17 de Outubro, 2009
Relação entre colesterol total (CT) e mortalidade numa população da cidade japonesa de Fukui e meta-análise dessa relação no Japão, ou como existem populações onde os indivíduos com MAIOR longevidade são justamente os que possuem colesterol mais ALTO (acima de 240 mg/dl)
Foto: Comida japonesa.
Mais colesterol, maior longevidade
No meu artigo recente intitulado "Lowest mortality observed when total cholesterol (t-C) is 200-240 mg/dl, low t-C linked to more infectious and parasitic diseases and also low t-C maybe associated with higher CHD", porventura o mais relevante neste blogue até ao momento e que já ultrapassou as 2.000 leituras, referi que 31,7% dos homens portugueses tinha colesterol acima de 240 mg/dl. E também acrescentei que isso não seria necessariamente mau, que até poderia ser um marcador de longevidade. Ora, essa minha sugestão não foi completamente fortuita, resultava do facto/suspeita de que, existindo relativamente poucos países no mundo com CT médio acima de 220 mg/dl, poderia porventura até dar-se o caso da curva de mortalidade cardiovascular não ser em forma de U, mas antes em forma de J. Isso mesmo, a mortalidade cardiovascular seria SEMPRE DECRESCENTE com o aumento do colesterol total. Quanto mais colesterol total, MENOR MORTALIDADE CARDIOVASCULAR, indefinidamente. Inverosímil? Vejamos se é mesmo impossível.
É claro que esta ideia tem algo de especulativo, não é propriamente ciência feita, mas não haja dúvida de que é assim que nascem as ideias, colocando a criatividade em funcionamento, e acima de tudo não se deixando aprisionar em ideias pré-concebidas do passado, como a Hipótese Lipídica, pois claro. Naturalmente que, à luz do "conhecimento" actual, esta possibilidade para a população portuguesa seria facilmente ridicularizada pelo "especialistas". Mas o facto é que, como você já se deve ter apercebido pela série de ideias que aqui tenho colocado, sempre devidamente fundamentadas por artigos científicos e epidemiologia actualizada, existe agora FORTÍSSIMA evidência científica e epidemiológica, de variadas fontes e países, suportando o conceito de que a MAIORES níveis de colesterol total, e portanto também de LDL, está realmente associada MAIOR longevidade humana, e portanto MENOR mortalidade. Surpreendido?! Vai ficar mais a seguir.
Hipercolesterolemia japonesa, uma vantagem
Hoje descobri, no jornal científico da Japan Society for Lipid Nutrition, uma série de artigos que ajudam a enquadrar todas estas questões, relacionadas com a mortalidade total em função do colesterol total e da sua fracção LDL no que respeita à população japonesa. Este jornal japonês é bastante recente, mas a julgar pela amostra de artigos que pode ver abaixo, começaram com o pé-direito, completamente desvinculados dos mitos da hipótese lipídica, das dietas low-fat, da idea de que o distrito de Okinawa (ainda) é o mais saudável, etc. Infelizmente muitos não estão disponíveis em inglês, apenas os seus sumários. Mas um desses artigos, publicado em 2008 com o título "The Relationship between Total Blood Cholesterol Levels and All-cause Mortality in Fukui City, and Meta-analysis of This Relationship in Japan", está integralmente acessível em inglês e, em meu entender, dá plena plausibilidade à ideia de que colesterol total SUPERIOR a 240 mg/dl pode, de facto, ser um marcador de longevidade aumentada face ao resto da população. Pelo menos para a população japonesa analisada neste estudo isto acontece! (Nota: o primeiro estudo deste tipo feito no Japão foi publicado em 2003 e pode ser lido aqui).
