Tamara A. Winkel

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.

Timing of pre-operative Beta-blocker treatment in vascular surgery patients: influence on post-operative outcome.

OBJECTIVES This study evaluated timing of β-blocker initiation before surgery and its relationship with: 1) pre-operative heart rate and high-sensitivity C-reactive-protein (hs-CRP) levels; and 2) post-operative outcome. BACKGROUND Perioperative guidelines recommend β-blocker initiation days to weeks before surgery, on the basis of expert opinions. METHODS In 940 vascular surgery patients, pre-operative heart rate and hs-CRP levels were recorded, next to timing of β-blocker initiation before surgery (0 to 1, >1 to 4, >4 weeks). Pre- and post-operative troponin-T measurements and electrocardiograms were performed routinely. End points were 30-day cardiac events (composite of myocardial infarction and cardiac mortality) and long-term mortality. Multivariate regression analyses, adjusted for cardiac risk factors, evaluated the relation between duration of β-blocker treatment and outcome. RESULTS The β-blockers were initiated 0 to 1, >1 to 4, and >4 weeks before surgery in 158 (17%), 393 (42%), and 389 (41%) patients, respectively. Median heart rate at baseline was 74 (±17) beats/min, 70 (±16) beats/min, and 66 (±15) beats/min (p < 0.001; comparing treatment initiation >1 with <1 week pre-operatively), and hs-CRP was 4.9 (±7.5) mg/l, 4.1 (±.6.0) mg/l, and 4.5 (±6.3) mg/l (p = 0.782), respectively. Treatment initiated >1 to 4 or >4 weeks before surgery was associated with a lower incidence of 30-day cardiac events (odds ratio: 0.46, 95% confidence interval [CI]: 0.27 to 0.76, odds ratio: 0.48, 95% CI: 0.29 to 0.79) and long-term mortality (hazard ratio: 0.52, 95% CI: 0.21 to 0.67, hazard ratio: 0.50, 95% CI: 0.25 to 0.71) compared with treatment initiated <1 week pre-operatively. CONCLUSIONS Our results indicate that β-blocker treatment initiated >1 week before surgery is associated with lower pre-operative heart rate and improved outcome, compared with treatment initiated <1 week pre-operatively. No reduction of median hs-CRP levels was observed in patients receiving β-blocker treatment >1 week compared with patients in whom treatment was initiated between 0 and 1 week before surgery.

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.

Temporary Perioperative Decline of Renal Function Is an Independent Predictor for Chronic Kidney Disease

BACKGROUND AND OBJECTIVES Acute kidney injury is an independent predictor of short- and long-term survival; however, data on the relationship between reversible transitory decline of kidney function and chronic kidney disease (CKD) are lacking. We assessed the prognostic value of temporary renal function decline on the development of long-term CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS The study included 1308 patients who were undergoing major vascular surgery (aortic aneurysm repair, lower extremity revascularization, or carotid surgery), divided into three groups on the basis of changes in Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) estimated GFR (eGFR) on days 1, 2, and 3 after surgery, compared with baseline: Group 1, improved or unchanged (change in CKD-EPI eGFR+/-10%); group 2, temporary decline (decline>10% at day 1 or 2, followed by complete recovery within 10% to baseline at day 3); and group 3, persistent decline (>10% decrease). Primary end point was the development of incident CKD during a median follow-up of 5 years. RESULTS Perioperative renal function was classified as unchanged, temporary decline, and persistent decline in 739 (57%), 294 (22%), and 275 (21%) patients, respectively. During follow-up, 272 (21%) patients developed CKD. In multivariate logistic regression analyses, temporary and persistent declines in renal function both were independent predictors of long-term CKD, compared with unchanged renal function. CONCLUSION Vascular surgery patients have a high incidence of temporary and persistent perioperative renal function declines, both of which were independent predictors for development of long-term incident CKD.

