Family history, subclinical atherosclerosis, and coronary heart disease risk: barriers and opportunities for the use of family history information in risk prediction and prevention.

Abstract

With completion of the human genome sequence, expectations are rising that a detailed catalogue will soon be available of all important common genetic susceptibility variants for human diseases, including coronary heart disease (CHD) and related atherosclerotic cardiovascular disease (CVD).1 In light of this seminal event in medical research, it is curious that the family history of CHD has not been accorded a more central role in risk prediction and disease prevention by clinicians and public health professionals. A positive family history of CHD is present in the majority of cases of premature-onset CHD.2 In cases of familial hypercholesterolemia and other rare forms of premature-onset CVD, CHD clearly segregates in a mendelian fashion. For most cases of premature-onset CHD, the mode of genetic transmission in families is less clear. Although the family history of CHD has been considered a putative risk factor for decades, it has not been incorporated along with other established risk factors such as hyperlipidemia, hypertension, and cigarette smoking in some widely applied multivariable risk algorithms,3 though other risk algorithms do incorporate family history information.4 See p 2150 This cautious approach to widespread application of family history information is not due to insufficient evidence. Risks for CHD death are greatest in monozygotic (identical) compared with dizygotic (nonidentical) twins, particularly when there is a premature (eg, <65 years) age of onset in the initially affected twin.5 In multiple prospective studies involving hundreds of thousands of men and women, a parental history of premature CHD is a significant risk factor for CVD even after multivariable adjustment. Relative risk estimates generally range from 1.2 to 2.0, as noted in the Physician’s Health Study and Women’s Health Study,6 although the estimated magnitude of risk associated with early-onset parental disease is substantially higher in some studies.7 …