Risk Factors Associated with Progression and Future Outcomes in Patients Undergoing Coronary Angiography

Abstract

Coronary artery disease (CAD) is a complex disease influenced by multifaceted risk factors, including genetics and novel biomarkers. Despite advancements in managing traditional cardiovascular risk factors, CAD continues to pose major risks of mortality and morbidity globally. Many patients sustain adverse outcomes and complications of CAD despite optimal medical therapy and excellent control of these risk factors. This persistent risk underscores the need for a deeper understanding of residual risk to better stratify patients with CAD, highlighting the importance of exploring novel biomarkers that could better predict the risk of outcomes, especially in a secondary prevention context. Given the high heritability of CAD, integrating genomic information plays an important role in patient risk stratification. Genetic factors, including germline variations–both monogenic, such as Familial Hypercholesterolemia (FH), and polygenic liabilities, as represented by a polygenic risk score (PRS)– and somatic variants, such as clonal hematopoiesis of indeterminate potential (CHIP) have been robustly linked to the incidence of CAD in large cohort studies. However, the role of these genomic drivers in a secondary prevention paradigm, particularly after coronary angiography, requires further extensive exploration. Lipoprotein(a) [Lp(a)] is another important marker of residual risk associated with major cardiovascular events. This low-density lipoprotein, whose circulating concentrations in the plasma are largely genetically determined, is elevated in approximately 20% of the world’s population. Every 50 nmol/L increase in Lp(a) is associated with an 11% increased risk of incident atherosclerotic cardiovascular disease. Currently, American and European guidelines recommend Lp(a) testing at least once in a lifetime for adults, regardless of traditional cardiovascular risk factors. Despite its recognized role, the impact of elevated Lp(a) on long-term outcomes following coronary angiography remains underexplored, necessitating further studies into its implications for secondary prevention. To investigate these aspects, we studied patients undergoing coronary angiography, the gold standard for diagnosing and evaluating coronary phenotypes and severity. In this cohort of individuals with CAD or a high likelihood for the disease, we aimed to understand whether (1) genomic predisposition to CAD and (2) the novel lipid biomarker, Lipoprotein(a), correlate with specific angiographic characteristics and track progression and future outcomes. We hypothesized that these factors are associated with more severe coronary phenotypes and increased risks of adverse outcomes, either clinically or angiographically, following initial coronary angiography.