Assessment of improved prediction beyond traditional risk factors: when does a difference make a difference?

The moderate predictive performance of cardiovascular disease risk models necessitates more studies that investigate the incremental value of novel biomarkers. In recent years, many new biomarkers have been evaluated for their ability to improve prediction of cardiovascular disease beyond traditional risk factors, including C-reactive protein, coronary artery calcium, and single-nucleotide polymorphisms in the 9p21 region.1 The interest in novel biomarkers is propelled, in part, by emerging discoveries from genomewide association studies of genetic variants associated with risk for many common diseases.2 Nonetheless, family history, an “old” tool in clinical practice—crucial for the diagnosis and management of genetic disorders—has not been adequately explored for its value in risk assessment and prevention of common diseases.3 Positive family history is a strong risk factor for cardiovascular diseases,4,5 reflecting the consequences of genetic and nongenetic risk factors that are shared among relatives. From a practical perspective, family history is a strong determinant of disease that is relatively easy to assess. For this reason, family history is advocated as a useful tool for identifying individuals at increased risk of disease and for tailoring preventive interventions.4,6,7 However, the challenge is to show that this knowledge has clinical utility for improving health.8