http://repub.eur.nl/res/aut/30213/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/24964/ 2009-11-01T00:00:00Z INTRODUCTION: N-terminal pro-B-type natriuretic peptide (NT-proBNP) predicts adverse cardiac outcome in patients undergoing vascular surgery. However, several conditions might influence this prognostic value, including anemia. In this study, we evaluated whether anemia confounds the prognostic value of NT-proBNP for predicting cardiac events in patients undergoing vascular surgery. METHODS:: A detailed cardiac history, resting echocardiography, and hemoglobin and NT-proBNP levels were obtained in 666 patients before vascular surgery. Anemia was defined as serum hemoglobin <13 g/dL for men and <12 g/dL for women. Troponin T measurements and 12-lead electrocardiograms were performed on postoperative days 1, 3, 7, and 30 and whenever clinically indicated. The primary end point of the study was the composite of 30-day postoperative cardiovascular death, nonfatal myocardial infarction, and troponin T release. Receiver operating characteristic curve analysis was used to assess the optimal cutoff value of NT-proBNP for the prediction of the composite end point. Multivariable regression analysis was used to assess the additional value of NT-proBNP for the prediction of postoperative cardiac events in nonanemic and anemic patients. RESULTS:: Anemia was present in 206 patients (31%) before surgery. Hemoglobin level was inversely related with the NT-proBNP levels (β coefficient = -2.242; P = 0.025). The optimal predictive cutoff value of NT-proBNP for predicting the composite cardiovascular outcome was 350 pg/mL. After adjustment for clinical cardiac risk factors, both anemia (odds ratio [OR] 1.53; 95% confidence interval [CI]: 1.07-2.99) and increased levels of NT-proBNP (OR 4.09; 95% CI: 2.19-7.64) remained independent predictors for postoperative cardiac events. However, increased levels of NT-proBNP were not predictive for the risk of adverse cardiac events in the subgroup of anemic patients (OR 2.16; 95% CI: 0.90-5.21). CONCLUSIONS:: Both anemia and NT-proBNP are independently associated with an increased risk for postoperative cardiac events in patients undergoing vascular surgery. NT-proBNP has less predictive value in anemic patients. Copyright http://repub.eur.nl/res/pub/32665/ 2009-09-03T00:00:00Z 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.) Copyright http://repub.eur.nl/res/pub/24745/ 2009-06-01T00:00:00Z Objective: This study evaluated the effectiveness and safety of beta-blockers and statins for the prevention of perioperative cardiovascular events in intermediate-risk patients undergoing noncardiovascular surgery. SUMMARY BACKGROUND DATA:: Beta-blockers and statins reduce perioperative cardiac events in high-risk patients undergoing vascular surgery by restoring the myocardial oxygen supply/demand balance and/or stabilizing coronary plaques. However, their effects in intermediate-risk patients remained ill-defined. METHODS:: In this randomized open-label 2 × 2 factorial design trial 1066 intermediate cardiac risk patients were assigned to bisoprolol, fluvastatin, combination treatment, or control therapy before surgery (median: 34 days). Intermediate risk was defined by an estimated risk of perioperative cardiac death and myocardial infarction (MI) of 1% to 6%, using clinical data and type of surgery. Starting dose of bisoprolol was 2.5 mg daily, titrated to a perioperative heart rate of 50 to 70 beats per minute. Fluvastatin was prescribed in a fixed dose of 80 mg. The primary end point was the composite of 30-day cardiac death and MI. This study is registered in the ISRCTN registry and has the ID number ISRCTN47637497. RESULTS:: Patients randomized to bisoprolol (N = 533) had a lower incidence of perioperative cardiac death and nonfatal MI than those randomized to bisoprolol-control (2.1% vs. 6.0% events; hazard ratios: 0.34; 95% confidence intervals: 0.17-0.67; P = 0.002). Patients randomized to fluvastatin experienced a lower incidence of the end point than those randomized to fluvastatin-control therapy (3.2% vs. 4.9% events; hazard ratios: 0.65; 95% confidence intervals: 0.35-1.10), but statistical significance was not reached (P = 0.17). CONCLUSION:: Bisoprolol was associated with a significant reduction of 