Microplastics and Nanoplastics in Atheromas and Cardiovascular Events.

BACKGROUND: Microplastics and nanoplastics (MNPs) are emerging as a potential risk factor for cardiovascular disease in preclinical studies. Direct evidence that this risk extends to humans is lacking. METHODS: We conducted a prospective, multicenter, observational study involving patients who were undergoing carotid endarterectomy for asymptomatic carotid artery disease. The excised carotid plaque specimens were analyzed for the presence of MNPs with the use of pyrolysis-gas chromatography-mass spectrometry, stable isotope analysis, and electron microscopy. Inflammatory biomarkers were assessed with enzyme-linked immunosorbent assay and immunohistochemical assay. The primary end point was a composite of myocardial infarction, stroke, or death from any cause among patients who had evidence of MNPs in plaque as compared with patients with plaque that showed no evidence of MNPs. RESULTS: A total of 304 patients were enrolled in the study, and 257 completed a mean (±SD) follow-up of 33.7±6.9 months. Polyethylene was detected in carotid artery plaque of 150 patients (58.4%), with a mean level of 21.7±24.5 µg per milligram of plaque; 31 patients (12.1%) also had measurable amounts of polyvinyl chloride, with a mean level of 5.2±2.4 µg per milligram of plaque. Electron microscopy revealed visible, jagged-edged foreign particles among plaque macrophages and scattered in the external debris. Radiographic examination showed that some of these particles included chlorine. Patients in whom MNPs were detected within the atheroma were at higher risk for a primary end-point event than those in whom these substances were not detected (hazard ratio, 4.53; 95% confidence interval, 2.00 to 10.27; P<0.001). CONCLUSIONS: In this study, patients with carotid artery plaque in which MNPs were detected had a higher risk of a composite of myocardial infarction, stroke, or death from any cause at 34 months of follow-up than those in whom MNPs were not detected. (Funded by Programmi di Ricerca Scientifica di Rilevante Interesse Nazionale and others; ClinicalTrials.gov number, NCT05900947.).

Endovascular treatment of an aortocaval fistula caused by a late type II endoleak.

An aortocaval fistula (ACF) is a rare complication of abdominal aortic aneurysms (AAAs) and constitute <1% of all AAAs, which increases from 2% to 6.7% in ruptured AAAs. Unlike other aortic ruptures, most ACFs are not associated with significant blood loss on admission. The traditional treatment strategy has been open surgery, which is associated with a high mortality rate. Endovascular repair has been performed; however, the results are difficult to interpret due to the low incidence of ACFs and the absence of cases reported with a long follow-up duration. We report the case of a 78-year-old man with previous endovascular aneurysm repair performed in 2015, who presented to our emergency department 6 years later with abdominal pain. A computed tomography angiography scan showed type Ia, Ib, and II endoleaks and an ACF. The endoleaks were selectively treated, and the ACF was covered with a polytetrafluoroethylene endograft inserted in the inferior vena cava. In our single-case experience with a medium-term follow-up of 24 months, our treatment was safe and effective for ACF closure, with no further signs of endoleak or graft thrombosis. We conducted a literature review of reported cases in which a covered stent graft was used for ACF treatment. Although no guidelines are currently available regarding this rare late complication after endovascular aneurysm repair, using a covered stent placed in the inferior vena cava to treat an ACF could be a viable option in selected cases.

Mid-Term Results of an Italian Multicentric Experience with the RoadsaverTM Dual-Layer Carotid Stent System.

BACKGROUND: Carotid artery stenting (CAS) using first-generation single-layer stents is widely accepted as a good alternative to standard carotid endarterectomy (CEA) but it is associated with worse outcomes in terms of both plaque prolapse and cerebral embolization. AIM: To evaluate the perioperative and midterm outcomes of CAS using the new-generation RoadsaverTM dual-layer micromesh-covered carotid stent. METHODS: Herein, we present the results of an observational, retrospective, multicentric study on non-consecutive patients who underwent the CAS procedure between January 2017 and December 2022 at three Italian, high-volume vascular surgery centers. The inclusion criteria were the patients' eligibility for the CAS procedure in accordance with the current Italian guidelines, and the implantation of a Roadsaver stent. Both symptomatic and asymptomatic patients were included in the study. The patients requiring reintervention for carotid restenosis following CEA were also included. Perioperative data regarding procedural success was defined as the successful implantation of the device in the desired position, less than 30% residual stenosis, and the absence of intraoperative neurological complications. The primary outcome was any adverse cerebrovascular event such as stroke or transient ischemic attack (TIA) during the procedure and/or after discharge. The secondary outcomes were the need for further intervention, and all-cause death following procedure. RESULTS: Three-hundred-fifty-three (353) patients were included in our study; the mean age was 74.3 years. A total of 5.9% of the patients were symptomatic on their operated side, while 7.3% had contralateral carotid occlusion. A cerebral embolic protection device (CPD) was employed in all patients. A total of 13.3% of the patients were operated on for restenosis after CEA Technical success was achieved in 96.9% of the cases with an intraoperative report of six TIAs (1.7%) and six ipsilateral strokes (1.7%). The mean hospital stay was 1.8 days. The thirty-day follow up showed one TIA and one more stroke. At the mean 35-month follow-up time, the primary outcome was present in six patients (1.7%), where four TIAs (1.1%) and two strokes (0.5%) were reported. Restenosis occurred in five patients (1.4%). Death for any cause was reported in 11 patients (3.1%). CONCLUSIONS: As most recent, high-quality studies show, the CAS procedure with second-generation devices such as the Roadsaver stent is safe and effective in preventing carotid-related cerebrovascular events in both symptomatic and asymptomatic patients. The intraoperative and postoperative cerebrovascular complication rate in high volume centers is very low, ensuring confidence in its employment for the CAS procedure along with a CPD as a valid alternative to CEA.

