【作者】 王雅静；

【导师】 宋春莉；

【作者基本信息】 吉林大学 ， 临床医学硕士（专业学位）， 2024， 硕士

【摘要】 研究背景:急性冠脉综合征(Acute coronary syndrome,ACS)是因动脉粥样硬化导致心肌急性缺血的一组临床综合征,随着年龄的增长其发病率和死亡率也呈上升趋势。衰弱(Frailty)是指一种以老年人生理储备减少而导致机体面对压力源时易感性增加为特征的老年综合征,其核心表型为体重减轻、自述疲劳、握力降低、步速减慢和身体活动减少。衰弱老年人在面对疾病等应激因素时更容易出现失能、跌倒等情况。研究发现,心血管病患者的衰弱患病率显著升高,并且冠心病被认为是衰弱的危险因素。此外,衰弱也与ACS患者的不良预后独立相关,衰弱可增加ACS患者出现不良心血管事件、再入院及死亡的风险。因此,积极治疗ACS的同时筛查和识别衰弱并进行合理干预对于改善ACS患者的不良预后具有重要意义,然而,目前关于衰弱的识别和干预尚无确切的措施。细胞间粘附分子-1(Intercellular adhesion molecule-1,ICAM-1)和血管细胞粘附分子-1(Vascular cell adhesion molecule-1,VCAM-1)是重要的细胞粘附分子,通过介导白细胞对内皮细胞的强粘附而发挥作用。可溶性细胞间粘附分子-1(soluble Intercellular adhesion molecule-1,sICAM-1)和可溶性血管细胞粘附分子-1(soluble Vascular cell adhesion molecule-1,sVCMA-1)分别为ICAM-1、VCAM-1的可溶性形式。有研究发现sICAM-1水平与社区人群的衰弱独立相关,sVCMA-1水平与老年人脑血流失调、步速减慢以及跌倒相关。而且,ICAM-1和VCAM-1可能通过参与慢性炎症及内皮功能障碍在ACS和衰弱中发挥重要作用。但是目前关于ICAM-1、VCAM-1对老年ACS患者合并衰弱是否影响及如何影响尚无相关报道。研究目的:通过检测老年ACS伴非重度衰弱患者的血清sICAM-1、sVCMA-1水平,分析其与ACS患者非重度衰弱之间的相关性,明确其对ACS患者非重度衰弱的影响及作用,以期早期识别,早期干预,为治疗伴发非重度衰弱的ACS患者的辅助治疗提供可能的靶点,以期改善老年ACS患者的预后。研究方法:选取2023年7月至2023年12月在吉林大学第二医院心血管内科住院治疗的老年ACS患者146例。收集所选患者的基本临床信息及检验检查资料,并采集患者入院当日或次日的空腹外周血,使用酶联免疫吸附法测定患者的血清sICAM-1、sICAM-1水平。衰弱评估使用7分制的临床衰弱量表(Clinical Frailty Scale,CFS),根据得分情况分为非衰弱组(CFS≤4分)和衰弱组(CFS≥5分),其中,衰弱组进一步分为轻度衰弱组(CFS=5分)和中度衰弱组(CFS=6分)。应用SPSS 29.0软件进行统计学分析,分析老年ACS患者衰弱的患病率,比较各组间基本临床信息和检验检查指标的差异,分析sICAM-1、sICAM-1水平在各组间是否存在差异,然后分析sICAM-1、sICAM-1水平和CFS评分的相关性。进一步分析老年ACS患者非重度衰弱的独立影响因素,以及sICAM-1和sVCMA-1对老年ACS患者非重度衰弱诊断的预测价值。研究结果:1.老年ACS患者的衰弱情况本研究共纳入患者146例,非衰弱组80人,衰弱组66人,老年ACS患者衰弱患病率为45.2%,其中,轻度衰弱48人(32.9%),中度衰弱18人(12.3%)。2.老年ACS患者基本临床信息和检验检查资料的组间比较相较于非衰弱患者,衰弱患者在年龄、总胆固醇、Gensini评分方面有统计学差异(P<0.05),在其他方面无统计学差异。衰弱不同亚组间在婚姻状况、血红蛋白含量(Hemoglobin,HGB)、红细胞压积(Hematocrit,Hct)和Gensini评分方面有统计学差异(P<0.05),而在其他方面无统计学差异。进一步行三组间两两比较显示,中度衰弱组HGB、Hct低于轻度衰弱组,非衰弱组和轻度衰弱组间、非衰弱组和中度衰弱组间HGB、Hct比较无统计学差异;中度衰弱组Gensini评分高于非衰弱组,而在其他组间比较无统计学差异。3.sICAM-1、sVCAM-1与老年ACS患者非重度衰弱的关系相较于非衰弱患者,衰弱患者有更高水平的sICAM-1(74.437μg/d L vs 56.318μg/d L,P<0.001)和sVCAM-1(92.339μg/d L vs 57.516μg/d L,P<0.001)。亚组间比较显示三组间sICAM-1、sVCAM-1水平的差别有统计学意义(P<0.05)。进一步行两两比较显示,轻度衰弱组和中度衰弱组的sICAM-1、sVCAM-1水平显著高于非衰弱组,而两因子水平在轻度和中度衰弱组的组间比较中无统计学差异。Spearman相关性分析结果显示sICAM-1、sVCAM-1水平均与CFS评分呈正相关(r=0.433,P<0.001、r=0.418,P<0.001)。对混杂因素进行调整后,二元Logistic回归结果显示,sICAM-1和sVCAM-1水平增高均使非重度衰弱的发生风险增加(OR=1.050,P<0.001、OR=1.017,P<0.001)。4.sICAM-1、sVCAM-1水平对老年ACS患者非重度衰弱的预测价值ROC曲线结果显示:sICAM-1诊断非重度衰弱的曲线下面积(Area under Curve,AUC)是0.741(95%CI=0.660～0.822,P<0.001),最佳截断值为78.343μg/d L,此时诊断非重度衰弱的灵敏度和特异度分别为0.515和0.887,最大约登指数为0.403。sVCAM-1诊断非重度衰弱的AUC为0.707(95%CI=0.623～0.791,P<0.001),最佳截断值为85.370μg/d L,此时诊断非重度衰弱的灵敏度和特异度分别为0.545和0.800,最大约登指数为0.345。sICAM-1和sVCAM-1联合应用诊断非重度衰弱的AUC为0.805(95%CI=0.734～0.877,P<0.001),其诊断非重度衰弱的灵敏度为0.652,特异度为0.875,最大约登指数为0.527。sICAM-1联合sVCAM-1对老年ACS患者非重度衰弱的诊断价值更高。研究结论:1、sICAM-1和sVCAM-1与老年ACS患者的非重度衰弱状态相关,二者可能是老年ACS患者非重度衰弱状态的独立危险因素,且sICAM-1、sVCAM-1水平越高,衰弱程度越重。2、sICAM-1和sVCAM-1对老年ACS患者非重度衰弱的诊断均具有一定的预测价值,且二者联合应用预测价值更优。更多还原

【Abstract】 Background:Acute Coronary Syndrome(ACS)is a clinical syndrome characterized by acute myocardial ischemia due to atherosclerosis,of which the incidence and mortality rates increase with advancing age.Frailty refers to a state that decreased physiological reserves in elderly people lead to increased susceptibility to stressors.And it is a typical geriatric syndrome.Core phenotypes of frailty include weight loss,self-reported fatigue,reduced grip strength,slow gait speed,and low physical activity.Frail elderly individuals are more prone to experiencing disability and falls when faced with stressors such as illness.Studies have found that the prevalence of frailty in patients with cardiovascular