30-day cardiac death and nonfatal MI, while fluvastatin showed a trend for improved outcome. Copyright http://repub.eur.nl/res/pub/24245/ 2009-05-01T00:00:00Z Background: Diabetes mellitus (DM) is an important risk factor in vascular surgery patients, influencing late outcome. Screening for diabetes is recommended by fasting glucose measurement. Oral glucose tolerance testing (OGTT) could enhance the detection of patients with impaired glucose tolerance (IGT) and DM. Aim: To assess the additional value of OGTT on top of fasting glucose levels in vascular surgery patients to predict long-term cardiovascular outcome. Methods: A total of 404 patients without signs or histories of IGT (plasma glucose 7.8-11.1 mmol/L) or DM (glucose ≥11.1 mmol/L) were prospectively included and subjected to OGTT. Cardiac risk factors were noted. Primary outcome was the occurrence of late cardiovascular events (composite of cardiovascular death, angina pectoris, myocardial infarction, percutaneous coronary intervention/coronary artery bypass grafting, or cerebral vascular accident/transient ischemic attack), and secondary outcome included all-cause and cardiovascular mortality rates, in survivors of vascular surgery. Median follow-up was 3.0 (interquartile range 2.4-3.8) years. Results: Impaired glucose tolerance (n = 104) and DM (n = 43) were detected by fasting glucose levels in 26 (25%) and 12 (28%) patients, and by OGTT in 78 (75%) and 31 (72%) patients, respectively. During follow-up, 131 patients experienced a cardiovascular event. With multivariable analysis, patients with IGT showed a significant increased risk for cardiovascular events (hazard ratio 2.77, 95% CI 1.83-4.20) and mortality (hazard ratio 2.06, 95% CI 1.03-4.12). Patients with DM showed a nonsignificant increased risk for cardiovascular events. Conclusion: Vascular surgery patients with IGT or DM detected by preoperative OGTT have an increased risk of developing cardiovascular events and mortality during long-term follow-up. It is recommended that nondiabetic vascular surgery patients should be tested for glucose regulation disorders before surgery. http://repub.eur.nl/res/pub/27139/ 2009-05-01T00:00:00Z OBJECTIVES: High-sensitivity C-reactive protein (hs-CRP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) are associated with the presence of coronary artery disease. The aim of this study was to assess the prognostic value of hs-CRP and NT-proBNP for postoperative cardiac events in noncardiac vascular surgery patients. METHODS: In 592 patients, cardiac history, hs-CRP, and NT-proBNP levels were assessed preoperatively. Levels of hs-CRP of at least 6.5 mg/l and NT-proBNP of at least 350 pg/ml were defined as the optimal cut-off values for the prediction of postoperative cardiac events. The end point was the composite of 30-day cardiovascular death, Q-wave myocardial infarction, and troponin T release. Multivariable regression analysis was used to evaluate the association between hs-CRP, NT-proBNP and the end point. The performance of the risk models based on cardiac risk factors alone and the addition of both biomarkers was determined using C statistics. RESULTS: After adjustment for cardiac risk factors, site of surgery and type of procedure, elevated levels of hs-CRP (odds ratio 2.54; 95% confidence interval 1.50-4.30) and NT-proBNP (odds ratio 4.78; 95% confidence interval 2.71-8.42) remained independent predictors for postoperative cardiac events. When hs-CRP and NT-proBNP were added to the cardiac risk score, the C statistic improved from 0.79 to 0.84. A combined elevation of hs-CRP and NT-proBNP provided a seven-fold higher risk for postoperative cardiac events. CONCLUSION: Both hs-CRP and NT-proBNP have additional value in the prediction of postoperative cardiac events in vascular surgery patients. Their integrated use improves cardiac risk stratification. http://repub.eur.nl/res/pub/25100/ 2009-01-01T00:00:00Z Background: Hyperhomocysteinaemia is independently associated with atherosclerotic disease. Methionine loading could improve the predictive value of hyperhomocysteinaemia by detecting mild disturbances in enzyme activity. The aims of this study were to determine the beneficial effect of methionine loading on the predictive value of homocysteine testing for long-term mortality and