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In patients with intermittent claudication (IC), short-term amputation rates from clinical trial data following lower extremity femoropopliteal (FP) peripheral vascular intervention (PVI) are <1% with unknown longer-term rates. The aim of this study was to identify revascularization and amputation rates following PVI in the FP segment and to assess 4-year amputation and revascularization rates after FP PVI for IC. From 2016 to 2020, 19,324 patients undergoing FP PVI for IC were included from the PINC AI Healthcare Database and evaluated by treatment level (superficial femoral artery [SFA], popliteal artery [POP], or both). The primary outcome was index limb amputation (ILA) assessed by Kaplan-Meier estimate. The secondary outcomes were index limb major amputation and repeat revascularization. HRs were estimated using Cox proportional hazard regression. The 4-year index limb amputation rate following FP PVI was 4.3% (95% CI: 4.0-4.7), with a major amputation rate of 3.2% (95% CI: 2.9-3.5). After POP PVI, ILA was significantly higher than SFA alone (7.5% vs 3.4%) or both segment PVI (5.5%). In multivariate analysis, POP PVI was associated with higher ILA rates at 4 years compared with isolated SFA PVI (HR: 2.10; 95% CI: 1.52-2.91) and index limb major amputation (HR: 1.98; 95% CI: 1.32-2.95). Repeat FP revascularization rates were 15.2%; they were highest in patients undergoing both SFA and POP PVI (18.7%; P < 0.0001) compared with SFA (13.9%) and POP (17.1%) only. IC patients undergoing FP PVI had 4-year rates of index limb repeat revascularization of 16.7% and ILA rates of 4.3%. Further risk factors for amputation requires further investigation. [Display omitted] [ABSTRACT FROM AUTHOR]

Deep venous thrombosis (DVT), (formation of a clot in a deep vein, usually in the thigh or pelvic area), can be a complication of orthopedic and general surgery patients. These clots may travel to the lungs and can be fatal. The rate of DVT after coronary artery bypass graft (CABG) surgery is not known because the edema (swelling from fluid retention), redness, and tenderness caused by vein harvesting make DVT difficult to diagnose. Now, high resolution ultrasonography with color Doppler imaging of the veins provides a noninvasive method of detecting DVT. Twenty-nine patients who underwent CABG surgery were examined using ultrasound to determine the incidence of DVT. Almost half had DVT that could not be detected clinically. The causes of DVT in these patients are probably similar to those in other surgical patients, including poor circulation, damage to the lining of the blood vessels, and an increased tendency for the blood to coagulate provoked by anesthetics and lack of mobility. However, CABG patients may face increased risk because of immobilization of the legs during and after surgery. The results indicate that the causes of DVT in CABG patients are different from those in patients undergoing other types of surgery. Routine postoperative treatment with aspirin does not prevent DVT, and patients who do not wear graded elastic compression stockings are probably at greater risk. (Consumer Summary produced by Reliance Medical Information, Inc.)

Antiplatelet agents are commonly used after peripheral endovascular intervention (PVI). However, the effect of full-dose anticoagulation on outcomes after PVI is not well-established. We sought to investigate whether full-dose anticoagulation after PVI is associated with adverse events. We utilized the Vascular Quality Initiative to study patients undergoing index PVI for claudication (2010-2019), stratified by the presence or absence of an anticoagulant on discharge. The primary outcomes were 2-year patency, major adverse limb events (MALE), and mortality. We built a propensity score adjusting for comorbidities and employed inverse probability weighting to estimate the association of anticoagulation with outcomes. We identified 26,240 patients; 9.1% were discharged on an anticoagulant. Patients receiving any anticoagulation had a significantly higher risk of mortality (adjusted hazard ratio [aHR], 1.61; 95% confidence interval [CI], 1.35-1.92), but not MALE, or patency loss. Patients receiving a vitamin K antagonist had a significantly higher risk of patency loss (aHR, 1.32; 95% CI, 1.09-1.60), MALE (aHR, 1.33; 95% CI, 1.13-1.57), and mortality (aHR, 1.46; 95% CI, 1.27-1.69). Patients on an oral Factor Xa inhibitors had a significantly lower risk of patency loss (aHR, 0.61; 95% CI, 0.41-0.93) but increased mortality (aHR, 1.51; 95% CI, 1.19-1.92). Therapeutic anticoagulation after PVI is associated with higher risk of all-cause mortality. Although oral Factor Xa inhibitors are associated with decreased risk of patency loss, vitamin K antagonists are associated with higher risk of patency loss, MALE, and death. Further prospective studies are necessary to study the safety and efficacy of full-dose anticoagulation after PVI. [Display omitted] [ABSTRACT FROM AUTHOR]

