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Atherosclerotic Reference Segments Affect the Progression and Process of Remodeling in Patients with Acute Coronary Syndrome: A Static Approach Study by Intravascular Ultrasound
Author: ZhuQing
Tutor: KangWeiQiang;GeZhiMing
School: Shandong University
Course: Internal Medicine
Keywords: Atherosclerotic reference segments artery remodeling acute coronary syndrome static approach study IVUS acute coronary syndrome IVUS DM patient with CHD intravascular ultrasound-virtual histology glycated serum album vulnerable plaques
CLC: R541.4
Type: PhD thesis
Year: 2011
Downloads: 31
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Abstract
BackgroundHistological studies have revealed that human coronary arterial may enlarge as atherosclerotic plaque grows. The artery wall tends to undergo adaptive remodeling in such a manner as to maintain stable flow and tensile stress. Glagov et al. demonstrated positive remodeling help to preserve lumen size when plaque area occupied less than 40 percent of the arterial cross-sectional area (CSA). In contrast, negative remodeling can shrink the internal elastic lamina (IEL) area at the site of lesion. In vivo studies using intravascular ultrasound (IVUS' dissertation">IVUS) method have also confirmed such arterial remodeling,extending its conception in cardiovascular event. Positive remodeling was regarded as the unstable lesion,characterized by a high lipid content and macrophage count, leading to easier rupture of the plaque [8,9]However, the natural process of artery remodeling is not fully understood due to the lack of complete in vivo serial approach. Qualitative and quantitative artery remodeling may not be consummated by IVUS or non-invasion techniques. In fact, IVUS cannot identify the IEM and the intima, and the remodeling index is limited with IVUS by stated approach because reference site may present remodeling. According to the 2001 consensus,positive remodeling is termed to define the increased external elastic membrane (EEM), while the process of EEM diminishing is termed as negative remodeling. As the original Glagov’s phenomenon, positive remodeling could almost compensate the reduced lumen area due to a process of "shrinkage" of the wall of affected vessel. However, it has not been tried to assess artery remodeling according to lumen by angiography, which is common and easy. In a variety of clinical settings, the relationship among plaque burden, EEM and lumen are still in debate.Objectives1. This IVUS static approach study presents a group of severe lesions in 103 acute coronary syndrome' dissertation">acute coronary syndrome (ACS) patients with time selecting operation.2. We investigated the atheroma burden of reference sites in order to understand atherosclerosis progression and process of remodeling.Methods1. Patients This study is a prospective, single center, and non-randomized trial from June 2005 to May 2008. The local institutional ethics committee approved the protocol, and informed consent was obtained from all patients and their relatives. The 103 consecutively enrolled patients with ACS underwent coronary artery angiography and IVUS with time selecting operation. The diagnosis of acute myocardial infarction (AMI) was defined as elevation of at least one of the positive biomarkers (creatine kinase-CK, CK-MB, and troponin I or T), characteristic electrocardiogram changes and a history of prolonged acute chest, epigastric, neck, jaw, or arm pain. Unstable angina (UA) was defined as either angina with a progressive crescendo pattern or angina that occurred at rest. All patients were treated with aspirin, glonoine, heparin and calcium orβ-receptor blocker. Patients receiving thrombolytic therapy were excluded from the study.2. IVUS imagingThe IVUS examinations were performed before percutaneous coronary intervention (PCI). The position of the lesion was defined using a dedicated image-in-image system (Siemens Angiostar, Germany). Between one and three arterial segments with stenosis were analyzed, as far as possible, to observe non-targeted plaques more than 20mm from the target site. The IVUS system was VOLCANO console (Volcano Corporation, version 4.2, USA). In brief, after intra-coronary administration of 0.2mg nitroglycerin, a transducer consisting of a rotating 20MHz transducer within a 