Secondary interventions following open vs endovascular revascularization for chronic limb threatening ischemia in the BEST-CLI trial.

OBJECTIVES: Patients undergoing revascularization for chronic limb-threatening ischemia experience a high burden of target limb reinterventions. We analyzed data from the Best Endovascular versus Best Surgical Therapy in Patients with Critical Limb Ischemia (BEST-CLI) randomized trial comparing initial open bypass (OPEN) and endovascular (ENDO) treatment strategies, with a focus on reintervention-related study endpoints. METHODS: In a planned secondary analysis, we examined the rates of major reintervention, any reintervention, and the composite of any reintervention, amputation, or death by intention-to-treat assignment in both trial cohorts (cohort 1 with suitable single-segment great saphenous vein [SSGSV], n = 1434; cohort 2 lacking suitable SSGSV, n = 396). We also compared the cumulative number of major and all index limb reinterventions over time. Comparisons between treatment arms within each cohort were made using univariable and multivariable Cox regression models. RESULTS: In cohort 1, assignment to OPEN was associated with a significantly reduced hazard of a major limb reintervention (hazard ratio [HR], 0.37; 95% confidence interval [CI], 0.28-0.49; P < .001), any reintervention (HR, 0.63; 95% CI, 0.53-0.75; P < .001), or any reintervention, amputation, or death (HR, 0.68; 95% CI, 0.60-0.78; P < .001). Findings were similar in cohort 2 for major reintervention (HR, 0.53; 95% CI, 0.33-0.84; P = .007) or any reintervention (HR, 0.71; 95% CI, 0.52-0.98; P = .04). In both cohorts, early (30-day) limb reinterventions were notably higher for patients assigned to ENDO as compared with OPEN (14.7% vs 4.5% of cohort 1 subjects; 16.6% vs 5.6% of cohort 2 subjects). The mean number of major (mean events per subject ratio [MR], 0.45; 95% CI, 0.34-0.58; P < .001) or any target limb reinterventions (MR, 0.67; 95% CI, 0.57-0.80; P < .001) per year was significantly less in the OPEN arm of cohort 1. The mean number of reinterventions per limb salvaged per year was lower in the OPEN arm of cohort 1 (MR, 0.45; 95% CI, 0.35-0.57; P < .001 and MR, 0.66; 95% CI, 0.55-0.79; P < .001 for major and all, respectively). The majority of index limb reinterventions occurred during the first year following randomization, but events continued to accumulate over the duration of follow-up in the trial. CONCLUSIONS: Reintervention is common following revascularization for chronic limb-threatening ischemia. Among patients deemed suitable for either approach, initial treatment with open bypass, particularly in patients with available SSGSV conduit, is associated with a significantly lower number of major and minor target limb reinterventions.

Specific plasma oxylipins increase the odds of cardiovascular and cerebrovascular events in patients with peripheral artery disease.

Oxylipins and fatty acids may be novel therapeutic targets for cardiovascular disease. The objective was to determine if plasma oxylipins or fatty acids can influence the odds of cardiovascular/cerebrovascular events. In 98 patients (25 female, 73 male) with peripheral artery disease, the prevalence of transient ischemic attacks, cerebrovascular accidents, stable angina, and acute coronary syndrome was n = 16, 10, 16, and 24, respectively. Risk factors such as being male, diagnosed hypertension, diabetes mellitus, and hyperlipidemia were not associated with events. Plasma fatty acids and oxylipins were analyzed with gas chromatography and HPLC-MS/MS, respectively. None of 24 fatty acids quantified were associated with events. In contrast, 39 plasma oxylipins were quantified, and 8 were significantly associated with events. These 8 oxylipins are known regulators of vascular tone. For example, every 1 unit increase in Thromboxane B2/Prostaglandin F1α and every 1 nmol/L increase in plasma 16-hydroxyeicosatetraenoic acid, thromboxane B2, or 11,12-dihydroxyeicosatrienoic acid (DiHETrE) increased the odds of having had ≥2 events versus no event (p < 0.05). The greatest predictor was plasma 8,9-DiHETrE, which increased the odds of acute coronary syndrome by 92-fold. In conclusion, specific oxylipins were highly associated with clinical events and may represent specific biomarkers and (or) therapeutic targets of cardiovascular disease.

Spontaneous resolution of cystic adventitial disease: a word of caution.

Spontaneous resolution of cystic adventitial disease has been occasionally reported in the literature. It is unclear, however, whether this resolution is permanent. In this case report, we describe recurrence of a popliteal artery cystic adventitial disease after spontaneous resolution, which was successfully treated with surgery. The underlying mechanism is proposed. Without definitive treatment, the patients with spontaneous resolution of cystic adventitial disease may need long-term follow-up, given the risk of recurrence.

