Published Online
on February 5, 2007

A more recent version of this article appeared on February 27, 2007

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Submitted on June 1, 2006
Accepted on December 11, 2006

C-Reactive Protein and Prediction of Coronary Heart Disease and Global Vascular Events in the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER)

Naveed Sattar MD^*, Heather M. Murray MSc, Alex McConnachie PhD, Gerard J. Blauw MD, Edward L.E.M. Bollen MD, Brendan M. Buckley FRCPI, Stuart M. Cobbe MD, Ian Ford PhD, Allan Gaw MD, Michael Hyland FRCPI, J. Wouter Jukema MD, Adriaan M. Kamper MD, Peter W. Macfarlane DSc, Michael B. Murphy MD, Chris J. Packard DSc, Ivan J. Perry MD, David J. Stott MD, Brian J. Sweeney FRCPI, Cillian Twomey FRCPI, Rudi G.J. Westendorp MD, James Shepherd PhD, for the PROSPER Study Group

From the Department of Vascular Biochemistry (N.S., C.J.P., J.S.), Division of Cardiovascular and Medical Sciences (S.M.C., P.W.M.), Department of Geriatric Medicine (D.J.S.), and Robertson Centre for Biostatistics (H.M., A.M., I.F.), University of Glasgow, Glasgow, Scotland; Clinical Trials Unit (A.G.), North Glasgow Division, Greater Glasgow Health Board, Glasgow, Scotland; Departments of Pharmacology and Therapeutics (B.M.B., M.B.M.), Epidemiology and Public Health (I.J.P.), Geriatric Medicine (M.H., C.T.), and Neurology (BS), Cork University Hospital, Wilton, Cork, Ireland; and Section of Gerontology and Geriatrics (G.J.B., R.G.J., A.M.K.) and Departments of Cardiology (J.W.J.) and Neurology (E.L.E.M.B.), Leiden University Medical Centre, Leiden, the Netherlands.

^* To whom correspondence should be addressed. E-mail: nsattar{at}clinmed.gla.ac.uk.

Background--The role of C-reactive protein (CRP) in predicting vascular events and response to statin therapy remains uncertain. Additional large prospective studies are required.

Methods and Results--Baseline CRP was related to risk over 3.2 years for primary a combined end point (definite or suspected death from coronary heart disease, nonfatal myocardial infarction, and fatal or nonfatal stroke; n=865 events) and secondary (coronary heart disease events or stroke alone) and tertiary (stroke plus transient ischemic attack) end points in the Prospective Study of Pravastatin in the Elderly at Risk (n=5804 men and women; age, 70 to 82 years). CRP levels were higher in subjects who had a subsequent primary end-point event compared with those who did not (geometric mean; 3.64 mg/L [SD, 3.08 mg/L] versus 3.01 mg/L [SD, 3.05 mg/L]; P<0.0001). CRP correlated positively with body mass index and smoking status and negatively with high-density lipoprotein cholesterol. The unadjusted hazard ratio for the primary end point was 1.48 (95% CI, 1.26 to 1.74) in a comparison of top and bottom thirds for CRP, falling to 1.36 (95% CI, 1.15 to 1.61) with adjustment for established predictors and body mass index. Similar results were obtained for other end points or when results were examined separately by history of vascular disease. However, baseline CRP added minimally to risk prediction beyond conventional predictors and did not relate to the magnitude of pravastatin benefit.

Conclusions--Elevated CRP minimally enhances cardiovascular disease prediction beyond established vascular risk factors and does not predict response to statin therapy in elderly subjects at risk. These data suggest that CRP has limited clinical value in cardiovascular disease risk stratification or predicting response to statin therapy in elderly people.

Key words: aged • cardiovascular diseases • forecasting • inflammation • risk factors • stroke

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