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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Advancements in understanding of the pathobiology of atherothrombosis have implicated inflammation as a central contributor to the progression of atherosclerotic vascular disease. Epidemiologic data demonstrate an association between the inflammatory marker hs-CRP and risk for future cardiovascular morbidity and mortality among those at high risk or with documented vascular disease. Moreover, a series of prospective studies provides consistent data documenting that mild elevation of baseline levels of hs-CRP among apparently healthy individuals is associated with higher long-term risk for future cardiovascular events. Among men and women, this predictive capacity of hs-CRP is independent of traditional cardiovascular risk factors and offers a prognostic advantage over measurement of lipids alone. Further, observations from the PHS and CARE trial suggest that the increased risk associated with systemic inflammation may be modified with certain preventive therapies and that inflammatory markers such as hs-CRP may help to identify those who would benefit most from these pharmacologic interventions. Given that high-throughput assays for inflammatory markers, including hs-CRP, are likely to become available for clinical use, carefully designed studies are needed to evaluate the clinical efficacy of hs-CRP as a new marker to stratify cardiovascular risk. Further, prospective, randomized trials are important to test directly the value of inflammatory markers in targeting specific preventive therapies. Finally, it is still undetermined as to whether elevation of these inflammatory markers reflects the degree of underlying atherosclerosis or plaque vulnerability or rather results from some other environmental or infectious stimulus or even has direct effects on platelet aggregation or coagulation [1]. Ongoing and future investigation will clarify the specific pathophysiologic relationships through which these markers correlate with adverse prognosis.
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PMID:C-reactive protein, inflammation, and coronary risk. 1462 48

Recent epidemiologic studies suggest that polymorphisms of glutathione-S-transferases M1 and T1 (GSTM1/GSTT1) modify the effects of cigarette smoking on risk of coronary heart disease (CHD). Since GSTs are able to detoxify numerous toxic compounds and products of oxidative stress, it is possible that GST genotypes may also modify the capacity of smoking to invoke a chronic inflammatory response. A cross-sectional analysis, using a subset of participants (n = 989) in a large (n = 15, 792) biracial cohort, was used to evaluate levels of nine markers of inflammation, hemostasis, and endothelial function by different combinations of GST genotypes and cigarette smoking status. Participants with the GSTM1 null (GSTM1-0) genotype and > or = 20 pack-years of smoking had the highest mean levels of CRP, fibrinogen, von Willebrand factor, ICAM-1, and VCAM-1 and lowest mean levels of albumin compared to other combinations of genotype and smoking. However, a formal test for interaction between GSTM1 genotype and smoking was statistically significant only for albumin. By contrast, participants who had the functional GSTT1 genotype (GSTT1-1) and smoked > or = 20 pack-years had the highest mean levels of only CRP and fibrinogen. The results of this study provide some limited evidence that GSTM1 and GSTT1 polymorphisms modify the effect of smoking on inflammation, hemostasis, and endothelial function.
Atherosclerosis 2003 Dec
PMID:Glutathione-S-transferase genotypes, smoking, and their association with markers of inflammation, hemostasis, and endothelial function: the atherosclerosis risk in communities (ARIC) study. 1464 96

The hypothesis was tested that metabolic syndrome (MS) plays a leading role in approximating the multivariate distribution of thrombogenic and metabolic blood variables in a population of postinfarction patients. The multivariate statistical technique of factor analysis was used to determine blood variable clustering 2 months after myocardial infarction. Five clusters resulted in two separate independent factors, dyslipidemia and metabolic, reflecting MS and the remaining interpreted as cholesterol-lipoprotein, vascular-inflammatory, and coagulation. All five factors accounted for 55% of total variance with MS-associated factors accounting for 20% and individual factor contributions as follows: 11.6, 8.6, 12.9, 11.9, and 9.6%, respectively. There were no interactions of metabolic variables with thrombogenic variables or CRP in any factor. Results of subgroup analysis in males and females and in patients on and not on statins were all similar to the total group. We conclude there is no interaction of variables of MS or cholesterol-lipoprotein factors with those of thrombogenic factors. This independence yields the potential for use of factors in evaluating CVD risk. Further, the importance of MS in this group of postinfarction patients is emphasized, as the largest contribution to total variance was from MS factors, meaning that these variables best approximate the original multivariate distribution.
Atherosclerosis 2003 Dec
PMID:Metabolic syndrome best defines the multivariate distribution of blood variables in postinfarction patients. 1464 7