disease increased significantly,and coronary artery disease has been recognized as a risk factor for frailty.Additionally,frailty has been found to be an influencing factor for adverse outcomes in patients with ACS,it can increase the incidence of adverse cardiovascular events,readmissions and death.Therefore,screening and identifying frailty while treating ACS and implementing appropriate interventions for frailty are crucial for improving the prognosis of patients with ACS.However,there are currently no definitive measures to identify and intervene frailty.Intercellular Adhesion Molecule-1(ICAM-1)and Vascular Cell Adhesion Molecule-1(VCAM-1)belong to the immunoglobulin superfamily of cell adhesion molecules,which exert their effects by mediating strong adhesion of leukocytes to endothelial cells.Soluble Intercellular Adhesion Molecule-1(sICAM-1)and Soluble Vascular Cell Adhesion Molecule-1(sVCAM-1)are soluble forms of ICAM-1 and VCAM-1.Research has found that sICAM-1 levels are independently associated with frailty in community populations,while sVCAM-1 levels are associated with cerebral blood flow dysregulation,slow walking speed,and falls in the elderly.Moreover,ICAM-1 and VCAM-1 may play important roles in ACS and frailty by participating in chronic inflammation and endothelial dysfunction.However,there are currently no reports on whether ICAM-1 and VCAM-1 affect and how they affect frailty in elderly patients with ACS.Objective:The study aims to explore the relationship between sICAM-1,sVCAM-1 and nonsevere frailty in elderly patients with ACS,and to elucidate their impact and role in nonsevere frailty among patients with ACS.The goal is to facilitate early identification and intervention,providing potential targets for adjunctive therapy in treating ACS patients with non-severe frailty,ultimately improving the prognosis of elderly patients with ACS.Methods:We enrolled 146 elderly patients with ACS who were hospitalized in the Department of Cardiology,the Second Hospital of Jilin University from July 2023 to December 2023.We collected basic clinical data,laboratory and examination data of the patients,and obtained fasting peripheral blood samples on the day of admission or on the next day.The serum levels of sICAM-1 and sVCAM-1 were measured by using enzyme-linked immunosorbent assay.Frailty was assessed by using the 7-point Clinical Frailty Scale(CFS),and according to which our patients were categorized into nonfrailty group(CFS score ≤ 4)and frailty group(CFS score ≥ 5).Within the frailty group,patients were further classified into mild frailty group(CFS score = 5)and moderate frailty group(CFS score = 6).Statistical analysis was conducted using SPSS 29.0software.First of all,we analyzed the prevalence of frailty in elderly patients with ACS.After that we compared the differences in basic clinical data,laboratory and examination data among different groups.Then we compared the differences in sICAM-1,sVCAM-1 levels among the groups and analyzed the correlation between sICAM-1,sVCAM-1 levels and CFS scores.Furthermore,we investigated the independent influencing factors for non-severe frailty and assessed the predictive value of sICAM-1,sVCAM-1 for diagnosing non-severe frailty in elderly ACS patients.Results:1.Condition of Frailty in Elderly Patients with ACSThe study involved 146 patients in total,of which 80 patients were non-frail and66 patients were frail.Therefore,the prevalence of frailty was 45.2% in elderly patients with ACS,among which 48 patients(32.9%)were classified as mild frailty and 