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We recently reported, in a meta-analysis of statin trials, a strong association between low concentrations of low-density lipoprotein cholesterol (LDL-C) and incident cancer risk. Interpretation of these data has been a point of significant debate. At issue is whether low LDL-C concentration signifies a predisposition to cancer development, or rather results from the presence of even a subclinical neoplastic process (reverse causality). Of pivotal importance to this debate is the duration of low LDL-C levels prior to cancer diagnosis. We explored this controversy using data from the Framingham Heart Study Offspring Cohort to assess the trend of LDL-C for an extended period prior to cancer diagnosis.
Incident cancer cases and control subjects (propensity score matched for age, gender, diabetes, tobacco use, blood pressure, and body mass index) without history of lipid-lowering therapy, were followed for 4 time points prior to cancer diagnosis. Linear mixed model regression analyses delineated the relationship of LDL-C between cancer and cancer-free participants over time.
201 incident cancer cases and 402 matched controls were identified. LDL-C values were lower in cancer subjects than matched controls at each point of assessment throughout an average of 18.7 years prior to diagnosis (F = 4.32, p = .038). The trend for lower LDL-C in cancer patients compared with control subjects was consistent throughout the duration of the study (F = .14, p = .968 for differences between time points). These findings did not change when controlling for high-density lipoprotein cholesterol levels.
Our analysis demonstrates an inverse association between LDL-C and cancer extending over 18 years prior to diagnosis. This is inconsistent with the reverse causality hypothesis, but rather supports that low levels of LDL-C can predate cancer diagnosis by decades. While not itself indicative of an etiologic role for LDL-C in predisposition to cancer, these findings underscore the need for further study in this area, particularly in light of current LDL-C lowering guidelines.
ACC Oral Contributions
McCormick Place South, S100c
Sunday, March 25, 2012, 8:51 a.m.-9:04 a.m.
Session Title: Prevention: Focus on Lipids
Abstract Category: 9. Prevention: Clinical
Presentation Number: 911-7
- 2012 American College of Cardiology Foundation