major adverse cardiac events (MACE). Methods: In an observational study, 1122 patients with suspected or known vascular disease, underwent homocysteine testing, which was measured fasting and again 6 h after methionine loading. Hyperhomocysteinaemia was defined as a fasting level ≥15 μmol/L and post-methionine loading level ≥45 μmol/L or an increase of ≥30 μmol/L above fasting levels. Primary end-points were death and MACE. Multivariate Cox regression analysis was used, adjusting for all cardiac risk factors. Results: During follow up (mean 8.9 ± 3.4 years), 98 patients died (8.7%), 86 had a MACE (7.7%), 579 patients had normal tests, 134 patients had only fasting hyperhomocysteinaemia, 226 only post-methionine hyperhomocysteinaemia and 183 patients had both. In multivariate analysis, overall survival and MACE-free survival were significantly worse for those with fasting hyperhomocysteinaemia, with hazard ratios of 1.86 (95% confidence interval (CI) 1.20-2.87) and 2.24 (95%CI 1.41-3.53), respectively. The addition of hyperhomocysteinaemia after methionine loading did not significantly increase the risk of death or MACE, with hazard ratios of 0.97 (95%CI 0.52-1.81) and 0.89 (95%CI 0.47-1.69), respectively. Conclusion: The presence of post-methionine hyperhomocysteinaemia did not significantly alter risk of death or MACE in patients with normal or increased fasting homocysteine levels, respectively. In conclusion, methionine loading does not improve the predictive value of homocysteine testing with regard to long-term mortality or MACE. http://repub.eur.nl/res/pub/29569/ 2008-12-01T00:00:00Z BACKGROUND: Acute myocardial infarction (MI) can occur in patients with previously normal stress myocardial perfusion imaging (MPI). It is not known whether the prognosis of these patients differ from those with MI who had an abnormal MPI on an earlier testing. The aim of this study was to compare the outcome of patients who sustained a MI during follow-up after stress MPI based on the presence or absence of perfusion abnormalities on the earlier test. METHODS: We studied 109 patients (age 62 ± 11 years, 73 men) who developed MI 2.1 ± 2.7 years after exercise or dobutamine stress Tc-99m tetrofosmin MPI. Subsequently, a follow-up was done for the occurrence of death during or after the acute event. RESULTS: Myocardial perfusion was normal in 31 patients and was abnormal in 78 (45 had reversible defects). During a mean follow-up of 3.1 ± 2.4 years after MI, death occurred in 35 (32%) patients. The death rate was 19% in patients with previously normal versus 33% in patients with abnormal perfusion (P < 0.01). In a Cox model, independent predictors of death were age (risk ratio (RR) 1.06, 95% CI: 1.02-1.10), heart failure (RR 2.7, CI: 1.3-5.5), and abnormal MPI (RR 2.5, CI: 1.3-4.5). CONCLUSION: Patients with a previously normal stress MPI are less likely to die after acute MI than patients who had an abnormal MPI. http://repub.eur.nl/res/pub/29031/ 2008-10-01T00:00:00Z The role of uric acid as an independent marker of cardiovascular risk is unclear. Therefore, our aim was to assess the independent contribution of preoperative serum uric acid levels to the risk of 30-day and late mortality and major adverse cardiac event (MACE) in patients scheduled for open vascular surgery. In total, 936 patients (76% male, age 68 ± 11 years) were enrolled. Hyperuricemia was defined as serum uric acid >0.42 mmol/l for men and >0.36 mmol/l for women, as defined by large epidemiological studies. Outcome measures were 30-day and late mortality and MACE (cardiac death or myocardial infarction). Multivariable logistic and Cox regression analysis were used, adjusting for age, gender, and all cardiac risk factors. Data are presented as odds ratios or hazard ratios, with 95% confidence intervals. Hyperuricemia was present in 299 patients (32%). The presence of hyperuricemia was associated with heart failure, chronic kidney disease, and the use of diuretics. Perioperatively, 46 patients (5%) died and 61 patients (7%) experienced a MACE. Mean follow-up was 3.7 years (range: 0 to 17 years). During follow-up, 282 patients (30%) died and 170 patients (18%) experienced a MACE. After adjustment for all clinical risk factors, the presence of hyperuricemia was not significantly associated with