Precision Medicine Approaches to Vascular Disease

• Published in: Journal of the American College of Cardiology 2021-05, Vol.77 (20), p.2531-2550
• Main Authors: Miller, Clint L., Kontorovich, Amy R., Hao, Ke, Ma, Lijiang, Iyegbe, Conrad, Björkegren, Johan L.M., Kovacic, Jason C.
• Format: Article
• Language: English
• Subjects: cardiovascular; genetics; polygenic risk score; precision medicine; vascular
• ISSN: 0735-1097; 1558-3597
• DOI: 10.1016/j.jacc.2021.04.001

In this second of a 5-part Focus Seminar series, we focus on precision medicine in the context of vascular disease. The most common vascular disease worldwide is atherosclerosis, which is the primary cause of coronary artery disease, peripheral vascular disease, and a large proportion of strokes and other disorders. Atherosclerosis is a complex genetic disease that likely involves many hundreds to thousands of single nucleotide polymorphisms, each with a relatively modest effect for causing disease. Conversely, although less prevalent, there are many vascular disorders that typically involve only a single genetic change, but these changes can often have a profound effect that is sufficient to cause disease. These are termed “Mendelian vascular diseases,” which include Marfan and Loeys-Dietz syndromes. Given the very different genetic basis of atherosclerosis versus Mendelian vascular diseases, this article was divided into 2 parts to cover the most promising precision medicine approaches for these disease types. [Display omitted] •Inherited vascular diseases include those associated with arterial enlargement (dilatation, ectasia, or aneurysm) or impaired arterial wall integrity (dissection or rupture).•Arterial dilatation, particularly in young patients, should prompt evaluation for a genetic etiology.•Atherosclerosis generally arises due to the interplay of environmental and lifestyle factors, and hundreds to thousands of single nucleotide polymorphisms, each with a relatively modest disease-causing effect.•Although the genetics of atherosclerosis and Mendelian arteriopathies may differ, integrated methods are emerging to apply precision medicine to these diseases.