Heart disease: researchers propose alternative to cholesterol testing

Measuring cholesterol levels in the blood has been used to identify individuals at high risk of cardiovascular disease for sixty years. But a new study, led by Chalmers University of Technology in Sweden and Harvard University in the USA, finds that a combination of two lipoprotein markers, measured in a simple blood test, gives more accurate information about individual risk of heart disease.

The authors say that instead of focusing on cholesterol itself, the focus should be on the protein that transport cholesterol. When cholesterol levels are too high, it can accumulate in the walls of blood vessels, forming deposits known as plaques. If a plaque ruptures, a clot can rapidly form and block the vessel entirely, leading to heart attack or stroke.

Cholesterol and other fats are carried through the blood by specialised particles called lipoproteins, which are divided into four main classes. Three of these classes have a special protein on their surface called apolipoprotein B (apoB). When present in excess, these lipoproteins can deposit cholesterol in the walls of blood vessels.

Testing for lipoprotein carriers

‘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 Dr Jakub Morze, lead author of the study and a postdoctoral fellow at Chalmers.

The researchers analysed 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

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,’ Dr Morze says. ‘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 researchers concluded that the total number of 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 showed that another 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. ‘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,’ says 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.’