an increased risk of 30-day mortality or MACE, odds ratios of 1.5 (0.8 to 2.8) and 1.7 (0.9 to 3.0), respectively. However, the presence of hyperuricemia was associated with an increased risk of late mortality and MACE, with hazard ratios of 1.4 (1.1 to 1.7) and 1.7 (1.3 to 2.3), respectively. In conclusion, the presence of preoperative hyperuricemia in vascular patients is a significant predictor of late mortality and MACE. http://repub.eur.nl/res/pub/29300/ 2008-04-25T00:00:00Z Background: In patients undergoing exercise testing a hypotensive response is associated with a poor prognosis. There is limited information regarding the prognostic significance of hypotension during dobutamine stress test. This study investigates the association between a severe hypotensive response during DSE and long-term prognosis. Methods: Patients (3381) underwent dobutamine stress echocardiography (DSE). Blood pressure was measured automatically at rest and at the end of every dose-step. Wall motion was scored using a 16-segement, 5-point score. Ischemia was defined by the presence of new wall motion abnormalities. Hypotensive response during DSE was defined as mild (MHR) when systolic blood pressure (SBP) dropped < 20 mmHg between rest and peak stress, and severe (SHR) when SBP dropped < 20 mmHg. During follow-up all cause mortality and MACE (cardiac death or non-fatal myocardial infarction) were noted. Results: MHR and SHR occurred in 936 (28%) and 521 (15%) patients, respectively. Independent predictors of SHR were older age, new or worsening wall motion abnormalities and history of hypertension. During follow-up of 4.5 (± 3.3) years, 920 patients died, of which 555 due to cardiac causes, and 713 patients experienced a MACE. After adjustment for baseline characteristics and DSE results SHR during DSE was independently associated with increased long-term cardiac death (HR: 1.3, 95% CI: 1.03-1.6) and MACE (HR: 1.34, 95% CI: 1.1-1.6), while MHR was not associated with a worse outcome. Conclusions: Severe hypotensive response during DSE independently predicts cardiac death and MACE in patients with known or suspected coronary artery disease. http://repub.eur.nl/res/pub/29119/ 2008-04-15T00:00:00Z Anemia is common in patients scheduled for vascular surgery and is a risk factor for adverse cardiac outcome. However, it is unclear whether this is an independent risk factor or an expression of underlying co-morbidities. In total, 1,211 patients (77% men, 68 ± 11 years of age) were enrolled. Anemia was defined as serum hemoglobin levels <13 g/dl for men and <12 g/dl for women and was divided into tertiles to compare mild (men 12.2 to 13.0, women 11.2 to 12.0), moderate (men 11.0 to 12.1, women 10.2 to 11.1), and severe (men 7.2 to 11.0, women 7.5 to 10.1) anemia with nonanemia. Outcome measurements were 30-day and 5-year major adverse cardiac events (MACEs; cardiac death or myocardial infarction). All risk factors were noted. Multivariable logistic and Cox regression analyses were used, adjusting for all cardiac risk factors, including heart failure and renal disease. Data are presented as hazard ratios with 95% confidence intervals. In total, 74 patients (6%) had 30-day MACEs and 199 (17%) had 5-year MACEs. Anemia was present in 399 patients (33%), 133 of whom had mild anemia, 133 had moderate anemia, and 133 had severe anemia. Presence of anemia was associated with renal dysfunction, diabetes, and heart failure. After adjustment for all clinical risk factors, 30-day hazard ratios for a MACE per anemia group were 1.8 for mild (0.8 to 4.1), 2.3 for moderate (1.1 to 5.4), and 4.7 for severe (2.6 to 10.9) anemia, and 5-year hazard ratios for MACE per anemia group were 2.4 for mild (1.5 to 4.2), 3.6 for moderate (2.4 to 5.6), and 6.1 for severe (4.1 to 9.1) anemia. In conclusion, the presence and severity of preoperative anemia in vascular patients are significant predictors of 30-day and 5-year cardiac events, regardless of underlying heart failure or renal disease. http://repub.eur.nl/res/pub/29767/ 2008-03-01T00:00:00Z Aims: Cardiac morbidity and mortality is high in patients undergoing high-risk surgery. This study investigated whether impaired glucose regulation and elevated glycated haemoglobin (HbA1c) levels are associated with increased cardiac ischaemic events