Prevalence of Nonatheromatous Lesions in Peripheral Arterial Disease

Abstract

Objective-The histopathology of peripheral arterial disease and the accompanying calcification are poorly defined, and it is not known whether this varies according to different risk factors. Approach and Results-Sections from 176 upper and lower leg arteries were examined histologically in specimens from amputations of 60 patients with peripheral arterial disease, of whom 58% had diabetes mellitus, 35% had end-stage renal disease, and 48% had a history of smoking. The most common findings were calcification of the media (72% of arteries) and intimal thickening without lipid (68% of arteries), with the presence of atheromas in only 23% of arteries. Intimal calcification occurred in 43% and was generally much less extensive than medial calcification. Nonatheromatous intimal thickening was frequently severe, resulting in complete occlusion in some vessels. The absence of lipid and macrophages was confirmed by staining with oil red O and staining for CD68. Other than a greater prevalence and severity of medial calcification in end-stage renal disease, the findings did not differ between diabetics, patients with end-stage renal disease, or smokers. Conclusions-The results indicate that the majority of arteries in patients with peripheral arterial disease have a vascular lesion that is distinct from atherosclerosis, suggesting a different pathogenesis. This pattern does not differ substantially between patients with different risk factors for peripheral arterial disease. ResultsSpecimens were examined from 60 patients, of which 29 had diabetes mellitus, 35 had a history of smoking, and 21 had ESRD, with many having >1 risk factor. Detailed characteristics of the patients are shown in Table I in the online-only Data Supplement. Other than the reduced prevalence of smoking in the ESRD patients, there were no significant differences between the groups. Only 4 patients did not have diabetes mellitus, ESRD, or a smoking history. Of the 15 patients receiving warfarin at the time of the amputation, 7 had atrial fibrillation, 4 had thrombotic disease, and 2 had mechanical heart valves. In the remaining 2, the indication was critical limb ischemia. Histopathology of the IntimaThe distribution of arteries examined and the histological findings in the intima are shown in Table 1. Many sections were labeled as margins, or proximal or distal, precluding the identification of specific arteries. Specimens frequently contained both tibial arteries, which could not be distinguished, and the peroneal artery was identified in only 4 specimens and was not analyzed separately. Because of the limited numbers of specific arteries, reliable comparisons could be made only between arteries above and below the knee. Intimal thickening was present in >90% of vessels (concentric in most cases) and did not differ between arteries above and below the knee. Thickening was associated with a greater patient age (66.0±1.2 versus 56.8±2.8 years; P<0.02) but not with sex. In the majority of arteries, other intimal changes were absent ( Figure 1A). Spec...

Association of cardiovascular and biochemical risk factors with tibial artery calcification

“…(17) Interestingly, we found that age, male sex, tobacco use, and diabetes maintained their association with tibial calcium even after adjusting for presence of PAD. This may reflect the more medial localization of calcification in the tibial vessels or the relatively higher proportion of non-atheromatous lesions recently reported by O’Neill et al(18) It also is possible that atherosclerosis and calcification share overlapping risk factors. This would support the concept that tibial calcification independently contributes to limb ischemia and poor outcomes; however the mechanisms behind these associations have not been identified.…”

Sex Differences in the Incidence of Peripheral Artery Disease in the Chronic Renal Insufficiency Cohort

“…In a study examining breast arterial calcification (BAC) in women with CKD, BAC was found exclusively in the media, was associated with peripheral arterial calcification, and was found to be a marker of generalized medial arterial calcification (MAC), a histologic finding common in amputated limbs. 34 In a follow-up study, BAC was independently associated with new PAD events in women with ESRD. 35 As these analyses did not include men, it is unknown if these histologic correlates indicate increased PAD risk in women, but they show that women with CKD have more MAC, and that MAC may be associated with a more accelerated form of PAD.…”

A Review of the Pathophysiology and Potential Biomarkers for Peripheral Artery Disease

“…A recent report on the histopathological assessment of PAD (176 upper and lower leg artery specimens) patients highlights that the most common observations were medial calcification (present in 72% of arteries examined) and intimal thickening without lipid (present in 68% of arteries examined). Classical atherosclerosis was only identified in 23% of arteries [139]. Non-atheromatous intimal thickening was frequently observed, resulting in complete occlusion in some vessels.…”