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Article(id=1241522930018997133, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1241522919977841545, articleNumber=null, orderNo=null, doi=10.20043/j.cnki.MPM.202311061, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1699027200000, receivedDateStr=2023-11-04, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1773931732897, onlineDateStr=2026-03-19, pubDate=1710000000000, pubDateStr=2024-03-10, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1773931732897, onlineIssueDateStr=2026-03-19, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1773931732897, creator=13701087609, updateTime=1773931732897, updator=13701087609, issue=Issue{id=1241522919977841545, tenantId=1146029695717560320, journalId=1227665162245664772, year='2024', volume='51', issue='5', pageStart='769', pageEnd='960', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1773931730503, creator=13701087609, updateTime=1773931880386, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1241523548695622547, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1241522919977841545, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1241523548695622548, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1241522919977841545, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=943, endPage=950, ext={EN=ArticleExt(id=1241522931361174443, articleId=1241522930018997133, tenantId=1146029695717560320, journalId=1227665162245664772, language=EN, title=Relationship between plasma omega-6/omega-3 fatty acid ratio and mortality in patients with cardiovascular disease, columnId=1228016569138213037, journalTitle=Modern Preventive Medicine, columnName=Clinical Medicine and Prevention, runingTitle=null, highlight=null, articleAbstract=
Objective

To analyze the relationship between the proportion of omega-6/omega-3 and mortality in patients with cardiovascular disease (CVD), so as to provide reference for reducing the risk of death in patients with CVD.

Methods

The data were collected from the UK perspective cohort (UK Biobank) database. The exposure variable was the proportion of plasma omega6/omega-3, and the outcomes were all- cause deaths, CVD deaths, ischemic heart disease (IHD) deaths, and stroke deaths. Multivariate Cox proportional hazard regression model was used to analyze the relationship between omega-6/omega-3 ratio and death risk of CVD patients. Hazard ratio (HR) and 95% confidence interval (CI) were calculated. Gender, age, and other risk factors were stratified and their interaction with omega-6/omega-3 ratio was analyzed. Restricted cubic spline (RCS) was used to describe the dose-response relationship. Sensitivity analysis was used to test the robustness of the model.

Results

A total of 35 096 participants were enrolled. Multivariate Cox proportional hazard regression model showed that all-cause deaths, CVD deaths, and ischemic heart disease deaths risk increased in CVD patients with the increase of the proportion of omega-6/omega-3. For each unit increase in omega-6/omega-3 ratio, the risk of all-cause, CVD, and IHD deaths increased by 2.1% (HR=1.021, 95%CI: 1.016-0.025), 1.9% (HR=1.019, 95%CI: 1.010-1.028), and 2.3% (HR=1.023, 95%CI:1.013-1.034), respectively. The proportion of omega-6/omega-3 was grouped according to quartile method and included in the model as a classified variable. Compared with Q1, the HR of all-cause, CVD, and IHD deaths of Q4 was 1.394 (95%CI: 1.267-1.534), 1.292 (95%CI: 1.085-1.540), and 1.528 (95%CI: 1.200-1.945), respectively, and no correlation was found between Q4 and stroke death risk (HR=0.987, 95%CI: 0.660-1.477). The results of RCS showed that the proportion of omega-6/omega3 was positively correlated with the risk of death.

Conclusion

The proportion of omega-6/omega-3 is a risk factor for death in patients with CVD.

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目的

分析Omega-6/Omega-3比例与心血管疾病(cardiovascular disease，CVD)患者死亡率的关联，为降低CVD患者死亡风险提供参考。

方法

本研究数据来源于英国前瞻性队列(UK Biobank)数据库，暴露变量为血浆Omega-6/Omega-3比例，结局为全因、CVD死亡、缺血性心脏病(ischemic heart disease，IHD)死亡和卒中死亡。采用多变量Cox比例风险回归模型分析Omega-6/Omega-3比例与CVD患者死亡风险的关联，计算风险比(hazard ratio，HR)和95%置信区间(confidence interval，CI)，对性别、年龄等危险因素分层并分析其与Omega-6/Omega-3比例的交互作用，采用限制性立方样条法(restricted cubric spline，RCS)描述其剂量反应关系，利用敏感性分析检验模型的稳健性。

结果

共纳入35 096名参与者，多变量Cox比例风险回归模型显示Omega-6/Omega-3比例增加，CVD患者的全因死亡、CVD死亡和缺血性心脏病死亡率均增加(均P趋势<0.05)。Omega-6/Omega-3比例每增加一个单位，全因、CVD和IHD死亡风险分别增加2.1%(HR=1.021，95%CI：1.016～0.025)、1.9%(HR=1.019，95%CI：1.010～1.028)和2.3%(HR=1.023，95%CI：1.013～1.034)。将Omega-6/Omega-3比例按四分位数法进行分组后作为分类变量纳入模型进行分析，与Q1相比，Q4的全因、CVD和IHD死亡风险HR分别为1.394(95%CI：1.267～1.534)、1.292(95%CI：1.085～1.540)和1.528(95%CI：1.200～1.945)，未发现与卒中死亡风险有关(HR=0.987，95%CI：0.660～1.477)。RCS结果显示Omega-6/Omega-3比例与死亡风险呈正相关。

结论

Omega-6/Omega-3比例是CVD患者的死亡风险的危险因素。

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梁会营，E-mail:
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李晴（1997—），女，硕士在读，研究方向：多不饱和脂肪酸与心血管疾病的临床流行病学研究

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李晴（1997—），女，硕士在读，研究方向：多不饱和脂肪酸与心血管疾病的临床流行病学研究

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李晴（1997—），女，硕士在读，研究方向：多不饱和脂肪酸与心血管疾病的临床流行病学研究

