CD163+ Macrophages Induce Endothelial-to-Mesenchymal Transition in Atheroma.

BACKGROUND: Cell phenotype switching is increasingly being recognized in atherosclerosis. However, our understanding of the exact stimuli for such cellular transformations and their significance for human atherosclerosis is still evolving. Intraplaque hemorrhage is thought to be a major contributor to plaque progression in part by stimulating the influx of CD163+ macrophages. Here, we explored the hypothesis that CD163+ macrophages cause plaque progression through the induction of proapoptotic endothelial-to-mesenchymal transition (EndMT) within the fibrous cap. METHODS: Human coronary artery sections from CVPath's autopsy registry were selected for pathological analysis. Athero-prone ApoE-/- and ApoE-/-/CD163-/- mice were used for in vivo studies. Human peripheral blood mononuclear cell-induced macrophages and human aortic endothelial cells were used for in vitro experiments. RESULTS: In 107 lesions with acute coronary plaque rupture, 55% had pathological evidence of intraplaque hemorrhage in nonculprit vessels/lesions. Thinner fibrous cap, greater CD163+ macrophage accumulation, and a larger number of CD31/FSP-1 (fibroblast specific protein-1) double-positive cells and TUNEL (terminal deoxynucleotidyl transferase-dUTP nick end labeling) positive cells in the fibrous cap were observed in nonculprit intraplaque hemorrhage lesions, as well as in culprit rupture sections versus nonculprit fibroatheroma sections. Human aortic endothelial cells cultured with supernatants from hemoglobin/haptoglobin-exposed macrophages showed that increased mesenchymal marker proteins (transgelin and FSP-1) while endothelial markers (VE-cadherin and CD31) were reduced, suggesting EndMT induction. Activation of NF-κB (nuclear factor kappa ß) signaling by proinflammatory cytokines released from CD163+ macrophages directly regulated the expression of Snail, a critical transcription factor during EndMT induction. Western blot analysis for cleaved caspase-3 and microarray analysis of human aortic endothelial cells indicated that apoptosis was stimulated during CD163+ macrophage-induced EndMT. Additionally, CD163 deletion in athero-prone mice suggested that CD163 is required for EndMT and plaque progression. Using single-cell RNA sequencing from human carotid endarterectomy lesions, a population of EndMT was detected, which demonstrated significant upregulation of apoptosis-related genes. CONCLUSIONS: CD163+ macrophages provoke EndMT, which may promote plaque progression through fibrous cap thinning.

Effect of EDTA with porous balloon on calcified lesion: An atherosclerotic cadaver study.

BACKGROUND: Ethylene diamine tetra-acetic acid (EDTA) is a chelating agent used to dissolve calcium deposits but evidence in decalcifying atherosclerotic lesions is limited. AIMS: We assessed the feasibility and efficacy of EDTA delivered via porous balloon to target calcified lesions in cadaveric below-the-knee (BTK) arteries. METHODS: Using porcine carotid arteries, EDTA concentration was measured in the arterial wall and outside the artery at the 0-, 0.5-, 4-, and 24-h circulation after the injection through a porous balloon. In cadaver BTK samples, the proximal and distal anterior tibial artery (ATA) and distal posterior tibial artery (PTA) were studied. EDTA-2Na/H2O or EDTA-3Na/H2O were administrated using a porous balloon, then circulated for 6 h for EDTA-3Na/H2O and 24 h for EDTA-2Na/H2O and EDTA-3Na/H2O. Micro-CT imaging of the artery segments before and after the circulation and cross-sectional analyses were performed to evaluate calcium burden. RESULTS: In the porcine carotid study, EDTA was delivered through a porous balloon present in the arterial wall and was retained there for 24 h. In BTK arteries, cross-sectional analyses of micro-CT revealed a significant decrease in the calcium area in the distal ATA segment under 24-h circulation with EDTA-2Na/H2O and in the distal ATA segment under 24-h circulation with EDTA-3Na/H2O. The proximal ATA segment under 6-h circulation with EDTA-3Na/H2O showed no significant change in any parameters of calcium CONCLUSION: EDTA-3Na/H2O or EDTA-2Na/H2O with longer circulation times resulted in greater calcium reduction in atherosclerotic lesion. EDTA may have a potential therapeutic option for the treatment of atherosclerotic calcified lesions.

