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C-reactive protein and angiographic characteristics of stable and unstable coronary artery disease: Data from the prospective PREVEND cohort

      Abstract

      Aims

      High sensitive-C-reactive protein (hs-CRP) is associated with coronary risk, which may be explained by an association with (unstable) coronary artery disease (CAD). Until now, histopathological and angiographic studies have failed to consistently demonstrate a strong relationship. However, most of these studies were limited by a cross-sectional design. Our aim was to prospectively evaluate the association between hs-CRP and plaque instability. Therefore, firstly, we investigated the relation between hs-CRP measured long before coronary angiography (CAG) and angiographic characteristics of stable and unstable CAD. In addition, we investigated the association with coronary events during follow up in the total PREVEND population.

      Methods and results

      Of the population based Prevention of Renal and Vascular Endstage Disease (PREVEND) study, 8139 subjects without previous documented CAD were followed for the incidence of CAG and coronary events from 1997 to 2003. For the qualitative angiographic analysis, 216 CAGs were available. Mean time to CAG was 37 ± 19 months. The 864 coronary vessels were graded as follows: 436 coronary vessels as normal, 175 as non-obstructive CAD, 179 as stable obstructive CAD and 74 as unstable obstructive CAD. Multilevel ordinal regression analysis was performed to study associations between baseline clinical variables and angiographic findings. Hs-CRP contributed significantly to the multivariate model after adjustment for age, gender, smoking, lipids and blood pressure. In 8139 subjects, 201 (2.5%) first coronary events occurred during follow up. Cox survival analysis showed age- and sex-adjusted hazard ratios for hs-CRP 1–3 and >3 mg/L of, respectively, 1.26 (95% CI 0.67–2.40) and 3.16 (95% CI 1.26–3.16), relative to hs-CRP <1 mg/L.

      Conclusion

      In the prospective PREVEND study of subjects without previous documented CAD, hs-CRP levels at baseline were associated with angiographic characteristics and clinical consequences of plaque instability during follow up. This observation supports the concept that hs-CRP significantly contributes to coronary atherogenesis.

      Keywords

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      References

        • Danesh J.
        • Wheeler J.G.
        • Hirschfield G.M.
        • et al.
        C-reactive protein and other circulating markers of inflammation in the prediction of coronary heart disease.
        N Engl J Med. 2004; 350: 1387-1397
        • Zairis M.N.
        • Papadaki O.A.
        • Manousakis S.J.
        • et al.
        C-reactive protein and multiple complex coronary artery plaques in patients with primary unstable angina.
        Atherosclerosis. 2002; 164: 355-359
        • Lindahl B.
        • Toss H.
        • Siegbahn A.
        • Venge P.
        • Wallentin L.
        Markers of myocardial damage and inflammation in relation to long-term mortality in unstable coronary artery disease. FRISC Study Group. Fragmin during Instability in Coronary Artery Disease.
        N Engl J Med. 2000; 343: 1139-1147
        • 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
        • Katritsis D.
        • Korovesis S.
        • Giazitzoglou E.
        • et al.
        C-Reactive protein concentrations and angiographic characteristics of coronary lesions.
        Clin Chem. 2001; 47: 882-886
        • Goldstein J.A.
        • Demetriou D.
        • Grines C.L.
        • et al.
        Multiple complex coronary plaques in patients with acute myocardial infarction.
        N Engl J Med. 2000; 343: 915-922
        • Burke A.P.
        • Tracy R.P.
        • Kolodgie F.
        • et al.
        Elevated C-reactive protein values and atherosclerosis in sudden coronary death: association with different pathologies.
        Circulation. 2002; 105: 2019-2023
        • Jialal I.
        • Devaraj S.
        • Singh U.
        C-reactive protein and the vascular endothelium: implications for plaque instability.
        J Am Coll Cardiol. 2006; 47: 1379-1381
        • Taylor K.E.
        • Giddings J.C.
        • van den Berg C.W.
        C-reactive protein-induced in vitro endothelial cell activation is an artefact caused by azide and lipopolysaccharide.
        Arterioscler Thromb Vasc Biol. 2005; 25: 1225-1230
        • 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
        • Avanzas P.
        • Arroyo-Espliguero R.
        • Cosin-Sales J.
        • et al.
        Multiple complex stenoses, high neutrophil count and C-reactive protein levels in patients with chronic stable angina.
        Atherosclerosis. 2004; 175: 151-157
        • Avanzas P.
        • Arroyo-Espliguero R.
        • Cosin-Sales J.
        • et al.
        Markers of inflammation and multiple complex stenoses (pancoronary plaque vulnerability) in patients with non-ST segment elevation acute coronary syndromes.
        Heart. 2004; 90: 847-852
        • Zairis M.N.
        • Lyras A.G.
        • Bibis G.P.
        • et al.
        Association of inflammatory biomarkers and cardiac troponin I with multifocal activation of coronary artery tree in the setting of non-ST-elevation acute myocardial infarction.
        Atherosclerosis. 2005; 182: 161-167
        • Smilde T.D.
        • Asselbergs F.W.
        • Hillege H.L.
        • et al.
        Mild renal dysfunction is associated with electrocardiographic left ventricular hypertrophy.
        Am J Hypertens. 2005; 18: 342-347
        • Bertrand M.E.
        • Simoons M.L.
        • Fox K.A.
        • et al.
        Management of acute coronary syndromes in patients presenting without persistent ST-segment elevation.
        Eur Heart J. 2002; 23: 1809-1840
        • Van de Werf F.
        • Ardissino D.
        • Betriu A.
        • et al.
        Management of acute myocardial infarction in patients presenting with ST-segment elevation. The Task Force on the Management of Acute Myocardial Infarction of the European Society of Cardiology.
        Eur Heart J. 2003; 24: 28-66
        • Pearson T.A.
        • Mensah G.A.
        • Alexander R.W.
        • et al.
        Markers of inflammation and cardiovascular disease: application to clinical and public health practice—a statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association.
        Circulation. 2003; 107: 499-511
        • Koenig W.
        • Sund M.
        • Frohlich M.
        • et al.
        C-Reactive protein, a sensitive marker of inflammation, predicts future risk of coronary heart disease in initially healthy middle-aged men: results from the MONICA (Monitoring Trends and Determinants in Cardiovascular Disease) Augsburg Cohort Study, 1984 to 1992.
        Circulation. 1999; 99: 237-242
        • Ridker P.M.
        • Cushman M.
        • Stampfer M.J.
        • Tracy R.P.
        • Hennekens C.H.
        Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men.
        N Engl J Med. 1997; 336: 973-979
        • Ridker P.M.
        • Hennekens C.H.
        • Buring J.E.
        • 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
        • Ridker P.M.
        • Buring J.E.
        • Cook N.R.
        • Rifai N.
        C-reactive protein, the metabolic syndrome, and risk of incident cardiovascular events: an 8-year follow-up of 14719 initially healthy American women.
        Circulation. 2003; 107: 391-397
        • Kaski J.C.
        • Cox I.D.
        Chronic infection and atherogenesis.
        Eur Heart J. 1998; 19: 366-367
        • Fuster V.
        • Moreno P.R.
        • Fayad Z.A.
        • Corti R.
        • Badimon J.J.
        Atherothrombosis and high-risk plaque. Part I: evolving concepts.
        J Am Coll Cardiol. 2005; 46: 937-954
        • Montero I.
        • Orbe J.
        • Varo N.
        • et al.
        C-reactive protein induces matrix metalloproteinase-1 and -10 in human endothelial cells: implications for clinical and subclinical atherosclerosis.
        J Am Coll Cardiol. 2006; 47: 1369-1378
        • Zwaka T.P.
        • Hombach V.
        • Torzewski J.
        C-reactive protein-mediated low density lipoprotein uptake by macrophages: implications for atherosclerosis.
        Circulation. 2001; 103: 1194-1197
        • Zouridakis E.
        • Avanzas P.
        • Arroyo-Espliguero R.
        • Fredericks S.
        • Kaski J.C.
        Markers of inflammation and rapid coronary artery disease progression in patients with stable angina pectoris.
        Circulation. 2004; 110: 1747-1753
        • Hill A.B.
        THE environment and disease: association or causation?.
        Proc R Soc Med. 1965; 58: 295-300
        • Ray K.K.
        • Cannon C.P.
        • Cairns R.
        • et al.
        Relationship between uncontrolled risk factors and C-reactive protein levels in patients receiving standard or intensive statin therapy for acute coronary syndromes in the PROVE IT-TIMI 22 trial.
        J Am Coll Cardiol. 2005; 46: 1417-1424
        • de Lemos J.A.
        • Blazing M.A.
        • Wiviott S.D.
        • et al.
        Early intensive vs a delayed conservative simvastatin strategy in patients with acute coronary syndromes: phase Z of the A to Z trial.
        JAMA. 2004; 292: 1307-1316
        • Burke A.P.
        • Farb A.
        • Malcom G.T.
        • et al.
        Plaque rupture and sudden death related to exertion in men with coronary artery disease.
        JAMA. 1999; 281: 921-926
        • Burke A.P.
        • Farb A.
        • Malcom G.T.
        • et al.
        Coronary risk factors and plaque morphology in men with coronary disease who died suddenly.
        N Engl J Med. 1997; 336: 1276-1282
        • Rioufol G.
        • Finet G.
        • Ginon I.
        • et al.
        Multiple atherosclerotic plaque rupture in acute coronary syndrome: a three-vessel intravascular ultrasound study.
        Circulation. 2002; 106: 804-808
        • Maehara A.
        • Mintz G.S.
        • Bui A.B.
        • et al.
        Morphologic and angiographic features of coronary plaque rupture detected by intravascular ultrasound.
        J Am Coll Cardiol. 2002; 40: 904-910
        • Rittersma S.Z.
        • van der Wal A.C.
        • Koch K.T.
        • et al.
        Plaque instability frequently occurs days or weeks before occlusive coronary thrombosis: a pathological thrombectomy study in primary percutaneous coronary intervention.
        Circulation. 2005; 111: 1160-1165
        • Burke A.P.
        • Kolodgie F.D.
        • Farb A.
        • et al.
        Healed plaque ruptures and sudden coronary death: evidence that subclinical rupture has a role in plaque progression.
        Circulation. 2001; 103: 934-940
        • Casscells W.
        • Naghavi M.
        • Willerson J.T.
        Vulnerable atherosclerotic plaque: a multifocal disease.
        Circulation. 2003; 107: 2072-2075
        • Proudfit W.J.
        • Bruschke A.V.
        • MacMillan J.P.
        • Williams G.W.
        • Sones Jr., F.M.
        Fifteen year survival study of patients with obstructive coronary artery disease.
        Circulation. 1983; 68: 986-997