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 65,817 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

About half of the patients presenting with myocardial infarction do not have the classic risk factors. This finding has stimulated a search for other factors that may be responsible and, when present, may help to predict which patients are at greatest risk for myocardial infarction and other cardiovascular events. With improved understanding of the pathogenesis of ischemic heart disease, new insights into potential markers of underlying atherosclerosis and cardiovascular risk have been gained. In recent years, data have accumulated demonstrating that certain markers of inflammation--both systemic and local--play a key role in the development of atherosclerosis. Specifically, elevated levels of one systemic marker of inflammation, C-reactive protein, are associated with an increased risk of cardiovascular disease events. Moreover, potentially important associations have been established between elevated markers of inflammation, such as C-reactive protein and increased efficacy of established therapies; and, in particular, lipid-lowering therapy with the hepatic hydroxymethylglutaryl coenzyme A reductase inhibitor pravastatin. This article discusses the pathogenesis of atherosclerosis, the role of endothelial dysfunction and plaque rupture, and evidence for the role of inflammation and reviews how therapy might reduce vascular inflammation.
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PMID:Inflammation and coronary heart disease: an overview. 1117 13

Inflammation plays a major role in atherothrombosis, and measurement of inflammatory markers such as high-sensitivity C-reactive protein (HSCRP) may provide a novel method for detecting individuals at high risk of plaque rupture. Several large-scale prospective studies demonstrate that HSCRP is a strong independent predictor of future myocardial infarction and stroke among apparently healthy men and women and that the addition of HSCRP to standard lipid screening may improve global risk prediction among those with high as well as low cholesterol levels. Because agents such as aspirin and statins seem to attenuate inflammatory risk, HSCRP may also have utility in targeting proven therapies for primary prevention. Inexpensive commercial assays for HSCRP are now available; they have shown variability and classification accuracy similar to that of cholesterol screening. Risk prediction algorithms using a simple quintile approach to HSCRP evaluation have been developed for outpatient use. Thus, although limitations inherent to inflammatory screening remain, available data suggest that HSCRP has the potential to play an important role as an adjunct for global risk assessment in the primary prevention of cardiovascular disease.
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PMID:High-sensitivity C-reactive protein: potential adjunct for global risk assessment in the primary prevention of cardiovascular disease. 1172 39

About half of patients presenting with myocardial infarction do not have the "classic" risk factors. This has stimulated a search for other factors that may be responsible and, when present, may help to predict which patients are at greatest risk for myocardial infarction and other cardiovascular events. With improved understanding of the pathogenesis of ischemic cardiovascular disease, we have gleaned new insights into potential markers of underlying atherosclerosis and cardiovascular risk. In recent years, data suggesting that certain markers of inflammation--both systemic and local--play a key role in the development and progression of atherosclerosis, and in its final clinical complications have accumulated. Specifically, elevated levels of one systemic marker of inflammation, C-reactive protein (CRP), are associated with an increased risk of cardiovascular disease events. Among several markers of systemic inflammation, CRP shows the strongest associations with vascular events, and the addition of CRP to total cholesterol dramatically improves risk prediction. CRP fulfils most of the requirements needed to serve as a new risk factor, but still several issues await further confirmation and clarification before this marker can ultimately be included in the routine risk profile. Moreover, potentially important associations have been established between elevated CRP levels and increased efficacy of established therapies, in particular lipid-lowering therapy with statins; CRP testing may enable us to tailor expensive cardiovascular medication to the individual patient. Such an improved prescription strategy might be especially valuable in the primary care setting where the absolute cardiovascular risk is considerably lower compared to that in secondary prevention.
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PMID:C-reactive protein: risk assessment in the primary prevention of atherosclerotic disease. Has the time come for including it in the risk profile? 1130 26

In the past year, evidence from epidemiological studies in patients with renal disease has confirmed associations between both elevated plasma total homocysteine concentrations and the inflammatory marker C-reactive protein with an increased risk of arteriosclerotic vascular disease. However, it remains to be determined whether lowering total homocysteine or reducing inflammation will prevent 'hard' clinical outcome events such as stroke, myocardial infarction, and vascular death. Randomized trials of homocysteine lowering are currently ongoing and should further clarify the nature of the observed association between elevated total homocysteine and cardiovascular risk in patients with or without renal disease, and whether it is causal and modifiable. There are currently no known therapeutic interventions that specifically lower C-reactive protein levels in individuals or the prevalence of elevated C-reactive protein in the population but randomized trials of anti-inflammatory therapy (e.g. using selective cyclo-oxygenase-2 inhibitors) aimed at preventing cardiovascular disease are currently being planned.
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PMID:Associations of homocysteine, C-reactive protein and cardiovascular disease in patients with renal disease. 1134 1

