A groundbreaking new tool created by an international team of scientists could help doctors spot people at higher risk for heart disease long before symptoms appear.
The tool focuses on genetic differences linked to high levels of “bad” cholesterol, also known as LDL, which can lead to clogged arteries and life-threatening heart problems.
The research, led by scientists at the University of Pittsburgh School of Medicine, was published in the journal Science. It aims to give doctors a clearer picture of who might be at risk of heart attacks or strokes due to their genes—not just lifestyle factors like diet or exercise.
Heart disease remains the number one cause of death in the United States, taking nearly 700,000 lives each year. While healthy habits like staying active and eating well are important, genes play a big role too.
Some people are born with a tendency to build up fatty plaque in their arteries, especially if they carry certain changes in the gene responsible for controlling LDL levels.
LDL stands for low-density lipoprotein. In normal amounts, it helps transport cholesterol, which is needed for building cells and making hormones and vitamins like vitamin D.
But when LDL levels get too high—especially due to a weak or faulty LDL receptor—the cholesterol can stick to artery walls, blocking blood flow and raising the risk of heart attacks.
Dr. Frederick Roth, the lead scientist on the project, said that even people with normal LDL numbers could still be at risk if they carry harmful genetic variants that affect how well their bodies clear LDL from the blood.
Identifying those variants early could allow doctors to take action, such as starting cholesterol-lowering medications or lifestyle changes, before serious problems develop.
To build their new resource, the team studied nearly 17,000 different changes in the LDL receptor gene. They also looked at how each of those changes affects the shape and function of the receptor protein itself. The result is a detailed chart that scores each variant based on how badly it affects the receptor’s ability to remove LDL from the bloodstream.
This tool could be a game changer for doctors who often come across genetic variants they don’t fully understand. Dr. Dan Roden of Vanderbilt University Medical Center, who co-authored the study, explained that these variant scores could increase the number of diagnosed cases of inherited high cholesterol tenfold.
The effort is part of a larger global project called the Atlas of Variant Effects Alliance, which includes more than 500 scientists from 50 countries. Their mission is to map how different genetic changes impact disease, making it easier for doctors to understand genetic test results and take action.
The study also made an unexpected discovery. Some LDL receptor variants were especially sensitive to high levels of VLDL, a type of fat particle that is a larger cousin of LDL. In those cases, VLDL seemed to block the receptor from working properly. The researchers now want to dig deeper to understand what this means for patients.
Dr. Daniel Tabet from the University of Toronto, the lead author, said this finding was surprising and exciting. Other key contributors included Dr. Atina Coté from Sinai Health in Toronto, Dr. Calum MacRae from Brigham and Women’s Hospital, and Dr. Megan Lancaster from Vanderbilt, who helped link the genetic findings to real-world heart health data.
Much like how BRCA1 gene testing has helped women manage their breast cancer risk, this new tool could help people manage their heart health by understanding their genetic risks early. With continued research and clinical use, it could help save countless lives.
If you care about heart health, please read studies that vitamin K helps cut heart disease risk by a third, and a year of exercise reversed worrisome heart failure.
For more health information, please see recent studies about supplements that could help prevent heart disease, stroke, and results showing this food ingredient may strongly increase heart disease death risk.
The study is published in Science.
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