Development of a biomarker panel for assessing cardiovascular risk in diabetic patients with chronic limb-threatening ischemia (CLTI): a prospective study.

BACKGROUND: Lower-extremity endovascular revascularization (LER) is often required for diabetic patients with chronic limb threatening ischemia (CLTI). During the post-revascularization period patients may unpredictably experience major adverse cardiac events (MACE) and major adverse limb events (MALE). Several families of cytokines are involved in the inflammatory process that underlies the progression of atherosclerosis. According to current evidence, we have identified a panel of possible biomarkers related with the risk of developing MACE and MALE after LER. The aim was to study the relationship between a panel of biomarkers - Interleukin-1 (IL-1) and 6 (IL-6), C-Reactive Protein (CRP), Tumor Necrosis Factor-α (TNF-α), High-Mobility Group Box-1 (HMGB-1), Osteoprotegerin (OPG), Sortilin and Omentin-1- at baseline, with cardiovascular outcomes (MACE and MALE) after LER in diabetic patients with CLTI. METHODS: In this prospective non-randomized study, 264 diabetic patients with CLTI undergoing endovascular revascularization were enrolled. Serum levels of each biomarker were collected before revascularization and outcomes' incidence was evaluated after 1, 3, 6 and 12 months. RESULTS: During the follow-up period, 42 cases of MACE and 81 cases of MALE occurred. There was a linear association for each biomarker at baseline and incident MACE and MALE, except Omentin-1 levels that were inversely related to the presence of MACE or MALE. After adjusting for traditional cardiovascular risk factors, the association between each biomarker baseline level and outcomes remained significant in multivariable analysis. Receiver operating characteristics (ROC) models were constructed using traditional clinical and laboratory risk factors and the inclusion of biomarkers significantly improved the prediction of incident events. CONCLUSIONS: Elevated IL-1, IL-6, CRP, TNF-α, HMGB-1, OPG and Sortilin levels and low Omentin-1 levels at baseline correlate with worse vascular outcomes in diabetic patients with CLTI undergoing LER. Assessment of the inflammatory state with this panel of biomarkers may support physicians to identify a subset of patients more susceptible to the procedure failure and to develop cardiovascular adverse events after LER.

Current Medical Therapy and Revascularization in Peripheral Artery Disease of the Lower Limbs: Impacts on Subclinical Chronic Inflammation.

Peripheral artery disease (PAD), coronary artery disease (CAD), and cerebrovascular disease (CeVD) are characterized by atherosclerosis and inflammation as their underlying mechanisms. This paper aims to conduct a literature review on pharmacotherapy for PAD, specifically focusing on how different drug classes target pro-inflammatory pathways. The goal is to enhance the choice of therapeutic plans by considering their impact on the chronic subclinical inflammation that is associated with PAD development and progression. We conducted a comprehensive review of currently published original articles, narratives, systematic reviews, and meta-analyses. The aim was to explore the relationship between PAD and inflammation and evaluate the influence of current pharmacological and nonpharmacological interventions on the underlying chronic subclinical inflammation. Our findings indicate that the existing treatments have added anti-inflammatory properties that can potentially delay or prevent PAD progression and improve outcomes, independent of their effects on traditional risk factors. Although inflammation-targeted therapy in PAD shows promising potential, its benefits have not been definitively proven yet. However, it is crucial not to overlook the pleiotropic properties of the currently available treatments, as they may provide valuable insights for therapeutic strategies. Further studies focusing on the anti-inflammatory and immunomodulatory effects of these treatments could enhance our understanding of the mechanisms contributing to the residual risk in PAD and pave the way for the development of novel therapies.

Statins in High Cardiovascular Risk Patients: Do Comorbidities and Characteristics Matter?

Atherosclerotic cardiovascular disease (ASCVD) morbidity and mortality are decreasing in high-income countries, but ASCVD remains the leading cause of morbidity and mortality in high-income countries. Over the past few decades, major risk factors for ASCVD, including LDL cholesterol (LDL-C), have been identified. Statins are the drug of choice for patients at increased risk of ASCVD and remain one of the most commonly used and effective drugs for reducing LDL cholesterol and the risk of mortality and coronary artery disease in high-risk groups. Unfortunately, doctors tend to under-prescribe or under-dose these drugs, mostly out of fear of side effects. The latest guidelines emphasize that treatment intensity should increase with increasing cardiovascular risk and that the decision to initiate intervention remains a matter of individual consideration and shared decision-making. The purpose of this review was to analyze the indications for initiation or continuation of statin therapy in different categories of patient with high cardiovascular risk, considering their complexity and comorbidities in order to personalize treatment.

