Thromb Haemost 2005; 94(05): 1048-1053
DOI: 10.1160/TH05-06-0384
Wound Healing and Inflammation/Infection
Schattauer GmbH

Complement C3 and C-reactive protein levels in patients with stable coronary artery disease

Ramzi Ajjan
1   Academic Unit of Molecular Vascular Medicine, Leeds Institute of Genetics Health and Therapeutics, Faculty of Medicine and Health, University of Leeds, Leeds, UK
,
Peter J. Grant
1   Academic Unit of Molecular Vascular Medicine, Leeds Institute of Genetics Health and Therapeutics, Faculty of Medicine and Health, University of Leeds, Leeds, UK
,
Timothy S. Futers
1   Academic Unit of Molecular Vascular Medicine, Leeds Institute of Genetics Health and Therapeutics, Faculty of Medicine and Health, University of Leeds, Leeds, UK
,
Jane M. Brown
1   Academic Unit of Molecular Vascular Medicine, Leeds Institute of Genetics Health and Therapeutics, Faculty of Medicine and Health, University of Leeds, Leeds, UK
,
Charlotte M. Cymbalista
1   Academic Unit of Molecular Vascular Medicine, Leeds Institute of Genetics Health and Therapeutics, Faculty of Medicine and Health, University of Leeds, Leeds, UK
,
May Boothby
1   Academic Unit of Molecular Vascular Medicine, Leeds Institute of Genetics Health and Therapeutics, Faculty of Medicine and Health, University of Leeds, Leeds, UK
,
Angela M. Carter
1   Academic Unit of Molecular Vascular Medicine, Leeds Institute of Genetics Health and Therapeutics, Faculty of Medicine and Health, University of Leeds, Leeds, UK
› Author Affiliations
Financial support:R. A. Ajjan is funded by a Clinician Scientist Award from the Department of Health, UK.
Further Information

Publication History

Received: 01 June 2005

Accepted after revision: 02 August 2005

Publication Date:
14 December 2017 (online)

Summary

The aim of this study was to determine whether complement C3 is an indicator of coronary artery disease (CAD). We measured plasma C3 and CRP levels in 278 patients undergoing coronary angiography for typical symptoms of CAD and 269 healthy age and sex matched controls. C3 levels were significantly higher in patients compared with controls (1.15 g/l and 0.92 g/l respectively; p<0.001). In the patient group, C3 levels correlated with BMI, fasting glucose, HbA1c, fibrinogen, CRP and HDL in both men and women. CRP levels were also higher in patients compared with controls (1.14 mg/l and 0.86 mg/l respectively; p=0.005) and correlated with markers of the metabolic syndrome. In a logistic regression model including C3, smoking, hypertension, cholesterol and diabetes, C3 was independently associated with CAD with an odds ratio of 3.20 for a 1 SD increase in C3 levels. In contrast, CRP was not independently associated with CAD in a similar regression analysis. In conclusion, both C3 and CRP plasma levels are elevated in patients with symptoms of CAD. However, C3 seems to be a better indicator of CAD than CRP in this study, suggesting that C3 could be an additional marker for risk stratification in atherosclerosis.

