Skip to main content
Top
Published in: Current Atherosclerosis Reports 2/2010

Open Access 01-03-2010

Role of C-Reactive Protein in Contributing to Increased Cardiovascular Risk in Metabolic Syndrome

Authors: Sridevi Devaraj, Simona Valleggi, David Siegel, Ishwarlal Jialal

Published in: Current Atherosclerosis Reports | Issue 2/2010

Login to get access

Abstract

Metabolic syndrome is associated with increased propensity for diabetes and cardiovascular disease. Low-grade inflammation is characteristic of metabolic syndrome. C-reactive protein, the best characterized biomarker of inflammation, is also an independent predictor of future cardiovascular events. This review outlines the role of high-sensitivity C-reactive protein in contributing to increased cardiovascular risk in metabolic syndrome by inducing endothelial cell dysfunction and activating monocytes.
Literature
1.
go back to reference Reaven GM: The insulin resistance syndrome: definition and dietary approaches to treatment. Annu Rev Nutr 2005, 25:391–406.CrossRefPubMed Reaven GM: The insulin resistance syndrome: definition and dietary approaches to treatment. Annu Rev Nutr 2005, 25:391–406.CrossRefPubMed
3.
go back to reference Haffner S, Cassells HB: Metabolic syndrome—a new risk factor of coronary heart disease? Diabetes Obes Metab 2003, 5:359–370.CrossRefPubMed Haffner S, Cassells HB: Metabolic syndrome—a new risk factor of coronary heart disease? Diabetes Obes Metab 2003, 5:359–370.CrossRefPubMed
4.
go back to reference Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults: Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III. JAMA 2001, 285:2486–2497.CrossRef Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults: Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III. JAMA 2001, 285:2486–2497.CrossRef
5.
go back to reference Ford ES: Prevalence of the metabolic syndrome defined by the International Diabetes Federation among adults in the U.S. Diabetes Care 2005, 28:2745–2749.CrossRefPubMed Ford ES: Prevalence of the metabolic syndrome defined by the International Diabetes Federation among adults in the U.S. Diabetes Care 2005, 28:2745–2749.CrossRefPubMed
6.
go back to reference Lakka HM, Laaksonen DE, Lakka TA, et al.: The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men. JAMA 2002, 288:2709–2716.CrossRefPubMed Lakka HM, Laaksonen DE, Lakka TA, et al.: The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men. JAMA 2002, 288:2709–2716.CrossRefPubMed
7.
go back to reference Alexander CM, Landsman PB, Teutsch SM, Haffner SM: Third National Health and Nutrition Examination Survey (NHANES III); National Cholesterol Education Program (NCEP). NCEP-defined metabolic syndrome, diabetes, and prevalence of coronary heart disease among NHANES III participants age 50 years and older. Diabetes 2003, 52:1210–1214.CrossRefPubMed Alexander CM, Landsman PB, Teutsch SM, Haffner SM: Third National Health and Nutrition Examination Survey (NHANES III); National Cholesterol Education Program (NCEP). NCEP-defined metabolic syndrome, diabetes, and prevalence of coronary heart disease among NHANES III participants age 50 years and older. Diabetes 2003, 52:1210–1214.CrossRefPubMed
8.
go back to reference Devaraj S, Rosenson RS, Jialal I: Metabolic syndrome: an appraisal of the pro-inflammatory and procoagulant status. Endocrinol Metab Clin North Am 2004, 33:431–453.CrossRefPubMed Devaraj S, Rosenson RS, Jialal I: Metabolic syndrome: an appraisal of the pro-inflammatory and procoagulant status. Endocrinol Metab Clin North Am 2004, 33:431–453.CrossRefPubMed
9.
go back to reference Hanson RL, Imperatore G, Bennett PH, Knowler WC: Components of the “metabolic syndrome” and incidence of type 2 diabetes. Diabetes 2002, 51:3120–3127.CrossRefPubMed Hanson RL, Imperatore G, Bennett PH, Knowler WC: Components of the “metabolic syndrome” and incidence of type 2 diabetes. Diabetes 2002, 51:3120–3127.CrossRefPubMed
10.
go back to reference Freeman D, Norrie J, Sattar N, et al.: Pravastatin and the development of diabetes mellitus: evidence for a protective treatment effect in the West of Scotland Coronary Prevention Study. Circulation 2001, 103:357–362.PubMed Freeman D, Norrie J, Sattar N, et al.: Pravastatin and the development of diabetes mellitus: evidence for a protective treatment effect in the West of Scotland Coronary Prevention Study. Circulation 2001, 103:357–362.PubMed
11.
go back to reference Assmann G, Nofer JR, Schulte H: Cardiovascular risk assessment in metabolic syndrome: view from PROCAM. Endocrinol Metab Clin North Am 2004, 33:377–392.CrossRefPubMed Assmann G, Nofer JR, Schulte H: Cardiovascular risk assessment in metabolic syndrome: view from PROCAM. Endocrinol Metab Clin North Am 2004, 33:377–392.CrossRefPubMed
12.
go back to reference Ridker PM, Hennekens CH, Buring JE, Rifai N: C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med 2000, 342:836–843.CrossRefPubMed Ridker PM, Hennekens CH, Buring JE, Rifai N: C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med 2000, 342:836–843.CrossRefPubMed
13.
go back to reference Ridker PM, Glynn RJ, Hennekens CH: C-reactive protein adds to the predictive value of total and HDL cholesterol in determining risk of first myocardial infarction. Circulation 1998, 97:2007–2011.PubMed Ridker PM, Glynn RJ, Hennekens CH: C-reactive protein adds to the predictive value of total and HDL cholesterol in determining risk of first myocardial infarction. Circulation 1998, 97:2007–2011.PubMed
14.
