Martin Dunkelgrun

Bisoprolol and fluvastatin for the reduction of perioperative cardiac mortality and myocardial infarction in intermediate-risk patients undergoing noncardiovascular surgery: a randomized controlled trial (DECREASE-IV).

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.

Plasma N-terminal pro-B-type natriuretic peptide as long-term prognostic marker after major vascular surgery

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.

Anemia as an Independent Predictor of Perioperative and Long-Term Cardiovascular Outcome in Patients Scheduled for Elective Vascular Surgery

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.

Impaired glucose regulation, elevated glycated haemoglobin and cardiac ischaemic events in vascular surgery patients

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.

Incremental value of high-sensitivity C-reactive protein and N-terminal pro-B-type natriuretic peptide for the prediction of postoperative cardiac events in noncardiac vascular surgery patients.

ObjectivesHigh-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. MethodsIn 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. ResultsAfter 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. ConclusionBoth 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.

Pro: Beta-blockers Are Indicated for Patients at Risk for Cardiac Complications Undergoing Noncardiac Surgery

Olaf Schouten, MD Jeroen J. Bax, MD, FESC Martin Dunkelgrun, MD Harm H.H. Feringa, MD Don Poldermans, MD, FESC Of the estimated 100 million adults undergoing noncardiac surgery annually, approximately 500,000 patients (0.5%) will experience cardiac death perioperatively (1). Lee et al. (2) reported an overall risk for myocardial infarction (MI) after noncardiac surgery to be 1.1%, translating into about 1.1 million MIs annually worldwide. Although the pathophysiology of perioperative MI is not entirely clear, coronary plaque rupture, leading to thrombus formation and subsequent vessel occlusion, is implicated, similar to MI in the nonoperative setting (3). The incidence of plaque rupture is possibly increased by the stress response to major surgery. This response includes sympathetic activation promoting sheer stress on arterial plaques, enhanced vascular reactivity conducive to the development of vasospasm, reduced fibrinolytic activity, platelet activation, and hypercoagulability (4). Heightened sympathetic tone further increases myocardial oxygen demand (e.g., tachycardia and increased contractility), leading to myocardial oxygen supply/demand mismatch that, when sustained, might lead to MI (4,5). At least two studies evaluating the pathophysiology of perioperative MI using noninvasive tests, coronary angiography, and autopsy have shown that coronary plaque rupture and thrombus formation occurred in 50% of all fatal MIs, whereas a sustained oxygen supply/demand mismatch was responsible for the remaining 50% (3,6).

Association Between Serum Uric Acid and Perioperative and Late Cardiovascular Outcome in Patients With Suspected or Definite Coronary Artery Disease Undergoing Elective Vascular Surgery

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.

Preoperative oral glucose tolerance testing in vascular surgery patients: Long-term cardiovascular outcome

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.

Usefulness of Preoperative Oral Glucose Tolerance Testing for Perioperative Risk Stratification in Patients Scheduled for Elective Vascular Surgery

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.

The interrelationship between preoperative anemia and N-terminal pro-B-type natriuretic peptide: the effect on predicting postoperative cardiac outcome in vascular surgery patients.

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 (&bgr; 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.