Skip Navigation

European Heart Journal 2000 21(19):1598-1606; doi:10.1053/euhj.2000.2128
Copyright © 2000 by the European Society of Cardiology.
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (27)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Garcia-Moll, X.
Right arrow Articles by Kaski, J.C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Garcia-Moll, X.
Right arrow Articles by Kaski, J.C.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

C-reactive protein in patients with chronic stable angina: differences in baseline serum concentration between women and men

X. Garcia-Moll, E. Zouridakis, D. Cole and J.C. Kaski

Coronary Artery Disease Research Unit, Cardiological Sciences, St. George's Hospital Medical School, London, U.K.

revised January 10, 2000; accepted January 14, 2000

Abstract

Aims Serum C-reactive protein has prognostic significance in apparently healthy men and women and in men with coronary artery disease. Little is known regarding the predictive role of C-reactive protein in women with coronary heart disease. We assessed whether differences exist in C-reactive protein levels and their prognostic value in men compared with women. We also assessed whether C-reactive protein concentrations differed in women receiving hormone replacement therapy vs those on no hormone replacement therapy.

Methods and Results We prospectively studied 911 consecutive patients (327 women) with typical exertional angina. All patients underwent clinical, biochemical and angiographic characterization at study entry. Serum C-reactive protein was measured using a highly sensitive assay and correlated with clinical events during follow-up (from 1·0 to 3·7 years). C-reactive protein was significantly higher in women than men (3·0mg.l–1[range 1·3-5·8] vs 2·1mg.l–1[range 1·0-4·2], P<0·001), even after multiple regression adjustment for other risk factors. C-reactive protein was also significantly higher in women receiving hormone replacement therapy than in women not using hormone replacement therapy (P=0·001). C-reactive protein was an independent predictor of cardiovascular risk (logistic regression P=0·033) in the whole group but, despite higher C-reactive protein concentration, women had a similar rate of cardiac events compared to men.

Conclusions Baseline C-reactive protein levels were higher in women than men but the event rate was similar in men and women. Women on hormone replacement therapy had significantly higher C-reactive protein than women not using hormone replacement therapy. In the group as a whole, increased C-reactive protein was associated with a higher cardiovascular risk.

Key Words: C-reactive protein in women, inflammation, stable angina

Correspondence: Professor Juan Carlos Kaski, MD, FRCP, FESC, FACC, Coronary Artery Disease Research Unit, Cardiological Sciences, St. George's Hospital Medical School, Cranmer Terrace, London SW17 0RE, U.K.

