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Aim: The "2024 ACC/AHA/AACVPR/APMA/ABC/SCAI/SVM/SVN/SVS/SIR/VESS Guideline for the Management of Lower Extremity Peripheral Artery Disease" provides recommendations to guide clinicians in the treatment of patients with lower extremity peripheral artery disease across its multiple clinical presentation subsets (ie, asymptomatic, chronic symptomatic, chronic limb-threatening ischemia, and acute limb ischemia)., Methods: A comprehensive literature search was conducted from October 2020 to June 2022, encompassing studies, reviews, and other evidence conducted on human subjects that was published in English from PubMed, EMBASE, the Cochrane Library, CINHL Complete, and other selected databases relevant to this guideline. Additional relevant studies, published through May 2023 during the peer review process, were also considered by the writing committee and added to the evidence tables where appropriate., Structure: Recommendations from the "2016 AHA/ACC Guideline on the Management of Patients With Lower Extremity Peripheral Artery Disease" have been updated with new evidence to guide clinicians. In addition, new recommendations addressing comprehensive care for patients with peripheral artery disease have been developed., (Copyright © 2024 American College of Cardiology Foundation and the American Heart Association, Inc. Published by Elsevier. Published by Elsevier Inc. All rights reserved.)

Background: Recent large clinical trials show lower rates of late cardiovascular events by extending clopidogrel >12 months after percutaneous coronary revascularization (PCI). However, concerns of increased bleeding have elicited support for limiting prolonged treatment to high-risk patients., Objectives: The aim of this analysis was to determine the effect of prolonging clopidogrel therapy >12 months versus ≤12 months after PCI on very late outcomes in patients with diabetes mellitus (DM)., Methods: Using the Veterans Health Administration, 28,849 patients undergoing PCI between 2002 and 2006 were categorized into 3 groups: 1) 16,332 without DM; 2) 9,905 with DM treated with oral medications or diet; and 3) 2,612 with DM treated with insulin. Clinical outcomes, stratified by stent type, ≤4 years after PCI were determined from the Veterans Health Administration and Medicare databases and risk was assessed by multivariable and propensity score analyses using a landmark analysis starting 1 year after the index PCI. The primary endpoint of the study was the risk of all-cause death or myocardial infarction (MI)., Results: In patients with DM treated with insulin who received drug-eluting stents (DES), prolonged clopidogrel treatment was associated with a decreased risk of death (hazard ratio [HR]: 0.59; 95% confidence interval [CI]: 0.42 to 0.82) and death or MI (HR: 0.67; 95% CI: 0.49 to 0.92). Similarly, in patients with noninsulin-treated DM receiving DES, prolonged clopidogrel treatment was associated with less death (HR: 0.61; 95% CI: 0.48 to 0.77) and death or MI (HR: 0.61; 95% CI: 0.5 to 0.75). Prolonged clopidogrel treatment was not associated with a lower risk in patients without DM or in any group receiving bare-metal stents., Conclusions: Extending the duration of clopidogrel treatment >12 months may decrease very late death or MI only in patients with DM receiving first-generation DES. Future studies should address this question in patients receiving second-generation DES., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: This study sought to define the relationship between oxidative biomarkers, cardiovascular disease (CVD) risk factors, and inflammatory and thrombosis biomarkers., Background: Elevated levels of oxidized phospholipids (OxPL) on apolipoprotein B particles (apoB) represent a novel biomarker of CVD. Previous studies suggest that an increase in OxPL/apoB reflects a positive response to statins and a low-fat diet., Methods: This study measured OxPL/apoB, lipoprotein (a) [Lp(a)], and oxidized low-density lipoprotein (OxLDL) biomarkers, consisting of immunoglobulin (Ig)G and IgM autoantibodies to malondialdehyde (MDA)-low-density lipoprotein (LDL) and IgG and IgM apoB-100 immune complexes (IC/apoB), at baseline and after 16 weeks of treatment with atorvastatin 80 mg/day or placebo in 2,342 patients with acute coronary syndromes (ACS) enrolled in the MIRACL (Myocardial Ischemia Reduction With Aggressive Cholesterol Lowering) trial., Results: At baseline, potentially atheroprotective IgM autoantibodies and IgM IC/apoB were lower in male patients, diabetic patients, and patients >65 years of age. Patients with an LDL level greater than the median (122 mg/dl) had higher levels of OxPL/apoB, Lp(a), and OxLDL biomarkers compared with those who had an LDL level less than the median. Atorvastatin resulted in significantly larger changes in all biomarkers in female patients, patients age <65 years, patients with LDL cholesterol <122 mg/dl, nonsmokers, and nondiabetic patients (p < 0.0001 for all). In particular, a significant increase in OxPL/apoB in response to atorvastatin was noted in all 20 subgroups evaluated. Weak or no significant correlations were noted between all OxLDL biomarkers and C-reactive protein, serum amyloid A, tissue plasminogen activator, interleukin-6, intercellular adhesion molecule, vascular cell adhesion molecule, P-selectin, and E-selectin at randomization and 16 weeks., Conclusions: In patients with ACS, baseline levels of oxidative biomarkers varied according to specific CVD risk factors and were largely independent of inflammatory biomarkers. Atorvastatin uniformly increased OxPL/apoB levels in all subgroups studied. Future studies are warranted to assess whether the increase in OxPL/apoB levels reflects the benefit of effective therapeutic interventions and prediction of new CVD events.