Oral anticoagulant and antiplatelet therapy and peripheral arterial disease.

BACKGROUND: Atherosclerotic peripheral arterial disease is associated with an increased risk of myocardial infarction, stroke, and death from cardiovascular causes. Antiplatelet drugs reduce this risk, but the role of oral anticoagulant agents in the prevention of cardiovascular complications in patients with peripheral arterial disease is unclear. METHODS: We assigned patients with peripheral arterial disease to combination therapy with an antiplatelet agent and an oral anticoagulant agent (target international normalized ratio [INR], 2.0 to 3.0) or to antiplatelet therapy alone. The first coprimary outcome was myocardial infarction, stroke, or death from cardiovascular causes; the second coprimary outcome was myocardial infarction, stroke, severe ischemia of the peripheral or coronary arteries leading to urgent intervention, or death from cardiovascular causes. RESULTS: A total of 2161 patients were randomly assigned to therapy. The mean follow-up time was 35 months. Myocardial infarction, stroke, or death from cardiovascular causes occurred in 132 of 1080 patients receiving combination therapy (12.2%) and in 144 of 1081 patients receiving antiplatelet therapy alone (13.3%) (relative risk, 0.92; 95% confidence interval [CI], 0.73 to 1.16; P=0.48). Myocardial infarction, stroke, severe ischemia, or death from cardiovascular causes occurred in 172 patients receiving combination therapy (15.9%) as compared with 188 patients receiving antiplatelet therapy alone (17.4%) (relative risk, 0.91; 95% CI, 0.74 to 1.12; P=0.37). Life-threatening bleeding occurred in 43 patients receiving combination therapy (4.0%) as compared with 13 patients receiving antiplatelet therapy alone (1.2%) (relative risk, 3.41; 95% CI, 1.84 to 6.35; P<0.001). CONCLUSIONS: In patients with peripheral arterial disease, the combination of an oral anticoagulant and antiplatelet therapy was not more effective than antiplatelet therapy alone in preventing major cardiovascular complications and was associated with an increase in life-threatening bleeding. (ClinicalTrials.gov number, NCT00125671 [ClinicalTrials.gov].).

Flaxseed consumption reduces blood pressure in patients with hypertension by altering circulating oxylipins via an α-linolenic acid-induced inhibition of soluble epoxide hydrolase.

UNLABELLED: In a randomized, double-blinded, controlled clinical trial, participants with peripheral arterial disease (75% hypertensive) consumed 30 g of milled flaxseed/d for 6 months. The flaxseed group exhibited significant reductions in systolic (-10 mm Hg) and diastolic (-7 mm Hg) blood pressure. Flaxseed contains the n3 fatty acid α-linolenic acid. Plasma α-linolenic acid increased with ingestion of flaxseed and was inversely associated with blood pressure. However, the antihypertensive mechanism was unclear. Oxylipins derived from polyunsaturated fatty acids regulate vascular tone. Therefore, the objective was to examine whether flaxseed consumption altered plasma oxylipins in a manner that influenced blood pressure. Plasma of FlaxPAD (Flaxseed for Peripheral Arterial Disease) participants underwent solid phase extraction and high-performance liquid chromatography-mass spectrometry/mass spectrometry analysis. The flaxseed group exhibited significant decreases in 8 plasma oxylipins versus control. Six of these (5,6-, 8,9-, 11,12-, 14,15-dihydroxyeicosatrienoic acid and 9,10- and 12,13-dihydroxyoctadecenoic acid) were products of soluble epoxide hydrolase, a pharmacological target for antihypertensive treatment. Patients exhibiting a decrease in total plasma soluble epoxide hydrolase-derived oxylipins, exhibited a significant decrease in systolic blood pressure (mean [95% confidence interval], -7.97 [-14.4 to -1.50] mm Hg) versus those who exhibited increased plasma soluble epoxide hydrolase-derived oxylipins (+3.17 [-4.78 to 11.13] mm Hg). These data suggest that a flaxseed bioactive may have decreased blood pressure via soluble epoxide hydrolase inhibition. Using a soluble epoxide hydrolase inhibitor screening assay, increasing concentrations of α-linolenic acid decreased soluble epoxide hydrolase activity (P=0.0048; ρ=-0.94). In conclusion, α-linolenic acid in flaxseed may have inhibited soluble epoxide hydrolase, which altered oxylipin concentrations that contributed to the antihypertensive effects in patients with peripheral arterial disease. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00781950.

The effect of dietary flaxseed on improving symptoms of cardiovascular disease in patients with peripheral artery disease: rationale and design of the FLAX-PAD randomized controlled trial.