2.9F imaging sheath was placed on the target artery. To reach the lesion, the IVUS catheter was carried by motorized transducer pullback system (0.5mm/s) until the aorto-ostial junction, and located at least 10mm distal or proximal from the target lesion and prior to any balloon inflation. Only during transducer pullback, the images were recorded onto high-resolution S-VHS videotape for offline analysis.2.1 IVUS analysisIVUS imaging was analyzed using a Medvision-2.06 Workstation. Measurements of EEM and plaque cross section area (EEM CSA-lumen CSA) were performed as previously described. The remodeling index (RI) was defined as lesion EEM CSA divided by the mean reference EEM CSA at the culprit vessel. Lesions with RI values equal or more than 1 were defined as positive remodeling, while those with RI value less than 1 were defined as negative remodeling. Plaque burden was calculated as (plaque CSA/EEM CSA)×100%. Soft plaque was classified when over 75 percent of the plaque was less bright than the adventitia. Calcium was bright than the adventitia with acoustic shadowing, and the arc of calcium was measured with a protractor centered on the lumen.2.2 Statistical methodAnalysis was performed with SPSS11.5 (SPSS Inc, Chicago) for Windows (Microsoft). The continuous data were expressed as mean±SD. Comparison between two remodeling groups was conducted using Student’s t test. Categorical variables were compared by chi-square test. Paired t test was applied to compare the difference between distal and proximal references, and between lesion and reference. The relationship between two variables was compared using linear regression analysis. Multivariate logistic regression analysis was performed to identify independent factors of the artery remodeling.2-sided values of P< 0.05 were considered statistically significant.Results1.Clinical characteristicsA total of 103 patients with 103 target plaques were analyzed in this study. Patients were divided into two groups according to RI values:RI≥1 group (67 cases) and RI<1 group (36 cases). There were significant differences in age, gender, hypertension history and DM history between the two groups. Moreover, single-vessel lesions were more popular in RI>1 group, while the frequency of three-vessel lesions were higher in RI<1 group. No significant alterations were detected in smoking status, AMI value, plaque rupture and soft plaque between two groups (Table 1). The multivariable linear regression analysis showed that age was an independent predictor of RI (Bate -0.37, 95% CI 0.93-1.08, P=0.04).2.Plaque morphology and RIAlmost all patients had severe diffuse atherosclerotic lesions, except one patient had no plaque at reference sites. In the analysis of 103 lesions and 102 reference sites, there was no significant difference in plaque burden, plaque CSA, Lumen CSA and Lesion EEM CSA between two groups (Table2). Lumen/Average lumen CSA was counted and there was no significant change (0.50±0.16 at RI≥1 vs 0.39±0.16 at RI<1,P=0.76).3. Distal and proximal referenceThe results of comparison between reference shown that distal plaque burden (39.76±12.54% vs.32.38±13.97%, P<0.001) and plaque CSA (6.14±3.20mm2 vs.4.75±3.07mm2, P=0.001) were larger than those at proximal reference. EEM CSA at distal reference was smaller than the proximal one (14.99±4.12 mm2 vs.28.37±4.48 mm2, P<0.001). Besides EEM CSA, these parameters also presented positive correlation between distal and proximal reference sites (Table 3).4. Comparison between lesion and referencesBecause one case had no plaque at references, only 102 patients were analyzed. The lesion lumen areas were diminished to references (71.76±9.17%,39.76±12.54%, 32.38±13.9, respectively, P<0.001). Plaque burdens at lesion were larger than those at references (3.81±1.09 mm2,8.91±2.43 mm2,9.03±2.16 mm2, P<0.001). EEM CSA of lesion was significantly increased when compared to proximal reference, but EEM CSA did not show statistical difference between lesion and distal reference (314.71±2.89mm2*,14.99±4.12mm2,28.37±4.48mm2*, respectively,*P<0.001). These results are summarized Figure 4.5. The relationship between diminished lumen and enlarged EEMEEM CSA of lesion was significantly increased when compared to proximal reference (14.71±2.89mm2 vs.28.37±4.48mm2, P<0.001, paired t test), but EEM CSA did not show statistical difference