ABI运动实验（Bruce方案）评估PAD高危患者下肢动脉粥样硬化病变的临床诊断价值研究
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摘要
背景
周围动脉硬化性疾病(PAD)是全身动脉粥样硬化的一个重要标记,被认为是冠心病的等危症,与心血管疾病(CVD)的发生和死亡密切相关,是亚临床冠心病的重要标记。随着动脉粥样硬化性疾病临床防治重心的前移,针对PAD下肢动脉粥样硬化的早期病变情况进行评估,对PAD的及早预防、减缓全身动脉硬化危害将具有重要临床价值。综观目前PAD相关诊断技术,尚无针对PAD早期病变的理想诊断技术。运动平板试验作为动态客观观察运动负荷情况下血管功能反应的敏感工具,对血流动力学意义的动脉狭窄的诊断具有重要意义,即对动脉粥样硬化的早期病变的评估具有重要临床价值。
目的
本课题针对PAD高危人群,观察该人群下肢动脉粥样硬化及动脉硬化病变情况,并评估踝臂指数(ABI)运动实验在诊断PAD高危人群下肢动脉粥样硬化病变情况的临床价值研究。
方法
1.随机选取331例PAD高危人群为研究对象,采用欧姆龙vp-1000检测ABI,同一周内完成下肢动脉超声检查。依据ABI值将研究人群分为临界低值组(ABI：0.91～0.99)、临界中值组(ABI：1.0～1.09)、临界高值组(ABI：1.1～1.29)及高值组(ABI≥1.3),据下肢动脉超声结果分析不同ABI值组患者的下肢动脉病变情况。2.随机选取173例ABI≥1的PAD高危人群为研究对象,采用欧姆龙vp-1000检测ABI、肱动脉-踝脉搏波速度(baPWV)、上行主动脉-踝脉搏波速度(haPWV)等动脉硬化相关指标,并于同一周内完成下肢动脉超声检查,以下肢动脉粥样硬化病变的不同程度进行分组,采用ANOVA方差分析,比较各组之间动脉硬化程度的差异性。
3.随机选取33例正常人群及236例PAD高危人群,同一周内完成运动平板试验(Bruce方案)、ABI检测及下肢动脉超声检查。以运动平板试验结束后1min ABI值变化情况分为ABI下降≥20%组、ABI下降≤20%组及ABI升高组。以正常人群为对照,分析比较三组人群的危险因素、运动后下肢血流动力学变化状态及各组下肢动脉粥样硬化的病变特点。
4.随机选取173例PAD高危人群,同一周内完成运动平板试验(Bruce方案)、ABI检测及下肢动脉超声检查。以下肢动脉超声结果为诊断标准,分析ABI运动试验诊断下肢动脉粥样硬化早期病变的敏感性、特异性、阳性似然比及阴性似然比,并采用ROC曲线评价其临床诊断价值。
结果
1.PAD高危人群中,57.7%患者下肢动脉均有不同程度的粥样硬化病变。临界低值组患者主要以动脉粥样斑块(Ⅲ级和Ⅳ级病变,67.7%)为主,而临界高值组患者以弥漫性病变(Ⅱ级病变,43.8%)为主,并且两组患者内中膜增厚比例均显著增高(p<0.05)；
2.临界低值组、临界中值组及临界高值组患者的下肢动脉粥样硬化病变位点以膝上动脉病变为主(84.2%,78.6%及79.7%),而高值组患者以膝下动脉病变为主(57.1%)；
3.无内中膜增厚组与内中膜增厚组患者baPWV、haPWV、脉压、踝压均无显著性差异(p>0.05)；
4.与无动脉粥样硬化病变组比较,弥漫性斑点状病变组与小粥样斑块(面积<20mm2)组的baPWV、haPWV显著增高(p<0.05),小斑块组的脉压显著增高(p<0.05),而大斑块(面积≥20 mm2)组的各个动脉硬化指标均无统计学差异(p>0.05)；
5.PAD高危人群进行ABI运动实验,运动结束后1min,ABI变化表现为ABI下降≥20%、ABI下降<20%及ABI升高。ABI下降≥20%患者运动后lmin及至恢复10min时踝压仍持续下降,该组患者下肢动脉的动脉粥样硬化病变程度最为严重,主要以动脉粥样硬化大斑块(面积>20mm2)病变为主(53.8%)。ABI升高的患者在运动后1minABI值及踝压均增高,且恢复10mi n时ABI值仍持续增高,该组患者下肢动脉病变主要以弥漫性点状病变为主(60.0%)。ABI下降<20%组病变主要表现为内中膜增厚(55.6%)；
6.PAD高危人群中下肢动脉存在病变的患者,运动后ABI值均有所下降,但随着下肢动脉粥样硬化病变的加重,运动后ABI下降的幅度越大。分别以下肢动脉存在动脉粥样硬化Ⅳ级(大斑块病变,面积>20mm2)、Ⅲ级(存在动脉粥样硬化斑块)及Ⅱ级(存在动脉粥样硬化病变)为阳性诊断标准,R值的ROC曲线下面积分别为0.802(95%CI,0.722,0.882)、0.78(95%CI,0.708,0.852)及0.599(95%CI,0.44,0.757)；
7.以下肢动脉粥样硬化大斑块病变(面积>20mm2)为阳性诊断,R值为0.8时,其敏感性54.0%,特异性96.7%,LR+为16.4,LR-为0.58,R值为0.85时,其敏感性70.0%,特异性91.9%,LR+为8.64,LR-为0.33；
8.173例PAD高危人群进行运动平板实验,同时检出心肌缺血阳性患者31例(占总人群的17.9%),其中既往无冠心病患者有15例(占总人群的8.6%,占阳性患者的48.4%),检出可疑存在心肌缺血患者有24例(占总人群的13.9%),其中既往无冠心病患者17例(占总人群9.8%,占可疑阳性患者的70.8%),发生室性心律失常者6例(3.5%)(1例为短阵室性心动过速,占总人群的0.6%),常规救治后迅速缓解,其余5例均为室早二联律(占总人群的2.9%)。
结论
1.PAD高危人群中57.7%的患者下肢动脉存在不同程度的动脉粥样硬化病变。其中临界低值组及高值组患者下肢动脉粥样硬化病变程度重,临界低值组患者主要以动脉粥样斑块(Ⅲ级和Ⅳ级病变)为主,病变位点主要位于股总动脉膝以上动脉,该组人群的危险因素主要为吸烟、吸烟程度,合并疾病主要有冠心病、高血压及糖尿病,这些均是动脉粥样斑块病变的主要危险因素及主要病变基础；而高值患者中以弥漫性病变(Ⅱ级病变)为主,病变位点主要位于膝以下远端动脉。并且两组人群的IMT增厚比例均显著增高。该组人群的危险因素及合并疾病为男性、吸烟程度、糖尿病、高血压,它们均是全身系统血管动脉硬化病变的危险因素及病变基础。因此,临床医生应对ABI值处于临界低值及高值的患者引起高度重视,并针对不同的危险因素及病变基础,及早采取不同的预防措施。
2.以动脉粥样硬化的代表性检测指标内中膜增厚为依据,有无内中膜增厚两组人群的各项动脉硬化指标baPWV、haPWV、脉压、踝压之间均无显著性差异,提示动脉硬化指标不能明确动脉粥样硬化指标—内中膜增厚病变程度；以下肢动脉粥样硬化斑块的病变程度分组,弥漫性斑点状病变组与小斑块组的baPWV、haPWV显著增高,然而大斑块组即下肢动脉粥样硬化病变程度相对最重的一组,所有动脉硬化指标与无病变组均无显著性差异,提示动脉硬化指标增高有助于检测出极早期动脉粥样硬化病变(如弥漫性病变或小斑块病变),但对较重的早期动脉粥样硬化病变(如斑块面积大于20mm2以上,存在动脉狭窄有血流动力学意义的早期动脉粥样硬化病变)预测价值甚微,因此,动脉硬化指标有助于预测动脉粥样硬化的极早期病变,但对于较重病变(如大斑块病变,面积>20mm2),其预测价值不高。临床医生对于动脉硬化检测指标结果正常的患者,不应认为不存在动脉粥样硬化病变,而应结合危险因素及临床症状作出综合科学的临床评估。
3.PAD高危人群运动试验后1min ABI下降≥20%的患者,下肢动脉病变表现为动脉粥样硬化性病变,且程度最为严重,和要以动脉粥样硬化大斑块(面积>20mm2)病变为主；运动后1min ABI升高的患者下肢动脉病变主要以弥漫性点状病变为主,提示该组人群动脉硬化程度高。可见,PAD高危人群进行ABI运动实验,不仅能够检测出下肢动脉存在大粥样硬化斑块(面积>20mm2)的人群,而且可以检测出动脉硬度增高,需加强改善动脉弹性治疗的人群。
4.PAD高危人群随着下肢动脉粥样硬化病变的加重,运动后ABI下降的幅度越大。分别以下肢动脉存在动脉粥样斑块面积>20mm2的大斑块、存在动脉粥样斑块及存在动脉粥样病变为阳性诊断标准,依据ROC曲线下面积值,显示ABI运动实验对下肢动脉存在粥样斑块>20mm2大斑块的病变诊断准确性最高,可以作为检测下肢动脉粥样硬化早期病变较为准确的客观工具。而且,R值为0.85作为ABI运动实验诊断下肢动脉粥样硬化大斑块病变(面积>20mm2)的阂值为宜。