Objectives: This study sought to assess the contribution of low-density lipoprotein (LDL)-dependent and LDL-independent effects of LDL-lowering therapies to changes in C-reactive protein (CRP) in healthy or stable subjects., Background: Correlations of change in LDL and CRP in individuals are lowered by their measurement variability. By using average changes in LDL and CRP in study groups, meta-analysis reduces this variability to better assess their correlation., Methods: A systematic search for randomized placebo-controlled trials reporting change in LDL and CRP with LDL-lowering interventions retrieved 23 studies with 57 groups treated with a variety of statins, nonstatin drugs, or other regimens. Meta-analysis techniques assessed the relationships between average mean differences (placebo - treatment) in change in CRP and LDL., Results: The overall reduction in CRP was 28% (95% confidence interval 26% to 30%). Significantly greater CRP reduction occurred in statin and statin-ezetimibe interventions, interventions using 80 mg/day of statins, and with greater LDL lowering. Meta-regression analysis showed a strong correlation between the change in LDL and CRP (r = 0.80, p < 0.001). Statin therapies had no significant effect on CRP after adjusting for the change in LDL. In a multivariate model applied to a range of LDL reduction typically seen with statins (20% to 60%), 89% to 98% of CRP change was related to LDL lowering and 2% to 11% was related to non-LDL effects of statins., Conclusions: In clinical practice, most of the anti-inflammatory effect of LDL-lowering therapies is related to the magnitude of change in LDL. The potential non-LDL effects of statins on inflammation are much smaller in magnitude.

Objectives: We tested whether long-term administration of antioxidant vitamins C and E improves coronary and brachial artery endothelial function in patients with coronary artery disease (CAD)., Background: Endothelial function is a sensitive indicator of vascular health. Oxidant stress and oxidized low-density lipoprotein (LDL) impair endothelial function by reducing nitric oxide bioavailability in the artery wall., Methods: We randomly assigned 30 subjects with CAD to combined vitamin E (800 IU per day) and C (1000 mg per day) or to placebos in a double-blind trial. Coronary artery endothelial function was measured as the change in coronary artery diameter to acetylcholine infusions (n = 18 patients), and brachial artery endothelial function was assessed by flow-mediated dilation (n = 25 patients) at baseline and six months. Plasma markers of oxidant stress (oxidized LDL and autoantibodies) were also measured., Results: Plasma alpha-tocopherol (p < 0.001) and ascorbic acid (p < 0.02) increased with active therapy. Compared to placebo, there was no improvement in coronary and brachial endothelial vasomotor function over six months. Although vitamins C and E tended to reduce F2-isoprostanes (p = 0.065), they failed to alter oxidized LDL or autoantibodies to oxidized LDL., Conclusions: Long-term oral vitamins C and E do not improve key mechanisms in the biology of atherosclerosis or endothelial dysfunction, or reduce LDL oxidation in vivo.