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Beneficial outcomes of omega-6 and omega-3 polyunsaturated fatty acids on human health: an update for 2021[J].Nutrients, 2021, 13(7): 2421., articleTitle=Beneficial outcomes of omega-6 and omega-3 polyunsaturated fatty acids on human health: an update for 2021, refAbstract=null), Reference(id=1241678344870228902, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241522930018997133, doi=null, pmid=null, pmcid=null, year=2017, volume=3, issue=4, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[19], rfOrder=18, authorNames=Bck M, journalName=Future Sci OA, refType=null, unstructuredReference=Bck M. Omega-3 fatty acids in atherosclerosis and coronary artery disease[J]. 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Nutrients, 2021, 13(5): 1489., articleTitle=Associations of arachidonic acid synthesis with cardiovascular risk factors and relation to ischemic heart disease and stroke: a univariable and multivariable mendelian randomization study, refAbstract=null), Reference(id=1241678346644419512, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241522930018997133, doi=null, pmid=null, pmcid=null, year=2011, volume=58, issue=2, pageStart=248, pageEnd=256, url=null, language=null, rfNumber=[23], rfOrder=22, authorNames=Noori N, Dukkipati R, Kovesdy CP, journalName=American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation, refType=null, unstructuredReference=Noori N, Dukkipati R, Kovesdy CP, et al. Dietary omega-3 fatty acid, ratio of omega-6 to omega-3 intake, inflammation, and survival in long-term hemodialysis patients[J]. American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation,2011, 58(2): 248-256., articleTitle=Dietary omega-3 fatty acid, ratio of omega-6 to omega-3 intake, inflammation, and survival in long-term hemodialysis patients, refAbstract=null)], funds=[Fund(id=1241678331905635123, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241522930018997133, awardId=2022B1212010011, language=CN, fundingSource=广东省人工智能医学图像分析与应用重点实验室(2022B1212010011), fundOrder=null, country=null)], companyList=[AuthorCompany(id=1241678292567257494, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241522930018997133, xref=1., ext=[AuthorCompanyExt(id=1241678292575646102, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241522930018997133, companyId=1241678292567257494, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=School of Public Health, China Medical University, Shenyang, Liaoning 110122, China), AuthorCompanyExt(id=1241678292743418263, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241522930018997133, companyId=1241678292567257494, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1.中国医科大学公共卫生学院，辽宁 沈阳 110122)]), AuthorCompany(id=1241678293238346152, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241522930018997133, xref=2., ext=[AuthorCompanyExt(id=1241678293246734761, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241522930018997133, companyId=1241678293238346152, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2.南方医科大学附属广东省人民医院（广东省医学科学院）医学大数据中心，广东 广州 510800)]), AuthorCompany(id=1241678293565501876, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241522930018997133, xref=3., ext=[AuthorCompanyExt(id=1241678293573890485, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241522930018997133, companyId=1241678293565501876, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=3.南方医科大学公共卫生学院)])], figs=[ArticleFig(id=1241678324959867615, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241522930018997133, language=EN, label=Figure 1, caption=Fully adjusted association between plasma Omega-6/Omega-3 ratio and all-cause mortality risk stratified by potential risk factors, figureFileSmall=J81Qjc8VKq8vb2O8AgEIuQ==, figureFileBig=OA2dt4cHYdnI3NLGMsTuRA==, tableContent=null), ArticleFig(id=1241678325341549285, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241522930018997133, language=CN, label=图1, caption=血浆Omega-6/Omega-3比例与全因死亡风险的完全调整关联按潜在风险因素分层, figureFileSmall=J81Qjc8VKq8vb2O8AgEIuQ==, figureFileBig=OA2dt4cHYdnI3NLGMsTuRA==, tableContent=null), ArticleFig(id=1241678326293656302, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241522930018997133, language=EN, label=Figure 2, caption=Fully adjusted association between plasma Omega-6/Omega-3 ratio and mortality risk in CVD and IHD stratified by potential risk factors, figureFileSmall=kT4TVheDezlLZhPkrMFlfg==, figureFileBig=ceEBeWB1dhdm/GDyMhwOIw==, tableContent=null), ArticleFig(id=1241678327031853813, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241522930018997133, language=CN, label=图2, caption=血浆Omega-6/Omega-3比例与CVD和IHD死亡风险的完全调整关联按潜在风险因素分层, figureFileSmall=kT4TVheDezlLZhPkrMFlfg==, figureFileBig=ceEBeWB1dhdm/GDyMhwOIw==, tableContent=null), ArticleFig(id=1241678327652610807, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241522930018997133, language=EN, label=Figure 3, caption=Dose response relationship between the Omega-6/Omega-3 ratio and the risk of all-cause and specific cause mortality, figureFileSmall=1iJYanYqgfnirCWCrqCEYQ==, figureFileBig=wTOO+/kjAm0FobSdJxiSGA==, tableContent=null), ArticleFig(id=1241678328290145025, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241522930018997133, language=CN, label=图3, caption=Omega-6/Omega-3比例与全因死亡和特定原因死亡风险的剂量反应关系, figureFileSmall=1iJYanYqgfnirCWCrqCEYQ==, figureFileBig=wTOO+/kjAm0FobSdJxiSGA==, tableContent=null), ArticleFig(id=1241678328625689350, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241522930018997133, language=EN, label=Table 1, caption=

Baseline characteristics of study participants grouped by the quartile of plasma Omega-6/Omega-3 ratio ［（），M（QR），n（%）］

