Relationship Between C-Reactive Protein and Subclinical Atherosclerosis: The Dallas Heart Study

Background— Elevated levels of C-reactive protein (CRP) are associated with increased risk for incident cardiovascular events on the basis of observations from several prospective epidemiological studies. However, less is known regarding the relationship between CRP levels and atherosclerotic burden. Methods and Results— We measured CRP in 3373 subjects 30 to 65 years of age who were participating in the Dallas Heart Study, a multiethnic, population-based, probability sample. Electron-beam CT scans were used to measure coronary artery calcification (CAC) in 2726 of these subjects, and MRI was used to measure aortic plaque in 2393. CRP levels were associated with most traditional cardiovascular risk factors. Subjects with CAC had higher median CRP levels than those without CAC (men: median, 2.4 versus 1.8 mg/L, P<0.001; women: median, 5.2 versus 3.6 mg/L, P<0.001), and there was a modest trend toward increasing CRP levels with increased CAC levels in men (P for trend=0.003) but not in women (P for trend=0.08). Male subjects with aortic plaque also had higher CRP levels than those without (median, 2.3 versus 1.8; P<0.001). In multivariate analysis adjusted for traditional cardiovascular risk factors, body mass index, and estrogen and statin medication use, the associations between CRP levels and CAC and CRP levels and aortic plaque were no longer statistically significant. Conclusions— In a large, population-based sample, subjects with higher CRP levels had a modest increase in the prevalence of subclinical atherosclerosis, but this association was not independent of traditional cardiovascular risk factors. CRP is a poor predictor of atherosclerotic burden.

[1]  Natalia S. Rost,et al.  Plasma Concentration of C-Reactive Protein and Risk of Ischemic Stroke and Transient Ischemic Attack: The Framingham Study , 2001, Stroke.

[2]  A. Hofman,et al.  Associations of C-reactive protein with measures of obesity, insulin resistance, and subclinical atherosclerosis in healthy, middle-aged women. , 1999, Arteriosclerosis, thrombosis, and vascular biology.

[3]  R. Detrano,et al.  Coronary artery calcium score combined with Framingham score for risk prediction in asymptomatic individuals. , 2004, JAMA.

[4]  A. Localio,et al.  C-Reactive Protein and Coronary Artery Calcification: The Study of Inherited Risk of Coronary Atherosclerosis (SIRCA) , 2003, Arteriosclerosis, thrombosis, and vascular biology.

[5]  Ren-Ke Li,et al.  A Self-Fulfilling Prophecy: C-Reactive Protein Attenuates Nitric Oxide Production and Inhibits Angiogenesis , 2002, Circulation.

[6]  E. Boerwinkle,et al.  Relation of C-reactive protein and fibrinogen to coronary artery calcium in subjects with systemic hypertension. , 2003, The American journal of cardiology.

[7]  David M Herrington,et al.  C-Reactive Protein, Carotid Intima-Media Thickness, and Incidence of Ischemic Stroke in the Elderly: The Cardiovascular Health Study , 2003, Circulation.

[8]  P. O'Malley,et al.  C-reactive protein is not associated with the presence or extent of calcified subclinical atherosclerosis. , 2001, American heart journal.

[9]  R. Detrano,et al.  Quantification of coronary artery calcium using ultrafast computed tomography. , 1990, Journal of the American College of Cardiology.

[10]  S. Grundy,et al.  African Americans and Caucasians have a similar prevalence of coronary calcium in the Dallas Heart Study. , 2004, Journal of the American College of Cardiology.

[11]  N. Rifai,et al.  Inflammatory markers in men with angiographically documented coronary heart disease. , 1999, Clinical chemistry.

[12]  D. Rader,et al.  Electron beam computed tomographic coronary calcium scanning: a review and guidelines for use in asymptomatic persons. , 1999, Mayo Clinic proceedings.

[13]  V. Fuster,et al.  High resolution ex vivo magnetic resonance imaging of in situ coronary and aortic atherosclerotic plaque in a porcine model. , 2000, Atherosclerosis.

[14]  D. Levy,et al.  C-Reactive Protein Is Associated With Subclinical Epicardial Coronary Calcification in Men and Women: The Framingham Heart Study , 2002, Circulation.

[15]  N Rifai,et al.  Evaluation of nine automated high-sensitivity C-reactive protein methods: implications for clinical and epidemiological applications. Part 2. , 2001, Clinical chemistry.

