Pathophysiology and Natural History Coronary Artery Disease

A family history of heart attack is reported to be an independent predictor of cardiovascular death in men. In a 9 year follow-up of 4014 adults from 40 to 79 years old in the Rancho Bemardo Study, men under 60 years of age with a family history of heart attack were at fivefold increased risk. In this study, we sought to determine whether modifiable risk factors, i.e., blood pressure, plasma cholesterol, obesity, and cigarette smoking, have a differential effect on cardiovascular risk in those with and without a family history of heart attack. For both sexes, cigarette smoking was a stronger predictor of cardiovascular disease in those with a family history of heart attack (relative risk of smokers vs nonsmokers was 2.5 for men and 4.0 for women) than in those with no such family history (relative risk of smokers vs nonsmokers was 1.1 for men and 1.7 for women). Conversely, an increased risk of cardiovascular mortality in men with a family history of heart attack was present predominantly in smokers (relative risk related to positive family history was 1.2 in nonsmokers, and 3.3 in smokers). An estimated 68% of the excess deaths in men with a family history of heart attack were attributable solely to the interaction of family history with smoking habit and were therefore potentially avoidable. The risk of cardiovascular disease associated with an apparently inherited predisposition appears to be profoundly affected by modifiable behavior. Circulation 74, No. 2, 239-244, 1986. A FAMILY HISTORY of heart disease has been reported to increase risk of coronary heart disease by twoto sevenfold in numerous studies. 1-' There is also familial aggregation, genetic or environmental, of known cardiovascular risk factors such as raised blood pressure, hyperlipidemia, and cigarette smoking.8'-3 The increased risk of coronary heart disease in those with a positive family history has been partly attributed to the familial occurrence of these risk factors. However, several studies have suggested that family history might itself predict cardiovascular disease independent of the effects of these risk factors.7 We have previously reported that a family history of heart attack was significantly predictive of cardiovascular mortality in men from 40 to 79 years old and that this association persisted after adjusting for level of blood cholesterol, blood pressure, and cigarette smoking.7 In this cohort, cardiovascular risk was increased to a similar From the Department of Community and Family Medicine, School of Medicine, University of California San Diego, La Jolla. Supported by NIH contracts NIH-NHLBI-HV-1-2160-L and NIHHIADDK-AM-31801-02. K-T. Khaw is a Daland Fellow of the American Philosophical Society. Address for correspondence: Dr. E. Barrett-Connor, Department of Community and Family Medicine, University of California San Diego, La Jolla, CA 92093. Received March 11, 1986; revision accepted May 8, 1986. extent in men who reported a family history of heart attack whether the relative's attack occurred before or after he was 50 years of age. No association was seen in women. In this study, we assessed whether modifiable risk factors contribute differently to the risk of death attributable to cardiovascular disease in those with and without a family history of heart attack.