Effect of Simvastatin Treatment on "In Vitro" NLRP1 Inflammasome Expression in Peripheral Arterial Disease.

BACKGROUND: Inflammatory stress stimuli in the plasma of patients with peripheral artery disease (PAD) are able to trigger the expression of NLRP1 inflammasome in human aortic endothelial cells (HAECs). Our objective was to elucidate the effect of simvastatin treatment on NLRP1 inflammasome expression in endothelial cells exposed to the plasma of PAD patients. METHODS: The study included 81 patients with PAD, 24 of them treated with simvastatin (20 mg/day) and 57 without statin therapy. HAECs between passages 3 and 6 were stimulated for 2 hr using the plasma samples of the study participants. NLRP1 gene transcription of HAECs exposed to the plasma of PAD patients was quantificated. RESULTS: HAECs exposed to the plasma of PAD patients with simvastatin therapy showed significantly higher expression of the NLRP1 gene compared with those exposed to the plasma of PAD patients without this treatment (relative quantitation [RQ] 1.12 ± 0.06 vs. 1.06 ± 0.07, P = 0.03). Furthermore, HAECs exposed to the plasma of patients with critical limb ischemia and treated with simvastatin responded with a higher NLRP1 expression than those exposed to the plasma of simvastatin-treated patients with claudication (RQ 1.1 ± 0.3 vs. 0.99 ± 0.14, P < 0.001). CONCLUSION: Simvastatin intake in PAD patients increases in vitro reactivity of NLRP1 inflammasome gene expression in HAECs, especially in critical limb ischemia patients.

Results of infrapopliteal endovascular procedures performed in diabetic patients with critical limb ischemia and tissue loss from the perspective of an angiosome-oriented revascularization strategy.

Our aim was to describe our experience with infrapopliteal endovascular procedures performed in diabetic patients with ischemic ulcers and critical ischemia (CLI). A retrospective study of 101 procedures was performed. Our cohort was divided into groups according to the number of tibial vessels attempted and the number of patent tibial vessels achieved to the foot. An angiosome anatomical classification of ulcers were used to describe the local perfusion obtained after revascularization. Ischemic ulcer healing and limb salvage rates were measured. Ischemic ulcer healing at 12 months and limb salvage at 24 months was similar between a single revascularization and multiple revascularization attempts. The group in whom none patent tibial vessel to the foot was obtained presented lower healing and limb salvage rates. No differences were observed between obtaining a single patent tibial vessel versus more than one tibial vessel. Indirect revascularization of the ulcer through arterial-arterial connections provided similar results than those obtained after direct revascularization via its specific angiosome tibial artery. Our results suggest that, in CLI diabetic patients with ischemic ulcers that undergo infrapopliteal endovascular procedures, better results are expected if at least one patent vessel is obtained and flow is restored to the local ischemic area of the foot.

Safety and efficacy outcomes of infrapopliteal endovascular procedures performed in patients with critical limb ischemia according to the Society for Vascular Surgery objective performance goals.

BACKGROUND: Objective performance goals (OPGs) are a set of standardized end points generated from well documented historical controls against which new therapeutic procedures may be compared in single-arm studies. Recently, the Society for Vascular Surgery suggested a set of OPGs designed from vein bypass controls that could be used to evaluate the safety and efficacy of endovascular devices applied to critical limb ischemia through a noninferiority analysis. Our aim is to analyze the results of infrapopliteal endovascular procedures performed in patients with critical limb ischemia according to these OPG end points. METHODS: This is a retrospective study of 121 infrapopliteal endovascular procedures. The tibial intervention was combined with a femoropopliteal angioplasty in 70 procedures. Major adverse cardiovascular events (MACEs), major adverse limb events (MALEs), and major amputations at 30 days were recorded as safety outcomes. Freedom from any MALE or perioperative death (Freedom from MALE + POD) and amputation-free survival were calculated as primary efficacy end points at both 12 months and at 8 years. The 95% confidence intervals (CIs) of all the end points were calculated to perform a noninferiority comparison using OPGs as the reference. RESULTS: The incidence of MACEs, MALEs, and amputation at 30 days were 5% (95% CI: 2-10% [OPG-MACE <10%]), 2.5% (95% CI: 0.5-7% [OPG-MALE <9%]), and 1.7% (95% CI: 0.2-6% [OPG-major amputation <4%]), respectively. We recorded a freedom from MALE + POD of 76% (95% CI: 67-83% [OPG-MALE + POD >67%]) and an amputation-free survival of 78% (95% CI: 69-85% [OPG-amputation-free survival >68%]) at 12 months. Freedom from MALE + POD and amputation-free survival at 8 years decreased to 60% (95% CI: 49-69%) and to 26% (95% CI: 11-44%), respectively. CONCLUSIONS: Infrapopliteal endovascular procedures performed in everyday vascular surgery practice could meet the main OPG end points proposed for catheter-based treatment of critical limb ischemia.

