2023 Volume 30 Issue 10 Pages 1305-1306
See article vol. 30: 1327-1335
Smoking, diabetes mellitus (DM), and end-stage renal disease (ESRD) are well-known risk factors for cardiovascular disease. These risk factors have a significant impact on the progression of systemic atherosclerosis, and compose “polyvascular disease” including coronary artery disease (CAD), cerebrovascular disease (CVD), and peripheral artery disease (PAD), leading to poor patient outcomes. Among PAD, lower extremity artery disease (LEAD) has become a major problem and target for treatment in patients with systemic atherosclerosis.
The advent of endovascular therapy (EVT) has led to significant progress in device development and interventional procedures. However, satisfactory long-term clinical outcomes after EVT in patients with LEAD have not yet been achieved1). This may be due to increase in the number of LEAD patients with DM and/or ESRD who have a very high risk of systemic atherosclerosis. The distribution patterns of vascular involvement differ. Although similar pathophysiological mechanisms have been identified, there is strong association between smoking/hypertension and CAD, DM/hypertension and CVD, and between ESRD and CAD/PAD2). Smoking, DM, and ESRD are significant risk factors for LEAD3). However, the distribution pattern of vascular involvement in the arteries of the lower extremities might be different in patients with LEAD due to a different set of cardiovascular risk factors.
Vascular lesions in LEAD are usually divided into aortoiliac, femoropopliteal, and infrapopliteal types. Historically, it is known that smokers are more prone to develop proximal lesions (aortoiliac), while DM and ESRD are more likely to be associated with distal lesions (infrapopliteal)4-7). Smoking is the most powerful predictor of progression in large-vessel LEAD, whereas DM and ESRD are significantly associated with involvement of more distal small vessels. The aortoiliac and crucial segments have characteristic risk profiles. However, the femoropopliteal lesion is a transitional zone located in the middle part of the lower limb arteries, and the significant risk factors have not yet been clearly elucidated. In this respect, it is important to elucidate the association between cardiovascular risk factors and popliteal lesions in femoropopliteal disease.
Takahara et al. clearly provided, for the first time, the association between cardiovascular risk factors including smoking, DM, and ESRD, and vascular involvement in femoropopliteal artery disease, particularly with popliteal lesions8). They precisely evaluated 1912 patients with de novo femoropopliteal lesions who underwent drug-coated balloon treatment. Smoking was inversely associated with popliteal lesions (adjusted odds ratio, 0.66), whereas dialysis-dependent ESRD was positively associated with popliteal lesions (adjusted odds ratio, 2.01) in patients with symptomatic femoropopliteal artery disease. DM was not significantly associated with popliteal lesions.
The heterogeneity in distribution patterns of atherosclerosis associated with different risk factors is thought to be due to histological and hemodynamic mechanisms. The vascular wall of proximal arteries is composed of more elastic tissue, whereas that of distal arteries is composed of more smooth muscle. Furthermore, the ratio of the arterial lumen to the wall thickness decreases from proximal to distal, thus altering arterial shear stress. In ESRD, the susceptibility to distal involvement might make the revascularization procedure more difficult, and increased muscular components might aggravate vascular calcification, which is a known characteristic feature in ESRD patients with LEAD. Knowledge of the heterogeneity of vascular involvement resulting from different risk factors might improve treatment strategies for such patients with critical limb-threatening ischemia (CLTI). Involvement of the distal arteries leads to deleterious outcomes because they are the terminal vascular beds. In CLTI patients with centrifugal involvement patterns such as in ESRD, it is important to improve the microcirculation concurrently with the revascularization procedure to effect better patient outcomes9).
Dr. Ohtake: no conflict of interest.
Dr. Kobayashi: clinical research funding from Nipro Corporation, Osaka, Japan, and lecture fees from Chugai Pharmaceutical Co. Ltd., Tokyo, Japan, and Bayer Yakuhin, Ltd., Tokyo, Japan.
