The Cholesterol Times, Issue #003 -- Statins, Stroke, and Dementia

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Tue, 30 Aug 2005 02:27:07 UT

" Christopher Masterjohn "

<The_Cholesterol_Times

The Cholesterol Times, Issue #003 -- Statins, Stroke, and

Dementia

 

 

#

Statins Increase Dementia Risk

 

A July, 2005 study by Rea et al., published in the Archives of

Neurology reported that ever-use of statins, contrary to their

hypothesis, was not associated with a lowering of the risk of

Alzheimer's or other dementia.

 

(As discussed in a two-part article on our website, the myth that

cholesterol causes Alzheimer's disease has led to the investigation of

using statins to lower the risk of Alzheimer's.)

 

Actually, the interesting part of the study is not the effect of

ever-use or current-use of statins on dementia risk, but the huge

association of former use of statins with dementia risk.

 

The report was an analysis of data from the Cardiovascular Health

Cognition Study, which studied a subset of patients (numbering 2,798)

from the Cardiovascular Health Study.

 

After adjusting for some possible confounding factors, ever-use of

statins was associated with an 8% increase of risk of all-cause

dementia, a 21% increase in risk of Alzheimer's disease alone, a 13%

decrease in risk of mixed Alzheimer's and vascular dementia, and a 36%

increase in risk of vascular dementia alone, all at 95% confidence.

 

Yet current use of statins showed a very mild association with reduced

risk of all-cause dementia, and with reduced risk for all forms except

vascular dementia, where it was associated with a 39% increase in

risk. There was no dose-response effect between duration of statin use

and decreased risk, meaning that a patient did not experience a

greater reduction in risk when statins were used for a longer period

of time. Dose-response analysis wasn't provided for dosage of statins

or the cholesterol-lowering effect of the statins.

 

Why the discrepancy between ever-use and current-use? Because former

use was associated, after adjusting for confounding factors, with a

whopping 88% increase in all-cause dementia, a 154% increase in

Alzheimer's disease, and a 61% increase in mixed Alzheimer's and

vascular dementia.

 

Put another way, someone who uses statins currently is 92% as likely

to develop Alzheimer's as someone who never used statins, yet someone

who previously used statins and stopped statin therapy is 254% as

likely to develop Alzheimer's disease than someone who never used statins.

 

The authors suggested that stopping and starting statin therapy might

somehow trigger the dementia process, but claimed it was more likely

that former use is a marker for declining health, and " patients and

physicians may be less inclined to maintain preventive treatments such

as statin use as overall health deteriorates. "

 

Remarkably, the authors did not suggest the possibility that a decline

in health may be caused by the statin therapy! After all, is it not

more likely for a patient to discontinue statin therapy if memory

loss, fatigue, or the widely reported problems with myopathy settle in?

 

It seems less likely that the author's suggestion-- patients and

physicians simply give up hope and don't bother with drugs if they see

health declining-- would occur, especially if statin therapy had

already been initiated. It would be much more likely that statin

therapy would be terminated due to the widely experienced adverse effects.

 

The protective effects of current use were mild, and the authors noted

that confounding factors could have been involved and that " additional

investigation is needed to determine whether and for whom statin use

may affect dementia risk. "

 

But the harmful effects of former use are very pronounced, leading to

an almost doubling of the risk of all-cause dementia and an even more

massive increase in Alzheimer's, by a factor of 2.54.

 

It may be that the extremely modest 10% reduction in all-cause

dementia of current statin users simply indicates that those who have

the most resilient health can tolerate the negative effects of statin

(lowering brain cholesterol, vitamin E, and coeznyme Q10 levels, for

example), while those who are vulnerable to these effects have their

mental health utterly ravaged, nearly doubling their risk of dementia.

 

For more information on the myth that cholesterol causes Alzheimer's

disease, please see our article, Myth: Cholesterol Causes Alzheimer's

Disease as well as Part II: The Real Causes of Alzheimer's.

 

Statins Double Risk of Stroke

 

Another July study in the New England Journal of Medicine by Wanner et

al., found that atorvastatin had no statistically significant (meaning

the liklihood the correlation was due to chance was less than 5%)

effect on total mortality in Type 2 diabetes patients undergoing

hemodialysis, but more than doubled the risk of stroke.