, figureFileSmall=null, figureFileBig=null, tableContent=
特征全部
(n=35 096)		Q1(0～<8.88)
(n=8 780)		Q2(6.88～<8.57)
(n=8 752)		Q3(8.57～<10.86)
(n=8 783)		Q4(≥10.86)
(n=8 781)		χ2/T/H值P值
年龄（岁）61.0±10.062.0±9.061.0±9.060.0±11.059.0±13.0962.670<0.001
性别（女性）16 391(46.7)4 554(51.9)4 273(48.8)3 898(44.4)3 666(41.7)215.490
汤森剥夺指数-1.99 (-3.56，0.97)-2.30(-3.70，0.34)-2.07 (-3.63,0.69)-1.97 (-3.55,1.05)-1.54 (-3.35,1.62)216.650<0.001
家庭收入(英镑)48.760<0.001
<18 00011 607(33.1)2 845(32.4)2 838(32.4)2 894(33.0)3 030(34.5)
18 000～30 9999 588(27.3)2 488(28.3)2 419(27.6)2 370(27.0)2 311(26.3)
31 000～51 9997 735(22.0)1 921(21.9)1 909(21.8)1 930(22.0)1 975(22.5)
52 000～100 0005 035(14.3)1 212(13.8)1 257(14.4)1 315(15.0)1 251(14.2)
>10 00001 131(3.22)314(3.58)329(3.76)274(3.12)214(2.44)
受教育资质65.150<0.001
大学9 228(26.3)2 556(29.1)2 337(26.7)2 232(25.4)2 103(23.9)
其他25 868(73.7)6 224(70.9)6 415(73.3)6 551(74.6)6 678(76.1)
种族297.000<0.001
白人33 017(94.1)8 215(93.6)8 284(94.7)8 321(94.7)8 197(93.3)
黑人866(2.47)336(3.83)222(2.54)172(1.96)136(1.55)
亚洲724(2.06)92(1.05)125(1.43)178(2.03)329(3.75)
混血178(0.51)40(0.46)43(0.49)44(0.50)51(0.58)
其他311(0.89)97(1.10)78(0.89)68(0.77)68(0.77)
IPAQ38.180<0.001
低7 487(21.3)1 775(20.2)1 855(21.2)1 892(21.5)1 965(22.4)
中等14 056(40.1)3 608(41.1)3 565(40.7)3 593(40.9)3 290(37.5)
高13 553(38.6)3 397(38.7)3 332(38.1)3 298(37.5)3 526(40.2)
吸烟状况331.320<0.001
从不吸烟17 686(50.4)4 486(51.1)4 380(50.0)4 396(50.1)4 424(50.4)
目前吸烟3 569(10.2)595(6.78)780(8.91)930(10.6)1 264(14.4)
曾经吸烟13 841(39.4)3 699(42.1)3 592(41.0)3 457(39.4)3 093(35.2)
饮酒状况99.960<0.001
从不饮酒1 781(5.07)400(4.56)381(4.35)446(5.08)554(6.31)
目前饮酒31 761(90.5)8 042(91.6)8 018(91.6)7 984(90.9)7 717(87.9)
曾经饮酒1 554(4.43)338(3.85)353(4.03)353(4.02)510(5.81)
熟蔬菜摄入量(份/d)393.050<0.001
<26 120(17.4)1 094(12.5)1 353(15.5)1 662(18.9)2 011(22.9)
2～425 079(71.5)6 548(74.6)6 429(73.5)6 250(71.2)5 852(66.6)
>43 897(11.1)1 138(13.0)970(11.1)871(9.92)918(10.5)
水果摄入量(份/d)510.420<0.001
<212 215(34.8)2 338(26.6)2 900(33.1)3 306(37.6)3 671(41.8)
2～419 989(57.0)5 539(63.1)5 118(58.5)4 800(54.7)4 532(51.6)
>42 892(8.24)903(10.3)734(8.39)677(7.71)578(6.58)
油性鱼摄入量(片/d)2 404.160<0.001
<228 028(79.9)5 549(63.2)6 948(79.4)7 519(85.6)8 012(91.2)
≥27 068(20.1)3 231(36.8)1 804(20.6)1 264(14.4)769(8.76)
抗高血压药使用179.270<0.001
否11 694(33.3)2 543(29.0)2 786(31.8)3 017(34.4)3 348(38.1)
是23 402(66.7)6 237(71.0)5 966(68.2)5 766(65.6)5 433(61.9)
胰岛素治疗4.7680.19
否34 244(97.6)8 573(97.6)8 553(97.7)8 577(97.7)8 541(97.3)
是852(2.43)207(2.36)199(2.27)206(2.35)240(2.73)
阿司匹林使用242.970<0.001
否24 176(68.9)5 635(64.2)5 820(66.5)6 204(70.6)6 517(74.2)
是10 920(31.1)3 145(35.8)2 932(33.5)2 579(29.4)2 264(25.8)
他汀类药物使用983.060<0.001
否22 234(63.4)4 775(54.4)5 072(58.0)5 766(65.6)6 621(75.4)
是12 862(36.6)4 005(45.6)3 680(42.0)3 017(34.4)2 160(24.6)
维生素补剂264.010<0.001
否24 360(69.4)5 584(63.6)5 954(68.0)6 316(71.9)6 506(74.1)
是10 736(30.6)3 196(36.4)2 798(32.0)2 467(28.1)2 275(25.9)
矿物质和其他膳食补充剂1 378.070<0.001
否19 595(55.8)3 697(42.1)4 555(52.0)5 325(60.6)6 018(68.5)
是15 501(44.2)5 083(57.9)4 197(48.0)3 458(39.4)2 763(31.5)
鱼油补剂1 774.440<0.001
否23 445(66.8)4 565(52.0)5 504(62.9)6 303(71.8)7 073(80.5)
是11 651(33.2)4 215(48.0)3 248(37.1)2 480(28.2)1 708(19.5)
舒张压(mm Hg)85.0 (78.0,92.0)84.0 (77.0,90.5)84.5 (78.0,91.5)85.5 (78.0,92.0)86.0 (78.5,93.0)168.610<0.001
收缩压(mm Hg)144 (132,156)144 (132,156)144 (132,156)144 (132,156)143 (131,156)16.9900.001
BMI (kg/m2)28.4±5.328.2±5.728.5±6.128.5±6.228.4±6.856.150<0.001
长期疾病9.4340.024
否18 340(52.3)4 643(52.9)4 478(51.2)4 672(53.2)4 547(51.8)
是16 756(47.7)4 137(47.1)4 274(48.8)4 111(46.8)4 234(48.2)
高血压0.7050.872
否2 440(6.95)622(7.08)595(6.80)618(7.04)605(6.89)
是32 656(93.0)8 158(92.9)8 157(93.2)8 165(93.0)8 176(93.1)
糖尿病33.981<0.001
否31 096(88.6)7 668(87.3)7 702(88.0)7 836(89.2)7 890(89.9)
是4 000(11.4)1 112(12.7)1 050(12.0)947(10.8)891(10.1)
), ArticleFig(id=1241678329456161550, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241522930018997133, language=CN, label=表1, caption=

