JACC Adv. 2026 Jun 11;5(7):102882. doi: 10.1016/j.jacadv.2026.102882. Online ahead of print.
ABSTRACT
BACKGROUND: Medial artery calcification (MAC) is a hallmark of lower extremity artery disease, yet its precise distribution and relationship with intimal artery calcification (IAC) remain poorly understood because current clinical imaging modalities have limited ability to reliably distinguish between the 2.
OBJECTIVES: The objectives of the study were to comprehensively characterize the histopathological distribution and morphology of MAC and to determine its spatial relationship with intimal atherosclerotic plaque.
METHODS: We performed a systematic, section-by-section histopathological analysis of 3,566 cross-sections from 125 arterial segments in 58 patients with lower extremity artery disease. Calcification was quantified by circumferential arc, and plaque morphology was classified according to the modified American Heart Association criteria.
RESULTS: MAC was highly prevalent (91.2% of segments) and significantly more extensive in below-the-knee than above-the-knee arteries, whereas IAC demonstrated the opposite distribution. Medial bone formation was identified in 16.0% of segments and was strongly associated with the greatest MAC burden, representing an advanced stage of the disease. In a section-level analysis (n = 3,003), the arcs of MAC and IAC were inversely correlated (r = -0.47; P < 0.0001) and showed minimal circumferential overlap, indicating distinct spatial segregation. Sections with extensive MAC were primarily associated with nonatherosclerotic intima, whereas advanced intimal plaques occurred predominantly in sections with minimal MAC.
CONCLUSIONS: MAC and IAC represent spatially distinct calcific pathologies with an inverse quantitative relationship. Advanced MAC may be associated with reduced development of intimal atherosclerotic plaque and may partly explain the limited response of below-the-knee lesions to conventional endovascular therapies.
PMID:42275686 | DOI:10.1016/j.jacadv.2026.102882