根据肌红蛋白的多少以及外观颜色的深浅，可将肉类分为“红肉”（如牛、羊、猪肉）和“白肉”（如鱼、禽肉）。一般认为，红肉能增大心血管病的发病风险，被称为“有害”健康的肉类，少吃为妙，而白肉不增大心血管病的发病风险，被称为“有益”健康的肉类，多吃无妨。 但是，官方机构发布的食品消费指南并无明确规定：白肉可多吃，红肉要少吃。比如，1992年美国USDA发布的Food Guid Pyramid就因未区分红肉与白肉而饱受诟病。为此，该指南于2005年推出修改的MyPyramid，但仍未明确红肉与白肉对健康的影响，仅把鱼、坚果、种子看做健康食品，可以经常食用，以取代肉类或禽类（fish, nuts, and seeds contain healthy oils, so choose these foods frequently instead of meat or poultry）。 到了2011年，USDA又推出新版MyPlate，再次未区分红肉与白肉，只是建议每周吃8盎司的鱼。不过，哈佛公共卫生学院于 同年发布了不同于USDA的Healthy Eating Plate，宣称食用过多红肉及腌制肉可增大心脏病、糖尿病和肠癌风险，所以不要吃腌制肉，红肉也要限制在每周不超过两次。用鱼、鸡、坚果、豆类代替红肉和腌制肉可以改善胆固醇水平，并能降低心脏病与糖尿病风险（ Eating a lot of red meat and processed meat has been linked to increased risk of heart disease, diabetes, and colon cancer. So it’s best to avoid processed meat, and to limit red meat to no more than twice a week. Switching to fish, chicken, nuts, or beans in place of red meat and processed meat can improve cholesterol levels and can lower the risk of heart disease and diabetes）。 由此可见，不管红肉或白肉，也不管是谁发布的食品指南，鱼肉对健康有益应该是普遍接受的共识。我昨天发表了一篇奇文（ 鱼肉也是肉，吃多也不妙 ），应声者寥寥，想必我的观点得不到普遍认同。今天我就来继续挖掘一下，用别人的实验数据说话，以免让大家觉得我只是一味地想当然。 首先来看一看“北欧健康食品”（全麦面包、燕麦片、苹果或梨、根菜类、卷心菜和鱼）对心血管病（缺血性心脏病、中风、心律不齐、血栓症和高血压病）的影响。今年5月19日在《内科学杂志》（J Intern Med）发表的一篇文章（ joim12378.pdf ）指出，在瑞典妇女中，北欧健康食品指数与心血管病风险之间没有相关性，说明不吃红肉、只吃白肉和蔬菜、水果并不能降低心血管病发生的风险。相反，风险来自吸烟，而该食谱对吸烟者有所改善。 下面再来看看鱼肉对痛风发作的影响。这里有一篇今年3月25日刚发表在《 关节炎与 类风湿病学》（Arthritis Rheumatol）上的最新研究论文，作者来自新加坡国立大学和美国匹兹堡大学。他们得出的结论是：来自禽类、鱼和海鲜的总蛋白摄入与痛风发作高风险有关，而食用黄豆及其他豆类则与痛风发作低风险有关。 具体来说，在 2167名 参试华裔痛风患者中，痛风发作风险最高的食品是总蛋白（1.27）和禽类（1.27），其次是鱼和海鲜（1.16），豆制品的风险较低（0.86），黄豆的风险最低（0.83）。至于摄入其他来源的蛋白质（红肉、蛋、奶制品、谷类、坚果和种子），并不显著增加风险。 最后来看看昨天提到的在北极圈内生活的爱斯基摩人与因纽特人的心脏病发作风险与“爱斯基摩膳食”（Eskimo Diets）之间的关系。此处的所谓“爱斯基摩膳食”由大量海豹及鲸脂（动物来源的油脂）组成，应该是人们最热衷的“深海鱼油”。 2014年8月，《加拿大心脏学杂志》（Can J Cardiol）发表了一篇由加拿大、德国和斯洛伐克学者共同撰写的综述文章，彻底否定了1970年代提出的“爱斯基摩膳食与低冠心病（CAD）发生率”的观点，并证实格林兰岛爱斯基摩人及北美因纽特人与非爱斯基摩人的CAD发病率相近（ file.pdf ）。 事实上，爱斯基摩人的脑血管中风死亡率比非爱斯基摩人翻了一番，其寿命也比非爱斯基摩人的丹麦人短了大约10年。这充分说明鱼肉既不能降低CAD风险，也不能延长人的寿命。由此推而广之，作者也不认为ω-3脂肪酸能降低 CAD风险。可是，仅美国就有1100万成年人及50万儿童服用深海鱼油胶囊。 2013年发表的一篇评论（ 1471-2318-13-41.pdf ）指出， 老年人服用鱼油适得其反，身体“似乎有轻微至中度变差，而且好像没有临床意义” （the potential for adverse events amongst older adults taking fish oil appear mild–moderate at worst and are unlikely to be of clinical significance）。这可能是因为鱼油中维生素A含量过高、毒素和污染物积累等原因造成的。 按照“硫酸软骨素-多形拟杆菌-硫酸盐还原菌”的食物链，吃鱼肉（含硫酸软骨素）和摄入鱼油及所含多不饱和脂肪酸（无硫酸软骨素）的结局是完全不同的，两者绝对不能等同。吃鱼的好处可能在于摄取具有抗炎作用的多不饱和脂肪酸，坏处在于它也能滋养破坏肠道完整性的肠道细菌，导致炎症。两者相抵，经常出现有效但不明显甚至矛盾的结果就不奇怪了（Omega-3 (n-3) fatty acids have previously been shown to reduce the risk of cardiac events, cardiac death, and all-cause mortality in randomized controlled trials. However, recent data have challenged the benefits of n-3 fatty acids in the current era of optimal medical therapy）。 总之， “ 多吃素、少吃肉有益健康”的说法应该暂时不会过时，而红肉与白肉对健康的影响 目前 尚有争议，建议大家尽量用豆类取代肉类，并适当补充蛋和奶，防止某些必需氨基酸（如含硫氨基酸）缺乏。希望你有一个健康的好身体，更好地为祖国、为人民服务。
本来我只有周末才能抽出时间写科普博客，但看了几篇相关 博文后有些最新感悟今天就想写出来跟各位分享。我这篇博客最早拟出的题目是“氧化与抗氧化：一个被忽视的科学原理”，但觉得这个说法只概括了在专业层面上我想说的话，而没有凝练出我真正想表达的意思，故改为现题。 话题的起因出自本月24日Science上的一篇新闻，文章题目译成中文是“科学家修正了关于饱和脂肪酸争议论文中的若干错误”（见附录）。该文提到的这篇所谓“争议”论文于 本月18日 在线发表于《内科学年报 》（Annals of Internal Medicine）上，文章的题目是“膳食、血液循环、脂肪酸补充剂与心脏风险的关系：系统研究和大数据分析”（ Association of Dietary, Circulating, and Supplement Fatty Acids With Coronary Risk : A Systematic Review and Meta-analysis ） 。 据说该文发表后收到了若干意见，作者根据这些意见已经对文章作了修改，估计我们现在见到的版本应该是更新版。 尽管作者对文章作了一些有针对性的修改，但最后结论仍然不变： 现有证据并不明确支持指南上关于鼓励多食用多价不饱和脂肪酸而少食用全饱和脂质的建议 （Current evidence does not clearly support guidelines that encourage high consumption of polyunsaturated fatty acids and low consumption of total saturated fats）。这个结论实际上正是该文被“围攻”的靶子，而修改并未如意“改邪归正”。黄油、肉类、巧克力、奶酪中富含饱和脂肪酸，而鱼类、坚果、植物油中富含不饱和脂肪酸。饱和脂肪酸能增大心血管病风险历来被认为是已成定论的“科学教条”，并被世界卫生组织、美国国家食品药品监督管理局和美、英、加、欧盟膳食协会等权威机构采纳，而这篇文章的结论恰恰挑战了这个定论。 以英国的“指南”为例，它是这样写的：男性每日摄入的饱和脂肪酸不应超过30克，女性每日摄入的饱和脂肪酸不应超过20克。这可视为对不同种类脂肪酸摄取的“清规戒律”，言下之意是过多摄入饱和脂肪酸有害，而适量摄入不饱和脂肪酸有益（或多多益善？）。因此，这篇文章的发表惹来了很多国际权威们的高调反对。哈佛大学公共卫生学院营养学系主任Walter Willett就批评道：“他们（对科学结论）已经造成很大损害”，还说：“我认为可以考虑像快速发表那样立即撤稿”。新西兰Otago大学的Jim Mann也表示：“如果这篇文章让我审稿，我也会建议退稿”。 究竟这篇文章的观点是对还是错呢？我们先看看NCBI就此组织的专题点评给出的结论：尽管存在一些不足，但这是一项令人印象深刻的详细而全面的研究（ Saturated fats and heart disease link unproven ）。以下仅贴出长篇点评中的Conclusion部分，供专业人士参考： In contrast to current recommendations, this systematic review found no evidence that saturated fat increases the risk of coronary disease, or that polyunsaturated fats have a cardioprotective effect. Similarly, there was no significant association between the levels of total omega-3 or omega-6 polyunsaturated fatty acids and coronary disease. This lack of association was seen in both cohort studies, which looked at dietary intake or circulating levels the in blood, and in randomised controlled trials that had looked at the effect of supplementation. There was also no significant association between total saturated fatty acids and coronary risk, both in studies using dietary intake and in those using circulating biomarkers. In addition, there was no significant association between total monounsaturated fatty acids and coronary risk – again, both in studies using dietary intake and those studying fatty acid composition. Dietary trans fatty acid intake was associated with increased coronary disease risk, although circulating levels were not. There are some limitations to this study: For the studies based on dietary intake, it is not clear over how long a period of time their diet was assessed. Dietary questionnaires can be inaccurate due to recall bias and may not be representative of diet over a number of years. The level of fat consumption is unclear – that is, how large the difference in fat consumption per day was between people in the top third compared with people in the bottom third. Some of the studies involved people with a pre-existing health condition, so the results may not be applicable to a healthy population. Despite these limitations, this was an impressively detailed and extensive piece of research, which is likely to prompt further study. Current UK guidelines remained unchanged: The average man should eat no more than 30g of saturated fat a day. The average woman should eat no more than 20g of saturated fat a day. Even if saturated fats don’t directly harm your heart, eating too much can lead to obesity, which in turn can damage it. The key to a healthy diet is “everything in moderation”. The occasional buttered scone or cream cake is not going to hurt you, but you need to be aware of your total calorie intake. Eating a healthy, balanced diet , being physically active and not smoking are the best ways to keep your heart healthy. Analysis by Bazian . Edited by NHS Choices . Follow Behind the Headlines on Twitter . Join the Healthy Evidence forum . 