Clonal Proliferation Within Smooth Muscle Cells in Unstable Human Atherosclerotic Lesions.

BACKGROUND: Studies in humans and mice using the expression of an X-linked gene or lineage tracing, respectively, have suggested that clones of smooth muscle cells (SMCs) exist in human atherosclerotic lesions but are limited by either spatial resolution or translatability of the model. METHODS: Phenotypic clonality can be detected by X-chromosome inactivation patterns. We investigated whether clones of SMCs exist in unstable human atheroma using RNA in situ hybridization (BaseScope) to identify a naturally occurring 24-nucleotide deletion in the 3'UTR of the X-linked BGN (biglycan) gene, a proteoglycan highly expressed by SMCs. BGN-specific BaseScope probes were designed to target the wild-type or deletion mRNA. Three different coronary artery plaque types (erosion, rupture, and adaptive intimal thickening) were selected from heterozygous females for the deletion BGN. Hybridization of target RNA-specific probes was used to visualize the spatial distribution of mutants. A clonality index was calculated from the percentage of each probe in each region of interest. Spatial transcriptomics were used to identify differentially expressed transcripts within clonal and nonclonal regions. RESULTS: Less than one-half of regions of interest in the intimal plaque were considered clonal with the mean percent regions of interest with clonality higher in the intimal plaque than in the media. This was consistent for all plaque types. The relationship of the dominant clone in the intimal plaque and media showed significant concordance. In comparison with the nonclonal lesions, the regions with SMC clonality had lower expression of genes encoding cell growth suppressors such as CD74, SERF-2 (small EDRK-rich factor 2), CTSB (cathepsin B), and HLA-DPA1 (major histocompatibility complex, class II, DP alpha 1), among others. CONCLUSIONS: Our novel approach to examine clonality suggests atherosclerosis is primarily a disease of polyclonally and to a lesser extent clonally expanded SMCs and may have implications for the development of antiatherosclerotic therapies.

Impact of lipoprotein(a) levels on primary patency after endovascular therapy for femoropopliteal lesions.

Lipoprotein(a) [Lp(a)] is a risk factor for peripheral artery disease (PAD). However, the relationship between Lp(a) levels and clinical events after endovascular therapy (EVT) for the femoropopliteal artery in PAD patients remains unclear. Thus, this study aimed to assess the impact of Lp(a) levels on primary patency after EVT for de novo femoropopliteal lesions in PAD patients. A retrospective analysis was conducted on 109 patients who underwent EVT for de novo femoropopliteal lesions, and Lp(a) levels were measured before EVT between June 2016 and December 2019. Patients were divided into low Lp(a) [Lp(a) < 30 mg/dL; 78 patients] and high Lp(a) [Lp(a) ≥ 30 mg/dL; 31 patients] groups. The main outcome was primary patency following EVT. Loss of primary patency was defined as a peak systolic velocity ratio > 2.4 on a duplex scan or > 50% stenosis on angiography. Cox proportional hazards analysis was performed to determine whether high Lp(a) levels were independently associated with loss of primary patency. The mean follow-up duration was 28 months. The rates of primary patency were 83 and 76% at 1 year and 75 and 58% at 2 years in the low and high Lp(a) groups, respectively (P = 0.02). After multivariate analysis, High Lp(a)[Lp(a) ≥ 30 mg/dL] (hazard ratio 2.44; 95% CI 1.10-5.44; P = 0.03) and female sex (hazard ratio 2.65; 95% CI 1.27-5.51; P < 0.01) were independent predictors of loss of primary patency. Lp(a) levels might be associated with primary patency after EVT for de novo femoropopliteal lesions.

