition and render less effective the prevention of intimal thickening after endothelial removal from the rat carotid artery. Bradykinin is a vasodilator that acts by increasing the release of endothelium-derived factors such as nitric oxide and prostacyclin, which may have antiproliferative activity. However, blockade of the renin-angiotensin system with an angiotensin II subtype 1-receptor antagonist is also effective in preventing cardiac hypertrophy and neointimal proliferation after endothelial injury. Therefore, the exact contribution of bradykinin to the beneficial effects of ACE inhibition on cardiovascular hypertrophy remains to be further explored.

Risk factor profile and management of cerebrovascular patients in the REACH Registry.

BACKGROUND: Cerebrovascular disease (CVD) is a global public health problem. CVD patients are at high risk of recurrent stroke and other atherothrombotic events. Prevalence of risk factors, comorbidities, utilization of secondary prevention therapies and adherence to guidelines all influence the recurrent event rate. We assessed these factors in 18,992 CVD patients within a worldwide registry of stable outpatients. METHODS: The Reduction of Atherothrombosis for Continued Health Registry recruited >68,000 outpatients (44 countries). The subjects were mainly recruited by general practitioners (44%) and internists (29%) if they had symptomatic CVD, coronary artery disease, peripheral arterial disease (PAD) and/or >or=3 atherothrombotic risk factors. RESULTS: The 18,992 CVD patients suffered a stroke (53.7%), transient ischemic attack (TIA) (27.7%) or both (18.5%); 40% had symptomatic atherothrombotic disease in >or=1 additional vascular beds: 36% coronary artery disease; 10% PAD and 6% both. The prevalence of risk factors at baseline was higher in the TIA subgroup than in the stroke group: treated hypertension (83.5/82.0%; p = 0.02), body mass index >or=30 (26.7/20.8%; p < 0.0001), hypercholesterolemia (65.1/52.1%; p < 0.0001), atrial fibrillation (14.7/11.9%; p < 0.0001) and carotid artery disease (42.3/29.7%; p < 0.0001). CVD patients received antiplatelet agents (81.7%), oral anticoagulants (17.3%), lipid-lowering agents (61.2%) and antihypertensives (87.9%), but guideline treatment targets were frequently not achieved (54.5% had elevated blood pressure at baseline, while 4.5% had untreated diabetes). CONCLUSIONS: A high percentage of CVD patients have additional atherothrombotic disease manifestations. The risk profile puts CVD patients, especially the TIA subgroup, at high risk for future atherothrombotic events. Undertreatment is common worldwide and adherence to guidelines needs to be enforced.

Premature atherosclerosis in patients with xanthelasma.

BACKGROUND: Only about half the patients with xanthelasma are hyperlipidemic. The clinical significance of xanthelasma as a marker of cardiovascular disease is not yet well defined. OBJECTIVE: To determine the risk of cardiovascular disease in patients with normolipidemic and hyperlipidemic xanthelasma. METHODS: Carotid ultrasonography (7 MHz using B-mode images, Advanced Technology Laboratories) was used to detect carotid plaques and measure the intima-media thickness (IMT) of the common carotid arteries. Seventeen patients with normolipidemic and hyperlipidemic xanthelasma were examined and compared with 21 age-matched normal subjects. RESULTS: The risk of cardiovascular disease was significantly increased in patients with xanthelasma. Carotid plaques were more frequent in patients with xanthelasma than in controls (64.7% and 23.8%, respectively; P = 0.020), and IMT was significantly higher (mean +/- SD: 1.1 +/- 0.1 and 0.6 +/- 0.2 mm, respectively; P < 0.001). The difference of carotid IMT between normolipidemic xanthelasma and hyperlipidemic xanthelasma was not statistically different (mean +/- SD: 1.1 +/- 0.1 and 1.1 +/- 0.2 mm, respectively; P = 0.577). CONCLUSION: Premature carotid atherosclerosis is observed in patients with normolipidemic and hyperlipidemic xanthelasma. Patients with xanthelasma should be considered to have an increased risk of cardiovascular disease independently to the level of plasma lipids. A larger number of patients is, however, needed to confirm this preliminary study.