The process of peer review has been the gold standard for evaluating medical science, but significant pressures from the recent COVID-19 pandemic, new methods of communication, larger amounts of research, and an evolving publication landscape have placed significant pressures on this system. A task force convened by the American College of Cardiology identified the 5 most significant controversies associated with the current peer-review process: the effect of preprints, reviewer blinding, reviewer selection, reviewer incentivization, and publication of peer reviewer comments. Although specific solutions to these issues will vary, regardless of how scientific communication evolves, peer review must remain an essential process for ensuring scientific integrity, timely dissemination of information, and better patient care. In medicine, the peer-review process is crucial because harm can occur if poor-quality data or incorrect conclusions are published. With the dramatic increase in scientific publications and new methods of communication, high-quality peer review is more important now than ever. [Display omitted] • Peer review of medical science is critical to providing clinicians with fairly vetted and accurate information. • The current process of peer review is often opaque, slow, and susceptible to conscious and unconscious bias. • Peer-review processes must evolve to incorporate contemporary methods of communication and respond to increasing clinical demands. [ABSTRACT FROM AUTHOR]

Objectives The aim of this study was to determine whether the reduction in peripheral revascularization with vorapaxar in patients with peripheral artery disease (PAD) is directionally consistent across indications, including acute limb ischemia, progressively disabling symptoms, or both. Background The protease-activated receptor–1 antagonist vorapaxar reduces peripheral revascularization in patients with PAD. Methods The TRA 2°P–TIMI 50 (Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events–Thrombolysis in Myocardial Infarction 50) trial randomized 26,449 patients with histories of myocardial infarction, stroke, or symptomatic PAD to vorapaxar or placebo on a background of standard therapy. A total of 5,845 patients had a known history of PAD at randomization. Peripheral revascularization procedures reported by the site were a pre-specified outcome. We explored whether the benefit of vorapaxar was consistent across indication and type of procedure. Results Of the 5,845 patients with known PAD, a total of 934 (16%) underwent at least 1 peripheral revascularization over 2.5 years (median). More than one-half (55%) were for worsening claudication, followed by critical limb ischemia (24%), acute limb ischemia (16%), and asymptomatic severe stenosis (4%). Vorapaxar significantly reduced peripheral revascularization (19.3% for placebo, 15.4% for vorapaxar; hazard ratio: 0.82; 95% confidence interval: 0.72 to 0.93; p = 0.003), with a consistent pattern of efficacy across indication. Conclusions Vorapaxar reduces peripheral revascularization in patients with PAD. This benefit of vorapaxar is directionally consistent across type of procedure and indication. (Trial to Assess the Effects of Vorapaxar [SCH 530348; MK-5348] in Preventing Heart Attack and Stroke in Patients With Atherosclerosis [TRA 2°P - TIMI 50] [P04737]; NCT00526474 ) [ABSTRACT FROM AUTHOR]

Two guidelines from the American College of Cardiology (ACC), the American Heart Association (AHA), and collaborating societies address the risk of aortic dissection in patients with bicuspid aortic valves and severe aortic enlargement: The “2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM Guidelines for the Diagnosis and Management of Patients With Thoracic Aortic Disease” ( J Am Coll Cardiol . 2010;55:e27-130) and the “2014 AHA/ACC Guideline for the Management of Patients With Valvular Heart Disease” ( J Am Coll Cardiol . 2014;63:e57-185). However, the 2 guidelines differ with regard to the recommended threshold of aortic root or ascending aortic dilatation that would justify surgical intervention in patients with bicuspid aortic valves. The ACC and AHA therefore convened a subcommittee representing members of the 2 guideline writing committees to review the evidence, reach consensus, and draft a statement of clarification for both guidelines. This statement of clarification uses the ACC/AHA revised structure for delineating the Class of Recommendation and Level of Evidence to provide recommendations that replace those contained in Section 9.2.2.1 of the thoracic aortic disease guideline and Section 5.1.3 of the valvular heart disease guideline. [ABSTRACT FROM AUTHOR]

Objective Inflammation contributes to the development of peripheral artery disease (PAD) and may contribute to intermittent claudication by adversely affecting vascular and skeletal muscle function. We explored the association of inflammation to maximal walking time (MWT) in patients with claudication. Methods Circulating inflammatory biomarkers, including tumor necrosis factor α (TNF-α), C-reactive protein (CRP), interleukin-6 (IL-6), and soluble intercellular adhesion molecule 1 (sICAM), were measured in 75 subjects with intermittent claudication as well as in 43 healthy subjects. Real-time polymerase chain reaction was used to quantify mRNA expression of TNF-α, IL-6, interferon-γ, and CD36 from peripheral blood monocytes. Treadmill testing was performed in PAD subjects to assess MWT. Results Compared with healthy subjects, PAD subjects had higher levels of circulating TNF-α ( P < .0001), CRP ( P = .003), sICAM ( P < .0001), and IL-6 ( P < .0001). Expression of both IL-6 ( P = .024) and CD36 ( P = .018) was greater in PAD subjects than in healthy subjects. Among subjects with PAD, higher gene expression of TNF-α was associated inversely with MWT ( P = .01). MWT was also associated inversely with greater levels of circulating TNF-α ( P = .028), CRP ( P = .024), IL-6 ( P = .03), and sICAM ( P = .018). Conclusions Systemic inflammation, as indicated by TNF-α inflammatory gene expression in peripheral blood monocytes and by circulating biomarker levels, is associated with impairment in walking time in patients with PAD and intermittent claudication. [ABSTRACT FROM AUTHOR]

