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饮酒预防心脏病的“神话”破灭?

已有 3020 次阅读 2014-7-11 11:06 |个人分类:期刊论文|系统分类:论文交流| 减肥, 喝酒, 心血管病

以往的流行病学研究指出,饮酒与2型糖尿病及冠心病的发生呈现“U型”关系,也就是滴酒不沾或酩酊大醉的心脏病发生率高,而少量饮酒则降低心脏病发生率。

可是,刚刚发表在《英国医学杂志》(BMJ)的一篇论文(Association between alcohol and cardiovascular disease: Mendelian randomisation analysis based on individual participant data)却否定了这一结论,认为饮酒对心脏健康没有好处。这个研究由英国心脏基金会和医学研究理事会共同赞助,其团队组成堪称豪华,共有来自英国、欧洲大陆、北美和澳洲的155位科学家共同参与研究。

这项大型研究的特点是使用了26万多个来自乙醇脱氢酶1B基因(ADH1B)单核苷酸多态性变异体rs1229984携带者的研究数据。携带这个变异基因的人不仅喝酒易脸红,而且喝酒后还有恶心、呕吐和全身不舒服的感觉,因此他们很少饮酒。

结果发现,rs1229984携带者每周饮酒量仅为17.5%个单位(1个单位等于10毫升或7.9克乙醇),其冠心病发生率比非携带者低,而且其收缩压、白介素6水平、腰围和体质指数(BMI)均较低!作者由此推论,即使对于少量至中量饮酒者,减少乙醇消耗对心血管健康是有益的。

然而,2010年丹麦科学家发表在PLoS One上的一篇论文(The Association of Alcohol and Alcohol Metabolizing Gene Variants with Diabetes and Coronary Heart Disease Risk Factors in a White Population)则得出不同结论:乙醇脱氢酶(ADH)及乙醛脱氢酶(ALDH)变异基因(包括rs1229984)对2型糖尿病及冠病的影响极小,也就是不会明显改变饮酒的健康效应,而且支持以往饮酒与健康的U型理论。

那么,面对以上两种截然相反的结论,公众究竟应该听谁的?呵呵,当然还是要听专家的,恰好BMJ专门为此配发了一篇编者按(Editorial)。尽管这篇Editorial肯定了文章的优点,但也不完全是说好话哦,有的话说得还很难听。我将Editorial链接在此(Alcohol and cardiovascular disease),仅择要翻译其主要观点如下:

1、把ADH1B多态性对心血管病风险的影响仅仅局限在饮酒上,而且饮酒量并未严格确定,但却认定他们饮酒量相同,也许中度饮酒的rs1229984携带者比中度饮酒的未携带者的饮酒量就少一点点,因此其得出的不饮酒有利于心脏健康的结论就值得质疑。

Challenging assumptions is an important part of interpreting all observational work, and justifying assumptions is an important part of reporting it. For example, mendelian randomisation studies assume that effects of ADH1B polymorphisms on cardiovascular disease risk operate only via drinking. Holmes and colleagues try to show this by exploring whether ADH1B predicts coronary heart disease among people with similar levels of alcohol consumption. Although estimates are imprecise, results (figs 1 and 2 of paper) suggest ADH1B predicts cardiovascular disease risk even within groups of people with similar alcohol use. This should make us cautious about the conclusions—the allele should not predict cardiovascular risk among adults who all drink roughly the same amount. But we cannot be sure because alcohol use is imperfectly measured, and it’s still possible that, for example, moderate drinkers with the A-allele drink slightly less than moderate drinkers without it.

2、ADH1B多态性可影响乙醇代谢,因而就要同时考虑乙醇及其代谢物的影响。如果是那些代谢物影响心血管病风险,那么该研究的孟德尔随机化就违背了其所依据的核心假说之一,因为它仅仅是以乙醇作为高危因素。

There is a further problem with this particular allele as a proxy for alcohol consumption. ADH1B polymorphisms influence alcohol metabolism, and therefore influence exposure to both alcohol and its metabolites.9 If these metabolites influence risk of cardiovascular disease, one of the core assumptions underlying mendelian randomisation is violated.