下面就来扼要谈谈我个人的看法： 首先，这涉及到心血管病的发病机理。现有证据表明，心血管病与慢性炎症息息相关，而炎症可以导致活性氧（ROS）与活性氮（RNS）的大量产生。不过，究竟是炎症本身还是ROS和RNS引起心血管病，现在还不清楚。假如是炎症直接导致心血管病，那么无论是饱和脂肪酸还是不饱和脂肪酸都没有抗炎作用，该文关于脂肪酸与心血管病无关的结论就是正确的。如果是 ROS和RNS引起心血管病，那就牵涉到下面要谈的另外一个问题。 其次，涉及到自由基的清除系统。假如过多的 ROS和RNS会导致心血管病，那么具有清除自由基能力的不饱和脂肪酸就能降低心血管病的风险，而饱和脂肪酸却没有这个作用。然而，人体具有完备的抗氧化系统，专门针对体内外环境中出现的氧化剂，小分子的有还原型谷胱甘肽（GSH）等，大分子的有各种抗氧化酶。实际上，外源抗氧化剂的摄入确实能清除自由基，但同时也抑制了内源抗氧化酶的诱导。 在人体中， 抗氧化剂与 抗氧化酶的关系类似于“矛”与“盾”的关系，用“水涨船高”来解释就很容易理解。 从这个意义上来说，不饱和脂肪酸充其量只是部分行使了抗氧化酶的功能，只不过外源抗氧化剂增加了，而内源抗氧化酶就会相应减少 ，这就能解释为什么不饱和脂肪酸与心血管病无关。 再次，还涉及到不饱和脂肪酸的作用。显然，不饱和脂肪酸不仅仅是作为抗氧化剂发挥作用，它们既然被定义为人体的“必需脂肪酸”，那就一定有着不可替代的作用。至于它们是否与心血管病有直接关系，恐怕还要开展更深入的研究。比如，Science文章中提到的一篇 A 2009 review 就这样描述过：用糖类代替饱和脂肪酸不能降低心脏病风险，用不饱和脂肪酸代替饱和脂肪酸就能降低心脏病风险。也就是说，不饱和脂肪酸至少跟心血管病有间接关系，今后的任务是要阐明这种间接关系。 另外，尽管这项研究来自大数据分析，而且以Review的形式发表，但它仍然开展了多人参与的临床研究，研究阵容也很豪华（来自哈佛、剑桥等）。既然能得出不饱和脂肪酸与心血管病无关的结论，那也是不会轻易被人否定的，用作者的话来说就是：结论是Valid的，证据是Hardest的，关键在于我们如何进行正确解读。上述专题评述对此的解读是：虽然饱和脂肪酸不会直接损害心脏，但吃得太多会引起肥胖，而肥胖反过来就能损害心脏。 我认为，心血管病的最大风险来自长期感染（如病原细菌）或非感染（如吸烟、肥胖）导致的经久不愈的慢性炎症，抗氧化剂或不饱和脂肪酸的抗氧化作用都不能消除炎症，因此可能与心血管病没有直接关系。不过，目前不能排除不饱和脂肪酸与心血管病的间接关系，即与发病机制相联系。它们也许可以延缓老年人心血管病的发病进程，因为老龄化会降低对食物中抗氧化剂的吸收及对体内抗氧化酶的诱导，因而削弱本身的抗氧化能力，但这个推测还需经过实验研究证实。 最后，我想说两句题外话：我总感觉在国外发表文章存在“潜规则”，若遇审稿人“看不顺眼”（来自中国？英文表达别扭？）就很难过他们的十指关。同样是中国人，在国外的工作容易发表，而回国后的工作就难以发表。因此，我非常推崇用“发表后评价”制度代替“发表前评审”制度。 附： Scientists Fix Errors in Controversial Paper About Saturated Fats 24 March 2014 3:15 pm 12 Comments Wikimedia Commons/Sage Ross Going nuts. Critics have panned a paper that questions whether unsaturated fats, common in nuts, are healthier than saturated ones. When a paper published on 17 March questioned whether fats from fish or vegetable oils are healthier than those in meat or butter, it quickly made headlines around the world ; after all, the study seemed to debunk a cornerstone of many dietary guidelines. But a new version of the publication had to be posted shortly after it appeared on the website of the Annals of Internal Medicine to correct several errors. And although the study's first author stands by the conclusions, a number of scientists are criticizing the paper and even calling on the authors to retract it. They have done a huge amount of damage, says Walter Willett, chair of the nutrition department at the Harvard School of Public Health in Boston. I think a retraction with similar press promotion should be considered. Health officials have long argued that so-called saturated fatty acids, which are found in butter, meat, chocolate, and cheese, increase the risk of heart disease, and that people should instead eat more unsaturated fatty acids, the type that dominates in fish, nuts, or vegetable oils. In the new study, a meta-analysis, scientists from Europe and the United States pooled 72 individual studies to gauge how different fats influence the risk of a heart attack or other cardiac events, such as angina. These included trials in which participants were randomly assigned to different diets, as well as observational studies in which participants' intake of fatty acids was determined by asking them about their diet or by measuring the fatty acids circulating in the bloodstream. When the researchers compared people with the highest and the lowest intake of saturated fats, they found no clear difference between the risk of heart disease or other cardiac events. Similarly, they found no significant difference between those consuming high or low amounts of the supposedly healthy unsaturated fats. Current evidence does not clearly support guidelines that encourage high consumption of polyunsaturated fatty acids and low consumption of total saturated fats, the authors concluded . But even before the paper was published, other scientists began pointing out errors, says first author Rajiv Chowdhury, an epidemiologist at the University of Cambridge in the United Kingdom. For instance, the authors took one study on omega-3 fats, one type of unsaturated fats, to show a slightly negative effect while, in fact, it had shown a strong positive effect. The correction means that the meta-analysis now says people who report eating lots of this particular fat have significantly less heart disease; previously, it said there was no significant effect. Critics also pointed out two important studies on omega-6 fatty acids that the authors had missed. The errors demonstrate shoddy research and make one wonder whether there are more that haven't been detected, writes Jim Mann, a researcher at the University of Otago, Dunedin, in New Zealand, writes in an e-mail. If I had been the referee I would have recommended rejection. Mann and others say the paper has other problems, too. For instance, it does not address what people who reduced their intake of saturated fats consumed instead. A 2009 review concluded that replacing saturated fats with carbohydrates had no benefit, while replacing them with polyunsaturated fats reduced the risk of heart disease. Several scientists say that should have been mentioned in the new paper. Chowdhury says the paper's conclusions are valid, however, even after the corrections. Randomized clinical trials are the hardest kind of evidence, he says, and they don't show a significant effect of saturated or unsaturated fats. But even one of the paper's authors, Dariush Mozaffarian, of the Harvard School of Public Health, admits that he is not happy with the key conclusion that the evidence does not support a benefit from polyunsaturated fats. Personally, I think the results suggest that fish and vegetable oils should be encouraged, he says. But the paper was written by a group of authors, he points out. And science isn't a dictatorship. Another study author, Emanuele Di Angelantonio of the University of Cambridge, says the main problem is that the paper was wrongly interpreted by the media. We are not saying the guidelines are wrong and people can eat as much saturated fat as they want. We are saying that there is no strong support for the guidelines and we need more good trials. Willett says correcting the paper isn't enough. It is good that they fixed it for the record, but it has caused massive confusion and the public hasn't heard about the correction. The paper should be withdrawn, he argues. The controversy should serve as a warning about meta-analyses, Willett adds. Such studies compile the data from many individual studies to get a clearer result. It looks like a sweeping summary of all the data, so it gets a lot of attention, Willett says. But these days meta-analyses are often done by people who are not familiar with a field, who don't have the primary data or don't make the effort to get it. And while drug trials are often very similar in design, making it easy to combine their results, nutritional studies vary widely in the way they are set up. Often the strengths and weaknesses of individual studies get lost, Willett says. It's dangerous.
