A randomised study of perioperative esmolol infusion for haemodynamic stability during major vascular surgery; rationale and design of DECREASE-XIII.

OBJECTIVES: This article describes the rationale and design of the DECREASE-XIII trial, which aims to evaluate the potential of esmolol infusion, an ultra-short-acting beta-blocker, during surgery as an add-on to chronic low-dose beta-blocker therapy to maintain perioperative haemodynamic stability during major vascular surgery. DESIGN: A double-blind, placebo-controlled, randomised trial. MATERIALS & METHODS: A total of 260 vascular surgery patients will be randomised to esmolol or placebo as an add-on to standard medical care, including chronic low-dose beta-blockers. Esmolol is titrated to maintain a heart rate within a target window of 60-80 beats per minute for 24 h from the induction of anaesthesia. Heart rate and ischaemia are assessed by continuous 12-lead electrocardiographic monitoring for 72 h, starting 1 day prior to surgery. The primary outcome measure is duration of heart rate outside the target window during infusion of the study drug. Secondary outcome measures will be the efficacy parameters of occurrence of cardiac ischaemia, troponin T release, myocardial infarction and cardiac death within 30 days after surgery and safety parameters such as the occurrence of stroke and hypotension. CONCLUSIONS: This study will provide data on the efficacy of esmolol titration in chronic beta-blocker users for tight heart-rate control and reduction of ischaemia in patients undergoing vascular surgery as well as data on safety parameters.

The impact of gender on prognosis after non-cardiac vascular surgery.

OBJECTIVES: The objective was to evaluate the impact of gender on long-term survival of patients who underwent non-cardiac vascular surgery. DESIGN, MATERIAL AND METHODS: Our prospectively collected data contained information on 560 patients undergoing carotid endarterectomy (CEA), 923 elective abdominal aortic aneurysm repairs (AAA) and 1046 lower limb reconstructions (LLR). Patient characteristics and long-term mortality of women were compared to that of men. Kaplan-Meier (KM) survival curves were constructed for men and women, on which we superimposed age- and sex-matched KM survival curves of the general population. Cox proportional hazards regression was used to identify risk factors for mortality. RESULTS: Men in the CEA group had statistically significant higher all-cause mortality, hazard rate ratio (HRR) 1.41 (95% CI 1.01-1.98) No differences in mortality between the genders were observed in the AAA and LLR groups. Overall, men had more co-morbidities but received more disease-specific medication compared to women. Women retained their higher life expectancy after CEA but lost it in the AAA and LLR groups. CONCLUSION: Women retain their higher life expectancy after CEA; however, after AAA repair and LLR, this advantage is lost. Both men and women received too little disease-specific medication, but women were worse off.

Aortic surgery complications evaluated by an implanted continuous electrocardiography device: a case report.

INTRODUCTION: Cardiac arrhythmias are a major cause for morbidity and mortality in patients undergoing non-cardiac vascular surgery. REPORT: An implantable loop recorder (Reveal(®) XT) was used for continuous heart rhythm monitoring to detect perioperative arrhythmias in a 69-year-old man undergoing major vascular surgery for an infected aortobifemoral prosthesis. The Reveal(®) detected several episodes of asymptomatic new-onset atrial fibrillation postoperatively, associated with elevated serum levels of troponin-T and N-terminal pro-B-type natriuretic peptide NT-proBNP). DISCUSSION: Continuous heart rhythm monitoring with assessment of serum cardiac biomarkers may allow early identification and treatment of patients at high risk of perioperative cardiovascular complications, in particular, cardiac arrhythmias.

Reprinted article "A combination of statins and beta-blockers is independently associated with a reduction in the incidence of perioperative mortality and nonfatal myocardial infarction in patients undergoing abdominal aortic aneurysm surgery".