go back to reference Ridker PM, Buring JE, Cook NR, Rifai N: C-reactive protein, the metabolic syndrome, and risk of incident cardiovascular events: an 8-year follow-up of 14,719 initially healthy American women. Circulation 2003,107:391–397.CrossRefPubMed Ridker PM, Buring JE, Cook NR, Rifai N: C-reactive protein, the metabolic syndrome, and risk of incident cardiovascular events: an 8-year follow-up of 14,719 initially healthy American women. Circulation 2003,107:391–397.CrossRefPubMed
15.
go back to reference Ballantyne CM, Hoogeveen RC, Bang H, et al.: Lipoprotein-associated phospholipase A2, high-sensitivity C-reactive protein, and risk for incident ischemic stroke in middle-aged men and women in the Atherosclerosis Risk in Communities (ARIC) study. Arch Intern Med 2005, 165:2479–2484.CrossRefPubMed Ballantyne CM, Hoogeveen RC, Bang H, et al.: Lipoprotein-associated phospholipase A2, high-sensitivity C-reactive protein, and risk for incident ischemic stroke in middle-aged men and women in the Atherosclerosis Risk in Communities (ARIC) study. Arch Intern Med 2005, 165:2479–2484.CrossRefPubMed
16.
go back to reference Downs JR, Clearfield M, Weis S, et al.: Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS. Air Force/Texas Coronary Atherosclerosis Prevention Study. JAMA 1998, 279:1615–1622.CrossRefPubMed Downs JR, Clearfield M, Weis S, et al.: Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS. Air Force/Texas Coronary Atherosclerosis Prevention Study. JAMA 1998, 279:1615–1622.CrossRefPubMed
17.
go back to reference Koenig W, Khuseyinova N, Baumert J, Meisinger C: Prospective study of high-sensitivity C-reactive protein as a determinant of mortality: results from the MONICA/KORA Augsburg Cohort Study, 1984–1998. Clin Chem 2008, 54:335–342.CrossRefPubMed Koenig W, Khuseyinova N, Baumert J, Meisinger C: Prospective study of high-sensitivity C-reactive protein as a determinant of mortality: results from the MONICA/KORA Augsburg Cohort Study, 1984–1998. Clin Chem 2008, 54:335–342.CrossRefPubMed
18.
go back to reference Eiriksdottir G, Aspelund T, Bjarnadottir K, et al.: Apolipoprotein E genotype and statins affect CRP levels through independent and different mechanisms: AGES-Reykjavik Study. Atherosclerosis 2006, 186:222–224.CrossRefPubMed Eiriksdottir G, Aspelund T, Bjarnadottir K, et al.: Apolipoprotein E genotype and statins affect CRP levels through independent and different mechanisms: AGES-Reykjavik Study. Atherosclerosis 2006, 186:222–224.CrossRefPubMed
19.
go back to reference Yudkin JS, Juhan-Vague I, Hawe E, et al.; The HIFMECH Study Group: Low-grade inflammation may play a role in the etiology of the metabolic syndrome in patients with coronary heart disease: the HIFMECH study. Metabolism 2004, 53:852–857.CrossRefPubMed Yudkin JS, Juhan-Vague I, Hawe E, et al.; The HIFMECH Study Group: Low-grade inflammation may play a role in the etiology of the metabolic syndrome in patients with coronary heart disease: the HIFMECH study. Metabolism 2004, 53:852–857.CrossRefPubMed
20.
go back to reference Festa A, D’Agostino R Jr, Howard G, et al.: Chronic subclinical inflammation as part of the insulin resistance syndrome: the Insulin Resistance Atherosclerosis Study (IRAS). Circulation 2000, 102:42–47.PubMed Festa A, D’Agostino R Jr, Howard G, et al.: Chronic subclinical inflammation as part of the insulin resistance syndrome: the Insulin Resistance Atherosclerosis Study (IRAS). Circulation 2000, 102:42–47.PubMed
21.
go back to reference Ford ES: The metabolic syndrome and C-reactive protein, fibrinogen, and leukocyte count: findings from the Third National Health and Nutrition Examination Survey. Atherosclerosis. 2003, 168:351–358.CrossRefPubMed Ford ES: The metabolic syndrome and C-reactive protein, fibrinogen, and leukocyte count: findings from the Third National Health and Nutrition Examination Survey. Atherosclerosis. 2003, 168:351–358.CrossRefPubMed
22.
go back to reference Sattar N, Gaw A, Scherbakova O, et al.: Metabolic syndrome with and without C-reactive protein as a predictor of coronary heart disease and diabetes in the West of Scotland Coronary Prevention Study. Circulation 2003, 108:414–419.CrossRefPubMed Sattar N, Gaw A, Scherbakova O, et al.: Metabolic syndrome with and without C-reactive protein as a predictor of coronary heart disease and diabetes in the West of Scotland Coronary Prevention Study. Circulation 2003, 108:414–419.CrossRefPubMed
23.
go back to reference Suzuki T, Katz R, Jenny NS, et al.: Metabolic syndrome, inflammation, and incident heart failure in the elderly: the Cardiovascular Health Study. Circ Heart Fail 2008, 1:242–248.CrossRefPubMed Suzuki T, Katz R, Jenny NS, et al.: Metabolic syndrome, inflammation, and incident heart failure in the elderly: the Cardiovascular Health Study. Circ Heart Fail 2008, 1:242–248.CrossRefPubMed
24.
go back to reference Malik S, Wong ND, Franklin SS, et al.: Impact of the metabolic syndrome on mortality from coronary heart disease, cardiovascular disease, and all causes in United States adults. Circulation 2004, 110:1245–1250.CrossRefPubMed Malik S, Wong ND, Franklin SS, et al.: Impact of the metabolic syndrome on mortality from coronary heart disease, cardiovascular disease, and all causes in United States adults. Circulation 2004, 110:1245–1250.CrossRefPubMed
25.