PM2.5增加心血管病死亡率 PM2.5可谓这个冬季常谈常新的话题，近日，人们又开始讨论为PM2.5起中文名字。其实，不管是叫“细颗粒物”还是叫“烟尘”、“细飘尘”，都意在提醒人们小心雾霾对健康带来的危害。 PM2.5可以进入肺部产生刺激作用，损害呼吸道和身体其他器官(通过血液循环产生)，从而可能诱发肺癌或其他癌症。所以，每当雾霾增加时，医院呼吸系统门急诊人数就会增加。不过，雾霾对健康的影响不仅限于此。 2月20日，《欧洲心脏期刊》（ The European Heart Journal ）刊登的一项研究结果表明，PM2.5与心脏病的死亡率有正相关关系，PM2.5浓度越高，心脏病患者的死亡率也越高。患有急性冠脉综合征的病人如果过度暴露在PM2.5浓度较高的空气中，死亡率也会上升。 英国伦敦卫生和热带医药学院的凯瑟琳·汤纳等人对英格兰和威尔士15.4万名心脏病患者进行了3年多的跟踪研究，这些人曾在2004年至2007年间因突发心脏病而住院。研究人员在这些人出院后继续调查他们的健康情况，其间有4万人死亡。 （来源：北京日报） Abstract Aims The aim of this study was to determine (i) whether long-term exposure to air pollution was associated with all-cause mortality using the Myocardial Ischaemia National Audit Project (MINAP) data for England and Wales, and (ii) the extent to which exposure to air pollution contributed to socioeconomic inequalities in prognosis. Methods and results Records of patients admitted to hospital with acute coronary syndrome (ACS) in MINAP collected under the National Institute for Cardiovascular Outcomes Research were linked to modelled annual average air pollution concentrations for 2004–10. Hazard ratios for mortality starting 28 days after admission were estimated using Cox proportional hazards models. Among the 154 204 patients included in the cohort, the average follow-up was 3.7 years and there were 39 863 deaths. Mortality rates were higher for individuals exposed to higher levels of particles with a diameter of ≤2.5 μm (PM 2.5 ; PM, particulate matter): the fully adjusted hazard ratio for a 10 μg/m 3 increase in PM 2.5 was 1.20 (95% CI 1.04–1.38). No associations were observed for larger particles or oxides of nitrogen. Air pollution explained socioeconomic inequalities in survival to only a small extent. Conclusion Mortality from all causes was higher among individuals with greater exposure to PM 2.5 in survivors of hospital admission for ACS in England and Wales. Despite higher exposure to PM 2.5 among those from more deprived areas, such exposure was a minor contribution to the socioeconomic inequalities in prognosis following ACS. Our findings add to the evidence of mortality associated with long-term exposure to fine particles. Particulate matter air pollution and cardiovascular disease: An update to the scientific statement from the american heart association Authors: Brook R.D., Rajagopalan S., Pope C.A., Brook J.R., Bhatnagar A., Diez-Roux A.V., Holguin F., Hong Y., Luepker R.V., Mittleman M.A., Peters A., Siscovick D., Smith S.C., Whitsel L., Kaufman J.D. Cited by: 232 Add time: 2012-11 Document Type: Review Source: Circulation,2010,121(21):2331-2378 全文 Abstract： In2004,thefirstAmericanHeartAssociationscientificstatementon"Air PollutionandCardiovascularDisease"concludedthatexposuretoparticulate matter(PM)airpollutioncontributestocardiovascularmorbidityandmortality. Intheinterim,numerousstudieshaveexpandedourunderstandingofthis associationandfurtherelucidatedthephysiologicalandmolecularmechanisms involved.ThemainobjectiveofthisupdatedAmericanHeartAssociation scientificstatementistoprovideacomprehensivereviewofthenewevidence linkingPMexposurewithcardiovasculardisease,withaspecificfocuson highlightingtheclinicalimplicationsforresearchersandhealthcareproviders. Thewritinggroupalsosoughttoprovideexpertconsensusopinionsonmany aspectsofthecurrentstateofscienceandupdatedsuggestionsforareasof futureresearch.Onthebasisofthefindingsofthisreview,severalnew conclusionswerereached,includingthefollowing:ExposuretoPM2.5μmin diameter(PM2.5)overafewhourstoweekscantriggercardiovasculardisease -relatedmortalityandnonfatalevents;longer-termexposure(eg,afewyears) increasestheriskforcardiovascularmortalitytoanevengreaterextentthan exposuresoverafewdaysandreduceslifeexpectancywithinmorehighlyexposed segmentsofthepopulationbyseveralmonthstoafewyears;reductionsinPM levelsareassociatedwithdecreasesincardiovascularmortalitywithinatime frameasshortasafewyears;andmanycrediblepathologicalmechanismshave beenelucidatedthatlendbiologicalplausibilitytothesefindings.Itisthe opinionofthewritinggroupthattheoverallevidenceisconsistentwitha causalrelationshipbetweenPM2.5exposureandcardiovascularmorbidityand mortality.Thisbodyofevidencehasgrownandbeenstrengthenedsubstantially sincethefirstAmericanHeartAssociationscientificstatementwaspublished. Finally,PM2.5exposureisdeemedamodifiablefactorthatcontributesto cardiovascularmorbidityandmortality. http://paper.sciencenet.cn/htmlpaper/20133111015383728114.shtm http://eurheartj.oxfordjournals.org/content/26/8/804.full?ijkey=ae4ca65b3c9a3b2f349dc8a607e835daa58ab278keytype2=tf_ipsecsha http://www.nasa.gov/topics/earth/features/health-sapping.html http://www.ncbi.nlm.nih.gov/pmc/?term=10.1289/ehp.0901623
The traditional Mediterranean diet is characterized by a high intake of olive oil, fruit, nuts, vegetables, and cereals; a moderate intake of fish and poultry; a low intake of dairy products, red meat, processed meats, and sweets; and wine in moderation, consumed with meals. 1 In observational cohort studies 2,3 and a secondary prevention trial (the Lyon Diet Heart Study), 4 increasing adherence to the Mediterranean diet has been consistently beneficial with respect to cardiovascular risk. 2-4 A systematic review ranked the Mediterranean diet as the most likely dietary model to provide protection against coronary heart disease. 5 Small clinical trials have uncovered plausible biologic mechanisms to explain the salutary effects of this food pattern. 6-9 We designed a randomized trial to test the efficacy of two Mediterranean diets (one supplemented with extra-virgin olive oil and another with nuts), as compared with a control diet (advice on a low-fat diet), on primary cardiovascular prevention. Methods Study Design The PREDIMED trial (Prevención con Dieta Mediterránea) was a parallel-group, multicenter, randomized trial. Details of the trial design are provided elsewhere. 