Simple Blood Test Better Predicts Heart Disease Risk

Cardiovascular diseases (CVDs) are the primary cause of death worldwide. A large proportion of these cases could be prevented by addressing lifestyle and environmental factors such as smoking, poor diet, and lack of physical activity. Early identification of risk factors is crucial to initiate effective preventive measures or management strategies. One of the major modifiable risk factors for cardiovascular disease is high blood cholesterol. Cholesterol is a fat-like substance in the blood that plays a crucial role in the formation of cells and the production of certain vitamins and hormones. However, when cholesterol levels become excessively high, it can accumulate in the walls of blood vessels, forming deposits known as plaques. If a plaque ruptures, it can lead to the rapid formation of a clot that blocks the vessel, potentially causing a heart attack or stroke. Cholesterol and other fats are transported through the blood by specialized particles called lipoproteins, which are classified into four main types. Three of these types have a specific protein on their surface called apolipoprotein B (apoB). When these lipoproteins are present in excess, they can deposit cholesterol in the walls of blood vessels, leading to what is commonly referred to as "bad cholesterol." In contrast, the fourth class of lipoproteins aids in removing excess cholesterol from the bloodstream and transports it back to the liver, often termed "good cholesterol" due to its protective effects.

For nearly 60 years, measuring cholesterol levels in the blood has been the standard method for identifying individuals at high risk of cardiovascular disease. To assess the short-term risk of heart disease, doctors typically evaluate whether the levels of "bad cholesterol" particles are sufficiently high to pose a risk. This is usually done by measuring cholesterol levels in a blood sample. However, because cholesterol cannot circulate or cause harm without its lipoprotein carrier, researchers have increasingly focused on measuring the lipoproteins responsible for transporting “bad cholesterol,” as they are considered a better predictor of future cardiovascular disease risk. In a new study led by Chalmers University of Technology (Gothenburg, Sweden) and Harvard University (Cambridge, MA, USA), researchers have demonstrated that a combination of two lipoprotein markers, measured in a simple blood test, can provide more accurate information about an individual's risk of heart disease than the traditional cholesterol test, potentially saving lives.

In their study, the researchers analyzed blood samples from over 200,000 individuals in the UK Biobank, all of whom had no prior history of heart disease, to measure the number and size of different cholesterol-carrying lipoproteins. They specifically focused on lipoproteins that carry a protein called apoB, which is present on all “bad cholesterol” carriers. By tracking the participants for up to 15 years, they identified the patterns of lipoprotein types and sizes most strongly associated with future heart attacks. These key findings were validated in a separate Swedish cohort study called ‘Simpler’. The combination of advanced blood profiling, large-scale prospective data, and independent replication provided the most comprehensive evaluation of how “bad cholesterol” lipoproteins contribute to the development of heart disease. The researchers concluded that apoB was the most reliable marker for assessing heart disease risk.

The researchers found that the total number of ‘bad cholesterol’ lipoproteins was the most crucial factor in determining the risk of future heart disease. Other factors, such as the size or type of lipoprotein, had minimal impact on overall risk. However, the study also revealed that another type of “bad cholesterol” lipoprotein, called lipoprotein(a), plays a significant role and should also be measured. The levels of lipoprotein(a) are largely genetically inherited in most individuals and typically make up less than 1 percent of all “bad cholesterol” lipoproteins in the general population. However, in certain individuals, these levels can be extremely high, greatly increasing the risk 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,” said Jakub Morze, lead author of the study and a postdoctoral fellow at Chalmers. “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.”

“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,” added Clemens Wittenbecher, one of the authors of the study and Assistant Professor of Precision Medicine and Diagnostics at Chalmers.

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Chalmers University of Technology
Harvard University