Objective: Successful adaptation of a vein graft to an arterial environment is incompletely understood. We sought to investigate whether early vein graft remodeling is predictive of subsequent patency. Methods: A prospective longitudinal study was conducted of 67 patients undergoing lower extremity bypass with autogenous vein between February 2004 and April 2008. Preoperative blood samples were drawn for biomarkers. During the bypass operation, a 5-cm index segment of the graft was registered for serial lumen diameter measurements at 0, 1, 3, 6, 9, and 12 months using duplex ultrasound imaging. The imaging substudy analysis included patients with at least two ultrasound assessments. Results: Patients (55% male) were a median age of 70 years (interquartile range [IQR], 59-76 years), 40% had diabetes mellitus, 49% had critical limb ischemia, 75% were taking a statin, and 91% were taking an antiplatelet medication. Median follow-up was 32 months (IQR, 15-47 months). The median baseline high-sensitivity C-reactive protein level (hsCRP) was 3.2 mg/L (IQR, 1.4-9.7 mg/L). The average intraoperative, postimplantation vein lumen diameter was 3.9 ± 1.0 mm, increasing to 4.7 ± 1.1 mm at 1 month, an average 24% ± 27% change per patient. By 3 months, the average lumen diameter was 5.1 ± 1.6 mm, with little subsequent change observed to 12 months. Nonwhite race, baseline hsCRP ≥5 mg/L, statin use, and initial lumen diameter were significantly associated with early (0- to 1-month) vein remodeling in a multivariable regression model. The primary patency rate for the cohort was 60% ± 6.3% at 2 years. Initial lumen diameter of the index segment was not associated with primary patency, whereas larger lumen diameter achieved at 1 month (≥5.1 mm) was positively associated with primary patency (log-rank, P = .03). Early (30-day) remodeling behavior was used to divide patients into “poor remodelers” (<−5% lumen diameter change, n = 6), “modest remodelers” (−5% to 25% change, n = 29), and “robust remodelers” (>+25% change, n = 30). Early remodeling category was significantly associated with primary patency rate at 2 years (log-rank, P = .02). A multivariable Cox proportional hazards model showed that modest remodelers (hazard ratio, 3.9; 95% confidence interval, 1.02-15; P = .04) and poor remodelers (hazard ratio, 13; 95% confidence interval; P = .008) had significantly higher hazard ratios for graft failure than robust early remodelers. Conclusions: Early remodeling of the arterialized vein appears to predict midterm bypass graft patency. In addition to baseline diameter, race, inflammation, hsCRP, and statin use are associated with early adaptive remodeling, but the mechanisms for these observations are not understood. [Copyright &y& Elsevier]

Background: Patients with advanced peripheral artery disease (PAD) have a high prevalence of cardiovascular (CV) risk factors and shortened life expectancy. However, CV risk factors poorly predict midterm (<5 years) mortality in this population. This study tested the hypothesis that baseline biochemical parameters would add clinically meaningful predictive information in patients undergoing lower extremity bypass operations. Methods: This was a prospective cohort study of patients with clinically advanced PAD undergoing lower extremity bypass surgery. The Cox proportional hazard model was used to assess the main outcome of all-cause mortality. A clinical model was constructed with known CV risk factors, and the incremental value of the addition of clinical chemistry, lipid assessment, and a panel of 11 inflammatory parameters was investigated using the C statistic, the integrated discrimination improvement index, and Akaike information criterion. Results: The study monitored 225 patients for a median of 893 days (interquartile range, 539-1315 days). In this study, 50 patients (22.22%) died during the follow-up period. By life-table analysis (expressed as percent surviving ± standard error), survival at 1, 2, 3, 4, and 5 years, respectively, was 90.5% ± 1.9%, 83.4% ± 2.5%, 77.5% ± 3.1%, 71.0% ± 3.8%, and 65.3% ± 6.5%. Compared with survivors, decedents were older, diabetic, had extant coronary artery disease, and were more likely to present with critical limb ischemia as their indication for bypass surgery (P < .05). After adjustment for the above, clinical chemistry and inflammatory parameters significant (hazard ratio [95% confidence interval]) for all-cause mortality were albumin (0.43 [0.26-0.71]; P = .001), estimated glomerular filtration rate (0.98 [0.97-0.99]; P = .023), high-sensitivity C-reactive protein (hsCRP; 3.21 [1.21-8.55]; P = .019), and soluble vascular cell adhesion molecule (1.74 [1.04-2.91]; P = .034). Of the inflammatory molecules investigated, hsCRP proved most robust and representative of the integrated inflammatory response. Albumin, eGFR, and hsCRP improved the C statistic and integrated discrimination improvement index beyond that of the clinical model and produced a final C statistic of 0.82. Conclusions: A risk prediction model including traditional risk factors and parameters of inflammation, renal function, and nutrition had excellent discriminatory ability in predicting all-cause mortality in patients with clinically advanced PAD undergoing bypass surgery. [Copyright &y& Elsevier]

