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Abstract: Purpose: The study’s objective was to evaluate the prognostic value of left ventricular ejection fraction and stress-induced ischemia during dobutamine stress echocardiography, in addition to ankle-brachial index measurements and clinical risk factors in patients with suspected or known peripheral arterial disease. Methods: In 852 patients with suspected or known peripheral arterial disease (mean age 63 years, 70% male), the ankle-brachial index was measured, left ventricular ejection fraction was assessed, and all patients underwent additional stress testing. Endpoints were all-cause mortality and hard cardiac events (cardiac death or nonfatal myocardial infarction). Results: During a mean follow-up of 7.6±4.4 years, death occurred in 288 patients (34%), and hard cardiac events occurred in 216 patients (25%). Mean left ventricular ejection fraction was 50%±17%, and stress-induced ischemia was observed in 352 patients (41%). In multivariate analysis with adjustment for clinical risk factors and ankle-brachial index, each 5% decrease in left ventricular ejection fraction was associated with increased all-cause mortality (hazard ratio [HR] 1.05, 95% confidence interval [CI], 1.02-1.09) and hard events (HR 1.14, 95% CI, 1.08-1.21). Stress-induced ischemia also independently predicted all-cause mortality (HR 2.01, 95% CI, 1.38-2.79) and hard events (HR 2.06, 95% CI, 1.39-3.08). Left ventricular ejection fraction and stress-induced ischemia provided incremental prognostic information over clinical data and ankle-brachial index values (P <.001). Conclusions: Left ventricular ejection fraction and stress-induced ischemia independently predict long-term outcome and improve prognostic risk assessment, in addition to ankle-brachial index and clinical risk factors in patients with suspected or known peripheral arterial disease. [Copyright &y& Elsevier]

Objective: There is a lack of consensus regarding the optimal antithrombotic therapy (ATT) after popliteal and infrapopliteal (PIP) endovascular therapy (EVT). Currently, dual antiplatelet therapy (DAPT) for 3 months and single antiplatelet therapy (SAPT) are the most prescribed regimens in the Netherlands. Thus far, no randomized comparison has been performed on the optimal ATT approach. Therefore, this study compared the efficacy and safety of 3-month DAPT with SAPT following PIP EVT., Design: Retrospective analysis of prospectively collected data from a multicenter registry., Methods: The Dutch chronic lower limb-threatening ischemia registry (THRILLER) collected prospective data on patients enrolled between January 2021 and October 2023. As for ATT, only patients prescribed antiplatelet therapy (APT), were included in this analysis. The primary efficacy outcome was a composite of 3-month major adverse cardiovascular events (MACEs, ie, myocardial infarction, cerebrovascular event, cardiovascular death), major adverse limb events (MALEs, ie, major amputation, reintervention), and non-cardiovascular death. Secondary efficacy outcomes were 3-month MACE, MALE, and all-cause mortality. The primary safety outcome was major bleeding according to the 'Thrombolysis In Myocardial Infarction' (TIMI) classification. Descriptive statistics and Cox proportional hazard models were applied., Results: In total, 460 of 840 THRILLER patients used DAPT or SAPT as ATT and were therefore included in the analysis. Of these, 322 (70%) received DAPT and 138 (30%) received SAPT. In total, 73 (15.9%) primary efficacy outcomes were observed of which 21 (15.2%) events in the SAPT group and 52 (16.1%) events in the DAPT group. No significant differences were observed between SAPT and DAPT for the primary efficacy outcomes or any of the secondary efficacy outcomes. In both groups, one case of major bleeding was observed., Conclusion: The findings suggest that 3 months of DAPT is not superior to SAPT. A well-powered randomized trial is warranted to assess the efficacy and safety of post-procedural DAPT in chronic limb-threatening ischemia (CLTI) patients undergoing PIP EVT., Clinical Impact: This manuscript reports on the efficacy and safety outcomes of 3 months of DAPT versus SAPT, which are commonly chosen therapies following popliteal and infrapopliteal endovascular therapy. No significant difference was found between the two groups regarding major adverse cardiovascular events, all-cause death, major amputation, or major bleeding. Therefore, 3 months of DAPT does not seem superior to SAPT. These results suggest that SAPT appears to be a sufficient alternative when considering 3 months of DAPT. Further research should verify these outcomes and focus on the efficacy and safety of prolonged DAPT suppletion after endovascular therapy., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The biofabrication of recombinant structural proteins with a range of mechanical or structural features usually relies on the generation of protein libraries displaying variations in terms of amino acid composition, block structure, molecular weight, or physical/chemical cross-linking sites. This approach, while highly successful in generating a wealth of knowledge regarding the links between design features and material properties, has some inherent limitations related to its low throughput. This slows down the pace of the development of de novo recombinant structural proteins. Here, we propose an approach to tune the viscoelastic properties of temperature-responsive hydrogels made of silk-elastin-like polypeptides (SELPs) without modifying their sequence. To do so, we subject purified SELPs to two different postprocessing methods─water annealing or EtOH annealing─that alter the topology of highly disordered SELP networks via the formation of ordered intermolecular β-sheet physical cross-links. Combining different analytical techniques, we connect the order/disorder balance in SELPs with their gelling behavior. Furthermore, we show that introducing a functional block (in this case, a biomineralizing peptide) in the sequence of SELPs can disrupt its self-assembly and that such disruption can only be overcome by EtOH annealing. Our results suggest that postprocessing of as-purified SELPs might be a simple approach to tune the self-assembly of SELPs into biomaterials with bespoke viscoelastic properties beyond the traditional approach of developing SELP libraries via genetic engineering.

