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Hypercholesterolaemia
Kinds of Hypercholesterolaemia Selected AbstractsThe prevalence of lipodystrophy in an ambulant HIV-infected population: it all depends on the definitionHIV MEDICINE, Issue 3 2001VM Carter Objectives This study's objective was to determine the prevalence of body shape changes and metabolic abnormalities in an ambulant population with HIV infection. Three different definitions of lipodystrophy were used to assess these changes. Patients' anthropometric measures and dual-energy X-ray absorptiometry (DEXA) scans were compared in order to estimate fat distribution in this population. We sought to evaluate potential predictors for lipodystrophy according to each of the three definitions. Methods We performed a cross-sectional study in the outpatient clinic of a tertiary referral hospital in Melbourne, Australia. We enrolled a total of 167 HIV-infected ambulatory patients over 3 months in mid-1998. Data on 159 males, 149 of whom were receiving triple combination antiretroviral therapy, were evaluated. Anthropometric measures, clinical examination, self-report of body shape changes, biochemical measures and DEXA scan were used to assess lipodystrophy and risk factors for cardiovascular disease. Patients described body shape changes in the face, trunk, arms and legs. Laboratory parameters measured included fasting triglyceride (TG), cholesterol, high-density lipoproteins (HDL), glucose, insulin, CD4 cell count and plasma HIV RNA. Current and past antiretroviral therapies were ascertained. Results According to one proposed Australian national definition of lipodystrophy (LDNC), the prevalence of lipodystrophy in this population was 65%. This definition included an objective assessment with major and minor criteria. Patient-defined lipodystrophy (LDP), which involved a subjective assessment of thinning arms and legs and central adiposity, occurred in 19%. Patient-defined lipoatrophy (LAP), which involved a subjective assessment of thinning arms and legs without central adiposity, occurred in 21.3%. No change in body habitus was noted by 37% of the cohort. Hypercholesterolaemia was recorded in 44%, hypertriglyceridaemia in 52% and elevated insulin levels in 23%. Anthropometry was predictive of the per cent total body fat recorded by DEXA scan, but produced consistently lower values. In multivariate analysis, LDP and LAP were significantly associated with stavudine (d4T) use, while LAP was also associated with zidovudine (ZDV) treatment. There were no treatment associations with LDNC. Protease inhibitor (PI) exposure was associated with metabolic changes but not patient perceived body shape changes, while d4T and ZDV exposure was associated with increased triglycerides and reduced peripheral fat stores. Conclusions The prevalence of body shape changes in a single population varied depending on the definition applied. The LDNC definition overestimated body shape abnormalities in comparison with patient perception. LAP was associated with significantly lower fat stores measured by anthropometry and DEXA scan than those identified under the LDNC definition. In contrast to LDNC, LAP was associated with d4T exposure, nucleoside reverse transcriptase inhibitor (NRTI) and ZDV duration of use, but not PI use. Until a consensus definition for lipodystrophy is developed, including agreement on objective measurement and thresholds for abnormality, careful description of the individual components of the syndrome is required to enable cohort comparisons so that predictors of the syndrome can be assessed more accurately and outcome studies made feasible. [source] A detailed microscopic study of the changes in the aorta of experimental model of postmenopausal rats fed with repeatedly heated palm oilINTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 3 2009Siti Khadijah Adam Summary Hypercholesterolaemia, increase in lipid peroxidation and hyperhomocysteinaemia may contribute to the pathogenesis of atherosclerosis. This study was performed to examine the effects of repeatedly heated palm oil mixed with 2% cholesterol diet on atherosclerosis in oestrogen-deficient postmenopausal rats. Ovariectomy causes disruption of tunica intima layer of the rat aorta simulating a postmenopausal condition in females. Twenty-four ovariectomized female Sprague,Dawley rats were divided into four groups. The control group received 2% cholesterol diet without palm oil. A diet with 2% cholesterol content fortified with fresh, once-heated and five-times-heated palm oil was given to the other treatment groups. The rats were sacrificed at the end of 4 months of study and the aortic arch tissue was processed for histomorphometry and electron microscopy. On observation, there was disruption of the intimal layer of the ovariectomized rat aorta. There was no obvious ultrastructural change in the aorta of the rats fed with fresh palm oil. The ultrastructural changes were minimal with once-heated palm oil, in which there was a focal disruption of the endothelial layer. The focal disruption was more pronounced with five-times-heated palm oil. The results of this study show that the ingestion of fresh palm oil may have a protective effect on the aorta but such a protective action may be lost when the palm oil is repeatedly heated. The study may be clinically important for all postmenopausal women who are susceptible to atherosclerosis. [source] Hypercholesterolaemia induces early renal lesions characterized by upregulation of MMP-9 and iNOS and ETAR: alleviated by a dual endothelin receptor antagonist CPU0213 and simvastatinJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 6 2009Lu Luo Abstract Objectives We aimed to investigate hypercholesterolaemia-induced early renal lesions which result in abnormal expression of endothelin A receptor (ETAR), induced nitric oxide synthase (iNOS) and matrix metalloproteinase 9 (MMP-9). We hypothesized that this is due to an upregulated endothelin (ET) pathway consequent to hypercholesterolaemia and that CPU0213, a dual ET antagonist, could mitigate these changes. Methods Rats were randomly divided into four groups: (1), control; (2), high-fat diet for 60 days (HFD); HFD rats medicated in the last 15 days with either (3) CPU0213 (30 mg/kg daily, s.c.) or (4) simvastatin (4 mg/kg daily, p.o.). Key findings Body weight, serum triglycerides, total cholesterol and low-density-lipoprotein cholesterol were significantly increased, whereas high-density lipoprotein cholesterol decreased in the HFD group, relative to normal. Meanwhile, these changes were associated with upregulation of mRNA and protein of ETAR, iNOS and MMP-9 in the kidney. The lipid-lowering effect of simvastatin was predominant, lessening abnormal expression of these molecules in the kidney dramatically. Interestingly, CPU0213 significantly normalized expression of mRNA and protein of ETAR, iNOS and MMP-9, comparable with simvastatin, leaving