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(Circulation. 2007;116:32-38.)
© 2007 American Heart Association, Inc.

Epidemiology

Association of Carotid Artery Intima-Media Thickness, Plaques, and C-Reactive Protein With Future Cardiovascular Disease and All-Cause Mortality

The Cardiovascular Health Study

Jie J. Cao, MD, MPH; Alice M. Arnold, PhD; Teri A. Manolio, MD, PhD; Joseph F. Polak, MD, MPH; Bruce M. Psaty, MD, PhD; Calvin H. Hirsch, MD; Lewis H. Kuller, MD, PhD; Mary Cushman, MD, MSc

From the National Heart, Lung, and Blood Institute (J.J.C.), and the National Human Genome Research Institute (T.A.M.), National Institutes of Health, Bethesda, Md; University of Washington, Seattle (A.M.A., B.M.P.); University of California at Davis (C.H.H.); New England Medical Center, Tufts University, Boston, Mass (J.F.P.); University of Pittsburgh, Pittsburgh, Pa (L.H.K.); and University of Vermont, Burlington (M.C.).

Correspondence to Jie J. Cao, MD, MPH, National Heart, Lung, and Blood Institute, National Institutes of Health, 10 Center Dr, MSC 1061, Bldg 10, Room B1D-416, Bethesda, MD 20892. E-mail caoj{at}nhlbi.nih.gov

Received June 22, 2006; accepted April 9, 2007.

Background— Carotid atherosclerosis, measured as carotid intima-media thickness or as characteristics of plaques, has been linked to cardiovascular disease (CVD) and to C-reactive protein (CRP) levels. We investigated the relationship between carotid atherosclerosis and CRP and their joint roles in CVD prediction.

Methods and Results— Of 5888 participants in the Cardiovascular Health Study, an observational study of adults aged 65 years, 5020 without baseline CVD were included in the analysis. They were followed up for as long as 12 years for CVD incidence and all-cause mortality after baseline ultrasound and CRP measurement. When CRP was elevated (>3 mg/L) among those with detectable atherosclerosis on ultrasound, there was a 72% (95% CI, 1.46 to 2.01) increased risk for CVD death and a 52% (95% CI, 1.37 to 1.68) increased risk for all-cause mortality. Elevated CRP in the absence of atherosclerosis did not increase CVD or all-cause mortality risk. The proportion of excess risk attributable to the interaction of high CRP and atherosclerosis was 54% for CVD death and 79% for all-cause mortality. Addition of CRP or carotid atherosclerosis to conventional risk factors modestly increased in the ability to predict CVD, as measured by the c statistic.

Conclusions— In older adults, elevated CRP was associated with increased risk for CVD and all-cause mortality only in those with detectable atherosclerosis based on carotid ultrasound. Despite the significant associations of CRP and carotid atherosclerosis with CVD, these measures modestly improve the prediction of CVD outcomes after one accounts for the conventional risk factors.

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