Rationale: Elastin-like polypeptides (ELPs) are elastic and thermoresponsive biopolymers composed of VPGXG repeats (X can be any amino acid except proline), used in biomedical applications, for example, tissue engineering and drug delivery. As different variants of ELP are mostly produced fermentatively, there is a need for the development of analysis methods that allow for absolute protein quantification in both complex matrices and purified samples and MW determination of the final products., Methods: ELPs were intracellularly expressed in Escherichia coli quantified after cell lysis and enzymatic digestion using a proline-specific protease ProAlanase (Promega) at acidic conditions. Resulting peptides were separated by liquid chromatography, and mass spectrometry analysis was conducted by electrospray ionization high-resolution mass spectrometry using an Orbitrap mass spectrometer. The addition of a stable isotopically labeled internal standard enabled quantification in complex matrices. Prior to intact mass analysis, ELPs were purified from fermentation broth by inverse temperature cycling. Intact protein analysis was performed using reversed-phase liquid chromatography, and mass spectrometry analysis was conducted by electrospray ionization high-resolution mass spectrometry using a time-of-flight mass spectrometer., Results: Absolute quantification of ELPs was achieved by utilizing ELP-specific properties, that is, proline-rich, soluble at low pH and low temperature. The repetitive nature of ELPs allows for sensitivity increase and use of higher dilution factors to minimize the matrix effects. Despite the lack of amino acids with charged side chains (Arg, His, Lys, Asp, and Glu) in ELP, we demonstrated successful intact protein analysis using reversed-phase LC coupled to electrospray ionization TOF MS. Moreover, truncated protein forms could be chromatographically separated and characterized as well as N-terminal modifications., Conclusions: Both methods combined enabled quantitative and qualitative characterization of fermentatively produced ELPs., (© 2024 John Wiley & Sons Ltd.)

The prolyl-alanyl-specific endoprotease (EndoPro) is an industrial enzyme produced in Aspergillus niger . EndoPro is mainly used for food applications but also as a protease in proteomics. In-depth characterization of this enzyme is essential to understand its structural features and functionality. However, there is a lack of analytical methods capable of maintaining both the structural and functional integrity of separated proteoforms. In this study, we developed an anion exchange (AEX) method coupled to native mass spectrometry (MS) for profiling EndoPro proteoforms. Moreover, we investigated purified EndoPro proteoforms with complementary MS-based approaches, including released N-glycan and glycopeptide analysis, to obtain a comprehensive overview of the structural heterogeneity. We showed that EndoPro has at least three sequence variants and seven N-glycosylation sites occupied by high-mannose glycans that can be phosphorylated. Each glycosylation site showed high microheterogeneity with ∼20 glycans per site. The functional characterization of fractionated proteoforms revealed that EndoPro proteoforms remained active after AEX-separation and the specificity of these proteoforms did not depend on N-glycan phosphorylation. Nevertheless, our data confirmed a strong pH dependence of EndoPro cleavage activity. Altogether, our study demonstrates that AEX-MS is an excellent tool to characterize complex industrial enzymes under native conditions.

Objectives: The aim of this study was to investigate the midterm performance of an everolimus-eluting, bioresorbable vascular scaffold (Absorb, Abbott Vascular, Santa Clara, California) for the treatment of focal tibial and distal popliteal lesions., Background: Drug-eluting stents are used below the knee to improve technical success and durability, but the ongoing presence of a permanent metal scaffold may have deleterious effects on the local vessel., Methods: Tibial and distal popliteal angioplasty with scaffold placement was performed using an everolimus-eluting, bioresorbable scaffold (Absorb). Clinical and ultrasound follow-up was performed at 1, 3, 6, 12, and 24 months to detect binary restenosis and evaluate safety, restenosis, and clinical improvement., Results: Thirty-eight limbs in 33 patients were treated for critical limb ischemia (68.4%) or severe claudication (31.6%). Fifty scaffolds were used to treat a total of 43 lesions, with a mean length of 19.2 ± 11.6 mm. During a mean follow-up period of 12.0 ± 3.9 months, 5 patients died, and all others were available for follow-up. Among the 38 treated limbs, clinical improvement was present in 30 (79%). Binary restenosis was detected in 3 of 50 scaffolds (6%). Using the Kaplan-Meier method, rates of primary patency were 96% and 84.6% at 12 and 24 months, respectively, and rates of freedom from clinically driven target lesion revascularization were 96% and 96% at 12 and 24 months, respectively. Complete wound healing occurred in 64% of those treated for tissue loss, with no major amputation and a limb-salvage rate of 100%., Conclusions: Twelve-month follow-up demonstrated excellent safety, patency, and freedom from target lesion revascularization using the Absorb bioresorbable vascular scaffold below the knee., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

