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遗传危险、坚持健康生活方式和冠心病之间的关系
Genetic Risk, Adherence to a Healthy Lifestyle, and Coronary Disease


Amit V. Khera ... 心脑血管疾病 • 2016.12.15
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遗传因素和生活方式与冠心病风险

 

鲁向锋†‡§,顾东风†‡§*

† 国家心血管病中心;‡ 中国医学科学院阜外医院;§ 心血管疾病国家重点实验室

* 通讯作者

 

冠心病是全球范围内第一致死性疾病,给人类健康带来极大危害。目前认为冠心病的危险因素主要包括:高血压、血脂异常、吸烟、糖尿病、肥胖等。利用危险因素预测高危个体并采取相应的防治措施,是预防心血管疾病的重要策略。既往有弗雷明翰风险评分,近期有“PCE”风险模型应用于心血管病预测。近年,冠心病基因组和遗传因素取得了重大进展,国际冠心病协作联盟(CARDIoGRAMplusC4D Consortium)跨种族基因组研究报道了50余个冠心病易感位点1。这些遗传因素是否同样在心血管疾病发病风险评估中扮演重要角色?与传统危险因素和生活方式相比孰重孰轻?

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摘要


背景

遗传因素和生活方式因素均在个体水平冠状动脉疾病危险中发挥作用。目前尚不清楚增高的遗传危险在多大程度上可以被健康的生活方式抵消。

 

方法

采用DNA序列多态性多基因评分,我们在基因型和协变量数据已知的3个前瞻性队列和1项横断面BioImage研究的4,260名参与者中,对冠状动脉疾病的遗传危险进行了量化。3个前瞻性队列的参与者为:社区中动脉粥样硬化危险(Atherosclerosis Risk in Communities,ARIC)研究中的7,814名,妇女基因组健康研究(Women’s Genome Health Study,WGHS)中的21,222名,马尔默饮食和癌症研究(Malmö Diet and Cancer Study,MDCS)中的22,389名。我们还采用由4个因素(当前不吸烟、不肥胖、规律的体力活动和健康饮食)组成的评分体系来确定参与者中对健康生活方式的依从性。

 

结果

高遗传危险的参与者(多基因评分的最高五分位数)新发冠脉事件的相对危险比处于低遗传危险的参与者(多基因评分的最低五分位数)高91%(风险比为1.91;95%可信区间[CI]为1.75~2.09)。无论遗传危险的类别如何,与不良的生活方式(定义为没有或只有1种健康生活方式因素)相比,良好的生活方式(定义为至少有4种健康生活方式因素中的3种)在很大程度上与更低的冠脉事件危险相关。在高遗传危险的参与者中,与不良生活方式相比,一种良好的生活方式可以降低冠脉事件相对危险46%(风险比为0.54;95% CI为0.47~0.63)。相应地,标准化10年冠脉事件发生率在ARIC中从不良生活方式组的10.7%降至良好生活方式组的5.1%,在WGHS中从4.6%降至2.0%,而在MDCS中从8.2%降至5.3%。在BioImage研究中,良好生活方式与每个遗传危险分类中冠状动脉钙化减少显著相关。

 

结论

在包括55,685名参与者的4项研究中,遗传因素和生活方式因素与冠状动脉疾病的易感性独立相关。在遗传危险高的参与者中,与不良生活方式相比,良好的生活方式与冠状动脉疾病相对危险降低近50%相关(由国立卫生研究院[National Institutes of Health]等机构资助)。





