8 replies to this topic

[Sillewater]

I was perusing this book: Healthy Agriculture, Healthy Nutrition, Healthy People (which I don't have access to, so I used Google Books). There is an interesting paper in there titled:

World Rev Nutr Diet. 2011;102:124-36. Epub 2011 Aug 5.New Cholesterol Guidelines for Longevity (2010).Okuyama H, Hamazaki T, Ogushi Y; Committee on Cholesterol Guidelines for Longevity, the Japan Society for Lipid Nutrition.

http://imageshack.us...534b534b53.jpg/

They show this picture which summarizes the gist of the author's opinion which says that higher LDL and TC are protective in terms of ALL-Cause mortality. They make the claim that ever since the Vioxx scandal the EU has been much tougher on drug companies, and in post-2004 studies done by INDEPENDENT scientists the studies show no benefit of statins. And they summarize it in this table:

http://imageshack.us...fjgfjgfjgf.jpg/

Anyway in the parts available on Google Books the authors cite some studies supporting their claim in Figure 1 (as in this post).

Japanese who are in a higher LDL-C level will live longer than those who are in a lower LDL-C level Yoichi Ogushi¹⁾ and Syoutai Kobayashi²⁾ 1) Department of Medical Informatics of Tokai University School of Medicine
2) Shimane University Hospital (Received October 30, 2008) (Accepted January 20, 2009)
Summary
The targets of lipid lowering therapy in Japan are severer than those in western countries. Two hundred twenty mg⁄dl for total cholesterol (TCH), 140mg⁄dl for LDL-C, 150 mg⁄dl for triglyceride (TG) are used for the target values. In western countries, those values are 270 mg⁄dl, 190 mg⁄dl and 1,000 mg⁄dl respectively for low risk persons. But, a morbidity rate of coronary heart disease in Japan is a third in western countries. Strange to say, the number of women who accepts the therapy is twice of that of men in Japan. We have verified the targets used in Japan by some kinds of studies. We established clinical reference intervals of TCH, LDL-C, TG and HDL-C from the results of health checkup of about 700,000 persons by the method comparable to NCCLS in USA. We performed cohort studies and found cutoff points where mortalities increased significantly. These results are equal to the targets used in western countries. People diagnosed as hyperlipidemia by Japanese standard have less morbidity of strokes. If they develop strokes, their clinical indexes are better than persons in normal lipid level. In conclusion, the guideline for hyperlipidemia in Japan should be revised according to Japanese evidences soon.

Are the upper limits for serum cholesterol levels necessary?
Serious problems found in Japan Atherosclerosis Society Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases Tomohito Hamazaki¹⁾ 1) Department of Clinical Sciences, Institute of Natural Medicine, University of Toyama (Received January 13, 2009) (Accepted January 20, 2009)
Summary
In 2007, Japan Atherosclerosis Society published Guidelines for prevention of atherosclerotic cardiovascular diseases. However, the Guidelines had serious flaws with regard to serum cholesterol levels. The followings are the list of those flaws: #1. They started to use LDL-cholesterol (LDL-C) levels instead of serum total cholesterol (TC) levels. In this case they must show at least some basic data on the relationship between LDL-C and mortality or morbidity from coronary heart disease (CHD). In the Guidelines there were no such data at all! #2. They recommended LDL-C be below 140 mg⁄dL or 3.6 mmol⁄L (corresponding to TC of 220 mg⁄dL or 5.7 mmol⁄L). These levels were unreasonable considering that TC levels of 240-260 are the best in terms of all-cause mortality in Japan. They did not show any data on all-cause mortality in the Guidelines. #3. There are big differences in mortality and morbidity from CHD between sexes. However, they discussed the matter without differentiating sexes, just counting being male as one risk factor. #4. Conflict of interest of editors of the Guidelines has never been disclosed as of the end of year 2008. #4. Diets for preventing CHD have never succeeded in Japan yet. #5. The only large-scaled study with a statin in Japan (MEGA Study) had incredible defects; the cholesterol-lowering strategy depended on that extremely unreliable study. #6. The astonishing results of 4S (Simvastatin Scandinavian Survival Study) has hardly been reproduced by any other trials. There are serious doubts about the data from pharmaceutical company-supported trials. In conclusion, familial hypercholesterolemia is probably the only target of statins.

Do people think this difference is due to the fact that the incidence of stroke is larger in Japan then elsewhere, thus moving the mortality optimum?

They also cite this stroke study:

Circulation. 2009 Apr 28;119(16):2136-45. Epub 2009 Apr 13.
Low-density lipoprotein cholesterol concentrations and death due to intraparenchymal hemorrhage: the Ibaraki Prefectural Health Study.