This study investigated the relationship between the circulating levels of the endothelial cell glycoproteins plasminogen activator inhibitor type 1 (PAI-1), tissue plasminogen activator (TPA), and thrombomodulin (TM) and the major vascular risk factors described in dialysis patients. In addition, the role of these endothelial cell products as independent predictors of coronary artery disease (CAD) was analyzed. Levels of TM, TPA antigen (Ag), TPA activity, PAI-1 Ag, PAI-1 activity, TPA/PAI complexes, thrombin-antithrombin complexes, fibrinopeptide A, C-reactive protein (CRP), interleukin-1beta and tumor necrosis factor-alpha, lipids, apoproteins A1 and B, and albumin were measured in a group of 200 nondiabetic dialysis patients and 100 healthy matched volunteers. When compared with healthy controls, dialysis patients showed increased levels of CRP, TM, TPA, and PAI-1 and evidence of increased thrombin-dependent fibrin formation. Increased levels of active PAI-1 were associated to a great extent with major classic vascular risk factors and to a lesser extent with CRP and serum triglycerides. Forty-six patients (23%) had evidence of CAD. Variables associated with CAD in the univariate analysis included age, time on dialysis, male gender, number of packs of cigarettes per year, high BP, fibrinogen, apolipoprotein B, albumin, PAI-1 activity, CRP, thrombin-antithrombin complexes, and fibrinopeptide A. Logistic regression analysis found age, high-density lipoprotein cholesterol, gender, high BP, CRP, time on dialysis, and PAI-1 activity to be independent predictors of CAD. This model classified correctly 85% of patients as having CAD and showed adequate goodness of fit for all risk categories. Our data support a pathogenic link among activated inflammatory response, endothelial injury, and CAD in hemodialysis patients and suggest that assessment of circulating PAI-1 levels could be an additional tool to identify dialysis patients who are at risk for developing atheromatous cardiovascular disease.
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PMID:Circulating levels of plasminogen activator inhibitor type-1, tissue plasminogen activator, and thrombomodulin in hemodialysis patients: biochemical correlations and role as independent predictors of coronary artery stenosis. 1137 50

The decline in cardiovascular mortality over the past decades is due to improved survival of patients with clinical events rather than to a declining incidence of these events. As a result, an increased prevalence of chronic coronary artery disease and especially congestive heart failure has been described. Further substantial reductions in coronary artery disease morbidity and mortality can only be anticipated if coronary artery disease is treated before the manifestation of clinical disease. Modern concepts of primary prevention incorporate an individualized approach to risk assessment. Medical history, physical examination, and established laboratory tests are the basic instruments which allow for quantitative risk assessment. Tables and simplified algorithms derived from large clinical trials enable the calculation of intermediate and long-term ("life-time") probability of cardiac events. In this setting of quantitative risk assessment, the importance of some risk factors is increasingly recognized, namely diabetes. Noninvasive diagnostic testing is used to detect preclinical atherosclerotic plaque disease. Direct imaging of coronary and peripheral arteries, the ankle-brachial index, and measurements of C-reactive protein represent novel methods which have become available for further risk stratification. Because they consider the pathophysiology of atherosclerosis and coronary artery disease, these methods may facilitate decision-making regarding preventive treatment in patients who have an intermediate risk on the basis of the traditional risk factors. The modern concept of primary prevention is aimed at identifying subjects whose risk is similarly high as that of patients with clinically established cardiovascular disease. These subjects can then be treated efficiently, and the strict distinction between primary and secondary prevention is blurred.
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PMID:[New concepts of primary prevention require rethinking]. 1139 90

The current understanding of the origin of atherosclerosis is that of an inflammatory process that involves the acute phase response -an innate biological response to a disturbance in homeostasis -infection, inflammation, tissue injury, neoplasm, or immune disturbance. The activation of the acute phase response, signaled by interleukin-6, produces proteins (fibrinogen, C-reactive protein (CRP), serum amyloid A) that lead to inflammatory reactions. The tissues themselves contain elevated levels of acute phase proteins and cytokines resulting in a localized inflammatory effect. Localized inflammatory responses in the intimal layer of the arterial wall have been shown to be responsible for many of the aspects of intimal thickening and plaque disruption, leading to acute cardiovascular events. The predictive value of plasma C-reactive protein as a risk factor for cardiovascular events has led some researchers to support the use of CRP as a main cardiovascular risk assessment tool, along with total cholesterol:HDL ratios and homocysteine levels. The ability of HMG-CoA reductase inhibitors to lower C-reactive protein levels has recently brought into question the mechanisms of action of the statin drugs. Because these medications lower incidences of acute cardiovascular events as well as decreasing morbidity and mortality well before the effects of lowered LDL cholesterol can be expected to occur, questions have been asked about whether they may work independently of LDL-lowering mechanisms. Red yeast rice contains a naturally-occurring statin (lovastatin) as well as other cholesterol-lowering compounds, some with antioxidant effects. Alpha-tocopherol also significantly lowers CRP levels in diabetics and nondiabetics, and minimizes other aspects of the acute phase response and inflammatory damage involved in atherosclerosis. This may account for alpha-tocopherol's positive effect on cardiovascular morbidity and mortality. Finally, polyphenolic compounds present in virgin olive oil also have anti-inflammatory and antioxidative effects in cardiovascular disease. The phenolic compounds in virgin olive oil may explain some of the protective effects found in epidemiological studies.
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PMID:Cardiovascular disease: C-reactive protein and the inflammatory disease paradigm: HMG-CoA reductase inhibitors, alpha-tocopherol, red yeast rice, and olive oil polyphenols. A review of the literature. 1141 71

