Genetics of Coronary Artery Disease: Discovery, Biology and Clinical Translation !

Genetics

Coronary artery disease is the leading global cause of mortality. Long recognized to be heritable, recent advances have started to unravel the genetic architecture of the disease. Common variant association studies have linked approximately 60 genetic loci to coronary risk. Large-scale gene sequencing efforts and functional studies have facilitated a better understanding of causal risk factors, elucidated underlying biology and informed the development of new therapeutics. Moving forwards, genetic testing could enable precision medicine approaches by identifying subgroups of patients at increased risk of coronary artery disease or those with a specific driving pathophysiology in whom a therapeutic or preventive approach would be most useful.

• Coronary artery disease is a heritable disorder that remains the leading cause of global mortality despite advances in treatment and prevention strategies. Human genetics studies have started to unravel the genetic underpinnings of this disorder.
• Gene discovery efforts have rapidly transitioned from family-based studies (for example, those that led to the discovery of familial hypercholesterolaemia) to large cohorts that facilitate both common and rare variant association studies.
• Common variant association studies have confirmed ∼60 genetic loci with a robust association with coronary disease, the majority of which are of modest effect size and in non-coding regions. Rare variant association studies have linked inactivating mutations in at least nine genes with risk of coronary artery disease.
• Human genetics and large-scale biobanks can facilitate drug development for coronary artery disease by highlighting causal biology and helping to understand the phenotypic consequences of lifelong deficiency of a given protein.
• Genomic medicine may provide patients and their health care providers with genetic data that will aid in coronary artery disease prevention and treatment.
• Genome editing to introduce mutations that are protective against coronary artery disease into the population could prove curative with a one-time injection, although substantial additional work is needed to confirm efficacy and safety, and to address the underlying ethics.

Observational epidemiology and translational research efforts have led to significant progress in improving the understanding of the pathophysiology underlying coronary artery disease (CAD). Prevention and treatment strategies developed on the basis of this knowledge led to a >50% decrease in age-adjusted CAD mortality rate in the United States between 1980 and 2000. However, despite these advances, CAD remains the leading global cause of mortality. Current predictions estimate that more than 900,000 individuals in the United States will suffer a myocardial infarction (heart attack) or die of CAD this year.

This review outlines research efforts to understand the genetic drivers of CAD, the role of human genetics in catalysing CAD drug discovery efforts and the promises and challenges of integrating genetic information into routine clinical practice.

Read More »

Blood Vessel-Forming Protein Could Offer Alternative to Heart Bypass Surgery

For patients with severe coronary artery disease, heart bypass surgery can reduce the risk of heart attack and improve overall quality of life. Now, researchers report the possibility of a new treatment that may be even more beneficial, without the surgery.

Coronary artery disease (CAD) is the most common form of heart disease in the United States, responsible for more than 370,000 deaths in the country every year.

The condition arises when plaque builds up in the coronary arteries, partially or fully blocking the flow of oxygen-rich blood to the heart muscle. This blockage can cause heart attack, angina - severe chest pain - and, over time, heart failure.

While lifestyle changes - such as adopting a healthy diet and regular physical activity - are considered key to improving CAD, some patients may require heart bypass surgery, which can help restore blood flow to the heart.

But, as with all surgery, it has its risks. These include chest wound infection, bleeding, stroke, heart attack, and kidney or lung failure.

Read more: Blood Vessel-Forming Protein Could Offer Alternative to Heart Bypass Surgery

Researchers say the protein AGGF1 could be a promising treatment for coronary heart disease and
heart attack.

Source: medicalnewstoday

MCQ 6. A Male Patients with Proven Coronary Disease

MCQ 6. A very high percentage of male patients with proven coronary disease and/or raised lipid levels had an increased level of "pre-beta" lipoproteins in their blood.

What is also referred to as these lipoproteins?
a. HDL
b. VLDL
c. LDL
d. Lipo B

Answers

Testosterone therapy by Shots and Gel Protects Men With Coronary Artery Disease from Heart Attack Risks.

Last year, the Food and Drug Administration required manufacturers of testosterone products to add new label information warning of a possible increased risk of heart attacks and strokes. A new study suggests this may be both unnecessary and unhealthy for some men. Testosterone therapy or T therapy helped men with preexisting coronary artery disease reduce their risks of strokes, heart attacks, and even death.

In fact, the men who did not receive testosterone as part of their treatment were 80 percent more likely to suffer an adverse event, such as a heart attack, than those taking T.

Testosterone is a sex hormone that is commonly thought to regulate sex drive, bone mass, fat distribution, muscle mass and strength, and to be responsible for the production of sperm and red blood cells in men. As men age, they generally make less testosterone at a rate of about 1 to 2 percent per year. A man in his 70s may have half the testosterone he had at age 20.

Though this may be normal, some men feel the effects more strongly than others. Low testosterone levels may contribute to depression, decreased bone density, increased body fat, insomnia, and diminished sexual desire.

Read more: Testosterone therapy by Shots and Gel Protects Men With Coronary Artery Disease from Heart Attack Risks.

Source: medicaldaily