between lesion and distal reference. The lesion lumens were the same to the lumens of reference in 5 patients, while lesion lumens were diminished to reference in the other patients (3.81±1.09mm2, P<0.001, comparing to references with paired t test). There was no a significant correlation between lumen/average lumen CSA and RI (r=0.38, P=0.07). Plaque burden related to RI (r=-0.84, P<0.001). EEM CSA (r=0.64, P<0.001) and lumen CSA (r=-0.74, P<0.001) (Figure 1). Lumen/average lumen CSA related to both plaque burden and Lumen (respectively, r=-0.85, P< 0.001; r=-0.72, P=0.004). There were no statistical relation between RI and the other parameters (Table 4).Conclusions1) The reference segments lay a severe diffuse atherosclerosis in the ACS patients, suggesting atherosclerotic reference may complicate the estimation of remodeling direction. The static approach may not reflect the dynamic remodeling response. 2) The reference disease may be early atherosclerosis, and dilative EEM CSA is related to the course of disease and plaque burden.3) Both EEM and lumen CSA were related to plaque burden at lesion, But RI was not related to plaque burden, EEM CSA and lumen CSA at lesion. The ratio of stenosis was associated with plaque burden and lumen CSA.4) The ratio of lumen CSA at lesion/average lumen CSA at references may be an important index to estimate artery plaque-dependent remodeling. BackgroundHistological studies have revealed that human coronary arterial may enlarge as atherosclerotic plaque grows. The artery wall tends to undergo adaptive remodeling in such a manner as to maintain stable flow and tensile stress [1,2]. Glagov et al. demonstrated positive remodeling help to preserve lumen size when plaque area occupied less than 40 percent of the arterial cross-sectional area (CSA). In contrast, negative remodeling can shrink the internal elastic lamina (IEL) area at the site of lesion1. In vivo studies using intravascular ultrasound (IVUS) method have also confirmed such arterial remodeling [3,4], extending its conception in cardiovascular event. Positive remodeling was regarded as the unstable lesion [5,6], characterized by a high lipid content and macrophage count [7], leading to easier rupture of the plaque [8,9].However, the natural process of artery remodeling is not fully understood due to the lack of complete in vivo serial approach. Qualitative and quantitative artery remodeling may not be consummated by IVUS or non-invasion techniques. In fact, IVUS cannot identify the IEM and the intima, and the remodeling index is limited with IVUS by stated approach because reference site may present remodeling [10]. According to the 2001 consensus [11], positive remodeling is termed to define the increased external elastic membrane (EEM), while the process of EEM diminishing is termed as negative remodeling. As the original Glagov’s phenomenon, positive remodeling could almost compensate the reduced lumen area due to a process of "shrinkage" of the wall of affected vessel [12]. However, it has not been tried to assess artery remodeling according to lumen by angiography, which is common and easy. In a variety of clinical settings, the relationship among plaque burden, EEM and lumen are still in debate.Objectives1. This IVUS static approach study presents a group of severe lesions in 103 acute coronary syndrome (ACS) patients with time selecting operation.2. We investigated the atheroma burden of reference sites in order to understand atherosclerosis progression and process of remodeling.Methods1. PatientsThis study is a prospective, single center, and non-randomized trial from June 2005 to May 2008. The local institutional ethics committee approved the protocol, and informed consent was obtained from all patients and their relatives. The 103 consecutively enrolled patients with ACS underwent coronary artery angiography and IVUS with time selecting operation. The diagnosis of acute myocardial infarction (AMI) was defined as elevation of at least one of the positive biomarkers (creatine kinase-CK, CK-MB, and troponin I or T), characteristic electrocardiogram changes and a history of prolonged acute chest, epigastric, neck, jaw, or arm pain. Unstable angina (UA) was defined as either angina with a progressive crescendo pattern or angina that occurred at rest. All patients were treated with