Perioperative asymptomatic cardiac damage after endovascular abdominal aneurysm repair is associated with poor long-term outcome

BACKGROUND Endovascular abdominal aortic aneurysm (AAA) repair (EVAR) is associated with a decreased incidence of perioperative cardiac complications compared with open repair. However, EVAR is not associated with long-term survival benefit. This study assessed the effect of perioperative asymptomatic cardiac damage after EVAR on long-term prognosis. METHODS In 220 patients undergoing elective EVAR, routine sampling for levels of cardiac troponin T and electrocardiography (ECG) were performed on days 1, 3, and 7 during the patients hospital stay. Elevated cardiac troponin T was defined as serum concentrations >or=0.01 ng/mL. Asymptomatic cardiac damage was defined as cardiac troponin T release without symptoms or ECG changes. The median follow-up was 2.9 years. Survival status was obtained by contacting the Office of Civil Registry. RESULTS Release of cardiac troponin T (median, 0.08 ng/mL) occurred in 24 of 220 patients, of whom 20 (83%) were asymptomatic and without ECG changes. Patients with asymptomatic cardiac damage had a mortality rate of 49% [corrected] after 2.9 years vs 15% [corrected] for patients without perioperative cardiac damage (P < .001). Also after adjustment for clinical risk factors and medication use applying multivariate Cox regression analysis, asymptomatic cardiac damage was associated with a 2.3-fold increased risk for death (95% confidence interval, 1.1-5.1). Statin use was associated with a reduced long-term risk for death (hazard ratio, 0.5; 95% confidence interval, 0.3-0.9). CONCLUSION Asymptomatic cardiac damage in patients undergoing EVAR is associated with poor long-term outcome. Routine perioperative cardiac screening after EVAR might be warranted.

Prognosis of Atrial Fibrillation in Patients with Symptomatic Peripheral Arterial Disease: Data from the REduction of Atherothrombosis for Continued Health (REACH) Registry

BACKGROUND Atrial fibrillation (AF) is a significant risk factor for cardiovascular (CV) mortality. This study aims to evaluate the prognostic implication of AF in patients with peripheral arterial disease (PAD). METHODS The International Reduction of Atherothrombosis for Continued Health (REACH) Registry included 23,542 outpatients in Europe with established coronary artery disease, cerebrovascular disease (CVD), PAD and/or > or =3 risk factors. Of these, 3753 patients had symptomatic PAD. CV risk factors were determined at baseline. Study end point was a combination of cardiac death, non-fatal myocardial infarction (MI) and stroke (CV events) during 2 years of follow-up. Cox regression analysis adjusted for age, gender and other risk factors (i.e., congestive heart failure, coronary artery re-vascularisation, coronary artery bypass grafting (CABG), MI, hypertension, stroke, current smoking and diabetes) was used. RESULTS Of 3753 PAD patients, 392 (10%) were known to have AF. Patients with AF were older and had a higher prevalence of CVD, diabetes and hypertension. Long-term CV mortality occurred in 5.6% of patients with AF and in 1.6% of those without AF (p<0.001). Multivariable analyses showed that AF was an independent predictor of late CV events (hazard ratio (HR): 1.5; 95% confidence interval (CI): 1.09-2.0). CONCLUSION AF is common in European patients with symptomatic PAD and is independently associated with a worse 2-year CV outcome.

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.

Intima media thickness of the common carotid artery in vascular surgery patients: A predictor of postoperative cardiovascular events

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.

Long-term cardiac outcome in high-risk patients undergoing elective endovascular or open infrarenal abdominal aortic aneurysm repair.

OBJECTIVES To assess long-term outcome of patients at high cardiac risk undergoing endovascular or open AAA repair. METHODS Patients undergoing open or endovascular infrarenal AAA repair with >or=3 cardiac risk factors and preoperative cardiac stress testing (DSE) at 2 university hospitals were studied. Main outcome was cardiac event free and overall survival. Multivariate Cox regression analysis was used to evaluate the influence of type of AAA repair on long-term outcome. RESULTS In 124 patients (55 endovascular, 69 open) the number and type of cardiac risk factors, medication use and DSE results were similar in both groups. In multivariable analysis, adjusting for cardiac risk factors, stress test results, medication use, and propensity score endovascular repair was associated with improved cardiac event free survival (HR 0.54; 95% CI 0.30-0.98) but not with an overall survival benefit (HR 0.73; 95% CI 0.37-1.46). Importantly, statin therapy was associated with both improved overall survival (HR 0.42; 95% CI 0.21-0.83) and cardiac event free survival (HR 0.45; 95% CI 0.23-0.86). CONCLUSIONS The perioperative cardiac benefit of endovascular AAA repair in high cardiac risk patients is sustained during long-term follow-up provided patients are on optimal medical therapy but it is not associated with improved overall long-term survival.

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.