Coronary artery disease (CHD) still remains the leading cause of death in all industrialized countries. In Germany, it claims the lives of an estimated 220,000 men and women and causes 200,000 non-lethal AMI's each year. Inspite of great efforts in the last 30 years, 25% of men and 40% of women still die within 12 months after they preliminary survived their first myocardial infarction. The total direct plus indirect expenses for CHD in the year 2000 sum up to approximately 57 billion Euro in Germany and to 100 billion US $ in the US. To date, management of coronary artery disease still consists mainly of a therapy designed to improve blood flow and oxygen supply to the heart or to reduce myocardial oxygen consumption. On this line angioplasty, bypass surgery, and more recently stenting of coronary arteries, have become leading techniques, but only a minority (<50%) of patients at risk for CHD received therapy to change the atherosclerotic process itself. However, only by means of a causal intervention with the pathmaker mechanism of atherosclerosis can we expect to decrease the financial burden of CHD. No question, one of the leading causal factors for early atherosclerosis and coronary heart disease is the abundance of LDL cholesterol in the blood, exceeding limits of 100 mg/dl. Thus, recommendations for therapy focus on LDL levels less than 100 mg/dl. With the introduction of the statins-a family of very potent lipid lowering agents-such target levels can be achieved in most patients, resulting in a drastic decrease of LDL concentrations, as well as in a reduction of cardiac and total mortality. There is, however, a remaining small group of patients, who are more or less resistant to an adequate combination of dietary and drug therapy. For these patients, various techniques of apheresis have been available for over 15 years. Some of them, e. g., H.E.L.P. System, KANEKA System, have been approved by the FDA in the US and comparable regulatory offices in Europe. The most extensive experimental and clinical experience was gathered with the H.E.L.P. System by B. Braun Melsungen, which differs from other apheresis techniques by its efficiency to eliminate LDL, Lp(a), fibrinogen and CRP simultaneously. The clinical results obtained to date with the H.E.L.P.-LDL-apheresis clearly demonstrate a significant reduction of risk factors and clinical events, as well as an excellent long-term tolerance. A comprehensive literature survey on H.E.L.P. is part of this communication.
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PMID:[LDL-apheresis in the treatment of coronary heart disease. Rationale for a specific adjuvant therapy]. 1466 97

The mechanism(s) by which low circulating levels of thyroid hormones may lead to development of premature atherosclerosis remain to be established. These mechanisms include indirect effects of thyroid hormones on cardiovascular risk factors such as plasma lipoproteins, homocysteine and fibrinogen. High-sensitivity C-reactive protein (hsCRP) has been identified as an independent predictor of cardiovascular events. We presently investigated the relationship between hsCRP and free thyroxine (FT4) levels in a large population of euthyroid hyperlipidemic patients (n=429, mean age: 47.1 years, 28% of current smokers). None of these subjects presented a recent history of infection or inflammatory disease and those taking drugs known to influence thyroid or hsCRP were excluded. Serum FT4 levels were measured by radioimmunoassay and CRP, by a high-sensitivity immunoassay. In the population of non-smokers, plasma FT4 levels were negatively and significantly correlated with those of hsCRP (r=-0.13, P=0.02). Significant correlations between FT4 levels and age (r=-0.16, P=0.003), glycemia (r=-0.14, P=0.01), and fibrinogen (r=-0.18, P=0.001) were equally observed. Upon division of the population on the basis of FT4 tertiles, the mean level of hsCRP was significantly higher in non-smoker patients with the lowest FT4 tertile as compared to those displaying the highest FT4 level (3.04mg/l versus 1.77mg/l, respectively, P<0.05). No correlation between FT4 levels and CRP was found in smokers.In conclusion, we demonstrate that hsC-reactive protein is significantly negatively correlated with free thyroxine levels in non-smoker hyperlipidemic patients, suggesting that low thyroxine levels in euthyroid hyperlipidemic subjects constitute a new biomarker of elevated cardiovascular risk.
Atherosclerosis 2004 Jan
PMID:Relationship of circulating C-reactive protein levels to thyroid status and cardiovascular risk in hyperlipidemic euthyroid subjects: low free thyroxine is associated with elevated hsCRP. 1470 51

