Abstract-The relevance of elevated levels of C-reactive protein (CRP) in cardiovascular disease is gaining increasing recognition. A family history of coronary artery disease is a major determinant of coronary artery disease in the offspring. In a cohort of 1048 individuals without clinical evidence of atherosclerosis, we investigated the relationships between CRP levels and a family history of myocardial infarction. We measured CRP, fibrinogen, plasminogen activator inhibitor-1, total cholesterol, triglycerides, and some genetic polymorphisms: plasminogen activator inhibitor-1 (4G/5G), fibrinogen (B-chain G3 A Ϫ455 ), and angiotensin-converting enzyme insertion/deletion (I/D). Clinical data were collected by a World Health Organization-modified questionnaire for cardiovascular disease. When compared with subjects without first-degree relatives who had suffered a myocardial infarction (nϭ867), subjects with such first-degree relatives (nϭ181) were older (Pϭ0.001), more often hypertensive (PϽ0.001), and homozygous for the 4G allele (4G/4G) of the plasminogen activator inhibitor-1 gene (Pϭ0.003). In addition, they had a higher body mass index (Pϭ0.036), raised plasma fibrinogen (PϽ0.007) and total cholesterol (PϽ0.001) concentrations, and CRP levels Ͼ0.33 mg/L (Pϭ0.005). In a multiple logistic regression analysis, age (odds ratio [OR] 1.03, 95% confidence interval [95% CI] 1.01 to 1.05), total cholesterol (OR 1.35, 95% CI 1.11 to 1.65), plasminogen activator inhibitor-1 4G/4G (OR 1.72, 95% CI 1.20 to 2.45), and CRP levels Ͼ0.33 mg/L (OR 1.75, 95% CI 1.05 to 2.91) were all independently associated with a positive family history of myocardial infarction. We therefore conclude that raised levels of CRP independently identify the offspring of patients with a myocardial infarction. (Arterioscler Thromb Vasc