Re: One more safe alternative to statins

Bill wrote:
:: "Juhana Harju" <shantigiri@xxxxxxxxxxxxx> wrote in message
:: news:3g2he7Fa7ihlU1@xxxxxxxxxxxxxxxxx
::: Bill wrote:
::::: "Juhana Harju" <shantigiri@xxxxxxxxxxxxx> wrote in message
::::: news:3g2bqqFa8nunU1@xxxxxxxxxxxxxxxxx
:::::: Jim Chinnis wrote:
:::::::: Susan <nevermind@xxxxxxxxxx> wrote in part:
::::::::
::::::::: We know that pantethine is safer than statins, and as
::::::::: effective without risk.
::::::::
:::::::: It would take thousand of patients to demonstrate statistically
:::::::: significant reductions in mortality. To my knowledge, those
:::::::: studies have not been done usining pantethine. Neither have the
:::::::: necessary studies been done to show whether pantethine reduces
:::::::: second heart attacks, strokes, etc.
::::::::
:::::::: Large retrospective studies have linked statins to increased
:::::::: risk of polyneuropathy and decreased risks of cancer. Have
:::::::: there been any large retrospective sties of pantethine and
:::::::: polyneuropathy or cancer?
::::::::
:::::::: Aren't the kinds of data that have been assembled for and
:::::::: against statins mostly missing on pantethine?
::::::
:::::: In women and in elder people statins do not lower all-cause
:::::: mortality, which is after all what really counts.
:::::
::::: The following paper suggests that is not true in the elderly with
::::: CAD. What evidence do you have that it is true?
:::
::: I would like to question the whole policy of trying to reduce
::: cholesterol in the elderly population (people over 70 years). The
::: Honolulu Heart Program study below shows that cholesterol is
::: positively associated with higher survival in elderly populations.
::: I think that adopting a Mediterranean diet (especially fish oils)
::: would be much more successful approach than statins. Remember that
::: in the Lyon Heart Study was achieved a remarkable 50-70% reduction
::: in all-cause and cardiovascular mortality by relatively simple
::: dietary changes. The Mediterraean diet is also very palatable - so
::: the patient compliance to the diet should be very good. At the
::: moment that diet is not actively promoted by the health care
::: system.
:::
::: From other approaches the mortality reduction achieved by
::: *policosanol* in the elderly population seems to be far better than
::: what is achieved by statins. See my policosanol tolerability post
::: but also the comment by Thomas Carter in the sci.life-extension to
::: the same study:
:::
:::
http://groups-beta.google.com/group/sci.life-extension/msg/71e415eb0ffecfb5?hl=fi
:::
:::
::
:: First, this really does not address the issue. You claimed the
:: statins do not improve all cause mortality in the elderly. I
:: provided a study that shows it does at least for those with CAD -
:: which is the group statins are usually prescribed to. You need to
:: provided a study to show this is untrue. (The cause for improvement
:: could be something unrelated to cholesterol.)

You should know that it is a controversial issue whether statins provide any
benefit to the elderly people. You provided just one study.

:: Second it is not relevant whether anything else might, in your
:: opinion, work better.

Of course it is relevant. This thread is about safe alternatives to statins.
If I claim that policosanol works better than statins in reducing mortality
I am sticking to the topic.

:: You would have to show that people will stick
:: to a Mediterranean diet, for example, and show this through a study
:: vs. statins.

Please show me any statin study where the overall mortality is reduced by
70% like in this study:

Lancet. 1994 Jun 11;343(8911):1454-9.

Mediterranean alpha-linolenic acid-rich diet in secondary prevention of
coronary heart disease.

de Lorgeril M, Renaud S, Mamelle N, Salen P, Martin JL, Monjaud I, Guidollet
J, Touboul P, Delaye J.

INSERM (Institut National de la Sante et de la Recherche Medicale), Units
63, Bron, France.

In a prospective, randomised single-blinded secondary prevention trial we
compared the effect of a Mediterranean alpha-linolenic acid-rich diet to the
usual post-infarct prudent diet. After a first myocardial infarction,
patients were randomly assigned to the experimental (n = 302) or control
group (n = 303). Patients were seen again 8 weeks after randomisation, and
each year for 5 years. The experimental group consumed significantly less
lipids, saturated fat, cholesterol, and linoleic acid but more oleic and
alpha-linolenic acids confirmed by measurements in plasma. Serum lipids,
blood pressure, and body mass index remained similar in the 2 groups. In the
experimental group, plasma levels of albumin, vitamin E, and vitamin C were
increased, and granulocyte count decreased. After a mean follow up of 27
months, there were 16 cardiac deaths in the control and 3 in the
experimental group; 17 non-fatal myocardial infarction in the control and 5
in the experimental groups: a risk ratio for these two main endpoints
combined of 0.27 (95% CI 0.12-0.59, p = 0.001) after adjustment for
prognostic variables. Overall mortality was 20 in the control, 8 in the
experimental group, an adjusted risk ratio of 0.30 (95% CI 0.11-0.82, p =
0.02). An alpha-linolenic acid-rich Mediterranean diet seems to be more
efficient than presently used diets in the secondary prevention of coronary
events and death. PMID: 7911176

