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Article(id=1241067205576684495, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1241067197318091153, articleNumber=null, orderNo=null, doi=10.20043/j.cnki.MPM.202411399, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1732204800000, receivedDateStr=2024-11-22, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1773823079722, onlineDateStr=2026-03-18, pubDate=1741536000000, pubDateStr=2025-03-10, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1773823079722, onlineIssueDateStr=2026-03-18, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1773823079722, creator=13701087609, updateTime=1773823079722, updator=13701087609, issue=Issue{id=1241067197318091153, tenantId=1146029695717560320, journalId=1227665162245664772, year='2025', volume='52', 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=1773823077754, creator=13701087609, updateTime=1773823268053, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1241067995544482681, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1241067197318091153, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1241067995544482682, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1241067197318091153, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=942, endPage=949, ext={EN=ArticleExt(id=1241067206402962401, articleId=1241067205576684495, tenantId=1146029695717560320, journalId=1227665162245664772, language=EN, title=Nested case - control study on risk factors of carotid artery plaques, columnId=1228016569138213037, journalTitle=Modern Preventive Medicine, columnName=Clinical Medicine and Prevention, runingTitle=null, highlight=null, articleAbstract=
Objective

To analyze the influencing factors of carotid artery plaque occurrence based on a prospective dynamic cohort.

Methods

A nested case-control study was adopted. A total of 1 150 newly-diagnosed patients with carotid artery plaques from March 2018 to November 2023 were selected as the case group. According to the principles of the same gender, age ± 3 years, and the same year and month of the initial examination, 1 150 individuals without carotid artery plaques were individually matched at a ratio of 1:1 as the control group. Finally, 2 300 subjects were included in the study. A conditional Logistic regression model was used to analyze the influencing factors of carotid artery plaque occurrence. Meanwhile, the dose-response relationship between different exposure factors and the risk of carotid artery plaque was analyzed by using tertile stratification and restricted cubic spline (RCS).

Results

The results of multivariate conditional Logistic regression analysis showed that abnormal serum high-density lipoprotein-cholesterol (HDL-C) (OR=1.370, 95%CI: 1.073-1.748), blood urea nitrogen/creatinine (OR=1.024, 95%CI: 1.004-1.044), and red blood cell distribution width-SD (OR=1.037, 95%CI: 1.003-1.072) were risk factors for carotid artery plaques, while total protein (OR=0.966, 95%CI: 0.944-0.988) was a protective factor.The RCS results showed that there was a negative linear dose-response relationship between HDL-C, total protein and the risk of carotid artery plaque, and a positive linear dose-response relationship between blood urea nitrogen/creatinine and the risk of carotid artery plaque (P overall < 0.05, P non-linear > 0.05). No dose-response relationship was found between red blood cell distribution width-SD and the risk of carotid artery plaque.

Conclusion

HDL-C, total protein, blood urea nitrogen/creatinine, and red blood cell distribution width-SD are associated with the occurrence of carotid artery plaques, and there is a linear dose-response relationship between HDL-C, blood urea nitrogen/creatinine, total protein and the risk of carotid artery plaque.

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目的

基于前瞻性动态队列分析颈动脉斑块发生的影响因素。

方法

采用巢式病例对照研究，以2018年3月—2023年11月新发1 150例颈动脉斑块患者为病例组，按照同性别、年龄±3岁、初检时间同年同月原则，1∶1个体匹配1 150例未发生颈动脉斑块者为对照组，最终纳入2 300名研究对象。采用条件logistic回归模型分析颈动脉斑块发生的影响因素，同时运用三分位数分层和限制性立方样条(restricted cubic spline,RCS)分析不同暴露因素对颈动脉斑块发病风险的剂量-反应关系。

结果

多因素条件logistic回归分析结果显示，血清高密度脂蛋白胆固醇（high density lipoprotein-cholesterol，HDL-C）异常（OR=1.370,95%CI:1.073～1.748）、尿素氮/肌酐（OR=1.024,95%CI:1.004～1.044）以及红细胞分布宽度-SD（OR=1.037,95%CI:1.003～1.072）是颈动脉斑块的危险因素，总蛋白（OR=0.966,95%CI:0.944～0.988）是颈动脉斑块的保护因素。RCS结果显示，HDL-C、总蛋白与颈动脉斑块发病风险呈负向线性剂量-反应关系，尿素氮/肌酐与颈动脉斑块发病风险呈正向线性剂量-反应关系( P for overall<0. 05，P for non-linear>0. 05)，未发现红细胞分布宽度-SD与颈动脉斑块发病风险间存在剂量-反应关系。

结论

HDL-C、总蛋白、尿素氮/肌酐和红细胞分布宽度-SD与颈动脉斑块的发病有关，且HDL-C、尿素氮/肌酐、总蛋白与颈动脉斑块的发病风险存在线性剂量-反应关系。

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孙小平，E-mail:
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孙小平与高宁为共同第一作者