Objective: This study was conducted to determine if there are sex-based differences in the inflammatory phenotype of patients undergoing lower extremity bypass (LEB) and if they correlate with clinical outcomes. Methods: This was a retrospective analysis of a prospective cohort of 225 patients (161 men and 64 women) who underwent autogenous vein LEB between February 2004 and May 2008. Fasting baseline blood samples were obtained before LEB, and the inflammatory biomarkers high-sensitivity C-reactive protein (CRP) and fibrinogen were assessed. All patients underwent ultrasound graft surveillance. CRP levels were dichotomized at 5 mg/L and fibrinogen levels at 600 mg/dL. Results: There were no significant differences in age, race, history of hypertension or diabetes mellitus, body mass index, or coronary artery disease between men and women. Men were more likely to be current smokers (P = .02), have a history of hypercholesterolemia (P = .02), and be taking statins (P = .02). Women were more likely to present with critical limb ischemia (P = .03) and had higher median baseline CRP levels (5.15 mg/L; interquartile range [IQR], 1.51-18.62 mg/L) than men (2.70; IQR, 1.24-6.98 mg/L; P = .02). Median follow-up was 893 days (IQR, 539-1315 days). A multivariable Cox proportional hazards model for primary vein graft patency showed a significant interaction between sex and CRP (P = .03) and fibrinogen (P = .02). After adjustment for key covariates, primary vein graft patency was significantly less in women with CRP >5 mg/L compared with women with CRP <5 mg/L (P = .02). No such difference was seen in men (P = .95). Primary graft patency was also decreased in women with fibrinogen >600 mg/dL vs women with fibrinogen <600 mg/dL (P = .002); again, this pattern was not evident in men (P = .19). Conclusions: Women undergoing LEB for advanced peripheral artery disease have a different inflammatory phenotype than men. Elevated baseline levels of CRP and fibrinogen are associated with inferior vein graft patency in women but not in men. These findings indicate an important interaction between sex and inflammation in the healing response of vein grafts for LEB. Women with elevated preoperative CRP and fibrinogen levels may benefit from more intensive postoperative graft surveillance protocols. [Copyright &y& Elsevier]

Objective: A significant portion of patients undergoing lower extremity bypass surgery (LEB) for peripheral arterial disease (PAD) will have cardiovascular or graft-related events. It has been previously demonstrated that systemic inflammation is associated with PAD and its clinical outcomes. We hypothesized that serum biomarkers of insulin resistance and inflammation would identify a subgroup at elevated risk for graft failure, limb loss, and mortality. Methods: This was a prospective longitudinal study of patients (n = 225) undergoing LEB using autogenous vein. Baseline blood samples were obtained prior to surgery in the fasting state. High-sensitivity C-reactive protein (hsCRP) and the adipokines resistin and high-molecular weight adiponectin (HMWA) were measured by enzyme-linked immunosorbent assay (ELISA). Median follow-up was 893 days. The major endpoints of primary patency (PP) and amputation-free survival (AFS) were examined using multivariable methods. Endpoints were screened against biomarkers and patient characteristics for univariate associations. Promising explanatory variables (P < .1) were included in multivariable Cox proportional hazard models. Results: The mean age of subjects was 67.6 years; 71.6% were male and 87.1% were Caucasian. One hundred thirty-three (59.1%) subjects underwent bypass for critical limb ischemia (CLI) and 73 (32.4%) had tissue loss. Patients with CLI and diabetes demonstrated elevated resistin and hsCRP levels. HMWA levels correlated with CLI and with a measure of insulin resistance (HOMA-IR) but not with clinical diabetes. Baseline biomarkers were higher in those presenting with tissue loss and in patients with postoperative events (mortality, limb loss). After multivariable analysis (including CLI, diabetes, age, estimated glomerular filtration rate [eGFR], adiponectin, resistin, and CRP), resistin (hazard ratio [HR] 1.75, 95% confidence interval [CI], 1.07-2.85; P = .025) and CRP (HR 2.39, 95% CI, 1.30-4.39; P = .005) were independently predictive of reduced AFS. However, only resistin maintained its significance when restricted to the diabetic cohort (HR 2.10, 95% CI, 1.10-3.99; P = .025). Higher levels of HMWA were found to be associated with primary graft patency (HR 0.73 for graft failure; 95% CI, 0.55 to 0.97; P = .031) in a multivariable model adjusting for diabetes, CRP, African-American race, CLI, high-risk conduits, and redo bypass procedures. Conclusion: These findings suggest that serum biomarkers of insulin resistance and inflammation may be predictive of clinical outcomes following LEB. Improving the systemic milieu of insulin resistance and inflammation in these high-risk patients may lead to reduced morbidity and mortality. [Copyright &y& Elsevier]