Superior flow for bridge to life with self-expanding venous cannulas.

BACKGROUND: Recently, a compact cardiopulmonary support (CPS) system designed for quick set-up for example, during emergency cannulation, has been introduced. Traditional rectilinear percutaneous cannulas are standard for remote vascular access with the original design. The present study was designed to assess the potential of performance increase by the introduction of next-generation, self-expanding venous cannulas, which can take advantage of the luminal width of the venous vasculature despite a relatively small access orifice. METHODS: Veno-arterial bypass was established in three bovine experiments (69+/-10 kg). The Lifebridge (Lifebridge GmbH, Munich, Germany) system was connected to the right atrium in a trans-jugular fashion with various venous cannulas; and the oxygenated blood was returned through the carotid artery with a 17 F percutaneous cannula. Two different venous cannulas were studied, and the correlation between the centrifugal pump speed (1500-3900 RPM), flow and the required negative pressure on the venous side was established: (A) Biomedicus 19 F (Medtronic, Tolochenaz, Switzerland); (B) Smart canula 18 F/36 F (Smartcanula LLC, Lausanne, Switzerland). RESULTS: At 1500 RPM, the blood flow was 0.44+/-0.26 l min(-1) for the 19 F rectilinear cannula versus 0.73+/-0.34 l min(-1) for the 18/36 F self-expanding cannula. At 2500 RPM the blood flow was 1.63+/-0.62 l min(-1) for the 19F rectilinear cannula versus 2.13+/-0.34 l min(-1) for the 18/36 F self-expanding cannula. At 3500 RPM, the blood flow was 2.78+/-0.47 l min(-1) for the 19 F rectilinear cannula versus 3.64+/-0.39 l min(-1) for the 18/36 F self-expanding cannula (p<0.01 for 18/36 F vs 19 F). At 1500 RPM, the venous line pressure was 18+/-8 mmHg for the 19F rectilinear cannula versus 19+/-5 mmHg for the 18/36 F self-expanding cannula. At 2500 RPM the venous line pressure accounted for -22+/-32 mmHg for the 19 F rectilinear cannula versus 2+/-5 mmHg for the 18/36 F self-expanding cannula. At 3500 RPM, the venous line pressure was -112+/-42 mmHg for the rectilinear cannula versus 28+/-7 mmHg for the 18/36 F self-expanding cannula (p<0.01 for 18 F/36 F vs 19 F). Conclusions: The negative pressure required to achieve adequate venous drainage with the self-expanding venous cannula accounts for approximately 31% of the pressure necessary with the 19 F rectilinear cannula. In addition, a pump flow of more than 4 l min(-1) can be achieved with the self-expanding design and a well-accepted negative inlet pressure for minimal blood trauma of less than 50 mmHg.

Limited role of the c-Jun N-terminal kinase pathway in a neonatal rat model of cerebral hypoxia-ischemia

D-JNKI1, a cell-permeable peptide inhibitor of the c-Jun N-terminal kinase (JNK) pathway, has been shown to be a powerful neuroprotective agent after focal cerebral ischemia in adult mice and young rats. We have investigated the potential neuroprotective effect of D-JNKI1 and the involvement of the JNK pathway in a neonatal rat model of cerebral hypoxia-ischemia. Seven-day-old rats underwent a permanent ligation of the right common carotid artery followed by 2h of hypoxia (8% oxygen). Treatment with D-JNKI1 (0.3mg/kg intraperitoneally) significantly reduced early calpain activation, late caspase-3 activation and, in the thalamus, autophagosome formation, indicating an involvement of JNK in different types of cell death: necrotic, apoptotic and autophagic. However the size of the lesion was unchanged. Further analysis showed that neonatal hypoxia-ischemia induced an immediate decrease in JNK phosphorylation (reflecting mainly P-JNK1) followed by a slow progressive increase (including P-JNK3 54kDa), whereas c-jun and c-fos expression were both strongly activated immediately after hypoxia-ischemia. In conclusion, unlike in adult ischemic models, JNK is only moderately activated after severe cerebral hypoxia-ischemia in neonatal rats and the observed positive effects of D-JNKI1 are insufficient to give neuroprotection. Thus, for perinatal asphyxia, D-JNKI1 can only be considered in association with other therapies.