no changes in hyperlipidaemia. Conclusions CPU0213 relieves renal lesions by blunting hypercholesterolaemia caused by the upregulated ET system, iNOS and MMP-9 in the kidney. This indicates that CPU0213 is promising in treating patients with end stage renal disease. [source] Prevalence and treatment of hypercholesterolaemia in patients with peripheral vascular diseaseBRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 4 2000S. M. Evans Background: Hypercholesterolaemia is a recognized risk factor for the development of arteriosclerosis. There is compelling evidence to support the use of lipid-lowering strategies in all hypercholesterolaemic patients with arteriosclerotic disease. In peripheral arterial disease (PAD), national guidelines recommend treatment if total cholesterol exceeds 5·0 mmol l,1. The prevalence of hypercholesterolaemia in patients with PAD was determined and the adequacy of lipid management before vascular referral was examined. Methods: This was a prospective study of 233 consecutive patients admitted electively to this vascular surgery unit between December 1997 and December 1998. Some 68 patients were admitted with carotid disease, 81 with an aneurysm and 84 with intermittent claudication. A fasting venous blood sample was obtained from each patient. Results: There were 175 men and 58 women, of median age 67 (range 37,85) and 68 (range 47,85) years respectively. Only 35 patients (15 per cent) were previously known to be hypercholesterolaemic; all but one were receiving treatment (one dietary, 33 statin). Of the remaining 198 patients, 124 (63 per cent) had a serum cholesterol level above 5·0 mmol l,1. A further 17 patients (9 per cent) had total cholesterol/high-density lipoprotein: cholesterol ratio greater than 5·0; these patients may also benefit from lipid-lowering therapy. In total, 141 (80 per cent) of 176 hypercholesterolaemic patients were undiagnosed at the time of hospital admission. Conclusion: Hypercholesterolaemia is an important and correctable risk factor found in the majority of patients with PAD, but despite national guidelines and clear evidence from randomized controlled trials it is simply not being diagnosed in primary care. All elective patients with PAD should be screened for hypercholesterolaemia during their admission. © 2000 British Journal of Surgery Society Ltd [source] The vitamin D receptor gene variant is associated with the prevalence of Type 2 diabetes mellitus and coronary artery diseaseDIABETIC MEDICINE, Issue 10 2001J. R. Ortlepp Abstract Aims, Vitamin D can influence lipolysis and insulin secretion. A common genetic polymorphism of the vitamin D receptor, which has been found to be associated with bone mineral density, has also been reported to be associated with insulin-dependent diabetes mellitus. To test the influence of the vitamin D receptor polymorphism on the prevalence of Type 2 diabetes mellitus and coronary artery disease we studied a population of high-risk patients, who were referred to our clinic for diagnostic coronary angiography. Methods, A total of 293 patients considered at high risk for coronary artery disease because of angina pectoris and known hypercholesterolaemia underwent diagnostic coronary angiography. The BsmI vitamin D receptor polymorphism was analysed by polymerase chain reaction. Results, Prevalence of Type 2 diabetes mellitus and coronary artery disease was gradually dependent on the number of B alleles (BB 28%, Bb 13%, bb 8% for Type 2 diabetes mellitus, P = 0.002; BB 88% Bb 72%, bb 66% coronary artery disease, P = 0.01). Patients with the BB genotype had an odds ratio of 3.64 (95% confidence interval 1.53,8.55, P = 0.002) to have Type 2 diabetes mellitus compared with patients with the bb genotype. Conclusions, The genotype of the vitamin D receptor polymorphism determines the prevalence of Type 2 diabetes mellitus and coronary artery disease in a high-risk cohort population. Diabet. Med. 18, 842,845 (2001) [source] Circulating mononuclear cells nuclear factor-kappa B activity, plasma xanthine oxidase, and low grade inflammatory markers in adult patients with familial hypercholesterolaemiaEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 2 2010J. T. Real Eur J Clin Invest 2010; 40 (2): 89,94 Abstract Background, Few data are available on circulating mononuclear cells nuclear factor-kappa B (NF-kB) activity and plasma xanthine oxidase (XO) activity in heterozygous familial hypercholesterolaemia (FH). The goal of the study was to analyse circulating mononuclear cells NF-kB and plasma XO activities in FH patients. Materials and methods, Thirty FH index patients and 30 normoglycaemic normocholesterolaemic controls matched by age, gender, body mass index, abdominal circumference and homeostasis model assessment index were studied. Plasma XO and inflammatory markers were measured by standard methods. NF-kB was assayed in circulating mononuclear cells. Results, Familial hypercholesterolaemia patients showed a significantly higher NF-kB (75·0 ± 20·7 vs. 42·7 ± 16·8 relative luminiscence units) and XO (0·44 ± 0·13 vs. 0·32 ± 0·09 mU mL,1) activities than controls. In addition, interleukin-1, interleukin-6, high sensitivity C reactive protein (hsCRP) and oxidized LDL (LDL-ox) were also significantly higher in FH patients. In the total group (FH and controls), XO was significantly associated with LDL-cholesterol (LDL-C), apolipoprotein B (apoB), NF-kB and hsCPR, and NF-kB activity was significantly associated with XO, hsCPR, LDL-ox, LDL-C and apoB plasma values. Using multiple regression analysis, XO was independently associated with hsCPR and NF-kB, and NF-kB activity in circulating mononuclear cells was independently associated with apoB and LDL-ox plasma values. Conclusion, Familial hypercholesterolaemia patients show increased activities of NF-kB and XO, and higher values of low grade inflammatory markers related to atherosclerosis. NF-kB activity was independently associated with apoB plasma values. These data could explain in part the high cardiovascular disease risk present in these patients. [source] Cardiovascular risk factors and collateral artery formationEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 12 2009D. De Groot Abstract Arterial lumen narrowing and vascular occlusion is the actual cause of morbidity and mortality in atherosclerotic disease. Collateral artery formation (arteriogenesis) refers to an active remodelling of non-functional vascular anastomoses to functional collateral arteries, capable to bypass the site of obstruction and preserve the tissue that is jeopardized by ischaemia. Hemodynamic forces such as shear stress and wall stress play a pivotal role in collateral artery formation, accompanied by the expression of various cytokines and invasion of circulating leucocytes. Arteriogenesis hence represents an important compensatory mechanism for atherosclerotic vessel occlusion. As arteriogenesis mostly occurs when lumen