Re: Good and bad LDL

Hi Alan S:

Finally, Dr Davis on the Heartscan blog promotes a rather
tighter ratio of 60:60:60 for trigs:HDL:LDL in mg/dl terms.
I must admit, for me that is still a distant goal.
http://tinyurl.com/3dvssz or
http://heartscanblog.blogspot.com/search/label/How%20tough%20is%20the%20Track%20Your%20Plaque%2060-60-60%20target%3F

http://tinyurl.com/3d73wb

I have been near or better than the 60 goals for HDL and TG for about 6 years. I have not gotten to the 60 on LDL and don't think I would unless I was on one of the more powerful statins. I have been on Lescol for about 15 years and most of the last 10 on a 40 mg/d dose. I have generally been pro-statin, but I do have my doubts. I tried going without Lescol for about 6 weeks to see if some pain would decrease, but this had no effect so I resumed it.

Dr. Davis said in his blog:
"In other words, we generally see best results when LDL is reduced to 60 mg/dl, HDL raised to 60 mg/dl, triglycerides reduced to 60 mg/dl. Now, these are not absolute requirements. Someone can have a spectacular drop in heart scan score even with an HDL of 56, LDL of 71. But the "Rule of 60" provides a useful target that is easy to remember, packs real power, and is clearly beyond that achieved with conventional approaches."

"Previous explorations of a link between statins, a cholesterol lowering medication, and cognitive decline have produced inconsistent results. New research reveals that the relationship between statin use and cognitive decline appears even more complex than had been thought. ... The researchers also compared use of statins and whether, if used, they were taken consistently. While cognitive decline in statin users was less than those who did not take statins, those who continued to take statins from 2001 to 2004 had greater cognitive decline than those who were taking statins in 2001 but were no longer taking them in 2004."
This news release was based on the study immediately below this link.
Study Of Relationship Between Statins And Cognitive Decline -
http://www.medicalnewstoday.com/articles/87841.php

Association of statin use with cognitive decline in elderly African Americans -
http://www.neurology.org/cgi/content/abstract/69/19/1873
"Results: Adjusting for age at baseline, gender, education, and the possession of ApoE {varepsilon}4 allele, baseline statin use was associated with less cognitive decline (p = 0.0177). There were no significant interactions of statin use when LDL-C and CRP were included. Logistic regression with the four independent variables showed that statin use may be associated with a reduction in incident dementia (OR = 0.32; p = 0.0673). Association with cognitive decline was less clear when investigating statin use over time. Significance remained only for those who discontinued prior to follow-up compared to continuous users or users who started after baseline.

Conclusions: The relationship between statin use and cognitive decline is complex and subjected to unknown confounders. This effect may not be associated with the cholesterol lowering or anti-inflammatory action of statins."

Another case where it would be nice to have access to the full article.

An earlier article that may have been referenced in the news release.
Cholesterol, APOE genotype, and Alzheimer disease -
http://www.neurology.org/cgi/content/abstract/66/2/223

Simvastatin Linked to Reduced Incidence of Dementia, Parkinson's
Disease

July 24, 2007 — Research links simvastatin to a reduction in the
incidence of both dementia and Parkinson's disease (PD) of greater
than 50%.

In contrast, atorvastatin is associated with a modest, but
insignificant, reduction in the incidence of the 2 diseases, and
lovastatin has no impact on incidence.

"This study suggests brain penetrant statins are more effective at
preventing neurodegenerative disease than impenetrant statins,"
principal investigator Benjamin Wolozin, MD, from Boston University
School of Medicine in Massachusetts, told Medscape.

"There are many statins out there. Some are very effective for
preventing cardiovascular disease but not all of them cross the blood-
brain barrier equally and, therefore, may not have the same impact on
neurodegenerative disease.

"Simvastatin crosses into the brain very effectively, whereas
atorvastatin just doesn't achieve as high a level [in the brain].
Lovastatin crosses the blood-brain barrier nicely but it is a first
generation statin and therefore is just not as potent as some of the
newer agents," he added.