During the last decades, the clinical and research interest in atherosclerosis has been mostly focused on coronary arteries. After the publications of the European Society Guidelines and AHA/ACC Guidelines on Peripheral artery diseases, and of the Registry REduction in Atherothrombosis for Continued Health Registry, there has been an increased interest in atherosclerosis of the lower extremity arteries and its presence in multifocal disease. However, awareness in the general population and the medical community of non-coronary artery diseases, and of its major prognostic implications remain relatively low. The aim of this general review stemming out of an ESC Working Group on Peripheral Circulation meeting in 2011 is to enhance awareness of this complex disease highlighting the importance of the involvement of atherosclerosis at different levels with respect to clinical presentation, diagnosis, and co-existence of the disease in the distinct arterial territories. We also emphasize the need of an interdisciplinary approach to face the broad and complex spectrum of multifocal disease, and try to propose a series of tentative recommendations and measures to be implemented in non-coronary atherosclerosis.

Background: The pathophysiology of new-onset cardiac arrhythmias is complex and may bring about severe cardiovascular complications. The relevance of perioperative arrhythmias during vascular surgery has not been investigated. The aim of this study was to assess risk factors and prognosis of new-onset arrhythmias during vascular surgery., Methods: A total of 513 vascular surgery patients, without a history of arrhythmias, were included. Cardiac risk factors, inflammatory status, and left ventricular function (LVF; N-terminal pro-B-type natriuretic peptide and echocardiography) were assessed. Continuous electrocardiography (ECG) recordings for 72 hours were used to identify ischemia and new-onset arrhythmias: atrial fibrillation, sustained ventricular tachycardia, supraventricular tachycardia, and ventricular fibrillation. Logistic regression analysis was applied to identify preoperative risk factors for arrhythmias. Cox regression analysis assessed the impact of arrhythmias on cardiovascular event-free survival during 1.7 years., Results: New-onset arrhythmias occurred in 55 (11%) of 513 patients: atrial fibrillation, ventricular tachycardia, supraventricular tachycardia, and ventricular fibrillation occurred in 4%, 7%, 1%, and 0.2%, respectively. Continuous ECG showed myocardial ischemia and arrhythmias in 17 (3%) of 513 patients. Arrhythmia was preceded by ischemia in 10 of 55 cases. Increased age and reduced LVF were risk factors for the development of arrhythmias. Multivariate analysis showed that perioperative arrhythmias were associated with long-term cardiovascular events, irrespective of the presence of perioperative ischemia (hazard ratio 2.2, 95% CI 1.3-3.8, P = .004)., Conclusion: New-onset perioperative arrhythmias are common after vascular surgery. The elderly and patients with reduced LVF show arrhythmias. Perioperative continuous ECG monitoring helps to identify this high-risk group at increased risk of cardiovascular events and death., (Copyright 2010 Mosby, Inc. All rights reserved.)

beta Blockers are widely used to improve the postoperative cardiac outcome in patients with coronary artery disease scheduled for noncardiac surgery. However, recently serious concerns regarding the safety of perioperative beta blockers have emerged. To assess the incidence, risk factors, and beta-blocker use associated with postoperative stroke in the Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress Echocardiography (DECREASE) trials, we evaluated all 3,884 patients of the DECREASE trials for postoperative stroke. All cardiac risk factors and medication use were assessed. The incidence of stroke within 30 days after surgery was recorded. The incidence of postoperative stroke in the DECREASE trials was 0.46% (18 of 3,884). For the beta-blocker users, the incidence was 0.5%. All the strokes had an ischemic origin. A history of stroke was associated with a greater incidence of postoperative stroke (odds ratio [OR] 3.79, 95% confidence interval [CI] 1.2 to 11.6). Statins and anticoagulants were not associated with postoperative stroke (OR 0.85, 95% CI 0.3 to 2.4; and OR 1.27, 95% CI 0.4 to 4.6, respectively). No association with bisoprolol therapy was found (OR 1.16, 95% CI 0.4 to 3.4). In conclusion, with a low-dose bisoprolol regimen started > or =30 days before surgery, no association was observed between beta-blocker use and postoperative stroke.