Risk factor impact on blood flow velocities and clinical outcomes of stented cervical and intracranial stenoses: preliminary observations.

OBJECTIVES: The role of angioplasty/stenting procedures, neurointerventionist experience, vascular risk factors, medical treatment and blood flow velocities were analysed to identify possible causes of intra-stent restenosis (ISR) following stenting of cervical and/or intracranial arteries, assuming progressive atherosclerosis to be the shared mechanism in both territories. Patients. 26 cerebrovascular patients subjected to stenting of severe (≥85%) symptomatic or asymptomatic carotid stenoses or moderate-to-severe (≥50%) intracranial or vertebral stenoses were included. METHODS: Clinical, radiological and ultrasonographic follow-up data were analysed retrospectively. RESULTS: Overall, stenting of the internal carotid artery (ICA) induced significant reductions in peak systolic velocities at 2 years (96±31cm/s vs. 358.2±24.9cm/s at baseline). The procedure-related ischemic complications rate was 7.4% (one hemispheric stroke and one TIA). The rate of ISR≤50% was 8% in the ICA at 2 years; was 50% in the common carotid artery (CCA) at 1 year, with concomitant distal ICA stenosis in 75% of CCA stenting, but all ISR were asymptomatic. Patients with ISR of the ICA were significantly younger (56.8±4.5 vs. 71.3±3.6 years, P=0.042) and had significantly more risk factors (5.5±0.9 vs. 3±0.3, P=0.012). No ISR≥70% was detected. CONCLUSIONS: ISR is relatively infrequent and, when present, it is mild and asymptomatic. Restenosis is more frequent in younger patients and those with several risk factors, and it may also be related to stenting of previous carotid endarterectomy.

Association between conventional risk factors and different ultrasound-based markers of atherosclerosis at carotid and femoral levels in a middle-aged population.

Ultrasound detection of sub-clinical atherosclerosis (ATS) may help identify individuals at high cardiovascular risk. Most studies evaluated intima-media thickness (IMT) at carotid level. We compared the relationships between main cardiovascular risk factors (CVRF) and five indicators of ATS (IMT, mean and maximal plaque thickness, mean and maximal plaque area) at both carotid and femoral levels. Ultrasound was performed on 496 participants aged 45-64 years randomly selected from the general population of the Republic of Seychelles. 73.4 % participants had ≥ 1 plaque (IMT thickening ≥ 1.2 mm) at carotid level and 67.5 % at femoral level. Variance (adjusted R2) contributed by age, sex and CVRF (smoking, LDL-cholesterol, HDL-cholesterol, blood pressure, diabetes) in predicting any of the ATS markers was larger at femoral than carotid level. At both carotid and femoral levels, the association between CVRF and ATS was stronger based on plaque-based markers than IMT. Our findings show that the associations between CVRF and ATS markers were stronger at femoral than carotid level, and with plaque-based markers rather than IMT. Pending comparison of these markers using harder cardiovascular endpoints, our findings suggest that markers based on plaque morphology assessed at femoral artery level might be useful cardiovascular risk predictors.

Lack of association between connexin40 polymorphisms and coronary artery disease.