go back to reference Pischon T, Hu FB, Rexrode KM, et al.: Inflammation, the metabolic syndrome, and risk of coronary heart disease in women and men. Atherosclerosis 2008, 197:392–399.CrossRefPubMed Pischon T, Hu FB, Rexrode KM, et al.: Inflammation, the metabolic syndrome, and risk of coronary heart disease in women and men. Atherosclerosis 2008, 197:392–399.CrossRefPubMed
26.
go back to reference Takeno M, Yasuda S, Otsuka Y, et al.: Impact of metabolic syndrome on the long-term survival of patients with acute myocardial infarction: potential association with C-reactive protein. Circ J 2008, 72:415–419.CrossRefPubMed Takeno M, Yasuda S, Otsuka Y, et al.: Impact of metabolic syndrome on the long-term survival of patients with acute myocardial infarction: potential association with C-reactive protein. Circ J 2008, 72:415–419.CrossRefPubMed
27.
go back to reference Zuliani G, Volpato S, Galvani M, et al.: Elevated C-reactive protein levels and metabolic syndrome in the elderly: the role of central obesity data from the InChianti study. Atherosclerosis 2009, 203:626–632.CrossRefPubMed Zuliani G, Volpato S, Galvani M, et al.: Elevated C-reactive protein levels and metabolic syndrome in the elderly: the role of central obesity data from the InChianti study. Atherosclerosis 2009, 203:626–632.CrossRefPubMed
28.
go back to reference Ridker PM, Pare G, Parker A, et al.: Loci related to metabolic-syndrome pathways including LEPR, HNF1A, IL6R, and GCKR associate with plasma C-reactive protein: the Women’s Genome Health Study. Am J Hum Genet 2008, 82:1185–1192.CrossRefPubMed Ridker PM, Pare G, Parker A, et al.: Loci related to metabolic-syndrome pathways including LEPR, HNF1A, IL6R, and GCKR associate with plasma C-reactive protein: the Women’s Genome Health Study. Am J Hum Genet 2008, 82:1185–1192.CrossRefPubMed
29.
go back to reference Meier-Ewert HK, Ridker PM, Rifai N, et al.: Absence of diurnal variation of C-reactive protein concentrations in healthy human subjects. Clin Chem 2001, 47:426–430.PubMed Meier-Ewert HK, Ridker PM, Rifai N, et al.: Absence of diurnal variation of C-reactive protein concentrations in healthy human subjects. Clin Chem 2001, 47:426–430.PubMed
30.
go back to reference Ockene IS, Matthews CE, Rifai N, et al.: Variability and classification accuracy of serial high-sensitivity C-reactive protein measurements in healthy adults. Clin Chem 2001, 47:444–450.PubMed Ockene IS, Matthews CE, Rifai N, et al.: Variability and classification accuracy of serial high-sensitivity C-reactive protein measurements in healthy adults. Clin Chem 2001, 47:444–450.PubMed
31.
go back to reference Ridker PM, Wilson PW, Grundy SM: Should C-reactive protein be added to metabolic syndrome and to assessment of global cardiovascular risk? Circulation 2004, 109:2818–2825.CrossRefPubMed Ridker PM, Wilson PW, Grundy SM: Should C-reactive protein be added to metabolic syndrome and to assessment of global cardiovascular risk? Circulation 2004, 109:2818–2825.CrossRefPubMed
32.
go back to reference Devaraj S, Singh U, Jialal I: Human C-reactive protein and the metabolic syndrome. Curr Opin Lipidol 2009, 20:182–189.CrossRefPubMed Devaraj S, Singh U, Jialal I: Human C-reactive protein and the metabolic syndrome. Curr Opin Lipidol 2009, 20:182–189.CrossRefPubMed
33.
go back to reference Al-Qaisi M, Kharbanda RK, Mittal TK, et al.: Measurement of endothelial function and its clinical utility for cardiovascular risk. Vasc Health Risk Manag 2008, 4:647–652.PubMed Al-Qaisi M, Kharbanda RK, Mittal TK, et al.: Measurement of endothelial function and its clinical utility for cardiovascular risk. Vasc Health Risk Manag 2008, 4:647–652.PubMed
34.
go back to reference Lamon BD, Hajjar DP: Inflammation at the molecular interface of atherogenesis: an anthropological journey. Am J Pathol 2008, 173:1253–1264.CrossRefPubMed Lamon BD, Hajjar DP: Inflammation at the molecular interface of atherogenesis: an anthropological journey. Am J Pathol 2008, 173:1253–1264.CrossRefPubMed
35.
go back to reference Bakker W, Eringa EC, Sipkema P, et al.: Endothelial dysfunction and diabetes: roles of hyperglycemia, impaired insulin signaling and obesity. Cell Tissue Res 2009, 335:165–189.CrossRefPubMed Bakker W, Eringa EC, Sipkema P, et al.: Endothelial dysfunction and diabetes: roles of hyperglycemia, impaired insulin signaling and obesity. Cell Tissue Res 2009, 335:165–189.CrossRefPubMed
36.
go back to reference Corretti MC, Anderson TJ, Benjamin EJ, et al.; International Brachial Artery Reactivity Task Force: Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: a report of the International Brachial Artery Reactivity Task Force. J Am Coll Cardiol 2002, 39:257–265.CrossRefPubMed Corretti MC, Anderson TJ, Benjamin EJ, et al.; International Brachial Artery Reactivity Task Force: Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: a report of the International Brachial Artery Reactivity Task Force. J Am Coll Cardiol 2002, 39:257–265.CrossRefPubMed
37.
go back to reference Vita JA, Keaney JF Jr: Endothelial function: a barometer for cardiovascular risk? Circulation 2002,106:640–642.CrossRefPubMed Vita JA, Keaney JF Jr: Endothelial function: a barometer for cardiovascular risk? Circulation 2002,106:640–642.CrossRefPubMed
38.
go back to reference Caballero AE: Endothelial dysfunction in obesity and insulin resistance: a road to diabetes and heart disease. Obes Res 2003, 11:1278–1289.CrossRefPubMed Caballero AE: Endothelial dysfunction in obesity and insulin resistance: a road to diabetes and heart disease. Obes Res 2003, 11:1278–1289.CrossRefPubMed
39.