孙小平（1984—），女，本科，副主任护师，研究方向：疾病早筛与健康管理；

高宁（2000—），女，硕士在读，研究方向：慢性病流行病学；

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American Journal of Medicine, 2005, 118(11): 1288., articleTitle=Proinflammatory state and circulating erythropoietin in persons with and without anemia, refAbstract=null)], funds=[Fund(id=1241067217291375127, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241067205576684495, awardId=23JRRA099; 24JRRA351, language=CN, fundingSource=甘肃省自然科学基金(23JRRA099; 24JRRA351), fundOrder=null, country=null), Fund(id=1241067217408815647, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241067205576684495, awardId=GSWSKY-2019-19, language=CN, fundingSource=甘肃省卫生行业科研计划项目(GSWSKY-2019-19), fundOrder=null, country=null), Fund(id=1241067217513673256, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241067205576684495, awardId=2023-02-27, language=CN, fundingSource=兰州市科技计划项目(2023-02-27), fundOrder=null, country=null)], companyList=[AuthorCompany(id=1241067207703195706, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241067205576684495, xref=1., ext=[AuthorCompanyExt(id=1241067207711584316, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241067205576684495, companyId=1241067207703195706, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=Health Management Center, The Second Hospital of Lanzhou University, Lanzhou, Gansu 730000, China), AuthorCompanyExt(id=1241067207719972927, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241067205576684495, companyId=1241067207703195706, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1.兰州大学第二医院健康管理中心，甘肃 兰州 730000)]), AuthorCompany(id=1241067207854190666, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241067205576684495, xref=2., ext=[AuthorCompanyExt(id=1241067207866773579, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241067205576684495, companyId=1241067207854190666, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2.兰州大学公共卫生学院流行病与卫生统计学研究所，甘肃 兰州 730000)])], figs=[ArticleFig(id=1241067215672373639, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241067205576684495, language=EN, label=Figure 1, caption=Flow chart for screening subjects in nested case-control studies, figureFileSmall=mzwdHE/qJ1wOkvi0kgxf/w==, figureFileBig=dthgw7Xrqd9x4n2HNz8UgA==, tableContent=null), ArticleFig(id=1241067215794008470, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241067205576684495, language=CN, label=图1, caption=巢式病例对照研究对象筛选流程图, figureFileSmall=mzwdHE/qJ1wOkvi0kgxf/w==, figureFileBig=dthgw7Xrqd9x4n2HNz8UgA==, tableContent=null), ArticleFig(id=1241067216020500906, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241067205576684495, language=EN, label=Figure 2, caption=Dose-response relationship between HDL-C, urea nitrogen/creatinine, red blood cell distribution width-SD, and total protein and risk of carotid plaque development, figureFileSmall=VWdGbvxktxaiZVtFQLUFxQ==, figureFileBig=jLmat7jNGU2t7DORn15ZUw==, tableContent=null), ArticleFig(id=1241067216116969906, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241067205576684495, language=CN, label=图2, caption=HDL-C、尿素氮/肌酐、红细胞分布宽度-SD和总蛋白与颈动脉斑块发生风险之间的剂量-反应关系

注：调整BMI、收缩压、舒张压、FPG、TC、TG、LDL-C、HDL-C（仅尿素氮/肌酐、红细胞分布宽度-SD和总蛋白）、尿素氮/肌酐（仅HDL-C、红细胞分布宽度-SD和总蛋白）、红细胞分布宽度-SD（仅HDL-C、尿素氮/肌酐和总蛋白）和总蛋白（仅HDL-C、尿素氮/肌酐和红细胞分布宽度-SD）因素；深色实线为颈动脉斑块的发病风险比（OR),浅色边框为95%置信区间（CI),黑色虚线为OR值为1；图A 为HDL-C与颈动脉斑块发生风险之间的剂量-反应关系；图B 为尿素氮/肌酐与颈动脉斑块发生风险之间的剂量-反应关系；图C为红细胞分布宽度-SD与颈动脉斑块发生风险之间的剂量-反应关系；图D 为总蛋白与颈动脉斑块发生风险之间的剂量-反应关系。

, figureFileSmall=VWdGbvxktxaiZVtFQLUFxQ==, figureFileBig=jLmat7jNGU2t7DORn15ZUw==, tableContent=null), ArticleFig(id=1241067216263770556, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241067205576684495, language=EN, label=Table 1, caption=

Comparison of baseline physiological and biochemical indexes of study subjects

, figureFileSmall=null, figureFileBig=null, tableContent=
变量病例组（n=1 150)对照组(n=1 150)Z/χ2值P值
n/M(%)/（P25，P75）n/M(%)/（P25，P75）
性别<0.0011.000
男886.00(77.00)886.00(77.00)
年龄(岁)55.00(49.75,63.00)55.50(51.00,63.00)-1.2170.224
BMI（kg/m2）24.52(22.57,26.56)24.16(22.31,26.34)-1.964<0.050
收缩压(mm Hg)127.50(115.00,141.00)126.00(115.00,138.00)-1.3710.170
舒张压(mm Hg)78.00(70.00,86.00)77.50(70.00,86.00)-0.3410.733
FPG(mmol/L)5.42(5.07,5.99)5.39(5.05,5.87)-1.5160.130
TC(mmol/L)4.54(3.99,5.14)4.45(3.95,5.01)-2.3870.017
TG(mmol/L)1.40(1.00,1.95)1.33(1.00,1.86)-1.9400.052
HDL-C(mmol/L)1.13(0.98,1.31)1.17(1.01,1.38)-3.3430.001
LDL-C(mmol/L)2.52(2.10,3.02)2.44(2.04,2.90)-3.3020.001
TyG8.76(8.39,9.13)8.68(8.36,9.08)-2.2950.022
TG/HDL-C2.86(1.88,4.32)2.61(1.78,3.97)-2.7980.005
METS-IR37.97(33.79,42.72)37.14(32.87,41.62)-3.0200.003
尿素(mmol/L)4.91(4.18,5.82 )4.94(4.18,5.79)-0.6270.530
肌酐(μmol/L)75.40(65.60,84.70)76.80(66.98,85.90)-2.1190.034
尿素氮/肌酐16.40(13.59,19.57)15.91(13.38,19.24)-2.1460.032
尿酸(μmol/L)353.29(303.51,408.13)350.05(298.98,403.17)-1.3620.173
谷丙转氨酶(U/L)20.50(14.60 ,29.73)19.20(14.10,27.80)-1.9660.049
谷草转氨酶(U/L)20.70(17.20 ,25.10)20.60(17.70,24.80)-0.0360.971
谷草/谷丙转氨酶1.00(0.77,1.31)1.05(0.79,1.33)-2.3930.017
总胆红素(μmol/L)13.45(10.10,17.70)13.60(10.50,18.20)-1.4140.157
直接胆红素(μmol/L)4.40(3.10,5.90)4.50(3.30,6.00)-0.9580.338
间接胆红素(μmol/L)9.25(6.30,12.60)9.40(6.50,12.70)-1.1500.250
谷氨酰基转移酶(U/L)30.90(20.90,38.63)30.20(19.40,36.69)-1.9050.057
碱性磷酸酶(U/L)83.69(69.78,93.03)83.69(69.45,90.43)-0.8650.387
总蛋白(g/L)71.07(68.38,73.10)71.07(69.10,73.50)-1.8040.071
白蛋白(g/L)44.08(42.40,45.60)44.08(42.70,45.80)-1.6440.100
球蛋白(g/L)27.00(24.60,29.00)27.00(24.70,29.40)-0.7170.473
白球比1.68(1.48,1.83)1.68(1.48,1.82)-0.0960.924
), ArticleFig(id=1241067216414765510, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241067205576684495, language=CN, label=表1, caption=