:: Third the study you quote is limited to Japanese/American men. It is
:: known that Asians respond differently to statins than those of
:: European origin. So I do not think you can generalize from this.

This is not the only study where a positive association is found between
cholesterol and survival in elderly population. Here are couple of Austrian
studies.

J Womens Health (Larchmt). 2004 Jan-Feb;13(1):41-53. Related Articles, Links

Why Eve is not Adam: prospective follow-up in 149650 women and men of
cholesterol and other risk factors related to cardiovascular and all-cause
mortality.

Ulmer H, Kelleher C, Diem G, Concin H.

Institute of Biostatistics and Documentation, Leopold Franzens University of
Innsbruck, Innsbruck, Austria. Hanno.Ulmer@xxxxxxxxxx

PURPOSE: To assess the impact of sex-specific patterns in cholesterol levels
on all-cause and cardiovascular mortality in the Vorarlberg Health
Monitoring and Promotion Programme (VHM&PP). METHODS : In this study, 67413
men and 82237 women (aged 20-95 years) underwent 454448 standardized
examinations, which included measures of blood pressure, height, weight, and
fasting samples for cholesterol, triglycerides, gamma-glutamyl transferase
(GGT), and glucose in the 15-year period 1985-1999. Relations between these
variables and risk of death were analyzed using two approaches of
multivariate analyses (Cox proportional hazard and GEE models). RESULTS:
Patterns of cholesterol levels showed marked differences between men and
women in relation to age and cause of death. The role of high cholesterol in
predicting death from coronary heart disease could be confirmed in men of
all ages and in women under the age of 50. In men, across the entire age
range, although of borderline significance under the age of 50, and in women
from the age of 50 onward only, low cholesterol was significantly associated
with all-cause mortality, showing significant associations with death
through cancer, liver diseases, and mental diseases. Triglycerides > 200
mg/dl had an effect in women 65 years and older but not in men. CONCLUSIONS:
This large-scale population-based study clearly demonstrates the contrasting
patterns of cholesterol level in relation to risk, particularly among those
less well studied previously, that is, women of all ages and younger people
of both sexes. For the first time, we demonstrate that the low cholesterol
effect occurs even among younger respondents, contradicting the previous
assessments among cohorts of older people that this is a proxy or marker for
frailty occurring with age. PMID: 15006277

You might also want to have a look at this illustrative slide presentation
( http://biostatistik.uibk.ac.at/ulmer/Presentation%20WHC%20Dublin.pdf ) by
Hanno Ulmer where he states that low cholesterol is "significantly
associated with all-cause mortality in men of all ages, and in women from
the age of 50 onwards only." This is the original full study:

http://eurheartj.oupjournals.org/cgi/reprint/24/11/1004

It seems that the reduction in mortality achieved by statins in the whole
population is not achieved so much by reduction in cholesterol but by other
mechanisms, perhaps by reduction in CRP. And this or course applies to
omega-3 fatty acids as well - they do not lower cholesterol, but still they
reduce mortality and even better than statins.

