Should your family history of coronary heart disease scare you?

Traditional risk factors explain most of the risk associated with coronary heart disease, and after adjustment for risk factors family history was believed to contribute very little to population-attributable risk of coronary heart disease. However, the INTERHEART study demonstrated an independent association of family history of coronary heart disease with acute myocardial infarction. To assess this relationship more comprehensively in multiple datasets in different populations, we carried out a detailed review of the available evidence. Case-control studies involving 17,202 cases and 30,088 controls yielded a pooled unadjusted odds ratio (random-effects model, overall I(2) = 64.6%, P = 0.000) of 2.03 (95% confidence interval: 1.79-2.30), whereas cohort studies that included 313,837 individuals yielded an unadjusted relative risk for future coronary heart disease (random-effects model, overall I(2) = 88.7%, P = 0.000) of 1.60 (95% confidence interval: 1.44-1.77). Although the presence of family history of coronary heart disease indicates a cumulative exposure of shared genes and environment, the risk estimates for family history did not attenuate significantly after adjustment for conventional coronary heart disease risk factors in several studies. It is probably an oversimplification to dichotomize the family history variable into a simple "yes" or "no" risk factor, as the significance of family history is influenced by several variables, such as age, sex, number of relatives, and age at onset of disease in the relatives. Moreover, a quantitative risk-assessment model for the family history variable, such as the "family risk score," has a positive linear relationship with coronary heart disease. More studies are warranted to assess the benefits and risks of intensive interventions, both targeted individually and at the family level, among individuals with a valid family history and borderline elevated risk factors.