研究对象的基线生理生化指标比较

, figureFileSmall=null, figureFileBig=null, tableContent=
变量病例组（n=1 150)对照组(n=1 150)Z/χ2值P值
n/M(%)/（P25，P75）n/M(%)/（P25，P75）
性别<0.0011.000
男886.00(77.00)886.00(77.00)
年龄(岁)55.00(49.75,63.00)55.50(51.00,63.00)-1.2170.224
BMI（kg/m2）24.52(22.57,26.56)24.16(22.31,26.34)-1.964<0.050
收缩压(mm Hg)127.50(115.00,141.00)126.00(115.00,138.00)-1.3710.170
舒张压(mm Hg)78.00(70.00,86.00)77.50(70.00,86.00)-0.3410.733
FPG(mmol/L)5.42(5.07,5.99)5.39(5.05,5.87)-1.5160.130
TC(mmol/L)4.54(3.99,5.14)4.45(3.95,5.01)-2.3870.017
TG(mmol/L)1.40(1.00,1.95)1.33(1.00,1.86)-1.9400.052
HDL-C(mmol/L)1.13(0.98,1.31)1.17(1.01,1.38)-3.3430.001
LDL-C(mmol/L)2.52(2.10,3.02)2.44(2.04,2.90)-3.3020.001
TyG8.76(8.39,9.13)8.68(8.36,9.08)-2.2950.022
TG/HDL-C2.86(1.88,4.32)2.61(1.78,3.97)-2.7980.005
METS-IR37.97(33.79,42.72)37.14(32.87,41.62)-3.0200.003
尿素(mmol/L)4.91(4.18,5.82 )4.94(4.18,5.79)-0.6270.530
肌酐(μmol/L)75.40(65.60,84.70)76.80(66.98,85.90)-2.1190.034
尿素氮/肌酐16.40(13.59,19.57)15.91(13.38,19.24)-2.1460.032
尿酸(μmol/L)353.29(303.51,408.13)350.05(298.98,403.17)-1.3620.173
谷丙转氨酶(U/L)20.50(14.60 ,29.73)19.20(14.10,27.80)-1.9660.049
谷草转氨酶(U/L)20.70(17.20 ,25.10)20.60(17.70,24.80)-0.0360.971
谷草/谷丙转氨酶1.00(0.77,1.31)1.05(0.79,1.33)-2.3930.017
总胆红素(μmol/L)13.45(10.10,17.70)13.60(10.50,18.20)-1.4140.157
直接胆红素(μmol/L)4.40(3.10,5.90)4.50(3.30,6.00)-0.9580.338
间接胆红素(μmol/L)9.25(6.30,12.60)9.40(6.50,12.70)-1.1500.250
谷氨酰基转移酶(U/L)30.90(20.90,38.63)30.20(19.40,36.69)-1.9050.057
碱性磷酸酶(U/L)83.69(69.78,93.03)83.69(69.45,90.43)-0.8650.387
总蛋白(g/L)71.07(68.38,73.10)71.07(69.10,73.50)-1.8040.071
白蛋白(g/L)44.08(42.40,45.60)44.08(42.70,45.80)-1.6440.100
球蛋白(g/L)27.00(24.60,29.00)27.00(24.70,29.40)-0.7170.473
白球比1.68(1.48,1.83)1.68(1.48,1.82)-0.0960.924
), ArticleFig(id=1241067216536400335, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241067205576684495, language=EN, label=Table 2, caption=

