老年冠心病患者脂肪细胞因子与冠状动脉病变严重程度的相关性
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摘要
目的探讨冠心病(CHD)患者血清内脂素、Chemerin、网膜素-1、Vaspin及SFRP5水平与冠状动脉病变程度的相关性。方法回顾性纳入本院2016年6月1日至2018年7月1日共187例CHD患者和45例健康体检者作为研究对象,根据Gensini积分将CHD患者分为轻、中度和重度病变组,评估CHD患者与对照组在性别、年龄、BMI、合并高血压及糖尿病、尿酸、血糖、血脂、hs-CRP、同型半胱氨酸及五种脂肪细胞因子的差异,采用Logistic回归分析Gensini积分的危险因素和Spearman相关分析脂肪细胞因子与hsCRP、同型半胱氨酸和LDL-c的相关性;利用受试者操作特征(ROC)曲线探讨脂肪细胞因子预测重度冠脉病变的临床效能。结果与对照组比较,CHD患者LDL-c、TC、TG、hs-CRP、尿酸、同型半胱氨酸、内脂素、Chemerin、网膜素-1水平及合并高血压和糖尿病比例均显著高于对照组,而Vaspin和SFRP5水平显著低于对照组,且差异均具有统计学意义(均P <0.05);Logistic回归分析显示,hs-CRP(OR=2.36)、同型半胱氨酸(OR=4.12)、LDL-c(OR=3.45)、内脂素(OR=6.36)、Chemerin(OR=4.69)水平升高是导致Gensini积分升高的危险因素(均P<0.05),而网膜素-1(OR=0.38)、Vaspin(OR=0.49)和SFRP5(OR=0.13)水平升高是导致Gensini积分升高的保护因素(均P <0.05)。CHD患者内脂素、Chemerin水平与hs-CRP、同型半胱氨酸和LDL-c均呈显著正相关性,网膜素-1、Vaspin和SFRP5水平与hs-CRP、同型半胱氨酸和LDL-c均呈显著负相关性。ROC曲线结果发现,内脂素、Chemerin、网膜素-1、Vaspin和SFRP5预测CHD患者冠脉重度病变的预测价值较好。结论 CHD患者脂肪细胞因子内脂素、Chemerin水平升高,与冠状动脉病变程度明显正相关,而网膜素-1、Vaspin和SFRP5水平下降,与冠状动脉病变程度明显负相关。
Objective To investigate the association between serum levels of Visfatin,Chemerin,Omenin-1,Vaspin and SFRP5 and coronary artery lesions in patients with coronary heart disease(CHD). Methods A total of 187 patients with CHD and 45 health controls from June 1,2016 to July 1,2018 were retrospectively enrolled in this study. Patients with CHD were divided into mild,moderate and severe lesion groups according to Gensini score. The differences between patients with CHD and control group were evaluated in sex,mean age,BMI,comorbidity of hypertension and diabetes mellitus,uric acid,blood glucose,blood lipid,hs-CRP,homocysteine,Visfatin,Chemerin,Omenin-1,Vaspin and SFRP5. The risk factors of Gensini score and the association between adipocytokines and hs-CRP,homocysteine and LDL-c was analyzed by Logistic regression and Spearman correlation,respectively. The value of adipocytokines in predicting severity of coronary artery lesions in patients with CHD was analyzed by Receiver Operating Characteristic(ROC)curve. Results The serum level of LDL-c,TC,TG,hs-CRP,uric acid,homocysteine,Visfatin,Chemerin,Omenin-1,comorbidity of hypertension and diabetes mellitus were significantly higher in patients than in control group,while the levels of Vaspin and SFRP 5 were significantly lower in patients than in control group(all P < 0.05). Logistic regression analysis showed that the increased levels of hs-CRP(OR = 2.36),homocysteine(OR = 4.12),LDL-c(OR = 3.45),Visfatin(OR = 6.36),Chemerin(OR = 4.69)were the risk factors for the increase of Gensini score(all P < 0.05),while the increased levels of Omenin-1(OR = 0.38),Vaspin(OR = 0.49)and SFRP5(OR = 0.13)were the protective factors(All P < 0.05).The levels of Visfatin and Chemerin were significantly positively correlated with hs-CRP,homocysteine and LDL-c,while the levels of Omenin-1,Vaspin and SFRP5 were significantly negatively correlated with hs-CRP,homocysteine and LDL-c. ROC curve results showed that Visfatin,Chemerin,Omenin-1,Vaspin and SFRP5 were good predictive value in predicting severity of coronary artery lesions in patients with CHD was good. Conclusions The level of Visfatin,Chemerin in patients with CHD was significantly correlated with the severity of coronary artery lesions,while the level of Omenin-1,Vaspin and SFRP5 was significantly negatively correlated with the severity of coronary artery lesions.