10-12 The trial was designed and conducted by the authors, and the protocol was approved by the institutional review boards at all study locations. The authors vouch for the accuracy and completeness of the data and all analyses and for the fidelity of this report to the protocol , which is available with the full text of this article at NEJM.org. Supplemental foods were donated, including extra-virgin olive oil (by Hojiblanca and Patrimonio Comunal Olivarero, both in Spain), walnuts (by the California Walnut Commission), almonds (by Borges, in Spain), and hazelnuts (by La Morella Nuts, in Spain). None of the sponsors had any role in the trial design, data analysis, or reporting of the results. Participant Selection and Randomization Eligible participants were men (55 to 80 years of age) and women (60 to 80 years of age) with no cardiovascular disease at enrollment, who had either type 2 diabetes mellitus or at least three of the following major risk factors: smoking, hypertension, elevated low-density lipoprotein cholesterol levels, low high-density lipoprotein cholesterol levels, overweight or obesity, or a family history of premature coronary heart disease. Detailed enrollment criteria are provided in the Supplementary Appendix , available at NEJM.org. All participants provided written informed consent. Beginning on October 1, 2003, participants were randomly assigned, in a 1:1:1 ratio, to one of three dietary intervention groups: a Mediterranean diet supplemented with extra-virgin olive oil, a Mediterranean diet supplemented with nuts, or a control diet. Randomization was performed centrally by means of a computer-generated random-number sequence. Interventions and Measurements The dietary intervention 8,10-13 is detailed in the Supplementary Appendix . The specific recommended diets are summarized in Table 1 Table 1 Summary of Dietary Recommendations to Participants in the Mediterranean-Diet Groups and the Control-Diet Group. . Participants in the two Mediterranean-diet groups received either extra-virgin olive oil (approximately 1 liter per week) or 30 g of mixed nuts per day (15 g of walnuts, 7.5 g of hazelnuts, and 7.5 g of almonds) at no cost, and those in the control group received small nonfood gifts. No total calorie restriction was advised, nor was physical activity promoted. For participants in the two Mediterranean-diet groups, dietitians ran individual and group dietary-training sessions at the baseline visit and quarterly thereafter. In each session, a 14-item dietary screener was used to assess adherence to the Mediterranean diet 8,14 (Table S1 in the Supplementary Appendix ) so that personalized advice could be provided to the study participants in these groups. Participants in the control group also received dietary training at the baseline visit and completed the 14-item dietary screener used to assess baseline adherence to the Mediterranean diet. Thereafter, during the first 3 years of the trial, they received a leaflet explaining the low-fat diet (Table S2 in the Supplementary Appendix ) on a yearly basis. However, the realization that the more infrequent visit schedule and less intense support for the control group might be limitations of the trial prompted us to amend the protocol in October 2006. Thereafter, participants assigned to the control diet received personalized advice and were invited to group sessions with the same frequency and intensity as those in the Mediterranean-diet groups, with the use of a separate 9-item dietary screener (Table S3 in the Supplementary Appendix ). A general medical questionnaire, a 137-item validated food-frequency questionnaire, 15 and the Minnesota Leisure-Time Physical Activity Questionnaire were administered on a yearly basis. 10 Information from the food-frequency questionnaire was used to calculate intake of energy and nutrients. Weight, height, and waist circumference were directly measured. 16 Biomarkers of compliance, including urinary hydroxytyrosol levels (to confirm compliance in the group receiving extra-virgin olive oil) and plasma alpha-linolenic acid levels (to confirm compliance in the group receiving mixed nuts), were measured in random subsamples of participants at 1, 3, and 5 years (see the Supplementary Appendix ). End Points The primary end point was a composite of myocardial infarction, stroke, and death from cardiovascular causes. Secondary end points were stroke, myocardial infarction, death from cardiovascular causes, and death from any cause. We used four sources of information to identify end points: repeated contacts with participants, contacts with family physicians, a yearly review of medical records, and consultation of the National Death Index. All medical records related to end points were examined by the end-point adjudication committee, whose members were unaware of the study-group assignments. Only end points that were confirmed by the adjudication committee and that occurred between October 1, 2003, and December 1, 2010, were included in the analyses. The criteria for adjudicating primary and secondary end points are detailed in the Supplementary Appendix . Statistical Analysis We initially estimated that a sample of 9000 participants would be required to provide statistical power of 80% to detect a relative risk reduction of 20% in each Mediterranean-diet group versus the control-diet group during a 4-year follow-up period, assuming an event rate of 12% in the control group. 10,17 In April 2008, on the advice of the data and safety monitoring board and on the basis of lower-than-expected rates of end-point events, the sample size was recalculated as 7400 participants, with the assumption of a 6-year follow-up period and underlying event rates of 8.8% and 6.6% in the control and intervention groups, respectively. Power curves under several assumptions can be found in Figure S1 in the Supplementary Appendix . Yearly interim analyses began after a median of 2 years of follow-up. With the use of O'Brien–Fleming stopping boundaries, the P values for stopping the trial at each yearly interim analysis were 5×10 −6 , 0.001, 0.009, and 0.02 for benefit and 9×10 −5 , 0.005, 0.02, and 0.05 for adverse effects. 