40.
go back to reference Hsueh WA, Quinones MJ: Role of endothelial dysfunction in insulin resistance. Am J Cardiol 2003, 92:10J–17J.CrossRefPubMed Hsueh WA, Quinones MJ: Role of endothelial dysfunction in insulin resistance. Am J Cardiol 2003, 92:10J–17J.CrossRefPubMed
41.
go back to reference Suzuki T, Hirata K, Elkind MS, et al.: Metabolic syndrome, endothelial dysfunction, and risk of cardiovascular events: the Northern Manhattan Study (NOMAs). Am Heart J 2008, 156:405–410.CrossRefPubMed Suzuki T, Hirata K, Elkind MS, et al.: Metabolic syndrome, endothelial dysfunction, and risk of cardiovascular events: the Northern Manhattan Study (NOMAs). Am Heart J 2008, 156:405–410.CrossRefPubMed
42.
go back to reference Hamburg NM, Larson MG, Vita JA, et al.: Metabolic syndrome, insulin resistance, and brachial artery vasodilator function in Framingham Offspring participants without clinical evidence of cardiovascular disease. Am J Cardiol 2008, 101:82–88.CrossRefPubMed Hamburg NM, Larson MG, Vita JA, et al.: Metabolic syndrome, insulin resistance, and brachial artery vasodilator function in Framingham Offspring participants without clinical evidence of cardiovascular disease. Am J Cardiol 2008, 101:82–88.CrossRefPubMed
43.
go back to reference Melikian N, Chowienczyk P, MacCarthy PA, et al.: Determinants of endothelial function in asymptomatic subjects with and without the metabolic syndrome. Atherosclerosis 2008, 197:375–382.CrossRefPubMed Melikian N, Chowienczyk P, MacCarthy PA, et al.: Determinants of endothelial function in asymptomatic subjects with and without the metabolic syndrome. Atherosclerosis 2008, 197:375–382.CrossRefPubMed
44.
go back to reference Rodriguez CJ, Miyake Y, Grahame-Clarke C, et al.: Relation of plasma glucose and endothelial function in a population-based multiethnic sample of subjects without diabetes mellitus. Am J Cardiol 2005, 96:1273–1277.CrossRefPubMed Rodriguez CJ, Miyake Y, Grahame-Clarke C, et al.: Relation of plasma glucose and endothelial function in a population-based multiethnic sample of subjects without diabetes mellitus. Am J Cardiol 2005, 96:1273–1277.CrossRefPubMed
45.
go back to reference Brook RD, Bard RL, Rubenfire M, et al.: Usefulness of visceral obesity (waist/hip ratio) in predicting vascular endothelial function in healthy overweight adults. Am J Cardiol 2001, 88:1264–1269.CrossRefPubMed Brook RD, Bard RL, Rubenfire M, et al.: Usefulness of visceral obesity (waist/hip ratio) in predicting vascular endothelial function in healthy overweight adults. Am J Cardiol 2001, 88:1264–1269.CrossRefPubMed
46.
go back to reference Wheatcroft SB, Shah AM, Li JM, et al.: Preserved glucoregulation but attenuation of the vascular actions of insulin in mice heterozygous for knockout of the insulin receptor. Diabetes 2004, 53:2645–2652.CrossRefPubMed Wheatcroft SB, Shah AM, Li JM, et al.: Preserved glucoregulation but attenuation of the vascular actions of insulin in mice heterozygous for knockout of the insulin receptor. Diabetes 2004, 53:2645–2652.CrossRefPubMed
47.
go back to reference Steinberg HO, Chaker H, Leaming R, et al.: Obesity/insulin resistance is associated with endothelial dysfunction. Implications for the syndrome of insulin resistance. J Clin Invest 1996, 97:2601–2610.CrossRefPubMed Steinberg HO, Chaker H, Leaming R, et al.: Obesity/insulin resistance is associated with endothelial dysfunction. Implications for the syndrome of insulin resistance. J Clin Invest 1996, 97:2601–2610.CrossRefPubMed
48.
go back to reference Teoh H, Quan A, Lovren F, et al.: Impaired endothelial function in C-reactive protein overexpressing mice. Atherosclerosis 2008, 201:318–325.CrossRefPubMed Teoh H, Quan A, Lovren F, et al.: Impaired endothelial function in C-reactive protein overexpressing mice. Atherosclerosis 2008, 201:318–325.CrossRefPubMed
49.
go back to reference Grad E, Golomb M, Mor-Yosef I, et al.: Transgenic expression of human C-reactive protein suppresses endothelial nitric oxide synthase expression and bioactivity after vascular injury. Am J Physiol Heart Circ Physiol 2007, 293:H489–H495.CrossRefPubMed Grad E, Golomb M, Mor-Yosef I, et al.: Transgenic expression of human C-reactive protein suppresses endothelial nitric oxide synthase expression and bioactivity after vascular injury. Am J Physiol Heart Circ Physiol 2007, 293:H489–H495.CrossRefPubMed
50.
