Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Almost half of first cardiovascular events occur in individuals with no known risk factors. Attempts in the last decade to predict cardiovascular risk more accurately have led to the emergence of a novel risk factor, C-reactive protein (CRP), which has proved to be as good a risk predictor as low-density lipoprotein cholesterol. C-reactive protein is an index of inflammation that is now believed to promote directly all stages of atherosclerosis, including plaque rupture. As measured by high-sensitivity assays, high-sensitivity CRP (hs-CRP) also independently predicts recurrent events in patients with known coronary artery diseases. Recent evidence implicates hs-CRP, and thus inflammation, in the metabolic syndrome and diabetes mellitus, particularly in women. As a clinical tool for cardiovascular risk assessment, hs-CRP testing enhances information provided by lipid screening or global risk assessment. Statin therapy and other interventions can lower hs-CRP. Whether or not such reductions can prevent cardiovascular events is under investigation.
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PMID:High-sensitivity C-reactive protein as a risk assessment tool for cardiovascular disease. 1625 Feb 63

Cardiovascular disease is a major cause of morbidity and mortality worldwide. During the last decade huge amount of laboratory and clinical evidence proved link between serum lipid concentration and the development of coronary heart disease. The Adult Treatment Panel III of the National Cholesterol Education Program issued an evidence-based set of guidelines on cholesterol management. Since the publication of these guidelines numbers of new clinical trials and experimental results have been published. Recently completed clinical trials have indicated that reduction of low-density lipoprotein cholesterol to goals lower than the previously considered appropriate 2,6 mmol/l, produce further cardiovascular risk reduction in high risk individuals. There is growing evidence of the role of inflammation in the development of atherosclerosis and cardiovascular disease. Numerous studies have demonstrated that elevated C-reactive protein may be an independent cardiovascular risk factor. Statin therapy has produced a greater cardiovascular risk reduction in those patients whose C-reactive protein level was high. Ezetimibe is a new intestinal cholesterol uptake inhibitor, which reduces LDL cholesterol in monotherapy or in combination with statins. Lately a variety of new antilipemic agents are being developed. The present review summarizes some of these new results and their effect on cholesterol lowering therapy.
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PMID:[New results in the management of hypercholesterolemia]. 1626 67

Using serial intravascular ultrasound (IVUS), we evaluated the natural evolution of non-culprit/non-target lesion ruptured coronary plaques and assessed the impact of statin therapy. Twenty-eight patients with non-stenotic ruptured plaques underwent baseline and 12-month follow-up IVUS studies; half were treated with statins. Standard IVUS analyses were performed. Complete healing of ruptured plaques was observed in four (29%) statin-treated patients and no non-statin-treated patients (p=0.049). Statin-treated patients had an increase in lumen area of 0.4+/-0.8 mm2 (versus a decrease in lumen area of -0.6+/-1.0 mm2 in non-statin-treated patients, p=0.007) and no change in plaque area (versus an increase in plaque area of 0.6+/-0.9 mm2, p=0.051). During 1-year follow-up, target lesion revascularization was performed in three non-statin-treated patients (21%) and no statin-treated patient (p=0.11). Compared to lesions that did not require revascularization, lesions requiring revascularization had a decrease in lumen area (-1.7+/-1.4 mm2 versus 0.1+/-0.8 mm2, p=0.001) as well as an increase in plaque area (1.6+/-1.0 mm2 versus 0.1+/-0.7 mm2, p=0.002). In conclusion, the current observational follow-up IVUS study showed beneficial effects of statin treatment on reduction of revascularization rates and stabilization of non-culprit/non-target lesion plaque ruptures without significant stenosis. Conversely, healing of non-statin-treated non-culprit/non-target lesion plaque ruptures can be responsible for lesion progression requiring revascularization.
Atherosclerosis 2007 Mar
PMID:Serial intravascular ultrasound evidence of both plaque stabilization and lesion progression in patients with ruptured coronary plaques: effects of statin therapy on ruptured coronary plaque. 1658 33

