Linking peripheral atherosclerosis to blood-brain barrier disruption: elucidating its role as a manifestation of cerebral small vessel disease in vascular cognitive impairment.

Aging plays a pivotal role in the pathogenesis of cerebral small vessel disease (CSVD), contributing to the onset and progression of vascular cognitive impairment and dementia (VCID). In older adults, CSVD often leads to significant pathological outcomes, including blood-brain barrier (BBB) disruption, which in turn triggers neuroinflammation and white matter damage. This damage is frequently observed as white matter hyperintensities (WMHs) in neuroimaging studies. There is mounting evidence that older adults with atherosclerotic vascular diseases, such as peripheral artery disease, ischemic heart disease, and carotid artery stenosis, face a heightened risk of developing CSVD and VCID. This review explores the complex relationship between peripheral atherosclerosis, the pathogenesis of CSVD, and BBB disruption. It explores the continuum of vascular aging, emphasizing the shared pathomechanisms that underlie atherosclerosis in large arteries and BBB disruption in the cerebral microcirculation, exacerbating both CSVD and VCID. By reviewing current evidence, this paper discusses the impact of endothelial dysfunction, cellular senescence, inflammation, and oxidative stress on vascular and neurovascular health. This review aims to enhance understanding of these complex interactions and advocate for integrated approaches to manage vascular health, thereby mitigating the risk and progression of CSVD and VCID.

Co-Morbidity Differences Associated With Long-Term Amputation and Repeat Revascularization Rates After Femoropopliteal Artery Intervention for Intermittent Claudication by Gender, Race, and Ethnicity.

Use of peripheral vascular intervention (PVI) for intermittent claudication (IC) continues to expand, but there is uncertainty whether baseline demographics, procedural techniques and outcomes differ by gender, race, and ethnicity. This study aimed to examine amputation and revascularization rates up to 4 years after femoropopliteal (FP) PVI for IC by gender, race, and ethnicity. Patients who underwent FP PVI for IC between 2016 and 2020 from the PINC AI Healthcare Database were analyzed. The primary outcome was any index limb amputation, assessed by Kaplan-Meier estimate. Secondary outcomes included index limb major amputation, repeat revascularization, and index limb repeat revascularization. Unadjusted and adjusted hazard ratios (HRs) were estimated using Cox proportional hazard regression models. This study included 19,324 patients with IC who underwent FP PVI, with 41.2% women, 15.6% Black patients, and 4.7% Hispanic patients. Women were less likely than men to be treated with atherectomy (45.1% vs 47.8%, p = 0.0003); Black patients were more likely than White patients to receive atherectomy (50.7% vs 44.9%, p <0.001), and Hispanic patients were less likely than non-Hispanic patients to receive atherectomy (41% vs 47%, p = 0.0004). Unadjusted rates of any amputation were similar in men and women (6.4% for each group, log-rank p = 0.842), higher in Black patients than in White patients (7.8% vs 6.1%, log-rank p = 0.007), and higher in Hispanic patients than in non-Hispanic patients (8.8% vs 6.3%, log-rank p = 0.031). After adjustment for baseline characteristics, Black race was associated with higher rates of repeat revascularization (adjusted HR 1.13, 95% confidence interval 1.04 to 1.22) and any FP revascularization (adjusted HR 1.10, 95% confidence interval 1.01 to 1.20). No statistical difference in amputation rate was observed among comparison groups. Women and men with IC had similar crude and adjusted amputation and revascularization outcomes after FP PVI. Black patients had higher repeat revascularization and any FP revascularization rates than did White patients. Black and Hispanic patients had higher crude amputation rates, but these differences were attenuated by adjustment for baseline characteristics. Black patients were more likely to receive atherectomy and had higher rates of any repeat revascularization and specifically FP revascularization. Further study is necessary to determine whether these patterns are related to disease-specific issues or practice-pattern differences among different populations.

Could the periodontal therapy improve the cardiologic patient health? A narrative review.