18 The stopping boundary for the benefit of the Mediterranean diets with respect to the primary end point was crossed at the fourth interim evaluation; on July 22, 2011, the data and safety monitoring board recommended stopping the trial on the basis of end points documented through December 1, 2010. All primary analyses were performed on an intention-to-treat basis by two independent analysts. Time-to-event data were analyzed with the use of Cox models with two dummy variables (one for the Mediterranean diet with extra-virgin olive oil and another for the Mediterranean diet with nuts) to obtain two hazard ratios for the comparison with the control group. To account for small imbalances in risk factors at baseline among the groups, Cox regression models were used to adjust for sex, age, and baseline risk factors. We tested the proportionality of hazards with the use of time-varying covariates. All analyses were stratified according to center. Prespecified subgroup analyses were conducted according to sex, age, body-mass index (BMI), cardiovascular-risk-factor status, and baseline adherence to the Mediterranean diet. Sensitivity analyses were conducted under several assumptions, including imputation of data for missing values and participants who dropped out (see the Supplementary Appendix ). Results Baseline Characteristics of the Study Participants From October 2003 through June 2009, a total of 8713 candidates were screened for eligibility, and 7447 were randomly assigned to one of the three study groups (Figure S2 in the Supplementary Appendix ). Their baseline characteristics according to study group are shown in Table 2 Table 2 Baseline Characteristics of the Participants According to Study Group. . Drug-treatment regimens were similar for participants in the three groups, and they continued to be balanced during the follow-up period (Table S4 in the Supplementary Appendix ). Participants were followed for a median of 4.8 years (interquartile range, 2.8 to 5.8). After the initial assessment, 209 participants (2.8%) chose not to attend subsequent visits, and their follow-up was based on reviews of medical records. By December 2010, a total of 523 participants (7.0%) had been lost to follow-up for 2 or more years. Dropout rates were higher in the control group (11.3%) than in the Mediterranean-diet groups (4.9%) (Figure S2 in the Supplementary Appendix ). As compared with participants who remained in the trial, those who dropped out were younger (by 1.4 years), had a higher BMI (the weight in kilograms divided by the square of the height in meters; by 0.4), a higher waist-to-height ratio (by 0.01), and a lower score for adherence to the Mediterranean diet (by 1.0 points on the 14-item dietary screener) (P0.05 for all comparisons). Compliance with the Dietary Intervention Participants in the three groups reported similar adherence to the Mediterranean diet at baseline ( Table 2 , and Figure S3 in the Supplementary Appendix ) and similar food and nutrient intakes. During follow-up, scores on the 14-item Mediterranean-diet screener increased for the participants in the two Mediterranean-diet groups (Figure S3 in the Supplementary Appendix ). There were significant differences between these groups and the control group in 12 of the 14 items at 3 years (Table S5 in the Supplementary Appendix ). Changes in objective biomarkers also indicated good compliance with the dietary assignments (Figure S4 and S5 in the Supplementary Appendix ). Participants in the two Mediterranean-diet groups significantly increased weekly servings of fish (by 0.3 servings) and legumes (by 0.4 servings) in comparison with those in the control group (Table S6 in the Supplementary Appendix ). In addition, participants assigned to a Mediterranean diet with extra-virgin olive oil and those assigned to a Mediterranean diet with nuts significantly increased their consumption of extra-virgin olive oil (to 50 and 32 g per day, respectively) and nuts (to 0.9 and 6 servings per week, respectively). The main nutrient changes in the Mediterranean-diet groups reflected the fat content and composition of the supplemental foods (Tables S7 and S8 in the Supplementary Appendix ). No relevant diet-related adverse effects were reported (see the Supplementary Appendix ). We did not find any significant difference in changes in physical activity among the three groups. End Points The median follow-up period was 4.8 years. A total of 288 primary-outcome events occurred: 96 in the group assigned to a Mediterranean diet with extra-virgin olive oil (3.8%), 83 in the group assigned to a Mediterranean diet with nuts (3.4%), and 109 in the control group (4.4%). Taking into account the small differences in the accrual of person-years among the three groups, the respective rates of the primary end point were 8.1, 8.0, and 11.2 per 1000 person-years ( Table 3 Table 3 Outcomes According to Study Group. ). The unadjusted hazard ratios were 0.70 (95% confidence interval , 0.53 to 0.91) for a Mediterranean diet with extra-virgin olive oil and 0.70 (95% CI, 0.53 to 0.94) for a Mediterranean diet with nuts ( Figure 1 Figure 1 Kaplan–Meier Estimates of the Incidence of Outcome Events in the Total Study Population. ) as compared with the control diet (P=0.015, by the likelihood ratio test, for the overall effect of the intervention). The results of multivariate analyses showed a similar protective effect of the two Mediterranean diets versus the control diet with respect to the primary end point ( Table 3 ). Regarding components of the primary end point, only the comparisons of stroke risk reached statistical significance ( Table 3 , and Figure S6 in the Supplementary Appendix ). The Kaplan–Meier curves for the primary end point diverged soon after the trial started, but no effect on all-cause mortality was apparent ( Figure 1 ). The results of several sensitivity analyses were also consistent with the findings of the primary analysis (Table S9 in the Supplementary Appendix ). Subgroup Analyses Reductions in disease risk in the two Mediterranean-diet groups as compared with the control group were similar across the prespecified subgroups ( Figure 2 Figure 2 Results of Subgroup Analyses. , and Table S10 in the Supplementary Appendix ). In addition, to account for the protocol change in October 2006 whereby the intensity of dietary intervention in the control group was increased, we compared hazard ratios for the