Another way “good” cholesterol is good: combatting inflammation
American
Heart Association Circulation Journal Report
Assessing levels of high-density lipoprotein (HDL) cholesterol, known as “good cholesterol,” are already a standard part of formulas used to predict cardiovascular risk.
A new test of the
anti-inflammatory function of HDL seems to provide additional information that
is independent of the quantity of HDL.
If
the results are confirmed in broader populations and a test developed for
clinical use, adding anti-inflammatory capacity to risk scores may improve risk
prediction and help people take steps to protect themselves against heart
disease.
“HDL are very complex particles with anti-atherosclerotic functions that are not reflected by measuring just the cholesterol quantity,” said senior study author Uwe J.F. Tietge, M.D., Ph.D., professor and head of the division of clinical chemistry at the Karolinska Institute in Stockholm, Sweden.
“Atherosclerosis
[plaque build-up in the arteries] underlying cardiovascular disease is
increasingly recognized as a disease with a strong inflammatory component, and
a central biological function of HDL is to decrease inflammation.”
This
study is the first to test whether better anti-inflammatory function of HDL
particles protects against heart attacks and other serious heart-related
events.
Participants
included 680 white adults (average age of 59, 70% male) living in the
Netherlands who were part of a large population study that began in 1997. All
were healthy when they enrolled in the study. From the larger study
participants were identified who’d had a first cardiovascular disease event
before the end of the study follow-up.
HDL
particles were analyzed in 340 people who experienced a first fatal or
non-fatal heart attack, were diagnosed with heart problems caused by narrowed
heart arteries (ischemic heart disease) or who required a procedure to open
clogged coronary arteries during the median 10.5-year follow-up period.
These
participants were matched to a control group of 340 people of the same
age (within 5 years), sex, smoking status and HDL cholesterol levels who had no
cardiovascular events during follow-up.
Several
lab tests were performed for all participants at enrollment, including
measuring the ability of isolated HDL particles to decrease the inflammatory
response of endothelial cells lining blood vessels (called the
anti-inflammatory capacity). Researchers also measured C-reactive protein, a
substance that rises when there is more inflammation throughout the body, and
cholesterol efflux capacity, a laboratory assessment of how efficiently HDL can
remove cholesterol from cells that resemble those found in plaque.
The researchers
found:
HDL
anti-inflammatory capacity was significantly higher in people who remained healthy
(31.6%) than in those who experienced a cardiovascular event (27%);
The
association of anti-inflammatory capacity with cardiovascular events was
independent of the established biomarkers of HDL cholesterol and C-reactive
protein levels, and was also independent of cholesterol efflux capacity;
For
every 22% increase in the ability of HDL particles to suppress inflammation in
endothelial cells, participants were 23% less likely to have a cardiovascular
event during the next decade;
The
amount of protection from increased HDL anti-inflammatory capacity was higher
in women than in men; and
Risk
prediction was improved by adding HDL anti-inflammatory capacity to the
Framingham Risk Score, or by replacing HDL cholesterol levels with this new
measure of HDL function.
“By
using a novel research tool, our results provide strong support for the concept
that plaque buildup in the arteries has an inflammatory component, and that the
biological properties of HDL particles have clinical relevance to
cardiovascular disease risk prediction,” said Tietge.
Although
the results raise intriguing possibilities for improved screening, the results
must be confirmed in different populations. In addition, a simpler and
hopefully automated test for anti-inflammatory capacity should be developed
first, researchers said.
“The
HDL cholesterol level is a good, established, simple and cost-efficient CVD
risk biomarker. Our results, however, demonstrate that the anti-inflammatory
capacity or assays looking at HDL function in general have the potential to
provide clinically relevant information beyond the static HDL cholesterol
measurements that are currently used,” Tietge said.
The
findings also raise the possibility that medications to improve HDL
anti-inflammatory capacity may be developed and used to lower heart disease
risk.
Study
limitations to be considered include that the study population was white and
genetically similar, thus results are not generalizable to other race and
ethnic groups. In addition, the researchers did not include stroke incidence in
their analysis so conclusions cannot be drawn about HDL and stroke.
Co-authors
are Congzhuo Jia, M.D.; Josephine L.C. Anderson, M.D.; Eke G. Gruppen, Ph.D.;
Yu Lei, Ph.D.; Stephan J.L. Bakker, M.D., Ph.D.; and Robin P.F. Dullaart, M.D.,
Ph.D. Disclosures are listed in the manuscript.
The
study was funded by the Netherlands Organization for Scientific Research and
the Swedish Heart-Lung Foundation.