BACKGROUND: Cardiovascular diseases (CVD) is the major cause of mortality globally, with increasing evidence suggesting a link between periodontitis, and CVD. This study aims to explore the association between periodontitis and CVD, and the impact of periodontal therapy on cardiovascular health. METHODS: This review synthesized findings from preclinical and clinical studies, without publication year restrictions, examining periodontitis and CVD through various lenses. Scientific databases were inspected with keywords related to periodontitis and CVD. RESULTS: The review identifies a substantial association between periodontitis and an increased risk of several CVD, supported by both epidemiological and interventional studies. Results suggest the complexity of the relationship, influenced by factors like the severity of periodontitis and the presence of other systemic conditions. Clinical data indicates that periodontal therapy, particularly non-surgical periodontal therapy, may reduce systemic inflammatory markers and thus may play a role in the primary and secondary prevention of CVD events, highlighting the potential of periodontal therapy to not only maintain oral health but also to modulate cardiovascular risk factors. CONCLUSIONS: Current evidence supports a significant association between periodontitis and increased cardiovascular risk, promoting integrated healthcare approaches that consider oral health as a key-component of cardiovascular care and wellbeing.

Covered Endovascular Reconstruction of the Iliac Artery Bifurcation (CERIB).

PURPOSE: The aim of this study was to present the covered endovascular reconstruction of the iliac artery bifurcation (CERIB) technique as a revascularization option for aorto-iliac occlusive disease (AIOD) involving the iliac artery bifurcation. METHODS: This was a retrospective single-center study including all patients undergoing a CERIB procedure from January 2021 until December 2022. Covered endovascular reconstruction of the iliac artery bifurcation procedures were performed percutaneously with bilateral femoral access, excepting cases where simultaneous open femoral artery reconstruction was required due to the extension of peripheral arterial occlusive disease. Standard patient, procedural, and follow-up (FU) data including survival and arterial reinterventions were gathered and analyzed. RESULTS: A total of 13 patients were included (11/13 male, median age=70 [60-76] years). Additional open and/or endovascular procedures included endarterectomy of the femoral bifurcation (n=6), rotational atherectomy (n=2), and 1 axillary artery cutdown for upper limb access (n=1). Median operating time was 2.9 hours (1.5-4.9 hours); median radiation duration and dose were 28.4 (14.3-63.3 minutes) and 4090.6 (384.4-9430.1 cGray/cm2), respectively. The stent grafts used for CERIB were BeGraft peripheral n=31, BeGraft Aortic n=4 and BeGraft peripheral plus n=1 (Bentley InnoMed GmbH, Hechingen, Germany). In 2 patients with prior stenting of the common iliac artery (CIA), only the internal and external iliac arteries (IIA and EIA) were treated in this study, and in 2 cases, additional uncovered stents were required for relining. Technical success was 100%. During a midterm FU (median 18 [4-31] months), 2 patients died from cardiovascular reasons and 1 patient with prior iliac stenting required reinterventions for recurring occlusion. CONCLUSION: Covered endovascular reconstruction of the iliac artery bifurcation is a straightforward option for treating AIOD involving the iliac artery bifurcation that allows preservation of internal iliac artery perfusion and shows good early and midterm results. Prior iliac artery stenting may be a risk factor for early occlusion after CERIB. CLINICAL IMPACT: Aorto-iliac occlusive disease with involvement of the internal iliac artery is encountered regularly in vascular surgical practice, but the internal iliac artery is often not included in the revascularization strategy. The present article will increase the awareness for the relevance of including the internal iliac artery in revascularization strategies and presents CERIB as another method to be added to the armamentarium of (endo-)vascular surgeons and interventionalists.

Relationship of apolipoprotein C-III proteoform composition with ankle-brachial index and peripheral artery disease in the Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND AND AIMS: Apolipoprotein C-III (apoC-III) proteoform composition shows distinct relationships with plasma lipids and cardiovascular risk. The present study tested whether apoC-III proteoforms are associated with risk of peripheral artery disease (PAD). METHODS: ApoC-III proteoforms, i.e., native (C-III0a), and glycosylated with zero (C-III0b), one (C-III1) or two (C-III2) sialic acids, were measured by mass spectrometry immunoassay on 5,734 Multi-Ethnic Study of Atherosclerosis participants who were subsequently followed for clinical PAD over 17 years. Ankle-brachial index (ABI) was also assessed at baseline and then 3 and 10 years later in 4,830 participants. RESULTS: Higher baseline C-III0b/C-III1 and lower baseline C-III2/C-III1 were associated with slower decline in ABI (follow-up adjusted for baseline) over time, independently of cardiometabolic risk factors, and plasma triglycerides and HDL cholesterol levels (estimated difference per 1 SD was 0.31 % for both, p < 0.01). The associations between C-III2/C-III1 and changes in ABI were stronger in men (-1.21 % vs. -0.27 % in women), and in Black and Chinese participants (-0.83 % and -0.86 % vs. 0.12 % in White). Higher C-III0b/C-III1 was associated with a trend for lower risk of PAD (HR = 0.84 [95%CI: 0.67-1.04]) that became stronger after excluding participants on lipid-lowering medications (0.73 [95%CI: 0.57-0.94]). Neither change in ABI nor clinical PAD was related to total apoC-III levels. CONCLUSIONS: We found associations of apoC-III proteoform composition with changes in ABI that were independent of other risk factors, including plasma lipids. Our data further support unique properties of apoC-III proteoforms in modulating vascular health that go beyond total apoC-III levels.