Pois bem, aqui está a primeira BOMBA deste artigo, que analisou 22.971 indivíduos, entre os 40 e os 79 anos, da cidade japonesa de Fukui. Concluiu que, para homens e mulheres agrupados, se observa MENOR MORTALIDADE na classe de colesterol total 240-259 mg/dl. Eu vou repetir isto devagar: numa população japonesa de 22.971 indivíduos, verifica-se MENOR mortalidade por qualquer causa nas pessoas com Colesterol Total entre 240 (duzentos e quarenta) e 259 (duzentos e cinquenta e nove) miligramas por decilitro! Sugiro-lhe que repare bem no quadro da página 70 deste estudo, onde estão detalhadas as mortalidades por idade, sexo e causa. Uma coisa é absolutamente óbvia e isso salta aos olhos de qualquer pessoa: colesterol total abaixo de 160 mg/dl, ou até mesmo 180 mg/dl não é bom em situação alguma. A níveis baixos de colesterol (tanto Total como de LDL) está sempre associada MAIOR mortalidade, por variadíssimas causas, e no caso das mulheres japonesas também MAIOR mortalidade cardiovascular (inacreditável, pois claro, mas olhe para os números), o que é mais um paradoxo a juntar à lista. Nos homens o padrão é altamente irregular, isto apenas para exemplificar que os lípidos como CT e LDL, ao contrário do que os lóbies estatineiro e margarineiro nos querem fazer crer, são fraquíssimos marcadores de doença cardiovascular.
"However important the effect of cholesterol on CHD might be, the risk of all-cause mortality is lower at higher cholesterol levels. This is because of a very low incidence of CHD death in Japan (see introduction). Wether or not high cholesterol levels are a cause or effect of a high mortality, it is clinically very important to note that low cholesterol levels are associated to a sizable and significant extent with all-cause mortality (…)
Swithcing to LDL-cholesterol from the total cholesterol in the Guidelines is good because hypercholesterolemia due to high HDL-cholesterol levels can be excluded. At the same time, this switching is very confusing. There are very few epidemiological data about the relationship between LDL-cholesterol and deaths. Considering the present meta-analisis, JAS Guidelines appear to face a serious paradox. If a doctor prescribes cholesterol lowering medicines to subjects with cholesterol levels above 240 mg/dl (6.22 mmol/l), the doctor is prescribing medicines to those who have the least chance to die.
Those whose risk fo death is smallest probably have the least need for medication. Japanese subjects with cholesterol levels above 240 mg/dl (6.22 mmol/dl) should not be regarded as hypercholesterolemic or dyslipidemic because they are in the safest ranges in terms of all-cause mortality except for some genetic disorders like FH cases. Further studies are warranted."
É isso mesmo, depois na meta-análise os autores chegam mesmo a concluir, tendo por base os resultados do seu estudo, que indivíduos com níveis de colesterol acima de 240 mg/dl não devem ser vistos como hipercolesterolémicos ou dislipidémicos, pois são justamente os que estão no grupo de MENOR mortalidade. O que é evidente, pois claro, portanto não faz qualquer sentido falar de hipercolesterolemias, como se isso fosse uma desvantagem, em pessoas que vivem mais anos (por causa disso mesmo?), excepto nas situações de distúrbio genético que são obviamente uma minoria mas que distorcem as conclusões porque concentram-se sempre nas gamas altas de CT. E já agora, os autores referem este óbvio paradoxo (mais um paradoxo a juntar à lipidologia moderna, como já são poucos): qual a lógica de um médico estar a receitar medicamentos (estatinas para baixar colesterol) aos indivíduos que estatisticamente são justamente os que possuem menor risco de morrer?
Conclusões e hipótese
No Japão é assim. Haverá razão para acreditar que nas restantes populações do mundo estas conclusões, pelo menos nos seus aspectos qualitativos, não se manterão na generalidade? Na população portuguesa, por exemplo, os indivíduos com colesterol total acima de 240 mg/dl não estarão efectivamente predestinados a ter maior longevidade? É que não existe nenhum estudo nacional a analisar colesterol total e mortalidade para desmentir esta possibilidade, e existem estudos epidemiológicos internacionais a mostrarem que esta é uma possibilidade muitíssimo real. Tão real que, de facto, até se verifica no Japão!