go back to reference Venugopal SK, Devaraj S, Jialal I: C-reactive protein decreases prostacyclin release from human aortic endothelial cells. Circulation 2003, 108:1676–1678.CrossRefPubMed Venugopal SK, Devaraj S, Jialal I: C-reactive protein decreases prostacyclin release from human aortic endothelial cells. Circulation 2003, 108:1676–1678.CrossRefPubMed
51.
go back to reference Schwartz R, Osborne-Lawrence S, Hahner L, et al.: C-reactive protein downregulates endothelial NO synthase and attenuates reendothelialization in vivo in mice. Circ Res 2007, 100:1452–1459.CrossRefPubMed Schwartz R, Osborne-Lawrence S, Hahner L, et al.: C-reactive protein downregulates endothelial NO synthase and attenuates reendothelialization in vivo in mice. Circ Res 2007, 100:1452–1459.CrossRefPubMed
52.
go back to reference Fichtlscherer S, Breuer S, Schächinger V, et al.: C-reactive protein levels determine systemic nitric oxide bioavailability in patients with coronary artery disease. Eur Heart J 2004, 25:1412–1428.CrossRefPubMed Fichtlscherer S, Breuer S, Schächinger V, et al.: C-reactive protein levels determine systemic nitric oxide bioavailability in patients with coronary artery disease. Eur Heart J 2004, 25:1412–1428.CrossRefPubMed
53.
go back to reference Fichtlscherer S, Rosenberger G, Walter DH, et al.: Elevated C-reactive protein levels and impaired endothelial vasoreactivity in patients with coronary artery disease. Circulation 2000,102:1000–1006.PubMed Fichtlscherer S, Rosenberger G, Walter DH, et al.: Elevated C-reactive protein levels and impaired endothelial vasoreactivity in patients with coronary artery disease. Circulation 2000,102:1000–1006.PubMed
54.
go back to reference Cleland SJ, Sattar N, Petrie JR, et al.: Endothelial dysfunction as a possible link between C-reactive protein levels and cardiovascular disease. Clin Sci 2000, 98:531–535.CrossRefPubMed Cleland SJ, Sattar N, Petrie JR, et al.: Endothelial dysfunction as a possible link between C-reactive protein levels and cardiovascular disease. Clin Sci 2000, 98:531–535.CrossRefPubMed
55.
go back to reference Venugopal SK, Devaraj S, Yuhanna I, et al.: Demonstration that C-reactive protein decreases eNOS expression and bioactivity in human aortic endothelial cells. Circulation 2002, 106:1439–1441.CrossRefPubMed Venugopal SK, Devaraj S, Yuhanna I, et al.: Demonstration that C-reactive protein decreases eNOS expression and bioactivity in human aortic endothelial cells. Circulation 2002, 106:1439–1441.CrossRefPubMed
56.
go back to reference Verma S, Wang CH, Li SH, et al.: A self-fulfilling prophecy: C-reactive protein attenuates nitric oxide production and inhibits angiogenesis. Circulation 2002, 106:913–919.CrossRefPubMed Verma S, Wang CH, Li SH, et al.: A self-fulfilling prophecy: C-reactive protein attenuates nitric oxide production and inhibits angiogenesis. Circulation 2002, 106:913–919.CrossRefPubMed
57.
go back to reference • Singh U, Devaraj S, Vasquez-Vivar J, Jialal I: C-reactive protein decreases endothelial nitric oxide synthase activity via uncoupling. J Mol Cell Cardiol 2007, 43:780–791. This study describes mechanisms by which CRP increases oxidative stress, resulting in uncoupling of eNOS and reduced eNOS bioactivity, possibly explaining its role in causing ED.CrossRefPubMed • Singh U, Devaraj S, Vasquez-Vivar J, Jialal I: C-reactive protein decreases endothelial nitric oxide synthase activity via uncoupling. J Mol Cell Cardiol 2007, 43:780–791. This study describes mechanisms by which CRP increases oxidative stress, resulting in uncoupling of eNOS and reduced eNOS bioactivity, possibly explaining its role in causing ED.CrossRefPubMed
58.
go back to reference •• Guan H, Wang P, Rutai H, et al.: Adeno-associated virus-mediated human C-reactive protein gene delivery causes endothelial dysfunction and hypertension in rats. Clin Chem 2009, 55:274–284. This study is an in vivo demonstration that administration of CRP results in ED and hypertension.CrossRefPubMed •• Guan H, Wang P, Rutai H, et al.: Adeno-associated virus-mediated human C-reactive protein gene delivery causes endothelial dysfunction and hypertension in rats. Clin Chem 2009, 55:274–284. This study is an in vivo demonstration that administration of CRP results in ED and hypertension.CrossRefPubMed
59.
go back to reference Devaraj S, Xu DY, Jialal I: C-reactive protein increases plasminogen activator inhibitor-1 expression and activity in human aortic endothelial cells: implications for the metabolic syndrome and atherothrombosis. Circulation 2003,107:398–404.CrossRefPubMed Devaraj S, Xu DY, Jialal I: C-reactive protein increases plasminogen activator inhibitor-1 expression and activity in human aortic endothelial cells: implications for the metabolic syndrome and atherothrombosis. Circulation 2003,107:398–404.CrossRefPubMed
60.
go back to reference Singh U, Devaraj S, Jialal I: C-reactive protein decreases tissue plasminogen activator activity in human aortic endothelial cells: evidence that C-reactive protein is a procoagulant. Arterioscler Thromb Vasc Biol 2005, 25:2216–2221.CrossRefPubMed Singh U, Devaraj S, Jialal I: C-reactive protein decreases tissue plasminogen activator activity in human aortic endothelial cells: evidence that C-reactive protein is a procoagulant. Arterioscler Thromb Vasc Biol 2005, 25:2216–2221.CrossRefPubMed
61.
