Polygenic score
Influential genes: FBN2, MMP13
Mutations in the FBN2 gene have been implicated in the development of CAD and other connective tissue disorders.
MMP13 is a gene linked to coronary artery disease (CAD), where the coronary arteries narrow, restricting blood flow to the heart.
Coronary artery disease (CAD) is a dynamic disease and as such it is characterized by a progressive build-up of deposits (plaques) in the walls of coronary arteries - blood vessels - which are responsible for the transport of oxygenated blood to the heart muscle itself (myocardium). This process is called atherosclerosis and it can lead to the narrowing or complete blockage of the arteries. In addition, the plaques can also rupture, causing platelets to clump together and form a blood clot that leads to further restriction of the flow. This clot sometimes breaks up on its own, but sometimes it completely blocks the already narrowed flow, thus definitively depriving the heart muscle of oxygen and nutrients, and causing a heart attack. (1, 4, 5)
Atherosclerosis is the leading mechanism behind CAD. The current evidence suggests that CAD begins with damage or injury to the inner layer (intima) of the coronary artery. This damage can be caused by a number of factors, the most common being toxins from cigarette smoke, high blood pressure, high cholesterol, obesity, or diabetes. Subsequently, fatty deposits made up of cholesterol, blood cells, and other small particles begin to accumulate at the site of damage, forming an atherosclerotic plaque. (5)
Fig 1: Atherosclerosis | Cleveland Clinic
CAD usually begins in childhood and first becomes clinically apparent in middle to late adulthood - depending on the presence of various risk factors and the rate of progression, which varies from person to person. (3)
Because of its dynamic nature, the disease can present itself in variable ways, which can be divided into two big groups - acute coronary syndromes (ACS) and chronic coronary syndromes (CCS). (1)
CHRONIC CORONARY SYNDROMES
Patients diagnosed with CCS most often have a history of stable angina pectoris with either concomitant risk factors for atherosclerosis or a personal history of atherosclerotic cardiovascular disease. (6)
Angina pectoris, also known as angina, refers to a condition accompanied by uncomfortable, most often painful chest sensations caused by inadequate coverage of the heart's oxygen requirements. Angina can be stable or unstable. If it is stable, it manifests predictably and at the same level of exertion; in addition, symptoms subside with rest or after administration of nitroglycerin. (6) Unstable angina refers to either the first manifestation of the disease or any subsequent worsening of angina (e.g. newly developed exertional angina, sudden aggravation of existing AP, an attack of AP at rest)
ACUTE CORONARY SYNDROMES
Patients diagnosed with ACS have either suspected or confirmed acute myocardial ischemia (restriction in blood supply) or infarction (irreversible death of cells). The common basis of all forms of ACS is an unstable, ruptured, or otherwise damaged atherosclerotic plaque in a coronary artery. As explained above, blood clotting and thrombus formation occur as a result, leading to either short-term acute myocardial ischemia without cell death (unstable AP) or prolonged acute ischemia with a transition to necrosis (myocardial infarction). The three traditional types of ACS are:
Coronary artery disease remains a leading cause of death worldwide and the most prevalent cardiovascular disorder. (8) According to recent studies, the worldwide prevalence of CAD is still on the rise. The estimated 2020 prevalence of 1,655 cases per 100,000 population (approx. 1:60) is projected to exceed 1,845 cases (approx. 1:54) by 2030. The highest prevalence of the disease is recorded in Eastern Europe. (8)
With such a high prevalence of this disease, it is obvious that understanding its risk factors is essential to prevent possible consequences as much as possible, especially because many of them can be modified. (2)
Other possible risk factors are the subject of ongoing studies. These might include high levels of hs-CRP, sleep apnea, high triglycerides, increased levels of homocysteine, alcohol consumption, autoimmune diseases, or preeclampsia. (5)
Coronary artery disease (CAD) is a complex and common disorder. Back in the 1950's it was hypothesized that CAD might be a heritable condition, and this was later confirmed by a study of over 20,000 Swedish twins. There is an existing increased risk of developing CAD among close relatives. Since 2007, researchers have been using larger sample cohorts in their studies to examine the genetic nature of the condition. That resulted in around 60 confirmed genetic loci (gene position on the chromosome) for the disorder. Recently, three large CAD consortia and collaborations across the world presented 321 loci showing significant association with CAD. (9, 10)
Studies and research have demonstrated that the development comes from the cumulative effect of many common risk alleles each with a small effect, rather than from the effect of rare variants with large effects. This progress has been enabled by technological advances, such as high-throughput DNA microarray technology. (11)
Here in Macromo, polygenic risk scores are used to determine the genetic risk. The polygenic risk score (PRS) is an estimate of the probability that an individual carries a given trait based on genetics, without considering environmental factors. Variants across their genome are summed and weighted according to their effect on the disease or trait. (12)
As the plaque builds up, less and less blood is supplied to the heart muscle, especially when the demand for oxygen increases during physical activity. Initially, it may not cause any symptoms, but as the plaque grows, several symptoms may appear:
All in all, if left untreated, coronary artery disease can (over time) lead to severe complications, namely:
The diagnosis of coronary artery disease is most often made after the first symptoms appear and the patient seeks medical attention. To diagnose CAD, several tests and methods may be used depending on the urgency of the situation: (4)
The best course of treatment varies from patient to patient depending on the presence of modifiable and other risk factors and the severity of coronary artery narrowing. (4, 5)
Lifestyle changes not only help people already diagnosed with CAD, but also everyone who wants to prevent the disease altogether. To lower the probability of CAD: (5)
It is estimated that CAD is the cause of approximately one in four deaths and is therefore the most common cause of death in the United States. According to the WHO, it is still the world's biggest killer, being responsible for 16% of all deaths worldwide. It is associated with approximately 17.8 million deaths per year. (13)
The coronary disease cannot technically be cured completely. However, with the right approach, it is possible to slow its progress and prevent it from worsening. (4)
Get the guidelines for a healthier and longer life. With Macromo tests, you'll learn your health risks and how to prevent them.
Continue to Shop