Intravascular lithotripsy in peripheral lesions with severe calcification and its use in TAVI procedure - a meta-analysis.

Background: Heavily calcified peripheral artery lesions increase the risk of vascular complications, constituting a severe challenge for the operator during catheter-based cardiovascular interventions. Intravascular Lithotripsy (IVL) technology disrupts subendothelial calcification by using localized pulsative sonic pressure waves and represents a promising technique for plaque modification in patients with severe calcification in peripheral arteries. Purpose: Our aim was to systematically review and summarize available data regarding the safety and efficacy of IVL in preparing severely calcified peripheral arteries and its use in Transcatheter Aortic Valve Implantation (TAVI). Patients and methods: This study was conducted according to the PRISMA guidelines. We systematically searched PubMed, SCOPUS, and Cochrane databases from their inception to February 23, 2023, for studies assessing the characteristics and outcomes of patients undergoing IVL in the peripheral vasculature. The diameter of the vessel lumen before and after IVL was estimated. The occurrence of peri-procedural complications was assessed using a random-effects model. Results: 20 studies with a total of 1,223 patients with heavily calcified peripheral lesions were analysed. The mean age of the cohort was 70.6 ± 17.4 years. Successful IVL delivery achieved in 100% (95% CI: 100%-100%, I2 = 0%), with an increase in the luminal diameter (SMD: 4.66, 95% CI: 3.41-5.92, I2 = 90.8%) and reduction in diameter stenosis (SMD: -4.15, 95% CI: -4.75 to -3.55, I2 = 92.8%), and a concomitant low rate of complications. The procedure was free from dissection in 97% (95% CI: 91%-100%, I2 = 81.4%) while dissections of any type (A, B, C, or D) were observed in 6% (95% CI: 2%-10%, I2 = 85.3%) of the patients. Several rare cases of abrupt closure, no-reflow phenomenon, perforation, thrombus formation, and distal embolization were recorded. Finally, the subgroup analysis of patients who underwent a TAVI with IVL assistance presented successful implantation in 100% (95% CI: 100%-100%, I2 = 0%) of the cases, with only 4% (95% CI: 0%-12%, I2 = 68.96%) presenting dissections of any sort. Conclusions: IVL seems to be an effective and safe technique for modifying severely calcified lesions in peripheral arteries and it is a promising modality in TAVI settings. Future prospective studies are needed to validate our results.

Associations between lipoprotein(a), oxidized phospholipids, and extra-coronary vascular disease.

The roles of lipoprotein(a) [Lp(a)] and related oxidized phospholipids (OxPL) in the development and progression of coronary disease is known, but their influence on extra-coronary vascular disease is not well-established. We sought to evaluate associations between Lp(a), OxPL apolipoprotein B (OxPL-apoB), and apolipoprotein(a) (OxPL-apo(a)) with angiographic extra-coronary vascular disease and incident major adverse limb events (MALE). 446 participants who underwent coronary and/or peripheral angiography were followed up for a median of 3.7 years. Lp(a) and OxPLs were measured before angiography. Elevated Lp(a) was defined as ≥150 nmol/L. Elevated OxPL-apoB and OxPL-apo(a) were defined as greater than or equal to the 75th percentile (OxPL-apoB ≥8.2 nmol/L and OxPL-apo(a) ≥35.8 nmol/L, respectively). Elevated Lp(a) had a stronger association with the presence of extra-coronary vascular disease compared to OxPLs and was minimally improved with the addition of OxPLs in multivariable models. Compared to participants with normal Lp(a) and OxPL concentrations, participants with elevated Lp(a) levels were twice as likely to experience a MALE (OR 2.14 95% CI: 1.03, 4.44) and the strength of the association as well as the C statistic of 0.82 was largely unchanged with the addition of OxPL-apoB and OxPL-apo(a). Elevated Lp(a) and OxPLs are risk factors for progression and complications of extra-coronary vascular disease. However, the addition of OxPLs to Lp(a) does not provide additional information about risk of extra-coronary vascular disease. Therefore, Lp(a) alone captures the risk profile of Lp(a), OxPL-apoB, and OxPL-apo(a) in the development and progression of atherosclerotic plaque in peripheral arteries. These results lay a foundation in support of studying Lp(a) lowering medications and their effect on limb-related complications.

