Multidimensional Assessment of Lower Extremity Peripheral Artery Disease

• Main Authors: Chi-Lun Huang, 黃啟倫
• Other Authors: 楊偉勛
• Format: Others
• Language: zh-TW
• Published: 2014
• Online Access: http://ndltd.ncl.edu.tw/handle/28860802350883649076

博士 === 國立臺灣大學 === 臨床醫學研究所 === 102 === Background: Peripheral artery disease (PAD) affects 15%-20% of persons older than 70 years of age, though its prevalence is probably even greater if we include asymptomatic persons. Apart from claudication, patients with PAD may experience many problems, such as ischemic rest pain, digital ulceration and gangrene changes, repeated hospitalizations, revascularizations, and finally limb loss. These lead to limited physical activity, poor quality of life, and high rate of depression. Moreover, various epidemiologic studies have shown that up to 50% of patients with PAD also have symptoms of coronary and cerebrovascular disease. They also have higher rate of cardiovascular and all-cause mortality compared with patients without PAD. Several techniques are currently being used to aid low extremity PAD diagnosis and severity assessment. These include ankle-brachial index, Duplex ultrasound, computed tomography angiography, magnetic resonance angiography, and catheter-based angiography. Unlike the multidimensional approachs in patients with clinical suspicion of CAD, these techniques focus on lower extremity arteries only, and provide limited information about stenotic severity, blood flow, and pressure gradients. Purposes: The aims of our study were to evaluate patients with PAD in multiple dimensions. We focused on skin temperature, muscular oxygenation, and arterial calcification, which were analyzed by infrared thermography, near-infrared spectroscopy (NIRS), and multidetector computed tomography (MDCT), respectively in three separate studies. Finally, the laboratory study analyzed the regulating roles of cilostazol, medication for PAD treatment, on adipocyte fatty acid-binding protein (A-FABP) and other foam cell formation-associated gene expression in THP-1 cell model. Research Designs and Results: 1. Fifty one subjects at high risk for lower extremity PAD were recruited from cardiovascular clinics. Patients with end-stage renal disease (ESRD) were also enrolled. The cutaneous temperatures of lower extremity before and after exercise were measured by a digital infrared thermal image system. The exercise was a six-minute walk test. The ankle-brachial index and three PAD-associated questionnaires were analyzed before examination. In this study, we demonstrated that there was no difference in rest temperature between PAD and non-PAD patients. However, the exercise-induced temperature changes were correlated with PAD severity, walking capacity, and daily physical activity. 2. Thirsty hypertensive subjects with at least another cardiovascular risk factor were enrolled and treated with 12-week olmesartan. Muscular microcirculation (estimated by half-time of tissue saturation recovery SatT50) and capacity of oxygenation extraction (estimated by deoxy-hemoglobin changes △deoxyHb) were analyzed by NIRS. The blood pressure, serum endothelial biomarkers (ICAM-1、VCAM-1、PAI-1), and above-mentioned examinations were performed before and after treatment. There were mild positive correlations between hemoglobin A1c, microalbuminuria, and NIRS derived parameters (SatT50 and △deoxyHb) at baseline. After 12-week olmesartan treatment, there was a trend of lower SatT50 and higher △deoxyHb. However, there was no significant change in endothelial function, serum biomarker levels, exercise duration, and maximal oxygen uptake. 3. Eighty two symptomatic PAD patients (Fontaine stage II-IV) with MDCT of lower extremity artery images in NTUH were analyzed retrospectively. The scoring of calcification started at the junction of descending aorta and common iliac artery, and ended at the ankle. The calcium score (CS) for each segments of interest was determined and expressed as Agatston score. The primary and secondary endpoints were all-cause mortality and amputation. Our study demonstrated that lower extremity arterial CS, which was higher in patients with old age, diabetes, hyperlipidemia, and ESRD, was independently associated with amputation and all-cause mortality in patients with symptomatic PAD. 4. In a small clinical study, we demonstrated that the levels of A-FABP were significantly higher in patients with PAD than normal controls. In THP-1 cell model, we analyzed the role of cilostazol, medication for PAD treatment, in regulating foam cell formation-associated gene expression. We demonstrated that cilostazol suppresses the upregulation of A-FABP induced by ox-LDL. The expression of CD36, ABCA-1, and MCP-1 were also modulated by cilostazol. Conclusions: In conclusion, our study demonstrated that the multidimensional assessment (skin, muscle, and artery) provided objective, functional, and outcome-predicting information of PAD. We believe that these techniques and parameters will contribute to PAD diasnosis in the future. Besides, we have explored the regulatory mechanism of cilostazol on A-FABP and other foam-cell formation associated gene expression. These results partially explained the anti-atherosclerotic and metabolic modulating effects of cilostazol observed in clinical practice.