5.ABI运动实验对PAD高危人群下肢动脉粥样硬化病变的评估不仅是一项非常安全可行的检测方法,还可以在评估下肢动脉粥样硬化病变的情况下,早期发现心肌缺血病变,可见,该检测方法对早期发现并及时预防全身动脉粥样硬化病变的发生发展能够提供重要临床依据。
Background
Peripheral atherosclerotic disease (PAD) is an important mark for systematic atherosclerosis, currently considered an equivalent to coronary heart disease. It is closely related with cardiovascular and cerebrovascular events. With the prevention and early treatment of atherosclerotic disease being emphasized clinically, the early diagnosis and management of atherosclerotic lesions of the lower extremity is important for preventing and treating PAD and mitigating systematic atherosclerotic lesions. So far, there is not ideal diagnosis method for diagnosing the early lesion of PAD. Exercise treadmill testing(ETT), as a sensitive tool to assess vascular reaction to workload in a dynamic, objective manner, may play an important role for diagnosing hemodynamic arteriostenosis, such as the early atherosclerotic lesion.
Objective
This study was to observe the lesion of atherosclerotic and arteriosclerosis in high-risk population for PAD and with their ABI value higher than or equal to 0.9, in additions, we prospectively evaluate the diagnostic value of ABI binding exercise treadmill testing (ETT) in assessing early atherosclerotic lesions of the lower extremity in this population.
Methods
1. A randomly enrolled cohort,331 high-risk patients for PAD with ABI value higher than or equal to 0.9, underwent simultaneously ABI testing and low extremity arterial duplex ultrasound within one week. According to the ABI value, they were divided into four groups:Borderline lower value (ABI:0.91～0.99), Borderline midvalue(ABI:1.0～1.09), Borderline higher value (ABI:1.1～1.29) and higher value group (ABI≥1.3). The manifestation of lower extremity atherosclerosis were determined based on the results of low extremity artery duplex ultrasound.
2. A randomly enrolled cohort,173 high-risk patients for PAD with ABI value higher than or equal to 1.0, underwent simultaneously ABI testing、brachial artery pulse wave velocity (baPWV)、up aorta PWV and low extremity arterial duplex ultrasound within one week. According to the result of lower extremity atherosclerosis, they were divided into different group, and were analysised their arteriosclerosis variability among those groups by the way of Analysis of Variance (ANOVA).
3. A randomly enrolled cohort,33 health patients and 236 high-risk patients for PAD, underwent simultaneously ETT (Bruce's proposal)、ABI test and low extremity arterial duplex ultrasound within one week. According to the change of ABI value at 1 min after ETT, they were divided into ABI descending greater than or equal to 20 per cent, ABI descending lower than 20 per cent and ABI elevating group. The normal population as control, we analyzed and compared the other three groups of risk factors, the hemodynamic changes after EET and the manifestation of lower extremity arterial atherosclerosis lesions.
4. A randomly enrolled cohort,173 high-risk patients for PAD, underwent simultaneously ETT (Bruce's proposal、ABI test and low extremity arterial duplex ultrasound within one week. The result of lower extremity arterial duplex as the diagnostic criteria, we analysized the sensitivity, specificity, positive likelihood ratio and negative likelihood ratio of ABI exercise test diagnosing the early atherosclerotic lesions in lower extremity, and assessed the clinical diagnostic value of ETT in diagnosing early atherosclerotic lesions of lower extremity by Receiver operator characteristics (ROC) analysis.
