A Breakthrough in Genetics and Prevention of Coronary Artery Disease and its Relevance to Prevention in LMIC

More than 60 genetic risk variants predisposing to coronary artery disease (CAD) have been confirmed. The genetic risk for CAD is related to the number of genetic risk variants present and can be expressed as a genetic risk score (GRS), by summing the product of the number of high-risk variants inherited by each individual times the log of the odds ratio. Studies show risk stratification for CAD, based on the GRS, is more discriminatory than conventional risk factors and predicts the response to statin therapy. A prospective trial showed individuals with high GRS had 91% greater risk of cardiac events, and individuals with a healthy lifestyle had 46% fewer cardiac events than an unfavorable lifestyle. GRS remains the same throughout one’s lifetime because your deoxyribonucleic acid does not change. GRS, determined as early as birth from saliva, is inexpensive and could transform the prevention of CAD in lowand middle-income countries. This work was supported by grants from the Canadian Institutes of Health Research (Grant No. MOP82810) and Canadian Foundation for Innovation (Grant No. 11966). Dr. Roberts is a consultant to Cumberland Pharmaceuticals. From the Department of Medicine, University of Arizona College of Medicine-Phoenix, Phoenix, AZ, USA. Correspondence: R. Roberts (rroberts2@email. arizona.edu). GLOBAL HEART © 2017 World Heart Federation (Geneva). Published by Elsevier Ltd. All rights reserved. VOL. -, NO. -, 2017 ISSN 2211-8160/$36.00. http://dx.doi. org/10.1016/ j.gheart. 2017.04. 001 The world is experiencing an era of globalization that has spread across all continents with an intensity never before experienced by mankind. Whereas globalization is affecting commerce, politics, and geopolitical issues, it is also influencing science and human health. The Western world in the 20th century was experiencing an epidemic of heart disease, whereas in the East, heart disease was less predominant. Today, heart disease is pandemic, being the number one killer in the world [1] with a significant decreasing trend in the West and an increasing trend in the East. This is based on the comprehensive assessment by the GBD (Global Burden of Disease) study launched by the World Bank and the World Health Organization [1]. GBD has assessed data from 187 countries involving 291 diseases associated with 1,160 sequelae. GBD claims these diseases are associated with 67 risk factors. It has been recognized by epidemiologists for decades that genetic risk accounts for probably 40% to 60% of susceptibility for coronary artery disease (CAD). Nevertheless, modification of risk factors for common diseases has not included genetic risk, because the technology to discover these genetic variants was not available until about 2005 [2]. The appropriate current goal in preventing CAD is to treat the well-recognized traditional risk factors of cholesterol, hypertension, obesity, and smoking. Future prevention must be comprehensive and to do so must include modification of acquired and genetic risk factors and preferably be initiated prior to the development of the disease. CAD, particularly in lowand middle-income countries, is usually not detected until the disease is severe enough to manifest symptoms such as a myocardial infarction (MI). Early detection and prevention may require sophisticated techniques such as myocardial imaging or GLOBAL HEART, VOL. -, NO. -, 2017 Month 2017: -cardiac catheterization, which can be expensive and in developing countries are not always freely available. The recent successful discovery of multiple genetic risk variants predisposing to CAD may be transforming, particularly in lowand middle-income countries, because it requires only a sample of saliva. Furthermore, genetic risk stratification for CAD can be determined as early as birth. This could transform primary and secondary prevention of CAD worldwide for individuals of all levels of income. To significantly attenuate the pandemic of heart disease may require physicians throughout the world to acquire a working knowledge of medical genetics. GENETIC PREDISPOSITION AND CAD Extensive studies have documented that heritance plays a role in CAD. These results have been based on epidemiological and familial studies suggesting that 40% to 60% of susceptibility to CAD is due to genetic predisposition [3]. The Framingham study shows that a family history of CAD is associated with a 2.4-fold increased risk of CAD in men and a 2.2-fold increase in women [4]. The Danish Twin Registry [5] shows a higher frequency of CAD in monozygotic twins than in dizygotic twins, averaging 44% versus 14%. After correcting for other risk factors [6], the INTERHEART (Effect of Potentially Modifiable Risk Factors Associated With Myocardial Infarction in 52 Countries) study showed a family history of CAD increases the risk of CAD 1.5-fold. In the PROCAM (Prospective Cardiovascular Münster) study, a family history of MI documented an independent risk factor of CAD [7]. It is perhaps worthy of note that epidemiological studies suggest genetic predisposition exists for essentially all diseases.