Comparison of baseline blood routine indexes of study subjects

, figureFileSmall=null, figureFileBig=null, tableContent=
变量病例组（n=1 150)对照组(n=1 150)Z值P值
M（P25，P75）M（P25，P75）)
白细胞计数(×109/L)5.86(4.90,6.80)5.67(4.80,6.61)-2.8760.004
中性粒细胞比率(%)60.00(54.80,65.00)60.20(54.40,65.20)-0.3050.761
淋巴细胞比率(%)31.30(26.68,36.20)31.15(26.40,36.30)-0.1990.842
单核细胞比率(%)5.70(4.80,6.60)5.60(4.80,6.60)-0.2460.805
嗜酸性粒细胞比率(%)1.80(1.10,3.00)1.80(1.10,3.00)-0.4120.681
嗜碱性粒细胞比率(%)0.50(0.30,0.60)0.50(0.30,0.60)-1.2170.224
中性粒细胞数(×109/L)3.44(2.81,4.22)3.33(2.74,4.12)-2.1920.028
淋巴细胞数(×109/L)1.80(1.46,2.17)1.71(1.42,2.10)-2.7930.005
单核细胞数(×109/L)0.33(0.27,0.40)0.32(0.25,0.39)-2.6080.009
嗜酸性粒细胞数(×109/L)0.11(0.06,0.17)0.11(0.06,0.17)-0.6750.500
嗜碱性粒细胞数(×109/L)0.03(0.02,0.04)0.03(0.02,0.04)-2.9410.003
红细胞计数(×1012/L)4.90(4.59,5.20)4.92(4.63,5.21)-1.2090.227
血红蛋白(g/L)154.00(145.00,163.00)155.00(145.00,163.00)-0.8400.401
红细胞压积(%)46.30(43.40,48.70)46.50(43.80,48.70)-1.0260.305
红细胞平均体积(fl)94.30(91.80,97.00)94.30(91.80,96.80)-0.4080.684
平均血红蛋白量(pg)31.40(30.40,32.40)31.40(30.40,32.30)-0.3890.697
平均血红蛋白浓度(g/L)333.00(327.00,338.00)333.00(327.00,338.00)-0.2570.797
红细胞分布宽度-SD(fl)44.00(42.38,45.80)43.80(42.20,45.60)-1.5740.116
红细胞分布宽度-CV(%)13.00(12.60,13.40)12.90(12.60,13.40)-1.0790.281
血小板计数(×109/L)195.00(162.00,230.00)189.00(157.00,224.00)-2.6790.007
血小板压积(%)0.20(0.17,0.23)0.20(0.17,0.23)-2.2650.024
血小板分布宽度（fl）16.40(16.20,16.70)16.40(16.20,16.70)-0.6640.507
平均血小板体积（fl)10.40(9.50,11.40)10.40(9.50,11.40)-1.2650.206
大血小板比率(%)30.20(24.20,37.10)30.80(24.80,37.73)-1.1360.256
NLR1.89(1.53,2.43)1.93(1.52,2.47)-0.2750.784
PLR108.16(85.57,136.80)107.99(86.76,136.41)-0.1650.869
SII374.34(280.85,490.01)361.99(267.75,481.81)-1.5350.125
AISI119.65(80.44,175.91)112.72(77.29,170.09)-2.3070.021
), ArticleFig(id=1241067216653840858, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241067205576684495, language=CN, label=表2, caption=

研究对象的基线血常规指标比较

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变量病例组（n=1 150)对照组(n=1 150)Z值P值
M（P25，P75）M（P25，P75）)
白细胞计数(×109/L)5.86(4.90,6.80)5.67(4.80,6.61)-2.8760.004
中性粒细胞比率(%)60.00(54.80,65.00)60.20(54.40,65.20)-0.3050.761
淋巴细胞比率(%)31.30(26.68,36.20)31.15(26.40,36.30)-0.1990.842
单核细胞比率(%)5.70(4.80,6.60)5.60(4.80,6.60)-0.2460.805
嗜酸性粒细胞比率(%)1.80(1.10,3.00)1.80(1.10,3.00)-0.4120.681
嗜碱性粒细胞比率(%)0.50(0.30,0.60)0.50(0.30,0.60)-1.2170.224
中性粒细胞数(×109/L)3.44(2.81,4.22)3.33(2.74,4.12)-2.1920.028
淋巴细胞数(×109/L)1.80(1.46,2.17)1.71(1.42,2.10)-2.7930.005
单核细胞数(×109/L)0.33(0.27,0.40)0.32(0.25,0.39)-2.6080.009
嗜酸性粒细胞数(×109/L)0.11(0.06,0.17)0.11(0.06,0.17)-0.6750.500
嗜碱性粒细胞数(×109/L)0.03(0.02,0.04)0.03(0.02,0.04)-2.9410.003
红细胞计数(×1012/L)4.90(4.59,5.20)4.92(4.63,5.21)-1.2090.227
血红蛋白(g/L)154.00(145.00,163.00)155.00(145.00,163.00)-0.8400.401
红细胞压积(%)46.30(43.40,48.70)46.50(43.80,48.70)-1.0260.305
红细胞平均体积(fl)94.30(91.80,97.00)94.30(91.80,96.80)-0.4080.684
平均血红蛋白量(pg)31.40(30.40,32.40)31.40(30.40,32.30)-0.3890.697
平均血红蛋白浓度(g/L)333.00(327.00,338.00)333.00(327.00,338.00)-0.2570.797
红细胞分布宽度-SD(fl)44.00(42.38,45.80)43.80(42.20,45.60)-1.5740.116
红细胞分布宽度-CV(%)13.00(12.60,13.40)12.90(12.60,13.40)-1.0790.281
血小板计数(×109/L)195.00(162.00,230.00)189.00(157.00,224.00)-2.6790.007
血小板压积(%)0.20(0.17,0.23)0.20(0.17,0.23)-2.2650.024
血小板分布宽度（fl）16.40(16.20,16.70)16.40(16.20,16.70)-0.6640.507
平均血小板体积（fl)10.40(9.50,11.40)10.40(9.50,11.40)-1.2650.206
大血小板比率(%)30.20(24.20,37.10)30.80(24.80,37.73)-1.1360.256
NLR1.89(1.53,2.43)1.93(1.52,2.47)-0.2750.784
PLR108.16(85.57,136.80)107.99(86.76,136.41)-0.1650.869
SII374.34(280.85,490.01)361.99(267.75,481.81)-1.5350.125
AISI119.65(80.44,175.91)112.72(77.29,170.09)-2.3070.021
), ArticleFig(id=1241067216758698470, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241067205576684495, language=EN, label=Table 3, caption=