aspirin, glonoine, heparin and calcium or P-receptor blocker. Patients receiving thrombolytic therapy were excluded from the study.2. IVUS imagingThe IVUS examinations were performed before percutaneous coronary intervention (PCI). The position of the lesion was defined using a dedicated image-in-image system (Siemens Angiostar, Germany). Between one and three arterial segments with stenosis were analyzed, as far as possible, to observe non-targeted plaques more than 20mm from the target site. The IVUS system was VOLCANO console (Volcano Corporation, version 4.2, USA). In brief, after intra-coronary administration of 0.2mg nitroglycerin, a transducer consisting of a rotating 20MHz transducer within a 2.9F imaging sheath was placed on the target artery. To reach the lesion, the IVUS catheter was carried by motorized transducer pullback system (0.5mm/s) until the aorto-ostial junction, and located at least 10mm distal or proximal from the target lesion and prior to any balloon inflation. Only during transducer pullback, the images were recorded onto high-resolution S-VHS videotape for offline analysis.3. IVUS analysisIVUS imaging was analyzed using a Medvision-2.06 Workstation. Measurements of EEM and plaque cross section area (EEM CSA-lumen CSA) were performed as previously described [11]. The remodeling index (RI) was defined as lesion EEM CSA divided by the mean reference EEM CSA at the culprit vessel. Lesions with RI values equal or more than 1 were defined as positive remodeling, while those with RI value less than 1 were defined as negative remodeling. Plaque burden was calculated as (plaque CSA/EEM CSA)×100%. Soft plaque was classified when over 75 percent of the plaque was less bright than the adventitia. Calcium was bright than the adventitia with acoustic shadowing, and the arc of calcium was measured with a protractor centered on the lumen.4. Statistical methodAnalysis was performed with SPSS11.5 (SPSS Inc, Chicago) for Windows (Microsoft). The continuous data were expressed as mean±SD. Comparison between two remodeling groups was conducted using Student’s t test. Categorical variables were compared by chi-square test. Paired t test was applied to compare the difference between distal and proximal references, and between lesion and reference. The relationship between two variables was compared using linear regression analysis. Multivariate logistic regression analysis was performed to identify independent factors of the artery remodeling.2-sided values of P< 0.05 were considered statistically significant.Results1. Clinical characteristicsA total of 103 patients with 103 target plaques were analyzed in this study. Patients were divided into two groups according to RI values:RI>1 group (67 cases) and RI<1 group (36 cases). There were significant differences in age, gender, hypertension history and DM history between the two groups. Moreover, single-vessel lesions were more popular in RI>1 group, while the frequency of three-vessel lesions were higher in RI<1 group. No significant alterations were detected in smoking status, AMI value, plaque rupture and soft plaque between two groups (Tablel). The multivariable linear regression analysis showed that age was an independent predictor of RI (Bate-0.37, 95% CI 0.93-1.08,P=0.04).2. Plaque morphology and RI Almost all patients had severe diffuse atherosclerotic lesions, except one patient had no plaque at reference sites. In the analysis of 103 lesions and 102 reference sites, there was no significant difference in plaque burden, plaque CSA, Lumen CSA and Lesion EEM CSA between two groups (Table2). Lumen/Average lumen CSA was counted and there was no significant change (0.50±0.16 at RI≥1 vs 0.39±0.16 at RI<1,P=0.76).3. Distal and proximal referenceThe results of comparison between reference shown that distal plaque burden (39.76±12.54% vs.32.38±13.97%, P<0.001) and plaque CSA (6.14±3.20mm2 vs.4.75±3.07mm2, P=0.001) were larger than those at proximal reference. EEM CSA at distal reference was smaller than the proximal one (14.99±4.12 mm2 v5.28.37±4.48 mm2, P<0.001). Besides EEM CSA, these parameters also presented positive correlation between distal and proximal reference sites (Table 3).4. Comparison between lesion and referencesBecause one case had no plaque at references, only 102 patients were analyzed. The lesion lumen areas were diminished to references (71.76±9.17%,39.76±12.54%, 32.38±13.9, respectively,P<0.001). Plaque burdens at lesion were larger than those at references (3.81±1.09 mm2,8.91±2.43 mm2,9.03±2.16 mm2, P<0.001). EEM CSA of lesion was significantly increased when compared to proximal reference, but EEM CSA did not show statistical difference between lesion and distal reference (314.71±2.89mm2*,14.99±4.12mm2,28.37±4.48mm2*,respectively,*P<0.001). These results are summarized Figure 4.5. The relationship between diminished lumen and enlarged EEMEEM CSA of lesion was significantly increased when compared to proximal reference (14.71±2.89mm2 vs.28.37±4.48mm2,P<0.001, paired t test), but EEM CSA did not show statistical difference between lesion and distal reference. The lesion lumens were the same to the lumens of reference in 5 patients, while lesion lumens were diminished to reference in the other patients (3.81±1.09mm2,P<0.001, comparing to references with paired t test). There was no a significant correlation between lumen/average lumen CSA and RI (r=0.38, P=0.07). Plaque burden related to RI (r=-0.84,P<0.001). EEM CSA (r=0.64, P<0.001) and lumen CSA (r=-0.74, P<0.001) (Figure 1). Lumen/average lumen CSA related to both plaque burden and Lumen (respectively, r=-0.85, P< 0.001; r=-0.72, P=0.004). There were no statistical relation between RI and the other parameters(Table 4).Conclusions1) The reference segments lay a severe diffuse atherosclerosis in the ACS patients, suggesting atherosclerotic reference may complicate the estimation of remodeling direction. The static approach may not reflect the dynamic remodeling response. 2) The reference disease may be early atherosclerosis, and dilative EEM CSA is related to the course of disease and plaque burden.3) Both EEM and lumen CSA were related to plaque burden at lesion, But RI was not related to plaque burden, EEM CSA and lumen CSA at lesion. The ratio of stenosis was associated with plaque burden and lumen CSA.4) The ratio of lumen CSA at lesion/average lumen CSA at references may be an important index to estimate artery plaque-dependent remodeling. To investigate the atherosclerotic reference segments impact on progression and process of remodeling in patients with acute coronary syndrome (ACS),103 patients with ACS were identified by intravascular ultrasound (IVUS) in a static approach study. Remodeling index (RI) (67 cases of RI≥1 vs 36 cases of RI<1) were compared, and the relationships among age, gender, history of hypertension & DM and arterial remodeling were analyzed. By compared between lesion and references, distal reference and proximal reference, by focus on plaque morphology and RI, and the relationship between diminished lumen and enlarged EEM, This study revealed that reference segments lay a severe diffuse atherosclerosis in the group of ACS, The ratio of lumen CSA at lesion/average lumen CSA at references maybe a important index to estimate artery plaque-dependent remodeling. ObjectiveTo analysis the tissue characteristics of the atherosclerotic plaques in DM-CHD patients by intravascular ultrasound-virtual histology (IVUS-VH)and discuss their clinical correlates with glycated serum album and HbAlc.MethodsIn 53 DM-CHD patients and 49 CHD patients, culprit lesions were detected with IVUS-VH to investigate the characteristics of the atherosclerotic plaque and its clinical relevance with glycated serum album and HbAlc.ResultsDM-CHD patients presented a significantly higher prevalence of vulnerable plaques than CHD patients(P< 0.05), with a clear clustering pattern, consisted mainly of fibro-fatty tissue and necrotic core-rich tissue。There were higher levels of fibrous tissue and dense calcium tissue in CHD patients compared with DM-CHD patients. There is much higher relevance between fibro-fatty tissue and glycated serum album than that between fibro-fatty tissue and HbAlc.ConclusionAs shown by IVUS-VH, the prevalence of vulnerable plaque in DM-CHD patients was much higher than that in CHD patients, coupled with different intra-plaque composition, which was associated with glycated serum album level.
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CLC: > Medicine, health > Internal Medicine > Heart, blood vessels ( circulatory ) disease > Heart disease > Coronary arteries ( atherosclerosis ),heart disease (CHD)
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