Background: Adverse cardiac events are common after vascular surgery. We hypothesized that perioperative statin therapy would improve postoperative outcomes., Methods: In this double-blind, placebo-controlled trial, we randomly assigned patients who had not previously been treated with a statin to receive, in addition to a beta-blocker, either 80 mg of extended-release fluvastatin or placebo once daily before undergoing vascular surgery. Lipid, interleukin-6, and C-reactive protein levels were measured at the time of randomization and before surgery. The primary end point was the occurrence of myocardial ischemia, defined as transient electrocardiographic abnormalities, release of troponin T, or both, within 30 days after surgery. The secondary end point was the composite of death from cardiovascular causes and myocardial infarction., Results: A total of 250 patients were assigned to fluvastatin, and 247 to placebo, a median of 37 days before vascular surgery. Levels of total cholesterol, low-density lipoprotein cholesterol, interleukin-6, and C-reactive protein were significantly decreased in the fluvastatin group but were unchanged in the placebo group. Postoperative myocardial ischemia occurred in 27 patients (10.8%) in the fluvastatin group and in 47 (19.0%) in the placebo group (hazard ratio, 0.55; 95% confidence interval [CI], 0.34 to 0.88; P=0.01). Death from cardiovascular causes or myocardial infarction occurred in 12 patients (4.8%) in the fluvastatin group and 25 patients (10.1%) in the placebo group (hazard ratio, 0.47; 95% CI, 0.24 to 0.94; P=0.03). Fluvastatin therapy was not associated with a significant increase in the rate of adverse events., Conclusions: In patients undergoing vascular surgery, perioperative fluvastatin therapy was associated with an improvement in postoperative cardiac outcome. (Current Controlled Trials number, ISRCTN83738615.), (Massachusetts Medical Society)

The incidence of postoperative stroke ranges from 0.08% to 0.7% in noncardiac surgery. Recently, the PeriOperative ISchemic Evaluation (POISE) study reported an incidence of postoperative stroke of 1% in patients scheduled for noncardiac surgery when beta blockers were initiated immediately before surgery. To assess the association between chronic beta-blocker use and postoperative stroke in noncardiac surgery, we undertook a case-control study among 186,779 patients who underwent noncardiac surgery from 2000 to 2008 at the Erasmus Medical Centre. Patients who were undergoing intracerebral surgery or carotid surgery or who had head and/or carotid trauma were excluded. The case subjects were 34 patients (0.02%) who had experienced a stroke within 30 days after surgery. Of the remaining patients, 2 controls were selected for each case and were stratified according to calendar year, type of surgery, and age. For cases and controls, information was obtained regarding beta-blocker use before surgery, the presence of cardiac risk factors, and the use of other cardiovascular medication. The use of beta blockers was as common in the cases as in the controls (29% vs 29%; p = 1.0). The adjusted odds ratio for postoperative stroke among beta-blocker users compared with nonusers was 0.4 (95% confidence interval 0.1 to 1.5). Similar results were obtained in the subgroups of patients stratified according to the use of cardiovascular therapy and the presence of cardiac risk factors. In conclusion, the present case-control study has shown no increased risk of postoperative stroke in patients taking chronic beta-blocker therapy.

Background: Cardiovascular (CV) complications are the leading cause of morbidity and mortality in vascular surgery patients. The Revised Cardiac Risk (RCR) index, identifying cardiac risk factors, is commonly used for preoperative risk stratification. However, a more direct marker of the underlying atherosclerotic disease, such as the common carotid artery intimamedia thickness (CCA-IMT) may be of predictive value as well. The current study evaluated the prognostic value of the CCA-IMT for postoperative CV outcome., Methods: In 508 vascular surgery patients, the CCA-IMT was measured using high-resolution B-mode ultrasonography. We recorded the RCR factors: ischemic heart disease, heart failure, cerebrovascular disease, diabetes mellitus, and renal dysfunction. Repeated Troponin T measurements and electrocardiograms were performed postoperatively. The study end point was the composite of 30-day CV events and long-term CV mortality. Multivariable regression analyses were used to assess the additional value of CCA-IMT for the prediction of cardiac events., Results: In total, 30-day events and long-term cardiovascular mortality were noted in 122 (24%) and 81 (16%) patients, respectively. The optimal predictive value of CCA-IMT, using receiver-operating characteristic curve analysis, for the prediction of CV events was calculated to be 1.25 mm (sensitivity 70%, specificity 80%). An increased CCA-IMT was independently associated with 30-day CV events (OR 2.20, 95% CI 1.38-3.52) and long-term CV mortality (HR 6.88, 95% CI 4.11-11.50), respectively., Conclusions: This study shows that an increased CCA-IMT has prognostic value in vascular surgery patients to predict 30-day CV events and long-term CV mortality, incremental to the RCR index.