Cardiovascular disease, the most common cause of death in the Western world, results mainly from atherosclerotic remodeling of the arterial system. Atherosclerosis defines a disease in which the arterial wall becomes thickened and loses elasticity. This is clearly not a static condition. Instead, atherogenesis reflects a continuous development over time, ranging from macroscopically intact arteries to ruptured sclerotic plaques. Different stages at different sites can be present simultaneously within one individual. The pathophysiology of atherogenesis comprises various important steps, including enhanced endothelial permeability, expression of adhesion molecules, monocyte adhesion and immigration, foam cell formation, fatty streaks, smooth muscle cell migration and plaque formation, and, finally, plaque rupture and thrombus formation. In recent years, atherosclerosis is more and more being recognized as a chronic inflammatory process. The hypothesis of a chronic inflammation in atherosclerosis is supported by the following findings: atherosclerosis is associated with enhanced serum levels of inflammation parameters, including in particular C-reactive protein (CRP, Table 1); the atherosclerotic artery produces different hydrolytic enzymes, adhesion molecules, cytokines, and growth factors as seen in chronic inflammation; cells found in early atherosclerotic lesions are typically inflammatory cells (monocytes/ macrophages and T-lymphocytes); and, there is convincing clinical and experimental evidence that formation of reactive oxygen species (ROS) is augmented during this chronic inflammatory process due to an imbalance between synthesis of ROS and neutralizing antioxidative defense mechanisms. Studies in the general population could clearly show that markers of inflammation, in particular CRP, predict the cardiovascular risk. It is the aim of this review to discuss the role of inflammatory processes for the development of atherosclerosis and cardiovascular disease. Pro-inflammatory substances contributing to oxidative stress are listed in Table 2, and particular emphasis is placed on pathophysiologic effects induced by oxidized LDL and angiotensin II. Figure 1 summarizes important reaction steps of oxidative stress reactions, based on formation of superoxide anion (O(2)(-)). Finally, therapeutic options are presented, although it has to be emphasized that treatment with antibiotics proved to be essentially ineffective, and treatment options with antioxidants are not sufficiently evaluated to allow a final statement. Meanwhile, however, there is accumulating evidence that established treatment regimens with statins or renin-angiotensin system inhibitors possess profound anti-inflammatory and antioxidative properties which may support their beneficial effects on cardiovascular disease.
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PMID:[Atherosclerosis and arteriitis: implications for therapy of cardiovascular disease]. 1496 36

CVD remains the greatest health risk in the U.S.. Assessment of laboratory data in establishing risk and treatment modalities has come to the forefront in patient primary care. Guidelines published in the ATP III document by the NCEP have incorporated lower limits of lipids and included a number of risk factors and conditions, such as the metabolic syndrome associated with insulin-resistance, as a means for earlier detection and intervention in CVD. Endothelial dysfunction and the associated inflammatory process, including soluble plasma markers, have lead to the addition of hs-CRP as an adjunct to other laboratory indicators of CVD. The precise mechanisms and interrelationships between these factors and atherosclerosis have yielded some confusing data, along with investigations of a number of associated substances and conditions. An emerging theme is the body's response to injury and stress; a lack of metabolic balance. While currently outside the domain of routine laboratory testing, future CVD risk assessment may include the metabolic by-products generated by chronic external pressures, including genetic predisposition or alterations associated with socioeconomic factors. Further studies are needed to better understand the significance each plays in assessing the individual's development and CVD risk.
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PMID:Update on selected markers used in risk assessment for vascular disease. 1501 80