To obtain reliable data on the epidemiology, co-morbidities and risk factor profile of peripheral arterial disease (PAD), we evaluated the clinical significance of the ankle brachial index (ABI) as an indicator of PAD in Chinese patients at high cardiovascular (CV) risk. ABI was measured in 5,646 Chinese patients at high CV risk, and PAD was defined as an ABI<0.9 in either leg. Multivariable logistic regression analyses were performed to identify factors associated with PAD. A total of 5,263 patients were analyzed, 52.9% male, mean age 67.3 years, mean body mass index (BMI) 24.2 kg/m2, mean systolic/diastolic blood pressure (SBP/DBP) 139/80.7 mmHg. The prevalence of PAD in the total group of patients was 25.4%, and the prevalence was higher in females than in males (27.1% vs. 23.9%; odds ratio [OR]: 1.64). Patients with PAD were older than those without PAD (72.3+/-9.9 years vs. 65.6+/-11.7 years; OR: 1.06), and more frequently had diabetes (43.3% vs. 31.3%; OR: 2.02), coronary heart disease (CHD) (27.0% vs. 18.8%; OR: 1.67), stroke (44.4% vs. 28.3%; OR: 1.78), lipid disorders (57.2% vs. 50.7%; OR: 1.3) and a smoking habit (42.7% vs. 38.6%; OR: 1.52). The ORs for the PAD group compared with the non-PAD group demonstrated that these conditions were inversely related to ABI. Statin, angiotensin-converting enzyme-inhibitors and antiplatelet agents were only used in 40.5%, 53.6% and 69.1% of PAD patients, respectively. The data demonstrated the high prevalence and low treatment of PAD in Chinese patients at high CV risk. A lower ABI was associated with generalized atherosclerosis. Based on these findings, ABI should be a routine measurement in high risk patients. Aggressive medication was required in these patients.
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PMID:Ankle brachial index as a marker of atherosclerosis in Chinese patients with high cardiovascular risk. 1671 50

Statins, inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase, have been used successfully in the treatment of hypercholesterolemia for more than a decade. Statins also exhibit overall clinical benefits on cardiovascular diseases independent of their effects on lowering serum cholesterol levels. These beneficial effects of statin therapy are believed to be due, at least in part, to the anti-inflammatory and immunomodulatory roles of statins. Statin treatment reduces the levels of inflammatory markers, decreases the activation and recruitment of immune cells, and delays the progression of atherosclerosis, a chronic inflammatory disease. However, little is known about the direct impact of statins on immune cells, particularly on macrophages. We report that lovastatin, a member of the statin family, effectively induces apoptosis in macrophages. Further investigation of the molecular mechanism has revealed that Rac1 and Cdc42, the small GTPase family members, may play an important role in lovastatin-induced macrophage apoptosis. Moreover, the activation of the JNK pathway may contribute to this event. Our findings provide a better understanding of the molecular basis underlying the anti-inflammatory clinical benefits of statin therapy in cardiovascular diseases.
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PMID:Lovastatin-induced apoptosis in macrophages through the Rac1/Cdc42/JNK pathway. 1678 63

CETP (cholesteryl ester transfer protein) and HL (hepatic lipase) play a role in the metabolism of plasma lipoproteins, but the effects of CETP and LIPC (gene encoding HL) genotypes on coronary atherosclerosis may be dependent on LDL (low-density lipoprotein)-receptor activity. Recently, the -1337 C>T polymorphism in the CETP gene has been reported in REGRESS (Regression Growth Evaluation Statin Study) to be a major determinant of promoter activity and plasma CETP concentration. In the present study, we have investigated the effects of the CETP promoter -1337 C>T and LIPC promoter -514 C>T polymorphisms on serum lipid profiles and risk of coronary atherosclerosis in 206 patients (154 males) with heterozygous FH (familial hypercholesterolaemia). To evaluate coronary atherosclerosis, we used CSI (coronary stenosis index) calculated from coronary angiograms. The CETP -1337 T allele was less frequent in subjects with a CSI > or =14 (mean value) in the group with coronary artery disease (P=0.04, as determined by chi(2) test). ANOVA revealed that HDL-C (high-density lipoprotein-cholesterol) and triacylglycerol (triglyceride) levels were not significantly higher in the presence of the CETP promoter -1337 T allele. Combined with LIPC promoter polymorphisms, HDL-C levels were highest and CSI were lowest with CETP -1337 CT+TT and LIPC -514 CC genotypes, but a significant interaction was not shown. A multiple logistic regression analysis revealed that, in patients with coronary atherosclerosis, the CETP- 1337 CC genotype was a significant genetic risk factor in FH (odds ratio=2.022; P=0.0256). These results indicate that the CETP promoter -1337C>T polymorphism is associated with the progression of coronary atherosclerosis in Japanese patients with FH, independent of HDL-C and triacylglycerol levels.
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PMID:CETP (cholesteryl ester transfer protein) promoter -1337 C>T polymorphism protects against coronary atherosclerosis in Japanese patients with heterozygous familial hypercholesterolaemia. 1682 36

Hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors represent the most successful class of drugs for the treatment of hypercholesterolaemia and dyslipidaemia implicated in the pathogenesis of coronary heart disease and atherosclerosis. However, the popular profile of statins in terms of efficacy has been maligned by its adverse events. The myotoxicity, ranging from mild myopathy to serious rhabdomyolysis, associated with HMG-CoA reductase inhibitors, during treatment of hypercholesterolaemia is of paramount importance. Rhabdomyolysis is a rare but idiosyncratic muscle wasting disorder of different etiologies. Statin-associated rhabdomyolysis causes skeletal muscle injury by self-perpetuating events leading to fatal irreversible renal damage through a series of biochemical reactions. Preferential distribution and action of statins in liver could be the key to minimise myotoxicity concerns. Hepato-specific distribution of statins is governed by various factors such as physicochemical properties, pharmacokinetic properties and selective transporter-mediated uptake in liver rather in extrahepatic cells. The interactions of statins with concomitant drugs of different classes merit attention for their safety profile. Although pharmacokinetic as well as pharmacodynamic interactions have been implicated in pathophysiology of statin-induced muscle wasting, the underlying mechanism is not clearly understood. Besides, pharmacokinetic and phramcodynamic factors, statin-associated myotoxcity may also implicate pharmacogenomic factors. The pharmacogenomics characterised by CYP polymorphism and other genetic factors is responsible for inter-individual variations to efficacy and tolerability of statins. The pathophysiological mechanisms may include statin-induced differences in cholesterol:phospholipid ratio, isoprenoid levels, small GTP binding proteins and apoptosis. However, the present understanding of pathophysiological mechanisms, does not offer a reliable approach to address the same at preclinical level. Although statin-associated myotoxicity affects compliance, quality of life of patient and discontinuation rate, yet the low incidence of myotoxicty including rhabdomyolysis and less severity of commonly occurring myopathy and myalgia do not raise doubts about the clinical efficacy and tolerability of statins. Medical management of myotoxicity seems to be pivotal for the proper compliance of patients with statin treatment. The appropriate and judicious use of drugs would substantially reduce the likelihood of developing clinically important myopathy.
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PMID:Statins and myotoxicity: a therapeutic limitation. 1690 55

Familial hypercholesterolemia (FH) is characterised by elevated plasma LDL-cholesterol levels and premature ischemic heart disease. Statin therapy is mandatory in order to prevent atherosclerosis in patients with heterozygous FH. Both genetic and environmental factors affect the statin-induced LDL-cholesterol lowering effect in patients with heterozygous FH. Recently published data suggest that plasma lipoprotein(a) levels may affect the efficacy of statin therapy in patients with nephrotic syndrome. However, no data are available concerning the effect of lipoprotein(a) levels on the efficacy of statin therapy in patients with heterozygous FH. This report demonstrates negative correlation between plasma lipoprotein(a) levels and the LDL-cholesterol lowering effect of statin therapy in 49 patients with heterozygous FH.
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PMID:Plasma lipoprotein(a) levels and LDL-cholesterol lowering response to statin therapy in patients with heterozygous familial hypercholesterolemia. 1695 Dec 79

Atherosclerosis is a lipid related chronic inflammatory disease in which immune mechanisms play a pivotal part. Its lesion is filled with large numbers of immune cells. In 1995 dendritic cells (DCs) were identified in atherosclerotic plaques and thought to play an important part in atherogenesis. DCs express MHCI and ll, HLA-DR, CD1a, ICAM-1 and VCAM1 on their surfaces, and this explains their unique ability to activate naive T cells. The risk factors for atherosclerosis are the factors for DCs' activation and migration. Mature DCs are capable of presenting antigen to T cells, which play an important part in progression of disease. Statin and diltiazem have been shown to protect endothelial function by suppressing the function of DCs and play an important part in preventing atherosclerosis.
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PMID:Potential role of dendritic cells for progression of atherosclerotic lesions. 1695 52

Atherothrombosis results from direct interaction between the atherosclerotic plaque and arterial thrombosis, and underlies most forms of cardiovascular disease (CVD). The pathophysiology of atherosclerosis is now recognised to involve endothelial dysfunction and dyslipidemia with cholesterol accumulation, as well as critical immuno-inflammatory and apoptotic dimensions. Erosion or rupture of a vulnerable, lipid-rich, inflammatory atherosclerotic plaque triggers the formation of a platelet-rich thrombus that may partially or completely occlude the artery, with resultant clinical scenarios including stable and unstable angina, acute myocardial infarction (MI) and ischaemic stroke. Insight into the pathophysiology of atherothrombosis indicates that an integrated risk factor approach, focusing particularly on management of dyslipidaemia (with a statin) and thrombosis (with aspirin), may constitute an optimal therapeutic approach. Both agents have established roles in secondary prevention. Statin action on atherogenic lipoproteins mediates plaque stabilisation, modification of plaque morphology and attenuation of inflammation, and may lead to plaque regression, while aspirin reduces platelet activation and aggregation, decreases release of inflammatory cytokines at sites of vascular injury and attenuates vasoconstriction. Given these complementary modes of action, this combination would be a logical choice for reducing atherothrombotic risk in patients with CVD. Meta-analysis of 5 major clinical studies has demonstrated that the combination of pravastatin plus aspirin was significantly more effective than either agent alone in reducing the relative risk of key cardiovascular endpoints including MI and ischaemic stroke. This combination may therefore represent an important, cost-efficient therapeutic approach to reduction of cardiovascular risk and prevention of recurrent events in stable CVD.
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PMID:From pathophysiology to targeted therapy for atherothrombosis: a role for the combination of statin and aspirin in secondary prevention. 1707 Sep 23


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