Results
1. Of 331 high-risk patients for PAD with ABI value higher than or equal to 0.9, 57.7% have different degrees of atherosclerosis in lower extremity artery. The atherosclerotic lesions of low extremities in Borderline lower value group mainly displayed large plaques causing reduction in luminal diameter (Ⅲgrade andⅣgrade of atherosclerosis,67.7%), while those in higher value group were mainly displayed as diffuse dot-like hyperechogenicity spots(Ⅱgrade,43.8%), furthermore, the incidence of intima-media thickness (IMT) in both groups were all significantly higher than other group (p<0.05);
2. In Borderline lower value, Borderline midvalue and Borderline higher value group, the atherosclerotic lesions all predominantly involved in the proximal segments of lower extremity artery (84.2%,78.6%2及79.7%), while, in higher value group, the atherosclerotic lesions predominantly involved in the distal segment of the lower extremity artery (57.1%);
3. There were no statistically significant differences on indictors such as baPWV, haPWV, pulse pressor and ankle pressor between patients with and without low limb artery intima-media thickness increasing (p>0.05)
4. Compared with no pathological changes group, the values of baPWV and haPWV in diffused pathological group and that in little atherosclerosis plaque group significantly increased (p<0.05),the values of pulse pressor of little atherosclerosis plaque group significantly increased (p<0.05), however, there were no statistically significant differences on indictors of arteries stiffness in large atherosclerosis plaque group (p>0.05);
5. After high-risk patients for PAD having undwent ABI exercise test, the ABI change showed ABI decreased up and equal to 20%(≥20%), lower than 20%(<20%) and elevated. The ankle pressure continued to decrease in patients with ABI declined≥20% after exercise lmin to 10min. The atherosclerotic lesion in this group was the most serious, mainly displayed large plaques (area> 20mm2) causing reduction in luminal diameter. While, the ABI value and ankle pressure in patients with ABI elevated were all increased at 1 min after exercise, and ABI value continued to increase, the atherosclerotic lesion in this group mainly displayed diffuse dot-like hyperechogenicity lesion (60.0%), whereas, the atherosclerotic lesion in ABI declined <20% group mainly displayed IMT (55.6%);
6. After exercise, ABI decreased in all patients. The more severe the atherosclerotic lesions of the lower extremity were, the larger the ABI decrement after exercise was. Ultrasonography was used as the standard in defining atherosclerotic lesions such as large, small plaques, and diffuse spotty atherosclerotic lesions, the respective areas under the ROC curve were 0.802 (95%CI,0.722,0.882),0.78 (95%CI,0.708,0.852), and 0.599 (95%CI,0.44,0.757);
7. Using the presence of large atherosclerotic plaques in lower extremities as positive diagnosis, R value was 0.8, with a sensitivity of 54.0%, a specificity of 96.7%, a LR+ of 16.4, and a LR- of 0.58, meanwhile, R value was 0.85, with a sensitivity of 70.0%, a specificity of 91.9%, a LR+ of 8.64, and a LR- of 0.33;
8. Of the 173 high-risk patients for PAD, the ETT result was positive in 31 patients (17.9% of the total population), among those, there were 15 cases of no previous diagnosis of coronary heart disease (8.6% of the total population, accounting for 48.4% of positive patients). while, the ETT result was suspected positive in 24 cases(13.9% of the total population), among those, there were 17 cases of no previous diagnosis of coronary heart disease (9.8% of the total population, accounting for 70.8% of suspected positive patients). Ventricular arrhythmia occurred in 6 patients (3.5%):one had paroxysmal ventricular tachycardia (0.6%), which disappeared after oxygen inhalation and sublingual administration of nitroglycerin, and the others had ventricular premature beats, i.e, bigeminy (2.9%).
Conclusions
1.57.7% of high-risk patients for PAD with ABI value higher than or equal to 0.9 have different degrees of atherosclerosis in lower extremity artery. Among those, the atherosclerotic lesion in Borderline lower value and High value groupp were the most serious. The atherosclerotic lesions of low extremities in Borderline lower value group mainly displayed large plaques (ⅢandⅣgrade lesion,67.7%), and predominantly involved in the proximal segments of lower extremity artery. Besides, the risk facotrs of patients mainly was atherosclerotic risk factors and the major atherosclerotic basis. However, The atherosclerotic lesions of low extremities in High value group mainly displayed as diffuse dot-like hyperechogenicity spots(II grade), and predominantly involved in the distal segment of the lower extremity artery. In additons, the risk factors in this group mainly was systemic atherosclerotic vascular disease risk factors. These findings suggest that the clinician should think highly of the patient with Borderline lower value and High value group, and positively take different prophylactic measures in time according to different risk factor and different pathological changes.
2. No statistically significant differences on indictors such as baPWV, haPWV, pulse pressor and ankle pressor between patients with and without IMT was observed, this founding suggests that the arteriosclerosis index can not define the IMT degree. Divided in the atherosclerotic lesions, the values of baPWV and haPWV in diffused pathological group and that in little atherosclerosis plaque group significantly increased, yet, there were no statistically significant differences in large atherosclerosis plaque group, these founds suggest that the atherosclerosis index increasing contributes to the early atherosclerotic lesions (such as diffuse disease or small plaque), but to heavier early atherosclerotic lesions, its predictive value was very low. These findings suggest that the clinician should not ignor the patients with the normal indicators of atherosclerosis, make a comprehensive and science evaluation combinating with risk factors and clinical symptoms.
3. The atherosclerotic lesions of high risk for PAD with ABI declined≥20% after exercise was the most serious, mainly deplayed large plaques (area> 20mn2); The atherosclerotic lesions of high risk for PAD with ABI elevated after exercise mainly deplayed the diffuse dot-like hyperechogenicity lesion, which suggests that the patient in this group has high degree of atherosclerosis. Obviously, the ABI exercise test can detect not only the existence of a large lower extremity arterial plaque(area> 20mm2), but also the increased arterial stiffness, these population should be strengthened to improve the arterial elasticity.
4. The more severe the atherosclerotic lesions of the lower extremity were, the larger the ABI decrement after exercise was. Respectively, the atherosclerotic lesions such as large, small plaques, and diffuse spotty atherosclerotic lesions, was used as the positive diagnostic criteriam, the result of ROC curve areas showed that the value of ABI exercise test for diagnosing large atherosclerotic plaque lesions of the lower extremity was very high, it can be used as an more accurate and objective tool to detect the early atherosclerotic lesions of the lower extremity. Besides, Immediately after exercise,0.85 is the cut-off R value appropriate for diagnosing large atherosclerotic plaques of the lower limb (area>20mm2).
5. ABI exercise test is a safe, effective tool for detecting early atherosclerotic lesions of the lower limb for high-risk for PAD, in additions, it can simultaneously detect the myocardial ischemia disease. Hence, the ABI exercise test can provide important clinical basis for early detection and timely prevention of systemic atherosclerotic disease occurrence and development.