Mortality is markedly elevated in patients with end-stage renal disease. The leading cause of death is cardiovascular disease. Lipoprotein levels are only slightly elevated in dialysis patients, and cardiovascular risk is inversely correlated with serum cholesterol, suggesting that a process other than hyperlipidemia plays a role in the incidence of cardiovascular disease. Hypoalbuminemia, ascribed to malnutrition, has been one of the most powerful risk factors that predict all-cause and cardiovascular mortality in dialysis patients. The presence of inflammation, as evidenced by increased levels of specific cytokines (interleukin-6 and tumor necrosis factor alpha) or acute-phase proteins (C-reactive protein and serum amyloid A), however, has been found to be associated with vascular disease in the general population as well as in dialysis patients. The process of inflammation, also called the acute-phase response, additionally causes loss of muscle mass and changes in plasma composition-decreases in serum albumin, prealbumin, and transferrin levels, also associated with malnutrition. Inflammation alters lipoprotein structure and function as well as endothelial structure and function to favor atherogenesis and increases the concentration of atherogenic proteins in serum, such as fibrinogen and lipoprotein (a). Inflammation in dialysis patients is episodic. The causes are likely to be multifactorial and include vascular access infection, less-than-sterile dialysate, dialysate back leak, and nonbiocompatible membranes in addition to clinically apparent infection. In addition, proinflammatory compounds, such as advanced glycation end products, accumulate in renal failure, and defense mechanisms against oxidative injury are reduced, contributing to inflammation and to its effect on the vascular endothelium.
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PMID:The microinflammatory state in uremia: causes and potential consequences. 1142 86

Patients with familial hypercholesterolemia (FH) are especially at risk for premature cardiovascular disease (CVD). Recent studies revealed C-reactive protein (CRP) as a strong predictor of future first or recurrent CVD events, suggesting that CRP plays an important role in the development of atherosclerosis. The aim of this study was to evaluate the effect of one year of simvastatin treatment on serum levels of CRP and to assess the influence of risk factors for CVD on CRP concentrations in patients with FH. We measured baseline CRP levels in 337 patients with FH. A second blood sample, collected after one year of treatment with simvastatin (20--40 mg once daily) was measured in a subgroup of 129 patients. Patients with CVD present at baseline had significantly higher serum levels of CRP (2.26 mg/l versus 1.55 mg/l, P<0.001). CRP levels were associated with smoking, body mass index, age, levels of triglycerides (TG), and the use of NSAIDs or anticoagulation drugs. Simvastatin therapy significantly improved lipid profiles in the intervention group. There was a small, but non-significant decrease of CRP levels upon treatment. CRP decreased from 1.51 mg/l median (interquartile range (IQR) 0.76--3.41) at baseline to 1.24 mg/l median (IQR 0.72--2.92) after treatment, (P=0.328). In conclusion, CRP levels were associated with the presence of CVD in FH patients. Simvastatin therapy had no significant effect on CRP levels in these patients.
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PMID:C-reactive protein in patients with familial hypercholesterolemia: no effect of simvastatin therapy. 1147 51

Estrogen replacement therapy decreases the risk of arterial disease while at the same time increases the risk for venous thrombosis. Whether a common mechanism(s) of coagulation and inflammation contributes to both responses is unclear. This study determined simultaneous effects of estrogen replacement therapy on regulators of the direct (extrinsic) pathway for activation of coagulation, coagulation, and the acute phase response. Plasma from 26 postmenopausal women without risk factors for cardiovascular disease was collected before (baseline) and after 3 months of treatment with either conjugated equine estrogen (Premarin, 0.625 mg/d) or placebo. Plasma lipids, tissue factor pathway inhibitor antigen and activity, plasminogen, prothrombin, P-selectin, alpha1-protease inhibitor, and C-reactive protein were measured. Estrogen replacement therapy significantly reduced mean concentrations of tissue factor pathway inhibitor (antigen and activity; P < 0.001), which were correlated significantly to decreases in low density lipoprotein (r2 = 0.71). Plasminogen and C-reactive protein increased significantly. Other parameters were unchanged. The results of this prospective study suggest that 3 months of estrogen replacement therapy in healthy postmenopausal women decreases low density lipoprotein with simultaneous decreases in tissue factor pathway inhibitor, a major inhibitor of the extrinsic coagulation pathway, and increases C-reactive protein, a component of the acute phase response. Concomitant changes in these parameters may reduce the risk for arterial disease while altering the threshold for thrombotic events.
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PMID:Prospective randomized study of effects of unopposed estrogen replacement therapy on markers of coagulation and inflammation in postmenopausal women. 1150 88


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