‘Good’ cholesterol doesn’t always lower heart attack risk

Posted by ngi2 at Mar 10, 2016 07:05 PM |
BHF-funded discovery challenges existing theories and offers hope of new drug

Issued by British Heart Foundation on 10 March 2016

Some people with high levels of ‘good’ high density lipoprotein cholesterol (HDL-C) are at increased risk of coronary heart disease (CHD), contrary to earlier evidence that people with more HDL-C are usually at lower heart disease risk (1). This finding comes from an international study involving researchers funded by the British Heart Foundation (BHF).

The discovery, published today in Science (2), could move researchers away from potentially ineffective HDL-raising drugs to treat CHD (3), and lead to the development of new heart disease treatments, helping to reduce their risk of heart attack.

The researchers studied people with a rare genetic mutation in the SCARB1 gene, called the P376L variant, which causes the body to have high levels of ‘good’ HDL-C (4). High levels of ‘good’ cholesterol are commonly associated with reduced risk for CHD (5). Challenging this view, the researchers unexpectedly found that people with the rare mutation, who had increased levels of HDL-C, had an 80 per cent increased relative risk of CHD (6) – a figure almost equivalent to the increased risk caused by smoking.

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 (7). CHD involves the build-up of fatty material, or plaque, in the coronary artery walls. If large quantities accumulate in the vessel walls, blood flow to the heart can become restricted or blocked, increasing risk of a heart attack.

The international team of scientists included BHF-funded researchers BHF Professor Sir Nilesh Samani at the University of Leicester and BHF Professor John Danesh at the University of Cambridge. They initially looked at the DNA of 328 individuals 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.  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 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.

“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. These discoveries also give researchers the knowledge we need to develop better treatments.”

Professor Peter Weissberg, Medical Director at the BHF, which supported the research, 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. Only by understanding the underlying biology that links HDL-C with heart attacks can we develop new treatments to prevent them. These unexpected findings pave the way for further research into the SCARB1 pathway to identify new treatments to reduce heart attacks in the future.”

Find out more about the BHF’s life saving science at bhf.org.uk/research.


To request interviews, or for more information, please call the BHF Press Office on 020 7554 0164 (07764 290 381 – out of hours) or email newsdesk@bhf.org.uk.

Notes to Editors

1, 5. Elsevier, 2014, HDL-cholesterol in coronary artery disease risk: Function or structure? http://www.sciencedirect.com/science/article/pii/S0009898113004853

2, 6. Science, 2016, Rare Variant in Scavenger Receptor BI raises HDL Cholesterol and Increases Risk of Coronary Heart Disease: (PDF of paper available on request)

3. Nature, 2012, The Not-so Simple HDL Story: is it Time to Revise the HDL Cholesterol Hypothesis? http://www.nature.com/nm/journal/v18/n9/full/nm.2937.html

4. High density lipoproteins are important for the transport of cholesterol (collectively known as HDL-C) to the liver for breakdown and removal. To enter the liver, HDL-C binds to receptors on the surface of liver cells allowing entry of HDL-C, like a lock and key. One of the major HDL-C receptors, encoded by the SCARB1 gene, is scavenger receptor BI (SR-BI).

The researchers identified a mutation in the SCARB1 gene, called the P376L variant, linked to increased levels of HDL-C, and unexpectedly, a greater risk of CHD. In particular, they found that this mutation alters the function of the SR-B1 receptor and HDL-C transport.

7. Statistics: https://www.bhf.org.uk/research/heart-statistics

About the British Heart Foundation (BHF)

Coronary heart disease is the UK’s single biggest killer. For over 50 years we’ve pioneered research that’s transformed the lives of people living with heart and circulatory conditions. Our work has been central to the discoveries of vital treatments that are changing the fight against heart disease. But so many people still need our help. From babies born with life-threatening heart problems to the many Mums, Dads and Grandparents who survive a heart attack and endure the daily battles of heart failure. Every pound raised, minute of your time and donation to our shops will help make a difference to people’s lives. For more information, visit bhf.org.uk.

Share this page: