Cardiovascular disease remains the world’s top killer, but early detection through better blood testing could dramatically shift outcomes.
A major study reveals that measuring the number of “bad cholesterol” carriers—specifically particles containing apoB—offers a much clearer prediction of heart disease risk than traditional cholesterol tests. Surprisingly, the study also highlights the overlooked importance of lipoprotein(a), a genetically inherited lipid that can sharply elevate risk in some individuals. With easy and affordable blood tests for apoB and lipoprotein(a) now available, a revolution in heart health screening could be within reach.
Early Detection Is Crucial for Cardiovascular Disease Prevention
Cardiovascular diseases (CVDs) are the leading cause of death worldwide, according to the World Health Organization (WHO). Yet, most cases could be prevented by addressing lifestyle and environmental factors such as smoking, poor diet, and lack of physical activity. Detecting risk early is crucial, allowing prevention strategies or treatment to start before serious problems develop.
“This is the largest study of its kind to date, and the results show for the first time the relative importance of the three major families of lipoprotein for the potential risk of heart disease,” says Jakub Morze, lead author of the study and a postdoctoral fellow at Chalmers.
Understanding Good and Bad Cholesterol
High blood cholesterol is one of the most important—and controllable—risk factors for cardiovascular disease. Cholesterol is a fat-like substance that the body needs to build cells and produce certain hormones and vitamins. However, too much cholesterol can build up inside blood vessel walls, forming deposits called plaques. If a plaque ruptures, it can trigger the formation of a blood clot, which may completely block the vessel and cause a heart attack or stroke.
Cholesterol and other fats move through the bloodstream inside special particles called lipoproteins, which are grouped into four main classes. Three of these classes carry a protein called apolipoprotein B (apoB) on their surface. When present in excess, these lipoproteins can deposit cholesterol into blood vessel walls, earning them the nickname “bad cholesterol.” Meanwhile, the fourth class helps remove cholesterol from the blood and return it to the liver for disposal. This group is often known as “good cholesterol” because of its protective effects.
Rethinking Risk Assessment: Lipoprotein Carriers Over Cholesterol Levels
When assessing for near-term risk of heart disease, a doctor needs to determine whether the levels of “bad cholesterol” particles are high enough to be harmful. Currently, this is done by measuring a blood sample for levels of cholesterol. However, since cholesterol cannot circulate or cause damage without its lipoprotein carrier, researchers have increasingly focused on measuring the lipoproteins that carry the ‘bad cholesterol’, as a likely better indicator of future cardiovascular disease risk.
“It was previously unclear if two patients with the same total level of “bad cholesterol,” but that differ in their carrier characteristics (lipoprotein type, size, lipid content), have the same risk of heart disease. So, the aim of this study was to determine the importance of these different parameters,” says Jakub Morze.
ApoB Count Emerges as the Strongest Heart Risk Indicator
The researchers analyzed blood samples from over 200,000 people in the UK Biobank who had no history of heart disease, to measure the number and size of different cholesterol-carrying lipoproteins in the blood. They focused specifically on lipoproteins that carry a protein called apoB, which is found on all the “bad cholesterol” carriers. By following participants for up to 15 years, they examined which patterns of lipoprotein types and sizes were most strongly linked to future heart attacks. Key findings were validated in a separate Swedish cohort study called ‘Simpler’. This combination of advanced blood profiling, large-scale prospective data, and independent replication allowed for the most comprehensive assessment of how ‘bad cholesterol’ lipoproteins contribute to the development of heart disease.
“We found that apoB is the best marker when testing for risk of heart disease. Since apoB indicates the total number of “bad cholesterol” particles measuring it offers a more accurate test than standard cholesterol measures. That does not mean conventional tests are ineffective; they generally perform well. However, in about one in twelve patients, standard cholesterol tests may underestimate heart disease risk, which is important to consider, since 20 – 40 percent of all first-time occurrences of CVD are fatal. By switching to apoB testing, we can improve that accuracy and potentially save lives,” says Jakub Morze.
The Critical Role of Lipoprotein(a) in Heart Health
The researchers concluded that the total number of ‘bad cholesterol’ lipoproteins was the most important factor to consider when testing for future risk of heart disease. Other factors such as size or type of lipoprotein did not affect the potential risk overall.
However, the study also showed that another ‘bad cholesterol’ lipoprotein, called lipoprotein(a) is an important part of the puzzle and should also be tested for. Its levels are genetically inherited in most individuals and represent less than 1 percent of all “bad cholesterol” lipoproteins on average in the general population. However, in some individuals, these values are extremely high, significantly raising heart disease risk.
A New Era for Blood Testing in Cardiovascular Risk Prediction
“Our results indicate that apoB particle count could eventually replace the standard blood cholesterol test in research and healthcare worldwide and that lipoprotein(a) also needs to be tested for to get a better picture of lipid-related CVD risk. The blood test for these two markers is commercially available now and would be cheap and easy enough to implement,” says Clemens Wittenbecher, one of the authors of the study and Assistant Professor of Precision Medicine and Diagnostics at Chalmers.
Reference: “ApoB-containing lipoproteins: count, type, size, and risk of coronary artery disease” by Jakub Morze, Giorgio E M Melloni, Clemens Wittenbecher, Mika Ala-Korpela, Andrzej Rynkiewicz, Marta Guasch-Ferré, Christian T Ruff, Frank B Hu, Marc S Sabatine and Nicholas A Marston, 28 April 2025, European Heart Journal.
DOI: 10.1093/eurheartj/ehaf207
In this study, the researchers observed and analysed data from more than 200,000 people within the UK Biobank, who had no prior history of heart disease, using a technique called nuclear magnetic resonance (NMR) spectroscopy.
The researchers for this study were Jakub Morze, Giorgio E Melloni, Clemens Wittenbecher, Mika Ala-Korpela, Andrzej Rynkiewicz, Marta Guasch-Ferre, Christian T. Ruff, Frank B. Hu, Marc S. Sabatine, and Nicholas A. Marston.
They were active at the following institutions at the time of the study: Chalmers University of Technology and Sahlgrenska Academy at the University of Gothenburg, Sweden; SGMK University, Poland; Brigham and Women’s Hospital and Harvard Medical School, USA; University of Oulu and Biocenter Oulu, Finland; University of Eastern Finland; University of Copenhagen, Denmark; Harvard T.H. Chan School of Public Health, USA.
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2 Comments
If cholesterol is the cause of plaque in the arteries, why is the composition of plaque made almost entirely of clotting tissue?
A clot is the result of plaque blocking the flow in an artery due to the buildup of plaque which is due to the formation of foam cells which, in turn, is due to the uptake (primarily) of modified LDL. Lower LD results in lower foam cell formation and decrease clot formation.