Cardiovascular Precision Medicine in the Genomics Era

Abstract

Precision medicine strives to delineate disease using multiple data sources-from genomics to digital health metrics-in order to be more precise and accurate in our diagnoses, definitions, and treatments of disease subtypes. By defining disease at a deeper level, we can treat patients based on an understanding of the molecular underpinnings of their presentations, rather than grouping patients into broad categories with one-size-fits-all treatments. In this review, the authors examine how precision medicine, specifically that surrounding genetic testing and genetic therapeutics, has begun to make strides in both common and rare cardiovascular diseases in the clinic and the laboratory, and how these advances are beginning to enable us to more effectively define risk, diagnose disease, and deliver therapeutics for each individual patient.

Keywords: CAD, coronary artery disease; CF, cystic fibrosis; CHD, coronary heart disease; CML, chronic myelogenous leukemia; CRS, conventional risk score; CVD, cardiovascular disease; CaM, calmodulin; DCM, dilated cardiomyopathy; DMD, Duchenne muscular dystrophy; FH, familial hypercholesterolemia; GRS, genomic risk score; HCM, hypertrophic cardiomyopathy; HDR, homology directed repair; IVF, in vitro fertilization; LDL-C, low-density lipoprotein cholesterol; LQTS, long QT syndrome; NGS, next-generation sequencing; PGD, preimplantation genetic diagnosis; SNP, single nucleotide polymorphism; genome sequencing; genomics; iPSC, induced pluripotent stem cells; precision medicine; ssODN, single-stranded oligodeoxynucleotide; targeted therapeutics.

Graphical abstract

Figure 1

Cardiovascular Precision Medicine Timeline This timeline highlights key events in the history of precision medicine, such as the introduction of the first precision medicine drugs and the announcement of the Precision Medicine Initiative, as well as specific case studies cited in this review. Notable in this presentation is the explosion of activity in the past 5 years as advances in genome sequencing and genome editing technologies have rapidly increased the speed of basic research and clinical application of precision medicine technologies in cardiovascular medicine. AHA = American Heart Association; CLIA = Clinical Laboratory Improvement Amendments; CML = chronic myelogenous leukemia; FDA = Food and Drug Administration; HCM = hypertrophic cardiomyopathy; iPSCs = induced pluripotent stem cells; LDL-C = low-density lipoprotein cholesterol; LQTS = long QT syndrome.

Central Illustration

Cardiovascular Precision Medicine Integrates Basic Science Techniques With Genomic Information As clinical genome sequencing becomes more common and basic science techniques like CRISPR and induced pluripotent stem cells begin to transition toward clinical applicability, the world of cardiovascular medicine moves toward one where we can be more precise and accurate with our diagnoses and treatment. Using knowledge gained from population sequencing projects, such as genome-wide association studies, and disease models in the laboratory, we can begin to develop deeper understandings of disease at a molecular level to predict the risk of a patient for developing a disease and present them with the right treatment when they do—or the right preventative strategy in advance. This review focuses on how precision medicine, genomics, and new genetic tools intertwine to create a new era of cardiovascular precision medicine. FH = familial hypercholesterolemia; HC = hypertrophic cardiomyopathy; iPSC = induced pluripotent stem cells; LQTS = long QT syndrome.