The study is published in the July 19 issue of BMC Medicine.
Previous Research Yielded Conflicting Results

According to Dr. Wolozin, previous research looking at a potential
protective effect of statins and dementia, including work by his
group, has yielded conflicting results. In part, this was because the
numbers of study subjects were not sufficiently powered to detect any
statistically significant effect of statins on incident dementia.

However, the current study used the Decision Support System database
of the US Veterans Affairs medical system. This large population-based
database contains diagnostic, medication, and demographic information
on 4.5 million subjects, 94.4% of whom are men.

Prescription utilization was tracked for every subject between 2003
and 2005. Lovastatin, simvastatin, and atorvastatin all had large
numbers of prescriptions during this period. Data were obtained for
727,128 subjects taking simvastatin, 53,869 subjects taking
atorvastatin, and 54,052 who were prescribed lovastatin.

Fluvastatin and pravastatin were also included. However, according to
the authors, the number of subjects taking pravastatin was too small
to produce reliable data. Furthermore, a marked increase in
fluvastatin during the study period meant subjects' duration of
exposure to this statin was much less than that for the other 3
agents. As a result, researchers did not pursue further studies of
fluvastatin or pravastatin.
Magnitude of Effect Surprising

Using 3 models for analysis, researchers looked at the incidence of
dementia and PD among subjects who had continuously used a statin for
at least 7 months.

The first model adjusted only for age; the second model, for 3 major
dementia risk factors, including cardiovascular disease, hypertension,
and diabetes; and the third model, for the Charlson index, which is an
index that provides a broad assessment of chronic disease.

With respect to dementia, researchers found simvastatin was associated
with significant reduction in the incidence of dementia using any of
the 3 models. In addition, said Dr. Wolozin, the study revealed a
similar decrease in incident PD associated with simvastatin.

"We were very surprised by the size of the effect associated with
simvastatin and that it worked for both Parkinson's disease and
dementia. We were also surprised that atorvastatin hardly had any
impact on the incidence of either disease," he said.

While a number of researchers have speculated that statins' apparent
protective effect against dementia is caused by an amyloid-lowering
mechanism, this study refutes that hypothesis.

"Dementia and Parkinson's disease are both neurodegenerative
conditions. Dementia is typically characterized by the build-up of β-
amyloid plaques, but this is not the case with Parkinson's. If you
accept that statins are acting by a similar mechanism in both diseases
it makes it very unlikely that it is acting through an amyloid-
lowering mechanism. The most likely mechanism, and one that is most
commonly accepted, is that statins protect the brain through an anti-
inflammatory mechanism," he said.
Potential Mechanisms

On the other hand, he said a "provocative and interesting" animal
study conducted by Johnson-Anuna and colleagues at the University of
Minnesota and published in the February 2005 issue of the Journal of
Pharmacology and Experimental Therapeutics suggests the
neuroprotective effect of statins may be related to their ability to
increase growth factors in the brain.

Based on the study's results, Dr. Wolozin said clinicians might want
to consider an individual patient's family history when choosing a
statin.

"If a patient has a family history of dementia, simvastatin may be a
better choice than other agents. On the other hand, we know
atorvastatin is somewhat better than simvastatin at preventing
morbidity from cardiovascular disease, so if a patient has no dementia
history but has cardiovascular risk factors, they may be better off
taking atorvastatin. It really boils down to personalized medicine,"
said Dr. Wolozin.

He added that these findings need to be prospectively confirmed in
other population-based studies.

BMC Med. Published online July 19, 2007.

Simvastatin is associated with a reduced incidence of dementia and
Parkinson's disease -
http://www.biomedcentral.com/content/pdf/1741-7015-5-20.pdf

Wolozin+simvastatin - http://tinyurl.com/3dljlo

Frank
.

Relevant Pages

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