OBJECTIVE: To investigate the combined beneficial effect of statin and beta-blocker use on perioperative mortality and myocardial infarction (MI) in patients undergoing abdominal aortic aneurysm surgery (AAA). BACKGROUND: Patients undergoing elective AAA-surgery identified by clinical risk factors and dobutamine stress echocardiography (DSE) as being at high-risk often have considerable cardiac complication rate despite the use of beta-blockers. METHODS: We studied 570 patients (mean age 69 ±9 years, 486 males) who underwent AAA-surgery between 1991 and 2001 at the Erasmus MC. Patients were evaluated for clinical risk factors (age>70 years, histories of MI, angina, diabetes mellitus, stroke, renal failure, heart failure and pulmonary disease), DSE, statin and beta-blocker use. The main outcome was a composite of perioperative mortality and MI within 30 days of surgery. RESULTS: Perioperative mortality or MI occurred in 51 (8.9%) patients. The incidence of the composite endpoint was significantly lower in statin users compared to nonusers (3.7% vs. 11.0%; crude odds ratio (OR): 0.31, 95% confidence interval (CI): 0.13-0.74; p = 0.01). After correcting for other covariates, the association between statin use and reduced incidence of the composite endpoint remained unchanged (OR: 0.24,95% CI: 0.10-0.70; p = 0.01). Beta-blocker use was also associated with a significant reduction in the composite endpoint (OR: 0.24, 95% CI: 0.11-0.54). Patients using a combination of statins and beta-blockers appeared to be at lower risk for the composite endpoint across multiple cardiac risk strata; particularly patients with 3 or more risk factors experienced significantly lower perioperative events. CONCLUSIONS: A combination of statin and beta-blocker use in patients with AAA-surgery is associated with a reduced incidence of perioperative mortality and nonfatal MI particularly in patients at the highest risk.

Perioperative cardiac damage in vascular surgery patients.

BACKGROUND: Patients undergoing vascular surgery are at increased risk for developing cardiac complications. Majority of patients with perioperative myocardial damage are asymptomatic. Our objective is to review the available literature addressing the prevalence and prognostic implications of perioperative myocardial damage in vascular surgery patients. METHODS: An Internet-based literature search was performed using MEDLINE to identify all published reports on perioperative myocardial damage in vascular surgery patients. Only those studies published from 2000 to 2010 evaluating myocardial damage using troponin I or T, with or without symptoms of angina pectoris were included. RESULTS: Thirteen studies evaluating the prevalence of perioperative myocardial ischaemia or infarction were included in the study. The incidence of perioperative myocardial ischaemia ranged from 14% to 47% and the incidence of perioperative myocardial infarction ranged from 1% to 26%. In addition, 10 studies evaluating the prognostic value of perioperative myocardial ischaemia towards postoperative mortality or the occurrence of major adverse cardiac events were included. In the retrieved studies, hazard ratios varied from 1.9 to 9.0. CONCLUSION: The high prevalence and asymptomatic nature of perioperative myocardial damage, combined with a substantial influence on postoperative mortality of vascular surgery patients, underline the importance of early detection and adequate management of perioperative myocardial damage. This article provides an extended overview regarding the prevalence and prognostic value of perioperative myocardial ischaemia and infarction in vascular surgery patients. In addition, treatment options to reduce the risk of perioperative myocardial damage are provided based on the current available literature.

Asymptomatic low ankle-brachial index in vascular surgery patients: a predictor of perioperative myocardial damage.

OBJECTIVES: This study evaluated the prognostic value of asymptomatic low ankle-brachial index (ABI) to predict perioperative myocardial damage, incremental to conventional cardiac risk factors imbedded in cardiac risk indices (Revised Cardiac index and Adapted Lee index). MATERIALS AND METHODS: Preoperative ABI measurements were performed in 627 consecutive vascular surgery patients (carotid artery or abdominal aortic aneurysm repair). An ABI<0.90 was considered abnormal. Patients with ABI>1.40 or (a history of) intermittent claudication were excluded. Serial troponin-T measurements were performed routinely before and after surgery. The main study endpoint was perioperative myocardial damage, the composite of myocardial ischaemia and infarction. Multivariate regression analyses, adjusted for conventional risk factors, evaluated the relation between asymptomatic low ABI and perioperative myocardial damage. RESULTS: In total, 148 (23%) patients had asymptomatic low ABI (mean 0.73, standard deviation+/-0.13). Perioperative myocardial damage was recorded in 107 (18%) patients. Multivariate regression analyses demonstrated that asymptomatic low ABI was associated with an increased risk of perioperative myocardial damage (odds ratio (OR): 2.4, 95% CI: 1.4-4.2) CONCLUSIONS: This study demonstrated that asymptomatic low ABI has a prognostic value to predict perioperative myocardial damage in vascular surgery patients, incremental to risk factors imbedded in conventional cardiac risk indices.