Impact of IVUS-Derived Vessel Size on Midterm Outcomes After Stent Implantation in Femoropopliteal Lesions.

Purpose: To identify intravascular ultrasound (IVUS) findings that predict midterm stent patency in femoropopliteal (FP) lesions. Materials and Methods: A retrospective analysis was undertaken of 335 de novo FP lesions in 274 consecutive patients (mean age 72.4±8.2 years; 210 men) who had IVUS assessment before and after successful stent implantation. The mean lesion length was 13.2±9.8 cm. The primary outcome was primary patency at 24 months, defined as freedom from major adverse limb event (MALE) and in-stent restenosis (ISR). MALE was defined as major amputation or any target lesion revascularization (TLR). ISR was defined by a peak systolic velocity ratio >2.4 by duplex ultrasonography. Logistic regression analyses were performed to identify independent predictors of stent patency at 24 months; the results are presented as the odds ratio (OR) and 95% confidence interval (CI). Receiver operator characteristic (ROC) curve analysis was performed to determine the optimal threshold for prediction of stent patency at 24 months. Results: Over the 24-month follow-up, 18 (7%) patients died and 43 (15%) of 286 lesions were responsible for MALE (42 TLRs and 1 major amputation). Primary patency was estimated at 82.5% (95% CI 78.1% to 86.9%) at 12 months and 73.2% (95% CI 67.9% to 78.5%) at 24 months. Multivariable analysis revealed that longer lesion length (OR 0.89, 95% CI 0.82 to 0.97, p<0.01) was an independent predictor of declining patency, while cilostazol use (OR 3.45, 95% CI 1.10 to 10.78, p=0.03) and increasing distal reference external elastic membrane (EEM) area (OR 1.18, 95% CI 1.02 to 1.37, p=0.03) were associated with midterm stent patency. ROC curve analysis identified a distal reference EEM area of 29.0 mm2 as the optimal cut-point for prediction of 24-month stent patency (area under the ROC curve 0.764). Kaplan-Meier estimates of 24-month primary patency were 83.7% (95% CI 78.3% to 89.2%) in lesions with a distal EEM area >29.0 mm2 vs 53.1% (95% CI 42.9% to 63.3%) in those with a distal EEM area ≤29.0 mm2 (p<0.001). Conclusion: In FP lesions with a larger distal vessel area estimated with IVUS, stent implantation can be considered as a reasonable treatment option, with the likelihood of acceptable midterm results.

Influence of Self-Expanding Paclitaxel-Eluting Stent Sizing on Neointimal Hyperplasia in Superficial Femoral Artery Lesions.

BACKGROUND: Although self-expanding drug-eluting stents (DES) have recently shown superior outcomes for superficial femoral artery (SFA) lesions, optimal sizing of DES diameter in SFA intervention is unclear.Methods and Results:A total of 40 de novo SFA lesions were randomized 1:1 to receive self-expanding DES with either a 1-mm or 2-mm larger diameter than the reference vessel diameter. Follow-up optical coherence tomography (OCT) was scheduled 6 months after DES implantation to evaluate the vascular response to the stents. Volume index (VI) was defined as volume divided by stent length. The primary endpoint was neointimal VI at 6 months. Baseline reference vessel diameter was similar between the 1-mm larger diameter group and the 2-mm larger diameter group (5.0±0.8 mm vs. 4.7±0.9 mm, P=0.35). Stent diameter was 6.3±0.6 mm in the 1-mm larger group and 7.1±0.6 mm in the 2-mm larger group (P<0.0001), and stent to reference vessel diameter ratio (SV ratio) was 1.3±0.2 and 1.5±0.2 (P<0.0001), respectively. At 6-month, neointimal VI was greater in the 2-mm larger diameter group (5.5±1.5 mm2vs. 9.6±3.4 mm2, P<0.001). The correlation analysis revealed that degree of neointimal VI was positively correlated with SV ratio (r=0.43, P<0.01). CONCLUSIONS: Implantation of self-expanding DES with a considerably high SV ratio resulted in neointimal hyperplasia in SFA lesions.