Multivariate conditional logistic regression analysis of carotid plaque

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变量OR值(95%CI)P值
HDL-C异常1.370(1.073～1.748)0.012
尿素氮/肌酐1.024(1.004～1.044)0.016
红细胞分布宽-SD(fl)1.037(1.003～1.072)0.032
总蛋白(g/L)0.966(0.944～0.988)0.002
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颈动脉斑块的多因素条件logistic回归分析

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变量OR值(95%CI)P值
HDL-C异常1.370(1.073～1.748)0.012
尿素氮/肌酐1.024(1.004～1.044)0.016
红细胞分布宽-SD(fl)1.037(1.003～1.072)0.032
总蛋白(g/L)0.966(0.944～0.988)0.002
), ArticleFig(id=1241067217001968123, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241067205576684495, language=EN, label=Table 4, caption=

Association of HDL-C, urea nitrogen/creatinine, red blood cell distribution width-SD, and total protein with the risk of carotid plaque development

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指标模型1模型2模型3
OR(95%CI)P值OR(95%CI)P值OR(95%CI)P值
HDL-C（mmol/L）
Q1(≤1.05)111
Q2(1.06～1.25)0.901(0.740～1.097)0.3010.900(0.738～1.097)0.2980.882(0.717～1.084)0.232
Q3(≥1.26)0.646(0.522～0.800)<0.0010.675(0.542～0.841)<0.0010.651(0.513～0.825)<0.001
尿素氮/肌酐
Q1(≤14.38)111
Q2(14.39～18.12)1.069(0.877～1.302)0.5081.053(0.863～1.284)0.6121.079(0.880～1.323)0.467
Q3(≥18.13)1.238(1.005～1.526)0.0451.247(1.010～1.539)0.0401.264(1.018～1.570)0.034
红细胞分布宽度-SD(fl)
Q1(≤42.90)111
Q2(42.91～45.00)1.029(0.846～1.250)0.7771.010(0.830～1.229)0.9201.029(0.843～1.257)0.776
Q3(≥45.01)1.181(0.956～1.460)0.1231.156(0.933～1.431)0.1841.192(0.957～1.484)0.117
总蛋白(g/L)
Q1(≤69.90)111
Q2(69.91～72.19)0.750(0.609～0.925)0.0070.740(0.599～0.914)0.0050.741(0.597～0.920)0.007
Q3(≥72.20)0.795(0.644～0.981)0.0320.774(0.626～0.957)0.0180.751(0.604～0.934)0.010
), ArticleFig(id=1241067217140380173, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241067205576684495, language=CN, label=表4, caption=

HDL-C、尿素氮/肌酐、红细胞分布宽度-SD和总蛋白与颈动脉斑块发生风险的关系

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指标模型1模型2模型3
OR(95%CI)P值OR(95%CI)P值OR(95%CI)P值
HDL-C（mmol/L）
Q1(≤1.05)111
Q2(1.06～1.25)0.901(0.740～1.097)0.3010.900(0.738～1.097)0.2980.882(0.717～1.084)0.232
Q3(≥1.26)0.646(0.522～0.800)<0.0010.675(0.542～0.841)<0.0010.651(0.513～0.825)<0.001
尿素氮/肌酐
Q1(≤14.38)111
Q2(14.39～18.12)1.069(0.877～1.302)0.5081.053(0.863～1.284)0.6121.079(0.880～1.323)0.467
Q3(≥18.13)1.238(1.005～1.526)0.0451.247(1.010～1.539)0.0401.264(1.018～1.570)0.034
红细胞分布宽度-SD(fl)
Q1(≤42.90)111
Q2(42.91～45.00)1.029(0.846～1.250)0.7771.010(0.830～1.229)0.9201.029(0.843～1.257)0.776
Q3(≥45.01)1.181(0.956～1.460)0.1231.156(0.933～1.431)0.1841.192(0.957～1.484)0.117
总蛋白(g/L)
Q1(≤69.90)111
Q2(69.91～72.19)0.750(0.609～0.925)0.0070.740(0.599～0.914)0.0050.741(0.597～0.920)0.007
Q3(≥72.20)0.795(0.644～0.981)0.0320.774(0.626～0.957)0.0180.751(0.604～0.934)0.010
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颈动脉斑块危险因素的巢式病例对照研究
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孙小平 1 , 高宁 2 , 陈睿迪 1 , 闫雯 1 , 王敏珍 2
现代预防医学 | 临床与预防 2025,52(5): 942-949
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现代预防医学 | 临床与预防 2025, 52(5): 942-949
颈动脉斑块危险因素的巢式病例对照研究
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孙小平1 , 高宁2, 陈睿迪1, 闫雯1, 王敏珍2
作者信息
  • 1.兰州大学第二医院健康管理中心，甘肃 兰州 730000
  • 2.兰州大学公共卫生学院流行病与卫生统计学研究所，甘肃 兰州 730000

    • 孙小平（1984—），女，本科，副主任护师，研究方向：疾病早筛与健康管理；

    高宁（2000—），女，硕士在读，研究方向：慢性病流行病学；

通讯作者:

孙小平，E-mail:
Nested case - control study on risk factors of carotid artery plaques
Xiao-ping SUN1 , Ning GAO2, Rui-di CHEN1, Wen YAN1, Min-zhen WANG2
Affiliations
  • Health Management Center, The Second Hospital of Lanzhou University, Lanzhou, Gansu 730000, China
出版时间: 2025-03-10 doi: 10.20043/j.cnki.MPM.202411399
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摘要
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目的