Smoking cessation has no influence on quality of life in patients with peripheral arterial disease 5 years post-vascular surgery.

OBJECTIVES: Smoking is an important modifiable risk factor in patients with peripheral arterial disease (PAD). We investigated differences in quality of life (QoL) between patients who quitted smoking during follow-up and persistent smokers. DESIGN: Cohort study. METHODS: Data of 711 consecutively enrolled patients undergoing vascular surgery were collected in 11 hospitals in the Netherlands. Smoking status was obtained at baseline and at 3-year follow-up. A 5-year follow-up to measure QoL was performed with the EuroQol-5D (EQ-5D) and Peripheral Arterial Questionnaire (PAQ). RESULTS: After adjusting for clinical risk factors, patients, who quit smoking within 3 years after vascular surgery, did not report an impaired QoL (EQ-5D: odds ratio (OR) = 0.63, 95% confidence interval (CI) = 0.28-1.43; PAQ: OR = 0.76, 95% CI = 0.35-1.65; visual analogue scale (VAS): OR = 0.88, 95% CI = 0.42-1.84) compared with patients, who continued smoking. Current smokers were significantly more likely to have an impaired QoL (EQ-5D: OR = 1.86, 95% CI = 1.09-3.17; PAQ: OR = 1.63, 95% CI = 1.00-2.65), although no differences in VAS scores were found (OR = 1.17, 95% CI = 0.72-1.90). CONCLUSIONS: There was no effect of smoking cessation on QoL in PAD patients undergoing vascular surgery. Nevertheless, given the link between smoking, complications and mortality in this patient group, smoking cessation should be a primary target in secondary prevention.

Process of care partly explains the variation in mortality between hospitals after peripheral vascular surgery.

OBJECTIVES: The aim of this study is to investigate whether variation in mortality at hospital level reflects differences in quality of care of peripheral vascular surgery patients. DESIGN: Observational study. MATERIALS: In 11 hospitals in the Netherlands, 711 consecutive vascular surgery patients were enrolled. METHODS: Multilevel logistic regression models were used to relate patient characteristics, structure and process of care to mortality at 1 year. The models were constructed by consecutively adding age, sex and Lee index, then remaining risk factors, followed by structural measures for quality of care and finally, selected process of care parameters. RESULTS: Total 1-year mortality was 11%, ranging from 6% to 26% in different hospitals. Large differences in patient characteristics and quality indicators were observed between hospitals (e.g., age>70 years: 28-58%; beta-blocker therapy: 39-87%). Adjusted analyses showed that a large part of variation in mortality was explained by age, sex and the Lee index (Akaike's information criterion (AIC)=59, p<0.001). Another substantial part of the variation was explained by process of care (AIC=5, p=0.001). CONCLUSIONS: Differences between hospitals exist in patient characteristics, structure of care, process of care and mortality. Even after adjusting for the patient population at risk, a substantial part of the variation in mortality can be explained by differences in process measures of quality of care.

Prognosis of vascular surgery patients using a quantitative assessment of troponin T release: is the crystal ball still clear?

BACKGROUND: Cardiac troponin T (cTnT) assays with increased sensitivity might increase the number of positive tests. Using the area under the curve (AUC) with serial sampling of cTnT an exact quantification of the myocardial damage size can be made. We compared the prognosis of vascular surgery patients with integrated cTnT-AUC values to continuous and standard 12-lead electrocardiography (ECG) changes. METHODS: 513 Patients were monitored. cTnT sampling was performed on postoperative days 1, 3, 7, 30 and/or at discharge or whenever clinically indicated. If cTnT release occurred, daily measurements of cTnT were performed, until baseline was achieved. CTnT-AUC was quantified and divided in tertiles. All-cause mortality and cardiovascular events (cardiac death and myocardial infarction) were noted during follow-up. RESULTS: 81/513 (16%) Patients had cTnT release. After adjustment for gender, cardiac risk factors, and site and type of surgery, those in the highest cTnT-AUC tertile were associated with a significantly worse cardiovascular outcome and long-term mortality (HR 20.2; 95% CI 10.2-40.0 and HR 4.0; 95% CI 2.0-7.8 respectively). Receiver operator analysis showed that the best cut-off value for cTnT-AUC was <0.01 days*ng m for predicting long-term cardiovascular events and all-cause mortality. CONCLUSION: In vascular surgery patients quantitative assessment of cTnT strongly predicts long-term outcome.

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.

Predicting patient-specific expansion of abdominal aortic aneurysms.

OBJECTIVE: Local anatomy and the patient's risk profile independently affect the expansion rate of an abdominal aortic aneurysm. We describe a hybrid method that combines finite element modelling and statistical methods to predict patient-specific aneurysm expansion. METHODS: The 3-D geometry of the aneurysm was imaged with computed tomography. We used finite element methods to calculate wall stress and aneurysm expansion. Expansion rate was adjusted by risk factors obtained from a database of 80 patients. Aneurysm diameters predicted with and without the risk profiles were compared with diameters measured with ultrasound for 11 patients. RESULTS: For this specific group of patients, local anatomy contributed 62% and the risk profile 38% to the aneurysmal expansion rate. Predictions with risk profiles resulted in smaller root mean square errors than predictions without risk profiles (2.9 vs. 4.0 mm, p < 0.01). CONCLUSIONS: This hybrid approach predicted aneurysmal expansion for a period of 30 months with high accuracy.

Relation between regional and global systolic function in patients with ischemic cardiomyopathy after beta-blocker therapy or revascularization.

BACKGROUND: To assess the relationship between improved regional and global myocardial function in patients with ischemic cardiomyopathy in response to beta-blocker therapy or revascularization. MATERIALS AND METHODS: Cardiovascular magnetic resonance (CMR) was performed in 32 patients with ischemic cardiomyopathy before and 8 +/- 2 months after therapy. Patients were assigned clinically to beta-blocker therapy (n = 20) or revascularization (n = 12). CMR at baseline was performed to assess regional and global LV function at rest and under low-dose dobutamine. Wall thickening was analyzed in dysfunctional, adjacent, and remote segments. Follow-up CMR included rest function evaluation. RESULTS: Augmentation of wall thickening during dobutamine at baseline was similar in dysfunctional, adjacent and remote segments in both patient groups. Therefore, baseline characteristics were similar for both patient groups. In both patient groups resting LV ejection fraction and end-systolic volume improved significantly (p < 0.05) at follow-up. Stepwise multivariate analysis revealed that improvement in global LV ejection fraction in the beta-blocker treated patients was significantly related to improved function of remote myocardium (p < 0.05), whereas in the revascularized patients improved function in dysfunctional and adjacent segments was more pronounced (p < 0.05). CONCLUSION: In patients with chronic ischemic LV dysfunction, beta-Blocker therapy or revascularization resulted in a similar improvement of global systolic LV function. However, after beta-blocker therapy, improved global systolic function was mainly related to improved contraction of remote myocardium, whereas after revascularization the dysfunctional and adjacent regions contributed predominantly to the improved global systolic function.

Decision-making in type-B dissection: current evidence and future perspectives.

Aortic dissection is a devastating cardiovascular condition with an incidence of 3,5:100 000. It is classified according to anatomic extent, mechanism of lesion, duration from index event and course (uncomplicated vs. complicated). Intramural hematoma and penetrating aortic ulcers share many of the features of classic dissections, but tend to occur in older patients with advanced atherosclerosis. In uncomplicated type-B dissection, conservative treatment with tight blood pressure and heart rate control is safe and effective. Early stent-graft implantation may, however, result in more favorable aortic remodeling and reduced late complications. For acute complicated cases intervention is usually required. Stent-graft coverage of the entry tear frequently resolves malperfusion, but the role of the false lumen in organ perfusion must be assessed and endovascular revascularization performed if necessary. In chronic type-B dissections, coverage of the entry tear likely results in continued pressurization of the false lumen due to rigidity of the dissecting membrane and distal fenestrations. Better understanding of the different disease mechanisms involved, imaging advances and introduction of dedicated stent-grafts are expected to further improve patient outcomes in the future. Primary and secondary pharmacological prevention, stricter follow-up protocols and screening of family members may also prove valuable. Better patient selection will allow preventive treatment with low morbidity for those at higher risk of complications.