Noda H, Iso H, Irie F, Sairenchi T, Ohtaka E, Doi M, Izumi Y, Ohta H.

Anyway, I don't have access to the full book, but I would love to read it. However I find what I have read to be interesting. When I tried sieving through all the data I found that

Just so its not all Japanese papers, here is an analysis done by the controversial Therapeutics Initiative in Canada: http://ti.ubc.ca/letter77 The conclusion is:

Conclusions

• Systematic reviews and meta-analyses are challenging and require much more than locating RCTs and plugging in the numbers.
• The claimed mortality benefit of statins for primary prevention is more likely a measure of bias than a real effect.
• The reduction in major CHD serious adverse events with statins as compared to placebo is not reflected in a reduction in total serious adverse events.
• Statins do not have a proven net health benefit in primary prevention populations and thus when used in that setting do not represent good use of scarce health care resources.

I would love to hear MR and Kismet's response to this.

N.B. for those olive oil lovers out there, apparently there is a carbon neutral olive oil out now: World Rev Nutr Diet.

2011;102:221-5. Epub 2011 Aug 5.
The first carbon neutral extra virgin olive oil in the world!

Kefalogiannis A.

Edited by Sillewater, 13 November 2011 - 07:10 AM.

[Sillewater]

They also quoted this study:

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

Source

Institute of Biostatistics and Documentation, Leopold Franzens University of Innsbruck, Innsbruck, Austria. Hanno.Ulmer@uibk.ac.at

Abstract

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.

I tried reading it but the analysis was complicated so I'll read it again later.

also here's an interesting site to peruse: http://www.health-he...cholesterol.htm

Edited by Sillewater, 13 November 2011 - 07:19 AM.

[Sillewater]

And a more recent skeptic:

J Eval Clin Pract. 2011 Sep 25. doi: 10.1111/j.1365-2753.2011.01767.x. [Epub ahead of print]
Is the use of cholesterol in mortality risk algorithms in clinical guidelines valid? Ten years prospective data from the Norwegian HUNT 2 study.
Petursson H, Sigurdsson JA, Bengtsson C, Nilsen TI, Getz L.

Rationale, aims and objectives  Many clinical guidelines for cardiovascular disease (CVD) prevention contain risk estimation charts/calculators. These have shown a tendency to overestimate risk, which indicates that there might be theoretical flaws in the algorithms. Total cholesterol is a frequently used variable in the risk estimates. Some studies indicate that the predictive properties of cholesterol might not be as straightforward as widely assumed. Our aim was to document the strength and validity of total cholesterol as a risk factor for mortality in a well-defined, general Norwegian population without known CVD at baseline. Methods  We assessed the association of total serum cholesterol with total mortality, as well as mortality from CVD and ischaemic heart disease (IHD), using Cox proportional hazard models. The study population comprises 52 087 Norwegians, aged 20-74, who participated in the Nord-Trøndelag Health Study (HUNT 2, 1995-1997) and were followed-up on cause-specific mortality for 10 years (510 297 person-years in total). Results  Among women, cholesterol had an inverse association with all-cause mortality [hazard ratio (HR): 0.94; 95% confidence interval (CI): 0.89-0.99 per 1.0 mmol L(-1) increase] as well as CVD mortality (HR: 0.97; 95% CI: 0.88-1.07). The association with IHD mortality (HR: 1.07; 95% CI: 0.92-1.24) was not linear but seemed to follow a 'U-shaped' curve, with the highest mortality <5.0 and ≥7.0 mmol L(-1) . Among men, the association of cholesterol with mortality from CVD (HR: 1.06; 95% CI: 0.98-1.15) and in total (HR: 0.98; 95% CI: 0.93-1.03) followed a 'U-shaped' pattern. Conclusion  Our study provides an updated epidemiological indication of possible errors in the CVD risk algorithms of many clinical guidelines. If our findings are generalizable, clinical and public health recommendations regarding the 'dangers' of cholesterol should be revised. This is especially true for women, for whom moderately elevated cholesterol (by current standards) may prove to be not only harmless but even beneficial.

PMID: 21951982

edit: added missing abstract text

Edited by niner, 14 November 2011 - 03:46 PM.

[Luminosity]

It's a little hard to follow but I have some opinions on blood fats and I happen to have spent a lot of time around Japanese people. Males from Japan smoke like chimneys. It's not uncommon for them to drink to excess, so that would be a factor in their health problems. On the positive side, people in Japan eat a lot of rice and fish, including raw fish and drink a lot of tea, especially green tea. Traditionally, they have not had as much sugar as we have and do not eat as much dairy. They don't usually overeat.

