2型糖尿病对急性STEMI患者经皮冠状动脉介入治疗后炎症反应及远期心肌重构的影响
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摘要
目的:探讨2型糖尿病(T2DM)对急性ST段抬高型心肌梗死(STEMI)患者直接经皮冠状动脉介入治疗(primary PCI)后炎症反应及远期心肌重构的影响,分析此类患者不良预后的可能机制。方法:纳入STEMI患者60例,其中合并T2DM者30例,测定在直接PCI术前、术后12 h、36 h、60 h各时间点肌酸激酶同工酶(CK-MB)、肌钙蛋白T(cTnT)、单核细胞趋化蛋白-1(MCP-1)、基质金属蛋白酶-9(MMP-9)、金属蛋白酶组织抑制因子-1(TIMP-1)、骨桥蛋白(OPN)的表达水平。所有患者在直接PCI术后1周及术后1年行超声心动图检查。主要终点指标为直接PCI术后1年主要不良心血管事件(MACE)发生率,包括心源性死亡、非致命性再次心肌梗死和再次靶血管血运重建;次要终点指标为心肌梗死溶栓治疗(TIMI)血流分级、血清学指标、左室射血分数(LVEF)、左室舒张末期容积(LVEDV)和左室收缩末期容积(LVESV)。结果:DM组患者CK-MB和cTnT峰值水平均明显高于非DM组患者(P<0.05);术后60 h,DM组患者MCP-1和MMP-9/TIMP-1比值水平均明显高于非DM组患者(P<0.05)。两组患者在直接PCI术后1周的LVEF、LVEDV和LVESV差异无统计学意义;但与非DM组患者相比,DM组患者在术后1年的LVEF明显降低(P<0.001),LVEDV和LVESV则明显增大(P<0.05)。结论:DM组患者在直接PCI术后心肌酶峰值、MCP-1表达及MMP-9/TIMP-1比值更高,术后1年LVEF更低、LVEDV和LVESV更大,提示STEMI合并T2DM患者更易发生远期心肌重构,其机制可能与更活跃的炎症反应有关。
Objective: To investigate the effect of type 2 diabetes mellitus(T2DM) on inflammatory reaction and long-term cardiac remodeling in patients with acute ST-elevation myocardial infarction(STEMI) underwent primary percutaneous coronary intervention(PCI). Methods: A total of 60 patients diagnosed with STEMI were selected, and 30 patients among whom also had T2DM(DM group). Creatinine kinase-MB(CK-MB), cardiac troponin T(cTnT), monocyte chemotactic protein-1(MCP-1), matrix metalloproteinase-9(MMP-9), tissue inhibitor of metalloproteinase-1(TIMP-1), and osteopontin(OPN) were measured before PCI and 12 h, 36 h, and 60 h after PCI. All patients took echocardiogram measurements in one week and one year after PCI. The primary end point was one year incidence of major adverse cardiovascular events(MACE), including cardiac death, nonfatal myocardial infarction, and target vessel revascularization. Secondary end points were thrombolysis in myocardial infarction(TIMI) flow grade, laboratory markers, left ventricular ejection fraction(LVEF), left ventricular end diastolic volume(LVEDV), and left ventricular end systolic volume(LVESV). Results: Compared with non-DM group, DM group(n=30) had higher peak levels of both CK-MB and cTnT after PCI(P<0.05). MCP-1 level and the ratio of MMP-9/TIMP-1 level were also higher in DM group 60 h after PCI(P<0.05). There were no significant differences in LVEFs, LVEDVs, or LVESVs one week after PCI between the groups. However, DM group had lower LVEFs(P<0.001) as well as larger LVEDVs and LVESVs(P<0.05) versus non-DM group one year after PCI. Conclusions: The peak myocardial enzyme, MCP-1 level, and MMP-9/TIMP-1 ratio are higher in DM group after direct PCI, LVEF is lower, LVEDV and LVESV are higher one year after PCI, suggesting that patients with STEMI complicated with T2DM are more prone to long-term myocardial remodeling, and the mechanism may be related to more active inflammatory reactions.