Objective To investigate the association between serum levels of Visfatin,Chemerin,Omenin-1,Vaspin and SFRP5 and coronary artery lesions in patients with coronary heart disease(CHD). Methods A total of 187 patients with CHD and 45 health controls from June 1,2016 to July 1,2018 were retrospectively enrolled in this study. Patients with CHD were divided into mild,moderate and severe lesion groups according to Gensini score. The differences between patients with CHD and control group were evaluated in sex,mean age,BMI,comorbidity of hypertension and diabetes mellitus,uric acid,blood glucose,blood lipid,hs-CRP,homocysteine,Visfatin,Chemerin,Omenin-1,Vaspin and SFRP5. The risk factors of Gensini score and the association between adipocytokines and hs-CRP,homocysteine and LDL-c was analyzed by Logistic regression and Spearman correlation,respectively. The value of adipocytokines in predicting severity of coronary artery lesions in patients with CHD was analyzed by Receiver Operating Characteristic(ROC)curve. Results The serum level of LDL-c,TC,TG,hs-CRP,uric acid,homocysteine,Visfatin,Chemerin,Omenin-1,comorbidity of hypertension and diabetes mellitus were significantly higher in patients than in control group,while the levels of Vaspin and SFRP 5 were significantly lower in patients than in control group(all P < 0.05). Logistic regression analysis showed that the increased levels of hs-CRP(OR = 2.36),homocysteine(OR = 4.12),LDL-c(OR = 3.45),Visfatin(OR = 6.36),Chemerin(OR = 4.69)were the risk factors for the increase of Gensini score(all P < 0.05),while the increased levels of Omenin-1(OR = 0.38),Vaspin(OR = 0.49)and SFRP5(OR = 0.13)were the protective factors(All P < 0.05).The levels of Visfatin and Chemerin were significantly positively correlated with hs-CRP,homocysteine and LDL-c,while the levels of Omenin-1,Vaspin and SFRP5 were significantly negatively correlated with hs-CRP,homocysteine and LDL-c. ROC curve results showed that Visfatin,Chemerin,Omenin-1,Vaspin and SFRP5 were good predictive value in predicting severity of coronary artery lesions in patients with CHD was good. Conclusions The level of Visfatin,Chemerin in patients with CHD was significantly correlated with the severity of coronary artery lesions,while the level of Omenin-1,Vaspin and SFRP5 was significantly negatively correlated with the severity of coronary artery lesions.
引文
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[7]KANG J,CHENG B,JIANG L.PPARγsignal transduction pathway in the foam cell formation induced by visfatin[J].Acta Physiologica Sinica,2010,62(5):427-432.
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[9]WU M H,TSAI C H,HUANG Y L,et al.Visfatin promotes IL-6 and TNF-αproduction in human synovial fibroblasts by repressing miR-199a-5p through ERK,p38 and JNK signaling pathways[J].Int J Mol Sci,2018,19(1):E190.
[10]李新萍.急性脑梗死患者血清内脂素含量的变化及对颈动脉粥样硬化斑块形成和稳定性的影响[J].中国实用神经疾病杂志,2016,19(3):103-104.
[11]AUGUET T,ARAGONES G,GUIU-JURADO E,et al.Adipo/cytokines in atherosclerotic secretomes:increased visfatin levels in unstable carotid plaque[J].BMC Cardiovasc Disord,2016,16(1):149.
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[13]GAO X,MI S,ZHANG F,et al.Association of chemerin mRNAexpression in human epicardial adipose tissue with coronary atherosclerosis[J].Cardiovascular Diabetology,2011,10(1):87.
[14]DIMITRIADIS G K,KAUR J,ADYA R,et al.Chemerin induces endothelial cell inflammation:activation of nuclear factor-kappa beta and monocyte-endothelial adhesion[J].Oncotarget,2018,9(24):16678-16690.
[15]ZYLLA S,DORR M,VOLZKE H,et al.Association of Circulating chemerin with sub-clinical parameters of atherosclerosis:Results of a population-based study[J].Arterioscler Thromb Vasc Biol,2018,38(7):1656-1664.
[16]SUZUKI Y,HONG Y H,SONG S H,et al.The Regulation of chemerin and cmklr1 genes expression by tnf-α,adiponectin,and chemerin analog in bovine differentiated adipocytes[J].Asian-Australas J Anim Sci,2012,25(9):1316-1321.
