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The Atherosclerosis Risk in Communities Study

Aaron R. Folsom, MD, MPH; Lloyd E. Chambless, PhD; Christie M. Ballantyne, MD; Josef Coresh, MD, PhD; Gerardo Heiss, MD; Kenneth K. Wu, MD, PhD; Eric Boerwinkle, PhD; Thomas H. Mosley, Jr, PhD; Paul Sorlie, PhD; Guoqing Diao, PhD; A. Richey Sharrett, MD, DrPH

Arch Intern Med. 2006;166:1368-1373.

Background  There has been interest in recent years in whether additional, and in particular novel, risk factors or blood markers, such as C-reactive protein, can enhance existing coronary heart disease (CHD) prediction models.

Methods  Using a series of case-cohort studies, the prospective Atherosclerosis Risk in Communities (ARIC) Study assessed the association of 19 novel risk markers with incident CHD in 15 792 adults followed up since 1987-1989. Novel markers included measures of inflammation, endothelial function, fibrin formation, fibrinolysis, B vitamins, and antibodies to infectious agents. Change in the area under the receiver operating characteristic curve (AUC) was used to assess the additional contribution of novel risk markers to CHD prediction beyond that of traditional risk factors.

Results  The basic risk factor model, which included traditional risk factors (age, race, sex, total and high-density lipoprotein cholesterol levels, systolic blood pressure, antihypertensive medication use, smoking status, and diabetes), predicted CHD well, as evidenced by an AUC of approximately 0.8. The C-reactive protein level did not add significantly to the AUC (increase in AUC of 0.003), and neither did most other novel risk factors. Of the 19 markers studied, lipoprotein-associated phospholipase A₂, vitamin B₆, interleukin 6, and soluble thrombomodulin added the most to the AUC (range, 0.006-0.011).

Conclusions  Our findings suggest that routine measurement of these novel markers is not warranted for risk assessment. On the other hand, our findings reinforce the utility of major, modifiable risk factor assessment to identify individuals at risk for CHD for preventive action.

Author Affiliations: Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis (Drs Folsom); Department of Biostatistics (Drs Chambless and Diao), and Department of Epidemiology, School of Public Health (Dr Heiss), University of North Carolina, Chapel Hill; Department of Medicine, Baylor College of Medicine (Dr Ballantyne), Hemostasis Laboratory, Division of Hematology (Dr Wu), and Human Genetics Center and Institute of Molecular Medicine (Dr Boerwinkle), University of Texas Health Science Center, Houston; Departments of Epidemiology (Drs Coresh and Sharrett) and Biostatistics and Medicine (Dr Coresh), Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Md; Department of Medicine (Geriatrics), University of Mississippi Medical Center, Jackson (Dr Mosley); and National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md (Dr Sorlie).

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