 

The study was a multicenter, randomized, double-blind prospective

study of 1255 subjects. The data were monitored, collected, and held

by Pfizer-supported organizations, but the data were analyzed by

independent, academic scientists.

 

The increase in risk of stroke was the only statistically significant

effect on any individual endpoint that was considered, but when all

cardiac events were grouped together, there was a significant 18%

reduction in all cardiac events.

 

The study did not provide information about the dose-reponse

relationship between cholesterol levels and endpoints, but they note

that the assumed relationship between cholesterol levels and heart

disease indicates a risk reduction of 30% or more for cardiac events,

whereas the risk reduction achieved was only 18%. Since statins have

some benefits (as well as major risks) that would be expected to lower

heart disease independent of cholesterol, this suggests that the

reduction in heart disease was not due to cholesterol-lowering.

 

The authors, in fact, noted that this risk reduction was " driven

mainly by differences in the rates of coronary-artery bypass grafting

and percutaneous transluminal coronary angioplasty, " -- not cholesterol

levels.

 

The reduction in cardiac events was compensated for by a more than

doubling of fatal stroke. Risk of fatal stroke was increased by

atorvastatin by a factor of 2.03.

 

While there was a 7% reduction in mortality among the atorvastatin

group (totaling a difference of 23 individual deaths), it did not even

approach statistical significance, with a 33% liklihood of being due

to chance. Additionally, patients in the atorvastatin group were 68%

more likely to discontinue the drug because of complications, which

alone totals an excess of 21 individual patients, which emphasizes the

meaninglessness of the reduction of total mortality, and the liklihood

of confounding factors.

 

What this study found is:

 

# supporting evidence that reduction in heart disease fatality with

statins is not due to their cholesterol-lowering activity

# statins offer a chance to trade dying of heart disease for dying of

stroke

 

Since there is evidence that statins cause cancer, and, as noted

above, that statins cause dementia, it may be that statins offer much,

much more in the risk department than the benefit department.

 

One must wonder how many patients would accept statin treatment if it

were described as a way to die of stroke rather than heart disease.

 

Oxidative Stress and Heart Disease

 

A third study from last month, published in the New England Journal of

Medicine by Tsimikas et al., found that, in people under the age of

60, it is oxidized phospholipids within LDLs, not the cholesterol, nor

the mere presence of LDLs, that contribute to obstructive coronary

artery disease.

 

Oxidative damage occurs when oxidizing agents (induced by smoking,

exercise, normal metabolism, pollutants, etc) exceeds the protective

effects of antioxidants (which includes many vitamins and other

compounds found in unrefined foods of both animal and plant origin).

 

In those younger than 60, the percentage of phospholipids associated

with lipoproteins that were oxidized was a better predictor (52%

increase per doubling) of obstructed arteries than LDL (46% per

doubling), but male sex was the most important variable, increasing

one's chance of obstructed arteries by 340%.

 

When combined with hypercholesterolemia, the predictive value of

oxidized phospholipids was enhanced roughly by a factor of 4. This, of

course, is an indication of the absolute amount of oxidized

phospholipids. For a constant percentage of LDL-associated

phospholipids that are oxidized, the more LDL there is, the more

oxidized phospholipids there are.

 

The proportion of oxidized phospholipids was strongly correlated with

lipoprotein A, or Lp(a). The authors cite evidence that Lp(a) is

involved in wound healing and preventing tumor growth, and that its

levels are elevated in centenarians, and suggest that it is involved

in " cleaning out " oxidized phospholipids from the body.

 

They also speculate that at chronic, high levels it could be

proatherogenic (meaning it causes atherosclerosis), but that it is

levels of oxidative stress that are the root cause of this phenomenon.

 

In patients over the age of 60, on the other hand, there was a very

weak negative correlation between the proportion of oxidized

phospholipids and coronary artery obstruction, but it was not

statistically significant. The association of obstructed arteries and

LDL also became very weak and not statistically significant above age 60.

 

It should be remembered that most heart attakcs occur above the age of

60 when we consider the importance of these findings.