Background: Prior investigations to define ethnic-related differences in the risks, medical treatment, and outcomes of patients with peripheral arterial disease (PAD) have been limited. Methods: The impact of ethnicity on the risk factor profiles, use of evidence-based medical therapies, and 2-year cardiovascular outcomes were investigated in 2,168 individuals (blacks n = 237, Hispanics n = 115, whites n = 1,816) from the United States with PAD from the international Reduction of Atherothrombosis for Continued Health Registry. Results: Blacks and Hispanics were more likely to have diabetes mellitus and hypertension, whereas whites had a higher rate of diagnosed hypercholesterolemia. Control of blood pressure and cholesterol levels differed significantly in the groups at baseline: elevated blood pressure was present in 55% of blacks versus 48% of Hispanics versus 38% of whites (P < .01), whereas 41% of blacks versus 31% of Hispanics versus 25% of whites had elevated total cholesterol (P < .01). Aspirin use (62% of blacks vs 68% of Hispanics vs 72% of whites, P < .01) and statin use (72% of blacks vs 68% of Hispanics vs 77% of whites, P = .03) also varied significantly. In this context, rates by ethnicity for cardiovascular death, myocardial infarction, or stroke seemed to be no different at 2 years, at 8.8% for the total population: 11.6% for blacks, 8.5% for whites, and 5.0% for Hispanics (P = .32). Fewer blacks (0.6%) had undergone peripheral arterial bypass surgery compared with whites (3.4%) and Hispanics (5.2%) (P = .02). Conclusions: Ethnic-related differences have been documented in the prevalence and treatment of several atherosclerotic risk factors known to be associated with PAD, including a variation in the use of surgical revascularization procedures. [Copyright &y& Elsevier]

Abstract: Background: Hypertension is an important risk factor for the development of heart failure with preserved ejection fraction. Although heart failure in hypertensive patients is usually ascribed to intrinsic myocardial abnormalities, noncardiac factors may contribute. Methods and Results: Using arterial tonometry and Doppler echocardiography, we assessed arterial stiffness and cardiac diastolic function in 53 individuals with ejection fraction >=0.50, including 23 with hypertension but no heart failure, 16 with hypertension and heart failure, and 14 healthy, normotensive controls. Relative to healthy controls and hypertensives, subjects with heart failure had higher systolic blood pressure, body mass index, creatinine, and left ventricular mass. Diastolic function, as estimated by myocardial relaxation velocity, was not different among the 3 groups. Peripheral arterial stiffness was similar across all groups, but key measures of central aortic stiffness (carotid-femoral pulse wave velocity, characteristic impedance, forward wave amplitude) steadily increased with progression from healthy to hypertensive to heart failure despite adjustment for body mass index, systolic blood pressure, and renal function and were positively correlated with both left ventricular mass and filling pressure. Conclusions: We conclude that patients with heart failure and preserved ejection fraction have increased central aortic stiffness relative to age-matched healthy and hypertensive subjects without heart failure. These changes exceed differences in diastolic function and suggest that abnormal ventricular-vascular coupling may contribute to the pathophysiology of heart failure with preserved ejection fraction. [Copyright &y& Elsevier]

