Genomic Medicine for Improved Prediction and Primordial Prevention of Cardiovascular Disease

George Thanassoulis,

Gina M. Peloso,

Christopher J. O’Donnell

+ Author Affiliations

From the McGill University Health Centre, Montreal, Quebec, Canada (G.T.); Massachusetts General Hospital, Boston, MA (G.M.P., C.J.O.D.); and National Heart, Lung and Blood Institute, Framingham, MA (C.J.O’D.).

Correspondence to Christopher J. O’Donnell, MD, MPH, Framingham Heart Study, 73 Mt. Wayte Ave, Suite 2, Framingham, MA 01702-5827. E-mail odonnellc@nhlbi.nih.gov

Key Words:

atherosclerosis

cholesterol

genetics

genomics

myocardial infarction

prediction

prevention

risk

During the past 10 years, large-scale genetic studies have identified hundreds of novel genetic variants for heart disease and other forms of cardiovascular (CV) disease and their risk factors.¹ Although highly successful in identifying novel genomic loci, genomic research has been criticized for its high costs, slow translation to clinical care, and many unfulfilled promises. It is now clear that the promised timeline to reap the genomic benefits for medicine was too short, and the benefits themselves, to some degree, were exaggerated.² But major progress continues to be made on several fronts in translating genomics to medicine. In this issue of Arteriosclerosis, Thrombosis, and Vascular Biology, 3 articles demonstrate 1 way by which the CV genomics community is using genomic discoveries to further our understanding of fundamental issues in the prediction and prevention of CV disease.

See accompanying articles on pages 2233, 2261, and 2267

Isaacs et al,³ using lipid genetic scores, add to the mounting evidence that lifelong alterations of both total cholesterol and low-density lipoprotein cholesterol, but not high-density lipoprotein cholesterol, promote atherosclerosis and vascular plaque, leading to a higher rate of CV events. Because these natural Mendelian randomization experiments take advantage of the lifelong nature of the genetic exposure^4,5 and are devoid of confounding and reverse causality, they provide important confirmatory evidence for the critical causal role of the cumulative effect of modifiable risk factors, such as low-density lipoprotein-cholesterol, in atherosclerosis, vascular disease, and CV events while furthering …

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