Objective: To investigate the effect of type 2 diabetes mellitus(T2DM) on inflammatory reaction and long-term cardiac remodeling in patients with acute ST-elevation myocardial infarction(STEMI) underwent primary percutaneous coronary intervention(PCI). Methods: A total of 60 patients diagnosed with STEMI were selected, and 30 patients among whom also had T2DM(DM group). Creatinine kinase-MB(CK-MB), cardiac troponin T(cTnT), monocyte chemotactic protein-1(MCP-1), matrix metalloproteinase-9(MMP-9), tissue inhibitor of metalloproteinase-1(TIMP-1), and osteopontin(OPN) were measured before PCI and 12 h, 36 h, and 60 h after PCI. All patients took echocardiogram measurements in one week and one year after PCI. The primary end point was one year incidence of major adverse cardiovascular events(MACE), including cardiac death, nonfatal myocardial infarction, and target vessel revascularization. Secondary end points were thrombolysis in myocardial infarction(TIMI) flow grade, laboratory markers, left ventricular ejection fraction(LVEF), left ventricular end diastolic volume(LVEDV), and left ventricular end systolic volume(LVESV). Results: Compared with non-DM group, DM group(n=30) had higher peak levels of both CK-MB and cTnT after PCI(P<0.05). MCP-1 level and the ratio of MMP-9/TIMP-1 level were also higher in DM group 60 h after PCI(P<0.05). There were no significant differences in LVEFs, LVEDVs, or LVESVs one week after PCI between the groups. However, DM group had lower LVEFs(P<0.001) as well as larger LVEDVs and LVESVs(P<0.05) versus non-DM group one year after PCI. Conclusions: The peak myocardial enzyme, MCP-1 level, and MMP-9/TIMP-1 ratio are higher in DM group after direct PCI, LVEF is lower, LVEDV and LVESV are higher one year after PCI, suggesting that patients with STEMI complicated with T2DM are more prone to long-term myocardial remodeling, and the mechanism may be related to more active inflammatory reactions.
引文
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[18] SEBBEN J C,PINTO RIBEIRO D R,LOPES R D,et al.The role of diabetes mellitus in the composition of coronary thrombi in patients presenting with acute ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention[J].Am Heart J,2016,172:26-33.
[19] AMIER R P,TEUNISSEN P F,MARQUES K M,et al.Invasive measurement of coronary microvascular resistance in patients with acute myocardial infarction treated by primary PCI[J].Heart,2014,100(1):13-20.
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[21] IWAKURA K,ITO H,IKUSHIMA M,et al.Association between hyperglycemia and the no-reflow phenomenon in patients with acute myocardial infarction[J].J Am Coll Cardiol,2003,41(1):1-7.
[22] LOW WANG C C,HESS C N,HIATT W R,et al.Clinical update:cardiovascular disease in diabetes mellitus atherosclerotic cardiovascular disease and heart failure in type 2 diabetes mellitus - mechanisms,management,and clinical considerations[J].Circulation,2016,133(24):2459-2502.
[23] KALKMAN D N,AQUINO M,CLAESSEN B E,et al.Residual inflammatory risk and the impact on clinical outcomes in patients after percutaneous coronary interventions[J].Eur Heart J,2018,39(46):4101-4108.
[24] ANDRAE J,GALLINI R,BETSHOLTZ C.Role of platelet-derived growth factors in physiology and medicine[J].Genes Dev,2008,22(10):1276-1312.
[25] RITTER A M V,FARIA A P C,SABBATINI A,et al.MCP-1 levels are associated with cardiac remodeling but not with resistant hypertension[J].Arq Bras Cardiol,2017,108(4):331-338.
[26] 孙青,李晓燕,刘娟,等.急性冠状动脉综合征合并2型糖尿病患者血浆过氧化物酶体增殖物激活受体γ与冠状动脉病变严重程度及斑块稳定性的相关性研究[J].中国介入心脏病学杂志,2014,22(8):497-500.
[ 2 ] JAFFE R,DICK A,STAUSS B H.Prevention and treatment of microvascular obstruction-related myocardial injury and coronary no-reflow following percutaneous coronary intervention:a systematic approach[J].JACC Cardiovasc Interv,2010,3(7):695-704.
[ 3 ] 陈章炜,钱菊英,马剑英,等.轻度冠状动脉微栓塞后TNF-α和cTNT的变化[J].中国分子心脏病学杂志,2010,10(5):310-313.
[ 4 ] 马剑英,钱菊英,葛均波,等.冠状动脉微栓塞后MCP-1变化的实验研究[J].中国分子心脏病学杂志,2008,8(3):149-152.
[ 5 ] CHEN Z W,QIAN J Y,MA J Y,et al.Glucocorticoid ameliorates early cardiac dysfunction after coronary microembolization and suppresses TGF-β1/Smad3 and CTGF expression[J].Int J Cardiol,2013,167(5):2278-2284.
[ 6 ] PICCOLO R,FRANZONE A,KOSKINAS K C,et al.Effect of diabetes mellitus on frequency of adverse events in patients with acute coronary syndromes undergoing percutaneous coronary intervention[J].Am J Cardiol,2016,118(3):345-352.
[ 7 ] XU L L,WARREN M K,ROSE W L,et al.Human recombinant monocyte chemotactic protein and other C-C chemokines bind and induce directional migration of dendritic cells in vitro[J].J Leukoc Biol,1996,60(3):365-371.