Objective: Datasets regarding patients with abdominal aortic aneurysm (AAA) have almost universally been restricted to single geographic regions. We aimed to obtain data on the risk factor profile and cardiovascular (CV) co-morbidity among multi-ethnic patients with known AAA in the global REACH (REduction of Atherothrombosis for Continued Health) Registry. Methods: The REACH Registry is an international, prospective, observational out-patient registry enrolling out-patients ≥45 years of age with established coronary artery disease (CAD), cerebrovascular disease (CVD) or peripheral arterial disease (PAD) or with at least three atherothrombotic risk factors. This report includes observations pertaining to 68,236 out-patients enrolled in 44 countries. Main outcome measures: Gender, ethnic origin, CV risk factors, established atherosclerotic disease (CAD, CVD and PAD) at baseline, and CV outcome events at 1-year were compared in patients with and without AAA. Results: An AAA was reported in 1722 (2.5%) of 68,236 out-patients enrolled in the REACH Registry. Older age (73 ± 8 vs 68 ± 10, P < .0001), male gender (81% vs 63%, P < .0001), White ethnicity (79% vs 67%, P < .0001) and a history of smoking (81% vs 55%, P < .0001) were independently related to the diagnosis of AAA. There was a weaker association with hypertension or hypercholesterolemia, and an inverse relation with diabetes. Fatal and non-fatal coronary and cerebrovascular event rates were not different between the AAA and non-AAA cohorts, but individuals with AAA suffered increased rates of other cardiovascular deaths (1.39% vs 0.94%, P = .0135), hospitalizations for atherothrombotic events (14.1% vs 9.3%, P < .0001) due to increased rates of revascularization procedures, and new or worsening PAD (3.7% vs 1.3%, P < .0001) at 1-year follow-up. Conclusion: This study, the largest published to date, presents the CV risk profile and outcome of patients with an established diagnosis of AAA from a cohort of patients with either overt manifestations of CV disease or multiple risk factors, and further defines these patients in a multi-ethnic, global context. [Copyright &y& Elsevier]

Objectives: Inflammatory markers such as high-sensitivity C-reactive protein (hsCRP) are associated with an increased risk of cardiovascular events and with the severity of peripheral arterial disease. The effects of inflammation on the development of vein graft disease remain speculative. We hypothesized that high levels of inflammatory markers would identify patients at increased risk for adverse events (graft failure, major cardiovascular events) after lower extremity bypass surgery. Methods: Patients (n = 91) scheduled to undergo lower extremity bypass using autogenous vein were enrolled into a prospective study at two institutions. Exclusion criteria included the presence of major infection. A baseline plasma sample was obtained on the morning of lower extremity bypass. Biomarkers for inflammation included hsCRP, fibrinogen, and serum amyloid A (SAA). Values between patients with and without critical limb ischemia were compared. Proportions of events among dichotomized populations (upper limit of normal of each laboratory assay) were compared by log-rank test. Results: Of the patients undergoing lower extremity bypass, 69% were men, 53% were diabetic, 81% were smokers, and their mean ankle-brachial index was 0.51 ± 0.19. The indication for lower extremity bypass was critical limb ischemia in 55%. There were no perioperative deaths and two early graft occlusions. During a mean follow-up of 342 days (range, 36-694 days) there were four deaths, 27 graft-related events, and 10 other cardiovascular events. No relationships were found between events and demographics, comorbidities, baseline ankle-brachial index, or statin use. High-sensitivity CRP (P = .005), fibrinogen (P < .001), and SAA (P = .0001) levels were associated with critical limb ischemia at presentation. Among patients with an elevated hsCRP (>5 mg/L) immediately before surgery, major postoperative vascular events occurred in 60% (21/35), compared with a 32% (18/56) rate in those with a baseline CRP <5 mg/L (P = .004, log-rank test). On multivariable analysis, only elevated hsCRP correlated with adverse graft-related or cardiovascular events (P = .018). Conclusions: The inflammatory biomarkers of hsCRP, fibrinogen, and SAA correlate with peripheral arterial disease severity at presentation in patients undergoing lower extremity bypass. Patients with elevated hsCRP are at increased risk for postoperative vascular events, most of which are related to the vein graft. These findings suggest a potential relationship between inflammation and outcomes after lower extremity vein bypass surgery. [Copyright &y& Elsevier]