[17]SATO K,SHIRAI R,YAMAGUCHI M,et al.Anti-atherogenic effects of vaspin on human aortic smooth muscle cell/macrophage responses and hyperlipidemic mouse plaque phenotype[J].Int JMol Sci,2018,19(6):1732.
[18]DUAN X Y,XIE P L,MA Y L,et al.Omentin inhibits osteoblastic differentiation of calcifying vascular smooth muscle cells through the PI3K/Akt pathway[J].Amino Acids,2011,41(5):1223-1231.
[19]YAMAWAKI H,KURAMOTO J,KAMESHIMA S,et al.Omentin,a novel adipocytokine inhibits TNF-induced vascular inflammation in human endothelial cells[J].Biochem Biophys Res Commun,2011,408(2):339-343.
[20]KATAOKA Y,SHIBATA R,OHASHI K,et al.Omentin prevents myocardial ischemic injury through AMP-activated protein kinase-and Akt-dependent mechanisms[J].J Am Coll of Cardiol,2014,63(24):2722-2733.
[21]HERDER C,OUWENS D M,CARSTENSEN M,et al.Adiponectin may mediate the association between omentin,circulating lipids and insulin sensitivity:results from the KORA F4 study[J].Eur J Endocrinol,2015,172(4):423-32.
[22]吴舒窈,刘艳,宋倩.冠心病发病及预后的影响因素研究[J].中国全科医学,2018,21(29):3562-3570.
[23]PHALITAKUL S,OKADA M,HARA Y,et al.Vaspin prevents TNF-α-induced intracellular adhesion molecule-1 via inhibiting reactive oxygen species-dependent NF-κB and PKCθactivation in cultured rat vascular smooth muscle cells[J].Pharmacol Res,2011,64(5):493-500.
[24]ALKURAISHY H M,ALGAREEB A I,ALBUHADILLY A K.Rosuvastatin improves vaspin serum levels in obese patients with acute coronary syndrome[J].Diseases,2018,6(1):9.
[25]杨雪,智永超,孙卓,等.冠心病患者血清中SFRP5水平及临床意义[J].中国循证心血管医学杂志,2018,10(7):870-872.
[26]BILKOVSKI R,SCHULTE D M,OBERHAUSER F,et al.Adipose tissue macrophages inhibit adipogenesis of mesenchymal precursor cells via wnt-5a in humans[J].Int J Obes(Lond),2011,35(11):1450-1454.
[27]BHATT P M,MALGOR R.Wnt5a:A player in the pathogenesis of atherosclerosis and other inflammatory disorders[J].Atherosclerosis,2014,237(1):155-162.
[28]NAKAMURA K,SANO S,FUSTER J J,et al.Secreted frizzledrelated protein 5 diminishes cardiac inflammation and protects the heart from ischemia/reperfusion injury[J].J Biol Chem,2015,291(6):2566-2575.2019-02-24
[2]MANCIO J,OIKONOMOU E K,ANTONIADES C.Perivascular adipose tissue and coronary atherosclerosis[J].Heart,2018,104(20):1654-1662.
[3]JEON E J,HONG S Y,LEE J H.Adipokines and insulin resistance according to characteristics of pregnant women with gestational diabetes mellitus[J].Diabetes Metab J,2017,41(6):457-465.
[4]FRANCISCO V,PINO J,GONZALEZ-GAY M A,et al.Adipokines and inflammation:is it a question of weight?[J].Br J Pharmacol,2018,175(10):1569-1579.
[5]GENSISI G.A more meaningful scoring system for determining the severity of coronary heart disease[J].Am J Cardiol,1983,51(3):606-606.
[6]CHUNG H S,CHOI K M.Adipokines and myokines:a pivotal role in metabolic and cardiovascular disorders[J].Curr Med Chem,2017,25(20):2401-2415.
[7]KANG J,CHENG B,JIANG L.PPARγsignal transduction pathway in the foam cell formation induced by visfatin[J].Acta Physiologica Sinica,2010,62(5):427-432.
[8]SOFIA G S,CHRISTOS G K,JOHN N V,et al.Adipokines in periaortic and epicardial adipose tissue:differential expression and relation to atherosclerosis[J].J Atheroscler Thromb,2010,17(2):115-130.
[9]WU M H,TSAI C H,HUANG Y L,et al.Visfatin promotes IL-6 and TNF-αproduction in human synovial fibroblasts by repressing miR-199a-5p through ERK,p38 and JNK signaling pathways[J].Int J Mol Sci,2018,19(1):E190.