in vascular surgery patients. Methods: Baseline glucose and HbA1cwere measured in 401 vascular surgery patients. Glucose < 5.6 mmol/l was defined as normal. Fasting glucose 5.6-7.0 mmol/l or random glucose 5.6-11.1 mmol/l was defined as impaired glucose regulation. Fasting glucose ≥ 7.0 or random glucose ≥ 11.1 mmol/l was defined as diabetes. Perioperative ischaemia was identified by 72-h Holter monitoring. Troponin T was measured on days 1, 3 and 7 and before discharge. Cardiac death or Q-wave myocardial infarction was noted at 30-day and longer-term follow-up (mean 2.5 years). Results: Mean (± sd) level for glucose was 6.3 ± 2.3 mmol/l and for HbA1c6.2 ± 1.3%. Ischaemia, troponin release, 30-day and long-term cardiac events occurred in 27, 22, 6 and 17%, respectively. Using subjects with normal glucose levels as the reference category, multivariate analysis revealed that patients with impaired glucose regulation and diabetes were at 2.2- and 2.6-fold increased risk of ischaemia, 3.8- and 3.9-fold for troponin release, 4.3- and 4.8-fold for 30-day cardiac events and 1.9- and 3.1-fold for long-term cardiac events. Patients with HbA1c> 7.0% (n = 63, 16%) were at 2.8-fold, 2.1-fold, 5.3-fold and 5.6-fold increased risk for ischaemia, troponin release, 30-day and long-term cardiac events, respectively. Conclusions: Impaired glucose regulation and elevated HbA1care risk factors for cardiac ischaemic events in vascular surgery patients. http://repub.eur.nl/res/pub/28903/ 2008-02-15T00:00:00Z Patients scheduled for major vascular surgery are screened for cardiac risk factors using standardized risk indexes, including diabetes mellitus (DM). Screening in patients without a history of DM includes fasting glucose measurement. However, an oral glucose tolerance test (OGTT) could significantly improve the detection of DM and impaired glucose tolerance (IGT) and the prediction of perioperative cardiac events. In a prospective study, 404 consecutive patients without signs or histories of IGT or DM were included and subjected to OGTT. The primary study end point was the composite of perioperative myocardial ischemia, assessed by 72-hour Holter monitoring using ST-segment analysis and troponin release. The primary end point was noted in 21% of the patients. IGT was diagnosed in 104 patients (25.7%), and new-onset DM was detected in 43 patients (10.6%). The OGTT detected 75% of the patients with IGT and 72% of the patients with DM. Preoperative glucose levels significantly predicted the risk for perioperative cardiac ischemia; odds ratios for DM and IGT were, respectively, 3.2 (95% confidence interval 1.3 to 8.1) and 1.4 (95% confidence interval 0.7 to 3.0). In conclusion, the prevalence of undiagnosed IGT and DM is high in vascular patients and is associated with perioperative myocardial ischemia. Therefore, an OGTT should be considered for all patients who undergo elective vascular surgery. http://repub.eur.nl/res/pub/28761/ 2008-01-01T00:00:00Z 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 m2), 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 m2and 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 ≥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 m2, 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 ≥90 ml/min/1.73 m2and has no prognostic value in patients with GFR <30 ml/min/1.73 m2. http://repub.eur.nl/res/pub/35049/ 2007-12-15T00:00:00Z Screening for abdominal aortic aneurysms (AAAs) in patients at risk will become more cost effective if a simple, inexpensive, and reliable ultrasound device is available. The aim of this study was to compare a 2-dimensional, handheld ultrasound device and a newly developed ultrasound volume scanner (based on bladder scan technology) with computed tomography (CT) for diagnosing AAA. A total of 146 patients (mean age 69 ± 10 years; 127 men) were screened for the presence of AAAs (diameter >3 cm) using CT. All patients were examined with the handheld ultrasound device and the volume scanner. Maximal diameters and volumes were used for the analyses. AAAs were diagnosed by CT in 116 patients (80%). The absolute difference of aortic diameter between ultrasound and CT was <5 mm in 88% of patients. Limits of agreement between ultrasound and CT (-6.6 to 9.4 mm) exceeded the limits of clinical acceptability (±5 mm). An excellent correlation between ultrasound and CT was observed (r = 0.98). The correlation coefficient between the volume scanner and CT was 0.86, with agreement of 90% and κ value of 0.73. Using an optimal cut-off value of >56 ml, defined by receiver-operating characteristic curve analysis, sensitivity, specificity, and the positive and negative predictive values of the volume scanner for detecting AAA were 90%, 90%, 97%, and 71%, respectively. In conclusion, this study shows that a 2-dimensional, handheld ultrasound device and a newly developed ultrasound volume scanner can effectively identify patients with AAAs confirmed by CT. http://repub.eur.nl/res/pub/35080/ 2007-12-01T00:00:00Z β-Blockers are known to improve postoperative outcome after major vascular surgery. We studied the effects of β-blockers in 2126 vascular surgery patients with and without kidney disease followed for 14 years. Creatinine clearance was calculated using the Cockcroft-Gault equation, and kidney function was categorized as Stage 1 for a reference group of 550 patients, Stage 2 with 808 patients, Stage 3 with 627 patients, and combined Stages 4 and 5 with 141 patients. Outcome measures were 30-day and long-term all-cause mortality with a mean follow-up of 6 years. Cox proportional hazards models were used to control cardiovascular risk factors, including propensity for β-blocker use. In all, 129 (6%) and 1190 (56%) patients died respectively. Mortality rates were three- and two-fold higher, respectively, for patients at Stages 3-5 compared to the reference group for the two outcomes. β-Blocker use was significantly associated with a lower risk of mortality after surgery. The overall adjusted hazard ratio was 0.35 and 0.62, respectively, for individuals at Stages 3-5 compared to the reference group for 30-day and long-term mortality. This study shows that kidney function is a predictor of all-cause mortality and β-blocker use is associated with a lower risk of death in kidney disease patients undergoing elective vascular surgery. http://repub.eur.nl/res/pub/36545/ 2007-12-01T00:00:00Z Objective: The Lee-risk index [Lee-index] was developed to predict major adverse cardiac events [MACE]. However, age is not included as a risk factor. The aim was to assess the value of the Lee-index in vascular surgery patients among different age categories. Methods: Of 2 642 patients cardiovascular risk factors were noted to calculate the Lee-index. Patients were divided into four age categories; ≤ 55(n = 396), 56-65 (n = 650), 66-75 (n = 1 058) and >75 years (n = 538). Outcome measures were postoperative MACE (cardiac death, MI, coronary revascularization and heart failure). The performance of the Lee-index was determined using C-statistics within the four age groups. Results: The incidence of MACE was 10.9%, for Lee-index 1, 2 and ≥3; 6%, 13% and 20%, respectively. However, the prognostic value differed among age groups. The predictive value for MACE was highest among patients under 55 year (0.76 vs 0.62 of patients aged > 75). The prediction of MACE improved in elderly (aged > 75) after adjusting the Lee-index with age, revised risk of operation (low, low-intermediate, high-intermediate and high-risk procedures) and hypertension (0.62 to 0.69). Conclusion: The prognostic value of the Lee-index is reduced in elderly vascular surgery patients, adjustment with age, risk of surgical procedure, and hypertension improves the Lee-index significantly. http://repub.eur.nl/res/pub/35114/ 2007-11-01T00:00:00Z 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 ≥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 ≥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. http://repub.eur.nl/res/pub/35928/ 2007-08-01T00:00:00Z 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. http://repub.eur.nl/res/pub/35312/ 2007-07-15T00:00:00Z 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. http://repub.eur.nl/res/pub/35374/ 2007-06-01T00:00:00Z 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. http://repub.eur.nl/res/pub/36205/ 2007-05-01T00:00:00Z 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 ≥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 (≥5 segments 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. http://repub.eur.nl/res/pub/36646/ 2007-05-01T00:00:00Z