narrowing by atherosclerotic plaques takes place, presence of cardiovascular risk factors (e.g. hypertension, hypercholesterolaemia and diabetes) is highly likely. Risk factors for atherosclerotic disease affect collateral artery growth directly and indirectly by altering hemodynamic forces or influencing cellular function and proliferation. Adequate collateralization varies significantly among atherosclerotic patients, some profit from the presence of extensive collateral networks, whereas others do not. Cardiovascular risk factors could increase the risk of adverse cardiovascular events in certain patients because of the reduced protection through an alternative vascular network. Likewise, drugs primarily thought to control cardiovascular risk factors might contribute or counteract collateral artery growth. This review summarizes current knowledge on the influence of cardiovascular risk factors and the effects of cardiovascular medication on the development of collateral vessels in experimental and clinical studies. [source] Genetic influence in antithrombotic actions of atorvastatin in hypercholesterolaemiaEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 1 2008L. Puccetti ABSTRACT Background, Recent data indicate that statins could offer coronary artery disease (CAD) benefit even by mechanisms beyond lipid lowering. Genetic influence has been shown for some antithrombotic actions of statins via oxidized-low-density lipoprotein cholesterol (ox-LDL) receptors and nitric oxide synthase (NOS) activity modulation. The present study was designed to evaluate the influence of ox-LDL lectin-like receptor-1 (LOX-1) and NOS polymorphisms in the incidence of cardiovascular events in pure hypercholesterolaemic subjects during statin treatment. Materials and methods, A prospective 4-year study involving 1039 event-free subjects (643 males, 396 females) treated with atorvastatin (10,40 mg day,1) to reach the appropriate Adult Treatment Panel-III LDL target of 3·36 mmol L,1. Enrolled subjects were evaluated every 6 months or at a clinical event. LOX-1 3,UTR/T-C and NOS G894T polymorphisms were detected by allelic discrimination assays (polymerase chain reaction), lipid profile by enzymatic-colorimetric method, ox-LDL by enzyme linked immunosorbent assay, platelet activation by P-selectin (P-sel) expression (FACScan), NOS activity (by intracellular citrullin recovery) and homocysteine (high performance liquid chromatography), C-reactive protein (CRP) by sensitive nephelometric technique. Results, LOX-1 3,UTR/T showed the strongest association with events in the whole cohort with respect to each other variable including LDL reduction and NOS G894T (OR 4·90, 95% CI 3·19,6·98, P < 0·00001). Smoking influenced events in LDL-targeted subjects (P < 0·0001). Ox-LDL and P-sel were better indicators than LDL or other variables according to 3,UTR/C genotype regardless of the magnitude of LDL reduction (OR 4·21, 95% CI 2·29,6·70 P < 0·0001). Conclusions, LOX-1 polymorphisms could influence statin effectiveness in CAD prevention by induction of sensitivity to antithrombotic mechanisms such as antiplatelet activity. [source] Increased inflammatory markers in children with familial hypercholesterolaemiaEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 3 2006T. Ueland Abstract Background, While data are abundant on increased levels of inflammatory markers in adult patients with hypercholesterolaemia, such data in children are limited. Therefore, we sought to investigate the degree and character of inflammation in children with heterozygous familial hypercholesterolaemia (FH) by measuring levels of neopterin, high-sensitivity C-reactive protein (hsCRP), and soluble CD40 ligand (sCD40L). Materials and methods, In the present study, we compared the concentration of inflammatory markers in children suffering from heterozygous FH (n = 207) with those in unaffected siblings (n = 84). Furthermore, we investigated the effect of 2-year treatment with pravastatin (20,40 mg qd) or placebo on plasma levels of those markers. Results, Our main finding was that serum levels of neopterin and hsCRP were significantly higher in FH children compared with healthy siblings, whereas sCD40L was not. Body mass index and high-density lipoprotein cholesterol levels were significant independent predictors of hsCRP and neopterin. Furthermore, pravastatin therapy decreased neopterin, but not hsCRP and sCD40L, in the FH children, but these changes were not different from the placebo group. Conclusion, These findings indicate low-grade monocyte/macrophage hyperactivity in the early stages of atherogenesis, but our findings also suggest that inflammation as well as anti-inflammatory effects of statins are less prominent features of atherosclerosis in FH children than in FH adults. [source] Pathogenesis, detection and treatment of Achilles tendon xanthomasEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 4 2005S. G. Tsouli Abstract Tendon xanthomatosis often accompanies familial hypercholesterolaemia, but it can also occur in other pathologic states. Achilles tendons are the most common sites of tendon xanthomas. Low-density lipoprotein (LDL) derived from the circulation accumulates into tendons. The next steps leading to the formation of Achilles tendon xanthomas (ATX) are the transformation of LDL into oxidized LDL (oxLDL) and the active uptake of oxLDL by macrophages within the tendons. Although physical examination may reveal Achilles tendon xanthomas (ATX), there are several imaging methods for their detection. It is worth mentioning that ultrasonography is the method of choice in everyday clinical practice. Although several treatments for Achilles tendon xanthomas (ATX) have been proposed (LDL apheresis, statins, etc.), they target mostly in the treatment of the basic metabolic disorder of lipid metabolism, which is the main cause of these lesions. In this review we describe the formation, detection, differential diagnosis and treatment of ATX as well as the relationship between tendon xanthomas and atheroma. [source] Impact of genetic defects on coronary atherosclerosis in patients suspected of having familial hypercholesterolaemiaEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 1 2003O. S. Descamps Abstract Background In the present study we assessed whether the presence of genetic mutations typical of familial hypercholesterolaemia (FH) was associated with greater atherosclerosis in the coronary vessels in patients with severe hypercholesterolaemia and a family history of early cardiovascular disease. Materials and methods Two hundred and thirty-five patients selected for having severe hypercholesterolaemia and a family history of cardiovascular disease were classified as FH (57 men and 38 women) or non-FH (84 men and 56 women) according to a genetic analysis of the LDL-R or ApoB genes. Coronary atherosclerosis was evaluated by performing a thoracic CT scan and exercise stress