[10]李新萍.急性脑梗死患者血清内脂素含量的变化及对颈动脉粥样硬化斑块形成和稳定性的影响[J].中国实用神经疾病杂志,2016,19(3):103-104.
[11]AUGUET T,ARAGONES G,GUIU-JURADO E,et al.Adipo/cytokines in atherosclerotic secretomes:increased visfatin levels in unstable carotid plaque[J].BMC Cardiovasc Disord,2016,16(1):149.
[12]HUNG W C,YU T H,HSU C C,et al.Plasma visfatin levels are associated with major adverse cardiovascular events in patients with acute ST-elevation myocardial infarction[J].Clin Invest Med,2015,38(3):100-109.
[13]GAO X,MI S,ZHANG F,et al.Association of chemerin mRNAexpression in human epicardial adipose tissue with coronary atherosclerosis[J].Cardiovascular Diabetology,2011,10(1):87.
[14]DIMITRIADIS G K,KAUR J,ADYA R,et al.Chemerin induces endothelial cell inflammation:activation of nuclear factor-kappa beta and monocyte-endothelial adhesion[J].Oncotarget,2018,9(24):16678-16690.
[15]ZYLLA S,DORR M,VOLZKE H,et al.Association of Circulating chemerin with sub-clinical parameters of atherosclerosis:Results of a population-based study[J].Arterioscler Thromb Vasc Biol,2018,38(7):1656-1664.
[16]SUZUKI Y,HONG Y H,SONG S H,et al.The Regulation of chemerin and cmklr1 genes expression by tnf-α,adiponectin,and chemerin analog in bovine differentiated adipocytes[J].Asian-Australas J Anim Sci,2012,25(9):1316-1321.
[17]SATO K,SHIRAI R,YAMAGUCHI M,et al.Anti-atherogenic effects of vaspin on human aortic smooth muscle cell/macrophage responses and hyperlipidemic mouse plaque phenotype[J].Int JMol Sci,2018,19(6):1732.
[18]DUAN X Y,XIE P L,MA Y L,et al.Omentin inhibits osteoblastic differentiation of calcifying vascular smooth muscle cells through the PI3K/Akt pathway[J].Amino Acids,2011,41(5):1223-1231.
[19]YAMAWAKI H,KURAMOTO J,KAMESHIMA S,et al.Omentin,a novel adipocytokine inhibits TNF-induced vascular inflammation in human endothelial cells[J].Biochem Biophys Res Commun,2011,408(2):339-343.
[20]KATAOKA Y,SHIBATA R,OHASHI K,et al.Omentin prevents myocardial ischemic injury through AMP-activated protein kinase-and Akt-dependent mechanisms[J].J Am Coll of Cardiol,2014,63(24):2722-2733.
[21]HERDER C,OUWENS D M,CARSTENSEN M,et al.Adiponectin may mediate the association between omentin,circulating lipids and insulin sensitivity:results from the KORA F4 study[J].Eur J Endocrinol,2015,172(4):423-32.
[22]吴舒窈,刘艳,宋倩.冠心病发病及预后的影响因素研究[J].中国全科医学,2018,21(29):3562-3570.
[23]PHALITAKUL S,OKADA M,HARA Y,et al.Vaspin prevents TNF-α-induced intracellular adhesion molecule-1 via inhibiting reactive oxygen species-dependent NF-κB and PKCθactivation in cultured rat vascular smooth muscle cells[J].Pharmacol Res,2011,64(5):493-500.
[24]ALKURAISHY H M,ALGAREEB A I,ALBUHADILLY A K.Rosuvastatin improves vaspin serum levels in obese patients with acute coronary syndrome[J].Diseases,2018,6(1):9.
[25]杨雪,智永超,孙卓,等.冠心病患者血清中SFRP5水平及临床意义[J].中国循证心血管医学杂志,2018,10(7):870-872.
[26]BILKOVSKI R,SCHULTE D M,OBERHAUSER F,et al.Adipose tissue macrophages inhibit adipogenesis of mesenchymal precursor cells via wnt-5a in humans[J].Int J Obes(Lond),2011,35(11):1450-1454.
[27]BHATT P M,MALGOR R.Wnt5a:A player in the pathogenesis of atherosclerosis and other inflammatory disorders[J].Atherosclerosis,2014,237(1):155-162.
[28]NAKAMURA K,SANO S,FUSTER J J,et al.Secreted frizzledrelated protein 5 diminishes cardiac inflammation and protects the heart from ischemia/reperfusion injury[J].J Biol Chem,2015,291(6):2566-2575.2019-02-24