FEMOROPOPLITEAL ARTERY CALCIFICATION IS ASSOCIATED WITH AGEING, DIABETES, ELASTIN FIBER DEGRADATION, AND ANISOTROPIC STIFFENING

Introduction: Arterial calcification and stiffening increase the risk of reconstruction failure, amputation, and mortality in patients with peripheral arterial disease, but underlying mechanisms and prevalence are unclear. ... [ view full abstract ]

Introduction: Arterial calcification and stiffening increase the risk of reconstruction failure, amputation, and mortality in patients with peripheral arterial disease, but underlying mechanisms and prevalence are unclear.

Methods: Fresh human femoropopliteal arteries (FPA) were obtained from n=351 tissue donors 13-82 years old (mean age 54±15 years). Arterial stiffness was assessed with planar biaxial testing and constitutive modeling, and histological features were determined using Verhoeff–Van Gieson staining. Calcium was quantified using a 7-stage grading scale and was correlated with structural and mechanical properties and clinical characteristics.

Results: Over half (52%) of the FPAs had identifiable medial calcification. Older arteries were more calcified (p<0.01), but small calcium deposits were observed in arteries as young as 18 years old. After controlling for age, positive correlations were observed between calcification, diabetes (p<0.01) and body mass index (p=0.01). Tobacco use demonstrated a negative correlation (p=0.01). More calcification was observed in subjects taking hyperlipidemia drugs (p<0.01), steroids (p=0.02), diuretics (p=0.01) and diabetes medications (p<0.01). More calcified arteries had thinner medial layers (p<0.01), with more discontinuous (p<0.001) and thinner external elastic laminae (p=0.01) and thinner elastin fibers (p<0.01). More calcified arteries were stiffer in both longitudinal and circumferential directions (p<0.01) and had smaller circumferential opening angles (p<0.01).

Conclusions: Although aging is the dominant risk factor for FPA calcification and stiffening, these processes appear to be linked and can begin at a young age. FPA elastic fiber degradation, diabetes and calcification are associated, suggesting overlapping molecular pathways that require further investigation.