Although the metabolic syndrome together with insulin resistance and their consequences are probably basic factors in pathogenesis of atherosclerosis, inflammatory and infectious aspects of this process are unquestionable only in some of the patients. Endothelial dysfunction was identified both in the experiment and in patients after herpes virus simplex 1 infection, cytomegaloviral infection, Chlamydia pneumoniae infection, or Helicobacter pylori infection. However, it is not clear whether it is always caused by direct specific activity of a given pathogen or whether it is a result of inflammatory cytokines activity, heat shock protein activity, or CRP activity. In recent years secondary antibiotic prevention in patients after myocardial infarction has been discussed. Lower mortality rate from acute myocardial infarction and cerebral vascular accidents were found in several observations of patients vaccinated against influenza. In patients with non-stable angina pectoris we have found significantly more frequent occurrence of IgG antibodies against Chlamydia pneumoniae. This occurrence was more frequent in diabetics compared to non-diabetics. Endothelia exposed to cyto-megaloviral infection exprimed adhesive molecules on their surfaces. After an increase of the concentration of glucose in medium to 11.0 mmol/l and 16.5 mmol/l the expression of adhesive molecules after cyto-megaloviral infection increased. Relationship of infection, inflammation, and atherosclerosis has been a subject of intensive investigation in recent years. Discussion of possible consequences of these findings, especially from viewpoint of atherosclerosis prevention and its organ complications, is of the same intensity. Hypothesis about participation of infection and inflammation in pathogenesis of atherosclerosis seems to be very attractive. In spite of the fact that findings supporting this hypothesis cumulate final conclusion can't be made yet.
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PMID:[Infectious and inflammatory factors in the etiology and pathogenesis of atherosclerosis]. 1504 Jan 64

Atherosclerosis is a chronic pathological process and it is generelly accepted that lipids, coagulation and inflammatory factors play an important role in its development. Environmental factors such as bed diet and cigarette smoking strongly stimulate initation and progression of atherosclerotic changes in the artery wall. It has been recognized that deeply processed food may be a source of various factors potentiating processes related to atherosclerosis development among which inflammatory processes are of great importance. The aim of our studies was to find out if the trans-unsaturated fatty acids as well as acrylamide present in foods have the potential to provoke pro-inflammatory states in the body and enhance atherosclerosis risk. The results of our in vitro studies have shown that trans fatty acids cause a significant increase in secretion of reactive oxygen species, interleukin-6, tumor necrosis factor a and metalloproteinase-9, and enhance apoptosis. It indicates that in vivo trans-fatty acids may distroy the endothelium integrity and cause plaque rupture. Our in vivo studies in the group of healthy volunteers have shown that the consumption of potato chips rich in acrylamide cause the significant increase in plasma C-reactive protein and homocysteine concentrations. Enhanced CRP and HCY levels are accepted markers of enhanced atherosclerosis risk.
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PMID:Trans-unsaturated fatty acids and acrylamide in food as potential atherosclerosis progression factors. Based on own studies. 1505 16

The incidence of both venous and arterial thrombosis increases exponentially with age in both men and women. Possible reasons include: increasing immobility, trauma, surgery and acute medical illness; increasing prevalence (and/or cumulative effects) of obesity, raised blood pressure, dyslipidaemia and glucose intolerance; increasing prevalence of atherosclerosis; and increasing circulating markers of inflammation (C-reactive protein, CRP) and thrombosis. While arterial thrombosis is less common in women, the relative risk for classical risk factors associated with myocardial infarction is at least as strong in women as in men, in prospective population-based studies using MONICA criteria (e.g. Scottish Heart Health Study, Reykjavik Study). Some of these risk factors (e.g. smoking, cholesterol, triglycerides) show decreasing hazard ratios with age. Ongoing studies of newer potential risk factors for venous and arterial thrombosis (e.g. homocysteine, haemostatic and inflammatory variables) should elucidate their roles in risk prediction, including thrombotic risks of sex hormones which have effects on these variables.
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PMID:Venous and arterial thrombosis: epidemiology and risk factors at various ages. 1506 77


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