Advertisement

Effect of obesity on the relationship between plasma C-reactive protein and coronary artery stenosis in patients with stable angina

      Abstract

      Introduction

      The association between plasma C-reactive protein (CRP) and the extent of coronary artery disease (CAD) in patients with stable angina remains controversial. Obesity is strongly associated with elevated CRP levels, potentially confounding the relationship between CRP and CAD severity.

      Methods and results

      We studied 830 subjects without CAD and 218 patients with CAD undergoing elective coronary angiography. Geometric means of CRP were computed in a two-way analysis of covariance model in which study participants were stratified into nine groups according to CAD status (no CAD, single-vessel disease or multivessel disease) and tertiles of BMI. There was a significant interaction between CAD and categories of BMI with regard to CRP level (P = 0.002). In the lower tertile of BMI, patients with CAD had markedly higher CRP concentration compared to control subjects (1.16, 1.80 and 2.82 mg/L in subjects without CAD, patients with single-vessel disease and patients with multivessel disease, respectively; P = 0.003). However, the relationship between CRP and CAD became weaker for patients in the second BMI tertile (P = 0.15), whereas no significant relationship was observed for patients in the third BMI tertile (P = 0.75). In patients undergoing coronary angioplasty (n = 195), BMI was independently related to the magnitude of the angioplasty-induced CRP elevations (P = 0.002).

      Conclusion

      The level of obesity is essential to the interpretation of the relationship between CRP and severity of CAD. The production of inflammatory mediators with increasing levels of obesity becomes the dominant determinant of plasma CRP levels and masks the vascular contribution due to CAD.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Atherosclerosis
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Schieffer B.
        • Schieffer E.
        • Hilfiker-Kleiner D.
        • et al.
        Expression of angiotensin II and interleukin 6 in human coronary atherosclerotic plaques: potential implications for inflammation and plaque instability.
        Circulation. 2000; 101: 1372-1378
        • Ishikawa T.
        • Imamura T.
        • Hatakeyama K.
        • et al.
        Possible contribution of C-reactive protein within coronary plaque to increasing its own plasma levels across coronary circulation.
        Am J Cardiol. 2004; 93: 611-614
        • Schwartz R.S.
        • Bayes-Genis A.
        • Lesser J.R.
        • et al.
        Detecting vulnerable plaque using peripheral blood: inflammatory and cellular markers.
        J Interv Cardiol. 2003; 16: 231-242
        • Munford R.S.
        Statins and the acute-phase response.
        N Engl J Med. 2001; 344: 2016-2018
        • Taniguchi H.
        • Momiyama Y.
        • Ohmori R.
        • et al.
        Associations of plasma C-reactive protein levels with the presence and extent of coronary stenosis in patients with stable coronary artery disease.
        Atherosclerosis. 2005; 178: 173-177
        • Haverkate F.
        • Thompson S.G.
        • Pyke S.D.
        • Gallimore J.R.
        • Pepys M.B.
        Production of C-reactive protein and risk of coronary events in stable and unstable angina. European Concerted Action on Thrombosis and Disabilities Angina Pectoris Study Group.
        Lancet. 1997; 349: 462-466
        • Rifai N.
        • Joubran R.
        • Yu H.
        • Asmi M.
        • Jouma M.
        Inflammatory markers in men with angiographically documented coronary heart disease.
        Clin Chem. 1999; 45: 1967-1973
        • Azar R.R.
        • Aoun G.
        • Fram D.B.
        • et al.
        Relation of C-reactive protein to extent and severity of coronary narrowing in patients with stable angina pectoris or abnormal exercise tests.
        Am J Cardiol. 2000; 86: 205-207
        • Hoffmeister H.M.
        • Ehlers R.
        • Buttcher E.
        • et al.
        Comparison of C-reactive protein and terminal complement complex in patients with unstable angina pectoris versus stable angina pectoris.
        Am J Cardiol. 2002; 89: 909-912
        • Zebrack J.S.
        • Muhlestein J.B.
        • Horne B.D.
        • Anderson J.L.
        C-reactive protein and angiographic coronary artery disease: independent and additive predictors of risk in subjects with angina.
        J Am Coll Cardiol. 2002; 39: 632-637
        • Arroyo-Espliguero R.
        • Avanzas P.
        • Cosin-Sales J.
        • et al.
        C-reactive protein elevation and disease activity in patients with coronary artery disease.
        Eur Heart J. 2004; 25: 401-408
        • Festa A.
        • D’Agostino Jr., R.
        • 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
        • Aronson D.
        • Bartha P.
        • Zinder O.
        • et al.
        Obesity is the major determinant of elevated C-reactive protein in subjects with the metabolic syndrome.
        Int J Obes Relat Metab Disord. 2004; 28: 674-679
        • Greenfield J.R.
        • Samaras K.
        • Jenkins A.B.
        • et al.
        Obesity is an important determinant of baseline serum C-reactive protein concentration in monozygotic twins, independent of genetic influences.
        Circulation. 2004; 109: 3022-3028
        • Mohamed-Ali V.
        • Goodrick S.
        • Rawesh A.
        • et al.
        Subcutaneous adipose tissue releases interleukin-6, but not tumor necrosis factor-alpha, in vivo.
        J Clin Endocrinol Metab. 1997; 82: 4196-4200
        • Wellen K.E.
        • Hotamisligil G.S.
        Obesity-induced inflammatory changes in adipose tissue.
        J Clin Invest. 2003; 112: 1785-1788
        • Pepys M.B.
        • Hirschfield G.M.
        C-reactive protein: a critical update.
        J Clin Invest. 2003; 111: 1805-1812
      1. World Health Organization Expert Committee. Physical status: the use and interpretation of anthropometry. WHO Tech Rep Ser No 854. 1995; Geneva: World Health Organization.