按血浆Omega-6/Omega-3比例四分位数分组的研究参与者的基线特征［（），M（QR），n（%）］

, figureFileSmall=null, figureFileBig=null, tableContent=
特征全部
(n=35 096)		Q1(0～<8.88)
(n=8 780)		Q2(6.88～<8.57)
(n=8 752)		Q3(8.57～<10.86)
(n=8 783)		Q4(≥10.86)
(n=8 781)		χ2/T/H值P值
年龄（岁）61.0±10.062.0±9.061.0±9.060.0±11.059.0±13.0962.670<0.001
性别（女性）16 391(46.7)4 554(51.9)4 273(48.8)3 898(44.4)3 666(41.7)215.490
汤森剥夺指数-1.99 (-3.56，0.97)-2.30(-3.70，0.34)-2.07 (-3.63,0.69)-1.97 (-3.55,1.05)-1.54 (-3.35,1.62)216.650<0.001
家庭收入(英镑)48.760<0.001
<18 00011 607(33.1)2 845(32.4)2 838(32.4)2 894(33.0)3 030(34.5)
18 000～30 9999 588(27.3)2 488(28.3)2 419(27.6)2 370(27.0)2 311(26.3)
31 000～51 9997 735(22.0)1 921(21.9)1 909(21.8)1 930(22.0)1 975(22.5)
52 000～100 0005 035(14.3)1 212(13.8)1 257(14.4)1 315(15.0)1 251(14.2)
>10 00001 131(3.22)314(3.58)329(3.76)274(3.12)214(2.44)
受教育资质65.150<0.001
大学9 228(26.3)2 556(29.1)2 337(26.7)2 232(25.4)2 103(23.9)
其他25 868(73.7)6 224(70.9)6 415(73.3)6 551(74.6)6 678(76.1)
种族297.000<0.001
白人33 017(94.1)8 215(93.6)8 284(94.7)8 321(94.7)8 197(93.3)
黑人866(2.47)336(3.83)222(2.54)172(1.96)136(1.55)
亚洲724(2.06)92(1.05)125(1.43)178(2.03)329(3.75)
混血178(0.51)40(0.46)43(0.49)44(0.50)51(0.58)
其他311(0.89)97(1.10)78(0.89)68(0.77)68(0.77)
IPAQ38.180<0.001
低7 487(21.3)1 775(20.2)1 855(21.2)1 892(21.5)1 965(22.4)
中等14 056(40.1)3 608(41.1)3 565(40.7)3 593(40.9)3 290(37.5)
高13 553(38.6)3 397(38.7)3 332(38.1)3 298(37.5)3 526(40.2)
吸烟状况331.320<0.001
从不吸烟17 686(50.4)4 486(51.1)4 380(50.0)4 396(50.1)4 424(50.4)
目前吸烟3 569(10.2)595(6.78)780(8.91)930(10.6)1 264(14.4)
曾经吸烟13 841(39.4)3 699(42.1)3 592(41.0)3 457(39.4)3 093(35.2)
饮酒状况99.960<0.001
从不饮酒1 781(5.07)400(4.56)381(4.35)446(5.08)554(6.31)
目前饮酒31 761(90.5)8 042(91.6)8 018(91.6)7 984(90.9)7 717(87.9)
曾经饮酒1 554(4.43)338(3.85)353(4.03)353(4.02)510(5.81)
熟蔬菜摄入量(份/d)393.050<0.001
<26 120(17.4)1 094(12.5)1 353(15.5)1 662(18.9)2 011(22.9)
2～425 079(71.5)6 548(74.6)6 429(73.5)6 250(71.2)5 852(66.6)
>43 897(11.1)1 138(13.0)970(11.1)871(9.92)918(10.5)
水果摄入量(份/d)510.420<0.001
<212 215(34.8)2 338(26.6)2 900(33.1)3 306(37.6)3 671(41.8)
2～419 989(57.0)5 539(63.1)5 118(58.5)4 800(54.7)4 532(51.6)
>42 892(8.24)903(10.3)734(8.39)677(7.71)578(6.58)
油性鱼摄入量(片/d)2 404.160<0.001
<228 028(79.9)5 549(63.2)6 948(79.4)7 519(85.6)8 012(91.2)
≥27 068(20.1)3 231(36.8)1 804(20.6)1 264(14.4)769(8.76)
抗高血压药使用179.270<0.001
否11 694(33.3)2 543(29.0)2 786(31.8)3 017(34.4)3 348(38.1)
是23 402(66.7)6 237(71.0)5 966(68.2)5 766(65.6)5 433(61.9)
胰岛素治疗4.7680.19
否34 244(97.6)8 573(97.6)8 553(97.7)8 577(97.7)8 541(97.3)
是852(2.43)207(2.36)199(2.27)206(2.35)240(2.73)
阿司匹林使用242.970<0.001
否24 176(68.9)5 635(64.2)5 820(66.5)6 204(70.6)6 517(74.2)
是10 920(31.1)3 145(35.8)2 932(33.5)2 579(29.4)2 264(25.8)
他汀类药物使用983.060<0.001
否22 234(63.4)4 775(54.4)5 072(58.0)5 766(65.6)6 621(75.4)
是12 862(36.6)4 005(45.6)3 680(42.0)3 017(34.4)2 160(24.6)
维生素补剂264.010<0.001
否24 360(69.4)5 584(63.6)5 954(68.0)6 316(71.9)6 506(74.1)
是10 736(30.6)3 196(36.4)2 798(32.0)2 467(28.1)2 275(25.9)
矿物质和其他膳食补充剂1 378.070<0.001
否19 595(55.8)3 697(42.1)4 555(52.0)5 325(60.6)6 018(68.5)
是15 501(44.2)5 083(57.9)4 197(48.0)3 458(39.4)2 763(31.5)
鱼油补剂1 774.440<0.001
否23 445(66.8)4 565(52.0)5 504(62.9)6 303(71.8)7 073(80.5)
是11 651(33.2)4 215(48.0)3 248(37.1)2 480(28.2)1 708(19.5)
舒张压(mm Hg)85.0 (78.0,92.0)84.0 (77.0,90.5)84.5 (78.0,91.5)85.5 (78.0,92.0)86.0 (78.5,93.0)168.610<0.001
收缩压(mm Hg)144 (132,156)144 (132,156)144 (132,156)144 (132,156)143 (131,156)16.9900.001
BMI (kg/m2)28.4±5.328.2±5.728.5±6.128.5±6.228.4±6.856.150<0.001
长期疾病9.4340.024
否18 340(52.3)4 643(52.9)4 478(51.2)4 672(53.2)4 547(51.8)
是16 756(47.7)4 137(47.1)4 274(48.8)4 111(46.8)4 234(48.2)
高血压0.7050.872
否2 440(6.95)622(7.08)595(6.80)618(7.04)605(6.89)
是32 656(93.0)8 158(92.9)8 157(93.2)8 165(93.0)8 176(93.1)
糖尿病33.981<0.001
否31 096(88.6)7 668(87.3)7 702(88.0)7 836(89.2)7 890(89.9)
是4 000(11.4)1 112(12.7)1 050(12.0)947(10.8)891(10.1)
), ArticleFig(id=1241678329913340693, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241522930018997133, language=EN, label=Table 2, caption=

Omega-6/Omega-3 ratio and outcome association [HR (95%CI)]

, figureFileSmall=null, figureFileBig=null, tableContent=
结局模型连续型四分位数
Q1Q2Q3Q4P趋势
全因死亡死亡人数3 7818808869241 091
模型11.017(1.013～1.022)11.026(0.934～1.126)1.059(0.965～1.163)1.219(1.178～1.415)<0.001
模型21.019(1.014～1.023)11.014(0.924～1.114)1.070(0.935～1.175)1.328(1.212～1.456)<0.001
模型31.021(1.016～0.025)11.027(0.935～1.129)1.100(1.001～1.210)1.394(1.267～1.534)<0.001
CVD死亡死亡人数1 090271242361316
模型11.012(1.002～1.022)10.896(0.753～1.066)0.937(0.789～1.112)1.137(0.962～1.344)0.104
模型21.016(1.007～1.025)10.882(0.741～1.015)0.955(0.804～1.134)1.205(1.019～1.425)0.017
模型31.019(1.010～1.028)10.902(0.758～1.075)0.989(0.830～1.179)1.292(1.085～1.540)0.002
IHD死亡死亡人数600134133154179
模型11.013(1.000～1.026)10.972(0.764～1.136)1.064(0.843～1.344)1.199(0.952～1.510)0.080
模型21.018(1.007～1.030)10.960(0.755～1.222)1.103(0.873～1.394)1.316(1.045～1.658)0.009
模型31.023(1.013～1.034)11.013(0.759～1.291)1.195(0.940～1.518)1.528(1.200～1.945)<0.001
卒中死亡死亡人数19060393952
模型11.001(0.967～1.036)10.674(0.450～1.010)0.683(0.455～1.026)0.972(0.662～1.428)0.810
模型21.003(0.970～1.038)10.680(0.453～1.019)0.702(0.467～1.056)1.009(0.686～1.483)0.962
模型31.002(0.968～1.038)10.668(0.445～1.003)0.690(0.456～1.045)0.987(0.660～1.477)0.985
), ArticleFig(id=1241678330315993881, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241522930018997133, language=CN, label=表2, caption=