Prophylactic coronary revascularization in vascular surgery patients with extensive coronary artery disease was not associated with an improved immediate postoperative outcome. However, the potential long-term benefit was unknown. This study was performed to assess the long-term benefit of prophylactic coronary revascularization in these patients. Of 1,880 patients scheduled for major vascular surgery, 430 had > or =3 risk factors (age >70 years, angina pectoris, myocardial infarction, heart failure, stroke, diabetes mellitus, and renal failure). All underwent cardiac testing using dobutamine echocardiography or nuclear stress imaging. Patients with extensive stress-induced ischemia (> or =5 segments or > or =3 walls) were randomly assigned to additional revascularization. In total, 101 patients showed extensive ischemia and were assigned to revascularization (n = 49) or no revascularization (n = 52). After 2.8 years, the overall survival rate was 64% for patients randomly assigned to no preoperative coronary revascularization versus 61% for patients assigned to preoperative coronary revascularization (hazard ratio [HR] 1.18, 95% confidence interval [CI] 0.63 to 2.19, p = 0.61). Rates for survival free of all-cause death, nonfatal myocardial infarction, and coronary revascularization were similar in both groups at 49% and 42% for patients allocated to medical treatment or coronary revascularization, respectively (HR 1.51, 95% CI 0.89 to 2.57, p = 0.13). Only 2 patients assigned to medical treatment required coronary revascularization during follow-up. Also, in patients who survived the first 30 days after surgery, there was no apparent benefit of revascularization on cardiac events (HR 1.35, 95% CI 0.72 to 2.52, p = 0.36). In conclusion, preoperative coronary revascularization in high-risk patients undergoing major vascular surgery was not associated with improved postoperative or long-term outcome compared with the best medical treatment.

Rationale: beta-Blocker use is associated with improved health outcomes in patients with cardiovascular disease. There is a general reluctance to prescribe beta-blockers in patients with chronic obstructive pulmonary disease (COPD) because they may worsen symptoms., Objectives: We investigated the relationship between cardioselective beta-blockers and mortality in patients with COPD undergoing major vascular surgery., Methods: We evaluated 3,371 consecutive patients who underwent major vascular surgery at one academic institution between 1990 and 2006. The patients were divided into those with and without COPD on the basis of symptoms and spirometry. The major endpoints were 30-day and long-term mortality after vascular surgery. Patients were defined as receiving low-dose therapy if the dosage was less than 25% of the maximum recommended therapeutic dose; dosages higher than this were defined as intensified dose., Measurements and Main Results: There were 1,205 (39%) patients with COPD of whom 462 (37%) received cardioselective beta-blocking agents. beta-Blocker use was associated independently with lower 30-day (odds ratio, 0.37; 95% confidence interval, 0.19-0.72) and long-term mortality in patients with COPD (hazards ratio, 0.73; 95% confidence interval, 0.60-0.88). Intensified dose was associated with both reduced 30-day and long-term mortality in patients with COPD, whereas low dose was not., Conclusions: Cardioselective beta-blockers were associated with reduced mortality in patients with COPD undergoing vascular surgery. In carefully selected patients with COPD, the use of cardioselective beta-blockers appears to be safe and associated with reduced mortality.

Objectives: This study was designed to compare the long-term outcomes of patients with peripheral arterial disease (PAD) with a risk factor matched population of coronary artery disease (CAD) patients, but without PAD., Background: The PAD is considered to be a risk factor for adverse late outcome., Methods: A total of 2,730 PAD patients undergoing vascular surgery were categorized into groups: 1) carotid endarterectomy (n = 560); 2) elective abdominal aortic surgery (AAA) (n = 923); 3) acute AAA surgery (r-AAA) (n = 200), and 4) lower limb reconstruction procedures (n = 1,047). All patients were matched using the propensity score, with 2,730 CAD patients who underwent coronary angioplasty. Survival status of all patients was obtained. In addition, the cause of death and complications after surgery in PAD patients were noted. The Kaplan-Meier method was used to compare survival between the matched PAD and CAD population and the different operation groups. Prognostic risk factors and perioperative complications were identified with the Cox proportional hazards regression model., Results: The PAD patients had a worse long-term prognosis (hazard ratio 2.40, 95% confidence interval 2.18 to 2.65) and received less medication (beta-blockers, statins, angiotensin-converting enzyme inhibitors, aspirin, nitrates, and calcium antagonists) than CAD patients did (p < 0.001). Cerebro-cardiovascular complications were the major cause of long-term death (46%). Importantly, no significant difference in long-term survival was observed between the AAA and lower limb reconstruction groups (log rank p = 0.70). After vascular surgery, perioperative cardiac complications were associated with long-term cardiac death, and noncardiac complications were associated with all-cause death., Conclusions: Long-term prognosis of vascular surgery patients is significantly worse than for patients with CAD. The vascular surgery patients receive less cardiac medication than CAD patients do, and cerebro-cardiovascular events are the major cause of late death.