OBJECTIVE: Cx40 is a gap junction protein important for cell-cell communication in the endothelium. Polymorphisms in the promoter region of the human Cx40 gene, -44G>A and +71A>G, were shown to reduce Cx40 transcription by half. As mice with an endothelial-specific deletion of Cx40 are more susceptible to atherosclerosis, this study was designed to discover a correlation between these polymorphisms and atherosclerosis in European populations.¦METHODS AND RESULTS: 803 patients referred to the Geneva University Hospitals for elective coronary angiography were divided according to the number of significantly stenosed vessels (from 0 to 3) and were genotyped for the Cx40 polymorphisms. Genotype distribution in the control group was -44GG/+71AA=59.8%, -44AG/+71AG=35.1% and -44AA/+71GG=5.2%. Surprisingly, this distribution was similar in the CAD group, with -44GG/+71AA=58.5%, -44AG/+71AG=37.6% and -44AA/+71GG=3.8% (p=0.67). Moreover, no significant association between histological carotid plaque composition of culprit lesions and Cx40 polymorphisms could be detected in 583 Dutch patients of the Athero-Express study.¦CONCLUSIONS: Despite a clear antiatherogenic role of Cx40 in mice, our study could not detect an association of Cx40 promoter polymorphisms and CAD in human. Moreover, a correlation with atherosclerotic plaque stability or hypertension could not be demonstrated either. Connexin polymorphisms affecting channel function may be of greater importance for cardiovascular disease than polymorphisms affecting the expression level of the protein.

Plastinated Ethmoidal Region : II. The Preparation and Use of Radio-Opaque Artery Casts in Clinical Teaching.

In endoscopic sinus surgery, knowledge of the course of the internal ethmoida and orbital arteries is crucial.The maxillary and the internal carotid arteries of cadavers were injected with radio-opaque , red colorede silicone. The ethmoidal regions were perpared and plastinated using the standard S10 technique. On some specimens, the ophtalmic and ethmoidal arteries were dissected prior to plastination. The plastinated specimens of the ethmoidal blocks were successfullyintroduced into clinical teaching of sinus anatomy and surgery as an aid to study vaascularization an dits relationship to surgical procedures. Among the advantages of this method are the long-lasting preservation of dissected tissue, visualization of arteries during endoscopic and radiological examinations, and invaluable teachjing and training resources for endoscopic sinus surgery.

Common variation in PHACTR1 is associated with susceptibility to cervical artery dissection.

Cervical artery dissection (CeAD), a mural hematoma in a carotid or vertebral artery, is a major cause of ischemic stroke in young adults although relatively uncommon in the general population (incidence of 2.6/100,000 per year). Minor cervical traumas, infection, migraine and hypertension are putative risk factors, and inverse associations with obesity and hypercholesterolemia are described. No confirmed genetic susceptibility factors have been identified using candidate gene approaches. We performed genome-wide association studies (GWAS) in 1,393 CeAD cases and 14,416 controls. The rs9349379[G] allele (PHACTR1) was associated with lower CeAD risk (odds ratio (OR) = 0.75, 95% confidence interval (CI) = 0.69-0.82; P = 4.46 × 10(-10)), with confirmation in independent follow-up samples (659 CeAD cases and 2,648 controls; P = 3.91 × 10(-3); combined P = 1.00 × 10(-11)). The rs9349379[G] allele was previously shown to be associated with lower risk of migraine and increased risk of myocardial infarction. Deciphering the mechanisms underlying this pleiotropy might provide important information on the biological underpinnings of these disabling conditions.

Diabetes and pre-diabetes are associated with cardiovascular risk factors and carotid/femoral intima-media thickness independently of markers of insuline resistance and adiposity

