Osteoid Metaplasia in Femoral Artery Plaques Is Associated With the Clinical Severity of Lower Extremity Artery Disease in Men

Abstract

Lamellar metaplastic bone, osteoid metaplasia (OM), is found in atherosclerotic plaques, especially in the femoral arteries. In the carotid arteries, OM has been documented to be associated with plaque stability. This study investigated the clinical impact of OM load in femoral artery plaques of patients with lower extremity artery disease (LEAD) by using a deep learning-based image analysis algorithm. Plaques from 90 patients undergoing endarterectomy of the common femoral artery were collected and analyzed. After decalcification and fixation, 4-μm-thick longitudinal sections were stained with hematoxylin and eosin, digitized, and uploaded as whole-slide images on a cloud-based platform. A deep learning-based image analysis algorithm was trained to analyze the area percentage of OM in whole-slide images. Clinical data were extracted from electronic patient records, and the association with OM was analyzed. Fifty-one (56.7%) sections had OM. Females with diabetes had a higher area percentage of OM than females without diabetes. In male patients, the area percentage of OM inversely correlated with toe pressure and was significantly associated with severe symptoms of LEAD including rest pain, ulcer, or gangrene. According to our results, OM is a typical feature of femoral artery plaques and can be quantified using a deep learning-based image analysis method. The association of OM load with clinical features of LEAD appears to differ between male and female patients, highlighting the need for a gender-specific approach in the study of the mechanisms of atherosclerotic disease. In addition, the role of plaque characteristics in the treatment of atherosclerotic lesions warrants further consideration in the future.

The Increase of The Relative Amount of Nodular Calcification In Femoral Plaques is Associated With Milder Lower Extremity Arterial Disease

“…ABI less than 0.4 and TP less than 30 mmHg were deemed as severe disease indicators. Fontaine class was categorized into two groups, patients with claudication were deemed to have mild symptoms and patients with rest pain, ischaemic ulcer or gangrene were considered to have severe symptoms [4].…”

“…Femoral plaque samples were collected during endarterectomy of the femoral artery bifurcation between October 2014 and January 2017 [4]. The severity of LEAD of the patients (N=90) was determined by ankle brachial index (ABI), toe pressure (TP), Fontaine classi cation of LEAD symptoms, and urgency of the operation.…”

“…Vascular calci cation is a bone-like formation continuum that presents different morphologies, which in turn impact differently on the plaque histology and the clinical presentation [3], [4]. It initiates as microcalci cation, which predestines the plaque to an unstable state [5].…”

“…The propagation of microcalci cation into macrocalci cation is believed to have a stabilizing effect on the plaque, despite its potential stenosing impact [6]. Macrocalci cation can occur in the form of a calci ed plate, called sheet calci cation (ShCa) or the form of osteoid metaplasia [4], [7]. Nodular calci cation (NodCa) may be caused by a fracture of ShCa and is accompanied by surrounding brin deposits [7], [8].…”

High relative amount of nodular calcification in femoral plaques is associated with milder lower extremity arterial disease

“…Vascular calcification is a continuum of osteoid metaplasia formation that is observed in various morphologies. The plaque histology is reflected on the clinical symptoms [3,4]. Vascular calcification initiates as microcalcification that may over time progress into macrocalcification [5].…”