作者信息

Amit V. Khera, M.D., Connor A. Emdin, D.Phil., Isabel Drake, Ph.D., Pradeep Natarajan, M.D., Alexander G. Bick, M.D., Ph.D., Nancy R. Cook, Ph.D., Daniel I. Chasman, Ph.D., Usman Baber, M.D., Roxana Mehran, M.D., Daniel J. Rader, M.D., Valentin Fuster, M.D., Ph.D., Eric Boerwinkle, Ph.D., Olle Melander, M.D., Ph.D., Marju Orho-Melander, Ph.D., Paul M Ridker, M.D., and Sekar Kathiresan, M.D.
From the Center for Human Genetic Research and Cardiology Division, Massachusetts General Hospital (A.V.K., P.N., S.K.), and the Division of Preventive Medicine, Department of Medicine, Brigham and Women’s Hospital (N.R.C., D.I.C., P.M.R.), Boston, and the Program in Medical and Population Genetics, Broad Institute, Cambridge (A.V.K., C.A.E., A.G.B., S.K.) — all in Massachusetts; the Department of Clinical Sciences, Lund University, Malmö, Sweden (I.D., O.M., M.O.-M.); the Cardiovascular Institute, Mount Sinai Medical Center, Icahn School of Medicine at Mount Sinai, New York (U.B., R.M., V.F.); Department of Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia (D.J.R.); and the University of Texas Health Science Center School of Public Health, Houston (E.B.). Address reprint requests to Dr. Kathiresan at the Center for Human Genetics Research, Massachusetts General Hospital, 185 Cambridge St., CPZN 5.252, Boston, MA 02114, or at skathiresan1@mgh.harvard.edu.

 

参考文献

1. Lozano R, Naghavi M, Foreman K, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 2012;380:2095-2128

2. Müller C. Xanthomata, hypercholesterolemia, angina pectoris. Acta Med Scand 1938;89:75-84

3. Gertler MM, Garn SM, White PD. Young candidates for coronary heart disease. J Am Med Assoc 1951;147:621-625

4. Slack J, Evans KA. The increased risk of death from ischaemic heart disease in first degree relatives of 121 men and 96 women with ischaemic heart disease. J Med Genet 1966;3:239-257

5. Marenberg ME, Risch N, Berkman LF, Floderus B, de Faire U. Genetic susceptibility to death from coronary heart disease in a study of twins. N Engl J Med 1994;330:1041-1046

6. Lloyd-Jones DM, Nam BH, D’Agostino RB Sr, et al. Parental cardiovascular disease as a risk factor for cardiovascular disease in middle-aged adults: a prospective study of parents and offspring. JAMA 2004;291:2204-2211

7. Samani NJ, Erdmann J, Hall AS, et al. Genomewide association analysis of coronary artery disease. N Engl J Med 2007;357:443-453

8. Helgadottir A, Thorleifsson G, Manolescu A, et al. A common variant on chromosome 9p21 affects the risk of myocardial infarction. Science 2007;316:1491-1493

9. McPherson R, Pertsemlidis A, Kavaslar N, et al. A common allele on chromosome 9 associated with coronary heart disease. Science 2007;316:1488-1491

10. Myocardial Infarction Genetics Consortium. Genome-wide association of early-onset myocardial infarction with single nucleotide polymorphisms and copy number variants. Nat Genet 2009;41:334-341

11. Erdmann J, Grosshennig A, Braund PS, et al. New susceptibility locus for coronary artery disease on chromosome 3q22.3. Nat Genet 2009;41:280-282

12. Coronary Artery Disease (C4D) Genetics Consortium. A genome-wide association study in Europeans and South Asians identifies five new loci for coronary artery disease. Nat Genet 2011;43:339-344

13. IBC 50K CAD Consortium. Large-scale gene-centric analysis identifies novel variants for coronary artery disease. PLoS Genet 2011;7:e1002260-e1002260

14. The CARDIoGRAMplusC4D Consortium. Large-scale association analysis identifies new risk loci for coronary artery disease. Nat Genet 2013;45:25-33

15. Nikpay M, Goel A, Won HH, et al. A comprehensive 1,000 Genomes-based genome-wide association meta-analysis of coronary artery disease. Nat Genet 2015;47:1121-1130

16. Kathiresan S, Melander O, Anevski D, et al. Polymorphisms associated with cholesterol and risk of cardiovascular events. N Engl J Med 2008;358:1240-1249

17. Ripatti S, Tikkanen E, Orho-Melander M, et al. A multilocus genetic risk score for coronary heart disease: case-control and prospective cohort analyses. Lancet 2010;376:1393-1400

18. Paynter NP, Chasman DI, Paré G, et al. Association between a literature-based genetic risk score and cardiovascular events in women. JAMA 2010;303:631-637