Aqui estão os artigos do Journal of Lipid Nutrition:
The Relationship between Total Blood Cholesterol Levels and All-cause Mortality in Fukui City, and Meta-analysis of This Relationship in Japan (pdf, 2.1 Mb)
Yuko Kirihara1), Kei Hamazaki1), Tomohito Hamazaki1), Yoichi Ogushi2), Hisako Tsuji3) and Shoichiro Shirasaki4)
1) Division of Clinical Application, Department of Clinical Sciences, Institute of Natural Medicine, University of Toyama
2) Department of Medical Informatics, Tokai University School of Medicine
3) Health Examination Center of Moriguchi-city
4) Public Health Center of Fukui
(Received July 17, 2007)
(Accepted October 2, 2007)
Shirasaki published a Japanese paper about the relationship between total cholesterol levels and all-cause mortality in Fukui City, Japan. His cholesterol data were not grouped according to ordinal 20mg⁄dL (0.52 mmol⁄L) intervals. In the present study, we re-calculated his data for meta-analysis. The relative risk (RR) of all-cause mortality adjusted for age and sex showed a decreasing trend with total cholesterol levels (p for trend In order to summarize the relationship between total cholesterol and all-cause mortality, literature describing this relationship in Japan was collected mainly using computer search engines. Literature published before 1995 was excluded. Reports with the total number of study subjects smaller than 5,000 were also excluded. Five reports were found suitable for meta-analysis of cholesterol levels and all-cause mortality. Meta-analysis revealed that the RR in the
Japanese who are in a higher LDL-C level will live longer than those who are in a lower LDL-C level (pdf, 2.8 Mb)
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)
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.
Major points at issue and my opinion on the Guideline for Diagnosis and Prevention of Atherosclerotic Cardiovascular Diseases (Japan Atherosclerosis Society, 2007) (pdf, 2.6 Mb)
1) Open Research Center for Lipid Nutrition, College of Pharmacy, Kinjo Gakuin University
(Received November 13, 2008)
(Accepted January 20, 2009)
1. In the Guideline (2007), diagnostic criteria were proposed in terms of LDL-C instead of total cholesterol (TC). In the Joint Panel Discussion, it was criticized that no available data in Japan support the criteria proposed. Moreover, LDL-C was revealed to be a predictor of longevity in the Koriyama-Isehara Study.
2. The Guideline described that high-LDL-C is a risk factor for CHD even in aged populations, citing several references. However, the cited references do not present LDL-C but TC, and that the association of TC with CHD mortality is weak and not conclusive. An example was reproduced here that a significantly negative association of TC with CHD changed to positive after adjustments for several confounding factors. Thus, the evidence presented so far does not justify hypocholesterolemic medications but it tells us that such medications are inappropriate for aged populations.
3. Those with inborn genetic factors such as familial hypercholesterolemia (FH) and an apo E genotype are different from hypercholesterolemic non-FH subjects in that the supply of LDL-carried lipids to peripheral tissues is restricted from young ages in the former but is fulfilled in the latter. The delegates from the Japan Atherosclerosis Society appeared not to accept this interpretation.
As a chairperson, I emphasize that the ω6⁄ω3 balance of dietary and tissue lipids rather than plasma cholesterol is a critical factor for atherosclerotic diseases, and that dietary recommendations in the Guideline (2007) need to be revised.
Are the upper limits for serum cholesterol levels necessary?
-Serious problems found in Japan Atherosclerosis Society Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases (pdf, 2.7 Mb)
1) Department of Clinical Sciences, Institute of Natural Medicine, University of Toyama
(Received January 13, 2009)
(Accepted January 20, 2009)
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.