Omega-6/Omega-3比例与结局关联[HR（95%CI）]

, figureFileSmall=null, figureFileBig=null, tableContent=
结局模型连续型四分位数
Q1Q2Q3Q4P趋势
全因死亡死亡人数3 7818808869241 091
模型11.017(1.013～1.022)11.026(0.934～1.126)1.059(0.965～1.163)1.219(1.178～1.415)<0.001
模型21.019(1.014～1.023)11.014(0.924～1.114)1.070(0.935～1.175)1.328(1.212～1.456)<0.001
模型31.021(1.016～0.025)11.027(0.935～1.129)1.100(1.001～1.210)1.394(1.267～1.534)<0.001
CVD死亡死亡人数1 090271242361316
模型11.012(1.002～1.022)10.896(0.753～1.066)0.937(0.789～1.112)1.137(0.962～1.344)0.104
模型21.016(1.007～1.025)10.882(0.741～1.015)0.955(0.804～1.134)1.205(1.019～1.425)0.017
模型31.019(1.010～1.028)10.902(0.758～1.075)0.989(0.830～1.179)1.292(1.085～1.540)0.002
IHD死亡死亡人数600134133154179
模型11.013(1.000～1.026)10.972(0.764～1.136)1.064(0.843～1.344)1.199(0.952～1.510)0.080
模型21.018(1.007～1.030)10.960(0.755～1.222)1.103(0.873～1.394)1.316(1.045～1.658)0.009
模型31.023(1.013～1.034)11.013(0.759～1.291)1.195(0.940～1.518)1.528(1.200～1.945)<0.001
卒中死亡死亡人数19060393952
模型11.001(0.967～1.036)10.674(0.450～1.010)0.683(0.455～1.026)0.972(0.662～1.428)0.810
模型21.003(0.970～1.038)10.680(0.453～1.019)0.702(0.467～1.056)1.009(0.686～1.483)0.962
模型31.002(0.968～1.038)10.668(0.445～1.003)0.690(0.456～1.045)0.987(0.660～1.477)0.985
), ArticleFig(id=1241678330798338850, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241522930018997133, language=EN, label=Table 3, caption=

Omega-6/Omega-3 ratio and outcome association after excluding subjects who died during the second year of follow-up[HR(95%CI)]

, figureFileSmall=null, figureFileBig=null, tableContent=
结局连续型四分位数
Q1Q2Q3Q4P趋势值
全因死亡死亡人数3 5698418398831 006
模型11.016(1.011～1.021)11.019(0.926～1.122)1.064(0.968～1.171)1.255(1.142～1.379)<0.001
模型21.018(1.013～1.023)11.008(0.916～1.109)1.074(0.976～1.181)1.290(1.173～1.417)<0.001
模型31.020(1.015～1.025)11.021(0.927～1.124)1.105(1.002～1.217)1.355(1.228～1.495)<0.001
CVD死亡死亡人数1 012254226252280
模型11.010(0.999～1.021)10.896(0.749～1.073)0.971(0.814～1.157)1.086(0.916～1.293)0.250
模型21.014(1.004～1.025)10.882(0.737～1.056)0.987(0.828～1.774)1.149(0.946～1.369)0.064
模型31.018(1.001～1.028)10.903(0.754～1.083)1.024(0.856～1.227)1.236(1.029～1.484)0.012
IHD死亡死亡人数553129120147157
模型11.011(0.997～1.026)10.915(0.713～1.174)1.062(0.937～1.348)1.107(0.871～1.406)0.238
模型21.017(1.005～1.030)10.904(0.705～1.161)1.098(0.864～1.394)1.214(0.955～1.543)0.044
模型31.023(1.011～1.034)10.957(0.745～1.231)1.195(0.935～1.526)1.418(1.104～1.823)0.002
卒中死亡死亡人数17853383849
模型11.001(0.966～1.037)10.748(0.492～1.136)0.761(0.499～1.158)1.049(0.703～1.568)0.866
模型21.004(0.969～1.039)10.753(0.496～1.144)0.779(0.511～1.881)1.087(0.727～1.626)0.729
模型31.001(0.965～1.039)10.739(0.485～1.125)0.761(0.496～1.169)1.051(0.690～1.601)0.857
), ArticleFig(id=1241678331075162921, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241522930018997133, language=CN, label=表3, caption=

排除在第二年随访期间死亡的受试者后Omega-6/Omega-3比例与结局关联[HR（95%CI）]

, figureFileSmall=null, figureFileBig=null, tableContent=
结局连续型四分位数
Q1Q2Q3Q4P趋势值
全因死亡死亡人数3 5698418398831 006
模型11.016(1.011～1.021)11.019(0.926～1.122)1.064(0.968～1.171)1.255(1.142～1.379)<0.001
模型21.018(1.013～1.023)11.008(0.916～1.109)1.074(0.976～1.181)1.290(1.173～1.417)<0.001
模型31.020(1.015～1.025)11.021(0.927～1.124)1.105(1.002～1.217)1.355(1.228～1.495)<0.001
CVD死亡死亡人数1 012254226252280
模型11.010(0.999～1.021)10.896(0.749～1.073)0.971(0.814～1.157)1.086(0.916～1.293)0.250
模型21.014(1.004～1.025)10.882(0.737～1.056)0.987(0.828～1.774)1.149(0.946～1.369)0.064
模型31.018(1.001～1.028)10.903(0.754～1.083)1.024(0.856～1.227)1.236(1.029～1.484)0.012
IHD死亡死亡人数553129120147157
模型11.011(0.997～1.026)10.915(0.713～1.174)1.062(0.937～1.348)1.107(0.871～1.406)0.238
模型21.017(1.005～1.030)10.904(0.705～1.161)1.098(0.864～1.394)1.214(0.955～1.543)0.044
模型31.023(1.011～1.034)10.957(0.745～1.231)1.195(0.935～1.526)1.418(1.104～1.823)0.002
卒中死亡死亡人数17853383849
模型11.001(0.966～1.037)10.748(0.492～1.136)0.761(0.499～1.158)1.049(0.703～1.568)0.866
模型21.004(0.969～1.039)10.753(0.496～1.144)0.779(0.511～1.881)1.087(0.727～1.626)0.729
模型31.001(0.965～1.039)10.739(0.485～1.125)0.761(0.496～1.169)1.051(0.690～1.601)0.857
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血浆Omega-6/Omega-3脂肪酸比例与心血管疾病患者死亡率的关联
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李晴 1, 2 , 李惠先 2 , 郑海清 2 , 李佳美 1, 2 , 陈紫英 3 , 孙佳琦 1, 2 , 梁会营 2, 1
现代预防医学 | 临床与预防 2024,51(5): 943-950
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现代预防医学 | 临床与预防 2024, 51(5): 943-950
血浆Omega-6/Omega-3脂肪酸比例与心血管疾病患者死亡率的关联
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李晴1, 2, 李惠先2, 郑海清2, 李佳美1, 2, 陈紫英3, 孙佳琦1, 2, 梁会营2, 1
作者信息
  • 1.中国医科大学公共卫生学院，辽宁 沈阳 110122
  • 2.南方医科大学附属广东省人民医院（广东省医学科学院）医学大数据中心，广东 广州 510800
  • 3.南方医科大学公共卫生学院