go back to reference Nakakuki T, Ito M, Iwasaki H, et al.: Rho/Rho-kinase pathway contributes to C-reactive protein-induced plasminogen activator inhibitor-1 expression in endothelial cells. Arterioscler Thromb Vasc Biol 2005, 25:2088–2093.CrossRefPubMed Nakakuki T, Ito M, Iwasaki H, et al.: Rho/Rho-kinase pathway contributes to C-reactive protein-induced plasminogen activator inhibitor-1 expression in endothelial cells. Arterioscler Thromb Vasc Biol 2005, 25:2088–2093.CrossRefPubMed
62.
go back to reference Ingelsson E, Hulthe J, Lind L: Inflammatory markers in relation to insulin resistance and the metabolic syndrome. Eur J Clin Invest 2008, 38:502–509.CrossRefPubMed Ingelsson E, Hulthe J, Lind L: Inflammatory markers in relation to insulin resistance and the metabolic syndrome. Eur J Clin Invest 2008, 38:502–509.CrossRefPubMed
63.
go back to reference Conen D, Rexrode KM, Creager MA, et al.: Metabolic syndrome, inflammation and risk of symptomatic PAD in women. Circulation 2009, 120:1041–1047.CrossRefPubMed Conen D, Rexrode KM, Creager MA, et al.: Metabolic syndrome, inflammation and risk of symptomatic PAD in women. Circulation 2009, 120:1041–1047.CrossRefPubMed
64.
go back to reference Kressel G, Trunz B, Bub A, et al.: Systematic and vascular markers of inflammation in relation to metabolic syndrome and insulin resistance in adults with elevated atherosclerosis risk. Atherosclerosis 2009, 202:263–271.CrossRefPubMed Kressel G, Trunz B, Bub A, et al.: Systematic and vascular markers of inflammation in relation to metabolic syndrome and insulin resistance in adults with elevated atherosclerosis risk. Atherosclerosis 2009, 202:263–271.CrossRefPubMed
65.
go back to reference Rosso LG, Benitez MB, Fornari MC, et al.: Alterations in cell adhesion molecules and other biomarkers of cardiovascular disease in patients with MetS. Atherosclerosis 2008, 199:415–423.CrossRef Rosso LG, Benitez MB, Fornari MC, et al.: Alterations in cell adhesion molecules and other biomarkers of cardiovascular disease in patients with MetS. Atherosclerosis 2008, 199:415–423.CrossRef
66.
go back to reference Devaraj S, Davis B, Simon SI, Jialal I: CRP promotes monocyte-endothelial cell adhesion via Fcgamma receptors in human aortic endothelial cells under static and shear flow conditions. Am J Physiol Heart Circ Physiol 2006, 291:H1170–H1176.CrossRefPubMed Devaraj S, Davis B, Simon SI, Jialal I: CRP promotes monocyte-endothelial cell adhesion via Fcgamma receptors in human aortic endothelial cells under static and shear flow conditions. Am J Physiol Heart Circ Physiol 2006, 291:H1170–H1176.CrossRefPubMed
67.
go back to reference Cermak J, Key NS, Bach RR, et al.: C-reactive protein induces human peripheral blood monocytes to synthesize tissue factor. Blood 1993, 82:513–520.PubMed Cermak J, Key NS, Bach RR, et al.: C-reactive protein induces human peripheral blood monocytes to synthesize tissue factor. Blood 1993, 82:513–520.PubMed
68.
go back to reference Devaraj S, Dasu MR, Singh U, et al.: C-reactive protein stimulates superoxide anion release and tissue factor activity in vivo. Atherosclerosis 2009, 203:67–74.CrossRefPubMed Devaraj S, Dasu MR, Singh U, et al.: C-reactive protein stimulates superoxide anion release and tissue factor activity in vivo. Atherosclerosis 2009, 203:67–74.CrossRefPubMed
69.
go back to reference Han KH, Hong KH, Park JH, et al.: C-reactive protein promotes monocyte chemoattractant protein-1 mediated chemotaxis through upregulating CC chemokine receptor 2 expression in human monocytes. Circulation 2004, 109:2566–2571.CrossRefPubMed Han KH, Hong KH, Park JH, et al.: C-reactive protein promotes monocyte chemoattractant protein-1 mediated chemotaxis through upregulating CC chemokine receptor 2 expression in human monocytes. Circulation 2004, 109:2566–2571.CrossRefPubMed
70.
go back to reference Williams TN, Zhang CX, Game BA, et al.: C-reactive protein stimulates MMP-1 expression in U937 histiocytes through Fc[gamma]RII and extracellular signal-regulated kinase pathway: an implication of CRP involvement in plaque destabilization. Arterioscler Thromb Vasc Biol 2004, 24:61–66.CrossRefPubMed Williams TN, Zhang CX, Game BA, et al.: C-reactive protein stimulates MMP-1 expression in U937 histiocytes through Fc[gamma]RII and extracellular signal-regulated kinase pathway: an implication of CRP involvement in plaque destabilization. Arterioscler Thromb Vasc Biol 2004, 24:61–66.CrossRefPubMed
71.
go back to reference Woollard KJ, Fisch C, Newby R, et al.: C-reactive protein mediates CD11b expression in monocytes through the non-receptor tyrosine kinase, Syk, and calcium mobilization but not through cytosolic peroxides. Inflamm Res 2005, 54:485–492.CrossRefPubMed Woollard KJ, Fisch C, Newby R, et al.: C-reactive protein mediates CD11b expression in monocytes through the non-receptor tyrosine kinase, Syk, and calcium mobilization but not through cytosolic peroxides. Inflamm Res 2005, 54:485–492.CrossRefPubMed
72.
