Should we lower cholesterol as much as possible?: Cholesterol is good?
BMJ 2006; 332 doi: https://doi.org/10.1136/bmj.332.7555.1453 (Published 15 June 2006) Cite this as: BMJ 2006;332:1453All rapid responses
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Dr Ravnskov is correct that no recommendations can be made with
regards to Q10 lowering until trials with clinical endpoints have been
performed. It would also be interesting to see whether these endpoints can
be modified by adding Q10 to a statin treatment regimen. Given that these
endpoints are themselves fairly rare, very high numbers of patients would
be needed to power such a study adequately.
A very large number of clinical trials exclude patients with active
cancer. This is not unique to the statin trials. There are various reasons
for this, such as to reduce confounding and to homogenise the study
population, but no statin trial has excluded cancer patients explicitly
because statins may modify cancer risk. A recent meta-analysis (1) should
reassure us with respect to statins and cancer risk.
I cannot disagree with Dr Ravnskov's point that high-dosed statin
therapy needs further study. While the TNT study showed a further 20% risk
reduction of coronary events (2), such a measure will need larger numbers
to warrant wide implementation, especially given the higher incidence of
raised transaminases in that study.
(1) Dale KM, Coleman CI, Henyan NN, Kluger J, White CM. Statins and
cancer risk. JAMA 2006;295:74-80
(2) LaRosa JC, Grundy SM, Waters DD, Shear C, Barter P, Fruchart JC, Gotto
AM, Greten H, Kastelein JJ, Shepherd J, Wenger NK; Treating to New Targets
(TNT) Investigators. Intensive lipid lowering with atorvastatin in
patients with stable coronary disease. N Engl J Med 2005;352:1425-35.
Competing interests:
None declared
Competing interests: No competing interests
In
his response1 to our paper about high-dose statin treatment2
Dr. de Wolff claims that our concern about resulting lowering of coenzyme
Q10 levels is unfounded because not enough patients have been studied, the
significance of the results is questionable and that we failed to explain why
any reduction in Q10 would be harmful. However,
we believe that most scientists would be quite concerned about any medication
that could cause a 50 % reduction in concentrations of a substance that is
crucial for maintaining normal mitochondrial function in all cells.3
Since proper energy production is particularly important for muscle cells one
might reasonably speculate that some of the well-known adverse effects of
statins are due to the resultant depletion of Q10.
Although a highly significant reduction of Q10 (p<_0.001 was="was" seen="seen" in="in" _34="_34" patients="patients" after="after" only="only" one="one" monthsup="monthsup"/>3 it might be necessary to treat
thousands of patients for several years to demonstrate any effect on mortality
rates.
De
Wolff also claims that statin treatment protects against cancer. As evidence he
refers to a case-control study of patients with colorectal cancer and healthy
control individuals, where 120/1833 in the former group (6.1 %) used statins
compared to 234/1781 in the latter (11.6 %).4 Case-control studies
cannot prove causality, however. This study could for instance be biased because
doctors who are aware of the potential carcinogenicity of statins would not
prescribe it in a patient with a history of or at increased risk of developing a
malignancy. If statins protect
against cancer can de Wolff explain why cancer patients have been excluded from
all trials published after the CARE trial,5 the first, but not the
only one,6 that found a significant increase of cancer in the
treatment group?
Whether high cholesterol is good or bad is irrelevant
because all evidence shows that the benefits from statin treatment are due to
pleiotropic effects, not to cholesterol lowering.
The issue here is whether high-dose statin therapy provides any proven
advantages or if the associated dangers outweigh any putative benefits.
-
De
Wolff JD. Should we lower cholesterol as much as possible? Cholesterol is
good? BMJ 2006;332:1453. [Abstract]. -
Ravnskov
U, Rosch PJ, Sutter MC, Houston MC. Should we lower cholesterol as much as
possible? BMJ 2006;332: 1330-2. (3 June.)[Full
text][PDF]
-
Rundek
T, Naini A, Sacco R, Coates K, DiMauro S. Atorvastatin decreases the
coenzyme Q10 level in the blood of patients at risk for cardiovascular
disease and stroke. Arch Neurol 2004;61: 889-92.[Abstract/Free
Full Text]. -
Poynter
JN, Gruber SB, Higgins PD, Almog R, Bonner JD, Rennert HS, et al. Statins
and the risk of colorectal cancer. N
Engl J Med
2005;352: 2184-92.[Abstract/Free
Full Text]. -
Sacks
FM, Pfeffer MA, Moye LA, et al. for the Cholesterol and Recurrent Events
Trial investigators. The effect of pravastatin on coronary events after
myocardial infarction in patients with average cholesterol levels. N
Engl J Med 1996; 335: 1001-9. [Free
Full Text). -
Shepherd
J, Blauw GJ, Murphy MB, Bollen EL, Buckley BM, Cobbe SM, et al. PROspective
Study of Pravastatin in the Elderly at Risk. Pravastatin in elderly
individuals at risk of vascular disease (PROSPER): a randomised controlled
trial. Lancet 2002;360:1623-30. [Free
Full Text]
Competing interests:
All authors have argued in the scientific press and elsewhere that high cholesterol is not the cause of atherosclerosis and coronary heart disease.
Competing interests: No competing interests
RE: Cholesterol is good?
Jacob F. de Wolff said "While the TNT study showed a further 20% risk
reduction of coronary events (2), such a measure will need larger numbers
to warrant wide implementation, especially given the higher incidence of
raised transaminases in that study."
What Jacob F. de Wolff didn't say was "There was no difference
between the two treatment groups in overall mortality."
Increasing the dose of atorvastatin by a factor of eight resulted in
no lives saved in a study of 10,001 people. That's not exactly what I
would call a result. Am I missing something, here?
(2) LaRosa JC, Grundy SM, Waters DD, Shear C, Barter P, Fruchart JC,
Gotto AM, Greten H, Kastelein JJ, Shepherd J, Wenger NK; Treating to New
Targets (TNT) Investigators. Intensive lipid lowering with atorvastatin in
patients with stable coronary disease. N Engl J Med 2005;352:1425-35.
Competing interests:
None declared
Competing interests: No competing interests