周围动脉硬化性疾病(PAD)是全身动脉粥样硬化的一个重要标记,被认为是冠心病的等危症,与心血管疾病(CVD)的发生和死亡密切相关,是亚临床冠心病的重要标记。随着动脉粥样硬化性疾病临床防治重心的前移,针对PAD下肢动脉粥样硬化的早期病变情况进行评估,对PAD的及早预防、减缓全身动脉硬化危害将具有重要临床价值。综观目前PAD相关诊断技术,尚无针对PAD早期病变的理想诊断技术。运动平板试验作为动态客观观察运动负荷情况下血管功能反应的敏感工具,对血流动力学意义的动脉狭窄的诊断具有重要意义,即对动脉粥样硬化的早期病变的评估具有重要临床价值。
目的
本课题针对PAD高危人群,观察该人群下肢动脉粥样硬化及动脉硬化病变情况,并评估踝臂指数(ABI)运动实验在诊断PAD高危人群下肢动脉粥样硬化病变情况的临床价值研究。
方法
1.随机选取331例PAD高危人群为研究对象,采用欧姆龙vp-1000检测ABI,同一周内完成下肢动脉超声检查。依据ABI值将研究人群分为临界低值组(ABI：0.91～0.99)、临界中值组(ABI：1.0～1.09)、临界高值组(ABI：1.1～1.29)及高值组(ABI≥1.3),据下肢动脉超声结果分析不同ABI值组患者的下肢动脉病变情况。2.随机选取173例ABI≥1的PAD高危人群为研究对象,采用欧姆龙vp-1000检测ABI、肱动脉-踝脉搏波速度(baPWV)、上行主动脉-踝脉搏波速度(haPWV)等动脉硬化相关指标,并于同一周内完成下肢动脉超声检查,以下肢动脉粥样硬化病变的不同程度进行分组,采用ANOVA方差分析,比较各组之间动脉硬化程度的差异性。
3.随机选取33例正常人群及236例PAD高危人群,同一周内完成运动平板试验(Bruce方案)、ABI检测及下肢动脉超声检查。以运动平板试验结束后1min ABI值变化情况分为ABI下降≥20%组、ABI下降≤20%组及ABI升高组。以正常人群为对照,分析比较三组人群的危险因素、运动后下肢血流动力学变化状态及各组下肢动脉粥样硬化的病变特点。
4.随机选取173例PAD高危人群,同一周内完成运动平板试验(Bruce方案)、ABI检测及下肢动脉超声检查。以下肢动脉超声结果为诊断标准,分析ABI运动试验诊断下肢动脉粥样硬化早期病变的敏感性、特异性、阳性似然比及阴性似然比,并采用ROC曲线评价其临床诊断价值。
结果
1.PAD高危人群中,57.7%患者下肢动脉均有不同程度的粥样硬化病变。临界低值组患者主要以动脉粥样斑块(Ⅲ级和Ⅳ级病变,67.7%)为主,而临界高值组患者以弥漫性病变(Ⅱ级病变,43.8%)为主,并且两组患者内中膜增厚比例均显著增高(p<0.05)；
2.临界低值组、临界中值组及临界高值组患者的下肢动脉粥样硬化病变位点以膝上动脉病变为主(84.2%,78.6%及79.7%),而高值组患者以膝下动脉病变为主(57.1%)；
3.无内中膜增厚组与内中膜增厚组患者baPWV、haPWV、脉压、踝压均无显著性差异(p>0.05)；
4.与无动脉粥样硬化病变组比较,弥漫性斑点状病变组与小粥样斑块(面积<20mm2)组的baPWV、haPWV显著增高(p<0.05),小斑块组的脉压显著增高(p<0.05),而大斑块(面积≥20 mm2)组的各个动脉硬化指标均无统计学差异(p>0.05)；
5.PAD高危人群进行ABI运动实验,运动结束后1min,ABI变化表现为ABI下降≥20%、ABI下降<20%及ABI升高。ABI下降≥20%患者运动后lmin及至恢复10min时踝压仍持续下降,该组患者下肢动脉的动脉粥样硬化病变程度最为严重,主要以动脉粥样硬化大斑块(面积>20mm2)病变为主(53.8%)。ABI升高的患者在运动后1minABI值及踝压均增高,且恢复10mi n时ABI值仍持续增高,该组患者下肢动脉病变主要以弥漫性点状病变为主(60.0%)。ABI下降<20%组病变主要表现为内中膜增厚(55.6%)；
6.PAD高危人群中下肢动脉存在病变的患者,运动后ABI值均有所下降,但随着下肢动脉粥样硬化病变的加重,运动后ABI下降的幅度越大。分别以下肢动脉存在动脉粥样硬化Ⅳ级(大斑块病变,面积>20mm2)、Ⅲ级(存在动脉粥样硬化斑块)及Ⅱ级(存在动脉粥样硬化病变)为阳性诊断标准,R值的ROC曲线下面积分别为0.802(95%CI,0.722,0.882)、0.78(95%CI,0.708,0.852)及0.599(95%CI,0.44,0.757)；
7.以下肢动脉粥样硬化大斑块病变(面积>20mm2)为阳性诊断,R值为0.8时,其敏感性54.0%,特异性96.7%,LR+为16.4,LR-为0.58,R值为0.85时,其敏感性70.0%,特异性91.9%,LR+为8.64,LR-为0.33；
8.173例PAD高危人群进行运动平板实验,同时检出心肌缺血阳性患者31例(占总人群的17.9%),其中既往无冠心病患者有15例(占总人群的8.6%,占阳性患者的48.4%),检出可疑存在心肌缺血患者有24例(占总人群的13.9%),其中既往无冠心病患者17例(占总人群9.8%,占可疑阳性患者的70.8%),发生室性心律失常者6例(3.5%)(1例为短阵室性心动过速,占总人群的0.6%),常规救治后迅速缓解,其余5例均为室早二联律(占总人群的2.9%)。
结论
1.PAD高危人群中57.7%的患者下肢动脉存在不同程度的动脉粥样硬化病变。其中临界低值组及高值组患者下肢动脉粥样硬化病变程度重,临界低值组患者主要以动脉粥样斑块(Ⅲ级和Ⅳ级病变)为主,病变位点主要位于股总动脉膝以上动脉,该组人群的危险因素主要为吸烟、吸烟程度,合并疾病主要有冠心病、高血压及糖尿病,这些均是动脉粥样斑块病变的主要危险因素及主要病变基础；而高值患者中以弥漫性病变(Ⅱ级病变)为主,病变位点主要位于膝以下远端动脉。并且两组人群的IMT增厚比例均显著增高。该组人群的危险因素及合并疾病为男性、吸烟程度、糖尿病、高血压,它们均是全身系统血管动脉硬化病变的危险因素及病变基础。因此,临床医生应对ABI值处于临界低值及高值的患者引起高度重视,并针对不同的危险因素及病变基础,及早采取不同的预防措施。
2.以动脉粥样硬化的代表性检测指标内中膜增厚为依据,有无内中膜增厚两组人群的各项动脉硬化指标baPWV、haPWV、脉压、踝压之间均无显著性差异,提示动脉硬化指标不能明确动脉粥样硬化指标—内中膜增厚病变程度；以下肢动脉粥样硬化斑块的病变程度分组,弥漫性斑点状病变组与小斑块组的baPWV、haPWV显著增高,然而大斑块组即下肢动脉粥样硬化病变程度相对最重的一组,所有动脉硬化指标与无病变组均无显著性差异,提示动脉硬化指标增高有助于检测出极早期动脉粥样硬化病变(如弥漫性病变或小斑块病变),但对较重的早期动脉粥样硬化病变(如斑块面积大于20mm2以上,存在动脉狭窄有血流动力学意义的早期动脉粥样硬化病变)预测价值甚微,因此,动脉硬化指标有助于预测动脉粥样硬化的极早期病变,但对于较重病变(如大斑块病变,面积>20mm2),其预测价值不高。临床医生对于动脉硬化检测指标结果正常的患者,不应认为不存在动脉粥样硬化病变,而应结合危险因素及临床症状作出综合科学的临床评估。
3.PAD高危人群运动试验后1min ABI下降≥20%的患者,下肢动脉病变表现为动脉粥样硬化性病变,且程度最为严重,和要以动脉粥样硬化大斑块(面积>20mm2)病变为主；运动后1min ABI升高的患者下肢动脉病变主要以弥漫性点状病变为主,提示该组人群动脉硬化程度高。可见,PAD高危人群进行ABI运动实验,不仅能够检测出下肢动脉存在大粥样硬化斑块(面积>20mm2)的人群,而且可以检测出动脉硬度增高,需加强改善动脉弹性治疗的人群。
4.PAD高危人群随着下肢动脉粥样硬化病变的加重,运动后ABI下降的幅度越大。分别以下肢动脉存在动脉粥样斑块面积>20mm2的大斑块、存在动脉粥样斑块及存在动脉粥样病变为阳性诊断标准,依据ROC曲线下面积值,显示ABI运动实验对下肢动脉存在粥样斑块>20mm2大斑块的病变诊断准确性最高,可以作为检测下肢动脉粥样硬化早期病变较为准确的客观工具。而且,R值为0.85作为ABI运动实验诊断下肢动脉粥样硬化大斑块病变(面积>20mm2)的阂值为宜。
5.ABI运动实验对PAD高危人群下肢动脉粥样硬化病变的评估不仅是一项非常安全可行的检测方法,还可以在评估下肢动脉粥样硬化病变的情况下,早期发现心肌缺血病变,可见,该检测方法对早期发现并及时预防全身动脉粥样硬化病变的发生发展能够提供重要临床依据。
Background
Peripheral atherosclerotic disease (PAD) is an important mark for systematic atherosclerosis, currently considered an equivalent to coronary heart disease. It is closely related with cardiovascular and cerebrovascular events. With the prevention and early treatment of atherosclerotic disease being emphasized clinically, the early diagnosis and management of atherosclerotic lesions of the lower extremity is important for preventing and treating PAD and mitigating systematic atherosclerotic lesions. So far, there is not ideal diagnosis method for diagnosing the early lesion of PAD. Exercise treadmill testing(ETT), as a sensitive tool to assess vascular reaction to workload in a dynamic, objective manner, may play an important role for diagnosing hemodynamic arteriostenosis, such as the early atherosclerotic lesion.