 
  • References

  • 1 Libby P, Ridker PM. Inflammation and atherosclerosis: role of C-reactive protein in risk assessment. Am J Med 2004; 116 Suppl 6A 9S-16S.
  • 2 Bhakdi S, Torzewski M, Klouche M. et al. Complement and atherogenesis: binding of CRP to degraded, nonoxidized LDL enhances complement activation. Arterioscler Thromb Vasc Biol 1999; 19: 2348-54.
  • 3 Bhakdi S, Lackner KJ, Han SR. et al. Beyond cholesterol: the enigma of atherosclerosis revisited. Thromb Haemost 2004; 91: 639-45.
  • 4 Hansson GK, Libby P, Schonbeck U. et al. Innate and adaptive immunity in the pathogenesis of atherosclerosis. Circ Res 2002; 91: 281-91.
  • 5 Vlaicu R, Niculescu F, Rus HG, Cristea A. Immunohistochemical localization of the terminal C5b-9 complement complex in human aortic fibrous plaque. Atherosclerosis 1985; 57: 163-77.
  • 6 Rus HG, Niculescu F, Constantinescu E. et al. Immunoelectron- microscopic localization of the terminal C5b-9 complement complex in human atherosclerotic fibrous plaque. Atherosclerosis 1986; 61: 35-42.
  • 7 Yasojima K, Schwab C, McGeer EG. et al. Complement components, but not complement inhibitors, are upregulated in atherosclerotic plaques. Arterioscler Thromb Vasc Biol 2001; 21: 1214-9.
  • 8 Muscari A, Bozzoli C, Puddu GM. et al. Association of serum C3 levels with the risk of myocardial infarction. Am J Med 1995; 98: 357-64.
  • 9 Muscari A, Massarelli G, Bastagli L. et al. Relationship of serum C3 to fasting insulin, risk factors and previous ischaemic events in middle-aged men. Eur Heart J 2000; 21: 1081-90.
  • 10 Muscari A, Massarelli G, Bastagli L. et al. Relationship between serum C3 levels and traditional risk factors for myocardial infarction. Acta Cardiol 1998; 53: 345-54.
  • 11 Onat A, Uzunlar B, Hergenc G. et al. Crosssectional study of complement C3 as a coronary risk factor among men and women. Clin Sci 2005; 108: 129-35.
  • 12 Danesh J, Collins R, Appleby P. et al. Association of fibrinogen, C-reactive protein, albumin, or leukocyte count with coronary heart disease: meta-analyses of prospective studies. JAMA 1998; 279: 1477-82.
  • 13 Mazer SP, Rabbani LE. Evidence for C-reactive protein’s role in (CRP) vascular disease: atherothrombosis, immuno-regulation and CRP. J Thromb Thrombolysis 2004; 17: 95-105.
  • 14 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: 2818-25.
  • 15 Reilly MP, Wolfe ML, Localio AR. et al. C-reactive protein and coronary artery calcification: The Study of Inherited Risk of Coronary Atherosclerosis (SIRCA). Arterioscler Thromb Vasc Biol 2003; 23: 1851-6.
  • 16 Redberg RF, Rifai N, Gee L. et al. Lack of association of C-reactive protein and coronary calcium by electron beam computed tomography in postmenopausal women: implications for coronary artery disease screening. J Am Coll Cardiol 2000; 36: 39-43.
  • 17 Hunt ME, O’Malley PG, Vernalis MN. et al. Creactive protein is not associated with the presence or extent of calcified subclinical atherosclerosis. Am Heart J 2001; 141: 206-10.
  • 18 Tanaka A, Shimada K, Sano T. et al. Multiple plaque rupture and C-reactive protein in acute myocardial infarction. J Am Coll Cardiol 2005; 45: 1594-9.
  • 19 Buono C, Come CE, Witztum JL. et al. Influence of C3 deficiency on atherosclerosis. Circulation 2002; 105: 3025-31.
  • 20 Choi D, Kim SK, Choi SH. et al. Preventative effects of rosiglitazone on restenosis after coronary stent implantation in patients with type 2 diabetes. Diabetes Care 2004; 27: 2654-60.
  • 21 Ebeling P, Teppo AM, Koistinen HA. et al. Troglitazone reduces hyperglycaemia and selectively acutephase serum proteins in patients with Type II diabetes. Diabetologia 1999; 42: 1433-8.
  • 22 Szeplaki G, Prohaszka Z, Duba J. et al. Association of high serum concentration of the third component of complement (C3) with pre-existing severe coronary artery disease and new vascular events in women. Atherosclerosis 2004; 177: 383-9.
  • 23 Muscari A, Bastagi L, Poggiopollini G. et al. Short term effect of atorvastatin and vitamin E on serum levels of C3, a sensitive marker of the risk of myocardial infarction in men. Cardiovasc Drugs Ther 2001; 15: 453-8.
  • 24 Mason JC, Ahmed Z, Mankoff R. et al. Statininduced expression of decay-accelerating factor protects vascular endothelium against complement-mediated injury. Circ Res 2002; 91: 696-703.
  • 25 Mantov S, Raev D. Additive effect of diabetes and systemic hypertension on the immune mechanisms of atherosclerosis. Int J Cardiol 1996; 56: 145-8.
  • 26 Alper CA, Johnson AM, Birtch AG. et al. Human C’3: evidence for the liver as the primary site of synthesis. Science 1969; 163: 286-8.
  • 27 Choy LN, Rosen BS, Spiegelman BM. Adipsin and an endogenous pathway of complement from adipose cells. J Biol Chem 1992; 267: 12736-41.