基于前瞻性动态队列分析颈动脉斑块发生的影响因素。

方法

采用巢式病例对照研究，以2018年3月—2023年11月新发1 150例颈动脉斑块患者为病例组，按照同性别、年龄±3岁、初检时间同年同月原则，1∶1个体匹配1 150例未发生颈动脉斑块者为对照组，最终纳入2 300名研究对象。采用条件logistic回归模型分析颈动脉斑块发生的影响因素，同时运用三分位数分层和限制性立方样条(restricted cubic spline,RCS)分析不同暴露因素对颈动脉斑块发病风险的剂量-反应关系。

结果

多因素条件logistic回归分析结果显示，血清高密度脂蛋白胆固醇（high density lipoprotein-cholesterol，HDL-C）异常（OR=1.370,95%CI:1.073～1.748）、尿素氮/肌酐（OR=1.024,95%CI:1.004～1.044）以及红细胞分布宽度-SD（OR=1.037,95%CI:1.003～1.072）是颈动脉斑块的危险因素，总蛋白（OR=0.966,95%CI:0.944～0.988）是颈动脉斑块的保护因素。RCS结果显示，HDL-C、总蛋白与颈动脉斑块发病风险呈负向线性剂量-反应关系，尿素氮/肌酐与颈动脉斑块发病风险呈正向线性剂量-反应关系( P for overall<0. 05，P for non-linear>0. 05)，未发现红细胞分布宽度-SD与颈动脉斑块发病风险间存在剂量-反应关系。

结论

HDL-C、总蛋白、尿素氮/肌酐和红细胞分布宽度-SD与颈动脉斑块的发病有关，且HDL-C、尿素氮/肌酐、总蛋白与颈动脉斑块的发病风险存在线性剂量-反应关系。

颈动脉斑块  /  危险因素  /  巢式病例对照研究
Objective

To analyze the influencing factors of carotid artery plaque occurrence based on a prospective dynamic cohort.

Methods

A nested case-control study was adopted. A total of 1 150 newly-diagnosed patients with carotid artery plaques from March 2018 to November 2023 were selected as the case group. According to the principles of the same gender, age ± 3 years, and the same year and month of the initial examination, 1 150 individuals without carotid artery plaques were individually matched at a ratio of 1:1 as the control group. Finally, 2 300 subjects were included in the study. A conditional Logistic regression model was used to analyze the influencing factors of carotid artery plaque occurrence. Meanwhile, the dose-response relationship between different exposure factors and the risk of carotid artery plaque was analyzed by using tertile stratification and restricted cubic spline (RCS).

Results

The results of multivariate conditional Logistic regression analysis showed that abnormal serum high-density lipoprotein-cholesterol (HDL-C) (OR=1.370, 95%CI: 1.073-1.748), blood urea nitrogen/creatinine (OR=1.024, 95%CI: 1.004-1.044), and red blood cell distribution width-SD (OR=1.037, 95%CI: 1.003-1.072) were risk factors for carotid artery plaques, while total protein (OR=0.966, 95%CI: 0.944-0.988) was a protective factor.The RCS results showed that there was a negative linear dose-response relationship between HDL-C, total protein and the risk of carotid artery plaque, and a positive linear dose-response relationship between blood urea nitrogen/creatinine and the risk of carotid artery plaque (P overall < 0.05, P non-linear > 0.05). No dose-response relationship was found between red blood cell distribution width-SD and the risk of carotid artery plaque.

Conclusion

HDL-C, total protein, blood urea nitrogen/creatinine, and red blood cell distribution width-SD are associated with the occurrence of carotid artery plaques, and there is a linear dose-response relationship between HDL-C, blood urea nitrogen/creatinine, total protein and the risk of carotid artery plaque.