The Clinical Impact of Access Site Selection for Successful Thrombolysis and Intervention in Acute Critical Lower Limb Ischaemia (RAD-ALI Registry).

Background: Acute limb ischaemia (ALI) is of great clinical importance due to its consequent serious complications and high comorbidity and mortality rates. The purpose of this study was to compare the acute success and complication rates of CDT performed via transradial, transbrachial, and transfemoral access sites in patients with acute lower limb vascular occlusion and to investigate the 1-year outcomes of CDT and MT for ALI. Methods: Between 2008 and 2019, 84 consecutive patients with ALI were treated with CDT in a large community hospital. Data were collected and retrospectively analysed. The primary ("safety") endpoints encompassed major adverse events (MAEs), major adverse limb events (MALEs), and the occurrence of complications related to the access site. Secondary ("efficacy") endpoints included both technical and clinical achievements, treatment success, fluoroscopy time, radiation dose, procedure time, and the crossover rate to an alternative puncture site. Results: CDT was started with radial (n = 17), brachial (n = 9), or femoral (n = 58) access. CDT was technically successful in 74/84 patients (88%), but additional MT and angioplasty and/or stent implantation was necessary in 17 (20.2%) and 45 cases (53.6%), respectively. Clinical success was achieved in 74/84 cases (88%). The mortality rate at 1 year was 14.3%. The cumulative incidence of MAEs and MALEs at 12 months was 50% and 40.5%, respectively. After conducting multivariate analysis, history of Rutherford stage IIB (hazard ratio [HR], 3.64; 95% confidence interval [CI], 1.58-8.41; p = 0.0025), occlusion of the external iliac artery (HR, 27.52; 95% CI, 2.83-267.33; p = 0.0043), being a case of clinically unsuccessful thrombolysis (HR, 7.72; 95% CI, 2.48-23.10; p = 0.0004), and the presence of diabetes mellitus (HR, 2.18; 95% CI, 1.01-4.71; p = 0.047) were independent predictors of a high MAE mortality rate at 12 months. For MALEs, statistically significant differences were detected with the variables history of Rutherford stage IIB (HR, 4.30; 95% CI, 1.99-9.31; p = 0.0002) and external iliac artery occlusion (HR, 31.27; 95% CI, 3.47-282.23; p = 0.0022). Conclusions: Based on the short-term results of CDT, acute limb ischaemia can be successfully, safely, and effectively treated with catheter-directed thrombolytic therapy with radial, brachial, or femoral access. However, radial access is associated with fewer access site complications. A history of Rutherford stage IIB, occlusion of external iliac artery, unsuccessful thrombolysis, and the presence of diabetes mellitus were independently associated with an increased risk of MAEs. A history of Rutherford stage IIB and external iliac artery occlusion are independent predictors of MALEs.

The Identification and Evaluation of Interleukin-7 as a Myokine Biomarker for Peripheral Artery Disease Prognosis.