Endovascular treatment of a wide-necked renal artery aneurysm with a flow diverter stent.

Renal artery aneurysm (RAA) is a rare, often asymptomatic disease (0.1% incidence in general population) and can be incidentally diagnosed during an abdominal imaging workup. The traditional, gold standard of treatment is open surgery, carrying with it, however, a high risk of nephrectomy, mortality, and collateral morbidity. The endovascular approach is currently the most valid alternative to treating RAAs reducing, as it does, the risks associated with the surgical approach/open surgery. Herein we report on our experience with a case of wide-necked RAA treated with the Pipeline Vantage (Medtronic) flow diverter stent. Wide-neck aneurysms are defined as having neck diameters greater than 4 mm. Our choice of endovascular treatment was preferred over the surgical option notwithstanding the large size of the neck and the involvement of the branching vessels.

Soluble PCSK9 Inhibition: Indications, Clinical Impact, New Molecular Insights and Practical Approach-Where Do We Stand?

Current research on cardiovascular prevention predominantly focuses on risk-stratification and management of patients with coronary artery disease (CAD) to optimize their prognosis. Several basic, translational and clinical research efforts aim to determine the etiological mechanisms underlying CAD pathogenesis and to identify lifestyle-dependent metabolic risk factors or genetic and epigenetic parameters responsible for CAD occurrence and/or progression. A log-linear association between the absolute exposure of LDL cholesterol (LDL-C) and the risk of atherosclerotic cardio-vascular disease (ASCVD) was well documented over the year. LDL-C was identified as the principal enemy to fight against, and soluble proprotein convertase subtilisin kexin type 9 (PCSK9) was attributed the role of a powerful regulator of blood LDL-C levels. The two currently available antibodies (alirocumab and evolocumab) against PCSK9 are fully human engineered IgG that bind to soluble PCSK9 and avoid its interaction with the LDLR. As documented by modern and dedicated "game-changer" trials, antibodies against soluble PCSK9 reduce LDL-C levels by at least 60 percent when used alone and up to 85 percent when used in combination with high-intensity statins and/or other hypolipidemic therapies, including ezetimibe. Their clinical indications are well established, but new areas of use are advocated. Several clues suggest that regulation of PCSK9 represents a cornerstone of cardiovascular prevention, partly because of some pleiotropic effects attributed to these newly developed drugs. New mechanisms of PCSK9 regulation are being explored, and further efforts need to be put in place to reach patients with these new therapies. The aim of this manuscript is to perform a narrative review of the literature on soluble PCSK9 inhibitor drugs, with a focus on their indications and clinical impact.

A Multicenter Experience of Three Different "Iliac Branched" Stent Grafts for the Treatment of Aorto-Iliac And/Or Iliac Aneurysms.

BACKGROUND: The aim of study was to assess the safety and effectiveness of 3 different commercial iliac branch devices (IBDs): the Zenith Branch Iliac Endovascular Graft; the Gore Excluder Iliac Branch System and the E-liac Stent Graft System for the treatment of aorto-iliac or iliac aneurysms. METHODS: From January 2017 to February 2020, a retrospective reviewed was conducted on a total of 96 patients. Primary endpoint was IBD instability rate at 24 months. Secondary endpoints included onset of any endoleaks, buttock claudication, IBD-related reintervention and all-death rates, postoperative acute kidney, and changes in maximum diameter from baseline of the aortic aneurysmal sac. RESULTS: At 24 months, the branch instability rate was similar among the 3 IBDs employed [Jotec 1/24 (4.1%), Gore 1/12 (8.3%), Cook 6/47 (12.7%), P-value = 0.502]. As well, no statistical difference in terms of branch occlusion and branch-related endoleaks was observed. The Jotec group showed a significant decrease in maximum diameter from the baseline of the aortic aneurysmal sac when compared to the Gore group alone. No other differences were found relevant to the onset of any endoleaks, reinterventions, and all-death rates. At 24 months, the Kaplan-Meier estimate of survival freedom from any branch instability was 95.8%, 91.6%, and 86.8% for Jotec, Gore and Cook groups, respectively. CONCLUSIONS: The use of IBDs represents a safe method for preserving patency of the IIA during treatment of aorto-iliac or iliac aneurysms providing a low rate of IBD instability.

