People at risk of early heart disease may be identified through health screening and genetic studies.

 

People at risk of early heart disease may be identified through health screening and genetic studies.

According to new research published today in the Journal of the American Heart Association, an open access, peer-reviewed journal of the American Heart Association, more than 1 million U.S. adults may carry a gene for familial hypercholesterolemia, a common genetic disorder that causes elevated low-density lipoprotein (LDL) cholesterol, also known as "bad cholesterol," which can lead to premature heart attack or death.

Familial hypercholesterolemia, according to the American Heart Association, is a hereditary genetic condition that affects how the body recycles harmful cholesterol. As a result, LDL levels in the blood remain extremely high; in extreme situations, levels in adults can exceed 190 milligrammes per deciliter (mg/dL). LDL cholesterol should be less than 100 mg/dL. Total blood cholesterol levels, on the other hand, should be assessed alongside other recognised cardiovascular disease risk factors.

In the United States, about one in every 250 persons carries at least one gene for familial hypercholesterolemia. If the condition is not treated, the average age for a first heart attack among people with one familial hypercholesterolemia gene is 50 years for men and 60 years for women, but the average age for a first heart attack in the general population is 66 years for men and 72 years for women. A considerably lower percentage of persons receive two genes for familial hypercholesterolemia (one from each parent), and they suffer from far more serious consequences, such as far greater bad cholesterol and heart disease, which often begin in childhood or adolescence.

"Most people with familial hypercholesterolemia are not diagnosed until they are in their 50s. If a young adult is diagnosed with familial hypercholesterolemia, they will almost certainly benefit from more aggressive treatment to prevent heart attacks and strokes "Brandon K. Bellows, Pharm.D., M.S., an assistant professor of medical sciences at Columbia University in New York City, is the study's lead author.

If the risk of heart disease remains low, the American Heart Association recommends that all persons aged 20 and up have their cholesterol and other traditional heart risk factors evaluated every four to six years. Screening for familial hypercholesterolemia is not routine and necessitates the proper collection of additional clinical data or diagnostic genetic testing. Although genetic testing is accessible, it may be out of reach for many people who do not have health insurance. According to a scientific statement released by the American Heart Association in 2020, genetic testing for cardiovascular diseases should be reserved for people who have a confirmed or suspected diagnosis of a condition, as well as those who have a known disease-causing gene variant in their family.

Researchers in this study calculated how many people with familial hypercholesterolemia could be identified if all adults were screened using clinical factors like cholesterol levels and the presence of early heart disease in an individual or close family member (parent, sibling, or child), both with and without genetic testing.

Clinical data and genetic test results for around 50,000 people aged 40 to 69 were obtained from the UK Biobank between 2006 and 2010. Based on their clinical data, they were able to assess the likelihood of each individual possessing a familial hypercholesterolemia genetic variant. The researchers applied the relationships observed in the UK Biobank to a dataset of nearly 40,000 adults (ages 20 and older) from the National Health and Nutrition Examination Survey to estimate familial hypercholesterolemia genetic variants in a U.S. population that did not have genetic test results (NHANES).

The UK Biobank is a vast biological database that contains genetic and health information on half a million people in the UK. NHANES is a nationally representative sample of adults in the United States that was collected from 1999 to 2016 and includes persons of various racial and ethnic backgrounds.

The researchers used the Dutch Lipid Clinic Network criteria to classify people with definite or probable familial hypercholesterolemia based on a scoring system that included a personal history of early heart disease; a family history of early heart attack or heart-related chest pain (angina) in a sibling, parent, or child; and high untreated bad cholesterol levels, with more points awarded for higher cholesterol levels.

The following are the estimated results using this multi-step approach:

Clinical criteria alone identified 3.7 cases of familial hypercholesterolemia per 1,000 persons evaluated, but genetic testing alone identified 3.8 cases per 1,000 adults screened.

When clinical criteria and genetic testing were combined, 6.6 cases of familial hypercholesterolemia were discovered for every 1,000 persons tested.

Clinical criteria alone identified 1.3 cases of familial hypercholesterolemia per 1,000 individuals tested in young adults aged 20 to 39 years, rising to 4.2 cases per 1,000 when genetic testing was included.

"We need to do more to encourage screening programmes for familial hypercholesterolemia," Bellows added. "Clinical variables and genetic testing should be used to screen for familial hypercholesterolemia. Individuals who have high cholesterol levels or who have a family member who has had a heart attack at a young age should be tested for familial hypercholesterolemia. The greatest method to lower the risk of an early heart attack or stroke is to diagnose and treat familial hypercholesterolemia as soon as possible."

Given the increased number of people found through genetic testing in addition to clinical criteria, many people with a genetic mutation may not present with the conventional clinical presentation at the time of screening. "Other research have confirmed this. The best approach to detect these people may be through universal screening programmes that include genetic testing. However, because this may be impractical, screening select populations, such as young adults, may enable for earlier detection and treatment of familial hypercholesterolemia "Bellows explained.

The study was limited by the fact that the U.K. biobank sample consisted primarily of older persons (ages 40-69) who self-identified as white. As a result, the UK Biobank dataset analysis may not be applicable to varied or younger populations.

Follow-up studies are being conducted to answer questions about the most useful and cost-effective strategies for familial hypercholesterolemia screening, such as the best age to begin screening and whether there is a difference in the number of heart attacks and strokes based on screening method, such as universal screening vs. screening of close family members with familial hypercholesterolemia.