References

  1. Ross R. Atherosclerosis—an inflammatory disease. N Engl J Med. 1999;340:115–126[Free Full Text]
  2. Ernst E. Fibrinogen as a cardiovascular risk factor: interrelationship with infections and inflammation. Eur Heart J. 1993;14:82–87
  3. Danesh J, Muir J, Wong YK, Ward M, Gallimore JR, Pepys MB. Risk factors for coronary heart disease and acute-phase proteins. A population-based study. Eur Heart J. 1999;20:954–959[Abstract/Free Full Text]
  4. Berk BC, Weintraub WS, Alexander RW. Elevation of C-reactive protein in 'active' coronary artery disease. Am J Cardiol. 1990;65:168–172[CrossRef][ISI][Medline]
  5. de Beer FC, Hind CR, Fox KM, Allan RM, Maseri A, Pepys MB. Measurement of plasma C-reactive protein concentration in myocardial ischemia and infarction. Br Heart J. 1982;47:239–243[Abstract/Free Full Text]
  6. Pietila K, Harmoinen A, Hermens W, Simoons ML, Van de Werf F, Verstraete M. Serum C-reactive protein and infarct size in myocardial infarct patients with a closed versus an open infarct-related coronary artery after thrombolytic therapy. Eur Heart J. 1993;14:915–919[Abstract/Free Full Text]
  7. Liuzzo G, Biasucci LM, Gallimore JR. The prognostic value of C-reactive protein and serum amyloid A protein in severe unstable angina. N Engl J Med. 1994;331:417–424[Abstract/Free Full Text]
  8. Thompson SG, Kienast J, Pyke SDM, Haverkate F, van de Loo JCW. Hemostatic factors and the risk of myocardial infarction or sudden death in patients with angina pectoris. N Engl J Med. 1995;332:635–641[Abstract/Free Full Text]
  9. Kuller LH, Tracy RP, Shaten J, Meilahn EN. Relation of C-reactive protein and coronary heart disease in the MRFIT nested case-control study. Am J Epidemiol. 1996;144:537–547[Abstract/Free Full Text]
  10. Ridker PM, Cushman M, Stampfer MJ, Tracy RP, Hennekens CH. Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. N Engl J Med. 1997;336:973–979[Abstract/Free Full Text]
  11. Haverkate F, Thompson SG, Pyke SDM, Gallimore JR, Pepys MB. Production of C-reactive protein and risk of coronary events in stable and unstable patients. Lancet. 1997;349:462–466[CrossRef][ISI][Medline]
  12. Krobot K, Hense HW, Cremer P, Eberle E, Keil U. Determinants of plasma fibrinogen: relation to body weight, waist-to-hip ratio, smoking, alcohol, age, and sex. Results from the Second MONICA Augsburg Survey, 1989–1990. Arterioscler Thromb. 1992;12:780–788[Abstract/Free Full Text]
  13. Ridker PM, Buring JE, Shih J, Matias M, Hennekens CH. Prospective study of C-reactive protein and the risk of future cardiovascular events among apparently healthy women. Circulation. 1998;98:731–733[Abstract/Free Full Text]
  14. Tracy RP, Lemaitre RN, Psaty BM. Relationship of C-reactive protein to risk of cardiovascular disease in the elderly. Results from the Cardiovascular Health Study and the Rural Health Promotion Study. Arterioscler Thromb Vasc Biol. 1997;17:1121–1127[Abstract/Free Full Text]
  15. 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[Abstract/Free Full Text]
  16. van Baal WM, Kenemans P, van der Mooren MJ, Kessel H, Emeis JJ, Stehouwer CD. Increased C-reactive protein levels during short-term hormone replacement therapy in healthy postmenopausal women. Thromb Haemost. 1999;81:925–928[ISI][Medline]
  17. Ridker PM, Hennekens CH, Rifai N, Buring JE, Manson JAE. Hormone replacement therapy and increased plasma concentration of C-reactive protein. Circulation. 1999;100:713–716[Abstract/Free Full Text]
  18. Cushman M, Legault C, Barrett-Connor E. Effect of postmenopausal hormones on inflammation-sensitive proteins: the Postmenopausal Estrogen/Proestin Interventions (PEPI) study. Circulation. 1999;100:717–722[Abstract/Free Full Text]
  19. Sattar N, Perera M, Small M, Lumsden MA. Hormone replacement therapy and sensitive C-reactive protein concentrations in women with type-2 diabetes. Lancet. 1999;354:487–488[CrossRef][ISI][Medline]
  20. Ischaemic heart disease registers, Geneva, World Health Organization, 1971
  21. Kaski JC, Chen L, Chester MR. Rapid angiographic progression of coronary artery disease in patients with angina pectoris. The role of complex stenosis morphology. Circulation. 1995;92:2058–2065[Abstract/Free Full Text]
  22. Kannel WB, D'Agostino RB, Belanger AJ. Fibrinogen, cigarrette smoking, and risk of cardiovascular disease: Insights from the Framingham Study. Am Heart J. 1987;113:1006–1010[CrossRef][ISI][Medline]
  23. Kannel WB, Wolf PA, Castelli WP, D'Agostino RB. Fibrinogen and risk of cardiovascular disease. J Am Med Assoc. 1987;258:1183–1186[Abstract]
  24. Meade TW, Haines AP, Imeson JD, Stirling Y, Thompson SG. Menopausal status and haemostatic variables. Lancet. 1983;1:22–24[ISI][Medline]