Background/Objectives: Myokines have been demonstrated to be associated with cardiovascular diseases; however, they have not been studied as biomarkers for peripheral artery disease (PAD). We identified interleukin-7 (IL-7) as a prognostic biomarker for PAD from a panel of myokines and developed predictive models for 2-year major adverse limb events (MALEs) using clinical features and plasma IL-7 levels. Methods: A prognostic study was conducted with a cohort of 476 patients (312 with PAD and 164 without PAD) that were recruited prospectively. Their plasma concentrations of five circulating myokines were measured at recruitment, and the patients were followed for two years. The outcome of interest was two-year MALEs (composite of major amputation, vascular intervention, or acute limb ischemia). Cox proportional hazards analysis was performed to identify IL-7 as the only myokine that was associated with 2-year MALEs. The data were randomly divided into training (70%) and test sets (30%). A random forest model was trained using clinical characteristics (demographics, comorbidities, and medications) and plasma IL-7 levels with 10-fold cross-validation. The primary model evaluation metric was the F1 score. The prognostic model was used to classify patients into low vs. high risk of developing adverse limb events based on the Youden Index. Freedom from MALEs over 2 years was compared between the risk-stratified groups using Cox proportional hazards analysis. Results: Two-year MALEs occurred in 28 (9%) of patients with PAD. IL-7 was the only myokine that was statistically significantly correlated with two-year MALE (HR 1.56 [95% CI 1.12-1.88], p = 0.007). For the prognosis of 2-year MALEs, our model achieved an F1 score of 0.829 using plasma IL-7 levels in combination with clinical features. Patients classified as high-risk by the predictive model were significantly more likely to develop MALEs over a 2-year period (HR 1.66 [95% CI 1.22-1.98], p = 0.006). Conclusions: From a panel of myokines, IL-7 was identified as a prognostic biomarker for PAD. Using a combination of clinical characteristics and plasma IL-7 levels, we propose an accurate predictive model for 2-year MALEs in patients with PAD. Our model may support PAD risk stratification, guiding clinical decisions on additional vascular evaluation, specialist referrals, and medical/surgical management, thereby improving outcomes.

The Role of Lipoprotein(a) in Peripheral Artery Disease.

Lipoprotein(a) is a low-density-lipoprotein-like particle that consists of apolipoprotein(a) bound to apolipoprotein(b). It has emerged as an established causal risk factor for atherosclerotic cardiovascular disease, stroke, and aortic valve stenosis through multifactorial pathogenic mechanisms that include inflammation, atherogenesis, and thrombosis. Despite an estimated 20% of the global population having elevated lipoprotein(a) levels, testing remains underutilized due to poor awareness and a historical lack of effective and safe therapies. Although lipoprotein(a) has a strong association with coronary artery disease and cerebrovascular disease, its relationship with peripheral artery disease is less well established. In this article, we review the epidemiology, biology, and pathogenesis of lipoprotein(a) as it relates to peripheral artery disease. We also discuss emerging treatment options to help mitigate major adverse cardiac and limb events in this population.

New Horizons in Peripheral Artery Disease.

Peripheral artery disease (PAD) is the lower limb manifestation of systemic atherosclerotic disease. PAD may initially present with symptoms of intermittent claudication, whilst chronic limb-threatening ischaemia (CLTI), the end stage of PAD, presents with rest pain and/or tissue loss. PAD is an age-related condition present in over 10% of those aged ≥65 in high-income countries. Guidelines regarding definition, diagnosis and staging of PAD and CLTI have been updated to reflect the changing patterns and presentations of disease given the increasing prevalence of diabetes. Recent research has changed guidelines on optimal medical therapy, with low-dose anticoagulant plus aspirin recommended in some patients. Recently published randomised trials highlight where bypass-first or endovascular-first approaches may be optimal in infra-inguinal disease. New techniques in endovascular surgery have increased minimally invasive options for ever more complex disease. Increasing recognition has been given to the complexity of patients with CLTI where a high prevalence of both frailty and cognitive impairment are present and a significant burden of multi-morbidity and polypharmacy. Despite advances in minimally invasive revascularisation techniques and reduction in amputation incidence, survival remains poor for many with CLTI. Shared decision-making is essential, and conservative management is often appropriate for older patients. There is emerging evidence of the benefit of specialist geriatric team input in the perioperative management of older patients undergoing surgery for CLTI. Recent UK guidelines now recommend screening for frailty, cognitive impairment and delirium in older vascular surgery patients as well as recommending all vascular surgery services have support and input from specialist geriatrics teams.

Association Between Pack-Years and Smoking Cessation on Outcomes After Vascular Interventions.

