Patients who do not complete cardiac rehabilitation have an increased risk of cardiovascular events during long-term follow-up.

BACKGROUND: Cardiac rehabilitation (CR) has favourable effects on cardiovascular mortality and morbidity. Therefore, it might reasonable to expect that incomplete CR participation will result in suboptimal patient outcomes. METHODS: We studied the 914 post-acute coronary syndrome patients who participated in the OPTImal CArdiac REhabilitation (OPTICARE) trial. They all started a 'standard' CR programme, with physical exercises (group sessions) twice a week for 12 weeks. Incomplete CR was defined as participation in <75% of the scheduled exercise sessions. Patients were followed-up for 2.7 years, and the incidence of cardiac events was recorded. Major adverse cardiac events (MACE) included all-cause mortality, non-fatal myocardial infarction and coronary revascularisation. RESULTS: A total of 142 (16%) patients had incomplete CR. They had a higher incidence of MACE than their counterparts who completed CR (11.3% versus 3.8%, adjusted hazard ratio [aHR] 2.86 and 95% confidence interval [CI] 1.47-5.26). Furthermore, the incidence of any cardiac event, including MACE and coronary revascularisation, was higher (20.4% versus 11.0%, aHR 1.54; 95% CI 0.98-2.44). Patients with incomplete CR were more often persistent smokers than those who completed CR (31.7% versus 11.5%), but clinical characteristics were similar otherwise. CONCLUSION: Post-ACS patients who did not complete a 'standard' 12-week CR programme had a higher incidence of adverse cardiac events during long-term follow-up than those who completed the programme. Since CR is proven beneficial, further research is needed to understand the reasons why patients terminate prematurely.

Prognostic value of the coronary artery calcium score in suspected coronary artery disease: a study of 644 symptomatic patients.

AIM: The long-term value of coronary artery calcium (CAC) scanning has not been studied extensively in symptomatic patients, but was evaluated by us in 644 consecutive patients referred for stable chest pain. METHODS: We excluded patients with a history of cardiovascular disease and with a CAC score of zero. CAC scanning was done with a 16-row MDCT scanner. Endpoints were: (a) overall mortality, (b) mortality or non-fatal myocardial infarction and (c) the composite of mortality, myocardial infarction or coronary revascularisation. Revascularisations within 1 year following CAC scanning were not considered. RESULTS: The mean age of the 320 women and 324 men was 63 years. Follow-up was over 8 years. There were 58 mortalities, while 22 patients suffered non-fatal myocardial infarction and 24 underwent coronary revascularisation, providing 104 combined endpoints. Cumulative 8­year survival was 95% with CAC score <100, 90% in patients with CAC score >100 and <400, and 82% with CAC score ≥400 Agatston units. Risk of mortality with a CAC score >100 and ≥400 units was 2.6 [95% confidence interval (CI) 1.23-5.54], and 4.6 (95% CI 2.1-9.47) respectively. After correction for clinical risk factors, CAC score remained independently associated with increased risk of cardiac events. CONCLUSIONS: Risk increased with increasing CAC score. Patients with CAC >100 or ≥400 Agatston units were at increased risk of major adverse cardiac events and are eligible for preventive measures. CAC scanning provided incremental prognostic information to guide the choice of diagnostic and therapeutic options in many subjects evaluated for chest pain.

Cardiac rehabilitation in patients who underwent primary percutaneous coronary intervention for acute myocardial infarction: determinants of programme participation and completion.

BACKGROUND: Hospital length of stay after acute myocardial infarction (AMI) treated with primary percutaneous coronary intervention (pPCI) has reduced, resulting in more limited patient education during admission. Therefore, systematic participation in cardiac rehabilitation (CR) has become more essential. We aimed to identify patient-related factors that are associated with participation in and completion of a CR programme. METHODS: We identified 3,871 consecutive AMI patients who underwent pPCI between 2003 and 2011. These patients were linked to the database of Capri CR, which provides dedicated, multi-disciplinary CR. 'Participation' was defined as registration at Capri CR within 6 months after pPCI. CR was 'complete' if a patient undertook the final exercise test. RESULTS: In total, 1,497 patients (39%) were registered at Capri CR. Factors independently associated with CR participation included age (<50 vs. >70 year: odds ratio (OR) 7.0, 95% confidence interval (CI) 5.1-9.6), gender (men vs. women: OR 1.9, 95% CI 1.3-1.8), index diagnosis (ST-elevation myocardial infarction [STEMI] vs. non-ST-elevation myocardial infarction [NSTEMI]: OR 2.4, 95% CI 2.0-2.7) and socio-economic status (high vs. low: OR 2.0, 95% CI 1.6-2.5). The model based on these factors discriminated well (c-index 0.75). CR programme completion was 80% and was inversely related with diabetes, current smoking and previous MI. The discrimination of the model based on these factors was poor (c-index 0.59). CONCLUSIONS: Only a minority of AMI/pPCI patients participated in a CR programme. Completion rates, however, were better. Increased physician and patient awareness of the benefits of CR are still needed, with focus on the elderly, women and patients with low socio-economic status.

