REYKJAVIK, Iceland,
Dec. 9, 2019 /PRNewswire/ --
Scientists at deCODE genetics and colleagues from the National University Hospital in Iceland today present the largest-scale study
to date of the role and public health impact of Lipoprotein(a) as a
risk factor for cardiovascular disease. The study appears today in
the online edition of the Journal of the American College of
Cardiology.
Lipoprotein(a), abbreviated as Lp(a), is an alipoprotein(a),
abbreviated as apo(a), bound to an LDL cholesterol particle and has
been known as a risk factor since the 1970s. But the high
variability of the apo(a) gene that controls its production, the
diverse isoforms of Lp(a) that result, the difficulty of assaying
them, and conflicting reports of how they impart risk left it
largely neglected alongside the clearer success story of LDL, the
statins and PCSK9 inhibitors. The deCODE team turned its unique
population-scale capabilities and data to address the complexity of
Lp(a) and discovered a simple answer: it is the molar concentration
of Lp(a) that directly correlates with increased risk of heart
disease, whatever the variety of apo(a) alleles and independently
of traditionally measured or treated HDL or LDL cholesterol.
"This study from our little island may well turn out to be an
important contribution to global public health," said Kari Stefansson, CEO of deCODE and a senior
author on the paper. "We have very effective LDL-lowering drugs,
but heart disease remains the biggest killer worldwide and
understanding Lp(a) is key to addressing the residual risk."
"What we show today, by analyzing an unprecedented amount of
both clinical and genetic data from across the Icelandic
population, is that by measuring Lp(a) in the blood we can identify
a quarter of the population that is from an additional 25% to
double the average risk of heart disease. This risk is independent
of other risk factors and is 95% genetically determined, so you
can't reduce it by improving your lifestyle or diet. The clear
message is therefore that we need to test for Lp(a) globally to
identify those at significantly elevated risk, and speed the
development of new therapies aimed at silencing the apo(a) gene.
The good news is that our colleagues at Amgen are already taking
such therapies into clinical trials," Dr Stefansson added.
"We know that Lp(a) is a causal, independent risk factor for
cardiovascular risk, and Amgen is proud of the work we have done
and continue to do investing in pursuing this therapeutic target,"
said David M Reese, MD, executive vice president of Research and
Development at Amgen. "This new study from deCODE will
help steer and inform research into the clinical development of
molecules targeting Lp(a), and is a great example of the potential
we are just beginning to uncover using genetic insights and
validation to power drug development. We believe we are still in
the early years of large-scale human genetic research, and most of
the major discoveries in this field still lie in the future.
That's why we are continuing to grow our investment in
genetics by increasing the scope and diversity of the data that
deCODE can access and analyze for research purposes."
The study utilized whole genome data from some 150,000
Icelanders participating in deCODE's genetics research, including
18,000 with coronary artery disease (CAD) and other cardiovascular
phenotypes, and 9,000 with type-2 diabetes. By directly measuring
molar concentration of Lp(a) from 12,000 participants and comparing
them with the sequence of participants' apo(a) genes, the research
team was able to establish how different variants in apo(a) and the
resulting Lp(a) isoforms affect the risk of coronary artery
disease. Imputing these results through the entire dataset and
correlating the results with disease status enabled the testing of
multiple previous findings related to Lp(a) and the discovery that
it is overall molar concentration of Lp(a) rather than specific
isoforms or isoform size itself that correlates with CAD risk. The
study also demonstrated that Lp(a) levels correlate with risk for
peripheral artery disease, aortic valve stenosis, heart failure and
lifespan. An important next step in this research is to validate
the results in other populations, to understand how the
contribution of Lp(a) levels to heart and other diseases may vary
between populations of different continental ancestry.
Based in Reykjavik, Iceland,
deCODE is a global leader in analyzing and understanding the human
genome. Using its unique expertise and population resources, deCODE
has discovered genetic risk factors for dozens of common diseases.
The purpose of understanding the genetics of disease is to use that
information to create new means of diagnosing, treating and
preventing disease. deCODE is a wholly-owned subsidiary of Amgen
(NASDAQ:AMGN).
Contact:
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Edward
Farmer
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Jón
Gustafsson
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efarmer@decode.is
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jon@decode.is
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+354 863
1923
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+354 664
1905
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SOURCE deCODE genetics