INTRODUCTION: The influence of pack-year history and smoking cessation timing on postoperative morbidity and mortality in a highly comorbid cohort is uncertain. We examined whether the association between smoking and adverse postoperative events is modified by pack-year history and smoking cessation timing. METHODS: We collected single-institution, retrospective data from consecutive patients undergoing open operations for carotid, aortic, and infrainguinal arterial disease. Active smoking was defined as smoking on the day of the index surgical intervention. Duration of smoking cessation was calculated as the time between smoking cessation and index surgery. The primary outcome was a composite of 30-day mortality and morbidity. Logistic and time-to-event Cox regressions estimated associations with interactions between cessation duration and pack-year history for nonactive smokers. RESULTS: Between 2010 and 2019, 1087 patients underwent 1640 high-risk vascular interventions. Median pack-year history was 40.0 pack-years (interquartile range [IQR]: 20.0-60.0) among nonactive smokers and 46.0 pack-years (IQR: 31.0-61.0) among active smokers (P < 0.001). The median smoking cessation time was 15.5 y (IQR: 4.4-30.9). Smoking status did not independently predict an increased risk of postoperative mortality or morbidity (odds ratio [OR] = 0.99, P = 0.96). Among nonactive smokers, neither smoking cessation duration (OR = 0.99, P = 0.16) nor pack-year history (OR = 1.00, P = 0.88) were significantly associated with adverse events (interaction P = 0.11). CONCLUSIONS: After high-risk vascular interventions in a single institution, active smoking, cessation period, and pack-year history are not associated with an increased risk of postoperative morbidity or mortality-highlighting the benefit of cessation as independent of frequency or intensity.

Oxidative stress and vascular dysfunction: Potential therapeutic targets and therapies in peripheral artery disease.

Peripheral artery disease (PAD) is the manifestation of atherosclerosis characterized by the accumulation of plaques in the arteries of the lower limbs. Interestingly, growing evidence suggests that the pathology of PAD is multifaceted and encompasses both vascular and skeletal muscle dysfunctions, which contributes to blunted physical capabilities and diminished quality of life. Importantly, it has been suggested that many of these pathological impairments may stem from blunted reduction-oxidation (redox) handling. Of note, in those with PAD, excessive production of reactive oxygen species (ROS) outweighs antioxidant capabilities resulting in oxidative damage, which may have systemic consequences. It has been suggested that antioxidant supplementation may be able to assist in handling ROS. However, the activation of various ROS production sites makes it difficult to determine the efficacy of these antioxidant supplements. Therefore, this review focuses on the common cellular mechanisms that facilitate ROS production and discusses how excessive ROS may impair vascular and skeletal muscle function in PAD. Furthermore, we provide insight for current and potential antioxidant therapies, specifically highlighting activation of the Kelch-like ECH-associated protein 1 (Keap1) - Nuclear Factor Erythroid 2-related factor 2 (Nrf2) pathway as a potential pharmacological therapy to combat ROS accumulation and aid in vascular function, and physical performance in patients with PAD. Altogether, this review provides a better understanding of excessive ROS in the pathophysiology of PAD and enhances our perception of potential therapeutic targets that may improve vascular function, skeletal muscle function, walking capacity, and quality of life in patients with PAD.

Intravascular Lithotripsy for Treatment of Severely Calcified Common Femoral Artery Disease: Results From the Disrupt PAD III Observational Study.

BACKGROUND: Surgical endarterectomy is currently considered the front-line therapy for the treatment of calcified lesions in the common femoral artery (CFA). Endovascular interventions have evolved, and their use is increasing in frequency. Intravascular lithotripsy (IVL) has shown promising safety and effectiveness in calcified CFA lesions in a small pilot study, but "real-world" evidence from a larger cohort is lacking. METHODS: The Disrupt PAD III Observational Study (NCT02923193) was a prospective, multicenter registry designed to assess the acute safety and effectiveness of IVL treatment for calcified peripheral arterial disease. Any concomitant treatment with other calcium-modifying technologies as well as definitive treatment strategies was at the discretion of the operators. Patients with CFA lesions were evaluated for acute angiographic safety and effectiveness outcomes following IVL treatment as determined by an independent angiographic core lab. RESULTS: Common femoral artery treatment was indicated in 177 patients (n=163 could be analyzed based on core-laboratory data) enrolled at 23 sites. Characteristics for 164 treated lesions included moderate-severe calcification 95.1%, diameter stenosis 74.8±17.7%, and lesion length 53.6±53.1 mm. Concomitant calcium-modifying therapy was used in 32.3% of lesions. Final therapy included drug-coated balloons in 68.9% and stenting in 16.5% of lesions. Post-IVL and final residual stenoses were 29.2±16.5%and 23.6±11.5%, respectively. No vascular complications (flow-limiting dissections, perforations, embolization, slow or no reflow, or abrupt closure) were present at the end of the procedure by core-laboratory assessment, with 1 (0.8%) flow-limiting dissection initially occurring immediately following IVL treatment. CONCLUSION: This study represents the largest real-world experience of IVL treatment in heavily calcified CFA lesions. Intravascular lithotripsy treatment showed significant stenosis reduction and favorable periprocedural safety in this challenging patient population. CLINICAL IMPACT: In this study we show that calcified common femoral artery disease can be safely and effectively treated with shockwave balloon angioplasty with high procedural success and low complication rates and in clinical practice can now be offered as an alternative to surgical treatment in those patients reluctant to or high risk for vascular surgery. This opens another option for clinicians to treat calcified common femoral artery disease without the risk of dissection, perforation or distal embolization that are associated with atherectomy. This study shows that shockwave lithoplasty offers an innovative plaque modification technology to tackle calcified disease in the common femoral artery.