Objectives: The objective of this study was to identify predictors of major adverse cardiac events after successful coronary angioplasty., Background: The acute complications of angioplasty are related to baseline clinical and angiographic variables, and early complications adversely affect long-term outcome. However, the predictors of enduring success after uncomplicated angioplasty are less well defined., Methods: Of 4,098 patients undergoing angioplasty in the Hirulog Angioplasty Study, 3,899 (95%) had a successful procedure without in-hospital death, emergent bypass surgery or clinical evidence of myocardial infarction. Baseline and procedural variables for these 3,899 patients were examined., Results: Major adverse cardiac events occurred in 22% of the patients with initially successful procedures at 6 months: death in 1%, myocardial infarction in 2% and repeat revascularization in 21%. Univariable predictors of increased events included successful salvage from abrupt vessel closure (p < 0.001), emergency stenting (p < 0.001), multilesion angioplasty (p < 0.001), diabetes (p=0.02), target lesion in the left anterior descending artery (p=0.02), unstable angina (p=0.03) and smaller final luminal diameter (p=0.04). There was a trend toward increased events among patients with prior angioplasty (p=0.08), but asymptomatic elevation of the creatine kinase was not predictive (p=0.5). In a multivariable model, abrupt vessel closure was the strongest independent predictor of major adverse cardiac events at 6 months (p < 0.001; odds ratio [95% confidence interval]=3.6 [2.5 to 5.1]), while multivessel angioplasty, target lesion in the left anterior descending artery and diabetes also remained independent predictors (all p < or = 0.02)., Conclusions: This analysis suggests that "uncomplicated" abrupt vessel closure is a powerful predictor of adverse clinical outcome following successful angioplasty. Improved techniques to reduce abrupt closure during angioplasty are thus urgently needed, and patients who experience "uncomplicated" closure require closer surveillance during follow-up.

Objectives: This study sought to examine whether lipoprotein(a) concentrations were risk factors for a first acute and recurrent myocardial infarction., Background: There is conflicting evidence concerning the risk of acute myocardial infarction from lipoprotein(a). No studies have examined the risk of recurrent acute myocardial infarction from lipoprotein(a), and few have addressed the risk in women., Methods: This was a population-based case-control study of 893 men and women 35 to 69 years old participating in the World Health Organization Monitoring Trends and Determinants in Cardiovascular Disease (MONICA) Project in Newcastle, Australia in 1993 to 1994. Case and control patients were classified into those with and without a previous myocardial infarction, and median lipoprotein(a) concentrations were compared after adjusting for other variables. Quintiles of lipoprotein(a) concentration were also examined., Results: Compared with control subjects without a previous myocardial infarction, median lipoprotein(a) concentrations increased from case patients with a first myocardial infarction (15 mg/liter higher, 95% confidence interval [CI] -36 to 60) to control patients with a previous myocardial infarction (159 mg/ liter higher, 95% CI 40 to 278) and case patients with a previous myocardial infarction (60 mg/liter higher, 95% CI -16 to 136, p < 0.01, test for trend). Women had significantly higher lipoprotein(a) concentrations than men (median 71 mg/liter higher, 95% CI 23 to 118). The highest quintile of lipoprotein(a) (>550 mg/liter) was a significant risk factor for a first acute myocardial infarction (odds ratio [OR] 1.77, 95% CI 1.03 to 3.03); but in those with a previous myocardial infarction, the highest quintile was not associated with recurrent myocardial infarction (OR 0.84, 95% CI 0.30 to 2.37)., Conclusions: High lipoprotein(a) concentrations may be a marker of vascular or tissue injury or may be associated with other genetic or environmental factors that cause acute myocardial infarction. Currently, lipoprotein(a) measurement cannot be recommended for assessment of risk for acute myocardial infarction.