testing. Results Familial hypercholesterolaemia individuals had a significantly higher prevalence of coronary calcification than the non-FH patients from among both the men (OR = 3·90; 95% CI 1·86,8·19; P < 0·001) and the women (OR = 2·34; 95% CI 1·01,5·48; P = 0·05). In exercise stress testing, ECG abnormalities suggestive of cardiac ischaemia were found with a higher prevalence in the FH patients than the non-FH patients from among both the men (OR 6·15; 95% CI 2·16,17·5; P < 0·001) and the women (OR 4·76; 95% CI 0·91,24·6; P = 0·06). All differences were statistically significant after adjusting for age and cholesterol and for most classical risk factors that differed between the FH and non-FH groups. Conclusion Among patients with severe hypercholesterolaemia and a family history of early cardiovascular disease, the presence of a genetically ascertained FH is associated with a higher prevalence of coronary artery calcifications and a positive exercise stress test. These results suggest that despite a similar phenotype, patients carrying mutations suggestive of FH may have a greater cardiovascular risk than patients without these mutations. [source] A metabolic syndrome of hypertension, hyperinsulinaemia and hypercholesterolaemia in the New Zealand obese mouseEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 3 2000Ortlepp Background New Zealand obese (NZO) mice exhibit a polygenic obesity associated with hyperinsulinaemia and hyperglycaemia. Here we show that the strain presents additional features of a metabolic syndrome, i.e. elevated blood pressure, serum cholesterol and serum triglyceride levels. Materials and methods A back-cross model of NZO mice with the lean Swiss Jackson Laboratory (SJL) strain was established in order to investigate further the correlation between hypertension, obesity, serum insulin and hyperglycaemia. Results Systolic blood pressure was significantly elevated at 6 weeks of age and appeared to parallel the weight gain of the animals. Serum insulin levels, presumably reflecting insulin resistance, and systolic blood pressure values were significantly correlated with the body mass index (r2 = 0.707 and 0.486, respectively) in the back-cross mice. In contrast, blood pressure was only weakly correlated with serum insulin (r2 = 0.288) in non-diabetic mice, and was independent of serum insulin levels in diabetic animals. Conclusion The data are consistent with the concept that hypertension and insulin resistance are a characteristic consequence of the genetic constellation leading to obesity in the NZO strain, and that these traits reflect related mechanisms. It appears unlikely, however, that hypertension is a direct consequence of hyperinsulinaemia. [source] Heart and carotid artery disease in stroke patients with intermittent claudicationEUROPEAN JOURNAL OF NEUROLOGY, Issue 5 2000X. F. Liu Much has been published on the natural history of intermittent claudication (IC), but little is known about the clinical features of stroke patients with IC. The purpose of this study was to examine clinical features and risk factors in stroke patients with or without IC, including heart disease and carotid artery disease. A hospital-based study was conducted of 3901 stroke patients, who were prospectively coded and entered into a computerized databank. Of these patients, 219 had symptoms of IC. Patients were subdivided by age into 10-year categories. There were at least 12 times more non-IC than IC patients in each category. An age-matched random sample was obtained containing 12 non-IC cases for each IC case, resulting in 219 cases of IC and 2628 non-IC cases. The prevalence of IC in the total stroke population was 5.6%. IC prevalence increased sharply with age until about 70 years. Cardiac ischaemia and internal carotid artery (ICA) disease were significantly more frequent in stroke with IC than without IC. IC patients also exhibited a higher prevalence of atherosclerotic disease as well as other risk factors such as smoking, hypercholesterolaemia, elevated haematocrit, and family history of stroke. Ischaemic heart disease and ICA disease are especially common in stroke with IC. IC, large artery disease and stroke share similar risk factors. IC symptoms in stroke patients may indicate extensive generalized atherosclerosis. [source] Guggul for treating hypercholesterolaemia , does it work?FOCUS ON ALTERNATIVE AND COMPLEMENTARY THERAPIES AN EVIDENCE-BASED APPROACH, Issue 2 2009Article first published online: 3 JUN 2010 [source] Impact of highly active antiretroviral therapy on blood pressure in HIV-infected patients.HIV MEDICINE, Issue 1 2006A prospective study in a cohort of naive patients Objectives To assess the impact of highly active antiretroviral therapy (HAART) on the blood pressure (BP) of naive patients after 1 year of treatment. Methods A prospective, observational study of 95 HIV-positive patients in our Unit starting HAART between January 2001 and October 2002 and maintaining the same regimen for 48 weeks of follow-up was carried out. Data on blood pressure (BP) and demographic, epidemiological, clinical, immunovirological and therapeutic characteristics related to HIV infection were collected prior to HAART and at week 48. High blood pressure (HBP) [systolic BP (SBP) ,140 mm Hg and/or diastolic BP (DBP) ,90 mm Hg] was defined according to international criteria. Results Of the 95 patients, 78 were men, 44% had AIDS and 68% were smokers, and their mean age was 40 years. At week 48 the prevalence of HBP was 26% and SBP, DBP and pulse pressure (PP) increased (121.8 versus 116.6 mm Hg, P=0.0001; 76.3 versus 69.7 mm Hg, P=0.004; 46.9 versus 43.8 mm Hg, P=0.001, respectively). Univariate analysis showed that HBP was associated with older age, higher body mass index (BMI), higher baseline lipids, and higher baseline BP. A linear regression model adjusting for age and sex suggested a significant impact of older age, higher baseline SBP, higher baseline hypercholesterolaemia and lower baseline CD4-cell count on SBP increase. Conclusions Blood pressure increased after 48 weeks of HAART, leading to an important prevalence of hypertension. The increase in SBP depended on age and baseline lipid profile and immunological status. BP should be periodically measured and treated when necessary in HIV-infected patients on HAART. [source] Surgical portosystemic shunts and the Rex bypass in children: a single-centre experienceHPB, Issue 3 2009Sukru Emre Abstract Objectives:, This study aimed to illustrate the indications for, and types and outcomes of surgical portosystemic shunt (PSS) and/or Rex bypass in a single centre. Methods:, Data were collected from children with a PSS and/or Rex bypass between 1992 and 2006 at Mount Sinai Medical Center, New York. Results:, Median age at surgery was 10.7 years (range 0.3,22.0 years). Indications included: (i) refractory gastrointestinal bleeding in portal hypertension associated with (a) compensated cirrhosis (n= 12), (b) portal vein thrombosis (n= 10), (c) hepatoportal sclerosis (n= 3); (ii) refractory ascites secondary to Budd,Chiari syndrome (n= 3), and (iii) familial hypercholesterolaemia (n= 4). There were 20 distal splenorenal, four portacaval, three Rex bypass, two mesocaval, two mesoatrial and one proximal splenorenal shunts. At the last follow-up (median 2.9 years, range 0.1,14.1 years), one shunt (Rex bypass) was thrombosed. Two patients had died and two had required a liver transplant. These had a patent shunt at last imaging prior to death or transplant. Conclusions:, Portosystemic shunts and Rex bypass have been used to manage portal hypertension with excellent outcomes. In selected children with compensated liver disease, PSS may act as a bridge to liver transplantation or represent an attractive alternative. [source] Safety and efficacy of ezetimibe monotherapy in 1624 primary hypercholesterolaemic patients for up to 2 yearsINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 9 2008C. A. Dujovne Summary Aims:, This report examined the safety and efficacy of treatment for up to 2 years with the cholesterol absorption inhibitor, ezetimibe (EZE). Methods:, Two identical, randomised, double-blind trials (starting with 827 and 892 patients), evaluated the efficacy and safety of EZE 10 mg/day vs. placebo for 12 weeks in patients with primary hypercholesterolaemia [low-density lipoprotein cholesterol (LDL-C) 3.3,5.1 mmol/l]. Upon completion of these base studies, patients were offered a 2-year, open-label extension study. Adverse event (AE) reports for EZE monotherapy-treated patients were summarised for 3-month intervals to allow for comparison with the placebo group of the 3-month base studies. The primary end-point for this analysis was the evaluation of the long-term safety and tolerability of EZE 10 mg monotherapy dosed daily for up to 24 months. Results:, The incidences of new AEs, treatment-related (TR) AEs, serious AEs (SAEs), TRSAEs and discontinuations as a result of AEs during any 3-month interval were comparable with the respective observations in the placebo group of the base studies. The incidences of AEs, TRAEs, SAEs, TRSAEs and discontinuations as a result of AEs decreased in almost every interval compared with earlier intervals throughout the 2-year study. In addition, the incidences of , 3-fold consecutive elevations of liver transaminases (0.7%) or , 10-fold increases in creatine phosphokinase (0.4%) for the entire 2-year treatment period were comparable with those of the placebo group (0.7% and 0.2% respectively). LDL-C reductions of ,18% were maintained throughout the study. Conclusions:, Compared with placebo, treatment with EZE for up to 2 years in 1624 patients showed no evidence of increased incidence of AEs with increased treatment duration, while showing sustained effects on LDL-C reduction. [source] Heterozygote men with familial hypercholesterolaemia may have an abnormal triglyceride response post-prandially.INTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 3 2005Evidence for another predictor of vascular risk in familial hypercholesterolaemia Summary Familial hypercholesterolaemia (FH) is associated with premature coronary heart disease (CHD). Post-prandial hypertriglyceridaemia has also been associated with cardiovascular disease. Thus, an abnormal post-prandial triglyceride (TG) clearance may contribute to the heterogeneity in the risk of CHD in heterozygous (h) FH. Therefore, we investigated the response of TG levels to a fatty meal in men with hFH. We studied 26 Greek men divided into two groups: the hFH group of 14 men, mean age 39 (SD = 11) years and the control group of 12 healthy men, mean age 43 (50:5) years. An increased TG response to the fatty meal was defined as a post-prandial TG concentration (at 4, 6 or 8 h) greater than the highest TG concentration in any hour in any control individual. All hFH patients had normal baseline fasting TG levels. However, seven hFH men showed an abnormal TG response after the fatty meal; these patients had higher baseline fasting TG levels than others [1.5 (0.2) vs. 1.0 (0.4) mmol/l, p = 0.005]. The hFH men constituted a heterogeneous group regarding their TG response to the fatty meal compared with healthy men because 50% with higher, but nevertheless ,normal' basal TG levels, had an abnormal post-prandial TG response. The reduced activity of low-density lipoprotein receptors in hFH together with other defects in TG handling may explain the abnormal rise of TG levels post-prandially. [source] Risk factors of Hong Kong Chinese patients with coronary heart diseaseJOURNAL OF CLINICAL NURSING, Issue 7 2007Sek Ying Chair RN Aims and objectives., The aims of the study were to describe the level of modifiable coronary risk factors and to explore the relationships among these risk factors in patients with coronary heart disease. Background., Appropriate patient education and therapies for coronary risk reduction will prevent recurrent cardiac events and progression of coronary heart disease. Therefore, having knowledge of the risk profile of these patients is essential so that appropriate contents and focus of patient educations can be developed. Methods., Coronary heart disease patients admitted for cardiac catheterization at the two studied hospitals in Hong Kong were recruited for this study. Demographic date and risk factors of blood pressure, smoking status, body mass index, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and exercise level were collected from subjects as well as from medical records for analysis. Results., The body mass index was significantly different among non-smoker, ex-smoker and smoker (p = 0·027). Non-smokers had the highest body mass index but smokers had the lowest body mass index among the three groups in this study. Physical inactivity, overweight and hypercholesterolaemia were the risk factors seen in about 50% of the studied subjects. Body mass index correlated positively with systolic blood pressure but negatively correlated with high-density lipoprotein cholesterol and hour of exercise. Conclusions., Heavier subjects had a higher systolic blood pressure but a lower level of high-density lipoprotein cholesterol. Heavier subjects also exercised less. The study results provided additional information on the database of the risk profile among Hong Kong cardiac patients. Relevance to clinical practice., Hypertension, obesity, physical inactivity, abnormal serum lipid levels and smoking are the modifiable risk factors for coronary heart diseases. As physical inactivity, overweight and hypercholesterolaemia were found in half of the studied subjects, the importance of risk factors control should be addressed to this group of patients. Nurses should be aware of their educator role to provide appropriate education to coronary heart disease patients with the focus on reducing and controlling of cardiac risk factors, which has been shown to