Statins Not Linked To Cancer Risk By Paula Rasich Reviewed by Elizabeth Klodas, MD, FACC  September 23, 2008--If you’re taking cholesterol-lowering statins, you may wonder if you run an increased risk of cancer. Evidence published a year ago led researchers to suspect that there may be a link. But a new study says not so.

In the original study---a combined analysis of 13 trials looking at statin-treated patients only---Richard H. Karas, MD, PhD, director of preventive cardiology at Tufts Medical Center in Boston, and colleagues didn’t find that statins actually cause cancer, but rather that lower levels of LDL, or “bad cholesterol”, made it more likely that a person might develop cancer over time. There was about a threefold increase in cancer going from the highest LDL levels to the lowest LDL levels, says Dr. Karas. 

To investigate the role of statins further, Karas and his colleagues conducted a follow up study. The second analysis included 15 randomized controlled trials involving nearly 52,000 statin users and 45,000 control subjects with an average follow up of four and a half years. When researchers compared statin-treated patients with placebo (inactive pill)-treated patients, they found that the average rate of cancer in both the placebo and the statin groups was similar---about 12.5 cancers per 1,000 patient years---even though LDL levels in the statin group were on average 40 points lower than the placebo group.  However, regardless of whether they were receiving statins or placebo, the patients with the lowest LDL levels were at higher risk of developing cancer during follow-up.

“Our analysis showed that despite their LDL lowering effects, statins are not associated with an increase in the risk of cancer,” says Dr. Karas.  But more research is needed to better understand the link between low LDL levels and higher risk of cancer, he adds.

What’s the connection? In an accompanying editorial, Daniel Steinberg, MD, PhD, of the University of California San Diego says that one potential explanation is the “unsuspected sickness phenomenon” (i.e., the lowering of cholesterol levels by disease that is not yet advanced enough to cause symptoms). We know that cancers can significantly lower cholesterol levels as much as 10 years before they surface clinically.”  In other words, the lower LDL is a result of the cancer, not the cause.  An explanation that is highly unlikely is that very low LDL levels themselves cause cancer.  Most mammals experience LDL levels in the 40-50 mg/dL range throughout their lives, and humans are born with similar levels.  And individuals with a rare genetic defect which results in extremely low LDL levels (10-20 mg/dL range), appear to have normal life expectancies - even tending towards longevity.  Aiming for very low LDL levels therefore still appears prudent in patients with, or at high risk for, cardiovascular disease.

In a second editorial, Anthony N. DeMaria, MD, and Ori Ben-Yehuda, MD, say that “the present guidelines adequately balance the clear benefit of LDL lowering with potential risks.”

This study and editorial comments are published in the September 30, 2008 issue of the Journal of the American College of Cardiology.

Sources:

Alsheikh-Ali AA et al. Statins, Low-Density Lipoprotein Cholesterol, and Risk of Cancer. Journal of the American College of Cardiology, 2008.

Ben-Yehuda O, DeMaria AN. Editorial Comment: Low LDL-C Levels and Cancer: Reassuring But Still Not Definitive. Journal of the American College of Cardiology, 2008.

Steinberg D. Editorial Comment: Statin Treatment Does Not Cause Cancer. Journal of the American College of Cardiology, 2008.

Richard Karas, MD, PhD, director of preventive cardiology at Tufts Medical Center, Boston, Massachusetts.