C-reactive protein as a risk factor versus risk marker

Maat, Moniek P.M. de; Trion, Astrid

doi:10.1097/00041433-200412000-00005

Cited by 51 publications

(36 citation statements)

References 64 publications

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“…CRP treatment often elicits proinflammatory and proatherosclerotic effects. 4 For instance, CRP activates endothelial cells to produce adhesion molecules, induces monocyte chemoattractant chemokine-1 (MCP-1) production facilitating leukocyte adhesion and diapedesis, contributes to the migration of smooth muscle cells, enhances uptake of native low-density lipoprotein by macrophages, and activates complement. [5][6][7][8][9][10][11] Furthermore, local CRP production by cells in the atherosclerotic lesion has been reported.…”

Section: See Page 1527mentioning

confidence: 99%

No Effect of C-Reactive Protein on Early Atherosclerosis Development in Apolipoprotein E*3-Leiden/Human C-Reactive Protein Transgenic Mice

Trion

Maat

Jukema

et al. 2005

ATVB

104

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Objective-C-reactive protein (CRP) has been associated with risk of cardiovascular disease. It is not clear whether CRP is causally involved in the development of atherosclerosis. Mouse CRP is not expressed at high levels under normal conditions and increases in concentration only several-fold during an acute phase response. Because the dynamic range of human CRP is much larger, apolipoprotein E*3-Leiden (E3L) transgenic mice carrying the human CRP gene offer a unique model to study the role(s) of CRP in atherosclerosis development. Methods and Results-Atherosclerosis development was studied in 15 male and 15 female E3L/CRP mice; E3L transgenic littermates were used as controls. The mice were fed a hypercholesterolemic diet to induce atherosclerosis development. Cholesterol exposure did not differ between E3L/CRP and E3L mice. Plasma CRP levels were on average 10.2Ϯ6.5 mg/L in male E3L/CRP mice, 0.2Ϯ0.1 mg/L in female E3L/CRP mice, and undetectable in E3L mice. Quantification of atherosclerosis showed that lesion area in E3L/CRP mice was not different from that in E3L mice. Key Words: atherosclerosis Ⅲ C-reactive protein Ⅲ inflammation Ⅲ mouse Ⅲ transgene C ardiovascular disease attributable to atherosclerosis is a major cause of mortality and morbidity in Western society. In recent years, inflammation has emerged as a key factor in atherosclerosis development. 1 The acute phase protein C-reactive protein (CRP) has been shown to predict the risk of cardiovascular events. 2 Because the plasma concentration of CRP reflects the inflammatory condition, it has been hypothesized that CRP levels reflect the inflammatory condition of the vascular wall. However, whether CRP itself contributes to atherosclerosis development is still unknown. Conclusion-This See page 1527CRP is a member of the highly conserved pentraxin family and is produced mainly by hepatocytes in response to infection or inflammation. Its production is stimulated by cytokines such as interleukin-6 (IL-6), IL-1, and tumor necrosis factor-␣ (TNF-␣). CRP binds to phosphatidylcholine in cell membranes and plasma lipoproteins in a Ca 2ϩ -dependent manner and has a role in opsonization of infectious agents and damaged cells. 3 In vitro studies have reported numerous effects of CRP on endothelial cells, smooth muscle cells, and monocytes. CRP treatment often elicits proinflammatory and proatherosclerotic effects. 4 For instance, CRP activates endothelial cells to produce adhesion molecules, induces monocyte chemoattractant chemokine-1 (MCP-1) production facilitating leukocyte adhesion and diapedesis, contributes to the migration of smooth muscle cells, enhances uptake of native low-density lipoprotein by macrophages, and activates complement. 5-11 Furthermore, local CRP production by cells in the atherosclerotic lesion has been reported. 12 Apolipoprotein E*3-Leiden (E3L) mice exhibit elevated plasma cholesterol and triglyceride levels, 13 resembling familial dysbetalipoproteinemia in humans. Plasma cholesterol levels in these mice can easily be titrated by d...

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Section: See Page 1527mentioning

confidence: 99%

No Effect of C-Reactive Protein on Early Atherosclerosis Development in Apolipoprotein E*3-Leiden/Human C-Reactive Protein Transgenic Mice

Trion

Maat

Jukema

et al. 2005

ATVB

104

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“…Multiple epidemiological studies have associated C-reactive protein (CRP), an acute-phase reactant and marker of inflammation, with CVD risk [16]. CRP is synthesised predominately by hepatocytes in the liver in response to interleukin-6 (IL-6), an inflammatory cytokine, which is secreted during acute injury [17].…”