    • 李晴（1997—），女，硕士在读，研究方向：多不饱和脂肪酸与心血管疾病的临床流行病学研究

通讯作者:

梁会营，E-mail:
Relationship between plasma omega-6/omega-3 fatty acid ratio and mortality in patients with cardiovascular disease
Qing LI1, 2, Hui-xian LI2, Hai-qing ZHENG2, Jia-mei LI1, 2, Zi-ying CHEN3, Jia-qi SUN1, 2, Hui-ying LIANG2, 1
Affiliations
  • School of Public Health, China Medical University, Shenyang, Liaoning 110122, China
出版时间: 2024-03-10 doi: 10.20043/j.cnki.MPM.202311061
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摘要
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目的

分析Omega-6/Omega-3比例与心血管疾病(cardiovascular disease，CVD)患者死亡率的关联，为降低CVD患者死亡风险提供参考。

方法

本研究数据来源于英国前瞻性队列(UK Biobank)数据库，暴露变量为血浆Omega-6/Omega-3比例，结局为全因、CVD死亡、缺血性心脏病(ischemic heart disease，IHD)死亡和卒中死亡。采用多变量Cox比例风险回归模型分析Omega-6/Omega-3比例与CVD患者死亡风险的关联，计算风险比(hazard ratio，HR)和95%置信区间(confidence interval，CI)，对性别、年龄等危险因素分层并分析其与Omega-6/Omega-3比例的交互作用，采用限制性立方样条法(restricted cubric spline，RCS)描述其剂量反应关系，利用敏感性分析检验模型的稳健性。

结果

共纳入35 096名参与者，多变量Cox比例风险回归模型显示Omega-6/Omega-3比例增加，CVD患者的全因死亡、CVD死亡和缺血性心脏病死亡率均增加(均P趋势<0.05)。Omega-6/Omega-3比例每增加一个单位，全因、CVD和IHD死亡风险分别增加2.1%(HR=1.021，95%CI：1.016～0.025)、1.9%(HR=1.019，95%CI：1.010～1.028)和2.3%(HR=1.023，95%CI：1.013～1.034)。将Omega-6/Omega-3比例按四分位数法进行分组后作为分类变量纳入模型进行分析，与Q1相比，Q4的全因、CVD和IHD死亡风险HR分别为1.394(95%CI：1.267～1.534)、1.292(95%CI：1.085～1.540)和1.528(95%CI：1.200～1.945)，未发现与卒中死亡风险有关(HR=0.987，95%CI：0.660～1.477)。RCS结果显示Omega-6/Omega-3比例与死亡风险呈正相关。

结论

Omega-6/Omega-3比例是CVD患者的死亡风险的危险因素。

Omega-6多不饱和脂肪酸  /  Omega-3多不饱和脂肪酸  /  比例  /  死亡率  /  前瞻性队列研究
Objective

To analyze the relationship between the proportion of omega-6/omega-3 and mortality in patients with cardiovascular disease (CVD), so as to provide reference for reducing the risk of death in patients with CVD.

Methods

The data were collected from the UK perspective cohort (UK Biobank) database. The exposure variable was the proportion of plasma omega6/omega-3, and the outcomes were all- cause deaths, CVD deaths, ischemic heart disease (IHD) deaths, and stroke deaths. Multivariate Cox proportional hazard regression model was used to analyze the relationship between omega-6/omega-3 ratio and death risk of CVD patients. Hazard ratio (HR) and 95% confidence interval (CI) were calculated. Gender, age, and other risk factors were stratified and their interaction with omega-6/omega-3 ratio was analyzed. Restricted cubic spline (RCS) was used to describe the dose-response relationship. Sensitivity analysis was used to test the robustness of the model.

Results

A total of 35 096 participants were enrolled. Multivariate Cox proportional hazard regression model showed that all-cause deaths, CVD deaths, and ischemic heart disease deaths risk increased in CVD patients with the increase of the proportion of omega-6/omega-3. For each unit increase in omega-6/omega-3 ratio, the risk of all-cause, CVD, and IHD deaths increased by 2.1% (HR=1.021, 95%CI: 1.016-0.025), 1.9% (HR=1.019, 95%CI: 1.010-1.028), and 2.3% (HR=1.023, 95%CI:1.013-1.034), respectively. The proportion of omega-6/omega-3 was grouped according to quartile method and included in the model as a classified variable. Compared with Q1, the HR of all-cause, CVD, and IHD deaths of Q4 was 1.394 (95%CI: 1.267-1.534), 1.292 (95%CI: 1.085-1.540), and 1.528 (95%CI: 1.200-1.945), respectively, and no correlation was found between Q4 and stroke death risk (HR=0.987, 95%CI: 0.660-1.477). The results of RCS showed that the proportion of omega-6/omega3 was positively correlated with the risk of death.

Conclusion

The proportion of omega-6/omega-3 is a risk factor for death in patients with CVD.