Background: The geometric and biomechanical changes that contribute to vein graft remodeling are not well established. We sought to measure patterns of adaptation in lower extremity vein grafts and assess their correlation with clinical outcomes. Methods: We conducted a prospective, longitudinal study of patients undergoing infrainguinal reconstruction with autogenous conduit. In addition to standard duplex surveillance, lumen diameter (of a defined index segment of the conduit) and pulse wave velocity (PWV) were assessed by ultrasound imaging at surgery and at 1, 3, and 6 months postoperatively. Graft dimensions and wall stiffness were correlated with clinical outcomes. Results: There were 92 patients and 96 limbs in this study. On average, vein graft lumen diameter increased during the first month of implantation from 0.37 ± .01 cm to 0.45 ± 0.02 cm (mean ± SEM; P = .002), representing a relative change of +21.6% (median ± 14%; range, −31 to +67%) during this period. Of the entire cohort, 72% of grafts demonstrated appreciable dilation of the index segment during the first month. Index segment lumen diameter did not change appreciably beyond 1 month, with the notable exception of arm vein conduits, which showed continued tendency to dilate. PWV increased during the first 6 months (17.2 ± 1.2 m/s to 23.2 ± 2.4 m/s; P = .008), reflecting a nearly 40% increase in conduit stiffness (2.0 ± .6 Mdynes/cm to 3.3 ± .8 Mdynes/cm, P = .01). The greatest relative increase (25%) in PWV occurred from months 1 to 3. Loss of primary patency occurred in 24 cases (19 revisions, 5 occlusions), with a mean reintervention time of 7.6 months. Grafts that demonstrated early positive remodeling (lumen dilatation) had a trend of increased primary patency (P = .08, log rank). Among the grafts that failed, a trend was noted toward greater wall stiffness at 1 month, 2.7 vs 1.5 Mdynes (P = .08). Conclusion: Vein graft remodeling appears to involve at least two distinct temporal phases. Outward remodeling of the lumen occurs early, and wall stiffness changes occur in a more delayed fashion. Early outward remodeling may be important for successful vein graft adaptation. [Copyright &y& Elsevier]

A Collaborative Report from the American Associations for Vascular Surgery/Society for Vascular Surgery,* Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients with Peripheral Arterial Disease)—Summary of Recommendations [Copyright &y& Elsevier]

Hydroxymethylglutaryl-coenzyme A reductase inhibitors or statins constitute one of the wonder drugs of the last 2 decades. Use of this hypolipidemic medication class reduces morbidity and mortality in patients with a wide variety of cholesterol levels. Beneficial effects of the medication are seen in advance of changes in lipids suggesting nonlipid mechanisms may play a role in mediating these benefits of statins. One important nonlipid mechanism by which statins may improve vascular outcomes is restoration of normal endothelial cell function. This review will discuss the nonlipid effects of statins on endothelial cell function to highlight other avenues of benefit conferred by these medications. [Copyright &y& Elsevier]

The vascular endothelium is a crucial regulator of vascular function and homeostasis. Nitric oxide (NO) is an important paracrine substance released by the endothelium to regulate vasomotor tone. Risk factors for atherosclerosis, as well as atherosclerosis per se, are associated with endothelial dysfunction and decreased bioavailablilty of NO. Indeed, endothelial dysfunction is integral to the pathogenesis of atherosclerosis and other cardiovascular diseases. Moreover, endothelial dysfunction relates to an increased risk of adverse cardiovascular outcomes. L-Arginine is an essential amino acid required by the constitutive enzyme, endothelial NO oxide synthase (eNOS), to produce NO. Administration of L-arginine improves endothelial function in animal models and in humans with hypercholesterolemia and with atherosclerosis. Clinical trials to date support potential clinical applications of L-arginine in the treatment of coronary artery disease and peripheral arterial disease, as well as in the prevention of in-stent restenosis. The mechanism of benefit of L-arginine on endothelial function is unclear, because intracellular concentrations of L-arginine far exceed that required by eNOS. One potential explanation of this ‘arginine paradox’ is that L-arginine restores endothelial function in atherosclerotic patients, in whom there are elevated levels of asymmetric dimethylarginine, an endogenous inhibitor of eNOS. Given the promising findings of early studies of L-arginine as a potential therapy for cardiovascular disorders, large-scale clinical trials are warranted. [ABSTRACT FROM AUTHOR]

BACKGROUND: There has been increasing recognition of the detrimental impact of peripheral arterial disease (PAD) on the health of Americans, and yet there is no common national program of public PAD education designed to diminish this effect. FORMAT: To heighten awareness of this problem, a 2-day PAD Public Education Strategy Meeting was recently attended by representatives of 17 professional societies and public health associations whose missions support the prevention, diagnosis, treatment, and rehabilitation of vascular diseases. This Public Education Strategy Meeting was intended to provide the rationale and structure to create a national PAD public awareness campaign to diminish the health effect of PAD, and to improve cardiovascular outcomes in the United States. This document: (i) Provides the rationale for creation of a national PAD public education program; (ii) reviews the development and success of national hypertension, hypercholesterolemia, and Women''s Heart Health public education programs as models of educational efficacy; (iii) elucidates how the work of many vascular professionals has led to a national consensus for creation of a national PAD public educational program; (iv) provides an overview of the National Heart, Lung and Blood Institute (NHLBI) PAD education meeting; and (v) outlines the “next steps” required to accomplish these goals. OUTCOME: This meeting achieved consensus that we share responsibility for developing accurate, unified messages to promote PAD awareness and improved care. Participants agreed that the creation of such messages should be linked to plans to disseminate them to all Americans at risk. A consensus was reached that such messages, when commonly created and offered to the public, are most likely to achieve the rewards in better health that all Americans deserve. The Vascular Disease Foundation, a not-for-profit foundation whose mission includes public education regarding the prevention, diagnosis, treatment, and rehabilitation of PAD, will devote its resources to guide a new coalition in this process and to create a national PAD awareness campaign. During 2003 and 2004, the coalition will create the organizational underpinnings and timeline for what will undoubtedly be a multiyear effort. CONCLUSION: Participants of the Public Education Strategy Meeting agreed to create a broad coalition to develop a National PAD Public Awareness Program, with the objectives to develop and disseminate public education messages on PAD. A successful national PAD education program will contribute to creation of a broader mandate to improve global cardiovascular health in the United States. [Copyright &y& Elsevier]