Mediterranean-diet groups (both groups merged vs. the control group) before and after this date. Adjusted hazard ratios were 0.77 (95% CI, 0.59 to 1.00) for participants recruited before October 2006 and 0.49 (95% CI, 0.26 to 0.92) for those recruited thereafter (P=0.21 for interaction). Discussion In this trial, an energy-unrestricted Mediterranean diet supplemented with either extra-virgin olive oil or nuts resulted in an absolute risk reduction of approximately 3 major cardiovascular events per 1000 person-years, for a relative risk reduction of approximately 30%, among high-risk persons who were initially free of cardiovascular disease. These results support the benefits of the Mediterranean diet for cardiovascular risk reduction. They are particularly relevant given the challenges of achieving and maintaining weight loss. The secondary prevention Lyon Diet Heart Study also showed a large reduction in rates of coronary heart disease events with a modified Mediterranean diet enriched with alpha-linolenic acid (a key constituent of walnuts). That result, however, was based on only a few major events. 4,19,20 There were small between-group differences in some baseline characteristics in our trial, which were not clinically meaningful but were statistically significant, and we therefore adjusted for these variables. In fully adjusted analyses, we found significant results for the combined cardiovascular end point and for stroke, but not for myocardial infarction alone. This could be due to stronger effects on specific risk factors for stroke but also to a lower statistical power to identify effects on myocardial infarction. Our findings are consistent with those of prior observational studies of the cardiovascular protective effects of the Mediterranean diet, 2,5 olive oil, 21-23 and nuts 24,25 ; smaller trials assessing effects on traditional cardiovascular risk factors 6-9 and novel risk factors, such as markers of oxidation, inflammation, and endothelial dysfunction 6,8,26-28 ; and studies of conditions associated with high cardiovascular risk — namely, the metabolic syndrome 6,16,29 and diabetes. 30-32 Thus, a causal role of the Mediterranean diet in cardiovascular prevention has high biologic plausibility. The results of our trial might explain, in part, the lower cardiovascular mortality in Mediterranean countries than in northern European countries or the United States. 33 The risk of stroke was reduced significantly in the two Mediterranean-diet groups. This is consistent with epidemiologic studies that showed an inverse association between the Mediterranean diet 2,34 or olive-oil consumption 22 and incident stroke. Our results compare favorably with those of the Women's Health Initiative Dietary Modification Trial, wherein a low-fat dietary approach resulted in no cardiovascular benefit. 35 Salient components of the Mediterranean diet reportedly associated with better survival include moderate consumption of ethanol (mostly from wine), low consumption of meat and meat products, and high consumption of vegetables, fruits, nuts, legumes, fish, and olive oil. 36,37 Perhaps there is a synergy among the nutrient-rich foods included in the Mediterranean diet that fosters favorable changes in intermediate pathways of cardiometabolic risk, such as blood lipids, insulin sensitivity, resistance to oxidation, inflammation, and vasoreactivity. 38 Our study has several limitations. First, the protocol for the control group was changed halfway through the trial. The lower intensity of dietary intervention for the control group during the first few years might have caused a bias toward a benefit in the two Mediterranean-diet groups, since the participants in these two groups received a more intensive intervention during that time. However, we found no significant interaction between the period of trial enrollment (before vs. after the protocol change) and the benefit in the Mediterranean-diet groups. Second, we had losses to follow-up, predominantly in the control group, but the participants who dropped out had a worse cardiovascular risk profile at baseline than those who remained in the study, suggesting a bias toward a benefit in the control group. Third, the generalizability of our findings is limited because all the study participants lived in a Mediterranean country and were at high cardiovascular risk; whether the results can be generalized to persons at lower risk or to other settings requires further research. As with many clinical trials, the observed rates of cardiovascular events were lower than anticipated, with reduced statistical power to separately assess components of the primary end point. However, favorable trends were seen for both stroke and myocardial infarction. We acknowledge that, even though participants in the control group received advice to reduce fat intake, changes in total fat were small and the largest differences at the end of the trial were in the distribution of fat subtypes. The interventions were intended to improve the overall dietary pattern, but the major between-group differences involved the supplemental items. Thus, extra-virgin olive oil and nuts were probably responsible for most of the observed benefits of the Mediterranean diets. Differences were also observed for fish and legumes but not for other food groups. The small between-group differences in the diets during the trial are probably due to the facts that for most trial participants the baseline diet was similar to the trial Mediterranean diet and that the control group was given recommendations for a healthy diet, suggesting a potentially greater benefit of the Mediterranean diet as compared with Western diets. In conclusion, in this primary prevention trial, we observed that an energy-unrestricted Mediterranean diet, supplemented with extra-virgin olive oil or nuts, resulted in a substantial reduction in the risk of major cardiovascular events among high-risk persons. The results support the benefits of the Mediterranean diet for the primary prevention of cardiovascular disease.