[16]  V. Fuster,et al.  In vivo magnetic resonance evaluation of atherosclerotic plaques in the human thoracic aorta: a comparison with transesophageal echocardiography. , 2000, Circulation.

[17]  E. Ford,et al.  Serum C-reactive protein and self-reported stroke: findings from the Third National Health and Nutrition Examination Survey. , 2000, Arteriosclerosis, thrombosis, and vascular biology.

[18]  R. Virmani,et al.  A comparison of the Framingham risk index, coronary artery calcification, and culprit plaque morphology in sudden cardiac death. , 2000, Circulation.

[19]  Vilmundur Gudnason,et al.  C-reactive protein and other circulating markers of inflammation in the prediction of coronary heart disease. , 2004, The New England journal of medicine.

[20]  L. Kuller,et al.  Lifetime smoking exposure affects the association of C-reactive protein with cardiovascular disease risk factors and subclinical disease in healthy elderly subjects. , 1997, Arteriosclerosis, thrombosis, and vascular biology.

[21]  B. Horne,et al.  C-reactive protein and angiographic coronary artery disease: independent and additive predictors of risk in subjects with angina. , 2002, Journal of the American College of Cardiology.

[22]  A. Döring,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. , 1999, Circulation.

[23]  J. Sasaki,et al.  Serum glycoproteins and severity of coronary atherosclerosis. , 1995, American heart journal.

[24]  A. Khera,et al.  Association among plasma levels of monocyte chemoattractant protein-1, traditional cardiovascular risk factors, and subclinical atherosclerosis. , 2004, Journal of the American College of Cardiology.

[25]  P. Ridker,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. , 2000, Journal of the American College of Cardiology.

[26]  Robert Detrano,et al.  Combined Use of Computed Tomography Coronary Calcium Scores and C-Reactive Protein Levels in Predicting Cardiovascular Events in Nondiabetic Individuals , 2002, Circulation.

[27]  Z. Fayad,et al.  In vivo magnetic resonance evaluation of associations between aortic atherosclerosis and both risk factors and coronary artery disease in patients referred for coronary angiography. , 2004, American heart journal.

[28]  Ronald M Peshock,et al.  The Dallas Heart Study: a population-based probability sample for the multidisciplinary study of ethnic differences in cardiovascular health. , 2004, The American journal of cardiology.

[29]  V. Fuster,et al.  Coronary plaque disruption. , 1995, Circulation.

[30]  L. Kuller,et al.  Coronary Artery Calcification in Older Adults to Age 99: Prevalence and Risk Factors , 2001, Circulation.

[31]  René M. Botnar,et al.  Age and Sex Distribution of Subclinical Aortic Atherosclerosis: A Magnetic Resonance Imaging Examination of the Framingham Heart Study , 2002, Arteriosclerosis, thrombosis, and vascular biology.

[32]  Blankenhorn Dh,et al.  The accuracy of arteriography and ultrasound imaging for atherosclerosis measurement. A review. , 1982 .

[33]  Y. Arad,et al.  Prediction of coronary events with electron beam computed tomography. , 2000, Journal of the American College of Cardiology.

[34]  A. Localio,et al.  Coronary artery calcification and cardiovascular risk factors: impact of the analytic approach. , 2004, Atherosclerosis.

[35]  V. Fuster,et al.  Coronary artery calcification: pathophysiology, epidemiology, imaging methods, and clinical implications. A statement for health professionals from the American Heart Association. Writing Group. , 1996, Circulation.

[36]  J. Rumberger,et al.  Coronary artery calcium area by electron-beam computed tomography and coronary atherosclerotic plaque area. A histopathologic correlative study. , 1995, Circulation.

[37]  D. Blankenhorn,et al.  The accuracy of arteriography and ultrasound imaging for atherosclerosis measurement. A review. , 1982, Archives of pathology & laboratory medicine.

[38]  J. Veselka,et al.  Relationship of C-reactive protein to presence and severity of coronary atherosclerosis in patients with stable angina pectoris or a pathological exercise test , 2002, Coronary artery disease.

[39]  V. Fuster,et al.  Atherosclerotic aortic component quantification by noninvasive magnetic resonance imaging: an in vivo study in rabbits. , 2001, Journal of the American College of Cardiology.