Carotid artery plaque  /  Risk factor  /  Nested case-control study
孙小平, 高宁, 陈睿迪, 闫雯, 王敏珍. 颈动脉斑块危险因素的巢式病例对照研究. 现代预防医学, 2025 , 52 (5) : 942 -949 . DOI: 10.20043/j.cnki.MPM.202411399
Xiao-ping SUN, Ning GAO, Rui-di CHEN, Wen YAN, Min-zhen WANG. Nested case - control study on risk factors of carotid artery plaques[J]. Modern Preventive Medicine, 2025 , 52 (5) : 942 -949 . DOI: 10.20043/j.cnki.MPM.202411399
正文
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随着城镇化和人口老龄化进程的加快，脑卒中和冠心病等心脑血管疾病发病率、致残率和致死率呈现不断上升趋势[1]，已成为全球范围内重要的公共卫生问题，严重威胁居民的生命健康。作为心脑血管疾病的重要危险因素和主要病理过程，颈动脉斑块的检出率呈上升趋势，且随年龄的增长而持续增加，2020年全球颈动脉斑块检出率高达21%[2]。由于位置表浅且易通过简单无创的高频超声检测，颈动脉斑块筛检已在健康体检中广泛开展[3]，可以早期筛查并评估颈动脉粥样硬化和心脑血管疾病的风险[4]。从健康管理角度如何加强颈动脉斑块的预防和管理，从而降低远端心脑血管疾病的发生显得尤为重要。多项研究表明，年龄、吸烟、高血压和糖尿病等因素与颈动脉斑块的发生密切相关[2]，但多为横断面研究，因果论证效力有限。为此本研究基于甘肃省兰州市某三甲医院健康管理中心平台近5年人群健康体检队列，采用巢式病例对照研究分析人群颈动脉斑块发生的影响因素，为颈动脉斑块及心脑血管疾病的预防提供数据支撑。
1　资料与方法
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1.1　研究对象
选取2018年3月18日—2023年11月14日在甘肃省兰州市某三甲医院接受颈动脉超声检查73 732例健康体检人群为研究对象，颈动脉斑块根据颈部超声影像学资料进行诊断。纳入标准：（1）有≥2次颈动脉超声检查结果者20 008例；（2)初次未检出颈动脉斑块者14 844例；（3）初次体检资料完整者9 266例。以随访期间新发的1 150例颈动脉斑块患者为病例组，按照同性别、年龄±3岁、初检时间同年同月的原则进行1∶1个体匹配，纳入1 150例随访未新发颈动脉斑块者为对照组，最终共纳入2 300例研究对象，筛选及匹配过程见图1。本研究健康体检数据库经匿名化处理后用于科学研究，不涉及知情同意书。本研究通过兰州大学第二医院医学伦理委员会审查（2023A-314）。
1.2　资料来源
由经统一规范化培训的研究人员从健康体检数据库中调取研究对象健康体检数据。（1）一般人口学特征:年龄、性别。（2）体格检查:身高、体重、血压、颈动脉超声检查结果等。（3）实验室检测：空腹血糖（fasting plasma glucose,FPG) 、血清总胆固醇（total cholesterol，TC）、血清甘油三酯（triglyceride，TG）、血清高密度脂蛋白胆固醇（high density lipoprotein-cholesterol，HDL-C）、血清低密度脂蛋白胆固醇（low density lipoprotein-cholesterol，LDL-C）、血常规、尿常规、肝肾功能等。健康体检数据由医院的专业医生参照标准化流程进行。其中身高体重由欧姆龙身高体重测量仪测得（HNH-318），血压由血压脉搏测量仪测得（ChioyABP-1000S），FPG和血脂等生化资料由迈瑞BS-2000全自动生化分析仪测定，血常规由迈瑞BC-6800全自动血细胞分析仪检测。
1.3　诊断标准及相关定义
1.3.1　颈动脉斑块检测方法与标准
由经验丰富的医生使用飞利浦C5-1彩色多普勒超声诊断仪（探头频率为1-5MHz）进行检测。受检者采取仰卧位，依次扫描双侧颈总动脉、颈动脉分叉部、颈内动脉，测量两侧颈总动脉远端距分叉部1 cm处的内中膜厚度（intimamedia thickness,IMT）。颈动脉斑块被定义为侵入动脉管腔内的局灶性结构>0.5 mm或超过周围IMT的50%或IMT>1.5 mm[5]。
1.3.2　其他定义
身体质量指数（body mass index,BMI)：BMI=体重/身高的二次方（kg/m2）。BMI<24 kg/m2为消瘦/正常，BMI≥24 kg/m2为超重/肥胖[6]。
血压：将90 mm Hg≤收缩压<140 mm Hg定义为收缩压正常；60 mm Hg≤舒张压<90 mm Hg定义为舒张压正常[7]。
血糖：将FPG<6.1 mmol/L定义为FPG正常[8]。
血脂：将TC<5.2 mmol/L定义为TC水平正常；TG<1.70 mmol/L定义为TG水平正常；HDL-C≥1.0 mmol/L定义为HDL-C水平正常；LDL-C<3.4 mmol/L定义为LDL-C水平正常[9]。
胰岛素抵抗替代指标：三酰甘油-葡萄糖指数(triglyceride-glucose index,TyG)=ln[(TG(mg/dl)×FPG(mg/dl)/2)][10]; TG/HDL-C=TG(mg/dl)/HDL-C(mg/dl)[11];胰岛素抵抗的代谢评分(metabolic score for IR, METS-IR)=ln[2×FPG(mg/dl)+TG(mg/dl)]×BMI(kg/m2)/ln[HDL-C(mg/dl)][12]。
炎症指标：中性粒细胞/淋巴细胞比值(neutrophil to lymphocyte ratio, NLR)=中性粒细胞计数/淋巴细胞计数；血小板/淋巴细胞比值(platelet to lymphocyte ratio, PLR)=血小板计数/淋巴细胞计数；系统免疫炎症指数(systemic immune-inflammation index, SII)= 外周血小板计数×中性粒细胞计数/淋巴细胞计数[13]；全身炎症聚集指数（aggregate inflammation systemic index，AISI）=血小板计数×中性粒细胞计数×单核细胞数/淋巴细胞数[14]。
1.4　统计学方法
