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Senior Citizen Health & Medicine
New Review Suggests Caution on Using Drugs to Raise
'Good' Cholesterol
Primary focus should be on lowering 'bad' cholesterol
By Maia Szalavitz, Health Behavior News Service
Aug. 17, 2007 - With 40 percent of all heart
attacks and related cardiovascular problems occurring in people who have
low levels of so-called “good” cholesterol, researchers have long sought
medications to increase the amount of this type of cholesterol in the
body’s circulation.
But a new review of 31 randomized controlled trials
published in the Journal of the American Medical Association suggests
that so far, only modest evidence supports the use of most medications
to raise levels of high-density lipoprotein (HDL) — good cholesterol.
Some are even harmful.
The authors concluded that while efforts to lower
low-density lipoprotein (LDL or “bad cholesterol”) “have consistently
reduced cardiovascular disease risk, HDL-based approaches are much more
complex and sometimes disappointing.” As a result, “the primary focus
should be on LDL,” said review co-author Mehdi Shishehbor, D.O., of the
Cleveland Clinic.
“The news is that not everything that raises HDL
will be beneficial,” said Ronald Krauss, M.D., spokesman for the
American Heart Association and director of atherosclerosis research at
Children's Hospital Oakland Research Institute in California.
“HDL is a much more complicated issue than LDL,”
said Prediman Shah, M.D., director of the Atherosclerosis Research
Center at Cedars-Sinai Medical Center in Los Angeles. “It’s not only
important how much HDL there is, but what kind it is. Quality is as
important as quantity. Is the function good or is it [a form of HDL]
that doesn’t do the job properly?”
There are many types of HDL, not all of which
nurture the heart and blood vessels. The good kinds seem to carry fat
out of arteries to the liver and perform functions in cell membranes and
elsewhere. However, HDLs vary considerably in size, density and other
chemical properties that change their ability to sustain health.
Certain kinds of HDL could even increase
inflammation, clogging arteries rather than clearing them, and doctors
currently do not have a simple way to tell this “bad” type of “good”
cholesterol from the genuinely beneficial kind in their patients. Right
now, only expensive tests used in research settings can sort this out.
Fortunately, lifestyle changes can help without
negative side effects, according to the review. “The safest way to raise
HDL is by weight loss, exercise and smoking cessation,” Shishehbor said.
Supports Moderate Alcohol Use
The review also found support for moderate alcohol
use — one or two drinks a day for men, one for women — although
physicians do not recommend that nondrinkers take up drinking to protect
their hearts. Raising HDL by eating fish or taking fish oil to increase
intake of omega-3 fatty acids is another effective strategy, the review
suggested.
As for pharmacological approaches, the review found
that the most effective currently available drug to raise HDL is the
vitamin niacin, taken in high doses. “Statins, niacin and fibrates are
available pharmacologic agents that increase HDL; however, they may be
associated with adverse side effects,” said Shishehbor, who recommended
close medical supervision.
At least one-third of patients cannot tolerate
high-dose niacin, according to Shah. “The most common side effect is
flushing and itching that drives some people nuts.” He said methods
exist to minimize the problem, but they do not work for everyone.
Meanwhile, new medications have proved
disappointing. Trials of one drug, torcetrapib, ended abruptly because
the drug increased mortality risk and raised blood pressure. The class
of diabetes drugs called thiazolidinediones (which include Avandia and
Actos) increase HDL, but also seem to raise the risk of cardiovascular
problems.
The once highly touted weight-loss drug rimonabant,
which blocks the brain receptors activated by marijuana, does raise HDL;
however, the U.S. Food and Drug Administration recently refused to
approve it because it also seems to elevate risk for psychiatric
problems like depression.
“I’m much more excited about the prospect of what’s
coming in this area in the next three to five years,” said Shah, who is
studying approaches to boosting HDL that use different mechanisms from
those that have been associated with problems. Clinical trials of a gene
therapy based on his research are currently under way.
“Despite the recent negative HDL trials, this field
is extremely exciting and the pace of discovery is unbelievably fast,”
Shishehbor said. At least one other drug with a novel mechanism of
action is also in trials — and at least three other approaches have led
to new drugs in the pipeline.
People with blood levels of HDL lower than 35 mg/dL
have eight times the risk of heart disease compared to those with 65mg/dL
or more. Some 16 percent to 18 percent of men have low levels, compared
with 3 percent to 6 percent of women.
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