The effect of statins on perioperative events in patients undergoing vascular surgery.

Despite recent advancements in perioperative care and guideline recommendations, patients undergoing vascular surgery remain at risk for perioperative cardiovascular complications. In this review, the results are summarized of the most recent studies on the effectiveness and safety of perioperative statin use for the prevention of these perioperative cardiovascular complications. Perioperative statin therapy was associated with an improvement in postoperative cardiovascular outcome and a reduction in serum lipid levels and levels of inflammation markers.

COPD and cancer mortality: the influence of statins.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with an increased risk of lung cancer, independently of smoking. However, the relationship between COPD and total cancer mortality is less certain. A study was undertaken to investigate the association between COPD and total cancer mortality and to determine whether the use of statins, which have been associated with cancer risk in other settings, modified this relationship. METHODS: The study included 3371 patients with peripheral arterial disease who underwent vascular surgery between 1990 and 2006; 1310 (39%) had COPD and the rest did not. The primary end point was cancer mortality (lung and extrapulmonary) over a median follow-up of 5 years. RESULTS: COPD was associated with an increased risk of both lung cancer mortality (hazard ratio (HR) 2.06; 95% CI 1.32 to 3.20) and extrapulmonary cancer mortality (HR 1.43; 95% CI 1.06 to 1.94). The excess risk was mostly driven by patients with moderate and severe COPD. There was a trend towards a lower risk of cancer mortality among patients with COPD who used statins compared with patients with COPD who did not use statins (HR 0.57; 95% CI 0.32 to 1.01). Interestingly, the risk of extrapulmonary cancer mortality was lower among statin users with COPD (HR 0.49; 95% CI 0.24 to 0.99). CONCLUSIONS: COPD was associated with increased lung and extrapulmonary cancer mortality in this large cohort of patients with peripheral arterial disease undergoing vascular surgery. The risk of lung cancer mortality increased with progression of COPD. Statins were associated with a reduced risk of extrapulmonary cancer mortality in patients with COPD.

Perioperative blood glucose monitoring and control in major vascular surgery patients.

Diabetes mellitus (DM) is an independent predictor for morbidity and mortality in the general population, which is even more apparent in patients with concomitant cardiovascular risk factors. As the prevalence of DM is increasing, with an ageing general population, it is expected that the number of diabetic patients requiring surgical interventions will increase. Perioperative hyperglycaemia, without known DM, has been identified as a predictor for morbidity and mortality in patients undergoing surgery. Moreover, early studies showed that intensive blood-glucose-lowering therapy reduced both morbidity and mortality among patients admitted to the postoperative intensive care unit (ICU). However, later studies have doubted the benefit of intensive glucose control in medical-surgical ICU patients. This article aims to comprehensively review the evidence on the use of perioperative intensive glucose control, and to provide recommendations for current clinical practice. A systematic review was performed of the literature on perioperative intensive glucose control. Based on this literature review, we observed that intensive glucose control in the perioperative period has no clear benefit on short-term mortality. Intensive glucose control may even have a net harmful effect in selected patients. In addition, concerns on the external validity of some studies are important barriers for widespread recommendation of intensive glucose control in the perioperative setting. We propose that guidelines recommending intensive glucose control should be re-evaluated. In addition, moderate tight glucose control should currently be regarded as the safest and most efficient approach to patients undergoing major vascular surgery.

Prognosis of transient new-onset atrial fibrillation during vascular surgery.