3、最令人诧异的结论是中度饮酒者减少饮酒量也有益,而文中数据分析并不足以支持这个结论,因为他们依据的是参试者自报的饮酒量。中度饮酒与重度饮酒应该作为两个变量进行多变量的辅助变量分析。

One of the most surprising conclusions by Holmes et al is that reduced drinking is beneficial even for light to moderate drinkers. The analyses presented in the paper cannot establish this claim, however, because they rely on how much alcohol use individuals actually report. To evaluate whether effects of reducing drinking for moderate drinkers are similar to effects for heavy drinkers, one approach would define moderate and heavy drinking as separate variables and conduct a multiple-variable instrumental variables analysis.10

姑且把这篇文章看成是万花丛中的一朵“奇葩”,但千万不要“见树不见林”,“听到风就是雨”!我认为,“创新”固然弥足珍贵,但决不可“喜新厌旧”,假如一篇文章就能颠覆传统的“旧”观念,我一定为它拍手叫好!


Drinking alcohol provides no heart health benefit, new study shows

Date:
July 10, 2014
Source:
University of Pennsylvania School of Medicine
Summary:
Reducing the amount of alcoholic beverages consumed, even for light-to-moderate drinkers, may improve cardiovascular health, including a reduced risk of coronary heart disease, lower body mass index and blood pressure, according to a new multi-center study. The latest findings call into question previous studies which suggest that consuming light-to-moderate amounts of alcohol may have a protective effect on cardiovascular health.


Reducing the amount of alcoholic beverages consumed, even for light-to-moderate drinkers, may improve cardiovascular health.
Credit: © ramoncin1978 / Fotolia

Reducing the amount of alcoholic beverages consumed, even for light-to-moderate drinkers, may improve cardiovascular health, including a reduced risk of coronary heart disease, lower body mass index (BMI) and blood pressure, according to a new multi-center study published in The BMJ and co-led by the Perelman School of Medicine at the University of Pennsylvania. The latest findings call into question previous studies which suggest that consuming light-to-moderate amounts of alcohol (0.6-0.8 fluid ounces/day) may have a protective effect on cardiovascular health.

The new research reviewed evidence from more than 50 studies that linked drinking habits and cardiovascular health for over 260,000 people. Researchers found that individuals who carry a specific gene which typically leads to lower alcohol consumption over time have, on average, superior cardiovascular health records. Specifically, the results show that individuals who consume 17 percent less alcohol per week have on average a 10 percent reduced risk of coronary heart disease, lower blood pressure and a lower Body Mass Index.

"These new results are critically important to our understanding of how alcohol affects heart disease. Contrary to what earlier reports have shown, it now appears that any exposure to alcohol has a negative impact upon heart health," says co-lead author Michael Holmes, MD, PhD, research assistant professor in the department of Transplant Surgery at the Perelman School of Medicine at the University of Pennsylvania. "For some time, observational studies have suggested that only heavy drinking was detrimental to cardiovascular health, and that light consumption may actually be beneficial. This has led some people to drink moderately based on the belief that it would lower their risk of heart disease. However, what we're seeing with this new study, which uses an investigative approach similar to a randomized clinical trial, is that reduced consumption of alcohol, even for light-to-moderate drinkers, may lead to improved cardiovascular health."

In the new study, researchers examined the cardiovascular health of individuals who carry a genetic variant of the 'alcohol dehydrogenase 1B' gene, which is known to breakdown alcohol at a quicker pace. This rapid breakdown causes unpleasant symptoms including nausea and facial flushing, and has been found to lead to lower levels of alcohol consumption over time. By using this genetic marker as an indicator of lower alcohol consumption, the research team was able to identify links between these individuals and improved cardiovascular health.

