A new international study has found that a simple blood test measuring two specific lipoprotein markers could offer a significantly more accurate assessment of an individual’s risk of heart disease than the standard cholesterol test. The research, led by scientists from Chalmers University of Technology (Sweden) and Harvard University (USA), could pave the way for improved early detection and prevention of cardio-vascular disease (CVD), the leading cause of death worldwide.
For nearly 60 years, the standard method for identifying individuals at risk of cardio-vascular problems has been to measure cholesterol levels in blood. However, this new study, the largest of its kind, shows that measuring the number of cholesterol-carrying particles—specifically those containing a protein called apolipoprotein B (apoB)—provides a more precise indication of cardio-vascular risk.
“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,” said Dr Jakub Morze, lead author of the study and a post-doctoral fellow at Chalmers.
Why Early Detection Matters
According to the World Health Organization (WHO), cardio-vascular diseases are the number one cause of death globally. Most cases could be prevented by addressing behavioural and environmental risk factors such as smoking, unhealthy diets and physical inactivity. That makes early and accurate detection of heart disease risk critical, so that preventive measures or treatments can begin before severe complications arise.
One of the most commonly cited risk factors for heart disease is high blood cholesterol. Cholesterol is a fat-like substance that is essential for various bodily functions, including building cell membranes and producing certain hormones and vitamins. However, when cholesterol levels are too high, the excess can accumulate on the walls of blood vessels, forming plaques. These plaques can eventually rupture causing blood clots that can block arteries and lead to heart attacks or strokes.
Cholesterol is transported through the bloodstream by particles called lipoproteins. These come in different forms, primarily divided into four main classes. Three of these carry a protein called apoB on their surface which is associated with harmful effects. These lipoproteins are commonly referred to as ‘bad cholesterol’ carriers because they can deposit cholesterol into artery walls. The fourth class, high-density lipoproteins (HDL), is known as ‘good cholesterol’ because it helps remove excess cholesterol and transport it back to the liver for disposal.
Shifting the Focus to Lipoprotein Carriers
Traditionally, cholesterol levels have been measured directly in blood samples to assess heart disease risk. But cholesterol cannot circulate or exert damaging effects on blood vessels without its carrier lipoproteins. This has led researchers to question whether measuring the number of these carriers might offer a better gauge of cardio-vascular 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,” said Dr Morze. “So, the aim of this study was to determine the importance of these different parameters.”
To answer this, the researchers turned to the UK Biobank, a large-scale biomedical database that includes health data from more than 500,000 people. They focused on 200,000 individuals who had no prior history of heart disease, measuring the number and size of different lipoproteins in their blood. In particular, they studied those carrying apoB which is present on all the main ‘bad cholesterol’ particles.
The team followed participants over a span of up to 15 years to see which individuals went on to experience heart attacks or other forms of cardio-vascular disease. Their analysis was further validated in a separate Swedish cohort study called ‘Simpler’, strengthening the credibility of their findings.
ApoB Outperforms Traditional Tests
The results were clear: the total number of apoB-containing lipoproteins was the strongest predictor of heart disease risk—stronger than total cholesterol or even LDL-C (low-density lipoprotein cholesterol) which is currently used in most clinical risk assessments.
“We found that apoB is the best marker when testing for risk of heart disease,” said DrMorze. “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.”
The Role of Lipoprotein(a)
The study also revealed that another lipoprotein, lipoprotein(a)—which also contains apoB—plays a key role in cardio-vascular risk. While lipoprotein(a) accounts for less than 1% of all ‘bad cholesterol’ particles in most people, its levels are genetically inherited and can be extremely elevated in some individuals, leading to significantly higher risk.
Although the size and type of lipoprotein particles did not significantly alter risk overall, the total number of apoB-containing particles and the presence of high levels of lipoprotein(a) were found to be critical markers.
“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,” said Prof Clemens Wittenbecher, one of the authors of the study and assistant professor of precision medicine and diagnostics at Chalmers. “The blood test for these two markers is commercially available now and would be cheap and easy enough to implement.”
Given the scale and strength of the study, these findings may influence future guidelines for cardio-vascular screening. By moving beyond cholesterol alone and considering apoB and lipoprotein(a), doctors could provide more precise risk assessments and potentially intervene earlier for high-risk patients.
The researchers stress that, while conventional cholesterol tests will likely remain useful, incorporating apoB testing into routine check-ups could help identify hidden risk in a significant portion of the population—especially since the test is simple, affordable and already accessible in many countries.