使用Excel、SPSS 26.0及R 4.3.2软件进行数据整理和分析。符合正态分布的计量资料使用均数和标准差描述，组间比较使用两独立样本t检验；不符合正态分布的计量资料以中位数和四分位数表示，组间比较使用非参数检验；计数资料以例数和百分比表示，组间比较采用χ2检验。将所有相关指标先纳入单因素条件logistic回归分析，筛选有意义的变量，再将有意义且无多重共线性（方差膨胀因子均<10）的变量纳入多因素条件logistic回归分析模型，分析颈动脉斑块发生的独立影响因素。采用三分位数分层和RCS分析相关暴露因素与人群颈动脉斑块发生的剂量-反应关系，RCS通过赤池信息准则(AIC)选取最优节点数，当P foroverall<0.05,且P fornon-linear<0.05时，说明两变量间存在非线性剂量-反应关系；当P foroverall<0.05，且P fornon-linear>0.05时说明两变量间存在线性剂量-反应关系。检验水准α=0.05。
2　结果
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2.1　研究对象的基线特征
2.1.1　生理生化指标的基线
本研究共纳入研究对象2 300人，年龄55.00岁，其中男性1 772人（77.00%）。计量资料均不符合正态分布，病例组和对照组在BMI、TC、HDL-C、LDL-C、TyG、TG/HDL-C、METS-IR、肌酐、尿素氮/肌酐、谷丙转氨酶和谷草/谷丙转氨酶等生理、生化指标间差异均有统计学意义（P<0.05)，见表1。
2.1.2　血常规的基线特征
病例组和对照组在白细胞计数、中性粒细胞数、淋巴细胞数、单核细胞数、嗜碱性粒细胞数、血小板计数、血小板压积和AISI等血常规及其衍生指标间差异均有统计学意义（P<0.05)，见表2。
2.2　颈动脉斑块发病的影响因素
将单因素条件logistic 回归分析差异有统计学意义（P<0.05) 的影响因素纳入多因素条件logistic回归分析模型进行分析。由表3所示，HDL-C异常、尿素氮/肌酐以及红细胞分布宽度-SD是总人群颈动脉斑块的危险因素（P<0.05)，总蛋白是总人群颈动脉斑块的保护因素（P=0.002)。
2.3　颈动脉斑块发病影响因素的剂量-反应关系
对颈动脉斑块发病影响因素进行三分位数分析，模型3发现HDL-C和总蛋白Q3组颈动脉斑块的发病风险最低，较Q1组分别降低34.9%(OR=0.651，95%CI：0.513～0.825)和24.9%(OR=0.751，95%CI：0.604～0.934);尿素氮/肌酐Q3组颈动脉斑块发病风险是Q1组的1.264倍(OR=1.264，95%CI：1.018～1.570)。RCS结果表明，HDL-C和总蛋白与颈动脉斑块发病风险呈负向线性剂量-反应关系，尿素氮/肌酐与颈动脉斑块发病风险呈正向线性剂量-反应关系，红细胞分布宽度-SD与颈动脉斑块发病风险无剂量-反应关系。见表4、图2。
3　讨论
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3.1　HDL-C和总蛋白是颈动脉斑块发病的保护因素
本研究发现，HDL-C和总蛋白是颈动脉斑块发病的保护因素，且随着HDL-C和总蛋白水平增高，颈动脉斑块的发病风险降低。郝萍萍[15]发现HDL-C是颈动脉斑块形成的保护因素。孔岩等[16]发现HDL-C与老年心脑血管疾病患者颈动脉斑块呈负相关。张良峰等[17]研究提示颈动脉粥样硬化可能与血清总蛋白和白蛋白水平降低有关，与本研究结果相似。作为心血管保护因子，HDL-C主要参与胆固醇的逆向转运、抗氧化并保护内皮细胞免受氧化的LDL-C的损伤[18]。此外，HDL-C具有抑制血栓形成、抗凋亡和抗炎作用，有助于维持内皮细胞的屏障功能，进而防止动脉粥样硬化的形成[19]。总蛋白与颈动脉粥样硬化之间的机制可能与白蛋白的自由基清除作用或抗凝作用有关。其中，自由基可促进动脉粥样硬化，而白蛋白可通过结合促进自由基产生的游离Cu2+，减少自由基的产生，进而减少动脉粥样硬化的发生[20-21]。
3.2　尿素氮/肌酐和红细胞分布宽度-SD是颈动脉斑块发病的危险因素
本研究发现尿素氮/肌酐和红细胞分布宽度-SD是颈动脉斑块发病的危险因素，且随着尿素氮/肌酐水平增高，颈动脉斑块的发病风险增大。王晓晖等[22]研究发现尿素氮/肌酐是临床高风险颈动脉斑块的独立保护因素，与本研究结果存在争议，可能与其纳入人群为已患颈动脉狭窄/颈动脉斑块患者、人群分解状态不同等有关。陈小会等[23]发现红细胞分布宽度是绝经后女性颈动脉斑块高Crouse评分最重要的危险因素。研究发现尿素氮/肌酐是反应机体分解代谢状况的标志物之一，当机体处于高分解状态时，蛋白质大量分解引起的尿素氮升高和肌肉丢失引起的肌酐下降均会导致尿素氮/肌酐值升高[24-25]。目前关于尿素氮/肌酐与颈动脉斑块间的机制还有待进一步研究。颈动脉斑块的发展是一个慢性的炎症反应，红细胞分布宽度与颈动脉斑块之间的机制可能与细胞因子介导的炎症反应有关[26]。Luigi Ferrucci等[27]发现非贫血患者中炎症标志物的数量与促红细胞生成素的浓度呈正相关，促红细胞生成素又会导致红细胞分布宽度的增加。
综上所述，HDL-C、总蛋白、尿素氮/肌酐和红细胞分布宽度-SD与颈动脉斑块的发病有关，且HDL-C、尿素氮/肌酐、总蛋白与颈动脉斑块的发病风险存在线性剂量-反应关系。
基金
收起
  • 甘肃省自然科学基金(23JRRA099; 24JRRA351)
  • 甘肃省卫生行业科研计划项目(GSWSKY-2019-19)
  • 兰州市科技计划项目(2023-02-27)
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doi: 10.20043/j.cnki.MPM.202411399
  • 接收时间：2024-11-22
  • 首发时间：2026-03-18
  • 出版时间：2025-03-10
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  • 收稿日期：2024-11-22
基金
甘肃省自然科学基金(23JRRA099; 24JRRA351)
甘肃省卫生行业科研计划项目(GSWSKY-2019-19)
兰州市科技计划项目(2023-02-27)
作者信息
    1.兰州大学第二医院健康管理中心，甘肃 兰州 730000
    2.兰州大学公共卫生学院流行病与卫生统计学研究所，甘肃 兰州 730000

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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
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
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