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TC = LDL + HDL + 0.2 X TG (values in mg/dL) TC = LDL + HDL + 0.46 X TG (values in mmol/L)

HDL values are typically 50 ± 10 mg/dL, and if TGs are at 150 mg/dL, they contribute only 30 the total. Increase TG to 200 and this only increases TC by 10. Thus TC reflects mainly LDL, and it can be argued that TC is a fairly good surrogate marker for LDL. The ascension of LDL to the position of villain is probably largely because higher levels of HDL were found to be beneficial and thus higher levels of LDL must be bad, given that TC was bad. But a decrease in the risk of CHD or even CHD mortality due to a drug therapy that reduces TC and LDL does not prove that TC and/or LDL are causative factors. For this to be the creditable, it must at least be

demonstrated that the only possible significant action of the

discussed below, this appears to cholesterol lowering drugs, which

be far from the truth.

To

today

are

mostly

statins,

is

drug is the lowering of cholesterol. As will be put it another way, if the beneficial effects of due to actions of the drug that do not involve

lowering levels dependence is responsible for

of cholesterol, then the cholesterol lowering itself is irrelevant in this observed. That is, the non-lipid lowering mechanism could be dose all the observed benefits.

context, even

if a dose

dependent as

well and

In fact the statin cholesterol lowering drugs impact a number of biological processes and this has become a hot research area. Also a number of problems exist which are related in part to inexplicable dose and level dependencies. For example, consider studies that have different initial LDL levels and produce similar percentage LDL lowering. These studies all give similar risk reduction, but the endpoint LDL in one study can be higher than the initial level in another study, and yet the same benefit accrues. There have been a number of such studies and taken together they suggest that the initial and terminal levels of LDL have nothing to do with the risk reduction. A review in 2007 put the matter this way when discussing the use of statin drugs to lower cholesterol: “The relative risk reduction is approximately 20-40% regardless of age, sex, pretreatment level of LDL-C, race or preexisting myocardial infarction” [1]. Such results have caused a number of researchers in this field to look at the possibility that the statin drugs prevent recurrent heart attacks by some other mechanism than cholesterol lowering, and the levels of either TC or LDL are in a large part unrelated to the benefit of the drug treatment. This is now a very active area of research and that alone should suggest just how unacceptable is the argument that the Cholesterol Hypothesis is proven in terms of a causal relationship by the fact that benefits,

mostly in lowering

secondary CHD outcomes, are produced by cholesterol lowering by drugs.

Proposed non-lipid

mechanisms

include

improvement

of

endothelial

dysfunction,

reduced

inflammatory

response,

stabilization that statins,

of atherosclerotic plaques and reduced thrombogenic (clot formation) response [1,2]. It turns out which block a critical step in the biosynthesis of cholesterol, also eliminate two precursors to a

number of biologically important molecules which in turn may be these drugs. Lipid lowering will be the subject of the third review

related to the

above

in this series

where

non-lipid lowering effects of more documentation will be

provided. But the essential point is that there are problems, both logical and factual, with the standard that because there is a decrease in risk of CHD when statins are used to lower TC and LDL, that it follows that TC and in particular LDL cause CHD, or atherosclerosis for that matter. It is also of interest

argument therefore that there

does not appear to be an explanation for just how LDL is supposed to cause atherosclerosis and disease [3]. Rather, it is “work in progress.” In what follows we will look at a number of studies inconsistent with the Cholesterol Hypothesis or appear to actually falsify it.

coronary heart that are either

AUTOPSY STUDIES If circulating cholesterol causes atherosclerosis and thus coronary heart disease, one might expect to see a correlation between the extent of atherosclerosis and cholesterol levels. The first significant study appears to have been reported back in 1936. Two pathologists from New York University, K. Landé and W. Sperry, studied a large group of individuals who had died from violent incidents [4]. They examined the extent of coronary atherosclerosis observed at autopsy and found no correlation with serum cholesterol levels. Some dismissed these results by claiming that cholesterol values measured after death were not a reliable measure of levels while alive. But other studies enable one to discount this objection. A Canadian study examined a large number of veterans at death [5]. Adequate pre-death cholesterol data were available and levels varied considerably among the individuals but for any given person, they were fairly constant. Autopsy studies on all the veterans who died revealed no connection between the degree of atherosclerosis and blood cholesterol levels. The same results were found in a study from India. Mathur and coworkers [6] studied the changes in cholesterol levels subsequent to death and found them to be stable for at least 16 hours. Thus samples collected shortly after

International Health News

November 2007

Page 11

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