Inherited risk of coronary artery disease: redefining care with imaging and genetics

Atherosclerotic cardiovascular disease remains a leading cause of morbidity and mortality globally, despite advances in preventative medicine. An individual's family history of premature coronary artery disease (CAD) captures the complex interplay among shared genetic, environmental and lifestyle factors within families and is a well-established, independent risk factor for CAD. Although family history has high predictive value, it is inconsistently defined, variably applied and under-recorded in routine cardiovascular risk assessment. Advances in cardiac imaging and genomic medicine offer an opportunity to redefine cardiovascular risk assessment, laying the foundation for a precise approach to prevention in families at high risk of CAD. In this Review, we synthesize the pathogenic mechanisms underlying the inherited risk of CAD, highlight limitations of using family history in current risk stratification models and explore the evolving role of cardiac imaging and polygenic risk scores in risk assessment. We discuss the implications of these methods for lifestyle modifications and therapeutic interventions, and how integrating traditional and emerging tools can enable a precision approach to prevention throughout life. Finally, we examine the limitations of current cardiovascular disease prevention guidelines and highlight the need for studies that will improve equity, evaluate cost-effectiveness and address barriers to integrating novel tools into preventative care.