Sahana Chibber and Kendall Lee

 

Abstract

Coronary artery disease (CAD) is a condition in which oxygen levels in the heart are deficient due to damage of an artery lining. CAD is one of the most widespread diseases due to the many factors that are a result of daily life. This review explains the genetic and hereditary components of CAD susceptibility and touches upon the outside factors that play a role as well. It examines the specific alleles on the LPA gene that correlate with increased lp(a) levels, in turn causing raised CAD risk. Differing lp(a) levels can be linked to different ethnic groups, directly affecting CAD risk. Amounts of larger weights of preventive molecules such as LpA-I present in arteries can also determine CAD risk. Identification of CAD risks can help increase treatment and advance studies on the subject.

 

Introduction

Coronary artery disease (CAD) is the result of an artery's inability to bring sufficient oxygen to the heart. An artery may be restricted due to atherosclerosis, the buildup of plaque or fatty deposits that line the artery. Atherosclerosis occurs when the lining of the artery is damaged, which can be caused by increased cholesterol, blood pressure, or inflammation. This allows the excess plaque and fatty deposits to seep into the blood vessels and impede blood flow. 

CAD is the leading cause of death nationally and affects approximately 5% of adults over the age of 20. Today, convenient access to foods containing high amounts of LDLs – a protein that carries cholesterol to tissues, and can lead to atherosclerosis when excessively present –saturated fats, and trans fats can leave people more predisposed to CAD than they have been previously. However, aside from environmental factors, genetic and hereditary details are important to consider, which will be further discussed in the paper. 

Currently, CAD treatment ranges from lifestyle changes to invasive procedures, none of which guarantee success or can get rid of the disease. Awareness of the causes and risks of CAD are important to know, as well as recognizing hereditary characteristics that may influence one’s chances of CAD. The following review investigates the background of specific genes and their roles in the development of CAD.

 

Source 1

In many cases, impairment of LDL receptors is caused by a mutation in the CASR gene. This gene is also a cause for familial hypercholesterolaemia (FH), a genetic precursor to CAD in later years of life. A study in 2020 by Michael Page and colleagues ran a trial involving patients with indication of possible FH. Only individuals without the mutation in the LDLR, APOB, and PCSK9 genes, three genes that have a direct impact on susceptibility to the disease, were selected. So therefore, people with minimal susceptibility. External factors such as sex, age, hypertension, or smoking status were put into consideration. Accounting for these factors culminated in the conclusion that the specific rs3798220-C allele on the LPA gene was an important indicator of CAD in those suspected to have FH. This allele is a polymorphism, which is a genetic variant that only affects the phenotype subtly. Specifically, rs3798220-C is a risk allele that alone cannot cause CAD, but increases the risk more substantially than other alleles on the LPA gene. The presence of the rs3798220-C allele along with the rs10455872-G, also on the LPA gene, respectively are affiliated with smaller lp(a) particles that show increased risk to CAD. Other documentations of relations between rs10455872-G and CAD show a positive connection. The study concluded that when analyzed alone, the rs10455872-G allele was not found to have an affiliation with increased CAD risk, but when other factors such as hypertension and age were considered, it had an impact.

 

Source 2

Another factor of coronary artery disease, or CAD, is the amount of high-density lipoproteins(HDLs) one has. This discovery is presented in Subclasses of LpA-I in coronary artery disease: distribution and cholesterol efflux ability, which demonstrates how a higher concentration of HDLs can decrease the risk of CAD. This has to do with HDLs’ ability to get rid of unnecessary cholesterol from peripheral cells and move it into the plasma, a process known as cholesterol efflux, that is important to prevent CAD. The source mentions past clinical, epidemiological and metabolic studies that provide evidence for the theory that the particular subclass of an HDL apolipoprotein could be an indicator of CAD risk. The specific study that the source focused on was surveying the amount of LpA-I particles–a type of HDL–through their molecular weight. The subjects included 11 men as a control group, as well as 34 other men who were CAD patients. Essentially, the study resulted in the distinction between three subclasses, L-LpA-I(Large), I-LpA-I(intermediate), and S-LpA-I(small). Multiple factors were also studied, investigating various aspects such as a subject's history of smoking. Additionally, along with LpA-I and HDL-cholesterol levels, triglyceride levels were also observed to place the distinctions between CAD and nonCAD subjects. The study also tracked the relationship between these three investigations, such as, studying whether the concentration of HDL-cholesterol was dependent on the molecular weight of LpA-I. The ultimate conclusion of this study was developing gPAGE, a method that allows researchers to determine subclasses of LpA-I by their molecular weight and determine CAD risk. There was less large LpA-I observed in the CAD group than in the control group, therefore the weight of the present LpA-I can help determine cholesterol efflux in the two groups. L-LpA-I could efficiently and effectively remove cholesterol to prevent CAD, while S-LpA-I is a likely predecessor to the disease.

 

Source 3

 

A new study utilizing the UK biobank’s data, has shown that increased Lipoprotein(a), or Lp(a), levels serve as a possible cause, among other factors, for cardiovascular disease. Written in 2021, The Impact of Race and Ethnicity on Lipoprotein(a) Levels and Cardiovascular Risk by Gissette Reyes-Soffer, ties cardiovascular disease to race and ethnicity through Lp(a) levels, illustrating the variations in Lp(a) measures across racial groups. The article highlights lack of data in some categories, which may lead to slightly inaccurate or biased results. It concluded that, overall, south Asians and Africans tended to have higher Lp(a) levels, increasing those groups’ risk for cardiovascular disease. The author then wrote that, below south Asians and Africans in Lp(a) levels were Europeans, followed by East Asians and Latin Americans. It is important to note, once again, that many groups were not represented in data collection or that data is very limited on some racial groups, such as Latin Americans. This and related research led the National Lipid Association to use a patient’s Lp(a) levels in order to suggest primary and secondary preventative actions. Additionally, many platforms of American endocrinology research now recommend people of south Asian and African descent, particularly with a family history of cardiovascular disease, to get their Lp(a) levels checked.

 

Conclusion

The ongoing efforts in developing a cure for CAD is a significant portion of current research as shown in the studies reviewed. Overall, studies have discovered the effects of race and ethnicity in susceptibility, along with certain genes as well as mutations of certain genes that may increase or decrease CAD risk. Understanding the risk of specific alleles involved with CAD susceptibility is important to develop more personalized treatments. Additionally, CAD awareness among different racial and ethnic groups can help treatment become more accessible and widespread. 

 

Bibliography

Page, M. M., Ellis, K. L., Pang, J., Chan, D. C., Hooper, A. J., Bell, D. A., Burnett, J. R., & Watts, G. F. (2020). Coronary artery disease and the risk-associated LPA variants, rs3798220 and rs10455872, in patients with suspected familial hypercholesterolaemia. Clinica Chimica Acta, 510, 211-215. https://doi.org/10.1016/j.cca.2020.07.029

 

Decossin, C., Castro, G., Derudas, B., Bertrand, M., Fruchart, J. C., & FiÉvet, C. (1997). Subclasses of lpa‐i in coronary artery disease: Distribution and cholesterol efflux ability. European Journal of Clinical Investigation, 27(4), 299-307. https://doi.org/10.1046/j.1365-2362.1997.1020654.x

Reyes-Soffer, G. (2021). The impact of race and ethnicity on lipoprotein(a) levels and cardiovascular risk. Current Opinion in Lipidology, 32(3), 163-166. https://doi.org/10.1097/mol.0000000000000753