Objective: Dobutamine stress echocardiography (DSE) provides an objective assessment of the presence and extent of coronary artery disease. Therefore we compared cardiac outcome in patients at high-cardiac risk undergoing open or endovascular repair of infrarenal AAA using preoperative DSE results. Methods: Consecutive patients with ≥3 cardiac risk factors (age >70 years, angina pectoris, myocardial infarction, heart failure, stroke, renal failure, and diabetes mellitus) undergoing infrarenal AAA repair were reviewed retrospectively. All underwent cardiac stress testing using DSE. Postoperatively data on troponin release and ECG were collected on day 1, 3, 7, before discharge, and on day 30. The main outcome measures were perioperative myocardial damage and myocardial infarction or cardiovascular death. Results: All 77 patients (39 endovascular, 38 open) had a history of cardiac disease. The number and type of cardiac risk factors were similar in both groups. Also DSE results were similar: 55 vs 56%, 24 vs 28%, and 21 vs 18% had no, limited, or extensive stress induced myocardial ischemia respectively. The incidence of perioperative myocardial damage (47% vs 13%, p = 0.001) and the combination of myocardial infarction or cardiovascular death (13% vs 0%, p = 0.02) was significantly lower in patients receiving endovascular repair. Conclusion: In patients with similar high cardiac risk, endovascular repair of infrarenal aortic aneurysms is associated with a reduced incidence of perioperative myocardial damage. http://repub.eur.nl/res/pub/36807/ 2007-04-01T00:00:00Z Background: Myocardial viability assessment in severely dysfunctional segments by dobutamine stress echocardiography (DSE) is less sensitive than nuclear scanning. Aim: To assess the additional value of using the recovery phase of DSE after acute beta-blocker administration for identifying viable myocardium. Methods: The study included 49 consecutive patients with ejection fraction (LVEF) ≤ 35%. All patients underwent DSE evaluation at low-high dose and during recovery phase, and dual-isotope single photon emission tomography (DISA-SPECT) evaluation for viability of severely dysfunctional segments. Patients with ≥ 4 viable segments were considered viable. Coronary revascularization followed within 3 months in all patients. Radionuclide evaluation of LVEF was performed before and 12 months after revascularization. Results: Viability with DISA-SPECT was detected in 463 (59%) segments, while 154 (19.7%) segments presented as scar. The number of viable segments increased from 415 (53%) at DSE to 463 (59%) at DSE and recovery, and the number of viable patients increased from 43 to 49 respectively. LVEF improved by ≥ 5% in 27 patients. Multivariate regression analysis showed that, DSE with recovery phase was the only independent predictor of ≥ 5% LVEF improvement after revascularization (OR 14.6, CI 1.4-133.7). Conclusion: In this study, we demonstrate that the recovery phase of DSE has an increased sensitivity for viability estimation compared to low-high dose DSE. http://repub.eur.nl/res/pub/36506/ 2007-02-01T00:00:00Z BACKGROUND: Patients undergoing noncardiac, nonvascular surgery are at risk for perioperative mortality owing to underlying (a)symptomatic coronary artery disease. We hypothesized that β-blocker and statin use are associated with reduced perioperative mortality. METHODS: We performed a case-control study in 75 581 patients who underwent 108 593 noncardiac, nonvascular surgery at the Erasmus Medical Center between 1991 and 2001. Cases were the 989 patients who died during hospital stay after surgery. From the remaining patients, 1879 matched controls (age, sex, calendar year and type of surgery) were selected. Information was then obtained regarding the use of β-blockers and statins and the presence of cardiac risk factors. RESULTS: The median age of the study population was 63 years; 61% were men. β-blockers were less often used in cases than in controls (6.2 vs. 8.2%; P=0.05), as were statins (2.4 vs. 5.5%; P<0.001). After adjustment for the propensity of β-blocker use and cardiovascular risk factors, β-blockers were associated with a 59% mortality reduction (odds ratio 0.41; 95% confidence interval 0.28-0.59). Statins were associated with a 60% mortality reduction (adjusted