(09-07-10) From Heartwire CME Higher HDL-Cholesterol Levels Associated With Lower Risk of Cancer CME/CE

June 17, 2010 ? An inverse and significant association exists between levels
of high-density lipoprotein (HDL) cholesterol and the risk of incident cancer,
according to the results of a new analysis [1]. Researchers report that even
after adjustment for multiple variables, there was a 36% lower risk of cancer
for every 10-mg/dL increase in HDL cholesterol.

The researchers, including Drs Richard Karas and Alawi Alsheikh-Ali (Tufts
University School of Medicine, Boston, MA), previously reported an inverse and
significant association between on-treatment LDL [low-density lipoprotein]-
cholesterol levels and cancer in statin-treated patients. That study, reported
by heartwire , also showed a similar relationship between LDL-cholesterol
levels and incident cancer among control patients not treated with statins,
suggesting that statin therapy, despite significantly reducing LDL-cholesterol
levels, was not associated with an increased risk of cancer.

"One of the limitations of the previous study with low LDL cholesterol and
cancer risk was that people with low levels of LDL cholesterol are unlikely to
die of heart disease," Karas told heartwire . "They're not dying of heart
disease, so they're just around and therefore available to get cancer. With the
HDL story, that's not the case. People with high levels of HDL cholesterol are
unlikely to die of heart disease, but we found that they were also less likely
to get cancer. It further strengthens the finding that there are these
associations between cholesterol levels and cancer."

The new study, with first author Dr Haseeb Jafri (Tufts University School of
Medicine), is published online June 14, 2010 in the Journal of the American
College of Cardiology. To heartwire , Karas said that while his group had been
thinking about the risk of cancer and LDL-cholesterol levels for a couple of
years, there has been little research activity examining any links between HDL
cholesterol and cancer.

Bigger Question About Cholesterol Levels and Cancer Risk

In this latest analysis, the researchers performed a meta-analysis of all
lipid-intervention randomized, controlled trials with more than 1000 person-
years of follow-up and baseline HDL-cholesterol levels and rates of incident
cancer. They identified 24 clinical trials, among them the 4S, WOSCOPS, CARE,
GISSI, ALLHAT-LLT, CORONA, and JUPITER studies, with more than 625 000 person-
years of follow-up and 8185 cases of incident cancer.

In the univariate random-effects meta-regression analysis, there was a
significant inverse relationship between baseline HDL-cholesterol levels and
the rate of incident cancer. For every 10-mg/dL increase in HDL cholesterol
levels, there was a 28% reduction in the risk of cancer. In a model that
controlled for other variables, including LDL cholesterol, age, body-mass index
(BMI), sex, and smoking status, there was a significant 36% lower risk of
cancer for every 10-mg/dL increase in HDL cholesterol.

"I want to underscore that these are associations, so we can never infer or
assume that it's cause and effect," said Karas. "But with that important
caveat, there are some very interesting ideas that provide biological
plausibility for this. We know that oxidants promote cancer, and there are a
lot of data that diets rich in antioxidants reduce the risk of cancer. HDL
cholesterol has antioxidant properties, so it's possible that the antioxidant
effects of higher levels of HDL cholesterol help to reduce the cancer risk."

In addition to protecting individuals via HDL's antioxidant properties, Karas
told heartwire that "immune surveillance," the process in which white blood
cells are on the lookout for abnormal cells, might also play a role. HDL
cholesterol has positive effects on the immune system, and higher levels of HDL
might be linked with improved immune surveillance, which could lower the risk
of cancer.

Low HDL as a Marker of Chronic Disease

In an editorial accompanying the study [2], Dr Jennifer Robinson (University
of Iowa, Iowa City) writes that in addition to the biological plausibility
supporting the link between HDL cholesterol and the risk of cancer, reverse
causality does not explain away the relationship between low HDL cholesterol
and cancer. In addition, there is a dose response observed between the lower
rates of cancer with increases in HDL cholesterol, providing support again for
the association. Still, alternative explanations have not been ruled out yet,
and no randomized trials--the gold standard for demonstrating causality--have
been conducted thus far.

"Data from ongoing trials are needed before drawing any firm conclusions
regarding the role of niacin or any other HDL-cholesterol?increasing drugs in
either cardiovascular disease or cancer prevention," writes Robinson. "At this
time, the evidence best supports low HDL cholesterol as a marker for an overall
increased risk of chronic disease."

Karas added that the findings underscore the importance of reporting cancer
rates in future lipid intervention trials.

References

Jafri H, Alsheikh-Ali AA, Karas RH. Baseline and on-treatment high-density
lipoprotein cholesterol and the risk of cancer in randomized controlled trials
of lipid-altering therapy. J Am Coll Cardiol 2010; 55:2846-54.
Robinson JG. Low high-density lipoprotein cholesterol and chronic disease
risk. J Am Coll Cardiol 2010; 55:2855-2857.

Source : Medscape

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