2010年 1.Yin K, Liao D, Tang CK(通讯作者). ATP-Binding Membrane Cassette Transporter A1 (ABCA1): A Possible Link between Inflammation and Reverse Cholesterol Transport. Mol Med. 2010, 16 (9-10): 438-449. (IF: 5.02). 2.Hu YW, Wang Q, Ma X, Li XX, Liu XH, Xiao J, Liao DF, Xiang J, Tang CK(通讯作者).TGF-beta1 Up-Regulates Expression of ABCA1, ABCG1 and SR-BI through Liver X Receptor alpha Signaling Pathway in THP-1 Macrophage-Derived Foam Cells. J Atheroscler Thromb. 2010, 17(5): 493-502. (IF: 3.048). 3.Liu XH, Xiao J, Mo ZC, Yin K, Jiang J, Cui LB, Tan CZ, Tang YL, Liao DF, Tang CK(通讯作者). Contribution of D4-F to ABCA1 Expression and Cholesterol Efflux in THP-1 Macrophage-Derived Foam Cells. J Cardiovasc Pharmacol. 2010, 56(3):309-19. ( IF:2.826) 4.Chen SG, Xiao J, Liu XH, Liu MM, Mo ZC, Yin K, Zhao GJ, Jiang J, Cui LB, Tan CZ, Yin WD, Tang CK(通讯作者). Ibrolipim increases ABCA1/G1 expression by the LXRα signaling pathway in THP-1 macrophage-derived foam cells. Acta Pharmacol Sin. 2010, 31(10):1343-9. (IF: 1.783). 5.Sun SW, Zu XY, Tuo QH, Chen LX, Lei XY, Li K, Tang CK(通讯作者), Liao Duan-fang(通讯作者).Caveolae and caveolin-1 mediate endocytosis and transcytosis of oxidized low density lipoprotein in endothelial cells. Acta Pharmacol Sin. 2010, 31 (10): 1336-42. (IF: 1.783). 6.Liu Q, Dai Z, Liu Z, Liu X, Tang C, Wang Z, Yi G, Liu L, Jiang Z, Yang Y, Yuan Z. Oxidized low-density lipoprotein activates adipophilin through ERK1/2 signal pathway in RAW264.7 cells . Acta Biochim Biophys Sin (Shanghai),2010, 42(9):635-645. 7.Qinkai Li, Weidong Yin(Corresponding author), Manbo Cai, Yi Liu, Hongjie Hou, Qingyun Shen, Chi Zhang, Junxia Xiao, Xiaobo Hu, Qishisan Wu, Makoto Funaki, and Yutaka Nakaya. NO-1886 suppresses diet-induced insulin resistance and cholesterol accumulation through STAT5-dependent upregulation of IGF1 and CYP7A1. J. Endocrinol., Jan 2010; 204: 47 - 56. 8. Lin J, Wang LY, Liu S, Wang XM, Yong Q, Yang Y, DU LP, Pan XD, Wang X, Jiang ZS.A novel mutation in proprotein convertase subtilisin/kexin type 9 gene leads to familial hypercholesterolemia in a Chinese family. Chin Med J (Engl). 2010 May;123(9):1133-8. 9.Hu B, He X, Li A, et al. Cystogenesis in ARPKD results from increased apoptosis in collecting duct epithelial cells of Pkhd1 mutant kidneys . Exp Cell Res, 2010. 10.曹冬黎，尹凯，莫中成，郝新瑞，胡炎伟，李晓旭，唐雅玲，唐朝克(通讯作者). 脂多糖通过核因子-κB途径下调泡沫细胞ABCA1的表达. 生物化学与生物物理学进展. 2010, 37 (5): 540-548. (IF: 0.193). 2009年 11.Jiang ZS, Wen GB, Tang ZH, Srisakuldee W, Fandrich RR, Kardami E. High molecular weight FGF-2 promotes postconditioning-like cardioprotection linked to activation of the protein kinase C isoforms Akt and p70 S6 kinase. Can J Physiol Pharmocol, 2009, 87:1-7 12.Srisakuldee W, Jeyaraman MM, Nickel BE, Tanguy S, Jiang ZS, Kardami E. Phosphorylation of connexin-43 at serine 262 promotes a cardiac injury-resistant state. Cardiovasc Res. 2009，83 (4):672-81. 13.Feng X, Chen Y, Zhao J, Tang C, Jiang Z, Geng B. Hydrogen sulfide from adipose tissue is a novel insulin resistance regulator. Biochem Biophys Res Commun. 2009，380：153-159（通讯作者） 14.Hu YW, Ma X, Li XX, Liu XH, Xiao J, Mo ZC, Xiang J, Liao DF, Tang CK(通讯作者). Eicosapentaenoic acid reduces ABCA1 serine phosphorylation and impairs ABCA1- dependent cholesterol efflux through cyclic AMP/protein kinase A signaling pathway in THP-1 macrophage-derived foam cells. Atherosclerosis. 2009, 204(2): e35-e43. (IF: 4.522). 15.Hao XR, Cao DL, Hu YW, Li XX, Liu XH, Xiao J, Liao DF, Xiang J, Tang CK(通讯作者). IFN-gamma down-regulates ABCA1 expression by inhibiting LXRalpha in a JAK/STAT signaling pathway-dependent manner. Atherosclerosis. 2009, 203(2): 417-428. ( IF:4.522) 16.Ma X, Hu YW, Mo ZC, Li XX, Liu XH, Xiao J, Yin WD, Liao DF, Tang CK(通讯作者). NO-1886 Up-regulates Niemann-Pick C1 Protein (NPC1) Expression Through Liver X Receptor alpha Signaling Pathway in THP-1 Macrophage-Derived Foam Cells. Cardiovasc Drugs Ther. 2009, 23(3): 199-206. (IF: 2.515) 17.Meihua She, Xiaojian Deng, Zhenyu Guo, Moshe Laudon, Zhuowei Hu, Duanfang Liao, Xiaobo Hu, Zehong Su,Weidong Yin. NEU-P11, a novel melatonin agonist, inhibits weight gain and improves insulin sensitivity in high-fat/high-sucrose-fed rats. Pharmacol Res 2009; 59(4) 248-253. 18.WEI Dang-heng, WANG Gui-xue, TANAG Chao-jun, LIU Lu-shang, WANG Zuo, TANG Chao-ke, RUAN Chang-geng. Effect of low density lipoprotein concentration polarization on endothelial cells adhesion. 2009 2nd International Conference on Biomedical Engineering and Informatics.2009,3:1343-1347 19.TANG Ya-ling, YANG Yong-zong, WANG Shuang。Mast cell degranulator compound 48-80 promotes atherosclerotic plaque in apolipoprotein E knockout mice with perivascular common carotid collar placement。Chinese Medical Journal(Engl)，2009；122（3）:319-325 20.刘录山，谢闵，姜志胜，杨琼，潘利红，武春艳，唐志晗，唐朝克，危当恒，王佐。pcsk9 siRNA对oxLDL诱导的THP-1源性巨噬细胞凋亡的影响。生物化学与生物物理进展，2009；36（3）：323-330 2008年 21.Dai XY, Ou X, Hao XR, Cao DL, Tang YL, Hu YW, Li XX, Tang CK(通讯作者). The Effect of T0901317 on ATP-Binding Cassette Transporter A1 and Niemann-Pick Type C1 in ApoE-/- Mice. J Cardiovasc Pharmacol. 2008, 51(5):467-475.( IF:2.826) 22.OU Xiang, DAI XiaoYan, LONG ZhiFeng, TANG YaLing, CAO DongLi, HAO XinRui, HU YanWei, LI XiaoXu, TANG ChaoKe(通讯作者). Liver X receptor agonist T0901317 reduces atherosclerotic lesions in apoE-/- mice by upregulating NPC1 expression. Science in China Series C: Life Sciences. 2008, 51(5): 418-429. (IF:0.661) 23.Xiaoyan Dai, Xiang Ou, Xinrui Hao, Dongli Cao, Yaling Tang, Yanwei Hu, Xiaoxu Li, Chaoke Tang (通讯作者) . A Synthetic LXR Agonist T0901317 Inhibits Semicarbazide-Sensitive Amine Oxidase Gene Expression and Activity in ApoE-/- Mice. Acta Biochim Biophys Sin , 2008，40(3): 261-268. (IF:1.086) 24.Yuan ZH, Madamanchi NR, Vendrov AE, Niu XL, Li JX, Runge MS. NADPH oxidase activity does not affect cellular cholesterol loading in vascular smooth muscle cells . Sheng Li Xue Bao,2008, 60(4):511-519. 25.LIN Jie, WANG Lu-ya, LIU Shu, XIA Jun-hui, YONG Qiang, DU Lan-ping, PAN Xiao-dong, XUE Hong, CHEN Bao-sheng and JIANG Zhi-sheng. Functional analysis of low-density lipoprotein receptor in homozygous familial hypercholesterolemia patients with novel 1439 C→T mutation of low-density lipoprotein receptor gene. Chin Med J 2008;121(9):776-781 26.Shuang Wang, Ying Zheng, Yun Yu, Li Xia, Guo-qiang Chen, Yong-zong Yang, Li-shun Wang. Differential proteomics research of camptothecin analog NSC606985 inducing apoptosis in U937 cells: phosphorylation of three kinds of cytoskeleton proteins. Cell Bio int.2008; 32(3):S35-S36 27.Shuang Wang, Ying Zheng, Yun Yu, Li Xia, Guo-qiang Chen, Yong-zong Yang, Li-shun Wang. Phosphorylation of β-actin by protein kinase C-delta in camptothecin analog-induced leukemic cell apoptosis. Acta Pharmacologica Sinica. 2008;29(1):135-142 28.刘录山，程艳丽，谢闵，杨琼，潘利红，姜志胜，唐朝克，危当恒，唐志晗。LDL、oxLDL对THP-1巨噬细胞PCSK9、LDLR表达的影响研究。生物化学与生物物理进展，2008；35（5）：540-547 29.胡炎伟, 唐朝克(通讯作者). 三磷酸腺苷结合盒转运体A1研究的最新进展. 生物化学与生物物理学进展. 2008, 35 (4): 373-379. (IF:0.211) 30.王佐，周晓峰，王仁，童中艺，姜志胜，王贵学。AMD3100对apoE~(-/-)小鼠骨髓源性内皮祖细胞增殖、迁移和黏附的影响 。生物化学与生物物理进展，2008；35(7)：807-813