Earlier this year, a 2-day Peripheral Arterial Disease (PAD) Public Education Strategy meeting was attended by representatives from various professional societies and public health associations. Marge Lovell, RN, CCRC, CVN, who also serves as the secretary for the Vascular Disease Foundation, and Patricia Lewis, MSN, RN, FNP, CVN, attended this meeting as SVN representatives. The purpose of this meeting was to develop a national PAD public awareness campaign focusing on the health impact of PAD with the goal to improve cardiovascular outcomes. The following article provides an overview of the rationale and mission of this consortium to develop and disseminate public education messages regarding PAD. This coalition will demonstrate a collaborative, multi-year partnership aimed to improve cardiovascular health.The American Radiological Nurses Association (ARNA) representative, Kathleen Gross MSN, RN,BC, CRN, joined SVN to offer nursing support and input into the early planning process. Nurses are recognized leaders in the development and implementation of patient education programs. In addition, SVN and ARNA members have previously participated in national PAD screening campaigns. The high level of support for nursing''s role in this particular endeavor was evident when Marge Lovell was appointed co-chair of the next phase of this campaign. She will share this role with Dr Alan Hirsch.Background: There has been increasing recognition of the detrimental effect of peripheral arterial disease (PAD) on the health of Americans, and yet there is no common national program of public PAD education designed to diminish this effect.Format: To heighten awareness of this problem, a 2-day PAD Public Education Strategy Meeting was recently attended by representatives of 17 professional societies and public health associations whose missions support the prevention, diagnosis, treatment, and rehabilitation of vascular diseases. This Public Education Strategy Meeting was intended to provide the rationale and structure to create a national PAD public awareness campaign to diminish the health effect of PAD and to improve cardiovascular outcomes in the United States. This document (1) provides the rationale for creation of a national PAD public education program; (2) reviews the development and success of national hypertension, hypercholesterolemia, and Women''s Heart Health public education programs as models of educational efficacy; (3) elucidates how the work of many vascular professionals has led to a national consensus for creation of a national PAD public educational program; (4) provides an overview of the National Heart, Lung, and Blood Institute PAD education meeting; and (5) outlines the “next steps” required to accomplish these goals.Outcome: This meeting achieved consensus that we share responsibility for developing accurate, unified messages to promote PAD awareness and improved care. Participants agreed that the creation of such messages should be linked to plans to disseminate them to all Americans at risk. A consensus was reached that such messages, when commonly created and offered to the public, are most likely to achieve the rewards in better health that all Americans deserve. The Vascular Disease Foundation, a not-for-profit foundation whose mission includes public education about the prevention, diagnosis, treatment, and rehabilitation of PAD, will devote its resources to guide a new coalition in this process and to create a national PAD awareness campaign. During 2003 and 2004, the coalition will create the organizational underpinnings and time line for what will undoubtedly be a multiyear effort.Conclusion: Participants of the Public Education Strategy Meeting agreed to create a broad coalition to develop a National PAD Public Awareness Program, with the objectives to develop and disseminate public education massages on PAD. A successful national PAD education program will contribute to creation of a broader mandate to improve global cardiovascular health in the United States. [Copyright &y& Elsevier]

Venous thromboembolism (VTE), composed of pulmonary embolism and deep venous thrombosis, is a significant cause of maternal mortality in the developed world. Normal physiological changes of pregnancy increase coagulability, which is compounded by patient-inherited and acquired risk factors. Depending on these risks and peripartum stage, the benefits of thromboprophylaxis can outweigh potential side effects. Diagnosis requires cautious clinical acumen because many symptoms of normal pregnancy mimic those of VTE and algorithmic tools used in the nonpregnant population are not equally applicable. Choice of imaging technique must account for potential risk to the fetus and altered test accuracy (sensitivity and specificity) in the setting of pregnancy. When VTE is diagnosed, anticoagulation is the backbone of treatment, with more advanced therapies being options for those with right ventricular dysfunction or unstable hemodynamics. Overall, pregnancy-associated VTE is complex, and management decisions should be individualized and informed by patient preferences. [ABSTRACT FROM AUTHOR]