Background Impaired glucose regulation (IGR) is associated with detrimental cardiovascular outcomes such as cardiovascular disease risk factors (CVD risk factors) or intima-media thickness (IMT). Our aim was to examine whether these associations are mediated by body mass index (BMI), waist circumference (waist) or fasting serum insulin (insulin) in a population in the African region. Methods Major CVD risk factors (systolic blood pressure, smoking, LDL-cholesterol, HDL-cholesterol,) were measured in a random sample of adults aged 25-64 in the Seychelles (n=1255, participation rate: 80.2%). According to the criteria of the American Diabetes Association, IGR was divided in four ordered categories: 1) normal fasting glucose (NFG), 2) impaired fasting glucose (IFG) and normal glucose tolerance (IFG/NGT), 3) IFG and impaired glucose tolerance (IFG/IGT), and 4) diabetes mellitus (DM). Carotid and femoral IMT was assessed by ultrasound (n=496). Results Age-adjusted levels of the major CVD risk factors worsened gradually across IGR categories (NFG < IFG/NGT < IFG/IGT < DM), particularly HDL-cholesterol and blood pressure (p for trend <0.001). These relationships were marginally attenuated upon further adjustment for waist, BMI or insulin (whether considered alone or combined) and most of these relationships remained significant. With regards to IMT, the association was null with IFG/NGT, weak with IFG/IGT and stronger with DM (all more markedly at femoral than carotid levels). The associations between IMT and IFG/IGT or DM (adjusted by age and major CVD risk factors) decreased only marginally upon further adjustment for BMI, waist or insulin. Further adjustment for family history of diabetes did not alter the results. Conclusions We found graded relationships between IGR categories and both major CVD risk factors and carotid/femoral IMT. These relationships were only partly accounted for by BMI, waist and insulin. This suggests that increased CVD-risk associated with IGR is also mediated by factors other than the considered markers of adiposity and insulin resistance. The results also imply that IGR and associated major CVD risk factors should be systematically screened and appropriately managed.

Efficiency of coronary artery disease screening guidelines in asymptomatic and atypical chest pain type 2 diabetic patients

RESUME Objectifs. Évaluer la prévalence de maladie coronarienne chez les patients diabétiques de type 2 asymptomatiques ou avec angor atypique selon les recommandations américaines de l'American Diabetes Association et de l'American College of Cardiology. Méthodes. Cent cinquante-quatre patients diabétiques de type 2 asymptomatiques ou avec angor atypique et présentant au minimum 2 facteurs de risque cardio-vasculaires additionnels ont été dépistés par échocardiographie de stress (71%, n=109), scintigraphie myocardique de perfusion (26%, n=40) ou l'association des 2 examens (3%, n=5). Résultats. L'échocardiographie de stress s'est révélée positive chez 16 patients (14%) et 14 ont eu une coronarographie révélant des sténoses significatives chez 12 (86%). La scintigraphie myocardique de perfusion était positive chez 16 patients (36%). Huit patients ont eu une coronarographie et 4 (50%) présentaient des sténoses significatives. Au total, 31 patients (20%) ont montré des signes d'ischémie lors de l'examen non-invasif et 15 (10%) ont présenté des sténoses significatives à la coronarographie. Les facteurs prédictifs indépendants de la maladie coronarienne étaient le tabagisme (OR 6.5, p=0.05), la microalbuminurie (OR 3.9, p=0.03), ainsi que les souffles fémoraux (OR 17.1, p=0.008). Conclusions. En suivant les recommandations américaines, un patient sur cinq présentait une ischémie lors des examens non-invasifs, tandis que 1 sur 10 avait des sténoses significatives à la coronarographie. L'analyse multivariée suggère que des marqueurs des complications micro- et macro-vasculaires en combinaison avec des facteurs de risque cardio-vasculaire classiques pourraient améliorer le pouvoir diagnostic de ces recommandations. SUMMARY Aims. We evaluated the prevalence of coronary artery disease in asymptomatic and atypical chest pain type 2 diabetic patients according to the American Diabetes Association and American College of Cardiology guidelines. Methods. Asymptomatic or atypical chest pain type 2 diabetic patients (n=154), with at least two additional cardiovascular risk factors, were screened for coronary artery disease using stress echocardiography (71%, n=109), myocardial perfusion imaging (26%, n=40) or both (3%, n=5). Results. Stress echocardiography was positive in 16 patients (14%) and 14 had a coronary angiography, revealing significant stenoses in 12 (86%). Myocardial perfusion imaging was positive in 16 patients (36%). Eight patients underwent angiography and 4 (50%) presented significant stenoses. Overall, 31 patients (20%) demonstrated signs of ischemia on non-invasive tests and 15 (10%) presented significant stenoses on coronary angiography. Independent predictors of coronary artery disease were smoking (OR 6.5, p=0.05), microalbuminuria (OR 3.9, p=0.03) and femoral murmur (OR 17.1, p=0.008). Conclusions. Following the guidelines, one in five diabetic patient presented ischemia on noninvasive tests, while one in ten presented significant coronary stenoses. Multivariate analysis suggests that adding markers of micro- and macro-vascular complications to classical cardiovascular risk factors may enhance the diagnostic efficiency of the guidelines.