Endovascular Therapy with a Covered Stent Graft for Pseudoaneurysm of the Peroneal Artery Complicating High Tibial Osteotomy-A Case Report.

Pseudoaneurysm of below-the-knee arteries after a high tibial osteotomy (HTO) is rare. A 69-year-old woman with history of right HTO a half year ago had performed a left HTO for osteoarthritis. Postoperatively, she had swelling and pain of the left lower leg. Computed tomography and echocardiography revealed the pseudoaneurysm of peroneal artery (PA). After the release of the covered stent graft, the pseudoaneurysm of the PA did not disappear, it was completely excluded in the completion angiogram.

Transformative elements of intercultural education for Japanese nursing students.

There has been little research exploring Japanese nursing students' experiences of having Western instructors in their nursing programs. The purpose of the present study was to describe Japanese nursing students' lived experiences of being taught by foreign faculty. A qualitative design using an interpretive phenomenology approach was used with purposeful sampling. Graduate and undergraduate nursing students (n = 13), who had the experience of being taught by a foreign faculty member for at least one semester, were recruited. Six themes emerged that suggested the participants went through an evolutionary process as they worked to understand and make meaning of these intercultural experiences: struggling with uncertainty, working to understand, discovering differences in teaching styles, opening my eyes to the world, thinking differently now, and wanting to know more. The work students must do to understand foreign teachers influences what they are able to learn, and must be taken into consideration by both faculty and students. To fully realize meaningful teaching outcomes within this intercultural context, it is essential that students have sustained exposure to foreign faculty.

One-pot synthesis of 2,5-dihydropyrroles from terminal alkynes, azides, and propargylic alcohols by relay actions of copper, rhodium, and gold.

Relay actions of copper, rhodium, and gold formulate a one-pot multistep pathway, which directly gives 2,5-dihydropyrroles starting from terminal alkynes, sulfonyl azides, and propargylic alcohols. Initially, copper-catalyzed 1,3-dipolar cycloaddition of terminal alkynes with sulfonyl azides affords 1-sulfonyl-1,2,3-triazoles, which then react with propargylic alcohols under the catalysis of rhodium. The resulting alkenyl propargyl ethers subsequently undergo the thermal Claisen rearrangement to give α-allenyl-α-amino ketones. Finally, a gold catalyst prompts 5-endo cyclization to produce 2,5-dihydropyrroles.

[The characteristics of urinary tract infection with urosepsis].

BACKGROUND AND PURPOSE: Urinary tract infections (UTIs) are frequently complicated with bacteremia. Many cases of this infection are diagnosed and treated by general practitioners. We retrospectively exam- ined the characteristics of UTIs presenting with urosepsis. METHODS: We assigned 57 UTI patients into two groups according to the results of the blood cultures. Patients were admitted to the Department of General Practice at Sakai City Hospital from January 1, 2011 to December 31, 2011. We investigated the medical records retrospectively. RESULTS: 22 patients presented with urosepsis and 35 did not. Urosepsis in the patients was significantly associated with diabetes mellitus and ureteral stones (diabetes: 32 vs. 3%, p = 0.004; ureteral stone: 23 vs. 3%, p = 0.03). Nausea or vomiting and hydronephrosis were seen in about one half of the patients with urosepsis and were significantly more frequent (nausea or vomiting: 45 vs. 17%, p = 0.03; hydronephrosis: 36 vs. 11%, p = 0.04). Leukocytosis (white blood cell (WBC) count > 12,000/gL) or leukopenia (WBC count < 4,000 /µL) were significantly more frequent (68% vs. 29%) but no significant association was found between urosepsis and body temperature or C-reactive proteins. CONCLUSIONS: Nausea or vomiting, ureteral stones or hydronephrosis, diabetes mellitus and leukocytosis or leukopenia had significantly higher rates in the patients with urosepsis.