Omega-6 polyunsaturated fatty acids  /  Omega-3 polyunsaturated fatty acids  /  Proportion  /  Mortality  /  Prospective cohort study
李晴, 李惠先, 郑海清, 李佳美, 陈紫英, 孙佳琦, 梁会营. 血浆Omega-6/Omega-3脂肪酸比例与心血管疾病患者死亡率的关联. 现代预防医学, 2024 , 51 (5) : 943 -950 . DOI: 10.20043/j.cnki.MPM.202311061
Qing LI, Hui-xian LI, Hai-qing ZHENG, Jia-mei LI, Zi-ying CHEN, Jia-qi SUN, Hui-ying LIANG. Relationship between plasma omega-6/omega-3 fatty acid ratio and mortality in patients with cardiovascular disease[J]. Modern Preventive Medicine, 2024 , 51 (5) : 943 -950 . DOI: 10.20043/j.cnki.MPM.202311061
正文
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心血管疾病(cardiovascular disease，CVD)已经成为全球关注的主要死因之一[1]。研究显示，少摄入饱和脂肪酸并用多不饱和脂肪酸（polyunsaturated fatty acids，PUFAs）替代可降低CVD的发生率[2-3]。多数观察性研究支持Omega-3PUFAs[4]及其生物标志物（Omega-3指数）的保护作用[5-6]。一些研究支持高水平Omega-6PUFAs增加炎症，从而加重CVD风险[7-8]，但也有研究显示无关联[9]。因此，单个或总的Omega-3或Omega-6PUFAs与CVD关联的研究尚不能提供清晰的生物学见解。
现代西化饮食Omega-6/Omega-3比例增加至旧石器时代的20～50倍[10]，比例失衡导致CVD、癌症和自身免疫性疾病等疾病[11]。一项来自英国的队列研究中，血浆Omega-6/Omega-3比例与全因、癌症和心血管疾病死亡风险的增加相关[6]。然而，来自中国和美国的两个独立队列的前瞻性研究没有发现饮食中的Omega-6/Omega-3比例与全因死亡率之间存在线性正相关[10]。为了进一步阐明Omega-6/Omega-3比例在CVD患者中对死亡率的影响，本研究采用来自UKBiobank基于人群的队列数据，调查血浆Omega-6/Omega-3比例与全因、CVD死亡、缺血性心脏病(ischemic heart disease，IHD)死亡和卒中死亡的关联。
1　对象与方法
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1.1　研究人群
研究对象在UK Biobank中获取，本研究将CVD患者定义为在入组前患有“医生诊断的血管/心脏问题”或“健康相关结局-首次出现时间-血浆系统紊乱”早于入组时间。其中，后者根据ICD-10编码，本研究纳入的CVD编码为I10～15、I20～25、I26、I42、I48、I50、I60～64、I69、I73、I80、G45。排除基线时未患有CVD的参与者（n=330 457）、基线时患有癌症（n=22 034）、缺少完整PUFAs数据（n=114 707）和失访（n=93）的参与者后，有35 096名参与者被纳入研究，在随访期间有3 781人死亡，其中1 090人死于CVD，600人死于IHD，190人死于卒中。
1.2　结局确定
本研究的主要结局是全因死亡和CVD死亡，次要结局是IHD死亡和卒中死亡。死亡日期和死因通过国家卫生服务（National Health Service，NHS）信息中心的死亡登记处确定，英格兰和威尔士的死亡数据截至2021年10月14日，苏格兰的死亡数据截至2021年11月6日。因此，将2021年10月14日定为本研究的截止日期。随访时间为入组日期与研究截止日期或死亡日期之间的时间，以先发生者为准。死亡原因根据ICD-10编码，CVD死亡代码：I00～I99，IHD死亡代码：I20～25，卒中死亡代码：I60～64和I69。
1.3　协变量的确定
基于以前的文献和生物学合理性[6,12-13]，在多变量模型中选择以下协变量：人口学因素（年龄、性别、种族、家庭收入、受教育资质）、社会经济地位（汤森剥夺指数）、生活习惯（酒精、吸烟状况）体重指数（body mass index，BMI）、国际体力活动问卷（international physical activity questionnaire，IPAQ）、基础疾病（长期疾病、高血压、糖尿病）、药物使用情况（胰岛素、阿司匹林）和生化指标（血浆载脂蛋白B、血浆胆固醇、血浆肌酐、血浆高密度脂蛋白胆固醇、血浆低密度脂蛋白直接、血浆脂蛋白A和血浆甘油三酯）。糖尿病以基线时医生诊断为准，高血压定义为基线时自我报告高血压史和正在服用抗高血压药物。
1.4　统计分析
利用多重插补技术填补缺失值。基线时Omega-6/Omega-3比例四分位数的参与者的特征使用描述性统计并比较。连续型资料若符合正态分布用（）表示，组间差异用方差分析描述，若不符合正态分布则用M(Q)表示，组间差异用秩和检验描述；定性资料用频数（%）表示，组间差异用χ2检验描述。
Omega-6/Omega-3比例分为连续变量和分类变量（按四分位数分组），多变量Cox比例风险回归模型计算HR和95%CI，分析其与全因和特异性死亡率的关联[14]。将Omega-6/Omega-3比例以分位数间距分组后转化为等级变量进行趋势性检验。在评估不同亚组人群之间Omega-6/Omega-3比例与死亡风险关联的潜在差异的分层分析中，按性别（男性或女性）、年龄（<60或≥60岁）、BMI（<30或≥30 kg/m2）、糖尿病（是或否）、阿司匹林服用情况（是或否）和当前吸烟状况（是或否）进行分层，利用模型3重复上述分析。然后再通过各分层变量与Omega-6/Omega-3比例的乘积项建模做交互作用，阐明比例与结局的关联在各亚组的不同水平上存在差异。使用RCS估计潜在的非线性关联和Omega-6/Omega-3比例与死亡风险的剂量反应关系（回归样条中使用4节）。
本研究使用三套模型：根据基线年龄（岁）、性别（男性或女性）、种族［白人、黑人、亚洲人（印度、巴基斯坦、孟加拉人或任何其他亚洲背景）、混血或其他种族］、汤森贫困指数、收入（<10 000英镑、18 000～30 999英镑、31 000～51 999英镑、52 000～100 000英镑或>10 000英镑）、受教育资质（大学水平或其他）、吸烟状况（从不、以前或现在）、身体活动（IPAQ低、中或高）、饮酒状况（从不、以前或现在）和熟蔬菜摄入量（<2、2～4或>4份/d）对基本模型l进行了调整。在调整模型2中，将胰岛素的使用（有或无）、阿司匹林的使用（有或无）、BMI（kg/m2）、长期疾病（是或否）、高血压（是或否）、糖尿病（是或否）添加到模型1中。在模型2的基础上进一步添加血浆生化指标作为协变量来调整完整模型3：血浆载脂蛋白B、血浆胆固醇、血浆肌酐、血浆高密度脂蛋白胆固醇、血浆低密度脂蛋白直接、血浆脂蛋白A和血浆甘油三酯。
在亚组分析时利用模型3按性别（男性或女性）、年龄（<60或≥60岁）、BMI（<30或≥30 kg/m2）、糖尿病（是或否）、阿司匹林的使用（有或无）和当前吸烟状况（是或否）进行分层，并检验上述危险因素与Omega-6/Omega-3比例的交互作用。
利用敏感性分析来检验结果的稳健性，排除随访两年内死亡的参与者以评估观察到的关联是否因反向因果关系而减弱。本研究认为P值小于0.05（双侧）或HR的95%CI不包括1.0具有统计学意义。所有分析均使用4.2.3版R软件进行。检验水准α=0.05。
2　结果
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2.1　基线特征