go back to reference Chang MK, Binder CJ, Torzewski M, et al.: C-reactive protein binds to both oxidized LDL and apoptotic cells through recognition of a common ligand: phosphorylcholine of oxidized phospholipids. Proc Natl Acad Sci U S A 2002, 99:13043–13048.CrossRefPubMed Chang MK, Binder CJ, Torzewski M, et al.: C-reactive protein binds to both oxidized LDL and apoptotic cells through recognition of a common ligand: phosphorylcholine of oxidized phospholipids. Proc Natl Acad Sci U S A 2002, 99:13043–13048.CrossRefPubMed
73.
go back to reference Wang X, Liao D, Bharadwaj U, et al.: C-reactive protein inhibits cholesterol efflux from human macrophage-derived foam cells. Arterioscler Thromb Vasc Biol 2008, 28:519–526.CrossRefPubMed Wang X, Liao D, Bharadwaj U, et al.: C-reactive protein inhibits cholesterol efflux from human macrophage-derived foam cells. Arterioscler Thromb Vasc Biol 2008, 28:519–526.CrossRefPubMed
74.
go back to reference • Singh U, Dasu MR, Yancey PG, et al.: Human C-reactive protein promotes oxidized low density lipoprotein uptake and matrix metalloproteinase-9 release in Wistar rats. J Lipid Res 2008, 49:1015–1023. In this study, the authors demonstrate in vivo that CRP induces oxidative stress and promotes cholesterol ester accumulation and foam cell formation.CrossRefPubMed • Singh U, Dasu MR, Yancey PG, et al.: Human C-reactive protein promotes oxidized low density lipoprotein uptake and matrix metalloproteinase-9 release in Wistar rats. J Lipid Res 2008, 49:1015–1023. In this study, the authors demonstrate in vivo that CRP induces oxidative stress and promotes cholesterol ester accumulation and foam cell formation.CrossRefPubMed
75.
go back to reference Singh U, Devaraj S, Jialal I: C-Reactive protein stimulates myeloperoxidase release from polymorphonuclear cells and monocytes. Clin Chem 2009, 55:361–364.CrossRefPubMed Singh U, Devaraj S, Jialal I: C-Reactive protein stimulates myeloperoxidase release from polymorphonuclear cells and monocytes. Clin Chem 2009, 55:361–364.CrossRefPubMed
76.
go back to reference Han KH, Hong KH, Park JH, et al.: C-reactive protein promotes monocyte chemoattractant protein-1—mediated chemotaxis through upregulating CC chemokine receptor 2 expression in human monocytes. Circulation 2004,109:2566–2571.CrossRefPubMed Han KH, Hong KH, Park JH, et al.: C-reactive protein promotes monocyte chemoattractant protein-1—mediated chemotaxis through upregulating CC chemokine receptor 2 expression in human monocytes. Circulation 2004,109:2566–2571.CrossRefPubMed
77.
go back to reference Esposito K, Pontillo A, Giugliano F, et al.: Association of low interleukin-10 levels with the metabolic syndrome in obese women. J Clin Endocrinol Metab 2003, 88:1055–1058.CrossRefPubMed Esposito K, Pontillo A, Giugliano F, et al.: Association of low interleukin-10 levels with the metabolic syndrome in obese women. J Clin Endocrinol Metab 2003, 88:1055–1058.CrossRefPubMed
78.
go back to reference Singh U, Devaraj S, Dasu MR, et al.: C-reactive protein decreases interleukin-10 secretion in activated human monocyte-derived macrophages via inhibition of cyclic AMP production. Arterioscler Thromb Vasc Biol 2006, 26:2469–2475.CrossRefPubMed Singh U, Devaraj S, Dasu MR, et al.: C-reactive protein decreases interleukin-10 secretion in activated human monocyte-derived macrophages via inhibition of cyclic AMP production. Arterioscler Thromb Vasc Biol 2006, 26:2469–2475.CrossRefPubMed
79.
go back to reference Bisoendial RJ, Birjmohun RS, Akdim F, et al.: C-reactive protein elicits white blood cell activation in humans. Am J Med 2009, 122:582.e1–9.CrossRef Bisoendial RJ, Birjmohun RS, Akdim F, et al.: C-reactive protein elicits white blood cell activation in humans. Am J Med 2009, 122:582.e1–9.CrossRef
80.
go back to reference Fortuño A, San José G, Moreno MU, et al.: Phagocytic NADPH oxidase overactivity underlies oxidative stress in metabolic syndrome. Diabetes 2006, 55:209–215.CrossRefPubMed Fortuño A, San José G, Moreno MU, et al.: Phagocytic NADPH oxidase overactivity underlies oxidative stress in metabolic syndrome. Diabetes 2006, 55:209–215.CrossRefPubMed
81.
go back to reference Keaney JF Jr, Larson MG, Vasan RS, et al.: Obesity and systemic oxidative stress: clinical correlates of oxidative stress in the Framingham Study. Arterioscler Thromb Vasc Biol 2003, 23:434–439.CrossRefPubMed Keaney JF Jr, Larson MG, Vasan RS, et al.: Obesity and systemic oxidative stress: clinical correlates of oxidative stress in the Framingham Study. Arterioscler Thromb Vasc Biol 2003, 23:434–439.CrossRefPubMed
82.
go back to reference Kobayashi S, Inoue N, Ohashi Y, et al.: Interaction of oxidative stress and inflammatory response in coronary plaque instability: important role of CRP. Arterioscler Thromb Vasc Biol 2003, 23:1398–1404.CrossRefPubMed Kobayashi S, Inoue N, Ohashi Y, et al.: Interaction of oxidative stress and inflammatory response in coronary plaque instability: important role of CRP. Arterioscler Thromb Vasc Biol 2003, 23:1398–1404.CrossRefPubMed
83.