Challenges and advances in device-related thrombus in left atrial appendage occlusion.

Oral anticoagulation therapy (OAC) is a mainstay for mitigating stroke and other embolic events in patients with atrial fibrillation (AF). Despite the demonstrated efficacy of OAC in reducing events, many patients are unable to tolerate OAC due to bleeding risks. Left atrial appendage occlusion (LAAO) devices were developed as implantable technologies to moderate stroke risk in patients with intolerance to OAC. Despite clinical data supporting near-comparable protection against thromboembolic events with OAC, device-related thrombus formation has emerged as a critical complication following LAAO that remains a potential limitation to the safety and efficacy of LAAO. Improved biocompatibility of LAAO devices with fluoropolymers, a well-established stent-coating technology used to reduce thrombus formation and promote endothelialization, may optimize outcomes after LAAO.

[Box: see text].

Spontaneous Coronary Artery Dissection Resulting in Acute Myocardial Infarction With Cardiac Rupture.

Spontaneous coronary artery dissection occurs predominantly in women and is associated with fibromuscular dysplasia. We illustrate a rare case of sudden coronary death as a result of cardiac rupture from spontaneous coronary artery dissection in a 54-year-old man without fibromuscular dysplasia. Cardiac rupture has been previously reported in 6 cases, mostly in women.

Mechanisms of Medial Wall Thinning in Chronic Total Occlusion.

BACKGROUND: The success rate of percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) is lower and the risk for complications higher compared with other non-CTO PCI. Although interventionalists focus on intimal plaque characteristics, the coronary media is an important (especially for techniques involving antegrade dissection and re-entry) but poorly understood structure in CTO PCI. OBJECTIVES: The aim of the present study was to investigate coronary medial wall thinning in CTO lesions and determine how this thinning might affect CTO PCI. METHODS: A total of 2,586 sections were investigated, from arteries with evidence of CTO from 54 subjects (n = 1,383 sections) and arteries without evidence of CTO from 54 subjects with non-coronary-related deaths (n = 1,203 sections) after matching for age, gender, body weight, and body height. RESULTS: The medial thickness in subjects with CTO was lower than that in those with non-coronary-related death (P < 0.001). In subjects with CTO, CTO lesions had thinner medial walls compared with those with lower luminal narrowing (P < 0.001). At the CTO distal segments, the 6- to 12-mm distal segment from the distal end of the CTO had significantly less luminal narrowing (P < 0.001), and similar medial thickness, compared with the distal end of the CTO. Immunohistochemical analysis revealed that short-duration CTO had more cleaved caspase-3-positive cells in media and had significantly more CD3+, CD4+, CD8+, and CD4+CD28null T cells compared with long-duration CTO. CONCLUSIONS: CTO lesions demonstrated coronary medial thinning compared with non-CTO lesions. Further investigation of the cause-and-effect relationship among inflammation, apoptosis, and coronary medial wall thinning is warranted in future mechanistic studies.

Stereoselective synthesis of 2,3-dihydropyrroles from terminal alkynes, azides, and α,ß-unsaturated aldehydes via N-sulfonyl-1,2,3-triazoles.

A stereoselective method for synthesis of trans-2,3-disubstituted 2,3-dihydropyrroles is reported. N-Sulfonyl-1,2,3-triazoles prepared from terminal alkynes generate α-imino rhodium carbene complexes, which when combined with α,ß-unsaturated aldehydes produce trans-2,3-disubstituted dihydropyrroles. The method can be successfully applied to a one-pot process starting from terminal alkynes.

Guide extension proximal locking method: standardization of maximum backup force in percutaneous coronary intervention.

