Statins and Pulmonary Mortality

[Update: Retired Doc's Thoughts has a more complete review of the varied potential benefits from statins.]



This
morning, Effect Measure href="http://scienceblogs.com/effectmeasure/2007/04/the_statin_story_continues_to.php">posted
about a retrospective study that indicates that there may be a
protective effect if statins are taken by persons with COPD (Chronic
Obstructive Pulmonary Disease.)  In also appeared that statins
lowered the risk of death from pneumonia.  



This is a so-called pleiotropic effect, meaning that the drug has an
effect other than that which is originally intended.  Statins
are used to lower the risk of death in persons with hyperlipidemia.
 



I've posted on this href="http://scienceblogs.com/corpuscallosum/2006/10/statins_prevent_lung_damage.php">before,
in reference to possible protection again some of the ravages of
cigarette smoking; Effect Measure href="http://scienceblogs.com/effectmeasure/2006/10/statins_for_h5n1_the_road_not.php">posted
before, raising the question of why there hasn't been more research
into the potential for use of statins against H5N1 flu.  



For a couple of years, there has been some interest in the notion that
the cardiovascular protection of statins may not stem entirely from the
effect of lowering cholesterol.  ( href="http://circ.ahajournals.org/cgi/content/full/109/23_suppl_1/III-39">Beneficial
Cardiovascular Pleiotropic Effects of Statins).
 There has been interest in the idea that statins may protect
against some of the destructive aspects of the body's inflammatory
response to massive infection.  ( href="http://circ.ahajournals.org/cgi/content/full/111/14/1735">Should
Treatment of Sepsis Include Statins?).



Now, there is interest in the notion that statins could reduce the risk
of death from lung disease.  The reason this latter effect is
generating interest, is that we really do not have a good defense
against bird flu right now.  



When the post was put up on Effect Measure, the article was not online
yet.  Now it is: href="http://www.chestjournal.org/cgi/content/abstract/131/4/1006">Influenza
and COPD Mortality Protection as Pleiotropic, Dose-Dependent Effects of
Statins. Unfortunately you need subscription-level access to
see the href="http://chestjournals.org/cgi/content/full/131/4/1006">full
thing.  

Background:
Published data on antiinflammatory and immunomodulatory effects of
statins suggest they may reduce mortality risks associated with an
unchecked immune response to selected infections, including influenza
and COPD. We assessed whether statin users had reduced mortality risks
from these conditions.

Methods: We conducted a matched cohort study (n 76,232) and two
separate case-control studies (397 influenza and 207 COPD deaths) to
evaluate whether statin therapy is associated with increased or
decreased mortality risk and survival time using health-care encounter
data for members of health maintenance organizations. For the cohort
study, baseline illness risks from all causes prior to initiation of
statin therapy were used to statistically adjust for the occurrence of
outcomes after initiation of treatment. Results: For moderate-dose
(> 4 mg/d) statin users, this cohort study found statistically
significant reduced odds ratios (ORs) of influenza/pneumonia death (OR,
0.60; 95% confidence interval [CI], 0.44 to 0.81) and COPD death (OR,
0.17; 95% CI, 0.07 to 0.42) and similarly reduced survival hazard
ratios. Findings were confirmed with the case-control studies.
Confounding factors not considered may explain some of the effects
observed.

Conclusions: This study found a dramatically reduced risk of COPD death
and a significantly reduced risks of influenza death among
moderate-dose statin users.

(CHEST 2007; 131:1006–1012)

Note tha the authors state they have no conflict of interst to
disclose.  Now that statins are going off-patent, it is not
likely, that anyone is going to make a ton of money if this finding
holds up (i.e. is replicable), or if it is found that statins protect
against death from H5N1.  



Effect Measure did a good job of covering the main points, even without
having access to the full article.  I just want to mention a
couple of things.  First of all, it is always interesting to
me, when it is learned that one molecule has diverse, unrelated effects
in different parts of the body.  It shows that side effects
are not always bad.  



Second, this study, and the related ones, show that we are going to
learn a lot by studying the pleiotropic effects of statins.
 The li[id metabolic pathways and the inflammatory response are
complex, not fully understood.  Sepsis is not fully
understood.  By teasing out the common elements, we may be
able to get a clearer picture of how the body works as a whole.



Third, when Effect Measure posted on this before, they asked: Statins
for H5N1. The road not taken. Why? One of the comments does
mention that the potential for big profits may not be there, which
could explain why there hasn't been a lot of funding.  



On the other hand, with national security being such a high priority
right now, and with the potential for a pandemic to threaten our
security, it seems as though this would be an important area that is
consistent with the agenda of the current administration.  



Furthermore, with the costs faced by the Medicare and VA health system
system going up, anything that could reduce morbidity in COPD could
have the potential to lead to great cost savings for government-funded
health programs.  So there are political and economic factors
that would seem to promote research into the area.