  25. Dotevall A, Johansson S, Wilhelmsen L. Association between fibrinogen and other risk factors for cardiovascular disease in men and women. Results from the Goteborg MONICA survey 1985. Ann Epidemiol. 1994;4:369–374[Medline]
  26. Takada Y, Takada A. Serum levels of t-PA, free PAI-1 and a complex of t-PA with PAI-1 in human males and females at various ages. Thromb Res. 1989;55:601–609[CrossRef][ISI][Medline]
  27. Balleisen L, Bailey J, Epping PH, Schulte H, van de Loo J. Epidemiological study on factor VII, factor VIII and fibrinogen in an industrial population: I. Baseline data on the relation to age, gender, body-weight, smoking, alcohol, pill-using, and menopause. Thromb Haemost. 1985;54:475–479[ISI][Medline]
  28. Conlan MG, Folsom AR, Finch A. Associations of factor VII and von Willebrand factor with age, race, sex, and risk factors for atherosclerosis. The Atherosclerosis Risk in Communities (ARIC) Study. Thromb Haemost. 1993;70:380–385[ISI][Medline]
  29. Meade TW, Dyer S, Howarth DJ, Imeson JD, Stirling Y. Antithrombin III and procoagulant activity: sex differences and effects of the menopause. Br J Haematol. 1990;74:77–81[ISI][Medline]
  30. Tait RC, Walker ID, Islam SI. Protein C activity in healthy volunteers—Influence of age, sex, smoking and oral contraceptives. Thromb Haemost. 1993;70:281–285[ISI][Medline]
  31. Siegert G, Bergmann S, Jaross W. Influence of age, gender and lipoprotein metabolite parameters on the activity of plasminogen activator inhibitor and the fibrinogen concentration. Fibrinolysis. 1992;6:47–51
  32. Haverkate F, Thompson SG, Duckert F. Haemostasis factors in angina pectoris; relation to gender, age and acute-phase reaction. Results of the ECAT Angina Pectoris Study Group. Thromb Haemost. 1995;73:561–567[ISI][Medline]
  33. Barrett-Connor E. Postmenopausal estrogen and prevention bias. Ann Intern Med. 1991;115:455–456[CrossRef][ISI][Medline]
  34. Hulley S, Grady D, Bush T. Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. J Am Med Assoc. 1998;280:605–613[Abstract/Free Full Text]
  35. Hall G, Pripp U, Schenck-Gustafsson K, Landgren BM. Long-term effects of hormone replacement therapy on symptoms of angina pectoris, quality of life and compliance in women with coronary artery disease. Maturitas. 1998;12:235–242
  36. Scarabin PY, Alhenc-Gelas M, Oger E, Plu-Bureau G. Hormone replacement therapy and circulating ICAM-1 in postmenopausal women—a randomised controlled trial. Thromb Haemost. 1999;81:673–675[ISI][Medline]
  37. Lindoff C, Peterson F, Lecander I, Martinsson G, Astedt B. Transdermal estrogen replacement therapy: beneficial effects on hemostatic risk factors for cardiovascular disease. Maturitas. 1996;24:43–50[CrossRef][ISI][Medline]
  38. Koh KK, Mincemoyer R, Bui MN. Efects of hormone-replacement therapy on fibrinolysis in postmenopausal women. N Engl J Med. 1997;336:683–690[Abstract/Free Full Text]
  39. Hahn L, Mattsson LA, Andersson B, Tengborn L. The effects of oestrogen replacement therapy on haemostatic variables in postmenopausal women with non-insulin-dependent diabetes mellitus. Blood Coagul Fibrinol. 1999;10:81–86[ISI][Medline]
  40. Gauldie J, Richards C, Northemann W, Frey G, Baumann H. IFNB2/BSF2/IL6 is the monocyte-derived HSF that regulates receptor-specific acute phase gene regulation in hepatocytes. Ann NY Acad Sci. 1989;557:46–59[ISI][Medline]
  41. Stein B, Yang MX. Repression of the Interleukin-6 promoter by estrogen receptor is mediated by NF-{kappa}B and C/EBPß. Mol Cell Biol. 1995;15:4971–4979[Abstract]
  42. Srivastava S, Weitzmann MN, Cenci S, Ross FP, Adler S, Pacifi R. Estrogen decreases TNF gene expression by blocking JNK activity and the resulting production of c-Jun and JunD. J Clin Invest. 1999;104:503–513[ISI][Medline]
  43. Papadopoulos NG, Georganas K, Skoutellas V, Konstantellos E, Lyritis GP. Correlation of interleukin-6 serum levels with bone density in postmenopausal women. Clin Rheumatol. 1997;16:162–165[CrossRef][ISI][Medline]
  44. Kania DM, Binkley N, Checovich M, Havighurst T, Schilling M, Ershler WB. Elevated plasma levels of interleukin-6 in postmenopausal women do not correlate with bone density. J Am Geriatr Soc. 1995;43:236–239[ISI][Medline]
  45. Jilka RL, Passeri G, Girasole G. Estrogen loss upregulates hematopoiesis in the mouse: a mediating role of IL-6. Exp Hematol. 1995;23:500–506[ISI][Medline]
  46. Holmes D Jr, Davis KB, Mock MB. The effect of medical and surgical treatment on subsequent sudden cardiac death in patients with coronary artery disease: a report from the Coronary Artery Surgery Study. Circulation. 1986;73:1254–1263[Abstract/Free Full Text]

Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 ANGIOLOGYHome page
A. Ulucay, R. Demirbag, R. Yilmaz, D. Unlu, M. Gur, S. Selek, and H. Celik
The Relationship Between Plasma C-Reactive Protein Levels and Presence and Severity of Coronary Stenosis in Patients With Stable Angina
Angiology, January 1, 2008; 58(6): 657 - 662.
[Abstract] [PDF]

Home page
 Eur Heart JHome page
J. Cosin-Sales, J. C. Kaski, M. Christiansen, P. Kaminski, C. Oxvig, M. T. Overgaard, D. Cole, and D. W. Holt
Relationship among pregnancy associated plasma protein-A levels, clinical characteristics, and coronary artery disease extent in patients with chronic stable angina pectoris
Eur. Heart J., October 2, 2005; 26(20): 2093 - 2098.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
T. C. Register, J. A. Cann, J. R. Kaplan, J. K. Williams, M. R. Adams, T. M. Morgan, M. S. Anthony, R. M. Blair, J. D. Wagner, and T. B. Clarkson
Effects of Soy Isoflavones and Conjugated Equine Estrogens on Inflammatory Markers in Atherosclerotic, Ovariectomized Monkeys
J. Clin. Endocrinol. Metab., March 1, 2005; 90(3): 1734 - 1740.
[Abstract] [Full Text] [PDF]

Home page
 Psychosom. Med.Home page
K. M. Douglas, A. J. Taylor, and P. G. O'Malley
Relationship Between Depression and C-Reactive Protein in a Screening Population
Psychosom Med, September 1, 2004; 66(5): 679 - 683.
[Abstract] [Full Text] [PDF]

Home page
 CirculationHome page
S. D. Wiviott, C. P. Cannon, D. A. Morrow, S. A. Murphy, C. M. Gibson, C. H. McCabe, M. S. Sabatine, N. Rifai, R. P. Giugliano, P. M. DiBattiste, et al.
Differential Expression of Cardiac Biomarkers by Gender in Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction: A TACTICS-TIMI 18 (Treat Angina with Aggrastat and determine Cost of Therapy with an Invasive or Conservative Strategy-Thrombolysis In Myocardial Infarction 18) Substudy
Circulation, February 10, 2004; 109(5): 580 - 586.
[Abstract] [Full Text] [PDF]

Home page
 CirculationHome page
A. Silvestri, O. Gebara, C. Vitale, M. Wajngarten, F. Leonardo, J. A.F. Ramires, M. Fini, G. Mercuro, and G. M.C. Rosano
Increased Levels of C-Reactive Protein After Oral Hormone Replacement Therapy May Not Be Related to an Increased Inflammatory Response
Circulation, July 1, 2003; 107(25): 3165 - 3169.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
J. C. Kaski
Overview of gender aspects of cardiac syndrome X
Cardiovasc Res, February 15, 2002; 53(3): 620 - 626.
[Abstract] [Full Text] [PDF]

Home page
 Eur Heart J SupplHome page
J.C. Kaski and E.G. Zouridakis
Inflammation, infection and acute coronary plaque events
Eur. Heart J. Suppl., August 1, 2001; 3(suppl_I): I10 - I15.
[Abstract] [PDF]

Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
L. K. Heilbronn, M. Noakes, and P. M. Clifton
Energy Restriction and Weight Loss on Very-Low-Fat Diets Reduce C-Reactive Protein Concentrations in Obese, Healthy Women
Arterioscler. Thromb. Vasc. Biol., June 1, 2001; 21(6): 968 - 970.
[Abstract] [Full Text] [PDF]

Home page
 Eur Heart JHome page
J. Danesh and M.B. Pepys
C-reactive protein in healthy and in sick populations
Eur. Heart J., October 1, 2000; 21(19): 1564 - 1565.
[PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (27)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Garcia-Moll, X.
Right arrow Articles by Kaski, J.C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Garcia-Moll, X.
Right arrow Articles by Kaski, J.C.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?