Four rare gene
mutations may protect against heart attacks by lowering levels of a type of fat
called triglycerides, according to research in the New England Journal of
Medicine.
Triglyceride
levels in the blood were 39 percent lower in carriers of the mutations, which
affect the APOC3 gene, than in non-carriers.
Researchers analysed
blood from nearly 4,000 participants from the USA's National Heart, Lung and
Blood Institute's Exome Sequencing Project. Around one in every 150 people carried
an APOC3 mutation and were found to have a 40 percent reduced risk of heart
attacks.
'Based
on our findings, we predict that lowering triglycerides specifically through
inhibition of APOC3 would have a beneficial effect by lowering disease risk',
said Professor Alex Reiner, senior co-author of the study from the University of
Washington.
Heart
problems are known to be linked to levels of a type of cholesterol, low density
lipoproteins (LDL). But the role of other blood lipids such as high density
lipoproteins (HDL) and triglycerides in heart disease is less clear.
Dr Sekar
Kathiresan, director of preventive cardiology at Massachusetts General
Hospital, senior author of the study, said: 'HDL and
triglycerides are both correlated with heart attack, and have an inverse
relationship with one another — the lower the HDL the higher the triglycerides'.
'It
has long been presumed that low HDL is the causal factor in heart disease and
triglycerides are just along for the ride. But our genetic data indicate that
the true causal factor may not be HDL after all, but triglycerides',
he added.
Current heart
disease prevention therapies such as statins target raised levels of LDL, the
so-called 'bad cholesterol'. However some patients go on to have further heart
attacks even after being treated with drugs to lower LDL. This study helps to
explain the origins of this residual risk.
'Although statins
remain a powerful arrow in the quiver, the notion of residual risk of coronary
heart disease continues to be a significant clinical problem',
commented Dr Kathiresan. 'Our study really reinvigorates the idea of
lowering triglycerides and specifically by blocking APOC3 as a viable
therapeutic strategy for addressing residual risk'.
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