be effective in reducing the progress of disease. [source] Crossing the barrier: oxysterols as cholesterol transporters and metabolic modulators in the brainJOURNAL OF INTERNAL MEDICINE, Issue 6 2006I. BJÖRKHEM Abstract. A normal brain function requires constant levels of cholesterol, and the need for constancy seems to be higher here than in any other organ. Nature has met this need by isolation of brain cholesterol by a highly efficient blood,brain barrier. As a low synthesis of cholesterol is present in the brain, a mechanism for compensatory elimination is required. A decade ago we made the unexpected finding that the favoured mechanism for this involves conversion into 24S-hydroxycholesterol, followed by diffusion over the blood,brain barrier. Recent studies by us and others on this new pathway have given new insights into the mechanisms by which cholesterol homeostasis is maintained in the brain. We recently demonstrated a flux of another oxygenated product of cholesterol, 27-hydroxycholesterol, in the opposite direction. The latter flux may be important for neurodegeneration, and may be the link between hypercholesterolaemia and Alzheimer's disease. An overview of the above studies is presented and the possibility that the cholesterol 24S-hydroxylase in the brain may be important for memory and learning and that it may be a new drug target is discussed. [source] Who should receive a statin these days?JOURNAL OF INTERNAL MEDICINE, Issue 4 2006Lessons from recent clinical trials Abstract. The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors or statins are the most successful cardiovascular drugs of all time. By interrupting cholesterol synthesis in the liver, they activate hepatocyte low-density lipoprotein (LDL) receptors and produce consistent and predictable reductions in circulating LDL cholesterol with resulting reproducible improvements in cardiovascular risk by retarding or even regressing the march of atherosclerosis in all major arterial trees (coronary, cerebral and peripheral). Clinical trials have demonstrated their capacity not only to extend life, but also to improve its quality by retarding the progression of diabetes mellitus and chronic renal disease and by enhancing central and peripheral blood flow. They are amongst the most extensively investigated pharmaceutical agents in current clinical use. In cardiovascular end-point trials they have proven ability to help prevent that first and all important myocardial infarction and to reduce the likelihood of a recurrence in those who do succumb. They are equally effective in men and women of all ages and at all levels of cardiovascular risk, whether caused by hypercholesterolaemia, hypertension, cigarette smoking, diabetes mellitus or the metabolic syndrome. In addition, they improve the outlook of patients with familial hypercholesterolaemia whose LDL receptor function is deficient or defective; and all of this comes at minimal risk to the recipient. Their most important potential side effect is myopathy, which on very rare occasions may lead to rhabdomyolysis. Clinical experience shows that myopathic symptoms with creatine kinase levels raised to more than 10 times the upper limit of normal is seen in <0.01% of recipients and progression to fatal rhabdomyolysis because of renal failure has been recorded in only 0.15 cases per million prescriptions. Liver function abnormalities are also, rarely, seen. Again, the frequency of raised aspartate or alanine aminotransferase to more than three times the normal limit is encountered in no more than 1,2% of all treated patients and is completely reversible upon withdrawal of treatment. Progression to hepatitis or liver failure does not occur. This constellation of benefits with little side effect penalty has resulted in the comparison of statins with antibiotics in the global battle against cardiovascular disease. [source] Prevalence and significance of cardiovascular risk factors in a large cohort of patients with familial hypercholesterolaemiaJOURNAL OF INTERNAL MEDICINE, Issue 2 2003P. R. W. De Sauvage Nolting Abstract., de Sauvage Nolting PRW, Defesche JC, Buirma RJA, Hutten BA, Lansberg PJ, Kastelein JJP (Academic Medical Center, Amsterdam; Clinical Research, Haarlem; Slotervaart Hospital, Amsterdam; the Netherlands). Prevalence and significance of cardiovascular risk factors in a large cohort of patients with familial hypercholesterolaemia. J Intern Med 2003; 253: 161,168. Objective., Patients with familial hypercholesterolaemia (FH) vary widely in terms of onset of cardiovascular disease (CVD). Design., The association between cardiovascular risk factors and prevalent CVD was examined in a cross-sectional study in order to elucidate their contribution to atherogenesis. Setting and subjects., Patients were recruited from 37 Dutch Lipid Clinics. The diagnosis of FH was based on a uniform diagnostic protocol, confirmed by DNA analysis in 62% of the cases. All patients were investigated free from any lipid-lowering drug for at least 6 weeks. Main outcome measures., Differences in lipids, lipoproteins and other risk factors for CVD were analysed in FH patients with and without CVD. Results., A total of 526 patients were assessed and more than 37% had a history of CVD with a mean age of onset of 46.8 years. Mean LDL cholesterol (LDL-C) levels were severely elevated (8.38 ± 2.13 mmol L,1). In univariate analysis, age, presence of hypertension or diabetes, body mass index, triglycerides (TG) and low HDL cholesterol (HDL-C) were all significantly associated with CVD. Also in multivariate analysis, all these risk factors, except TG and diabetes, were significantly linked to CVD. Conclusion., A high CVD risk in this large well-documented characterized sample of FH patients is not only conferred by elevated LDL-C but also by low HDL-C. [source] What cause of mortality can we predict by cholesterol screening in the Japanese general population?JOURNAL OF INTERNAL MEDICINE, Issue 2 2003T. Okamura Abstract., Okamura T, Kadowaki T, Hayakawa T, Kita Y, Okayama A, Ueshima H (Shiga University of Medical Science, Shiga, Japan; Iwate Medical University, Morioka, Iwate, Japan). What cause of mortality can we predict by cholesterol screening in the Japanese general population? J Intern Med 2003; 253: 169,180. Objective., In a population with a markedly lower coronary mortality such as in Japan, the benefit of cholesterol screening may be different from Western populations. We attempted to assess the importance of cholesterol screening in Japan. Design., A 13.2-year cohort study for cause-specific mortality. Setting., Three hundred randomly selected districts throughout Japan in which the National Survey on Circulatory Disorders 1980 was performed. Subjects., A total of 9216 community dwelling persons aged 30 years and over, with standardized serum cholesterol measurement and without a past history of cardiovascular disease. Results., There were 1206 deaths, which included 462 deaths due to cardiovascular disease with 79 coronary heart diseases. Hypercholesterolemia (>6.21 mmol L,1) showed a significant positive relation to coronary mortality (relative risk; 2.93, 95% confidence interval; 1.52,5.63) but not to stroke. Although hypocholesterolemia (<4.14 mmol L,1) was significantly associated with an increased risk of liver cancer, noncardiovascular, noncancer disease and all-cause mortality, these associations, except for liver cancer, disappeared after excluding deaths in the first 5 years of the follow-up. The multivariate adjusted attributable risk of hypercholesterolaemia for coronary disease was 0.98 per 1000 person-years, which was threefold higher than that of hypocholesterolemia for liver cancer: 0.32 per 1000 person-years. The attributable risk percentage of hypercholesterolaemia was 66% for coronary heart disease. Conclusion., Similar to Western populations, it is recommended to provide screening for hypercholesterolaemia in Japan, especially for males, although its attributable risk for coronary disease might be small. [source] Prediction of five-year survival for patients admitted to a department of internal medicineJOURNAL OF INTERNAL MEDICINE, Issue 5 2001B. O. Eriksen Abstract.,Eriksen BO, Kristiansen IS, Pape JFr (University Hospital of Tromsø and University of Tromsø, Tromsø, Norway). Prediction of five-year survival for patients admitted to a department of internal medicine. J Intern Med 2001; 250: 435,440. Objective.,The effect of many common forms of therapy, as medication for mild hypertension or hypercholesterolaemia, only reaches clinical significance after years of treatment. The meaningful application of such therapy presupposes that physicians can, at least to some extent, predict the remaining lifetime of patients. We investigated whether clinicians from different disciplines were able to predict the 5-year survival of patients admitted to a department of internal medicine. Design.,The members of two groups, each consisting of an internist, a surgeon and a general practitioner, made individual predictions of the expected remaining lifetime of discharged patients from written summaries of clinical information. Each patient was randomized to be assessed by the members of either of the two groups. The predictions were compared with actual 5-year survival. Setting.,Department of internal medicine at a university hospital. Subjects.,Patients admitted consecutively during a 6-week period. Main outcome measures.,Sensitivity, specificity, positive and negative predictive values and areas under the receiver operating characteristic (ROC) curves for predictions of 5-y ear survival for each of the six experts. Results.,A total of 402 patients were included. Five-year survival was 0.63. The sensitivity of the predictions ranged from 0.81 to 0.95, the specificity from 0.61 to 0.77, the positive predictive value from 0.78 to 0.87 and the negative predictive value from 0.68 to 0.87. The areas under the ROC curves ranged from 0.84 to 0.91. Conclusion.,The quality of predictions of 5-year survival made by experienced clinicians should permit the rational use of treatments with long-term effects. [source] Association of coronary heart disease with age-adjusted aortocoronary calcification in patients with familial hypercholesterolaemiaJOURNAL OF INTERNAL MEDICINE, Issue 4 2000J. M. Jensen Abstract. Jensen JM, Gerdes LU, Jensen HK, Christiansen TM, Brorholt-Petersen JU, Faergeman O (Aarhus Amtssygehus University Hospital, Aarhus, Denmark). Association of coronary heart disease with age-adjusted aortocoronary calcification in patients with familial hypercholesterolaemia. J Intern Med 2000; 247: 479,484. Objectives. Existing algorithms of risk of coronary heart disease (CHD) do not pertain to patients with familial hypercholesterolaemia (FH), whose arteries have been exposed to hypercholesterolaemia since birth. We studied a cohort of FH patients to compare four diagnostic models of CHD: traditional risk factors of CHD (age, sex, cholesterol, hypertension, smoking and body mass index), cholesterol year score, and aortic as well as coronary calcium measured by spiral computed tomography (CT). Subjects. We invited 88 individuals with molecularly defined FH of whom 80 (91%) decided to participate. Results. Analysis of receiver operating characteristic curves showed that the age-adjusted coronary calcium score was more strongly associated with clinical manifestations of CHD than were traditional risk factors (P < 0.002), cholesterol year score (P << 0.0001), and the age-adjusted aortic calcium score (P < 0.0004). Conclusions. Age-adjusted coronary calcium score shows promise as an indicator of CHD in FH patients. [source] Hypercholesterolaemia induces early renal lesions characterized by upregulation of MMP-9 and iNOS and ETAR: alleviated by a dual endothelin receptor antagonist CPU0213 and simvastatinJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 6 2009Lu Luo Abstract Objectives We aimed to investigate hypercholesterolaemia-induced early renal lesions which result in abnormal expression of endothelin A receptor (ETAR), induced nitric oxide synthase (iNOS) and matrix metalloproteinase 9 (MMP-9). We hypothesized that this is due to an upregulated endothelin (ET) pathway consequent to hypercholesterolaemia and that CPU0213, a dual ET antagonist, could mitigate these changes. Methods Rats were randomly divided into four groups: (1), control; (2), high-fat diet for 60 days (HFD); HFD rats medicated in the last 15 days with either (3) CPU0213 (30 mg/kg daily, s.c.) or (4) simvastatin (4 mg/kg daily, p.o.). Key findings Body weight, serum triglycerides, total cholesterol and low-density-lipoprotein cholesterol were significantly increased, whereas high-density lipoprotein cholesterol decreased in the HFD group, relative to normal. Meanwhile, these changes were associated with upregulation of mRNA and protein of ETAR, iNOS and MMP-9 in the kidney. The lipid-lowering effect of simvastatin was predominant, lessening abnormal expression of these molecules in the kidney dramatically. Interestingly, CPU0213 significantly normalized expression of mRNA and protein of ETAR, iNOS and MMP-9, comparable with simvastatin, leaving no changes in hyperlipidaemia. Conclusions CPU0213 relieves renal lesions by blunting hypercholesterolaemia caused by the upregulated ET system, iNOS and MMP-9 in the kidney. This indicates that CPU0213 is promising in treating patients with end stage renal disease. [source] Risk of vascular disease in adults with diagnosed coeliac disease: a population-based studyALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 1 2004J. West Summary Background :,It has been suggested that vascular disease mortality may be reduced in coeliac disease because of lower levels of blood pressure, cholesterol and body mass. Aim :,To examine whether people with coeliac disease are at reduced risk of various