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Researchers at Chalmers University of Technology in Sweden have identified biological mechanisms that may explain why some people develop heart disease even after lowering their bad cholesterol to recommended levels
The findings suggest that other fat-carrying particles in the bloodstream can contribute to cardiovascular damage through inflammatory processes and changes in blood vessel walls, highlighting potential new approaches to preventing heart disease.
Cardiovascular diseases remain among the world’s leading causes of death, claiming nearly 17.9 million lives annually, according to the World Health Organization (WHO). Heart attacks and strokes account for more than 80% of these deaths.
Lowering low-density lipoprotein (LDL), commonly known as bad cholesterol, is an established way to reduce the risk of heart attacks. However, some patients continue to develop coronary heart disease despite achieving recommended LDL levels, suggesting that other factors contribute to the remaining risk.
“For this study, we wanted to understand what happens beyond the accumulation of cholesterol in artery walls, whether different fat-carrying particles can damage the blood vessels differently and why the remaining risk of heart disease still occurs,” said Jakub Morze, lead author and a postdoctoral researcher at Chalmers University of Technology.
The research examined three types of fat-carrying particles: LDL, triglyceride-rich lipoproteins (TRL) and lipoprotein(a), or Lp(a). All three can contribute to cholesterol deposits in artery walls, but they may affect cardiovascular health through different biological mechanisms.
To investigate these differences, the scientists used proteomics analysis, a technique that examines proteins in biological samples to identify changes associated with disease.
They analysed nearly 3,000 blood proteins and compared the findings with genetic information and long-term health records. This enabled them to identify protein patterns associated with different lipoprotein particles and their potential effects on blood vessels.
One of the most significant findings was the substantial similarity between the protein patterns associated with TRL and Lp(a). These overlapping patterns were also linked to the subsequent development of heart disease.
The researchers found that proteins associated with these particles could attract immune cells, potentially promoting inflammation and structural changes in blood vessel walls. This suggests that TRL and Lp(a) may contribute to cardiovascular disease through shared inflammatory and vascular processes, rather than solely through cholesterol accumulation.
LDL, by contrast, showed a different protein pattern, with its associated proteins primarily linked to cholesterol accumulation in artery walls.
“The overlap for TRL and Lp(a) is one of the most interesting findings,” Morze said. He added that the results suggest these particles may affect some of the same inflammatory and vascular processes, potentially helping researchers identify more targeted approaches to prevention.
The findings could improve understanding of why some people remain at risk of heart disease even after successfully lowering LDL cholesterol. They may also help scientists develop more personalised strategies to identify and address cardiovascular risks.
However, further research will be needed to establish how these biological mechanisms can be translated into new preventive treatments.