Haemolysis as a first sign of thromboembolic event and acute pump thrombosis in patients with the continuous-flow left ventricular assist device HeartMate II.

BACKGROUND: Despite advances in pump technology, thromboembolic events/acute pump thrombosis remain potentially life-threatening complications in patients with continuous-flow left ventricular assist devices (CF-LVAD). We sought to determine early signs of thromboembolic event/pump thrombosis in patients with CF-LVAD, which could lead to earlier intervention. METHODS: We analysed all HeartMate II recipients (n = 40) in our centre between December 2006 and July 2013. Thromboembolic event/pump thrombosis was defined as a transient ischaemic attack (TIA), ischaemic cerebrovascular accident (CVA), or pump thrombosis. RESULTS: During median LVAD support of 336 days [IQR: 182-808], 8 (20 %) patients developed a thromboembolic event/pump thrombosis (six TIA/CVA, two pump thromboses). At the time of the thromboembolic event/pump thrombosis, significantly higher pump power was seen compared with the no-thrombosis group (8.2 ± 3.0 vs. 6.4 ± 1.4 W, p = 0.02), as well as a trend towards a lower pulse index (4.1 ± 1.5 vs. 5.0 ± 1.0, p = 0.05) and a trend towards higher pump flow (5.7 ± 1.0 vs. 4.9 ± 1.9 L m, p = 0.06). The thrombosis group had a more than fourfold higher lactate dehydrogenase (LDH) median 1548 [IQR: 754-2379] vs. 363 [IQR: 325-443] U/L, p = 0.0001). Bacterial (n = 4) or viral (n = 1) infection was present in 5 out of 8 patients. LDH > 735 U/L predicted thromboembolic events/pump thrombosis with a positive predictive value of 88 %. CONCLUSIONS: In patients with a CF-LVAD (HeartMate II), thromboembolic events and/or pump thrombosis are associated with symptoms and signs of acute haemolysis as manifested by a high LDH, elevated pump power and decreased pulse index, especially in the context of an infection.

Prognostic value of type D personality for 10-year mortality and subjective health status in patients treated with percutaneous coronary intervention.

OBJECTIVE: Given the debate around limitations and controversies in type D personality studies, we aimed to evaluate the prognostic value of 'synergistically' analyzed type D personality (interaction z-scores negative affectivity NA, and social inhibition SI) on 10-year mortality and on 10-year subjective health status in percutaneous coronary intervention (PCI) patients. METHODS: This prospective study comprised a cohort of 1190 consecutive patients who underwent PCI between October 2001 and September 2002 (73% male, mean age: 62years, range [27-90]years). At baseline, type D personality (DS14), and depression/anxiety (HADS) were assessed. Primary endpoint was 10year all-cause mortality; secondary endpoint was 10-year subjective health status (SF-36). RESULTS: After a median follow-up of 10.3years (IQR 9.8-10.8), 293 deaths of any cause (24.6%) were recorded. After adjustment for significant baseline characteristics, personality categories approached and dichotomously approached type D personality were associated with 10-year mortality, p<.05. Synergistically approached type D personality was not associated with all-cause mortality or subjective health status at 10years. In survivors, higher NA was associated with lower subjective health status. Type D was not associated with mortality after adjusting for continuous depression and anxiety in all approaches. CONCLUSIONS: Synergistically analyzed type D was not associated with 10-year all-cause mortality in PCI patients whereas dichotomous type D was. However, after adjustment for depression most of the findings had disappeared. Depression played an important role in this. Type D was not associated with 10-year subjective health status.

Peripheral arterial tonometry cannot detect patients at low risk of coronary artery disease.