N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) is related to stress-induced myocardial ischemia and/or volume overload, both common in patients with renal dysfunction. This might compromise the prognostic usefulness of NT-pro-BNP in patients with renal impairment before vascular surgery. We assessed the prognostic value of NT-pro-BNP in the entire strata of renal function. In 356 patients (median age 69 years, 77% men), cardiac history, glomerular filtration rate (GFR, ml/min/1.73 m(2)), and NT-pro-BNP level (pg/ml) were assessed preoperatively. Troponin T and electrocardiography were assessed postoperatively on days 1, 3, 7, and 30. The end point was the composite of cardiovascular death, Q-wave myocardial infarction, and troponin T release. Multivariate analysis was used to evaluate the interaction between GFR, NT-pro-BNP and their association with postoperative outcome. Median GFR was 78 ml/min/1.73 m(2) and the median concentration of NT-pro-BNP was 197 pg/ml. The end point was reached in 64 patients (18%); cardiac death occurred in 7 (2.0%), Q-wave myocardial infarction in 34 (9.6%), and non-Q-wave myocardial infarction in 23 (6.5%). After adjustment for confounders, NT-pro-BNP levels and GFR remained significantly associated with the end point (p = 0.005). The prognostic value of NT-pro-BNP was most pronounced in patients with GFR > or =90 (odds ratio [OR] 1.18, 95% confidence interval [CI] 0.80 to 1.76) compared with patients with GFR 60 to 89 (OR 1.04, 95% CI 1.002 to 1.07), and with GFR 30 to 59 (OR 1.12, 95% CI 1.03 to 1.21). In patients with GFR <30 ml/min/1.73 m(2), NT-pro-BNP levels have no prognostic value (OR 1.00, 95% CI 0.99 to 1.01). In conclusion, the discriminative value of NT-pro-BNP is most pronounced in patients with GFR > or =90 ml/min/1.73 m(2) and has no prognostic value in patients with GFR <30 ml/min/1.73 m(2).

Background: Little is known about the association between baseline kidney function, statin therapy, and outcome after vascular surgery in patients with and without chronic kidney disease., Methods: A total of 2126 patients underwent elective major vascular surgery and were divided into 2 categories based on baseline creatinine clearance (CrCl), calculated using the Cockcroft-Gault equation: CrCl > or = 60 mL/min (n = 1358, reference) and CrCl < 60 mL/min (n = 768). Outcome measures were 30-day and long-term all-cause, cardiac, and cerebrocardiovascular mortality. Mean follow-up was 6.0 +/- 3.7 years. Multivariate Cox regression analysis, including potential confounders and propensity score for statin use, was applied. Data are presented as hazard ratios (HRs) with 95% CI., Results: Thirty-day all-cause, cardiac, and cerebrocardiovascular mortality rates were 3.8% versus 10.2%, 1.3% versus 4.2%, and 2.7% versus 7.8%, respectively, according to the 2 categories of kidney function. In addition, long-term all-cause, cardiac, and cerebrocardiovascular mortality rates were 46.6% versus 72.5%, 14.6% versus 26.4%, and 23.0% versus 40.6%, respectively. Statin therapy was associated with an overall significant improved 30-day and long-term all-cause mortality, independent of other important confounders. However, in patients with a CrCl > or = 60 mL/min, the long-term cardiac and cerebrocardiovascular beneficial effects did not reach statistical significance (HR 0.93, 95% CI 0.61-1.41 and HR 0.89, 95% CI 0.63-1.24, respectively) when compared with patients with a CrCl of < 60 mL/min (HR 0.63, 95% CI 0.41-0.96 and HR 0.67, 95% CI 0.48-0.94, respectively)., Conclusions: The level of kidney function is an independent predictor of short- and long-term outcome after major noncardiac surgery. In addition, perioperative statin use in patients with kidney disease is associated with a reduction in the short- and long-term all-cause, cardiac, and cerebrocardiovascular mortality.

Glycemic control may be an underestimated risk factor in diabetic patients with peripheral arterial disease (PAD). Chronic statin therapy may improve glycemic control and outcome in these patients. In an observational cohort study of 425 consecutive diabetic patients with PAD, chronic statin therapy was noted, the ankle-brachial index was measured, and serial glycemic hemoglobin (HbA(1c)) measurements were obtained. During follow-up (median 7 years), all-cause mortality and cardiac death occurred in 37% and 22%, respectively. Decreases in HbA(1c) and HbA(1c) variability independently predicted outcome in addition to baseline ankle-brachial index values. Patients with chronic statin therapy were more likely to have decreasing HbA(1c) values (adjusted hazard ratio [HR]= 1.86, 95% confidence interval [CI] 1.27-2.74) and HbA(1c) values <7% (adjusted HR = 2.58, 95% CI 1.49-4.48) during follow-up. Statins were also significantly associated with lower all-cause mortality (adjusted HR = 0.39, 95% CI 0.26-0.61) and cardiac death rate (adjusted HR = 0.40, 95% CI 0.24-76). Based on the results of the current observational study, we conclude that serial HbA(1c) measurements can improve risk stratification in diabetic patients with PAD. In addition, statin therapy is associated with desirable glycemic control and improved long-term outcome.