Abdominal Aortic Aneurysm: Natural History, Pathophysiology and Translational Perspectives.

An abdominal aortic aneurysm (AAA) is a degenerative pathology that affects the infrarenal segment of the aorta, leading to its progressive dilatation and eventually rupture. The infrarenal segment is involved in 80% of the aortic aneurisms, and represents alone 30% of all aneurysms. The natural history of the disease is characterized by the progressive increase of the aortic diameter associated with proportionally higher risk of rupture, particularly for cases with diameter greater than 5.5 cm. In case of rupture the mortality rate is very high, independently from the endovascular or surgical treatment. The most important risk factors are older age, smoking, hypertension, dyslipidemia, and family history of AAA. The most frequent form is "atherosclerotic", but infectious, collagen disease-related, immune dysregulation-related, and post-traumatic AAA have also been described. Albeit multiple pathogenetic hypotheses have been proposed, the role of metallo-proteinases in the degeneration of the aortic wall seem to play a central role. Early detection of AAA is crucial for the identification and treatment before the onset of potentially life-threatening complications. Moreover, the individual risk stratification is fundamental for the clinical management and follow-up. The growing knowledge about the pathophysiology of AAA has the potential to lead to significant translational advances. The challenge for the next years is to employ bioinformatic and genetic models, also based on artificial intelligence and machine learning approach, to develop novel screening methods and to stratify individuals at higher-risk or in the early stages of AAA.

Efficacy and Safety of Jotec E-Ventus BX Stent Graft for Iliac Branch Device Procedure: A Retrospective Clinical Study.

BACKGROUND: The endovascular aneurysm repair (EVAR) is a successful treatment for aorto-iliac aneurysms. The success of EVAR is enhanced by the use of devices that maintain the patency of targeted arteries namely the iliac branch device (IBD) With this study we aimed to evaluate the association between the use of Jotec E-ventus during EVAR with IBD and prognosis in patients with aorto-iliac aneurysms. METHODS: This is a retrospective, multicentric study enrolling patients referred to our Vascular Surgery Units from January 2015 to January 2020. All patients underwent EVAR with IBD using Jotec E-ventus as bridging stent. Primary endpoint was the development of types I and III endoleaks. Secondary endpoint was the onset of device occlusion with loss of vascular patency. RESULTS: We studied 32 patients (mean age 71.7±4.5y). Of these, 25 patients were treated with standard EVAR procedure whereas 7 were treated with isolated IBD due to extension of disease involving iliac bifurcation. Median follow-up lasted 15[IQR11-27] months. During follow-up, incidence rates for endoleaks and occlusion were 3.98(95%CI 0.48-14.41) and 1.99(95%CI 0.05-11.12) per 100 pts/year. CONCLUSIONS: Jotec E-ventus during EVAR is associated with a low rate of severe complications in a small cohort of patients with aorto-iliac aneurysms.

Single systemic transfer of a human gene associated with exceptional longevity halts the progression of atherosclerosis and inflammation in ApoE knockout mice through a CXCR4-mediated mechanism.

AIMS: Here, we aimed to determine the therapeutic effect of longevity-associated variant (LAV)-BPIFB4 gene therapy on atherosclerosis. METHODS AND RESULTS: ApoE knockout mice (ApoE-/-) fed a high-fat diet were randomly allocated to receive LAV-BPIFB4, wild-type (WT)-BPIFB4, or empty vector via adeno-associated viral vector injection. The primary endpoints of the study were to assess (i) vascular reactivity and (ii) atherosclerotic disease severity, by Echo-Doppler imaging, histology and ultrastructural analysis. Moreover, we assessed the capacity of the LAV-BPIFB4 protein to shift monocyte-derived macrophages of atherosclerotic mice and patients towards an anti-inflammatory phenotype. LAV-BPIFB4 gene therapy rescued endothelial function of mesenteric and femoral arteries from ApoE-/- mice; this effect was blunted by AMD3100, a CXC chemokine receptor type 4 (CXCR4) inhibitor. LAV-BPIFB4-treated mice showed a CXCR4-mediated shift in the balance between Ly6Chigh/Ly6Clow monocytes and M2/M1 macrophages, along with decreased T cell proliferation and elevated circulating levels of interleukins IL-23 and IL-27. In vitro conditioning with LAV-BPIFB4 protein of macrophages from atherosclerotic patients resulted in a CXCR4-dependent M2 polarization phenotype. Furthermore, LAV-BPIFB4 treatment of arteries explanted from atherosclerotic patients increased the release of atheroprotective IL-33, while inhibiting the release of pro-inflammatory IL-1ß, inducing endothelial nitric oxide synthase phosphorylation and restoring endothelial function. Finally, significantly lower plasma BPIFB4 was detected in patients with pathological carotid stenosis (>25%) and intima media thickness >2 mm. CONCLUSION: Transfer of the LAV of BPIFB4 reduces the atherogenic process and skews macrophages towards an M2-resolving phenotype through modulation of CXCR4, thus opening up novel therapeutic possibilities in cardiovascular disease.