vascular diseases. Methods :,We identified 3790 adults with diagnosed coeliac disease and 17 925 age- and sex-matched controls in the General Practice Research Database. We estimated odds ratios for diagnosed hypertension, hypercholesterolaemia and atrial fibrillation and hazard ratios for myocardial infarction and stroke. Results :,Adults with coeliac disease, compared with controls, were less likely to have had a diagnosis of hypertension [11% vs. 15%, odds ratio 0.68 (95% confidence interval: 0.60,0.76)] or hypercholesterolaemia [3.0% vs. 4.8%, odds ration 0.58 (95% confidence interval: 0.47,0.72)] but slightly more likely to have had atrial fibrillation [2.1% vs. 1.7%, odds ratio 1.26 (95% confidence interval: 0.97,1.64)]. The hazard ratio for myocardial infarction was 0.85 (95% confidence interval: 0.63,1.13), while the hazard ratio for stroke was 1.29 (95% confidence interval: 0.98,1.70). Conclusions :,Although rates of myocardial infarction and stroke were not substantially different, adults with coeliac disease do have a lower prevalence of hypertension and hypercholesterolaemia compared with the general population. The effect of a gluten-free diet on cardiovascular risk factors should be determined before any screening programmes for coeliac disease are instituted. [source] Long-term graft function with tacrolimus and cyclosporine in renal transplantation: Paired kidney analysisNEPHROLOGY, Issue 8 2009CHI YUEN CHEUNG SUMMARY: Aim: The first prospective, randomized trial with paired kidney analysis was conducted to compare the efficacy and safety of tacrolimus with cyclosporine-based immunosuppressive therapy in renal transplant recipients. This paper reports the long-term follow-up results of the authors' previously published study, with the main focus on graft survival and renal function. Methods: Chinese patients transplanted in our centre between June 1998 and June 2005 with their first deceased renal transplant were included. Patients were included if both kidneys were received by the authors' centre, thus allowing a paired analysis. Patients were randomized to receive triple immunosuppressive therapy with either tacrolimus or Neoral cyclosporine, concomitantly with prednisolone and azathioprine therapy. Results: Seventy-six patients received cadaveric kidneys from 38 donors. Each pair of kidneys was randomly assigned to a separate group (38 subjects/group). The mean follow-up duration was 6.1 ± 1.8 years. The mean calculated creatinine clearance was significantly higher in patients receiving tacrolimus-based therapy. The rate of biopsy-proven acute rejection was lower in the tacrolimus group (18.4% vs 42.1%, P = 0.03). The patient and graft survival were comparable in both treatment arms. Significantly fewer patients on tacrolimus-based therapy developed hypercholesterolaemia (P = 0.05). However, there was no significant difference in the development of post-transplant diabetes mellitus, hypertension, opportunistic infection and malignancy between both groups. Conclusion: Using the immunosuppressive regimen, tacrolimus-based therapy provided adequate immunosuppression with better renal function and less acute rejection, as compared with cyclosporine-based therapy. [source] Perceived health of adults after prenatal exposure to the Dutch faminePAEDIATRIC & PERINATAL EPIDEMIOLOGY, Issue 4 2003Tessa J. Roseboom Summary People who were undernourished in early gestation are more obese, have a more atherogenic lipid profile, and altered blood coagulation and seem to have an increased risk of coronary heart disease. We now report on whether they also feel less healthy. We therefore assessed the perceived health of 50-year-old-men and women born alive as singletons around the time of the Dutch famine in the Wilhelmina Gasthuis in Amsterdam. People who had been exposed to famine in early gestation, but not those exposed in mid- or late gestation, more often rated their health as poor (10.3% vs. to 4.9% in the unexposed, odds ratio (OR) 2.2 [1.0, 4.8]). The effect of exposure to famine in early gestation on perceived health could only partly be explained by an increased prevalence of coronary heart disease, respiratory diseases, hypertension, type 2 diabetes, hypercholesterolaemia or cancer (adjusted OR 2.2 [0.9, 5.2]). Adjustment for adult risk factors (BMI, LDL/HDL cholesterol ratio, blood pressure, smoking, lung function) also attenuated the results to some extent (adjusted OR 1.9 [0.6, 5.5]). People who were exposed to famine in early gestation were not only less healthy in terms of objective measures of health but they also felt less healthy. Because poor perceived health is a strong predictor of mortality, we may expect increased mortality in people who were exposed to famine in early gestation in the future. [source] Corresponding distributions of increased endothelin-B receptor expression and increased endothelin-1 expression in the aorta of apolipoprotein E-deficient mice with advanced atherosclerosisPATHOLOGY INTERNATIONAL, Issue 12 2000Tsutomu Kobayashi Endothelin (ET)-1 causes proliferation of vascular smooth muscle cells (VSMC). Although it has been reported that stimulation of ETB receptors as well as ETA receptors promote proliferation of VSMC, the precise distribution of each receptor subtype in atherosclerotic vessels is unknown. Previous studies demonstrated that apolipoprotein E (apoE)-deficient mice have hypercholesterolaemia and develop severe atherosclerosis. To investigate the pathophysiological roles of vascular ET system in atherosclerosis, we examined preproET-1 messenger ribonucleic acid expression in the aorta of apoE-deficient mice, and performed immunohistochemical staining for ET-1 and each ET receptor subtype (ETA and ETB receptors) in the atherosclerotic lesions of these mice. The level of preproET-1 mRNA in the aorta was significantly higher in the apoE-deficient mice than in the control mice. Strong ET-1 staining was observed in the macrophage-foam cells, intimal and medial VSMC in the atherosclerotic lesions of the apoE-deficient mice. In addition, in the atherosclerotic lesions, strong ETB receptor staining was observed in the macrophage-foam cells, intimal and medial VSMC, which distribution corresponded closely to that of ET-1. ETA receptor staining was observed in the medial VSMC of both groups, but not in the macrophage-foam cells of the apoE-deficient mice. ETA receptor staining in the medial VSMC was stronger in the apoE-deficient mice than in the control mice. These results suggest that the vascular ET system, including ET-1 and ET receptors, is activated in the atherosclerotic lesions of apoE-deficient mice. Since the distribution of strong ETB receptor staining corresponded closely to that of ET-1, it is suggested that the ET system, mediated by ETB receptors, has an important role in the pathophysiology of the atherosclerotic lesions of apoE-deficient mice. [source] | ||||||||||||||||||||||||||||||||||