Low LDL cholesterol levels tentatively linked to cancer risk

Cardiovascular News

Low LDL cholesterol levels tentatively linked to cancer risk

26 July 2007

MedWire News: An explorative analysis has found an association between the risk for cancer and achieved level of low-density lipoprotein (LDL) cholesterol in statin trials.

“This analysis doesn’t implicate the statin in increasing the risk of cancer,” stressed study author Richard Karas (Tufts University School of Medicine, Boston, Massachusetts, USA).

“The demonstrated benefits of statins in lowering the risk of heart disease remain clear; however, certain aspects of lowering LDL with statins remain controversial and merit further research.”

The investigators included statin-treated participants from 23 trials in their analysis, giving 309,506 person-years of follow-up.

The magnitude of LDL cholesterol reduction achieved by patients was not associated with cancer risk, or with the patients’ risk for elevated liver enzymes or rhabdomyolysis.

Their results are published in the Journal of the American College of Cardiology. In a related comment, journal editors Anthony DeMaria and Ori Ben-Yehuda (University of California at San Diego, USA) observed that over the past 5 years, “no other manuscript has stimulated such intense scrutiny and discussion.”

The only clear treatment-related effect that the researchers detected was an increasing risk for elevated liver enzymes with rising statin dose.

This rate of elevated liver enzymes rose from about 100 per 100,000 person-years with low statin doses to about 250 per 100,000 person-years with high doses. The absolute and percent LDL cholesterol reductions were not associated with the risk for cancer.

But the team found an inverse relationship between achieved LDL cholesterol levels and the risk for cancer, at an R2 of 0.43. In other words, 43% of the variance in cancer incidence could be accounted for by achieved cholesterol levels, although this was not adjusted for confounders.

In their discussion, Karas et al observe that their findings are consistent with epidemiologic studies showing a link between low cholesterol levels and cancer. But they also note that researchers who previously compiled a review of such studies failed to draw any definitive conclusions, and suggested that the proposed association could be due to confounding.

“One potential explanation is the possibility that low cholesterol levels are simply the effect of the disease rather than the cause, and is present before clinical manifestation of the cancer,” say Karas and team.

In an accompanying editorial, John LaRosa (State University of New York Downstate Medical Center, USA) noted that the link between LDL cholesterol levels and cancer can be further studied without the need for more trials, as many LDL-lowering studies have not published data on cancer.

“Lowering LDL represents an intervention of long duration, and we must continue to be vigilant in ensuring that its benefit clearly outweighs its risk,” he said.

“On the other hand, we must not allow that vigilance to deny the benefits of LDL lowering to those who need it.”

LINK:

Primary source: Journal of the American College of CardiologySource reference: Alsheikh-Ali AA et al. "Effect of the magnitude of lipid lowering on risk of elevated liver enzymes, rhabdomyolysis, and cancer." J Am Coll Cardiol 2007;50:409-418.

J Am Coll Cardiol 2007; 50: 409–418