在35 096名参与者的队列中，平均年龄为61岁，94.1%为白人，男性居多，占53.3%。不同Omega-6/Omega-3比例组别的CVD患者在人口学特征、社会经济地位、生活习惯、基础疾病、药物使用情况和生化指标方面存在差异（P<0.05）。比例最高四分位数人群和（或）更年轻者居多，男性占58.3%，从不吸烟者占50.4%。此外，他们目前饮酒占87.9%，身体活动活跃占40.2%，没有大学资格占76.1%，不频繁吃油性鱼类占91.2%，长期疾病占48.2%；糖尿病的患病率较低，为10.1%，而高血压的患病率较高，为93.1%。同时，最高四分位数人群更可能服用抗高血压药物，占61.9%，但较少服用阿司匹林、他汀类药物、维生素补充剂和矿物质及其他膳食补充剂，分别为25.8%、24.6%、25.9%、31.5%。见表1。
2.2　Omega-6/Omega-3比例与死亡风险的关系
血浆Omega-6/Omega-3比例与全因和特定原因死亡风险的关联见表2，模型3中，Omega-6/Omega-3比例与全因死亡、CVD死亡和IHD死亡率呈正相关(均P趋势<0.05)。在将Omega-6/Omega-3比例视为连续变量的模型3中，Omega-6/Omega-3比例每增加一个单位，全因、CVD和IHD死亡风险分别增加2.1%(HR=1.021，95%CI：1.016～0.025)、1.9%(HR=1.019，95%CI：1.010～1.028)和2.3%(HR=1.023，95%CI：1.013～1.034)。将Omega-6/Omega-3比例按四分位数法进行分组后作为分类变量纳入模型进行分析，与Q1相比，Q4全因、CVD和IHD死亡风险HR分别为1.394(95%CI：1.267～1.534)、1.292(95%CI：1.085～1.540)和1.528(95%CI：1.200～1.945)，未发现与卒中死亡风险有关(HR=0.987，95%CI：0.660～1.477)。
2.3　分层分析
根据对年龄、性别、BMI、糖尿病、是否服用阿司匹林和吸烟状况进行分层分析，见图1、2。对于全因死亡，与Q1人口相比，Q4组Omega-6/Omega-3比例与全因死亡率的相关性在服用阿司匹林者和目前吸烟者中更强（分别P交互<0.001和P交互=0.012）；对于CVD死亡和IHD死亡率，未发现其他风险因素的显著交互作用（均P交互≥0.05）。
2.4　限制性三次样条图
Omega-6/Omega-3比例与全因死亡、CVD死亡和IHD死亡率呈正相关（均P<0.001），见图3。在这些正相关中，全因死亡率（P<0.001）、心血管疾病死亡率（P=0.008）和IHD死亡风险（P=0.015）均存在非线性关系。死亡风险均先在较低的比例下降，然后开始升高，拐点在8.57左右。
2.5　敏感性分析
排除UK Biobank中在随访两年内发生结局事件的CVD患者，Omega-6/Omega-3 PUFAs比例按潜在风险因素分层与全因死亡、CVD死亡、IHD死亡和卒中死亡的风险评估显示模型稳健。见表3。
3　讨论
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这项基于人群的前瞻性研究发现，血浆Omega-6/Omega-3比例失衡与CVD患者的全因、CVD和IHD死亡率呈正相关。虽然这种关联的确切机制尚不完全清楚，但是这可能与通过导致内皮功能障碍、和促炎等过程从而影响CVD的发生发展[15-16]。例如，Omega-3PUFAs可以扩张血管，减少血栓形成和炎症，从而减轻动脉粥样硬化的风险[17-18]，Omega-3PUFAs还可以通过诱导涉内皮细胞祖细胞的新生血管形成，从而防止缺血性损伤[19-20]；此外，循环中较高的Omega-3PUFAs有利于减缓衰老过程，从而降低各种死亡风险。另一方面，Omega-6PUFAs的增加可能导致白细胞介素6、肿瘤坏死因子-α和C反应蛋白等炎性生物标志物出现，这些标志物与CVD风险和死亡率增加有关[8,21-22]。总的来说，Omega-6/Omega-3比例失衡，不论是Omega-3PUFAs降低还是Omega-6PUFAs增加，都不利于CVD患者的生存。
既往研究也提示了Omega-6/Omega-3比例与全因死亡率或特异性死亡率之间存在类似的联。2019年一项基于中国和美国的两个前瞻性队列的研究显示，最高四分位数人群与最低四分位数人群相比，膳食摄入的Omega-6/Omega-3比例对死亡率的影响不显著（中国HR=0.95，95%CI:0.80～1.14；美国HR=0.99, 95%CI:0.89～1.11）[10]。另一项涉及2001—2007年来自南加州8家透析诊所的血液透析患者的队列结果发现，相对于膳食Omega-6/Omega-3最低的四分位数人群，比例高的人群的全因死亡风险为HR=0.39（95%CI:0.14～1.08），尽管效果不显著，但考虑到样本量和研究人群，仍提示饮食摄入较低Omega-6/Omega-3比例对过早死亡潜在的保护趋势[23]。一个支持本研究结果的是2023年的一项基于人群的前瞻性队列研究，随着血浆Omega-6/Omega-3比例的增加，全因、CVD和癌症三种死亡结局的风险均增加（均P<0.001）[6]。这些研究与本文的不同之处以及结果有差别可能的原因在于：采用的暴露指标不同，本研究利用血浆NMR的Omega-6/Omega-3比例这一客观指标，降低了回忆偏差以及估计的膳食摄入量不准确导致的偏倚；此外，研究对象种族差异、所患有的基础疾病不同也是重要因素。
本研究还发现Omega-6/Omega-3比例与全因死亡率的关联在当前吸烟者和服用阿司匹林者中关联更强，死亡风险先在保持在较低的水平，然后在8.57左右开始迅速增加。Zhang Y等人[6]的发现与我们的结果类似：死亡风险在8左右开始迅速升高。由此，我们发现CVD患者适宜的Omega-6/Omega-3比例与普通人群相差不大，比例维持在较低水平有助于降低死亡率。此外，交互作用的结果也提示Omega-6/Omega-3比例较高的CVD患者应积极检查、改善不良生活和Omega-6/Omega-3比例的调整，有助于早期发现CVD并得到尽早治疗和干预。
本研究有以下优势：首先，对CVD患者的死亡风险展开研究，并且结局较多，虽然不同结局之间风险比差别不大，但也提示降低CVD患者血浆中Omega-6/Omega-3比例对全因乃至其他因CVD过早死亡的风险的保护趋势。其次，研究的暴露因素采用血浆中客观检测的PUFAs水平代替饮食问卷中的估计摄入量，降低了暴露评估时可能会产生的偏倚。最后，本研究是基于人群的一项样本量大、随访时间长的大型队列研究，包含了较多潜在混杂变量的详细信息，大大降低了反向因果关系的可能和混杂偏倚。
存在的局限性：一是血浆NMR在在基线时仅测量一次，可能会导致错误分类；二是尽管分析囊括不同种族，但白人占比高达94%，未来还需要进一步探讨本研究的结果在全球人口的普适性。
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  • 广东省人工智能医学图像分析与应用重点实验室(2022B1212010011)
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2024年第51卷第5期
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doi: 10.20043/j.cnki.MPM.202311061
  • 接收时间：2023-11-04
  • 首发时间：2026-03-19
  • 出版时间：2024-03-10
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  • 收稿日期：2023-11-04
基金
广东省人工智能医学图像分析与应用重点实验室(2022B1212010011)
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    1.中国医科大学公共卫生学院，辽宁 沈阳 110122
    2.南方医科大学附属广东省人民医院（广东省医学科学院）医学大数据中心，广东 广州 510800
    3.南方医科大学公共卫生学院

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鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
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红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
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