Genetics, its role in preventing the pandemic of coronary artery disease

Abstract

Epidemiologists have claimed for decades that about 50% of predisposition for coronary artery disease (CAD) is genetic. Advances in technology made possible the discovery of hundreds of genetic risk variants predisposing to CAD. Multiple clinical trials have shown that cardiac events can be prevented by drugs to lower plasma low‐density lipoprotein cholesterol (LDL‐C). A major barrier to primary prevention is the lack of markers to identify those individuals at risk prior to the development of symptoms of the disease. Conventional risk factors are age‐dependent, occurring mostly in the sixth or seventh decade, which is less than desirable for early primary prevention. A polygenic risk score, derived from the number of genetic risk variants predisposing to CAD inherited by an individual, has been evaluated in over 1 million individuals. The risk for CAD is stratified into high, intermediate, and low. Polygenic risk scores derived from retrospective genotyping of several clinical trials evaluating the effect of statin therapy or PCSK9 inhibitors show the genetic risk is reduced 40%–50% by decreasing plasma LDL‐C. Prospective randomized placebo‐controlled clinical trials document a 40%–50% reduction in cardiac events in individuals at high genetic risk associated with favorable lifestyle changes and increased physical activity. The polygenic risk score is not age‐dependent and remains the same throughout life. Thus, the GRS is superior to conventional risk factors in identifying asymptomatic individuals at risk for CAD early in life for primary prevention. These results indicate clinical embracement of the GRS in primary prevention would be a paradigm shift in the treatment of the number one killer, CAD.

Association of APOE (rs429358 and rs7412) and PON1 (Q192R and L55M) Variants with Myocardial Infarction in the Pashtun Ethnic Population of Khyber Pakhtunkhwa, Pakistan

“…Among the former, some major factors to mention are physical activity, diet, smoking habits, obesity, etc. About the latter, information from different studies has recommended a 40–80% genetic link [ 9 , 10 ]. A person with parental history of premature atherosclerosis has a 1.5- to 2-fold risk of developing the same [ 11 ].…”

A life-threatening arrhythmia detection method based on pulse rate variability analysis and decision tree

“…In recent years, cardiovascular diseases have the highest mortality rate and are the "number one killer" of human beings (Roberts and Fair 2021). Among them, acute cardiovascular diseases such as myocardial infarction (MI) and cerebral infarction (CI) have the high suddenness and lethality (Du et al, 2021).…”

Integrating a Polygenic Risk Score for Coronary Artery Disease as a Risk Enhancing Factor in the Pooled Cohort Equation is Cost-effective in a US Health System

“…39,40 CAD-PRS has greater benefits when implemented in young adults given the limitations of traditional risk factors in identifying the risk of ASCVD at a younger age. 6 Our results indicate higher QALYs gained and cost-savings when PCE+PRS was implemented in a 40-vs 75-year-old cohort, primarily due to the long term benefits from prevention of adverse health outcomes in young adults (Figure 4). Previous work has demonstrated that individuals who receive their genetic results are more likely to report behavior changes.…”

“…The pooled cohort equation (PCE) is used to determine an individual's 10-year risk of atherosclerotic cardiovascular disease (ASCVD) but it does not identify all individuals at high risk 1,2 leading to missed opportunies to intervene and prevent adverse health outcomes. Strong evidence shows a substantial proportion of coronary artery disease (CAD) is attributable to genetic factors [3][4][5][6] which are not currently considered in the PCE. The integration of such genetic risk factors into the primary prevention setting remains limited and the cost-effectiveness is unknown.…”