Background: Little is known about acute changes in renal function in the postoperative period and the outcome of patients undergoing major vascular surgery. Specifically, data are scarce for patients in whom renal function temporarily decreases and returns to baseline at 3 days after surgery., Study Design: Retrospective cohort study., Setting & Participants: 1,324 patients who underwent elective open abdominal aortic aneurysm surgery in a single center., Predictor: Renal function (creatinine clearance was measured preoperatively and on days 1, 2, and 3 after surgery. Patients were divided into 3 groups: group 1, improved or unchanged (change in creatinine clearance, +/-10% of function compared with baseline); group 2, temporary worsening (worsening > 10% at day 1 or 2, then complete recovery within 10% of baseline at day 3); and group 3, persistent worsening (>10% decrease compared with baseline)., Outcomes & Measurements: All-cause mortality., Results: 30-day mortality rates were 1.3%, 5.0%, and 12.6% in groups 1 to 3, respectively. Adjusted for baseline characteristics and postoperative complications, 30-day mortality was the greatest in patients with persistent worsening of renal function (hazard ratio [HR], 7.3; 95% confidence interval [CI], 2.7 to 19.8), followed by those with temporary worsening (HR, 3.7; 95% CI, 1.4 to 9.9). During 6.0 +/- 3.4 years of follow-up, 348 patients (36.5%) died. Risk of late mortality was 1.7 (95% CI, 1.3 to 2.3) in the persistent-worsening group followed by those with temporary worsening (HR, 1.5; 95% CI, 1.2 to 1.4)., Limitations: No steady state was achieved to assess renal function., Conclusion: Although renal function may recover completely after aortic surgery, temporary worsening of renal function was associated with greater long-term mortality.

The discontinuation of statin therapy in patients with acute coronary syndromes has been associated with an increase of adverse coronary events. Patients who undergo major surgery frequently are not able to take oral medication shortly after surgery. Because there is no intravenous formula for statins, the interruption of statins in the postoperative period is a serious concern. The objective of this study was to assess the effect of perioperative statin withdrawal on postoperative cardiac outcome. Also, the association between outcome and type of statin was studied. In 298 consecutive statin users who underwent major vascular surgery, detailed cardiac histories were obtained, and medication use was noted. Postoperatively, troponin levels were measured on days 1, 3, 7, and 30 and whenever clinically indicated by electrocardiographic changes. End points were postoperative troponin release, myocardial infarction, and a combination of nonfatal myocardial infarction and cardiovascular death. Multivariate analyses and propensity score analyses were performed to assess the influence of type of statin and the discontinuation of statins for these end points. Statin discontinuation was associated with an increased risk for postoperative troponin release (hazard ratio 4.6, 95% confidence interval 2.2 to 9.6) and the combination of myocardial infarction and cardiovascular death (hazard ratio 7.5, 95% confidence interval 2.8 to 20.1). Extended-release fluvastatin was associated with fewer perioperative cardiac events compared with atorvastatin, simvastatin, and pravastatin. In conclusion, the present study showed that statin withdrawal in the perioperative period is associated with an increased risk for perioperative adverse cardiac events. Furthermore, there seemed to be better outcomes in patients who received statins with extended-release formulas.

Background: Left ventricular hypertrophy (LVH) is associated with an increased risk of cardiac death. Data on the prognostic value of myocardial perfusion imaging (MPI) in patients with LVH are limited. The aim of this study is to assess the independent value of stress technetium 99m tetrofosmin MPI in predicting the long-term mortality rate in patients with LVH., Methods and Results: We studied 177 patients (mean age, 59 +/- 12 years; 134 men) with LVH by electrocardiographic criteria who underwent dobutamine or exercise stress Tc-99m tetrofosmin MPI. Endpoints during follow-up were cardiac and all-cause death and hard cardiac events. A normal scan was detected in 42 patients (24%). Myocardial perfusion abnormalities were fixed in 59 patients (33%) and reversible in 76 (43%). Perfusion abnormalities were observed in a single-vessel distribution in 79 patients and in a multivessel distribution in 56. During a mean follow-up period of 5.5 +/- 2 years, 60 patients (34%) died. Death was considered cardiac in 42 patients (24%). Nonfatal myocardial infarction occurred in 10 patients (6%). The annual mortality rate was 1.4% in patients with normal perfusion, 3.2% in those with perfusion abnormalities in a single-vessel distribution, and 8% in those with a multivessel distribution. In a multivariate analysis independent predictors of death were age (risk ratio [RR], 1.05; 95% confidence interval [CI], 1.02-1.07), male gender (RR, 1.9; 95% CI, 1.1-3.6), hypercholesterolemia (RR, 1.7; 95% CI, 1.0-2.9), and abnormal perfusion (RR, 2.7; 95% CI, 1.5-4.8)., Conclusion: In patients referred for stress MPI, LVH is associated with a high mortality rate, with approximately one third of patients dying over a period of 5 years. Stress Tc-99m tetrofosmin MPI provides independent information for predicting death in these patients.