      2. Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus.
        Diab Care. 1997; 20: 1183-1197
        • Lemieux I.
        • Pascot A.
        • Prud’homme D.
        • et al.
        Elevated C-reactive protein: another component of the atherothrombotic profile of abdominal obesity.
        Arterioscler Thromb Vasc Biol. 2001; 21: 961-967
        • Van Der Meer I.M.
        • De Maat M.P.
        • Hak A.E.
        • et al.
        C-reactive protein predicts progression of atherosclerosis measured at various sites in the arterial tree: the Rotterdam Study.
        Stroke. 2002; 33: 2750-2755
        • Azar R.R.
        • McKay R.G.
        • Kiernan F.J.
        • et al.
        Coronary angioplasty induces a systemic inflammatory response.
        Am J Cardiol. 1997; 80: 1476-1478
        • Gaspardone A.
        • Crea F.
        • Versaci F.
        • et al.
        Predictive value of C-reactive protein after successful coronary–artery stenting in patients with stable angina.
        Am J Cardiol. 1998; 82: 515-518
        • Versaci F.
        • Gaspardone A.
        • Tomai F.
        • et al.
        Predictive value of C-reactive protein in patients with unstable angina pectoris undergoing coronary artery stent implantation.
        Am J Cardiol. 2000; 85: A98
        • Lincoff A.M.
        • Kereiakes D.J.
        • Mascelli M.A.
        • et al.
        Abciximab suppresses the rise in levels of circulating inflammatory markers after percutaneous coronary revascularization.
        Circulation. 2001; 104: 163-167
        • Liuzzo G.
        • Buffon A.
        • Biasucci L.M.
        • et al.
        Enhanced inflammatory response to coronary angioplasty in patients with severe unstable angina.
        Circulation. 1998; 98: 2370-2376
        • Gottsauner-Wolf M.
        • Zasmeta G.
        • Hornykewycz S.
        • et al.
        Plasma levels of C-reactive protein after coronary stent implantation.
        Eur Heart J. 2000; 21: 1152-1158
        • Farb A.
        • Sangiorgi G.
        • Carter A.J.
        • et al.
        Pathology of acute and chronic coronary stenting in humans.
        Circulation. 1999; 99: 44-52
        • Saadeddin S.M.
        • Habbab M.A.
        • Sobki S.H.
        • Ferns G.A.
        Association of systemic inflammatory state with troponin I elevation after elective uncomplicated percutaneous coronary intervention.
        Am J Cardiol. 2002; 89: 981-983