The findings go against previous evidence that suggests those with more HDL-C are at lower heart disease risk. The results also suggest supplements such as niacin and omega-3 fatty acids that increase HDL-C levels may not be as beneficial to the heart as previously thought.
Coronary heart disease (CHD) causes nearly 70,000 deaths every year in the UK. The condition is characterised by the build-up of fatty material in the coronary artery walls. Blood flow to the heart can become restricted or blocked, increasing risk of a heart attack.
Researchers from the University of Cambridge and Leiden University in the Netherlands looked at subjects with an unusual genetic mutation in the SCARB1 gene. The mutation is called the P376L variant and causes high levels of HDL-C.
They began by taking the DNA of 328 subjects with very high levels of HDL-C in the blood and compared them to 398 people with relatively low HDL-C. As the P376L variant they found was so rare, they then looked at its effects on HDL-C and heart disease in more than half a million additional people.
The team found that people with this mutation, who had elevated levels of HDL-C, also had an 80% increased risk of the disease. This figure is similar to the increased risk caused by smoking.
“Large-scale collaborative research like this paves the way for further studies of rare mutations that might be significantly increasing people’s risk of a deadly heart attack,” said Dr Adam Butterworth, from the Cardiovascular Epidemiology Unit, University of Cambridge, and co-investigator of this study.
“These discoveries also give researchers the knowledge we need to develop better treatments.”
The study is one of the first to show high levels of 'good' cholesterol are linked to a higher risk of heart disease, challenging current thinking and studies which suggest otherwise.
The role of niacin
The study also brings into focus the role of niacin, a supplement that is used routinely by people looking to control their cholesterol levels or prevent heart disease.
“Niacin has been shown to substantially raise HDL-cholesterol levels but the mechanism is not clear,” said Keith Frayn, emeritus Professor of human metabolism at the University of Oxford.
“Niacin has been shown to reduce the risk of CHD in some studies, although for niacin this has not been borne out in larger studies.
“It is worth noting that exercise both increases HDL and reduces the risk of heart disease,” noted Dr Tim Chico, reader in cardiovascular medicine and consultant cardiologist at the University of Sheffield.
“These results suggest that the beneficial effect of exercise is probably not caused by higher HDL levels, although more research is needed to fully understand the complex relationship between HDL and risk of heart disease.”
Published online ahead of print, DOI: 10.1126/science.aad3517
“Rare Variant in Scavenger Receptor BI raises HDL Cholesterol and Increases Risk of Coronary Heart Disease.”
Authors: Zanoni, P et al.