Objective
This study was to observe the lesion of atherosclerotic and arteriosclerosis in high-risk population for PAD and with their ABI value higher than or equal to 0.9, in additions, we prospectively evaluate the diagnostic value of ABI binding exercise treadmill testing (ETT) in assessing early atherosclerotic lesions of the lower extremity in this population.
Methods
1. A randomly enrolled cohort,331 high-risk patients for PAD with ABI value higher than or equal to 0.9, underwent simultaneously ABI testing and low extremity arterial duplex ultrasound within one week. According to the ABI value, they were divided into four groups:Borderline lower value (ABI:0.91～0.99), Borderline midvalue(ABI:1.0～1.09), Borderline higher value (ABI:1.1～1.29) and higher value group (ABI≥1.3). The manifestation of lower extremity atherosclerosis were determined based on the results of low extremity artery duplex ultrasound.
2. A randomly enrolled cohort,173 high-risk patients for PAD with ABI value higher than or equal to 1.0, underwent simultaneously ABI testing、brachial artery pulse wave velocity (baPWV)、up aorta PWV and low extremity arterial duplex ultrasound within one week. According to the result of lower extremity atherosclerosis, they were divided into different group, and were analysised their arteriosclerosis variability among those groups by the way of Analysis of Variance (ANOVA).
3. A randomly enrolled cohort,33 health patients and 236 high-risk patients for PAD, underwent simultaneously ETT (Bruce's proposal)、ABI test and low extremity arterial duplex ultrasound within one week. According to the change of ABI value at 1 min after ETT, they were divided into ABI descending greater than or equal to 20 per cent, ABI descending lower than 20 per cent and ABI elevating group. The normal population as control, we analyzed and compared the other three groups of risk factors, the hemodynamic changes after EET and the manifestation of lower extremity arterial atherosclerosis lesions.
4. A randomly enrolled cohort,173 high-risk patients for PAD, underwent simultaneously ETT (Bruce's proposal、ABI test and low extremity arterial duplex ultrasound within one week. The result of lower extremity arterial duplex as the diagnostic criteria, we analysized the sensitivity, specificity, positive likelihood ratio and negative likelihood ratio of ABI exercise test diagnosing the early atherosclerotic lesions in lower extremity, and assessed the clinical diagnostic value of ETT in diagnosing early atherosclerotic lesions of lower extremity by Receiver operator characteristics (ROC) analysis.
Results
1. Of 331 high-risk patients for PAD with ABI value higher than or equal to 0.9, 57.7% have different degrees of atherosclerosis in lower extremity artery. The atherosclerotic lesions of low extremities in Borderline lower value group mainly displayed large plaques causing reduction in luminal diameter (Ⅲgrade andⅣgrade of atherosclerosis,67.7%), while those in higher value group were mainly displayed as diffuse dot-like hyperechogenicity spots(Ⅱgrade,43.8%), furthermore, the incidence of intima-media thickness (IMT) in both groups were all significantly higher than other group (p<0.05);
2. In Borderline lower value, Borderline midvalue and Borderline higher value group, the atherosclerotic lesions all predominantly involved in the proximal segments of lower extremity artery (84.2%,78.6%2及79.7%), while, in higher value group, the atherosclerotic lesions predominantly involved in the distal segment of the lower extremity artery (57.1%);
3. There were no statistically significant differences on indictors such as baPWV, haPWV, pulse pressor and ankle pressor between patients with and without low limb artery intima-media thickness increasing (p>0.05)
4. Compared with no pathological changes group, the values of baPWV and haPWV in diffused pathological group and that in little atherosclerosis plaque group significantly increased (p<0.05),the values of pulse pressor of little atherosclerosis plaque group significantly increased (p<0.05), however, there were no statistically significant differences on indictors of arteries stiffness in large atherosclerosis plaque group (p>0.05);
5. After high-risk patients for PAD having undwent ABI exercise test, the ABI change showed ABI decreased up and equal to 20%(≥20%), lower than 20%(<20%) and elevated. The ankle pressure continued to decrease in patients with ABI declined≥20% after exercise lmin to 10min. The atherosclerotic lesion in this group was the most serious, mainly displayed large plaques (area> 20mm2) causing reduction in luminal diameter. While, the ABI value and ankle pressure in patients with ABI elevated were all increased at 1 min after exercise, and ABI value continued to increase, the atherosclerotic lesion in this group mainly displayed diffuse dot-like hyperechogenicity lesion (60.0%), whereas, the atherosclerotic lesion in ABI declined <20% group mainly displayed IMT (55.6%);
6. After exercise, ABI decreased in all patients. The more severe the atherosclerotic lesions of the lower extremity were, the larger the ABI decrement after exercise was. Ultrasonography was used as the standard in defining atherosclerotic lesions such as large, small plaques, and diffuse spotty atherosclerotic lesions, the respective areas under the ROC curve were 0.802 (95%CI,0.722,0.882),0.78 (95%CI,0.708,0.852), and 0.599 (95%CI,0.44,0.757);
7. Using the presence of large atherosclerotic plaques in lower extremities as positive diagnosis, R value was 0.8, with a sensitivity of 54.0%, a specificity of 96.7%, a LR+ of 16.4, and a LR- of 0.58, meanwhile, R value was 0.85, with a sensitivity of 70.0%, a specificity of 91.9%, a LR+ of 8.64, and a LR- of 0.33;
8. Of the 173 high-risk patients for PAD, the ETT result was positive in 31 patients (17.9% of the total population), among those, there were 15 cases of no previous diagnosis of coronary heart disease (8.6% of the total population, accounting for 48.4% of positive patients). while, the ETT result was suspected positive in 24 cases(13.9% of the total population), among those, there were 17 cases of no previous diagnosis of coronary heart disease (9.8% of the total population, accounting for 70.8% of suspected positive patients). Ventricular arrhythmia occurred in 6 patients (3.5%):one had paroxysmal ventricular tachycardia (0.6%), which disappeared after oxygen inhalation and sublingual administration of nitroglycerin, and the others had ventricular premature beats, i.e, bigeminy (2.9%).