[ 8 ] TURNER N A,PORTER K E.Regulation of myocardial matrix metalloproteinase expression and activity by cardiac fibroblasts[J].IUBMB LIFE,2012,64(2):143-150.
[ 9 ] MANY G M,YOKOSAKI Y,UAESOONTRACHOON K,et al.OPN-a induces muscle inflammation by increasing recruitment and activation of pro-inflammatory macrophages[J].Exp Physiol,2016,101(10):1285-1300.
[10] STAMLER J,VACCARO O,NEATON J D,et al.Diabetes,other risk factors,and 12-yr cardiovascular mortality for men screened in the Multiple Risk Factor Intervention Trial[J].Diabetes Care,1993,16(2):434-444.
[11] HAFFNER S M,LEHTO S,RONNEMAA T,et al.Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction[J].N Engl J Med,1998,339(4):229-234.
[12] ERTELT K,BRENER S J,MEHRAN R,et al.Comparison of outcomes and prognosis of patients with versus without newly diagnosed diabetes mellitus after primary percutaneous coronary intervention for ST-elevation myocardial infarction (the HORIZONS-AMI Study) [J].Am J Cardiol,2017,119(12):1917-1923.
[13] TIMMER J R,HOEKSTRA M,NIJSTEN M W,et al.Prognostic value of admission glycosylated hemoglobin and glucose in nondiabetic patients with ST-segment-elevation myocardial infarction treated with percutaneous coronary intervention[J].Circulation,2011,124(6):704-711.
[14] REINSTADLER S J,STIERMAIER T,EITEL C,et al.Relationship between diabetes and ischaemic injury among patients with revascularized ST-elevation myocardial infarction[J].Diabetes Obes Metab,2017,19(12):1706-1713.
[15] CLAESSEN B E,HOEBERS L P,VAN DER SCHAAF R J,et al.Prevalence and impact of a chronic total occlusion in a non-infarct-related artery on long-term mortality in diabetic patients with ST elevation myocardial infarction[J].Heart,2010,96(24):1968-1972.
[16] GIACOPPO D,MADHAVAN M V,BABER U,et al.Impact of contrast-induced acute kidney injury after percutaneous coronary intervention on short- and long-term outcomes:pooled analysis from the HORIZONS-AMI and ACUITY trials[J].Circ Cardiovasc Interv,2015,8(8):e002475.
[17] SINGLA A,ANTONINO M J,BLIDEN K P,et al.The relation between platelet reactivity and glycemic control in diabetic patients with cardiovascular disease on maintenance aspirin and clopidogrel therapy[J].Am Heart J,2009,158(5):784.e1-6.
[18] SEBBEN J C,PINTO RIBEIRO D R,LOPES R D,et al.The role of diabetes mellitus in the composition of coronary thrombi in patients presenting with acute ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention[J].Am Heart J,2016,172:26-33.
[19] AMIER R P,TEUNISSEN P F,MARQUES K M,et al.Invasive measurement of coronary microvascular resistance in patients with acute myocardial infarction treated by primary PCI[J].Heart,2014,100(1):13-20.
[20] BAHREHMAND M,SADEGHI E,SHAFIEE A,et al.Predictors of delayed and no-reflow as recognized with thrombolysis in myocardial infarction [TIMI] flow grade following primary percutaneous coronary angioplasty[J].J Med Life,2015,8(Spec Iss 3):59-65.
[21] IWAKURA K,ITO H,IKUSHIMA M,et al.Association between hyperglycemia and the no-reflow phenomenon in patients with acute myocardial infarction[J].J Am Coll Cardiol,2003,41(1):1-7.
[22] LOW WANG C C,HESS C N,HIATT W R,et al.Clinical update:cardiovascular disease in diabetes mellitus atherosclerotic cardiovascular disease and heart failure in type 2 diabetes mellitus - mechanisms,management,and clinical considerations[J].Circulation,2016,133(24):2459-2502.
[23] KALKMAN D N,AQUINO M,CLAESSEN B E,et al.Residual inflammatory risk and the impact on clinical outcomes in patients after percutaneous coronary interventions[J].Eur Heart J,2018,39(46):4101-4108.
[24] ANDRAE J,GALLINI R,BETSHOLTZ C.Role of platelet-derived growth factors in physiology and medicine[J].Genes Dev,2008,22(10):1276-1312.
[25] RITTER A M V,FARIA A P C,SABBATINI A,et al.MCP-1 levels are associated with cardiac remodeling but not with resistant hypertension[J].Arq Bras Cardiol,2017,108(4):331-338.
[26] 孙青,李晓燕,刘娟,等.急性冠状动脉综合征合并2型糖尿病患者血浆过氧化物酶体增殖物激活受体γ与冠状动脉病变严重程度及斑块稳定性的相关性研究[J].中国介入心脏病学杂志,2014,22(8):497-500.