BACKGROUND: Flaxseed is an important source of alpha-linolenic acid an essential omega-3 fatty acid. The possibility that a supplementation of the diet with foods rich in alpha-linolenic acid, antioxidants and fiber (like flaxseed) has not been investigated. METHODS/DESIGN: The primary objective is to determine whether consumption of a diet rich in FLAXseed over a one year period has any beneficial cardiovascular effects in patients with Peripheral Arterial Disease (FLAX-PAD study). This is a single center, prospective, double blinded, randomized controlled clinical trial aimed at in 110 patients over 40 years old and with peripheral arterial disease. Patients will receive 30 g of milled flaxseed (or placebo) per day. Primary endpoints are incidence of myocardial infarction and stroke. Secondary measures include: requirement for surgical interventions, exercise and cardiopulmonary performance, cardiac arrhythmias, serum lipid profile, arterial sufficiency, blood pressure, inflammatory profile, platelet function, changes in drug dosage levels, as well as nutrigenomic and biomarker profiles in the blood. Recruitment and baseline examinations started in October 2008. Baseline data of the 110 patients is shown. CONCLUSIONS: FLAX-PAD will generate data on the safety, tolerability, cardiovascular efficacy and genomic response to a diet rich in flaxseed. It will determine the effects on primary and secondary events (stroke, myocardial infarctions, angina pectoris, cardiac arrhythmias) as well as in secondary endpoints (exercise performance, blood pressure and circulating lipid levels) in patients with PAD.

Risk factors and prevalence of perioperative cognitive dysfunction in abdominal aneurysm patients.

BACKGROUND: Perioperative delirium is common in high-risk surgery and is associated with age, education, preoperative cognitive functioning, pre-existing medical conditions, and postoperative complications. We investigated these factors as well as lifestyle and demographic variables by using cognitive measures that were more sensitive than those used in previous studies. METHODS: Extensive medical and demographic data were collected on 102 patients between 41 and 88 years of age to identify comorbidities and lifestyle considerations preoperatively. Elective abdominal aortic aneurysm surgery was performed under combined general/epidural anesthesia with postoperative epidural analgesia. A battery of sensitive, cognitive measures was administered preoperatively, at the time of discharge from hospital, and 3 months postoperatively. Symptoms of delirium were assessed during the first 6 postoperative days using Diagnostic and Statistical Manual of Mental Disorders-4th Edition criteria. Intraoperative and postoperative data, including medications, vital signs, conduct of the surgery and anesthesia, complications, and details of pain control, were collected. RESULTS: Delirium occurred in 33% of the patients during the first 6 days after surgery. Longer duration of delirium was related to lower education, preoperative depression, and greater preoperative psychoactive medication use. Characteristics of the surgery and hospital stay were unrelated to the development of delirium. Patients who were diagnosed with delirium had lower cognitive scores during each of the three assessment periods, even when controlling for age and education. Logistic regression analysis indicated that the most powerful preoperative predictors of delirium were number of pack years smoked (P = .001), mental status scores (P = .003), and number of psychoactive medications (P = .005). CONCLUSION: A significant proportion of patients undergoing elective abdominal aortic aneurysm repair are susceptible to the development of delirium and are at risk for cognitive dysfunction after surgery. Our findings have implications for promoting long-term lifestyle changes, including smoking cessation and improved management of mental health as risk-reduction strategies.

Variable ventilation improves perioperative lung function in patients undergoing abdominal aortic aneurysmectomy.

BACKGROUND: Optimizing perioperative mechanical ventilation remains a significant clinical challenge. Experimental models indicate that "noisy" or variable ventilation (VV)--return of physiologic variability to respiratory rate and tidal volume--improves lung function compared with monotonous control mode ventilation (CV). VV was compared with CV in patients undergoing abdominal aortic aneurysmectomy, a patient group known to be at risk of deteriorating lung function perioperatively. METHODS: After baseline measurements under general anesthesia (CV with a tidal volume of 10 ml/kg and a respiratory rate of 10 breaths/min), patients were randomized to continue CV or switch to VV (computer control of the ventilator at the same minute ventilation but with 376 combinations of respiratory rate and tidal volume). Lung function was measured hourly for the next 6 h during surgery and recovery. RESULTS: Forty-one patients for aneurysmectomy were studied. The characteristics of the patients in the two groups were similar. Repeated-measures analysis of variance (group x time interaction) revealed greater arterial oxygen partial pressure (P = 0.011), lower arterial carbon dioxide partial pressure (P = 0.012), lower dead space ventilation (P = 0.011), increased compliance (P = 0.049), and lower mean peak inspiratory pressure (P = 0.013) with VV. CONCLUSIONS: The VV mode of ventilation significantly improved lung function over CV in patients undergoing abdominal aortic aneurysmectomy.