INTERACTIVE MEDICAL CASE. A Man with Bizarre Behavior.

Background Inflammation may be important in the pathogenesis of atherothrombosis. We studied whether inflammation increases the risk of a first thrombotic event and whether treatment with aspi­ rin decreases the risk. Methods We measured plasma C­reactive protein, a marker for systemic inflammation, in 543 appar­ ently healthy men participating in the Physicians’ Health Study in whom myocardial infarction, stroke, or venous thrombosis subsequently developed, and in 543 study participants who did not report vascular disease during a follow­up period exceeding eight years. Subjects were randomly assigned to receive as­ pirin or placebo at the beginning of the trial. Results Base­line plasma C­reactive protein con­ centrations were higher among men who went on to have myocardial infarction (1.51 vs. 1.13 mg per liter, P,0.001) or ischemic stroke (1.38 vs. 1.13 mg per liter, P 5 0.02), but not venous thrombosis (1.26 vs. 1.13 mg per liter, P 5 0.34), than among men without vascu­ lar events. The men in the quartile with the highest C­reactive protein values had three times the risk of myocardial infarction (relative risk, 2.9; P,0.001) and two times the risk of ischemic stroke (relative risk, 1.9; P 5 0.02) of the men in the lowest quartile. Risks were stable over long periods, were not modified by smoking, and were independent of other lipid­relat­ ed and non–lipid­related risk factors. The use of as­ pirin was associated with significant reductions in the risk of myocardial infarction (55.7 percent reduction, P 5 0.02) among men in the highest quartile but with only small, nonsignificant reductions among those in the lowest quartile (13.9 percent, P 5 0.77). Conclusions The base­line plasma concentration of C­reactive protein predicts the risk of future myo­ cardial infarction and stroke. Moreover, the reduc tion associated with the use of aspirin in the risk of a first myocardial infarction appears to be directly related to the level of C­reactive protein, raising the pos­ sibility that antiinflammatory agents may have clini­ cal benefits in preventing cardiovascular dis ease. (N Engl J Med 1997;336:973­9.) ©1997, Massachusetts Medical Society. From the Divisions of Preventive Medicine (P.M.R., C.H.H.) and Car­ diovascular Disease (P.M.R.) and the Channing Laboratory (M.J.S.), De­ partment of Medicine, Brigham and Women’s Hospital; the Department of Ambulatory Care and Prevention, Harvard Medical School (C.H.H.); and the Departments of Epidemiology (M.J.S., C.H.H.) and Nutrition (M.J.S.), Harvard School of Public Health — all in Boston; and the Lab­ oratory for Clinical Biochemistry Research, University of Vermont, Bur ­ lington (M.C., R.P.T.). Address reprint requests to Dr. Ridker at the Divi­ sion of Preventive Medicine, Brigham and Women’s Hospital, 900 Commonwealth Ave. E., Boston, MA 02215­1204. HROMBUS formation is the proximate cause of myocardial infarction, but ath­ erosclerosis, the chief underlying cause, is a chronic disease that progresses over dec­ ades of life.1 Laboratory and pathological data sup­ port the idea that inflammation has a role in both the initiation and the progression of atherosclerosis, and antiinflammatory agents may have a role in the prevention of cardiovascular disease.2­5 However, there are few data to indicate whether inflammation increas­ es the risk of first myocardial infarction, stroke, and venous thrombosis or whether antiinflammatory ther­ apy decreases that risk. C­reactive protein is an acute­phase reactant that is a marker for underlying systemic inflammation. Elevated plasma concentrations of C­reactive protein have been reported in patients with acute ischemia6 or myocardial infarction7,8 and have been found to predict recurrent ischemia among those hospitalized with unstable angina.9 C­reactive protein is also as­ sociated with a risk of myocardial infarction among patients with angina pectoris10 and with a risk of fa­ tal coronary disease among smokers with multiple risk factors for atherosclerosis.11 However, since con­ centrations of C­reactive protein and other acute­ phase reactants increase after acute ischemia6 and are directly related to cigarette smoking,11,12 it has been uncertain whether associations observed in previous studies of acutely ill patients9 or high­risk popula ­ T