A Novel Sirolimus-Coated Balloon for the Treatment of Femoropopliteal Lesions: The SELUTION SFA Japan Trial.

BACKGROUND: Sirolimus-coated balloons (SCB) for the treatment of femoropopliteal (FP) lesions have not been systematically studied, but initial outcomes from early studies are promising. OBJECTIVES: The authors sought to evaluate the safety and efficacy of the SELUTION SLR SCB, composed of proprietary microreservoir technology combining sirolimus and biodegradable polymer, when used to treat mild-to-moderate FP disease in a Japanese population. METHODS: This multicenter, prospective, single-arm study (SELUTION SFA JAPAN) enrolled 134 patients with FP disease. It was independently adjudicated by an imaging core laboratory and clinical events committee. The primary endpoint was 12-month primary patency, defined as peak systolic velocity ratio ≥2.5 by duplex ultrasound and compared against a prespecified performance goal of 60% based on established angioplasty data. RESULTS: The mean age was 73.8 ± 6.9 years, and 60.3% of patients had diabetes mellitus. The mean lesion length was 127.4 ± 59.7 mm, 17.2% were chronic total occlusions, and 47.8% involved the popliteal artery. Data on 12-month restenosis were available in 127 patients (94.8%). The 12-month primary patency rate was 87.9%, and the freedom from clinically driven target lesion revascularization (CD-TLR) was 97.0% per Kaplan-Meier estimate. The major adverse event rate was 6.7%, driven by 4 CD-TLRs and 5 deaths, none of which were related to the device or procedure. Ankle-brachial index data improved significantly from 0.73 ± 0.16 at baseline to 0.96 ± 0.14 at 30 days postprocedure and was sustained through 12 months (0.94 ± 0.13). CONCLUSIONS: The SELUTION SFA JAPAN trial demonstrated that a novel SELUTION SCB is a safe and effective treatment option for FP disease in symptomatic patients.

Sex and age significantly modulate cardiovascular disease presentation in type 2 diabetes: a large population-based cohort study.

Aims: We aimed to describe and compare the incidence of the first cardiovascular event and its major subtypes, coronary heart disease (CHD), cerebrovascular disease, heart failure (HF), or peripheral artery disease (PAD), according to age and sex in a population-based cohort of individuals with type 2 diabetes (T2D) from a Mediterranean region. Material and methods: We used linked primary care electronic medical reports, pharmacy-invoicing data, and hospital admission disease registry records from the SIDIAP database, which contains linked data for 74% of the Catalonian population. We selected individuals with T2D aged 30 to 89 years free of cardiovascular disease (CVD). The primary outcome was the first presentation of CVD. Results: The study cohort included 247,751 individuals (48.6% women, 66.8 ± 11.9 years). During a 6.99-year follow-up, the cumulative incidence of the first cardiovascular event was 23.4%. Men were at higher risk for CVD (hazard ratio [HR]: 1.47 95%CI: 1.45-1.50), CHD (HR: 1.52 95%CI: 1.47-1.57), cerebrovascular disease (HR:1.07 95%CI: 1.03-1.10) and PAD (HR: 2.30 95%CI: 2.21-2.39) than women but at a lower risk for HF (HR:0.70 95%CI: 0.68-0.73). CHD and PAD were the most frequent CVD presentations among men (28.1% and 27.5%) and HF (40.1%) in women. CHD predominated among young participants of both sexes, while HF predominated among women older than 65 and men older than 75. Conclusions: In individuals with T2D, the overall risk and the type of first CVD manifestation largely varied by sex and age. This epidemiological evidence should be considered in clinical practice.