Conclusions
1.57.7% of high-risk patients for PAD with ABI value higher than or equal to 0.9 have different degrees of atherosclerosis in lower extremity artery. Among those, the atherosclerotic lesion in Borderline lower value and High value groupp were the most serious. The atherosclerotic lesions of low extremities in Borderline lower value group mainly displayed large plaques (ⅢandⅣgrade lesion,67.7%), and predominantly involved in the proximal segments of lower extremity artery. Besides, the risk facotrs of patients mainly was atherosclerotic risk factors and the major atherosclerotic basis. However, The atherosclerotic lesions of low extremities in High value group mainly displayed as diffuse dot-like hyperechogenicity spots(II grade), and predominantly involved in the distal segment of the lower extremity artery. In additons, the risk factors in this group mainly was systemic atherosclerotic vascular disease risk factors. These findings suggest that the clinician should think highly of the patient with Borderline lower value and High value group, and positively take different prophylactic measures in time according to different risk factor and different pathological changes.
2. No statistically significant differences on indictors such as baPWV, haPWV, pulse pressor and ankle pressor between patients with and without IMT was observed, this founding suggests that the arteriosclerosis index can not define the IMT degree. Divided in the atherosclerotic lesions, the values of baPWV and haPWV in diffused pathological group and that in little atherosclerosis plaque group significantly increased, yet, there were no statistically significant differences in large atherosclerosis plaque group, these founds suggest that the atherosclerosis index increasing contributes to the early atherosclerotic lesions (such as diffuse disease or small plaque), but to heavier early atherosclerotic lesions, its predictive value was very low. These findings suggest that the clinician should not ignor the patients with the normal indicators of atherosclerosis, make a comprehensive and science evaluation combinating with risk factors and clinical symptoms.
3. The atherosclerotic lesions of high risk for PAD with ABI declined≥20% after exercise was the most serious, mainly deplayed large plaques (area> 20mn2); The atherosclerotic lesions of high risk for PAD with ABI elevated after exercise mainly deplayed the diffuse dot-like hyperechogenicity lesion, which suggests that the patient in this group has high degree of atherosclerosis. Obviously, the ABI exercise test can detect not only the existence of a large lower extremity arterial plaque(area> 20mm2), but also the increased arterial stiffness, these population should be strengthened to improve the arterial elasticity.
4. The more severe the atherosclerotic lesions of the lower extremity were, the larger the ABI decrement after exercise was. Respectively, the atherosclerotic lesions such as large, small plaques, and diffuse spotty atherosclerotic lesions, was used as the positive diagnostic criteriam, the result of ROC curve areas showed that the value of ABI exercise test for diagnosing large atherosclerotic plaque lesions of the lower extremity was very high, it can be used as an more accurate and objective tool to detect the early atherosclerotic lesions of the lower extremity. Besides, Immediately after exercise,0.85 is the cut-off R value appropriate for diagnosing large atherosclerotic plaques of the lower limb (area>20mm2).
5. ABI exercise test is a safe, effective tool for detecting early atherosclerotic lesions of the lower limb for high-risk for PAD, in additions, it can simultaneously detect the myocardial ischemia disease. Hence, the ABI exercise test can provide important clinical basis for early detection and timely prevention of systemic atherosclerotic disease occurrence and development.
引文
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16. Hiatt WR, Hirsch A, Regensteiner JG, Brass EP. Clinical trials for claudication, assessment of exercise performance, functional status and clinical end points. Circulation 1995; 92:614-21.
17. Oka RK, Altman M, Giacomini JC, Szuba A, Cooke JP. Abnormal cardiovascular response to exercise in patients with peripheral arterial disease:Implications for management.J Vasc Nurs. 2005 Dec;23(4):130-6; quiz 137-8.
1. Abul-Khoudoud O. Diagnosis and risk assessment of lower extremity peripheral arterial disease.J Endovasc Ther.2006 Feb;13 Suppl 2:1110-8.
2. Stein R, Hriljac I, Halperin JL.Limitation of the resting ankle-brachial index in symptomatic patients with peripheral arterial disease.Vasc Med.2006 Feb;11(1):29-33.
3. McDermott MM. The magnitude of the problem of peripheral arterial disease:epidemiology and clinical significance.Cleve Clin J Med.2006 Oct;73 Suppl 4:S2-7.
4. Ludyga T, Kuczmik WB, Kazibudzki M. Ankle-brachial pressure index estimated by laser Doppler in patients suffering from peripheral arterial obstructive disease. Ann Vase Surg. 2007 Jul;21(4):452-7. Epub 2007 Mar 26.
5. Harada S, Takeda K.Pulse wave velocity(PWV).Nippon Rinsho.2004 Jun;62(6):1136-42.
6. Cai KY, Zhang WZ, Qiu HL. Clinical factors relating to the arterial elastic function measured by PWV, C1/C2 and AI in hypertensive patients.Zhonghua Xin Xue Guan Bing Za Zhi.2007 Mar;35(3):237-40.
7. Khaleghi M, Kullo IJ. Aortic augmentation index is associated with the ankle-brachial index: a community-based study.Atherosclerosis.2007 Dec;195(2):248-53.
8. Yamasaki Y, Katakami N. Measurement of IMT by echotomography.Nippon Rinsho.2006 Dec 28;64 Suppl 9:521-5.
9. Alnaeb ME, Crabtree VP, Boutin A. Prospective assessment of lower-extremity peripheral arterial disease in diabetic patients using a novel automated optical device.Angiology.2007 Oct-Nov;58(5):579-85.
10. Gerhard-Hennana, Julius M Gardinb, Michael Jaffc. Guidelines for noninvasive vascular laboratory testing:a report from the American Society of Echocardiography and the Society for Vascular Medicine and Biology Marie.Vascular Medicine 2006; 11:183-200.
11. Flanigan DP,Gray B,Sduler JJ,etal.Utility of wide and narrow blood pressure cuffs in the hemodynamic assessment of aoroiliac occlusive disease.Surgery,1982,92:16-20.
12. Goraya,-T-Y; Jacobsen,-S-J; Pellikka,-P-A.Prognostic value of treadmill exercise testing in elderly persons. Ann-Intern-Med.2000 Jun 6; 132(11):862-70.
13. Ludyga T, Kuczmik WB, Kazibudzki M. Ankle-brachial pressure index estimated by laser Doppler in patients suffering from peripheral arterial obstructive disease.Ann Vase Surg. 2007 Jul;21(4):452-7.
