The age-driven risk dilemma: Why younger adults with significant cardiovascular disease risk factors often don’t qualify for preventive therapies
Cardiovascular disease (CVD) is a leading cause of mortality worldwide, and preventive measures are crucial in reducing the burden of this disease. However, a significant dilemma exists in preventive cardiology: younger adults with substantial risk factors for cardiovascular disease often do not qualify for preventive therapies.
Age is a significant factor in the American College of Cardiology (ACC) and American Heart Association (AHA) guidelines for assessing atherosclerotic cardiovascular disease (ASCVD) risk. This makes intuitive sense, as most heart attacks and strokes occur in older adults. However, this age-centric approach means younger adults with significant risk factors often don’t qualify for preventive therapies like statins.
Indeed, in a study of myocardial infarction (MI) patients under 50 (YOUNG-MI study), a shocking 49% were ineligible for statins under current guidelines. Yet, heart disease doesn’t start at 50. The seeds of atherosclerosis are sown early, often in childhood, and grow silently over decades.
This age-driven risk dilemma poses a serious challenge for clinicians and patients alike, as it can lead to missed opportunities for early intervention and prevention. How can we overcome the dominant effect of age?
Beyond the numbers: Realizing the lifetime risk
Consider a 25-year-old with very high LDL cholesterol but no other immediate risk factors. Current models may indicate less than a 1% 10-year risk of a heart event, yet his lifetime risk skyrockets to nearly 50%. If we are to curb the lifelong trajectory of heart disease, a broader perspective that goes beyond short-term risk is essential. 
Family history and genetic insights
Family history is a crucial piece of the puzzle often overlooked in standard risk calculations. Studies show that a positive family history is associated with 1.5- to 2.0-fold higher CAD risk, independent of conventional risk factors. Genetic susceptibility factors that we are born with affect our predisposition towards ASCVD and can be categorized as monogenic risk (carrying a rare pathogenic/likely pathogenic (P/LP) variant with relatively large effects) and polygenic risk (additive effects of several common variants each with small effect). We have studied the interplay of these factors previously.
Social determinants and evolutionary context
The role of ancestry and social determinants of health also cannot be ignored. For instance, South Asians have been shown to have more than double the risk of CAD, independent of conventional risk factors. Additionally, socioeconomic challenges like poverty and adverse childhood experiences further complicate risk profiles and demand a more nuanced approach.
Emerging biomarkers and imaging: Comprehensive screening tools
Novel biomarkers such as lipoprotein(a), high-sensitivity troponins, and screening imaging techniques, including coronary artery calcification, offer promising avenues for early risk detection. Elevated lipoprotein(a) levels can be identified early and are linked with a twofold increased risk of ASCVD. A unique characteristic of Lp(a) is that its levels are determined mainly by genetics and do not change much over time. Similarly, noninvasive imaging tools, which detect atherosclerosis even in young adults, could revolutionize early intervention strategies.
Future directions
The future of coronary artery disease risk prediction in young adults lies in a multifaceted approach that moves beyond the dominant age factor. By recognizing the limitations of current models and leveraging emerging science, we stand on the brink of a new era in cardiovascular prevention. It’s time to make every heartbeat matter, from youth to old age.
By Drs. Seyedmohammad Saadatagah, Department of Medicine and Center for Translational Research on Inflammatory Diseases, Baylor College of Medicine; Mini G. Varughese, Section of Cardiology, Department of Medicine, Baylor College of Medicine; and Vijay Nambi, Section of Cardiology, Department of Medicine, Baylor College of Medicine and Michael E. DeBakey VA Medical Center.