Novel components in the nuclear factor-kappa B (NF-κB) signaling pathways of endothelial cells under hyperglycemic-ischemic conditions.

Diabetes worsens the outcomes of a number of vascular disorders including peripheral arterial disease (PAD) at least in part through induction of chronic inflammation. However, in experimental PAD, recovery requires the nuclear factor-kappa B (NF-κB) activation. Previously we showed that individually, both ischemia and high glucose activate the canonical and non-canonical arms of the NF-κB pathway, but prolonged high glucose exposure specifically impairs ischemia-induced activation of the canonical NF-κB pathway through activation of protein kinase C beta (PKCß). Although a cascade of phosphorylation events propels the NF-κB signaling, little is known about the impact of hyperglycemia on the canonical and non-canonical NF-κB pathway signaling. Moreover, signal upstream of PKCß that lead to its activation in endothelial cells during hyperglycemia exposure have not been well defined. In this study, we used endothelial cells exposed to hyperglycemia and ischemia (HGI) and an array of approximately 250 antibodies to approximately 100 proteins and their phosphorylated forms to identify the NF-κB signaling pathway that is altered in ischemic EC that has been exposed to high glucose condition. Comparison of signals from hyperglycemic and ischemic cell lysates yielded a number of proteins whose phosphorylation was either increased or decreased under HGI conditions. Pathway analyses using bioinformatics tools implicated BLNK/BTK known for B cell antigen receptor (BCR)-coupled signaling. Inhibition of BLNK/BTK in endothelial cells by a specific pharmacological inhibitor terreic acid attenuated PKC activation and restored the IκBα degradation suggesting that these molecules play a critical role in hyperglycemic attenuation of the canonical NF-κB pathway. Thus, we have identified a potentially new component of the NF-κB pathway upstream of PKC in endothelial cells that contributes to the poor post ischemic adaptation during hyperglycemia.

Korean Multicenter Registry of ELUVIA Stent for Femoropopliteal Artery Disease: K-ELUVIA Registry.

BACKGROUND AND OBJECTIVES: The K-ELUVIA study aimed to investigate the clinical effectiveness and safety of Eluvia™, a polymer-coated, paclitaxel-eluting stent, for femoropopliteal artery disease using data from a prospective Korean multicenter registry. METHODS: A total of 105 patients with femoropopliteal artery disease who received endovascular treatment (EVT) with Eluvia™ stents at 7 Korean sites were enrolled in a prospective cohort and followed for 2 years. The primary endpoint was the 2-year clinical patency. The secondary endpoint was 2-year freedom from clinically driven target lesion revascularization (TLR). RESULTS: Mean patient age was 68.2±10.4 years, and most patients (82.7%) were male. Mean lesion length was 168.3±117.6 mm. Chronic total occlusion was found in 57.7% of patients. Trans-Atlantic Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II) type C or D lesions were present in 46.1% of patients. Procedural success was achieved in 99.0% of patients. The clinical patency rate was 84.4% at 1 year after EVT and 76.3% at 2 years post-EVT. The freedom from TLR rate was 89.1% at 1 year after EVT and 79.1% at 2 years post-EVT. Chronic total occlusion (hazard ratio [HR], 3.53; 95% confidence interval [CI], 1.08-11.67; p=0.039) and smaller mean stent diameter (HR, 0.40; 95% CI, 0.16-0.98; p=0.044) were identified as independent predictors of loss of clinical patency at 2 years. CONCLUSIONS: The K-ELUVIA study demonstrated favorable 2-year clinical effectiveness and safety outcomes of Eluvia stent for femoropopliteal artery lesions in real-world practice.

Transforming Health Care from Volume to Value: Targeting Essential Therapies for Improved Health.

The healthcare landscape is evolving rapidly due to escalating costs from the traditional fee-for-service model. Value-based care has emerged as a viable solution, and initiatives focus on areas prone to overuse, waste, or high costs, such as advanced imaging and avoidable acute care resource utilization. Improving medication use is an important component of this work, and it requires organizational commitment, interdisciplinary collaboration, and targeted strategies for specific therapeutic areas. This review article discusses the value-based care approach to optimizing medications and blood product prescribing, spotlighting opportunities to reduce the overuse of opioid, antimicrobial, and proton pump inhibitor medications, alongside the underuse of guideline-based medical therapies in managing chronic diseases like coronary artery disease, heart failure, and chronic obstructive pulmonary disease.