We developed the smallest diameter guide-extension catheter (GUIDE PLUS® 5Fr) to enable a new technique, the guide-extension proximal locking method (GP-Lock), and assessed its efficacy in the present experimental and clinical study. Sufficient guide catheter backup is sometimes crucial for PCI. We developed the KIWAMI-Lock direct anchoring method to obtain the strongest backup force by locking a Kiwami® 4Fr child catheter (Terumo Corp. Tokyo, Japan) directly to the coronary artery by ballooning from outside the child catheter. However, this method is complicated due to the requirement for a child catheter. We compared the backup power of the GP-Lock method and other conventional methods in an experimental study and compared the procedural outcomes of 17 cases treated using the initial GP-Lock method with 17 cases using the recent KIWAMI-Lock method before GP-Lock. The GP-Lock method had the highest backup force among the methods examined (GP-Lock: 293.7 ± 10.2 g force (gf), KIWAMI-Lock: 270.4 ± 12.9 gf, side branch balloon anchoring technique: 182.7 ± 8.1 gf, respectively, P < 0.0001). The preparation time was significantly shorter for the GP-Lock group than the KIWAMI-Lock group (5.0 [4.0, 5.0] min vs. 11.0 [8.0, 13.0] min, respectively, P < 0.001). The GP-Lock method makes it possible to easily obtain the strongest backup force, which can overcome situations where devices cannot pass through, especially in complex PCI procedures.

Impact of lipoprotein (a) on long-term outcome after percutaneous coronary intervention in the era of new generation drug-eluting stents.

BACKGROUND: High lipoprotein (a) [Lp (a)] levels are associated with worse long-term outcomes in patients undergoing percutaneous coronary intervention (PCI). However, there are limited studies investigating association between Lp (a) levels and long-term outcomes in the era of new generation drug-eluting stents (DES). METHODS: A total of 495 patients with available data on Lp (a) who underwent PCI for de novo lesions with new generation DES were enrolled between 2013 and 2017. The primary endpoint was the major adverse cardiovascular event (MACE), which was defined as a composite of cardiac death, myocardial infarction, stent thrombosis, clinically driven target lesion revascularization, and revascularization for new lesions during 3 years. Patients were divided into 2 groups according to the Lp (a) level: high Lp (a) group (≥30 mg/dL: n = 109) and low Lp (a) group (30 mg/dL>: n = 386). Multivariate Cox regression analysis was performed to identify the predictors for 3-year MACE. RESULTS: The incidence of 3-year MACE was significantly higher in high Lp (a) group than low Lp (a) group (33.0% vs. 15.9%, p < 0.001). Multivariable analysis showed that Lp (a) level of ≥30 mg/dL was an independent predictor for 3-year MACE (HR 2.01, 95%CI 1.30-3.11, p = 0.002). CONCLUSION: High Lp (a) level was associated with worse long-term outcome even in the era of new generation DES.

Potential of optical frequency domain imaging for differentiation between early and advanced coronary atherosclerosis.

PURPOSE: This study evaluated whether optical frequency domain imaging (OFDI) accurately distinguish between fibroatheroma (FA) and pathological intimal thickening (PIT) compared with histopathology. METHODS: A total of 631 histological cross-sections from 14 autopsy hearts were analyzed for the comparison between OFDI and histological images. Of those, 190 (30%) sections were diagnosed with PIT and 120 (19%) with FA. The OFDI signal attenuation rate was calculated from an exponential. The lipid length was measured longitudinally by detection of sequential OFDI frames within a plaque segment containing lipids. The lipid arc was measured with a protractor centered in the center of the lumen. The fibrous cap thickness was defined as the minimum thickness of the signal rich band overlying PIT and FA. RESULTS: There was no significant difference in the OFDI signal attenuation rate between FA and PIT (3.09 ± 1.04 versus 2.79 ± 1.20, p = 0.13). However, the lipid length was significantly longer, the maximum lipid arc was significantly larger, and the fibrous cap thickness was significantly thinner in FA than in PIT (7.5 [4.3-10.3] mm versus 4.3 [2.7-5.8] mm, p < 0.0001, 125 [101-174]° versus 96 [74-131]°, p < 0.0001, and 220 [167-280] µm versus 260 [190-332] µm, p = 0.019). CONCLUSIONS: This study revealed OFDI may have the potential capability for discriminating FA from PIT based on the longitudinal and circumferential extent of lipid plaque, although the OFDI signal attenuation rate was similar between FA and PIT.