I think that good fats are good for you, especially those in fresh raw fish, nuts, organic dairy and a few other things. I don't think you can hurt yourself eating good quality seafood or nuts. I personally would have concerns about taking Western drugs to lower cholesterol when I think there are better, more natural ways. I feel it's best never to eat hydrogenated oils, margarine or shortening. Personally, I think if you eat the right things and exercise then you will probably be fine with your blood fats, but if not, then there are natural remedies to pursue.

[kismet]

Just so its not all Japanese papers, here is an analysis done by the controversial Therapeutics Initiative in Canada: http://ti.ubc.ca/letter77 The conclusion is:

What are they and do they have an axe to grind? A recent Cochrane analysis DID confirm mortality benefits in primary prevention, with some ifs and buts. My post:
http://www.longecity...post__p__461490

Briefly:
The cholesterol-mortality link is attributed to short follow-up and reverse causation. You must find studies with >>10y of follow-up that support your (their) hypothesis, I am looking myself.

classical paper
Am J Epidemiol. 1992 Jun 1;135(11):1251-8.
Short- and long-term association of serum cholesterol with mortality. The 25-year follow-up of the Finnish cohorts of the seven countries study. Pekkanen et al.

[Sillewater]

Thanks kismet, I have been looking through papers too and some with 12-14 year follow-ups show low cholesterol associated with increased cancer. Does pre-clinical cancers really affect that far back, or would it be the lifestyle combined with the age causing the decrease in cholesterol. In CR-folk hormone levels and cholesterol levels are maintained, while those with unhealthy lifestyles would find decreases in various biomarkers (and increases in others). Anyway, I am still looking through a lot of studies, I just find it odd that a lot of Japanese papers (with >10year follow-ups) find this inverse association. However looking at this paper:

J Natl Cancer Inst. 2011 Mar 16;103(6):508-19. Epub 2011 Feb 1.Low-density lipoprotein cholesterol and the risk of cancer: a mendelian randomization study.Benn M, Tybjærg-Hansen A, Stender S, Frikke-Schmidt R, Nordestgaard BG.

has made me feel safer with my lower cholesterol levels.

[kismet]

J Natl Cancer Inst. 2011 Mar 16;103(6):508-19. Epub 2011 Feb 1.Low-density lipoprotein cholesterol and the risk of cancer: a mendelian randomization study.Benn M, Tybjærg-Hansen A, Stender S, Frikke-Schmidt R, Nordestgaard BG.

has made me feel safer with my lower cholesterol levels.

This is an elegant way to study the question (or part of it: a reduction of cholesterol might still lead to increased cancer risk vs inherited low cholesterol) Many other study designs are also reassuring, particularly, meta-analyses of statin drug trials.

Which (Japanese) cohorts in particular? I'll take a look if I find them
at least JPHC is consistent with no risk:
After exclusion for first 3-year incident cases and advanced cases with metastasis, the inverse association diminished for total and stomach cancers but remained for liver cancer… our findings do not support that low serum total cholesterol levels increase risks of total cancer and other major sites.

Int J Cancer. 2009 Dec 1;125(11):2679-86.
Serum cholesterol levels in relation to the incidence of cancer: the JPHC study cohorts.
Iso H, Ikeda A, Inoue M, Sato S, Tsugane S; JPHC Study Group.

Surprisingly, the most recent meta-analysis I found is from the 90s (can someone access the full pdf?):

1994. Low cholesterol and risk of non-coronary mortality
R. John Simes

...and they excluded only - yes, only - the first 5 years. And there was some residual risk, but 5 years is on the short side.

Many studies find that cholesterol decreases loong before death:

"The mean fall in serum total cholesterol in the 4- to 6-year period before cancer death is 8.06 (95% confidence interval = 4.58-11.54) mg per dl, with some evidence of lowered cholesterol before that period. This pattern is corroborated by evidence of a substantially increased odds of cancer death if a large fall in cholesterol occurs over any 4- to 6-year period."

Epidemiology. 1997 Mar;8(2):132-6.
Time trends in serum cholesterol before cancer death.
Sharp SJ, Pocock SJ.

Cancers can have latencies of >20y, so this is plausible. Other effects may also be at play.

[Jay]

If you haven't already read Chris Masterjohn's write up on serum cholesterol and CVD, you should: http://www.cholester...erol-blog.html.

I can't figure out how to link to the article on his blog that is most relevant but search for "Genes, LDL-Cholesterol Levels, and the Central Role of LDL Receptor Activity In Heart Disease," written on Monday, March 14, 2011.

Edited by Jay, 18 November 2011 - 08:27 PM.

[Sillewater]

I've read his stuff, don't believe him.

Thanks kismet for that last study, wow greater then 6 years! That would make a lot more studies make sense. I'll post up some of those cohort studies later.