BACKGROUND: Chronic atrial fibrillation (AF) in a non-surgical setting is associated with cardiovascular events. However, the prognosis of transient new-onset AF during vascular surgery is unknown. OBJECTIVE: The purpose of this study is to investigate the prognosis of new-onset AF during vascular surgery using continuous electrocardiographic monitoring (continuous-ECG). METHODS: In this study, 317 patients, all in sinus rhythm, scheduled for major vascular surgery were screened for cardiac risk factors. Continuous-ECG recordings for 72h and standard ECG on days 3, 7 and 30 were used to identify new-onset AF. Cardiac troponin T (cTnT) was measured routinely after surgery. Study endpoint was a composite of cardiac death, myocardial infarction, unstable angina and stroke (cardiovascular events) at 30 days after surgery and during late follow-up. Median follow-up was 12 (interquartile range 2-28) months. RESULTS: New-onset AF was noted in 15 (4.7%) patients. All but three patients returned spontaneously to sinus rhythm. The composite endpoint of cardiovascular events within 30 days and during late follow-up occurred in 34 (11%) and 62 (20%) patients, respectively. Multivariate regression analysis showed that new-onset AF was associated with perioperative (hazard ratio (HR) 6.0; 95% CI: 2.4-15) and late cardiovascular events (HR 4.2, 95% CI: 2.1-8.8). CONCLUSION: New-onset AF during vascular surgery is associated with an increased incidence of 30-day and late cardiovascular events.

The prevalence of polyvascular disease in patients referred for peripheral arterial disease.

OBJECTIVE: To objectively assess the presence of polyvascular disease in patients with peripheral arterial disease and its relation to inflammation and clinical risk factors. METHODS: A total of 431 vascular surgery patients (mean age 68 years, men 77%) with atherosclerotic disease were enrolled. The presence of atherosclerosis was assessed using ultrasonography. Affected territories were defined as: (1) carotid, stenosis of common or internal carotid artery of >or=50%, (2) cardiac, left ventricular wall motion abnormalities, (3) abdominal aorta, diameter >or=30 mm and (4) lower limb, ankle-brachial pressure index <0.9. Cardiovascular risk factors and high-sensitivity C-reactive protein (hs-CRP) levels were noted in all. RESULTS: One vascular territory was affected in 29% of the patients, whereas polyvascular disease was found in 71%: two affected territories in 45%, three in 23% and four in 3% of patients. Levels of hs-CRP increased with the number of affected vascular territories (p<0.001). Multivariable logistic regression analysis showed age >or=70 years, male gender, body mass index (BMI)>or=25 kg m(-2), and hs-CRP to be independently associated with polyvascular disease. CONCLUSION: Polyvascular disease is a common condition in patients who have undergone vascular surgery. The level of systemic inflammation, reflected by hs-CRP levels, is moderately associated with the extent of polyvascular disease.

The prognostic value of impaired walking distance on long-term outcome in patients with known or suspected peripheral arterial disease.

OBJECTIVES: To assess the predictive value of walking distance after an exercise test on long-term outcome in patients with normal and impaired ankle-brachial index (ABI). DESIGN: A total of 2191 patients with known or suspected peripheral arterial disease (PAD), who were referred for a single-stage treadmill exercise test to diagnose or evaluate their PAD, were enrolled in an observational study between 1993 and 2006. MATERIALS AND METHODS: They were divided into two groups: normal ABI (>or=0.90) and impaired ABI (<0.90). Walking distance was divided into quartiles (no (reference), mild, moderate or severe impairment). RESULTS: In patients with normal ABI, severe walking distance was, after adjustment, associated with higher mortality risk (hazard ratio (HR): 2.60 (range: 1.16-5.78)). In patients with impaired ABI, all walking distance impairment quartiles were associated with higher mortality (mild HR: 1.26 (range: 0.95-1.67), moderate HR: 1.52 (range: 1.13-2.05) and severe HR: 1.69 (range: 1.26-2.27)). Furthermore, comparable associations were observed between all walking distance quartiles, cardiac death or major adverse cerebrovascular and cardiac events. CONCLUSIONS: Our study illustrated that walking impairment is a strong prognostic indicator of long-term outcome in patients with impaired and normal ABI, which should be a warning sign to physicians to monitor these patients carefully and to provide them optimal treatment.

Methionine loading does not enhance the predictive value of homocysteine serum testing for all-cause mortality or major adverse cardiac events.

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 > or =15 micromol/L and post-methionine loading level > or =45 micromol/L or an increase of > or =30 micromol/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.