Section: Introductionmentioning

confidence: 99%

Effect of supplementation with B vitamins and antioxidants on levels of asymmetric dimethylarginine (ADMA) and C-reactive protein (CRP): a double-blind, randomised, factorial design, placebo-controlled trial

et al. 2010

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Woodside, J. (2010). Effect of supplementation with B vitamins and antioxidants on levels of asymmetric dimethylarginine (ADMA) and Creactive protein (CRP): a double-blind, randomised, factorial design, placebo-controlled trial. European Journal of Nutrition, 49(8) AbstractPurpose Cardiovascular risk factors such as elevated levels of asymmetric dimethylarginine (ADMA)/C-reactive protein (CRP) and homocysteine are potentially related to essential micronutrients such as certain B vitamins and antioxidant vitamins. The aim of the present study was to investigate whether supplementation with moderate doses of B vitamins and/or antioxidants could alter either ADMA and/or CRP concentrations in middle-aged, apparently healthy men with mildly elevated homocysteine levels. Methods A randomised, double-blind, factorial design, intervention study was carried out on 132 men with mildly elevated homocysteine levels, allocated to four groups (a) B vitamins alone-1 mg folic acid, 7.2 mg pyridoxine, 0.02 mg cyanocobalamin daily, (b) antioxidants alone-150 mg ascorbic acid, 67 mg vitamin E, 9 mg b-carotene daily, (c) B vitamins with antioxidant vitamins, or (d) placebo. A total of 101 men completed the study to 8 weeks.Results When the percentage of baseline ADMA and CRP was examined at 8 weeks, no statistically significant differences were observed between the four groups (p = 0.21 and p = 0.90, respectively). Similar non-significant results were observed when analysis was stratified based on baseline CRP levels (\1.0 mg/L, p = 0.10; C1.0 mg/L, p = 0.64) and smoking status (all p C 0.05). Conclusions Supplementation with moderate doses of B vitamins and/or antioxidants did not alter either ADMA or CRP concentrations in these middle-aged, apparently healthy men with mildly elevated homocysteine levels.

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“…However, there are also indications that CRP is directly involved in the occurrence of cardiovascular events. 29 Recent studies show that lower CRP levels on statin therapy go indeed hand in hand with a reduced risk of recurrent myocardial infarction and coronary artery disease, supporting a causal role of inflammation in cardiovascular disease. 30,31 Although our results confirm a possible causal relationship between CRP and stroke, the receiver operating characteristic curve analyses imply that CRP measurement does not contribute to individual stroke risk estimation, similar to what has been found for coronary disease.…”

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confidence: 98%

High Serum C-Reactive Protein Level Is Not an Independent Predictor for Stroke

et al. 2006

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Background-Current guidelines recommend the assessment of C-reactive protein (CRP) levels with a high-sensitivity assay in cardiovascular risk prediction. Recent studies have put forward that although elevated CRP is a risk factor for cardiovascular disease, it is not helpful in the prediction of cardiovascular disease risk. We studied the importance of CRP as a risk factor and as a risk predictor of future stroke. Methods and Results-The present study was based on 6430 participants of the Rotterdam Study who at baseline (1990 -1993) were Ն55 years of age, were stroke free, and had blood taken. Strokes were classified as hemorrhagic, ischemic, or unspecified. Ischemic strokes were further subclassified. Whether stroke risk varied with baseline CRP serum levels was assessed with Cox proportional hazards models. Whether CRP was helpful in the prediction of individual stroke risk was assessed with receiver operating characteristic curves and by comparing the distribution of strokes between predicted risk strata. During an average of 8.2 years of follow-up, 498 first-ever strokes occurred. High CRP levels were significantly associated with risk of any stroke (age-and sex-adjusted hazard ratio per SD, 1.14; 95% confidence interval, 1.04 to 1.24) and risk of ischemic stroke (age-and sex-adjusted hazard ratio per SD, 1.17; 95% confidence interval, 1.04 to 1.32). Taking CRP levels into account did not improve the individual stroke risk prediction, however, regardless of whether it was based on the Framingham stroke risk score or on age and sex only. Conclusions-Although

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C-reactive protein as a risk factor versus risk marker

Abstract: We review here the most recent evidence on mechanisms by which CRP is involved as a causal factor in the precipitation of cardiovascular disease. Evidence for such a role is accumulating.

Cited by 51 publications

References 64 publications

No Effect of C-Reactive Protein on Early Atherosclerosis Development in Apolipoprotein E*3-Leiden/Human C-Reactive Protein Transgenic Mice

No Effect of C-Reactive Protein on Early Atherosclerosis Development in Apolipoprotein E*3-Leiden/Human C-Reactive Protein Transgenic Mice

Effect of supplementation with B vitamins and antioxidants on levels of asymmetric dimethylarginine (ADMA) and C-reactive protein (CRP): a double-blind, randomised, factorial design, placebo-controlled trial

High Serum C-Reactive Protein Level Is Not an Independent Predictor for Stroke

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