Response to Mikail

To the Editor:

Thank you, Dr. Mikail, for your thoughtful response to the issues put forth in the recent article by Frezzo and colleagues ¹ and the accompanying editorial ² regarding use of family history to improve prevention efforts for common chronic diseases.

More than a noble vision, there are several reasons to believe that collection and interpretation of family history to identify and stratify risk and to guide screening and prevention recommendations could improve prevention efforts for most common chronic diseases and ultimately save lives. (1) There is under-utilization of many interventions known to be effective in improving health care. ³ This may be due in part to the lack of effectiveness of a “one size fits all” approach to prevention. Personalized prevention messages with intensive management in high-risk individuals have the power to motivate behavior changes that can lead to improved prevention. ⁴ (2) Family history is a powerful predictor of risk for many chronic diseases. It reflects not only genetic susceptibility but also the interactions between genetic, environmental, cultural, and behavioral risk factors. (3) Stratification of familial risk into different risk categories (e.g., average, moderate, and high) is possible by considering the number of affected family members, their degree of relationship to an index case, their ages of onset, the occurrence of associated conditions, and for some disorders, the gender of the affected family members. ⁵ For many chronic disorders, this risk stratification should have greater clinical validity than assessing only the presence or absence of a family history, which is typical for most risk assessment instruments, such as the “Put Prevention into Practice” materials ⁶ or the Adult Treatment Panel III guidelines for treatment of lipid disorders. ⁷ (4) Familial risk stratification that recognizes high-risk cases and familial patterns of disease consistent with mendelian disorders can identify individuals who might benefit from genetic consultation and genetic testing to assess susceptibility to chronic diseases. Although the sequencing of the human genome holds great promise for clinical medicine and public health, it is unlikely that population-based applications of genetic testing for chronic diseases will develop in the near future due to our lack of understanding regarding prevalence and penetrance of disease susceptibility alleles, as well as gene-gene and gene-environment interactions. Rather, applications of genetic testing for chronic disease susceptibility will likely remain a clinical intervention based on personal and family history characteristics for many years to come. (5) Lastly, because risk factors for chronic diseases aggregate in families, ⁸ a family-based approach to risk factor modification can be an effective strategy to promote healthy behaviors. ^9–11

Dr. Mikail states that steps have already been taken to improve disease prevention efforts with programs like “Putting Prevention into Practice,” and that approaches to genetic risk prediction might best be integrated into established prevention initiatives. Certainly this would be one avenue for use of a family history tool. However, it is also reasonable to consider a family history tool that will stand on its own, particularly because one instrument has the ability to assess risk for multiple disorders. Regardless of how a family history collection and interpretation tool will be applied, research demonstrating the added value of the tool is necessary. ¹² It must have improved clinical validity (the ability to stratify and predict risk) compared to existing risk assessment methods. In addition, research proving feasibility and clinical utility is necessary before implementation into preventive medicine and public health practice. Without this proof, there will be little incentive for health care practitioners and consumers to change their behaviors and adhere to this approach. Ethical, legal, and social issues must also be researched to determine the acceptability of using a population-based family history tool. This research agenda will address the critical issues pertaining to integration of genetic information and technology into preventive medicine and public health practice. If successful, the results have the potential to revolutionize our approach to prevention and we will move closer to the paradigm shift Dr. Mikail speaks of, from reactive and disease-oriented practice to proactive and health-based care.