19. Thanassoulis G, Peloso GM, Pencina MJ, et al. A genetic risk score is associated with incident cardiovascular disease and coronary artery calcium: the Framingham Heart Study. Circ Cardiovasc Genet 2012;5:113-121

20. Brautbar A, Pompeii LA, Dehghan A, et al. A genetic risk score based on direct associations with coronary heart disease improves coronary heart disease risk prediction in the Atherosclerosis Risk in Communities (ARIC), but not in the Rotterdam and Framingham Offspring, Studies. Atherosclerosis 2012;223:421-426

21. Ganna A, Magnusson PK, Pedersen NL, et al. Multilocus genetic risk scores for coronary heart disease prediction. Arterioscler Thromb Vasc Biol 2013;33:2267-2272

22. Mega JL, Stitziel NO, Smith JG, et al. Genetic risk, coronary heart disease events, and the clinical benefit of statin therapy: an analysis of primary and secondary prevention trials. Lancet 2015;385:2264-2271

23. Tada H, Melander O, Louie JZ, et al. Risk prediction by genetic risk scores for coronary heart disease is independent of self-reported family history. Eur Heart J 2016;37:561-567

24. Abraham G, Havulinna AS, Bhalala OG, et al. Genomic prediction of coronary heart disease. Eur Heart J 2016 September 21 (Epub ahead of print)

25. Stampfer MJ, Hu FB, Manson JE, Rimm EB, Willett WC. Primary prevention of coronary heart disease in women through diet and lifestyle. N Engl J Med 2000;343:16-22

26. Folsom AR, Yatsuya H, Nettleton JA, Lutsey PL, Cushman M, Rosamond WD. Community prevalence of ideal cardiovascular health, by the American Heart Association definition, and relationship with cardiovascular disease incidence. J Am Coll Cardiol 2011;57:1690-1696

27. Yang Q, Cogswell ME, Flanders WD, et al. Trends in cardiovascular health metrics and associations with all-cause and CVD mortality among US adults. JAMA 2012;307:1273-1283

28. Xanthakis V, Enserro DM, Murabito JM, et al. Ideal cardiovascular health: associations with biomarkers and subclinical disease and impact on incidence of cardiovascular disease in the Framingham Offspring Study. Circulation 2014;130:1676-1683

29. Chomistek AK, Chiuve SE, Eliassen AH, Mukamal KJ, Willett WC, Rimm EB. Healthy lifestyle in the primordial prevention of cardiovascular disease among young women. J Am Coll Cardiol 2015;65:43-51

30. Akesson A, Larsson SC, Discacciati A, Wolk A. Low-risk diet and lifestyle habits in the primary prevention of myocardial infarction in men: a population-based prospective cohort study. J Am Coll Cardiol 2014;64:1299-1306

31. Lloyd-Jones DM, Hong Y, Labarthe D, et al. Defining and setting national goals for cardiovascular health promotion and disease reduction: the American Heart Association’s strategic Impact Goal through 2020 and beyond. Circulation 2010;121:586-613

32. White PD. Genes, the heart and destiny. N Engl J Med 1957;256:965-969

33. The Atherosclerosis Risk in Communities (ARIC) Study: design and objectives. Am J Epidemiol 1989;129:687-702

34. Ridker PM, Chasman DI, Zee RY, et al. Rationale, design, and methodology of the Women’s Genome Health Study: a genome-wide association study of more than 25,000 initially healthy American women. Clin Chem 2008;54:249-255

35. Berglund G, Elmstähl S, Janzon L, Larsson SA. The Malmo Diet and Cancer Study: design and feasibility. J Intern Med 1993;233:45-51

36. Baber U, Mehran R, Sartori S, et al. Prevalence, impact, and predictive value of detecting subclinical coronary and carotid atherosclerosis in asymptomatic adults: the BioImage study. J Am Coll Cardiol 2015;65:1065-1074

37. Price AL, Patterson NJ, Plenge RM, Weinblatt ME, Shadick NA, Reich D. Principal components analysis corrects for stratification in genome-wide association studies. Nat Genet 2006;38:904-909

38. Mozaffarian D. Dietary and policy priorities for cardiovascular disease, diabetes, and obesity: a comprehensive review. Circulation 2016;133:187-225

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