::: Lancet. 2001 Aug 4;358(9279):351-5.
:::
::: Cholesterol and all-cause mortality in elderly people from the
::: Honolulu Heart Program: a cohort study.
:::
::: Schatz IJ, Masaki K, Yano K, Chen R, Rodriguez BL, Curb JD.
:::
::: Clinical Epidemiology and Geriatrics Division, Department of
::: Medicine, John A Bums School of Medicine, University of Hawaii at
::: Manoa, 1356 Lusitana Street, 7th Floor, Honolulu, HI 96813-2427,
::: USA.
:::
::: BACKGROUND: A generally held belief is that cholesterol
::: concentrations should be kept low to lessen the risk of
::: cardiovascular disease. However, studies of the relation between
::: serum cholesterol and all-cause mortality in elderly people have
::: shown contrasting results. To investigate these discrepancies, we
::: did a longitudinal assessment of changes in both lipid and serum
::: cholesterol concentrations over 20 years, and compared them with
::: mortality. METHODS: Lipid and serum cholesterol concentrations were
::: measured in 3572 Japanese/American men (aged 71-93 years) as part
::: of the Honolulu Heart Program. We compared changes in these
::: concentrations over 20 years with all-cause mortality using three
::: different Cox proportional hazards models. FINDINGS: Mean
::: cholesterol fell significantly with increasing age. Age-adjusted
::: mortality rates were 68.3, 48.9, 41.1, and 43.3 for the first to
::: fourth quartiles of cholesterol concentrations, respectively.
::: Relative risks for mortality were 0.72 (95% CI 0.60-0.87), 0.60
::: (0.49-0.74), and 0.65 (0.53-0.80), in the second, third, and fourth
::: quartiles, respectively, with quartile 1 as reference. A Cox
::: proportional hazard model assessed changes in cholesterol
::: concentrations between examinations three and four. Only the group
::: with low cholesterol concentration at both examinations had a
::: significant association with mortality (risk ratio 1.64, 95% CI
::: 1.13-2.36). INTERPRETATION: We have been unable to explain our
::: results. These data cast doubt on the scientific justification for
::: lowering cholesterol to very low concentrations (<4.65 mmol/L) in
::: elderly people. PMID: 11502313
:::
:::
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11502313&dopt=Abstract
:::
:::
::::: See the paragraph that I marked with *****
:::::
::::: Bill
:::::
::::: Evidence-based Management of Coronary Artery Disease in the
::::: Elderly -- Current Perspectives CME
:::::
:::::
::::: Nanette Kass Wenger, MD Tarek Helmy, MD, FACC Amar D. Patel,
::::: MD Stamatios Lerakis, MD, FACC, FASE
:::::
::::: Medscape General Medicine 7(2):, 2005. © 2005 Medscape
::::: [...]
:::
::::: *******
:::::
::::: Lipid-lowering agents such as hydroxyl-methylglutaryl coenzyme A
::::: (HMG CoA) reductase inhibitors ("statins") also have survival
::::: benefit in hypercholesterolemic patients with CAD. In the 4S
::::: clinical trial, 2282 of the 4444 patients enrolled were at least
::::: 60 years of age and were randomized to either simvastatin or
::::: placebo. The relative risk reduction in death/MI was
::::: approximately 30% compared with placebo at a mean follow-up of 5
::::: years.[18] Treatment of elderly patients (aged >/= 60 years) with
::::: pravastatin with average cholesterol levels (total cholesterol
::::: 209 ± 17 mg/dL, high-density lipoprotein 39 ± 9 mg/dL, LDL 139 ±
::::: 15 mg/dL) in the Cholesterol and Recurrent Events (CARE) trial
::::: revealed a 27% relative risk reduction compared with placebo and
::::: a 26% relative risk reduction compared with patients aged younger
::::: than 60 years.[19] The Long-Term Intervention with Pravastatin in
::::: Ischaemic Disease (LIPID) Study Group demonstrated similar
::::: results, in addition to a reduction in UA events requiring
::::: hospitalization (29% relative risk reduction).[20] Benefit from
::::: simvastatin therapy is maintained in patients 70 years of age or
::::: older as evidenced by data from the Heart Protection Study.[21]
::::: The Prospective study of Pravastatin in the Elderly at Risk
::::: (PROSPER) study group specifically addressed the use of statin
::::: therapy in the elderly population. Approximately 5804 patients
::::: (average age 75 years [range 70-82 years]; 48% men) with a
::::: history of, or risk factors for, vascular disease were randomized
::::: to pravastatin 40 mg or placebo and followed for a mean duration
::::: of 3.2 years. Primary end points were CHD death, nonfatal MI, and
::::: stroke.[22] The follow-up data revealed a significant reduction
::::: in the composite primary end point with a 15% relative risk
::::: reduction compared with placebo. However, when analyzed
::::: separately, there was no significant reduction in cerebrovascular
::::: event rates. Further, the incidence of new cancer diagnoses was
::::: higher in the pravastatin group, but no evidence of heterogeneity
::::: of increased risk was observed when comparing these results with
::::: other statin trials. These data suggest benefit for aggressive
::::: lipid lowering in the elderly population. The Fluvastatin
::::: Assessment of the Morbidity/Mortality in the Elderly (FAME) trial
::::: will provide more elderly-specific data. [...]
:::
:::::: There are no reason to use statins in these
:::::: very large population groups. In women, increasing HDL and
:::::: lowering trglyserides is important if you want to lower
:::::: cardiovascular and all-cause mortality. Contary to statins these
:::::: alternatives are better in increasing HDL and decreasing
:::::: triglyserides, which is likely to benefit these large population
:::::: groups.
:::
::: --
::: Juhana

--
Juhana


.

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