Abstract 713: Effects of Demographics and Clinical Risk Factors on Human Femoropopliteal Artery Histopathology

Abstract

Introduction: Disease of the femoropopliteal artery (FPA) is associated with significant morbidity and quality of life impairment. End-stage lesions may be too advanced to determine how demographics and clinical risk factors impact arterial wall damage and lesion development; therefore we investigated the influence of these patient characteristics on various stages of human FPA histopathology. Methods: FPAs were obtained from 14-80 year-old human tissue donors ( n =120). Proximal segments of the arteries were mechanically tested and labeled with Verhoeff-Van Gieson stains. FPA intimal-medial damage severity was assessed and correlated with histology, mechanical properties, subject demographics, risk factors, and physiological stresses and stretches using Pearson correlation r with two-tailed significance levels. Results: Age correlated strongest ( r =0.664, p<0.01) with the degree of FPA intimal-medial damage, explaining 50% of the variation alone. Primarily due to medial calcification, more damaged FPAs were stiffer and demonstrated lower physiological circumferential stretch ( r =-0.510, p<0.01), circumferential stress and longitudinal stress ( r =-0.355, r =-0.379, p<0.01). More damage was associated with larger arterial radii ( r =0.470, p<0.01), thickened arterial walls ( r =0.238, p<0.01), decreased in situ longitudinal pre-stretch ( r =-0.537, p<0.01), less elastin in the arterial wall ( r =-0.432, p<0.01), thinner individual elastin fibers ( r =-0.571, p<0.01), and thinner, less dense, and more discontinuous external elastic laminae ( r =-0.252, r =-0.456, r =0.588, p<0.01). Damage was positively associated with male gender ( r =0.265, p<0.01), higher BMI ( r =0.224, p=0.01), hypertension ( r =0.266, p<0.01), diabetes ( r =0.265, p<0.01) and coronary artery disease ( r =0.375, p<0.01), but not with dyslipidemia ( r =0.117, p=0.161) or smoking history ( r =0.041, p=0.626). Conclusions: More severely damaged FPAs demonstrate elastin loss, medial calcification and increased stiffness compared to less damaged arteries. FPA damage correlates with most classical cardiovascular risk factors, but not with dyslipidemia or tobacco history, suggesting possible unique pathophysiological mechanisms that require further investigation.