Good HDL cholesterol and heart disease

10 March 2016        

John Danesh

A new discovery, from researchers we fund, challenges existing theories of 'good' cholesterol and risk of heart disease.

The findings, published today in the journal Science, could help scientists develop new heart disease treatments which target how HDL is handled, helping to reduce their risk of heart attack. Researchers may also now move away from potentially ineffective HDL-raising drugs to treat heart disease onto a more targeted approach.

Coronary heart disease is responsible for nearly 70,000 deaths every year, almost entirely through heart attacks, making it the UK's single biggest killer. The condition involves the build-up of fatty material, or plaque, in the coronary artery walls through a process called atherosclerosis. If large quantities accumulate in the vessel walls, blood flow to the heart can become restricted or blocked, increasing risk of a heart attack.

What is 'good' cholesterol?

Molecules called high density lipoproteins are important for the transport of cholesterol (collectively known as HDL-C) to the liver for breakdown and removal. Because these molecules transport cholesterol away from the arteries to the liver, HDL-C is commonly viewed as 'good' cholesterol and has been associated with reduced risk of coronary heart disease.

This research follows findings from our researchers into new genes involved increasing heart attack risk.

What did the international team find?

Professor Nilesh SamaniContrary to previous evidence linking 'good' cholesterol to reduced risk of coronary heart disease, researchers we fund, including BHF Professor Sir Nilesh Samani (pictured right) at the University of Leicester and BHF Professor John Danesh (pictured above) at the University of Cambridge, have found a mutation, in a gene called SCARB1, associated with high HDL levels and an increased risk of heart disease in people with this mutation.

They found that this mutation led to an increased relative risk of coronary heart disease in these people of up to 80 per cent – a figure almost the same as the risk caused by smoking or diabetes.

New heart disease treatments

Dr Adam Butterworth, Lecturer in Cardiovascular Epidemiology at the BHF-funded University of Cambridge Cardiovascular Epidemiology Unit and co-investigator of this study, said:

"We found that people carrying a rare genetic mutation causing higher levels of the so-called 'good' HDL-cholesterol are, unexpectedly, at greater risk of heart disease.

"This discovery could lead to new drugs that improve the processing of HDL-C to prevent devastating heart attacks."

Handling of HDL more important than levels

Our Medical Director, Professor Peter Weissberg, said: 

"This is an important study that sheds light on one of the major puzzles relating to cholesterol and heart disease, which is that despite strong evidence showing HDL-C reduces heart disease risk, clinical trials on the effects of HDL-C-raising drugs have been disappointing. 

"These new findings suggest that the way in which HDL-C is handled by the body is more important in determining risk of a heart attack than the levels of HDL-C in the blood."

Research like this is important because by understanding the underlying biology that links HDL-C with heart attacks that we can develop new treatments to prevent them. The discovery could trigger further research into the SCARB1 gene to identify new treatments that help prevent people dying suddenly from a heart attack.

Fund future findings

Alongside support from the BHF, the research was funded in the USA by the National Center for Research Resources and the National Center for Advancing Translational Sciences of the National Institute of Health (NIH)Dr Daniel Rader at the University of Pennsylvania Perelman School of Medicine led the research in collaboration with the BHF-funded teams at Cambridge and Leicester.

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