This is a contribution from a member of THINCS,
The International Network of Cholesterol Skeptics

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Should a 39-year old, healthy woman with heredity for breast cancer start a life-long statin treatment as recently recommended in a paper in JAMA?

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.

To 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 ¹ 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. ^2,3
     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 

1. Mittleman MA. A 39-year-old woman with hypercholesterolemia. JAMA. 2006; 296: 319-326.
2. Ong HT. The statin studies: from targeting hypercholesterolaemia to targeting the high-risk patient. Q J Med. 2005; 98: 599-614.
3. Ravnskov U, Rosch PJ, Sutter MC, Houston MC. Should we lower cholesterol as much as possibile? BMJ. 2006; 332: 1330-1332.
4. Thompson PD, Clarkson P, Karas RH. Statin-associated myopathy. JAMA. 2003; 289: 1681-1690.
5. 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.
6. 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

1. Mittleman MA. A 39-year-old woman with hypercholesterolemia. JAMA 2006;296:319-326.
2. Jacobs D, Blackburn H, Higgins M et al. Report of the Conference on Low Blood Cholesterol: Mortality Associations. Circulation 1992;86:1046-1060.
3. Walsh JM, Pignone M. Drug treatment of hyperlipidemia in women. JAMA 2004;291:2243-2252.
4. Ravnskov U, Rosch PJ, Sutter MC, Houston MC. Should we lower cholesterol as much as possible? BMJ 2006;332:1330-1332.
5. 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.

Both letters were rejected with the same wordening:

Dear Dr. 

Thank you for your recent letter to the editor. Unfortunately, because of the many submissions we receive and our space limitations in the Letters section, we are unable to publish your letter in JAMA.

After considering the opinions of our editorial staff, we determined your letter did not receive a high enough priority rating for publication in JAMA. We are able to publish only a small fraction of the letters submitted to us each year, which means that published letters must have an extremely high rating.

We encourage you to contact the corresponding author of the article, although we cannot guarantee a response. We do appreciate you taking time to write to us and thank you for the opportunity to look at your letter.

Sincerely yours,

Robert M. Golub, MD
Letters Section Editor, JAMA

Confidentiality Note: This communication, including any attachments, is solely for the use of the addressee, may contain privileged, confidential or proprietary information, and may not be redistributed in any way without the sender's consent. Thank you.

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