The Atherosclerosis Burden Score (ABS): a Convenient Ultrasound-Based Score of Peripheral Atherosclerosis for Coronary Artery Disease Prediction.

Ultrasonographic detection of subclinical atherosclerosis improves cardiovascular risk stratification, but uncertainty persists about the most discriminative method to apply. In this study, we found that the "atherosclerosis burden score (ABS)", a novel straightforward ultrasonographic score that sums the number of carotid and femoral arterial bifurcations with plaques, significantly outperformed common carotid intima-media thickness, carotid mean/maximal thickness, and carotid/femoral plaque scores for the detection of coronary artery disease (CAD) (receiver operating characteristic (ROC) curve area under the curve (AUC) = 0.79; P = 0.027 to <0.001 with the other five US endpoints) in 203 patients undergoing coronary angiography. ABS was also more correlated with CAD extension (R = 0.55; P < 0.001). Furthermore, in a second group of 1128 patients without cardiovascular disease, ABS was weakly correlated with the European Society of Cardiology chart risk categories (R (2) = 0.21), indicating that ABS provided information beyond usual cardiovascular risk factor-based risk stratification. Pending prospective studies on hard cardiovascular endpoints, ABS appears as a promising tool in primary prevention.

Aneurysms of saphenous vein grafts as late complication of coronary artery bypass surgery: successful exclusion by percutaneous transcatheter embolization.

We report a case of a 71-year-old man with a long coronary artery disease history and two sets of coronary artery bypass grafts. He developed large aortocoronary saphenous vein graft aneurysms in the two grafts from the first set of aortocoronary saphenous venous 20 years later. During the previous 3 years, the aneurysms grew in diameter from 22 to 50 mm. Because of severe renal insufficiency, and in order to avoid jeopardizing the late normal coronary artery bypass grafts by further thoracic surgery, we excluded successfully these altered grafts percutaneously by using 13 coils during the same procedure.

Heterogeneity of atherosclerotic plaque phenotypes and composition in four different arterial beds: an intravascular ultrasound virtual histology study

Purpose: The purpose of this study was to compare the plaque morphology between coronary and peripheral arteries using intravascular ultrasound (IVUS). Methods: IVUS was performed in 68 patients with coronary and 93 with peripheral artery lesions (29 carotid, 50 renal, and 14 iliac). Plaques were classified as fibroatheroma (VH-FA) (further subclassified as thin-capped [VH-TCFA] and thick-capped [VH-ThCFA]), fibrocalcific plaque (VH-FC) and pathological intimal thickening (VH-PIT). Results: Plaque rupture (13% of coronary, 7% of carotid, 6% of renal, and 7% of iliac arteries; P=NS) and VH-TCFA (37% of coronary, 24% of carotid, 16% of renal, and 7% of iliac arteries; P=0.02) was observed in all arteries. Compared to coronary arteries, VH-FA was less frequently observed in renal (P<0.001) and iliac arteries (P<0.006), while VH-PIT and VH-FC were prevalent in both of these peripheral arteries. Lesions with positive remodeling demonstrated more characteristics of VH-FA in coronary, carotid, and renal arteries compared to those with intermediate/negative remodeling (all P<0.01). There was positive relationship between RI and percent necrotic core area in all four arteries. Conclusions: Atherosclerotic plaque phenotypes were heterogeneous among four different arteries. In contrast, the associations of remodeling mode with plaque phenotype and composition were similar among the various arterial beds.