14. Watanabe,-T; Matsushita,-M; Nishikimi,-N.Near-infrared spectroscopy with treadmill exercise to assess lower limb ischemia in patients with atherosclerotic occlusive disease. Surg-Today.2004; 34(10):849-54.
15. Rozanski A,Qureshi E, Bauman M. Peripheral arterial responses to treadmill exercise among healthy subjects and atherosclerotic patients.Circulation.2001 Apr 24;103(16):2084-9.
16. Kramer CM. Peripheral arterial disease assessment:wall, perfusion, and spectroscopy.Top Magn Reson Imaging.2007 Oct;18(5):357-69.
17. Begelman SM, Jaff MR.Cleve Clin J Med.2006 Oct;73 Suppl 4:S22-9. Noninvasive diagnostic strategies for peripheral arterial disease.
18. De, Ouwendijk R, Flobbe K. Peripheral arterial disease:clinical and cost comparisons between duplex US and contrast-enhanced MR angiography-a multicenter randomized trial.Ned Tijdschr Geneeskd.2007 Aug 11; 151 (32):1789-94.
19. Eiberg JP, Hansen MA, Jensen F. Ultrasound contrast-agent improves imaging of lower limb occlusive disease.Eur J Vasc Endovasc Surg.2003 Jan;25(1):23-8.
20. Heijenbrok-Kal MH, Kock MC, Hunink MG. Lower extremity arterial disease:multidetector CT angiography meta-analysis.Radiology.2007 Nov;245(2):433-9.
21. Dellegrottaglie S, Sanz J, Macaluso F. Technology Insight:magnetic resonance angiography for the evaluation of patients with peripheral artery disease.Nat Clin Pract Cardiovasc Med. 2007 Dec;4(12):677-87.
22. Collins R, Cranny G, Burch J. A systematic review of duplex ultrasound, magnetic resonance angiography and computed tomography angiography for the diagnosis and assessment of symptomatic, lower limb peripheral arterial disease.Health Technol Assess.2007 May; 11 (20):ⅳ-ⅳ, ；ⅹⅰ-ⅹⅲ,1-184.
23. Jaff MR.Lower extremity arterial disease. Diagnostic aspects. Cardiol Clin.2002 Nov;20(4):491-500.
2. Stein R, Hriljac I, Halperin JL.Limitation of the resting ankle-brachial index in symptomatic patients with peripheral arterial disease. Vasc Med.2006 Feb;11(1):29-33.2.
3. Matthew A. Allison, William R. Hiatt, Alan T. Hirsch, Joseph R. Coll, and Michael H. Criqui.A High Ankle-Brachial Index Is Associated With Increased Cardiovascular Disease Morbidity and Lower Quality of Life.J. Am. Coll. Cardiol. Apr 2008; 51:1292-1298.
4. McDermott MM, Liu K, Criqui MH, et al. Ankle-brachial index and subclinical cardiac and carotid disease:the Multi-Ethnic Study of Atherosclerosis. Am J Epidemiol 2005; 162:33-41.
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9. 《2007年下肢动脉粥样硬化疾病诊治中国专家建议》
10. Resnick HE, Lindsay RS, McDermott MM, et al. Relationship of high and low ankle brachial index to all-cause and cardiovascular disease mortality. The Strong Heart Study. Circulation 2004; 109:733-739.
11. Diehm N, Shang A, Silvestro A, Do DD.Association of cardiovascular risk factors with pattern of lower limb atherosclerosis in 2659 patients undergoing angioplasty.Eur J Vasc Endovasc Surg, January 1,2006; 31(1):59-63.
12. Kim Sutton-Tyrrell, Samer S. Najjar, Robert M. Boudreau.Elevated Aortic Pulse Wave Velocity, a Marker of Arterial Stiffness, Predicts Cardiovascular Events in Well-Functioning Older Adults. Circulation, Jun 2005; 111:3384-3390.
13. Tine Willum Hansen,Jan A. Staessen,Christian Torp-Pedersen.Prognostic Value of Aortic Pulse Wave Velocity as Index of Arterial Stiffness in the General Population. Circulation.2006; 113:664-670.
14. K Motobe, H Tomiyama, Y Koji, M Yambe.Cut-off value of the ankle-brachial pressure index at which the accuracy of brachial-ankle pulse wave velocity measurement is diminished. Circ J, January 1,2005; 69(1):55-60.
15. Yamashina A, Tomiyama H, Arai T, et al Brachial-ankle pulse wave velocity as a marker of atherosclerotic vascular damage and cardiovascular risk. Hypertens Res,2003,26:615-622.
16.贾新术,魏盟,陆志刚.脉搏波传导速度对冠心病的诊断价值.诊断学理论与实践,2006,5：332-335.
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19. JL Megnien, A Simon, N Denarie, M Del-Pino. Aortic stiffening does not predict coronary and extracoronary atherosclerosis in asymptomatic men at risk for cardiovascular disease. Am J Hypertens, March 1,1998; 11(3 Pt 1):293-301.
20. DJ Farrar, MG Bond, WA Riley. Anatomic correlates of aortic pulse wave velocity and carotid artery elasticity during atherosclerosis progression and regression in monkeys. Circulation, May 1991; 83:1754-1763.
21. H Yokoyama, T Shoji, E Kimoto. Pulse wave velocity in lower-limb arteries among diabetic patients with peripheral arterial disease. J Atheroscler Thromb, Jan 2003; 10(4):253-8.
1. Murabito JM, Evans JC, Nieto K, et al. Prevalence and clinical correlates of peripheral arterial disease in the Framingham Offspring Study. Am Heart J.2002;143:961-965.
2. Stein R, Hriljac I, Halperin JL.Limitation of the resting ankle-brachial index in symptomatic patients with peripheral arterial disease.Vasc Med.2006 Feb;11(1):29-33.2.
3. K Ouriel, AE McDonnell, CE Metz, and CK Zarins.Critical evaluation of stress testing in the diagnosis of peripheral vascular disease.Surgery, Jun 1982; 91(6):686-93.
4. Oka RK, Altman M, Giacomini JC, Szuba A, Cooke JP. Abnormal cardiovascular response to exercise in patients with peripheral arterial disease:Implications for management. J Vasc Nurs. 2005 Dec;23(4):130-6; quiz 137-8.
5. 《2007年下肢动脉粥样硬化疾病诊治中国专家建议》
6. Fletcher GF, Froelicher VF, Hartley LH, et al. Exercise standards:a statement for health professionals from the American Heart Association. Circulation 1990; 82:2286-2321. Revised Circulation 1995; 91:580-632.
7. Alan T. Hirsch, Ziv J. Haskal, Norman R. Hertzer,etal.ACC/AHA PRACTICE GUIDELINES:ACC/AHA 2005 Practice Guidelines for the Management of Patients With Peripheral Arterial Disease (Lower Extremity, Renal, Mesenteric, and Abdominal Aortic):A Collaborative Report from the American Association for Vascular Surgery/Society for Vascular Surgery,* Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease):Endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; and Vascular Disease Foundation.Circulation, Mar 2006; 113:e463-e465.
