Inverse relationship between LDL levels, cancer diagnosis identified

CHICAGO — Researchers identified an inverse relationship between LDL levels and cancer that persisted for more than 18 years before cancer diagnosis in a group of individuals from the Framingham Heart Study Offspring Cohort.

Paul M. Lavigne, MD, of Tufts Medical Center in Boston, said the relationship between total serum cholesterol and malignancy was first reported 30 years ago and has since been validated in multiple subsequent studies.

“More recently, we have seen an inverse relationship between low LDL and cancer,” Lavigne said during a presentation at the American College of Cardiology’s 61st Scientific Sessions. While there is general agreement that lower LDL levels are seen in patients near the time of cancer diagnosis, there is significant controversy regarding interpretation of that relationship, he said.

“One hypothesis — termed reverse causality — postulates that the cancer itself is responsible for the observed depressed LDL levels in cancer patients,” Lavigne said. “An alternative interpretation is the forward causality hypothesis, which postulates that depressed LDL is a precursor to cancer incidence and itself reflects an increased risk for cancer development.”

The objective of the current study was to confirm the link between lower LDL and cancer incidence.

The matched case-control study included data from the Framingham Heart Study’s Offspring Cohort, where 5,124 individuals were followed during a series of visits at 4-year intervals. Eligible patients had LDL values for four time points predating cancer diagnosis. The main exclusion criteria were a known history of cancer and a history of cholesterol-lowering therapy.

Each cancer case was matched with two controls with regard to age, sex, tobacco use, diabetes status, blood pressure and BMI. Regression analysis was conducted to observe cholesterol levels throughout time.

There were 201 patients with cancer and 402 controls in the final analysis.

Lavigne and colleagues found that LDL levels were significantly lower in patients with cancer than controls at each point of assessment during an average of 18.7 years prior to diagnosis (P=.038). The trend for lower LDL in patients with cancer compared with those who were free of cancer was consistent throughout the duration of the study (P=.968 for differences between time points). These findings did not change when controlling for HDL levels.

The stable inverse association between LDL cholesterol and cancer prior to diagnosis argues against the hypothesis that the observed lower LDL in cancer patients results entirely from preclinical disease, according to Lavigne.

“There is no evidence to indicate that lowering cholesterol with a medication in any way predisposes to a risk for cancer,” Lavigne stated in a press release. “We suspect there may be some underlying mechanism affecting both cancer and low LDL, but we can only say definitively that the relationship between the two exists for many years prior to cancer diagnosis, and therefore underscores the need for further examination.” – by Rob Volansky

For more information:

Lavigne PM. 911-7. Presented at: the American College of Cardiology 61st Scientific Sessions & Expo; March 24-27, 2012; Chicago.

Disclosure: Dr. Lavigne reports no relevant financial disclosures.