Possible mechanisms of PAD-to-CLI progression identified

MUNICH — Histopathological analysis of arteries in patients who underwent lower-limb amputation indicates that thrombotic luminal occlusion associated with insignificant atherosclerosis is common in critical limb ischemia and may suggest the possibility of thromboembolic disease.

Currently, with little data available, the pathology and plaque composition of lower-extremity arteries in patients with peripheral artery disease are thought to be similar to the pathology of atherosclerosis in the coronary and carotid arteries, researchers reported at the European Society of Cardiology Congress and in a simultaneous publication in the Journal of the American College of Cardiology.

“The present study was performed in above-knee amputation and below-knee amputation specimens to describe the pathology of lower-extremity arteries in patients with CLI to better understand the mechanisms leading to amputation in patients with CLI,” Navneet Narula, MD, from New York University Langone Medical Center, and colleagues wrote.

The researchers examined lower-extremity arteries of 121 amputations performed on 95 patients, including 75 with CLI, who underwent amputation at Weill Cornell Medicine from 2014 to 2017.

Of the 299 arteries examined, 239 were from patients with CLI. In the arteries from patients with CLI, atherosclerotic plaques were more common in femoral and popliteal arteries than in infrapopliteal arteries (67.6% vs. 38.5%; adjusted OR = 5.47; P = .003).

Additionally, 69% of all 239 arteries had at least 70% stenosis. This was attributable to significant pathological intimal thickening, fibroatheroma, fibrocalcific lesions or restenosis in 27.3% of arteries and luminal thrombi with significant atherosclerotic lesions in 23.6% or luminal thrombi without significant atherosclerotic lesions in 49.1% of arteries.

Results also showed that chronic luminal thrombi were significantly more likely to be found in arteries with insignificant atherosclerosis (OR = 16.7; P = .0002) and were twice as common in the infrapopliteal arteries vs. femoral and popliteal arteries (OR = 2.14; P = .0041).

However, infrapopliteal arteries were less likely than femoral and popliteal arteries to have evidence of acute thrombotic occlusion (OR = 0.27; P = .0067).

Medial calcification was also present in 71% of 239 large arteries, according to the data.

This histopathological characterization of the lower leg vessels in CLI suggests the possibility of thromboembolic phenomenon, the researchers concluded, noting that medial calcification in these vessels was also frequent.

“The in situ thrombosis secondary to plaque rupture as classically reported in coronary disease is less common,” they wrote. “The pathological findings in lower-extremity arteries suggest possible mechanisms of progression of PAD to CLI, and may support the preventive role of antithrombotic agents.” – by Melissa Foster

References:

Narula N, et al. Late-Breaking Basic and Translational Science 4145. Presented at: European Society of Cardiology Congress; Aug. 25-29, 2018; Munich.

Narula N, et al. J Am Coll Cardiol. 2018;doi:10.1016/j.jacc.2018.08.002.

Disclosure: Narula reports no relevant financial disclosures. Please see the study for a full list of the authors’ relevant financial disclosures.