is a contribution from a member of THINCS,
The International Network of Cholesterol Skeptics
Should a 39-year old, healthy woman with heredity for breast
cancer start a life-long statin treatment as recently recommended in a paper
Of course not; read why. First a
summary of the JAMA paper:
Mittleman MA. A 39-year-old woman with
hypercholesterolemia JAMA. 2006 Jul 9;296(3):319-26
Ms T, a 39-year-old woman, has a total cholesterol
level of 277 mg/dL (7.17 mmol/L) and well-controlled hypertension; her
brother had a stroke in his 30s. She is primarily concerned with her
mother's history of breast cancer, but she would like to know if she can
take a dietary supplement or if she needs to take cholesterol-lowering
medication, and if so, whether she will need to continue it as well as
adhere to her diet for the rest of her life. Her estimated 10-year risk of
developing coronary heart disease (CHD) is 1% to 2% using the Framingham
Risk Score, but that may underestimate her true risk as an African American
woman with a family history of CHD. Recommendations for her, her longer-term
risk for CHD, and evidence for lipid-lowering therapies are discussed.
And here come our responses:
A 39-Year-Old Woman With Hypercholesterolemia.
the Editor: In his
Clinical Crossroads article about a 39-year-old African American woman with
a family history of breast cancer, a well-controlled hypertension, and a
recently diagnosed hypercholesterolemia, Dr Mittleman
recommended treatment with a low dose of statin. We disagree
with this recommendation which might also be considered as counterproductive.
It is well established that statins should no
longer be seen as therapy for hypercholesterolemia per se, but should be
regarded as a treatment to reduce and prevent clinical cardiovascular
events. Therefore, patients requiring statins are those at high risk,
regardless of the baseline lipid levels, which represent only one of the
many clinical parameters to be considered. 2
Low-risk individuals with hypertension have been
shown to not benefit from statin therapy, and this is not surprising because
in persons not at high-risk of coronary deaths, cholesterol lowering therapy
cannot do very much to lower mortality, as the patients are more likely to
die to non-cardiovascular causes. Furthermore, as Dr Mittleman
acknowledged, lipid lowering in women may only reduce the incidence of
non-fatal cardiovascular events and does not appear to have a beneficial
effect on total mortality. Because many non-fatal events resolve with little
residual damage or discomfort, the evaluation of statin adverse side-effect
should have been better considered. 3
Muscle complaints in patients taking statins
may have deleterious effects especially during physical activity: it has
been postulated that statins may affect adversely the muscle's ability to
appropriately respond to physical exertion 4, which represent a useful tool for reducing
cardiovascular and all-cause mortality in the primary prevention setting in
both sexes. 5
Another issue is that related to cancer. Although meta-analysis of clinical
trial data with a follow-up of 2 to 10 years have found no association of
statin therapy with cancer, it is to be considered that a 39-year-old
patient is likely to have to take the drug up to 40 years. In patients on
statin therapy the increased cancer incidence in those at increased risk of
cancer (like the elderly population) or the increased incidence of
non-melanoma skin cancer (a pathology easily detectable) is disturbing.
Finally, the “cosmetic” effect of statin
on serum cholesterol levels may distract the patients to watch their diet.
Diet generally produces only modest serum cholesterol reduction. However,
greater adherence to the traditional Mediterranean diet has been shown to be
associated with a significant reduction in total mortality, which is also
evident with respect to deaths due to cancer. 6
Comando Brigata alpina “Julia”
Ospedale di San Vito al Tagliamento
San Vito al Tagliamento, Italy
- Mittleman MA. A 39-year-old woman with
2006; 296: 319-326.
- Ong HT. The statin studies: from targeting
hypercholesterolaemia to targeting the high-risk patient. Q
J Med. 2005; 98: 599-614.
- Ravnskov U, Rosch PJ, Sutter MC, Houston MC.
Should we lower cholesterol as much as possibile? BMJ. 2006; 332:
- Thompson PD, Clarkson P, Karas RH.
Statin-associated myopathy. JAMA. 2003; 289: 1681-1690.
- Barengo NC, Hu G, Lakka TA, Pekkarinen H,
Nissinen A, Tuomilehto J. Low physical activity as a predictor for total
and cardiovascular disease mortality in middle-aged men and women in
Finland. Eur Heart J. 2004; 25: 2204-2211.
- Trichopoulou A, Costacou T, Bamia C,
Trichopoulos D. Adherence to a Mediterranean diet and survival in a
Greek population. N Engl J Med. 2003; 348: 2599-2608.
A 39-Year-Old Woman With Hypercholesterolemia
To the Editor. There are
four strong arguments against statin treatment of a woman with
well-controlled hypertension, elevated cholesterol and heredity for breast
cancer. First, high cholesterol is not a risk factor for cardiovascular
mortality in women. This was stated already in 1992 on a NHLBI conference
based on 18 cohort studies (eleven from the US) including 12,881 deaths in
124,814 women.2 Second, a recent meta-analysis of all
cholesterol-lowering trials found no effect on coronary or total mortality
for women without cardiovascular disease.3 Third, there are many
arguments for the view that side effects are grossly underreported in the
trial reports.4 In support is a study of fifty consecutive new
patients on statin therapy by Langsjoen et al. They found that all of the
patients had one or more side effects, including myalgia, fatigue, dyspnea,
memory loss and peripheral neuropathy, and that in the large majority these
symptoms disappeared after discontinuation of the drug. Finally there is
concern that statin treatment may produce cancer.5 Relevant in
this case is that in the CARE trial 12 women in the treatment group got
breast cancer, some of which were recurrences, against one in the control
group. Breast cancer has not been reported from the more recent trials, but
this is not reassuring because since then cancer has been an exclusion
criterion and also because chemical carcinogenesis may not appear in ten
years, the longest follow-up of statin treatment hitherto reported.
Uffe Ravnskov, MD, PhD
Magle Stora Kyrkogata 9, S-22350 Lund, Sweden
- Mittleman MA. A 39-year-old woman with hypercholesterolemia. JAMA
- Jacobs D, Blackburn H, Higgins M et al.
Report of the Conference on Low Blood Cholesterol: Mortality
Associations. Circulation 1992;86:1046-1060.
- Walsh JM, Pignone M. Drug treatment of
hyperlipidemia in women. JAMA 2004;291:2243-2252.
- Ravnskov U, Rosch PJ, Sutter MC, Houston MC.
Should we lower cholesterol as much as possible? BMJ
- Langsjoen PH, Langsjoen JO, Langsjoen AM,
Lucas LA. Treatment of statin adverse effects with supplemental Coenzyme
Q10 and statin drug discontinuation. Biofactors 2005;25:147-152.
letters were rejected with the same wordening:
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