Circulating anti-beta2-glycoprotein I antibodies are associated with endothelial dysfunction, inflammation, and high nitrite plasma levels in patients with intermittent claudication.

Our aim is to investigate a possible association of circulating anti-beta2-glycoprotein I antibodies (ABGPI) with the endothelial dysfunction, nitric oxide bioactivity dysregulation, and the inflammatory status that surrounds peripheral arterial disease. We carried out an observational translational study, including 50 male patients with intermittent claudication and a healthy control group of 10 male subjects, age and sex matched with the cases. Flow-mediated arterial dilatation (FMAD) was assessed as a surrogate of endothelial dysfunction, and C-reactive protein (hsCRP) was determined as a marker of inflammation. Nitrite plasma levels were measured by colorimetric analysis. Circulating ABGPI titer was detected with indirect immunofluorescence. Titers <1 : 10 represented the reference range and the lower detection limit of the test. Circulating ABGPI titer ≥1 : 10 was detected in 21 (42%) patients and in none of the control subjects (P < 0.01). Patients with ABGPI titer ≥1 : 10 had a lower FMAD (P = 0.01). The CRP levels were higher in patients with ABGPI titer ≥1 : 10 (P = 0.04). The nitrite plasma levels were higher in patients with ABGPI titer ≥1 : 10 (P < 0.01). These data suggest that these circulating ABGPI may collaborate in the development of atherosclerosis; however, further prospective studies are required to establish a causal relationship.

Inflammatory burden predicts long-term outcomes in endovascular therapy in peripheral arterial disease.

BACKGROUND: Peripheral arterial disease (PAD) is a systemic inflammatory disorder that affects the entire vascular system. Endovascular therapy (EVT) is the first surgical treatment choice in a large number of patients who suffer from this disease. However, late clinical failure after primarily successful interventions, with the need of a new reintervention, is the major drawback of this technique. The aim of this study is to determine the possible association between serum high sensitivity C-reactive protein (hsCRP) and fibrinogen levels both preintervention and during follow-up, and the outcomes of EVT and their association with the incidence of cardiovascular events or death in these patients. METHODS: This is a prospective cohort study in patients diagnosed with PAD in the iliac, femoral, popliteal, or distal sectors, within Rutherford category 3-5 who underwent EVT de novo. We determined levels of hsCRP and fibrinogen before surgery and during the follow-up period (at 1, 3, 6, and 12 months). We analyzed the possible association among inflammatory markers levels before EVT, during 1 year of follow-up and its variation during that year, and the incidence of reintervention, reintervention-free survival, and the occurrence of cardiovascular events or death. RESULTS: Over the course of 1 year, 246 patients underwent a revascularizing treatment of the lower limbs; 64 patients qualified for inclusion in this study. In these 64 patients, a significant increase between basal hsCRP and fibrinogen levels and the incidence of reintervention (P=0.002 and 0.013, respectively) and death (P=0.001 and 0.013, respectively) during follow-up was found. A significant increase between higher hsCRP basal levels and the incidence of cardiovascular events during the follow-up period was also noted (P=0.004). Levels of basal hsCRP were related to reintervention-free survival after EVT (P=0.04). On the basis of the rate of hsCRP variation and its association with reintervention-free survival, we observed a progressive reduction of the levels of hsCRP until 12 months after the primary procedure. CONCLUSIONS: Basal levels of inflammatory markers and their variation during follow-up allowed us to identify a subgroup of patients with PAD that will require a greater number of (and earlier) reinterventions after EVT and who will have higher rates of cardiovascular morbidity and mortality.