CORRESPONDENCE: LETTER TO THE EDITOR
Low Low-Density Lipoprotein Cholesterol and Cancer Risk
Timo E. Strandberg, MD, PhD*
* Department of Public Health and General Practice, University of Oulu and University Hospital, P.O. Box 5000, FIN-90014 Oulun Yliopisto, Finland (Email: timo.strandberg{at}oulu.fi).
The central finding in the report by Alsheikh-Ali et al. (1) was Figure 9, which suggested a relationship between achieved low-density lipoprotein (LDL) cholesterol and newly diagnosed cancers in 13 arms of statin trials. I suggest that the relationship is confounded by age in various trials. The authors accounted for sample size, but seemingly not for age, which is a bit surprising, as age-adjustment is one of the most frequent procedures in epidemiologic research. Are there some specific reasons for not doing so? In any case, reasons are not stated.
Consequently, I made further simple calculations based on Table 2 in the study by Alsheikh-Ali et al. (1). There was a significant correlation between achieved LDL and cancer per 100,000 person-years (r = –0.75, p = 0.003), but also between mean age in trials (median age 65 years for the HPS [Heart Protection Study]) and cancer incidence (r = 0.82, p = 0.0006). This is naturally expected as cancer risk increases with age. In multivariate analyses, adjusted for sample size, achieved LDL was a significant predictor of cancer incidence (p = 0.03). However, when age was included in the model, age (p = 0.008)—but not achieved LDL (p = 0.42)—was a significant predictor of cancer risk.
I think that these findings, together with totality of evidence including data from the TNT (Treating to New Targets) study (2) and also from the IDEAL (Incremental Decrease in Clinical Endpoints Through Aggressive Lipid Lowering) study (3), at this stage refute a true link between achieved LDL and cancer risk.
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Footnotes
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Please note: Dr. Strandberg has had cooperation with various companies marketing lipid-lowering drugs and has been an investigator in several statin trials (e.g., 4S, 3T, IDEAL).
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References
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1. Alsheikh-Ali AA, Maddukuri PV, Han H, Karas RH. The effect of the magnitude of lipid lowering on risk of elevated liver enzymes, rhabdomyolysis, and cancer: insights from large randomized statin trials J Am Coll Cardiol 2007;50:409-418.[Abstract/Free Full Text]2. LaRosa JC. Means and ends of statins and low-density lipoprotein cholesterol lowering J Am Coll Cardiol 2007;50:419-420.[Free Full Text] 3. Pedersen TR, Faergeman O, Kastelein JJ, et al. High-dose atorvastatin vs usual-dose simvastatin for secondary prevention after myocardial infarction: the IDEAL study: a randomized controlled trial JAMA 2005;294:2437-2445.[Abstract/Free Full Text]
Related Article
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- Alawi A. Alsheikh-Ali and Richard H. Karas
J. Am. Coll. Cardiol. 2008 51: 92.
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