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New evidence links low cholesterol with increased risk of cancer and death..

Posted Sep 16 2008 6:55am

At the risk of repeating myself, today I’d like to share with you the results of a study which has found a link between low cholesterol levels and heightened risk of cancer. After all, it was only last Friday that I reported on a recently published study which found precisely the same thing. The study that I report on today has even more interesting revelations for us, I think.

The study in question assessed 6000 diabetics for an average of almost 5 years [1]. In this group of people, the relationship between (supposedly ‘unhealthy’) LDL-cholesterol and risk of cancer was assessed.

The researchers first of all looked at this relationship in just those who were not were not taking statin (cholesterol reducing) medication. Here’s the first thing, the relationship was found to be U-shaped. In other words, both high and low levels of LDL cholesterol were found to be associated with an increased risk of cancer.

And now this is where things get interesting. Because, the lowest risk of cancer (the bottom of the U) was found to correspond to an LDL level of 3.28 mmol/l. (127 mg/dL). It is perhaps interesting to compare this value with the most recent recommendations for LDL levels that came from the National Cholesterol Education Programme in the USA in 2004. This panel recommended that:

For patients at high risk of heart disease LDL should be lower than 2.59 mmol/l (100 mg/dL)

For patients at very high risk of heart disease LDL should be lower than 1.81 mmol/l (70 mg/dL)

But there’s more: The researchers involved in this study went on look at the relative risk of cancer in 3 groups of individuals divided according to their LDL levels. The three ‘bands’ were:

LDL level of less than 2.8 mmol/L (108 mg/dL)

LDL level of between 2.8 up to 3.8 mmol/L (108 - 147 mg/dL)

LDL level of 3.8 mmol/L (147 mg/dL) or above

Compared to those in the middle band, those individuals with lower cholesterol levels were found to be, overall, at a 74 per cent increased risk of cancer.

Those in the higher band were found to be 87 per cent increased risk of cancer.

The researchers went on to add into the mix those who were taking statins (combining statin-takers and non-takers together). This changed the nature of the association between LDL levels and cancer risk, and in particular resulted in a less association between the two at higher cholesterol levels. The authors wrote: “Our detailed analysis also indicated that the use of statins had major effects on the association between LDL cholesterol and all-site cancer, obscuring the true nature of the association.”

The authors went further though, and analysed not just the risk of cancer, but the overall risk of death, in each of the three LDL-cholesterol bands.

In patients not using statins, and after controlling for certain confounding factors including waist circumference, ‘healthy’ HDL-cholesterol levels and smoking.

The results revealed that:

Compared to those in the middle band, those individuals with lower cholesterol levels were found to be, overall, at a 50 per cent increased risk of death.

Those in the higher band were found to be 56 per cent increased risk of death.

So, in short, what this study shows is that in this group of diabetics, an LDL level of more than 3.8 mmol/L is associated with an increased risk of cancer and overall risk of death, and so is (and this is quite important, I think) an LDL cholesterol level of less than 2.8 mmol/L.

Now, let’s go back to those NCEP LDL-cholesterol guidelines. They are:

For patients at high risk of heart disease LDL should be lower than 2.59 mmol/l (100 mg/dL)

For patients at very high risk of heart disease LDL should be lower than 1.81 mmol/l (70 mg/dL)

Well, according to this latest study, having cholesterol down where the NCEP suggests may not be such a good thing. And this study is not the only one which has found lower levels of cholesterol to be associated with an increased risk of cancer. We had one come out last week, remember. And the authors of this latest study also point to the fact that: “Several prospective analyses, including the US National Health and Nutrition Examination Survey [2], have demonstrated an inverse relation between serum total cholesterol and cancer incidence and mortality in the general population,”

Now, getting back once again to those NCEP guidelines, even when cardiovascular disease is the focus odes everyone agree that the recommended LDL-levels stand up to scrutiny. The authors of an independent review of basis for these recommendations which appeared in the Annals of Internal Medicine stated: “In this review, we found no high-quality clinical evidence to support current treatment goals for [LDL] cholesterol”. They went on to say that the recommended practice of adjusting statin dose to achieve recommended cholesterol levels was not scientifically proven to be “beneficial or safe” [3]. I don’t suppose it will give us any more confidence in these guidelines to know that the NCEP panel was made up of 9 members, all but one of whom had potential financial conflicts of interest that you can read here. And one final thing: curiously, these conflicts of interest were only revealed after the publication of the NCEP recommendations.

References:

1. Yang X, et al. Independent associations between low-density lipoprotein cholesterol and cancer among patients with type 2 diabetes mellitus. Canadian Medical Association Journal. 2008;179(5):427-437

2. Schatzkin A, et al. Serum cholesterol and cancer in the NHANES I epidemiologic followup study. National Health and Nutrition Examination Survey. Lancet 1987;2:298-301.

3. Hayward RA, et al. Narrative review: lack of evidence for recommended low-density lipoprotein treatment targets: a solvable problem. Ann Int Med 2006;145:520-530

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