Genomic Innovation in Early Life Cardiovascular Disease Prevention and Treatment

Abstract

Cardiovascular disease (CVD) is a leading cause of morbidity and mortality globally. Although CVD events do not typically manifest until older adulthood, CVD develops gradually across the life-course, beginning with the elevation of risk factors observed as early as childhood or adolescence and the emergence of subclinical disease that can occur in young adulthood or midlife. Genomic background, which is determined at zygote formation, is among the earliest risk factors for CVD. With major advances in molecular technology, including the emergence of gene-editing techniques, along with deep whole-genome sequencing and high-throughput array-based genotyping, scientists now have the opportunity to not only discover genomic mechanisms underlying CVD but use this knowledge for the life-course prevention and treatment of these conditions. The current review focuses on innovations in the field of genomics and their applications to monogenic and polygenic CVD prevention and treatment. With respect to monogenic CVD, we discuss how the emergence of whole-genome sequencing technology has accelerated the discovery of disease-causing variants, allowing comprehensive screening and early, aggressive CVD mitigation strategies in patients and their families. We further describe advances in gene editing technology, which might soon make possible cures for CVD conditions once thought untreatable. In relation to polygenic CVD, we focus on recent innovations that leverage findings of genome-wide association studies to identify druggable gene targets and develop predictive genomic models of disease, which are already facilitating breakthroughs in the life-course treatment and prevention of CVD. Gaps in current research and future directions of genomics studies are also discussed. In aggregate, we hope to underline the value of leveraging genomics and broader multiomics information for characterizing CVD conditions, work which promises to expand precision approaches for the life-course prevention and treatment of CVD.

Atherosclerosis Residual Lipid Risk-Overview of Existing and Future Pharmacotherapies

“…Therefore, characterising the risk at an individual level may allow tailored therapy and precise intervention to reduce future cardiovascular events. The use of blood, imaging, or genomic biomarkers may enable us to understand future risks and offer patients intensive therapies accordingly [4][5][6][7]. This is important given the recent advances in pharmacotherapy, particularly in the field of lipidology.…”

Introduction to the Compendium on Early Cardiovascular Disease

“…The second segment of the Compendium illustrates the importance of molecular genetics and omic technologies to elucidate risk. The contributions of Li et al 19 and Ordovas and Baccarelli 20 provide a state-of-the-art perspective on how genomic and epigenetic information—potentially useful before clinical risk factors are manifest—might be leveraged to inform approaches for CVD prevention throughout the life course, with a specific focus on early life. Tahir and Gerszten 21 next summarize how high-throughput molecular assays capable of quantifying thousands of circulating molecules—part of the omic revolution in modern molecular science—have been successfully used to focus phenotyping and detection of early CVD risk (precision medicine).…”