Comparison of coronary atherosclerotic disease burden between ST-elevation myocardial infarction and non-ST-elevation myocardial infarction: Non-culprit Gensini score and non-culprit SYNTAX score.

BACKGROUND: Patients with non-ST-elevation myocardial infarction (NSTEMI) have worse long-term prognoses than those with ST-elevation myocardial infarction (STEMI). HYPOTHESIS: It may be attributable to more extended coronary atherosclerotic disease burden in patients with NSTEMI. METHODS: This study consisted of consecutive 231 patients who underwent coronary intervention for myocardial infarction (MI). To assess the extent and severity of atherosclerotic disease burden of non-culprit coronary arteries, two scoring systems (Gensini score and synergy between percutaneous coronary intervention with Taxus and cardiac surgery [SYNTAX] score) were modified by subtracting the score of the culprit lesion: the non-culprit Gensini score and the non-culprit SYNTAX score. RESULTS: Patients with NSTEMI had more multi-vessel disease, initial thrombolysis in myocardial infarction (TIMI) flow grade 2/3, and final TIMI flow grade 3 than those with STEMI. As compared to STEMI, patients with NSTEMI had significantly higher non-culprit Gensini score (16.3 ± 19.8 vs. 31.2 ± 25.4, p < 0.001) and non-culprit SYNTAX score (5.8 ± 7.0 vs. 11.1 ± 9.7, p < 0.001). CONCLUSIONS: Patients with NSTEMI had more advanced coronary atherosclerotic disease burden including non-obstruction lesions, which may at least in part explain higher incidence of cardiovascular events in these patients.

Relationship Between Lipoprotein(a) and Angiographic Severity of Femoropopliteal Lesions.

AIM: High levels of lipoprotein(a) [Lp(a)] are a risk factor for peripheral artery disease (PAD). However, the relationship between Lp(a) levels and the severity of femoropopliteal lesions in patients with PAD has not been systematically studied. This study aimed to assess the impact of Lp(a) levels on angiographic severity of femoropopliteal lesions in patients with PAD. METHODS: We retrospectively analyzed a single-center database including 108 patients who underwent endovascular therapy for de novo femoropopliteal lesions and measured the Lp(a) levels before therapy between June 2016 and September 2019. Patients were divided into low Lp(a) [Lp(a) ＜30 mg/dL; 77 patients] and high Lp(a) [Lp(a) ≥ 30 mg/dL; 31 patients] groups. Trans-Atlantic Inter-Society Consensus (TASC) II classification, calcification [referring to the peripheral arterial calcium scoring system (PACSS) classification], and lesion length were compared between the groups. RESULTS: The prevalence of TASC II class D (13% vs 38%, P＜0.01) and severe calcification (PACSS 4) (6% vs 23%, P=0.02) was significantly higher and the lesion length longer (123±88 mm vs 175±102 mm, P＜0.01) in the high Lp(a) group than in the low Lp(a) group. In multivariate analysis, Lp(a) ≥ 30 was an independent predictor for the prevalence of TASC II class D (HR=3.67, 95% CI 1.27-10.6, P=0.02) and PACSS 4 (HR=4.97, 95% CI 1.27-19.4, P=0.02). CONCLUSION: The prevalence of TASC II class D and severe calcification of femoropopliteal lesions was higher in patients with high Lp(a) than those with low Lp(a).