18patients(12.3%)as moderate frailty.2.Comparison of Basic Clinical Data,Laboratory and Examination Data between Groups in Elderly Patients with ACSCompared to non-frail patients,frail patients exhibited statistically significant differences in age,total cholesterol and Gensini score(P < 0.05),while there were no statistically significant differences observed in other aspects(P > 0.05).The comparison among subgroups indicated that the differences in marital status,hemoglobin(HGB),hematocrit(Hct),and Gensini score were statistically significant(P < 0.05),while there were no differences in other aspects(P > 0.05).Pairwise comparisons among the groups revealed that HGB and Hct were lower in the moderate frailty group compared to the mild-frailty group.However,there were no differences observed in HGB,Hct between pairwise comparisons of the other groups.Additionally,the Gensini score was higher in the moderate frailty group compared to the non-frailty group,while there were no statistically significant differences in the comparisons between other groups.3.The Relationship between sICAM-1,sVCAM-1 and Non-severe Frailty in Elderly Patients with ACSCompared to non-frail patients,frail patients exhibited higher levels of sICAM-1(74.437 μg/d L vs 56.318 μg/d L,P < 0.001)and sVCAM-1(92.339 μg/d L vs 57.516μg/d L,P < 0.001).The comparison among subgroups indicated that the levels of sICAM-1 and sVCAM-1 among the subgroups were not entirely equal,and the differences were statistically significant(P <0.05).Pairwise comparisons among the three groups revealed that both the mild and moderate frailty groups exhibited significantly higher levels of sICAM-1 and sVCAM-1 compared to the non-frailty group.However,there were no differences observed in comparisons between the mild and moderate frailty groups.The results of Spearman correlation analysis indicated a moderate correlation between the levels of sICAM-1,sVCAM-1 with CFS scores(r=0.433,P<0.001;r=0.418,P<0.001).After adjusting for confounding factors,the binary logistic regression analysis revealed elevated levels of sICAM-1 and sVCAM-1 are associated with an increased risk of non-severe frailty(OR=1.050,P <0.001;OR=1.017,P <0.001).4.Predictive Value of sICAM-1 and sVCAM-1 for Non-severe Frailty in Elderly Patients with ACSThe results of ROC curve showed the area under the curve(AUC)for sICAM-1was 0.741(95% CI=0.660～0.822,P <0.001)in diagnosing non-severe frailty,with a sensitivity of 0.515,specificity of 0.887,and a maximum Youden index of 0.403 at the optimal cut-off value of 78.343 μg/d L.Similarly,the AUC for sVCAM-1 was 0.707(95% CI=0.623～0.791,P < 0.001),with a sensitivity of 0.545,specificity of 0.800,and a maximum Youden index of 0.345 at the optimal cut-off value of 85.370 μg/d L.The combined diagnostic value of sICAM-1 and sVCAM-1 for non-severe frailty had an AUC of 0.805(95% CI=0.734～0.877,P < 0.001),with sensitivity and specificity of0.652 and 0.875,and a maximum Youden index of 0.527.Thus,the combined use of sICAM-1 and sVCAM-1 demonstrated higher diagnostic value for non-severe frailty in elderly patients with ACS.Conclusion:1.sICAM-1 and sVCAM-1 are associated with non-severe frailty in elderly patients with ACS,and both of them may be independent risk factors for non-severe frailty in elderly patients with ACS.Moreover,Higher levels of sICAM-1 and sVCAM-1 are associated with greater severity of frailty.2.Both sICAM-1 and sVCAM-1 have predictive value in diagnosing non-severe frailty in elderly patients with ACS,and their combined application has superior predictive value.更多还原