Objectives: The purpose of this research was to perform a feasibility study of prophylactic coronary revascularization in patients with preoperative extensive stress-induced ischemia., Background: Prophylactic coronary revascularization in vascular surgery patients with coronary artery disease does not improve postoperative outcome. If a beneficial effect is to be expected, then at least those with extensive coronary artery disease should benefit from this strategy., Methods: One thousand eight hundred eighty patients were screened, and those with > or =3 risk factors underwent cardiac testing using dobutamine echocardiography (17-segment model) or stress nuclear imaging (6-wall model). Those with extensive stress-induced ischemia (> or =5 segments or > or =3 walls) were randomly assigned for additional revascularization. All received beta-blockers aiming at a heart rate of 60 to 65 beats/min, and antiplatelet therapy was continued during surgery. The end points were the composite of all-cause death or myocardial infarction at 30 days and during 1-year follow-up., Results: Of 430 high-risk patients, 101 (23%) showed extensive ischemia and were randomly assigned to revascularization (n = 49) or no revascularization. Coronary angiography showed 2-vessel disease in 12 (24%), 3-vessel disease in 33 (67%), and left main in 4 (8%). Two patients died after revascularization, but before operation, because of a ruptured aneurysm. Revascularization did not improve 30-day outcome; the incidence of the composite end point was 43% versus 33% (odds ratio 1.4, 95% confidence interval 0.7 to 2.8; p = 0.30). Also, no benefit during 1-year follow-up was observed after coronary revascularization (49% vs. 44%, odds ratio 1.2, 95% confidence interval 0.7 to 2.3; p = 0.48)., Conclusions: In this randomized pilot study, designed to obtain efficacy and safety estimates, preoperative coronary revascularization in high-risk patients was not associated with an improved outcome.

Background: Adverse perioperative cardiac events occur frequently despite the use of beta (beta)-blockers. We examined whether higher doses of beta-blockers and tight heart rate control were associated with reduced perioperative myocardial ischemia and troponin T release and improved long-term outcome., Methods and Results: In an observational cohort study, 272 vascular surgery patients were preoperatively screened for cardiac risk factors and beta-blocker dose. Beta-blocker dose was converted to a percentage of maximum recommended therapeutic dose. Heart rate and ischemic episodes were recorded by continuous 12-lead electrocardiography, starting 1 day before to 2 days after surgery. Serial troponin T levels were measured after surgery. All-cause mortality was noted during follow-up. Myocardial ischemia was detected in 85 of 272 (31%) patients and troponin T release in 44 of 272 (16.2%). Long-term mortality occurred in 66 of 272 (24.2%) patients. In multivariate analysis, higher beta-blocker doses (per 10% increase) were significantly associated with a lower incidence of myocardial ischemia (hazard ratio [HR], 0.62; 95% confidence interval [CI], 0.51 to 0.75), troponin T release (HR, 0.63; 95% CI, 0.49 to 0.80), and long-term mortality (HR, 0.86; 95% CI, 0.76 to 0.97). Higher heart rates during electrocardiographic monitoring (per 10-bpm increase) were significantly associated with an increased incidence of myocardial ischemia (HR, 2.49; 95% CI, 1.79 to 3.48), troponin T release (HR, 1.53; 95% CI, 1.16 to 2.03), and long-term mortality (HR, 1.42; 95% CI, 1.14 to 1.76)., Conclusions: This study showed that higher doses of beta-blockers and tight heart rate control are associated with reduced perioperative myocardial ischemia and troponin T release and improved long-term outcome in vascular surgery patients.

Background: Accurately assessing the probability of perioperative mortality can be useful in preoperative risk assessment and management. This study aimed to revise and customize the revised cardiac risk (Lee) index to estimate the probability of perioperative all-cause mortality in patients undergoing noncardiac vascular surgery., Methods: We studied 2310 patients (mean age, 67.8 +/- 11.3 years; 1747 males) who underwent acute or elective major noncardiac vascular surgery between January 1, 1991, and December 31, 2000, at the Erasmus Medical Center, Rotterdam, the Netherlands. A total of 1537 patients were assigned for model development, in which the associations between predictor variables and mortality occurring within 30 days after surgery were identified to modify the Lee index, which was then evaluated in a validation cohort of 773 patients., Results: The perioperative mortality rates were similar in the development (n = 103 [6.7%]) and validation (n = 50 [6.5%]) populations. The customized risk-prediction model for perioperative mortality identified type of vascular surgery, ischemic heart disease, congestive heart failure, previous stroke, hypertension, renal dysfunction, and chronic pulmonary disease as being associated with increased risk, whereas beta-blocker and statin use were associated with a lower risk of mortality. The performance of the customized index had excellent discriminative ability in both derivation and validation populations (concordance statistic, 0.88 and 0.85, respectively)., Conclusions: The customized index provides more detailed information than the Lee index about the type of vascular procedure, clinical risk factors, and concomitant medication use. The customized probability model can be a useful tool to estimate the risk of perioperative all-cause mortality and facilitate subsequent treatment strategies.