基因组将为人们找到合适药物 http://news.sciencenet.cn/htmlnews/2011/1/243041.shtm 国际心血管病专家、美国斯克利普斯转化科学研究所所长埃里克·托普尔表示，10年前，测序一个完整的人类基因组可能要30亿美元；2010年其成本降到1万美元左右。2011年，其成本有望降到4000美元。而且，随着测序成本不断降低，基因组研究领域在2011年将会出现更多的医学突破。他说：“这个领域正如雨后春笋一般，蓬勃发展。” Prediction 6: Genomics will find medicines that work for you. Sequencing an entire human genome cost about $3 billion a decade ago. Last year it cost around $10,000, according to Dr. Eric Topol, director of the Scripps Translational Science Institute in La Jolla, Calif. Topol said he expects to see the price drop again in 2011, to about $4,000. And with lower financial barriers, he said, more medical advances from genomic research will come in the next year. http://www.myhealthnewsdaily.com/seven-predicted-medical-advances-in-2011-0949/ Genomics and medicines http://www.gopubmed.org/web/gopubmed/1?WEB018e95z6bgci1oIeI1I00h001000j100200010 信息分析报告 Genomics and medicines 1-19.docx
http://www.gopubmed.org/web/gopubmed/ 1,049 of 1,612,398 documents semantically analyzed Cardiovascular Disease and Type 2 Diabetes Mellitus Risk Factors top author statistics Top Years Publications 2009 672 2008 214 2010 163 2006 1 1 2 3 4 Top Countries Publications USA 273 Italy 66 United Kingdom 65 Germany 39 China 37 Australia 37 Japan 36 France 29 Canada 29 Sweden 28 Netherlands 28 Spain 26 Denmark 20 India 18 Turkey 18 Greece 15 Iran 12 Belgium 12 Taiwan 11 Poland 11 1 2 3 4 1 2 3 ... 21 Top Cities Publications Boston 26 New York 16 London 15 Shanghai 12 Toronto 12 Istanbul 12 Athens 10 Melbourne 10 Utrecht 10 Copenhagen 10 Paris 9 Barcelona 8 Stockholm 8 Lige 8 Amsterdam 7 Tehran 7 San Antonio 7 Baltimore 7 Rome 7 Philadelphia 7 1 2 3 ... 21 1 2 3 ... 24 Top Journals Publications Diabetes Care 40 Diabet Med 28 Metabolism 25 Diabetes Res Clin Pract 21 Diabetologia 19 Am J Cardiol 14 Circulation 13 Vasc Health Risk Manag 11 Cardiovasc Diabetol 11 Diabetes 10 Atherosclerosis 10 Metab Syndr Relat Disord 9 J Hypertens 9 Curr Diab Rep 9 Prim Care Diabetes 9 Am J Clin Nutr 8 Lancet 8 Postgrad Med 8 Bmj 8 Nutr Metab Cardiovasc Dis 8 1 2 3 ... 24 1 2 3 ... 150 Top Terms Publications Risk Factors 1,049 Diabetes Mellitus, Type 2 1,045 Humans 1,001 Cardiovascular Diseases 635 Patients 611 Middle Aged 545 Diabetes Mellitus 439 Aged 424 Adult 364 Hypertension 333 Obesity 331 Metabolism 320 metabolic process 320 Glucose 297 Blood Pressure 283 Prevalence 260 Pressure 254 Insulin 244 receptor binding 233 Syndrome 232 1 2 3 ... 150 1 2 3 ... 269 Top Authors Publications Dekker J 4 Scheen A 4 Haffner S 4 Dahl J 3 Nilsson P 3 Zarich S 3 Hu F 2 Anderson R 2 Taub N 2 Walker B 2 Simmons R 2 Knig W 2 Barnett A 2 ADVANCE Collaborative Group 2 Misra A 2 Steiner G 2 Cannon C 2 Howard B 2 Teede H 2 Sieradzki J 2 1 2 3 ... 269 医学新证据 http://plus.mcmaster.ca/EvidenceUpdates/NewArticles.aspx?Page=1ArticleID=34211#Data He M, van Dam RM, Rimm E, et al. Whole-Grain, Cereal Fiber, Bran, and Germ Intake and the Risks of All-Cause and Cardiovascular Disease-Specific Mortality Among Women With Type 2 Diabetes Mellitus. Circulation. 2010 May 10. (Original) PMID: 20458012 ReadAbstract ReadComments Clinical Evidence Topic: Glycaemiccontrolindiabetes:type2 DISCIPLINE RELEVANCE TO PRACTICE IS THIS NEWS? General Internal Medicine-Primary Care(US) General Practice(GP)/Family Practice(FP) Endocrine Print Save Article Delete Article Email this article to a colleague Abstract BACKGROUND: -Although whole-grain consumption has been associated with a lower risk of cardiovascular diseases (CVD) and mortality in the general population, the association of whole grain with mortality in diabetic patients remains to be determined. This study investigated whole grain and its components cereal fiber, bran, and germ in relation to all-cause and CVD-specific mortality in patients with type 2 diabetes mellitus. Methods and Results-We followed 7822 US women with type 2 diabetes mellitus in the Nurses` Health Study. Dietary intakes and potential confounders were assessed with regularly administered questionnaires. We documented 852 all-cause deaths and 295 CVD deaths during up to 26 years of follow-up. After adjustment for age, the highest versus the lowest fifths of intakes of whole grain, cereal fiber, bran, and germ were associated with 16% to 31% lower all-cause mortality. After further adjustment for lifestyle and dietary risk factors, only the association for bran intake remained significant (P for trend=0.01). The multivariate relative risks across the fifths of bran intake were 1.0 (reference), 0.94 (0.75 to 1.18), 0.80 (0.64 to 1.01), 0.82 (0.65 to 1.04), and 0.72 (0.56 to 0.92). Similarly, bran intake was inversely associated with CVD-specific mortality (P for trend=0.04). The relative risks across the fifths of bran intake were 1.0 (reference), 0.95 (0.66 to 1.38), 0.80 (0.55 to 1.16), 0.76 (0.51 to 1.14), and 0.65 (0.43 to 0.99). Similar results were observed for added bran alone. Conclusions-Whole-grain and bran intakes were associated with reduced all-cause and CVD-specific mortality in women with diabetes mellitus. These findings suggest a potential benefit of whole-grain intake in reducing mortality and cardiovascular risk in diabetic patients. Comments from Clinical Raters General Internal Medicine-Primary Care(US) This story is ongoing, unfortunately most of the chapters are in nutrition, epidemiology and lipidology journals and only a few make their way into main-stream medical journals. It's nice to see this in Circulation. If fiber and bran were sold by a pharmaceutical company they would be hawked at multiple meetings and pushed in multiple journals and rightly so since these are inexpensive, reasonably healthy approaches to a number of medical problems, for eg. type 2 diabetes, obesity, hyperlipidemia and hypertension. Actually high fiber/bran diets are not the most palatable choices and are boring, but they are beneficial. The authors are cautious in their claims and conclusions but their analysis needs to be taken seriously.
标签: 心血管病
![[转载]PM2.5增加心血管病死亡率](http://image.sciencenet.cn/album/201303/18/162022qf9cq0yxfkkcpdb8.jpg.thumb.jpg)
