of heart disease: At least 15 to 20 percent
of people who suffer a heart attack lack
any apparent risk factor for the Big One,
such as high cholesterol, hypertension,
diabetes or a smoking habit.
Some researchers had already speculated that the hidden culprit might be
chronic inflammation in the body, since
plaques in the heart’s coronary arteries contain inflammatory immune cells.
Meanwhile, lab work and studies looking
at statins’ effects on the heart had suggested the drugs played a role against
inflammation.
Ridker and colleagues decided to
actually tackle the question: Did statins
help prevent heart disease by reducing inflammation? His team assigned
healthy people with normal LDL but
elevated inflammation to get either
Crestor or a placebo. The five-year trial
was stopped early when it became clear
that the statin recipients were having
fewer heart attacks and strokes, the
researchers reported in 2008 in the New
England Journal of Medicine.
The following year, a second analysis
of the data showed that roughly twice as
many people getting placebos as receiving Crestor had experienced an episode
of deep-vein thrombosis — a blood clot,
often in the leg. Because clotting in veins
is linked to inflammation and not plaque
formation, the researchers concluded
19
Upped use the percentage of people in the
United states reportedly taking statins has
increased among most age groups in recent
years. While some researchers are concerned
about overprescription, others attribute the
boost to the drugs’ successful track record.
People on statins in last 30 days
Men, 45–64
15
1999–2002
2008
2005–
Women, 45–64
18
10
Sex and age range
16
26
50
24
Women, 65–74
36
Men, 75+
Men, 65–74
45
18
0 10 20 30 40 50
Women, 75+
39
Percent of respondents
soUrce: nchs/cdc
www.sciencenews.org
that statins’ anticlotting effects in this
case were independent of its benefits
against heart attacks.
“Statins are twofers,” Ridker says.
“They both lower cholesterol and seem
to inhibit inflammation.”
Suddenly earlier studies hinting at an
anti-inflammatory role for statins took
on a new gloss, as did work by scientists
who, in relative obscurity, had been look-
ing into statins’ effects on infections,
trauma and other inflammation-related
assaults on the body.
Multipronged switch
A steady stream of lab studies have since
solidified the scientific basis for this
inflammation-fighting effect. By attaching to HMGCR, statins flip a switch that
does more than reduce cholesterol. The
flip also knocks down production of
compounds known as isoprenoids. Data
now show that the knockdown influences basic immune function in a host of
ways — a largely unexpected discovery.
“The whole history of science is filled
with serendipity,” Lipkin says.
James Liao, a vascular biologist and
cardiologist at Harvard and Brigham
and Women’s Hospital, and others have
tracked the fallout of statins’ other
career in recent years. The researchers have found that inhibiting isoprenoids prevents some immune cells from
secreting inflammatory proteins and
hampers other cells’ ability to exacerbate existing inflammation. Statins even
seem to tilt some immune cells away
from an inflammatory bent toward a
more quiescent role, and provide a
bonus by maintaining good health in the
all-important cells lining the insides of
blood vessels. Such findings “have put
into question whether cholesterol was
entirely, or even mainly, the benefit of
statin therapy,” Liao says.
Make no mistake, inflammation is a
helpful response to infection or injury
and has served humans well over time,
particularly in the rough-and-tumble
Stone Age. But inflammatory cells and
proteins can overstay their welcome,
damaging healthy tissues in blood vessels, swollen joints and infected lungs.
Forked effects When statins attach to an
enzyme called hMGcr, they prevent hMG-coa
from becoming mevalonic acid. this hinders
a cholesterol-making reaction, as well as
inhibiting a host of processes that promote
inflammation and cancer.
HMG-CoA
Mevalonic acid
Statins attach to
HMGCR to block
this reaction
Isopentenyl-PP
Geranyl-PP
Isoprenoids
Farnesyl-PP
Ras
Cholesterol
In;ammation
Geranylgeranyl-PP
Cell
proliferation
RhoA
Rac1
Cell
proliferation
Blood vessel
proliferation
Oxidative
stress
soUrce: M. BardoU ET AL/GU T 2010
Statins’ additional role “opens up a
whole new therapeutic window,” Liao
says. There is plenty of work out there
for an easy-to-take anti-inflammatory.
Randomized trials have shown that
statins may ease rheumatoid arthritis
and tame inflammation in a lethal condition called sepsis, a whole-body immune
reaction to bacterial infection. Statins
may also treat osteoarthritis, researchers reported in 2010: Statins prevent cartilage loss in mice and decrease enzymes
known to abet inflammation and degrade
cartilage in human cells. And then there’s
trauma. Anti-inflammatory effects are
consistent with a 2011 study finding that
older people taking statins were much
less likely than nonusers to die in the
hospital following a head injury.
Liao says statins’ immune benefits
go beyond fighting inflammation. The
drugs don’t appear to wipe out inflammation wholesale, as a steroid drug
might, he says, but instead bring overwrought inflammation signalers “back
to a normal state.”