Pleiotropic effects of hypocholesterolemic drug statin
: Its merits and demerits (pdf, 3.3 Mb)
1) Tokyo Metropolitan Institute of Gerontology
(Received January 16, 2009)
(Accepted January 20, 2009)
Statins are potent inhibitors of cholesterol biosynthesis and have been used for the reduction of serum cholesterol levels to prevent cardiovascular diseases according to the cholesterol hypothesis of atherosclerosis. However, a wide varieties of beneficial effects of statins are known to rather actually occur earlier than serum cholesterol goes down, indicating cholesterol-independent effects. The effects beyond cholesterol lowering are socalled "pleiotropic effects" of statins, including eNOS expression, anti-oxidative function, anti-inflammatory action, osteomorphogenesis and so on. In addition to those, the effects of statins against carcinogenesis and degenerative processes in the brain leading to Alzheimer’s disease and Parkinson’s disease are examined in the literature.
The pleiotropic effects of statins observed so far might be the reverse of a coin, where serious impairments of physiological functions of the intermediates of cholesterol biosynthesis take place. Adverse effects may happen to be manifested in the course of long-term use of statins. Considering the not much size of the benefits, statins should not be given to a large population to avoid terrible side-effects or demerits. Statin use may rather be better to be confined to patients with familial hypercholesterolemia who definitely obtain merits.
Inspect the beginning of the fat heavy theory -One examination into about "the fat and the health" based on political science and lipid nutrition (pdf, 4.2 Mb)
1) Functional Foods Division, NOF CORPORATION
(Received November 12, 2007)
(Accepted January 30, 2008)
Though the fat are necessary to a body, it is a nutrient given a wide unfavorable compound in our country. The starting point of this minus image is measures of the cardiovascular disease that the U.S. Government shows the high prevalence in the country. As the nutrition guidance for anti- cardiovascular disease, decrease of the meal intake fat was carried out politically. The harm that had too much a fat intake, the fat heavy theory was that is to say proposed by McGovern report. The U.S. Government spent enormous expense and time and a talented person to prove this opinion, but the clinical data to support was not provided. The U.S. Government carried out the large-scale intervention examination of the long term of low-fat dietary, but the risk of a cardiovascular disease and breast cancer and the colorectal cancer did not fall down.
This proof was important as a political measure, but failed clinically. Adaptation to our country by the literal translation of the McGovern report led to the spread of the minus image of fat. The cause of the mistake is the difference of the fat intake volume between Japan and U.S.A. and a difference of the nutrient-related genetic polymorphism of the two countries.
If we control total calorie intake and enforce an exercise custom, we can erase the negative action of fats.
Animal food intakes and lipid nutrition in Okinawa prefecture (pdf, 586 kb)
Terue Kawabata1), Noriko Iwama2), Shigeji Miyagi1) and Kyoko Hasegawa1)
1) Faculty of Nutrition, Kagawa Nutrition University
2) Junior College of Kagawa Nutrition University
It has been revealed that the consumption level of meat (especially pork) in Japan is higher in the people from Okinawa than that reported by the Japanese National Nutritional survey. Therefore, we were prompted to conduct a detailed survey of the methods of cooking and eating pork in Okinawa prefecture. The results revealed that pork and pork products are often cooked with food groups such as green vegetables, beans, potatoes, and seaweeds. We considered that the cooking of pork and pork products was a major factor influencing the efficiency of consumption of various nutrients such as vitamins and minerals. In our dietary survey of the main Okinawa island conducted in 1997, the fat-energy ratio in the diet of male subjects 40-59 years was over 32%, which was considered to be due to the use of large amounts of vegetable oil for preparing stir-fried dishes (Champuru) and deep-fried dishes. The EPA(%) of erythrocyte membrane phospholipids was lower in young women about 20 years old of Okinawa as compared with that in their counterparts in the Kanto region, because of the low level of intake of fishes and shellfishes by the Okinawan women. Recently, the life expectancy for men in Okinawa Prefecture fell sharply to 26th among the 47 prefectures of Japan, perhaps attributable to the upward trend of the mortality rate from ischemic heart disease and the cerebrovascular disease. Thus, management of lipid nutrition in the Okinawan people is becoming a more and more important issue that must be addressed.