odds ratio 0.40; 95% confidence interval 0.24-0.68). A significant interaction between β-blockers and statins was observed (P<0.001). In the presence of each other, statins and β-blockers were not associated with reduced mortality (adjusted odds ratio 2.0 and 95% confidence interval 0.74-5.7 and adjusted odds ratio 1.3 and 95% confidence interval 0.52-3.2). It should be, however, noted that only nine cases and 29 controls used both agents simultaneously. CONCLUSION: This case-control study provides evidence that β-blockers and statins are individually associated with a reduction of perioperative mortality in patients undergoing noncardiac, nonvascular surgery. http://repub.eur.nl/res/pub/36829/ 2007-02-01T00:00:00Z Objective: To assess the long-term prognostic value of plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) after major vascular surgery. Design: A single-centre prospective cohort study. Patients: 335 patients who underwent abdominal aortic aneurysm repair or lower extremity bypass surgery. Interventions: Prior to surgery, baseline NT-proBNP level was measured. Patients were also evaluated for cardiac risk factors according to the Revised Cardiac Risk Index. Dobutamine stress echocardiography (DSE) was performed to detect stress-induced myocardial ischaemia. Main outcome measures: The prognostic value of NT-proBNP was evaluated for the endpoints all-cause mortality and major adverse cardiac events (MACE) during long-term follow-up. Results: In this patient cohort (mean age: 62 years, 76% male), median NT-proBNP level was 186 ng/l (interquartile range: 65-444 ng/l). During a mean follow-up of 14 (SD 6) months, 49 patients (15%) died and 50 (15%) experienced a MACE. Using receiver operating characteristic curve analysis for 6-month mortality and MACE, NT-proBNP had the greatest area under the curve compared with cardiac risk score and DSE. In addition, an NT-proBNP level of 319 ng/l was identified as the optimal cut-off value to predict 6-month mortality and MACE. After adjustment for age, cardiac risk score, DSE results and cardioprotective medication, NT-proBNP ≥319 ng/l was associated with a hazard ratio of 4.0 for all-cause mortality (95% CI: 1.8 to 8.9) and with a hazard ratio of 10.9 for MACE (95% CI: 4.1 to 27.9). Conclusion: Preoperative NT-proBNP level is a strong predictor of long-term mortality and major adverse cardiac events after major non-cardiac vascular surgery. http://repub.eur.nl/res/pub/35632/ 2007-01-01T00:00:00Z http://repub.eur.nl/res/pub/36344/ 2007-01-01T00:00:00Z Objective: To determine the relationship between preoperative glucose levels and perioperative mortality in noncardiac, nonvascular surgery. Research design and methods: We performed a case-control study in a cohort of 108 593 patients who underwent noncardiac surgery at the Erasmus MC during 1991-2001. Cases were 989 patients who underwent elective noncardiac, nonvascular surgery and died within 30 days during hospital stay. From the remaining patients, 1879 matched controls (age, sex, calendar year, and type of surgery) were selected. Information was obtained regarding the presence of cardiac risk factors, medication, and preoperative laboratory results. Preoperative random glucose levels < 5.6 mmol/l (110 mg/dl) were normal. Impaired glucose levels in the range of 5.6-11.1 mmol/l were prediabetes. Glucose levels ≥ 11.1 mmol/l (200 mg/dl) were diabetes. Results: Preoperative glucose levels were available in 904 cases and 1247 controls. A cardiovascular complication was the primary cause of death in 207 (23%) cases. Prediabetes glucose levels were associated with a 1.7-fold increased mortality risk compared with normoglycernic levels (adjusted odds ratio (OR) 1.7 and 95% confidence interval (CI) 1.4-2.1; P<0.001). Diabetes glucose levels were associated with a 2.1-fold increased risk (adjusted OR 2.1 and 95% CI 1.3-3.5; P<0.001). In cases with cardiovascular death, prediabetes glucose levels had a threefold increased cardiovascular mortality risk (adjusted OR 3.0 and 95% CI 1.7-5.1) and diabetes glucose levels had a fourfold increased cardiovascular mortality risk (OR 4.0 and 95% CI 1.3-12). Conclusions: Preoperative hyperglycemia is associated with increased (cardiovascular) mortality in patients undergoing noncardiac, nonvascular surgery.