Analysis of completion intraoperative venography during first rib resection for venous thoracic outlet syndrome.

BACKGROUND: We evaluated the impact of completion intraoperative venography on clinical outcomes for axillosubclavian vein (AxSCV) thrombosis owing to venous thoracic outlet syndrome (vTOS). METHODS: We performed a retrospective, single-center review of all patients with vTOS treated with first rib resection (FRR) and intraoperative venography from 2011 to 2023. We reviewed intraoperative venographic films to classify findings and collected demographics, clinical and perioperative variables, and clinical outcomes. Primary end points were symptomatic relief and primary patency at 3 months and 1 year. Secondary end points were time free from symptoms, reintervention rate, perioperative complications, and mortality. RESULTS: Fifty-one AxSCVs (49 patients; mean age, 31.3 ± 12.6 years; 52.9% female) were treated for vTOS with FRR and external venolysis followed by completion intraoperative venography with a mean follow up of 15.5 ± 13.5 months. Before FRR, 32 underwent catheter-directed thrombolysis (62.7%). Completion intraoperative venography identified 16 patients with no stenosis (group 1, 31.3%), 17 with no stenosis after angioplasty (group 2, 33.3%), 10 with residual stenosis after angioplasty (group 3, 19.7%), and 8 with complete occlusion (group 4, 15.7%). The overall symptomatic relief was 44 of 51 (86.3%) and did not differ between venographic classifications (group 1, 14 of 16; group 2, 13 of 17; group 3, 10 of 10; and group 4, 7 of 8; log-rank test, P = .5). The overall 3-month and 1-year primary patency was 42 of 43 (97.7%) and 32 of 33 (97.0%), respectively (group 1, 16 of 16 and 9 of 9; group 2, 16 of 17 and 12 of 13; group 3, 10 of 10, 5 of 5; group 4, primary patency not obtained). There was one asymptomatic rethrombosis that resolved with anticoagulation, and three patients underwent reintervention with venous angioplasty for significant symptom recurrence an average 2.89 ± 1.7 months after FRR. CONCLUSIONS: Our single-center retrospective study demonstrates that FRR with completion intraoperative venography has excellent symptomatic relief and short- and mid-term patency despite residual venous stenosis and complete occlusion. Although completion intraoperative venographic classification did not correlate with adverse outcomes, this protocol yielded excellent results and provides important clinical data for postoperative management. Our results also support a conservative approach to AxSCV occlusion identified after FRR.

The role of Klotho and FGF23 in cardiovascular outcomes of diabetic patients with chronic limb threatening ischemia: a prospective study.

Cardiovascular complications after lower extremity revascularization (LER) are common in diabetic patients with peripheral arterial disease (PAD) and chronic limb threatening ischemia (CLTI). The Klotho-fibroblast growth factor 23 (FGF23) axis is associated with endothelial injury and cardiovascular risk. We aimed to analyze the relationship between Klotho and FGF23 serum levels and the incidence of major adverse cardiovascular events (MACE) and major adverse limb events (MALE) after LER in diabetic patients with PAD and CLTI. Baseline levels of Klotho and FGF23, and their association with subsequent incidence of MACE and MALE were analyzed in a prospective, non-randomized study in a population of diabetic patients with PAD and CLTI requiring LER. A total of 220 patients were followed for 12 months after LER. Sixty-three MACE and 122 MALE were recorded during follow-up period. Baseline lower Klotho serum levels (295.3 ± 151.3 pg/mL vs. 446.4 ± 171.7 pg/mL, p < 0.01), whereas increased serum levels FGF23 (75.0 ± 11.8 pg/mL vs. 53.2 ± 15.4 pg/mL, p < 0.01) were significantly associated with the development of MACE. Receiver operating characteristic (ROC) analysis confirmed the predictive power of Klotho and FGF23 baseline levels. Furthermore, decreased Klotho levels were associated with the occurrence of MALE after LER (329.1 ± 136.8 pg/mL vs 495.4 ± 183.9 pg/mL, p < 0.01). We found that Klotho and FGF23 baseline levels are a potential biomarker for increased cardiovascular risk after LER in diabetic patients with PAD and CLTI.