8. Sharman JE, McEniery CM, Campbell RI, Coombes JS, Wilkinson IB, and Cockcroft JR.The effect of exercise on large artery haemodynamics in healthy young men.Eur J Clin Invest, Dec 2005; 35(12):738-44.
9. Neubauer B, Christensen NJ, Christensen T, Gundersen HJ, and Jorgensen J.Diabetic macroangiopathy. Medial calcifications, narrowing, rugosities, stiffness, norepinephrine depletion and reduced blood flow capacity in the leg arteries.Acta Med Scand Suppl,1984; 687:37-45.
10. Chu K. An introduction to sensitivity, specificity, predictive values and likelihood ratios. Emerg Med 1999; 11:175-181.
11. Hiatt WR, Nawaz D, Regensteiner JG, Hossack KF. The evaluation of exercise performance in patients with peripheral vascular disease. J Cardiopulmon Rehabil 1988; 12:525-32.
12. Gardner AW, Skinner JS, Smith LK. Effects of handrail support on claudication and hemodynamic responses to single-stage and progressive treadmill protocols in vascular occlusive disease. Am J Cardiol 1991; 68:99-105.
13. Cameron AEP, Porter A, Rosser S, Da Silva AECF, De Cossart LM. The Stresst'er ergometer as an alternative to treadmill testing in patients with claudication. Eur J Vasc Endovasc Surg 1997; 14:433-8.
14. Bruce RA, Kusumi F, Hosmer D.Maximal oxygen intake and nomographic assessment of functional aerobic impairment in cardiovascular disease. Am Heart J 1973; 85:546-62.
15. Gardner AW. Claudication pain and hemodynamic responses to exercise in younger and older peripheral arterial disease patients. J Gerontol 1993; 48:M231-6.
16. Hiatt WR, Hirsch A, Regensteiner JG, Brass EP. Clinical trials for claudication, assessment of exercise performance, functional status and clinical end points. Circulation 1995; 92:614-21.
17. Oka RK, Altman M, Giacomini JC, Szuba A, Cooke JP. Abnormal cardiovascular response to exercise in patients with peripheral arterial disease:Implications for management.J Vasc Nurs. 2005 Dec;23(4):130-6; quiz 137-8.
1. Abul-Khoudoud O. Diagnosis and risk assessment of lower extremity peripheral arterial disease.J Endovasc Ther.2006 Feb;13 Suppl 2:1110-8.
2. Stein R, Hriljac I, Halperin JL.Limitation of the resting ankle-brachial index in symptomatic patients with peripheral arterial disease.Vasc Med.2006 Feb;11(1):29-33.
3. McDermott MM. The magnitude of the problem of peripheral arterial disease:epidemiology and clinical significance.Cleve Clin J Med.2006 Oct;73 Suppl 4:S2-7.
4. Ludyga T, Kuczmik WB, Kazibudzki M. Ankle-brachial pressure index estimated by laser Doppler in patients suffering from peripheral arterial obstructive disease. Ann Vase Surg. 2007 Jul;21(4):452-7. Epub 2007 Mar 26.
5. Harada S, Takeda K.Pulse wave velocity(PWV).Nippon Rinsho.2004 Jun;62(6):1136-42.
6. Cai KY, Zhang WZ, Qiu HL. Clinical factors relating to the arterial elastic function measured by PWV, C1/C2 and AI in hypertensive patients.Zhonghua Xin Xue Guan Bing Za Zhi.2007 Mar;35(3):237-40.
7. Khaleghi M, Kullo IJ. Aortic augmentation index is associated with the ankle-brachial index: a community-based study.Atherosclerosis.2007 Dec;195(2):248-53.
8. Yamasaki Y, Katakami N. Measurement of IMT by echotomography.Nippon Rinsho.2006 Dec 28;64 Suppl 9:521-5.
9. Alnaeb ME, Crabtree VP, Boutin A. Prospective assessment of lower-extremity peripheral arterial disease in diabetic patients using a novel automated optical device.Angiology.2007 Oct-Nov;58(5):579-85.
10. Gerhard-Hennana, Julius M Gardinb, Michael Jaffc. Guidelines for noninvasive vascular laboratory testing:a report from the American Society of Echocardiography and the Society for Vascular Medicine and Biology Marie.Vascular Medicine 2006; 11:183-200.
11. Flanigan DP,Gray B,Sduler JJ,etal.Utility of wide and narrow blood pressure cuffs in the hemodynamic assessment of aoroiliac occlusive disease.Surgery,1982,92:16-20.
12. Goraya,-T-Y; Jacobsen,-S-J; Pellikka,-P-A.Prognostic value of treadmill exercise testing in elderly persons. Ann-Intern-Med.2000 Jun 6; 132(11):862-70.
13. Ludyga T, Kuczmik WB, Kazibudzki M. Ankle-brachial pressure index estimated by laser Doppler in patients suffering from peripheral arterial obstructive disease.Ann Vase Surg. 2007 Jul;21(4):452-7.
14. Watanabe,-T; Matsushita,-M; Nishikimi,-N.Near-infrared spectroscopy with treadmill exercise to assess lower limb ischemia in patients with atherosclerotic occlusive disease. Surg-Today.2004; 34(10):849-54.
15. Rozanski A,Qureshi E, Bauman M. Peripheral arterial responses to treadmill exercise among healthy subjects and atherosclerotic patients.Circulation.2001 Apr 24;103(16):2084-9.
16. Kramer CM. Peripheral arterial disease assessment:wall, perfusion, and spectroscopy.Top Magn Reson Imaging.2007 Oct;18(5):357-69.
17. Begelman SM, Jaff MR.Cleve Clin J Med.2006 Oct;73 Suppl 4:S22-9. Noninvasive diagnostic strategies for peripheral arterial disease.
18. De, Ouwendijk R, Flobbe K. Peripheral arterial disease:clinical and cost comparisons between duplex US and contrast-enhanced MR angiography-a multicenter randomized trial.Ned Tijdschr Geneeskd.2007 Aug 11; 151 (32):1789-94.
19. Eiberg JP, Hansen MA, Jensen F. Ultrasound contrast-agent improves imaging of lower limb occlusive disease.Eur J Vasc Endovasc Surg.2003 Jan;25(1):23-8.
20. Heijenbrok-Kal MH, Kock MC, Hunink MG. Lower extremity arterial disease:multidetector CT angiography meta-analysis.Radiology.2007 Nov;245(2):433-9.
21. Dellegrottaglie S, Sanz J, Macaluso F. Technology Insight:magnetic resonance angiography for the evaluation of patients with peripheral artery disease.Nat Clin Pract Cardiovasc Med. 2007 Dec;4(12):677-87.
22. Collins R, Cranny G, Burch J. A systematic review of duplex ultrasound, magnetic resonance angiography and computed tomography angiography for the diagnosis and assessment of symptomatic, lower limb peripheral arterial disease.Health Technol Assess.2007 May; 11 (20):ⅳ-ⅳ, ；ⅹⅰ-ⅹⅲ,1-184.
23. Jaff MR.Lower extremity arterial disease. Diagnostic aspects. Cardiol Clin.2002 Nov;20(4):491-500.