go back to reference Ehara S, Ueda M, Naruko T: Elevated levels of oxidized low-density lipoprotein show a positive relationship with the severity of acute coronary syndromes. Circulation 2001, 103:1955–1960.PubMed Ehara S, Ueda M, Naruko T: Elevated levels of oxidized low-density lipoprotein show a positive relationship with the severity of acute coronary syndromes. Circulation 2001, 103:1955–1960.PubMed
84.
go back to reference Holvoet P, Kritchevsky SB, Tracy RP, et al.: The metabolic syndrome, circulating oxidized LDL, and risk of myocardial infarction in well-functioning elderly people in the health, aging, and body composition cohort. Diabetes 2004, 53:1068–1073.CrossRefPubMed Holvoet P, Kritchevsky SB, Tracy RP, et al.: The metabolic syndrome, circulating oxidized LDL, and risk of myocardial infarction in well-functioning elderly people in the health, aging, and body composition cohort. Diabetes 2004, 53:1068–1073.CrossRefPubMed
85.
go back to reference Diamant M, Nieuwland R, Pablo RF, et al.: Elevated numbers of tissue-factor exposing microparticles correlate with components of the metabolic syndrome in uncomplicated type 2 diabetes mellitus. Circulation 2002, 106:2442–2447.CrossRefPubMed Diamant M, Nieuwland R, Pablo RF, et al.: Elevated numbers of tissue-factor exposing microparticles correlate with components of the metabolic syndrome in uncomplicated type 2 diabetes mellitus. Circulation 2002, 106:2442–2447.CrossRefPubMed
86.
go back to reference Goncalves FM, Jacob-Ferreira AL, Gomes VA, et al.: Increased circulating levels of MMP-8, MMP-9 and pro-inflammatory markers in patients with metabolic syndrome. Clin Chim Acta 2009, 403:173–177.CrossRefPubMed Goncalves FM, Jacob-Ferreira AL, Gomes VA, et al.: Increased circulating levels of MMP-8, MMP-9 and pro-inflammatory markers in patients with metabolic syndrome. Clin Chim Acta 2009, 403:173–177.CrossRefPubMed
87.
go back to reference Barnes PJ, Karin M: Nuclear factor-kappaB: a pivotal transcription factor in chronic inflammatory diseases. N Engl J Med 1997, 336:1066–1071.CrossRefPubMed Barnes PJ, Karin M: Nuclear factor-kappaB: a pivotal transcription factor in chronic inflammatory diseases. N Engl J Med 1997, 336:1066–1071.CrossRefPubMed
88.
go back to reference Ghanim H, Aljada A, Hofmeyer D, et al.: Circulating mononuclear cells in the obese are in a proinflammatory state. Circulation 2004, 110:1564–1571.CrossRefPubMed Ghanim H, Aljada A, Hofmeyer D, et al.: Circulating mononuclear cells in the obese are in a proinflammatory state. Circulation 2004, 110:1564–1571.CrossRefPubMed
89.
go back to reference Devaraj S, Chan E, Jialal I: Direct demonstration of an anti-inflammatory effect of simvastatin in subjects with the metabolic syndrome. J Clin Endocrinol Metab 2006, 91:4489–4496.CrossRefPubMed Devaraj S, Chan E, Jialal I: Direct demonstration of an anti-inflammatory effect of simvastatin in subjects with the metabolic syndrome. J Clin Endocrinol Metab 2006, 91:4489–4496.CrossRefPubMed
90.
go back to reference •• Ridker PM, Danielson E, Fonseca F, et al.: Rosuvastatin to prevent vascular events in men and women with elevated c-reactive protein. N Engl J Med 2008, 359:2195–2207. This primary prevention trial with rosuvastatin showed a significant 37% reduction in cardiovascular events. Although rosuvastatin reduced LDL cholesterol by 50%, the reduction in cardiovascular events in JUPITER was almost twice that predicted based on LDL cholesterol reduction, and CRP levels were significantly reduced by 37%. Most importantly, in those with no risk factors except a high CRP, there was an equivalent benefit, supporting the hypothesis that CRP may mediate atherothrombosis.CrossRefPubMed •• Ridker PM, Danielson E, Fonseca F, et al.: Rosuvastatin to prevent vascular events in men and women with elevated c-reactive protein. N Engl J Med 2008, 359:2195–2207. This primary prevention trial with rosuvastatin showed a significant 37% reduction in cardiovascular events. Although rosuvastatin reduced LDL cholesterol by 50%, the reduction in cardiovascular events in JUPITER was almost twice that predicted based on LDL cholesterol reduction, and CRP levels were significantly reduced by 37%. Most importantly, in those with no risk factors except a high CRP, there was an equivalent benefit, supporting the hypothesis that CRP may mediate atherothrombosis.CrossRefPubMed
91.
go back to reference Jialal I, Devaraj S: Statin therapy for the metabolic syndrome. The evidence base. Met Syndr Relat Disord 2009, 7:393–395.CrossRef Jialal I, Devaraj S: Statin therapy for the metabolic syndrome. The evidence base. Met Syndr Relat Disord 2009, 7:393–395.CrossRef
Metadata
Title
Role of C-Reactive Protein in Contributing to Increased Cardiovascular Risk in Metabolic Syndrome
Authors
Sridevi Devaraj
Simona Valleggi
David Siegel
Ishwarlal Jialal
Publication date
01-03-2010
Publisher
Current Science Inc.
Published in
Current Atherosclerosis Reports / Issue 2/2010
Print ISSN: 1523-3804
Electronic ISSN: 1534-6242
DOI
https://doi.org/10.1007/s11883-010-0098-3

Other articles of this Issue 2/2010

Current Atherosclerosis Reports 2/2010 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine