Elsevier

American Heart Journal

Volume 144, Issue 2, August 2002, Pages 233-238
American Heart Journal

Clinical Investigations: Acute Ischemic Heart Disease
C-reactive protein and incident coronary heart disease in the Atherosclerosis Risk In Communities (ARIC) study,☆☆,

https://doi.org/10.1067/mhj.2002.124054Get rights and content

Abstract

Background Recent evidence implicates inflammation in the pathogenesis of coronary heart disease (CHD). C-reactive protein, a plasma marker of inflammation, is a marker of CHD risk but has been studied in few prospective investigations of the general population. Methods and Results We prospectively examined the association of CRP with incident CHD among middle-aged adults in the Atherosclerosis Risk In Communities (ARIC) study. With the use of a nested case-cohort approach, we measured CRP in stored, baseline blood samples of 2 groups of subjects in whom CHD developed during follow-up (242 incident cases from 1987 to 1993 and 373 from 1990 to 1995) and, for comparison, 2 stratified random samples of noncases. In analyses adjusted for demographic variables and traditional CHD risk factors, the relative risk of CHD across quintiles of CRP was 1.0, 0.8, 1.6, 1.9, and 1.5 for events from 1987 to 1995 (P for trend =.01). As expected, inclusion of fibrinogen, intracellular adhesion molecule-1, and white blood cell count (other potential markers of the inflammatory reaction) attenuated the association of CRP with CHD incidence. In a supplemental cross-sectional analysis, CRP was not associated with carotid intima-media thickness after adjustment for major risk factors. Conclusions C-reactive protein is a moderately strong marker of risk of CHD in this cohort of middle-aged adults, consistent with the role of inflammation in the pathogenesis of CHD events. The association was not specific to CRP because other markers of inflammation could largely account for the finding. (Am Heart J 2002;144:233-8.)

Section snippets

Study population and baseline measurements

In 1987 through 1989, the ARIC Study24 recruited a population-based cohort of 15,792 persons aged 45 to 64 years from 4 US communities. ARIC reexamined participants in 1990 to 1992 (93% return rate), 1993 to 1995 (86% return), and 1995 to 1997 (80% return).

Technicians measured resting blood pressure 3 times with a random-zero sphygmomanometer and averaged the last 2 measurements for analysis. We expressed physical activity as a sport index ranging from 0 (low) to 5 (high).25 Trained technicians

Relations of CRP with other risk factors

C-reactive protein values at visit 1 were higher in women than in men, higher in African-Americans than in whites, and higher in diabetic subjects than in nondiabetic subjects (Table I).

. Adjusted* mean values or prevalences of study covariates by quintiles of CRP: ARIC baseline cohort random sample (n = 590), 1987 to 1989

Empty CellCRP quintiles (mg/L)
Variable<0.830.83-2.072.08-3.853.86-6.09>6.09P
No.118118118118118
Age (y)55.855.356.257.757.5<.001
Sex (% male)66.467.857.752.043.4.002
Race (% African-American)

Discussion

The main finding of this prospective study was that higher blood levels of CRP in middle-aged adults were moderately strongly associated with increased incidence of CHD. The association was weakened but still significant after adjustment for traditional risk factors. Adjustment for other inflammatory markers (fibrinogen, WBC count, and ICAM-1), not unexpectedly, weakened the association further. CRP was not independently associated with prevalent carotid atherosclerosis.

A recent meta analysis1

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    Supported by contracts N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, and N01-HC-55022 from the United States National Heart, Lung, and Blood Institute.

    ☆☆

    Reprint requests: Aaron R. Folsom, MD, Division of Epidemiology, School of Public Health, University of Minnesota, Suite 300, 1300 S Second St, Minneapolis, MN 55454-1015.

    E-mail: [email protected]

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