The study was funded by the British Heart Foundation and the Medical Research Council, and was an international collaboration that included 155 investigators from the UK, continental Europe, North America, and Australia.

Story Source:

The above story is based on materials provided by University of Pennsylvania School of Medicine. Note: Materials may be edited for content and length.

Journal Reference:

  1. M. V. Holmes, C. E. Dale, L. Zuccolo, R. J. Silverwood, Y. Guo, Z. Ye, D. Prieto-Merino, A. Dehghan, S. Trompet, A. Wong, A. Cavadino, D. Drogan, S. Padmanabhan, S. Li, A. Yesupriya, M. Leusink, J. Sundstrom, J. A. Hubacek, H. Pikhart, D. I. Swerdlow, A. G. Panayiotou, S. A. Borinskaya, C. Finan, S. Shah, K. B. Kuchenbaecker, T. Shah, J. Engmann, L. Folkersen, P. Eriksson, F. Ricceri, O. Melander, C. Sacerdote, D. M. Gamble, S. Rayaprolu, O. A. Ross, S. McLachlan, O. Vikhireva, I. Sluijs, R. A. Scott, V. Adamkova, L. Flicker, F. M. v. Bockxmeer, C. Power, P. Marques-Vidal, T. Meade, M. G. Marmot, J. M. Ferro, S. Paulos-Pinheiro, S. E. Humphries, P. J. Talmud, I. M. Leach, N. Verweij, A. Linneberg, T. Skaaby, P. A. Doevendans, M. J. Cramer, P. v. d. Harst, O. H. Klungel, N. F. Dowling, A. F. Dominiczak, M. Kumari, A. N. Nicolaides, C. Weikert, H. Boeing, S. Ebrahim, T. R. Gaunt, J. F. Price, L. Lannfelt, A. Peasey, R. Kubinova, A. Pajak, S. Malyutina, M. I. Voevoda, A. Tamosiunas, A. H. Maitland-van der Zee, P. E. Norman, G. J. Hankey, M. M. Bergmann, A. Hofman, O. H. Franco, J. Cooper, J. Palmen, W. Spiering, P. A. d. Jong, D. Kuh, R. Hardy, A. G. Uitterlinden, M. A. Ikram, I. Ford, E. Hypponen, O. P. Almeida, N. J. Wareham, K.-T. Khaw, A. Hamsten, L. L. N. Husemoen, A. Tjonneland, J. S. Tolstrup, E. Rimm, J. W. J. Beulens, W. M. M. Verschuren, N. C. Onland-Moret, M. H. Hofker, S. G. Wannamethee, P. H. Whincup, R. Morris, A. M. Vicente, H. Watkins, M. Farrall, J. W. Jukema, J. Meschia, L. A. Cupples, S. J. Sharp, M. Fornage, C. Kooperberg, A. Z. LaCroix, J. Y. Dai, M. B. Lanktree, D. S. Siscovick, E. Jorgenson, B. Spring, J. Coresh, Y. R. Li, S. G. Buxbaum, P. J. Schreiner, R. C. Ellison, M. Y. Tsai, S. R. Patel, S. Redline, A. D. Johnson, R. C. Hoogeveen, H. Hakonarson, J. I. Rotter, E. Boerwinkle, P. I. W. d. Bakker, M. Kivimaki, F. W. Asselbergs, N. Sattar, D. A. Lawlor, J. Whittaker, G. Davey Smith, K. Mukamal, B. M. Psaty, J. G. Wilson, L. A. Lange, A. Hamidovic, A. D. Hingorani, B. G. Nordestgaard, M. Bobak, D. A. Leon, C. Langenberg, T. M. Palmer, A. P. Reiner, B. J. Keating, F. Dudbridge, J. P. Casas. Association between alcohol and cardiovascular disease: Mendelian randomisation analysis based on individual participant data. BMJ, 2014; 349 (jul10 6): g4164 DOI: 10.1136/bmj.g4164




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