BACKGROUND: Endothelial dysfunction precedes coronary artery disease (CAD) and can be measured by peripheral arterial tonometry (PAT). We examined the applicability of PAT to detect a low risk of CAD in a chest pain clinic. METHODS: In 93 patients, PAT was performed resulting in reactive hyperaemia (RHI) and augmentation (AIx) indices. Patients were risk classified according to HeartScore, Diamond and Forrester pretest probability (DF), exercise testing (X-ECG), and computed tomography calcium scoring (CCS) and angiography (CTA). Correlations, risk group differences and prediction of revascularisation within 1 year were calculated. RESULTS: RHI correlated with HeartScore (r = - 0.21, p = 0.05), AIx with DF (r = 0.26, p = 0.01). However, both were not significantly different between normal and ischaemic X-ECG groups. In addition RHI and AIx were similar between low risk as compared with intermediate-to-high risk, based on risk algorithms (RHI: 1.98 (0.67) vs 1.94 (0.78); AIx: 0.0 (21) vs 5.0 (25); p = NS), or CCS and CTA (RHI: 1.99 (0.58) vs 1.89 (0.82); AIx: - 2.0 (24) vs 4.0 (25); p = NS). Finally, RHI and AIx failed to predict revascularisation (RHI: OR 1.42, CI 0.65-3.1; AIx: OR 1.02, CI 0.98-1.05). CONCLUSIONS: PAT cannot detect a low risk of CAD, possibly because RHI and AIx versus X-ECG, CCS and CTA represent independent processes.

Predicting non-adherence in patients with familial hypercholesterolemia.

PURPOSE: Familial hypercholesterolemia (FH) is an autosomal dominant disorder associated with a high risk of premature coronary heart disease (CHD). CHD prevention consists of lifestyle changes combined with lifelong statin treatment. Good adherence to statins reduces the risk of events substantially. This study was designed to identify determinants of non-adherence and to develop a model predicting non-adherence. METHODS: A single centre survey included all consecutive heterozygous FH patients above age 18 years, who were treated by a specialized team in the outpatient clinic of a university hospital in The Netherlands between 2008 and 2009. In addition to clinical data, patients completed a questionnaire concerning medication adherence. RESULTS: We analyzed 321 patients (169 women) with a statin prescription whose mean age was 46 ± 14 years (± S.D.), and 13 % of the patients had CHD. The untreated mean total cholesterol was 10 ± 2.3 mmol/l. On average, patients were ten years on cholesterol-lowering therapy (range 1-29 years). Adherence was reported by 89 % of the patients (> 90 % adherence). Non-adherence was associated with younger age (OR = 10.64, 95 % CI 2.86-39.68), high total cholesterol level during prescription (OR = 4.29, 95 % CI 1.86-9.89) and a relatively low untreated total cholesterol level (OR = 3.94 95 % CI 1.39-11.14). A prediction model based on these three determinants had a c-index of 0.78 and a calibration with P = 0.88. CONCLUSION: Based on three independent determinants, a prediction model is developed to identify non-adherent FH patients. This model needs to be tested in future prospective research. It might be a first step in improving statin adherence in this extremely high risk group.

Hyperglycemia at admission and during hospital stay are independent risk factors for mortality in high risk cardiac patients admitted to an intensive cardiac care unit.

AIMS: Hyperglycemia is associated with increased mortality in cardiac patients. However, the predictive value of admission- and average glucose levels in patients admitted to an intensive cardiac care unit (ICCU) has not been described. METHODS: Observational study of patients admitted to the ICCU of a tertiary medical center in whom glucose levels were measured at and during admission. Over a 19-month period, 1713 patients were included. Mean age was 63±14 years, 1228 (72%) were male, 228 (17%) had known diabetes. Median (interquartile) glucose levels at admission were 7.9 (6.5-10.1) mmol/l; median glucose levels during ICCU admission (873 patients with three or more measurements) were 7.3 (6.7-8.3) mmol/l. Cox regression analysis was performed including the variables age, gender, admission diagnosis, length of stay, prior (cardio)vascular disease and diabetes. RESULTS: A 1 mmol/l increase in admission glucose level (above 9 mmol/l) was associated with a 10% (95% confidence interval (CI): 7 -13%) increased risk for all-cause mortality. A 1 mmol/l higher average glucose level (above 8 mmol/l) was an additional independent predictor of mortality (HR 1.11, 95% CI: 1.03 - 1.20). At 30 days, 16.8% (97/579) of the patients with an admission glucose level in the highest tertile (>9.8 mmol/L) had died vs 5.2% (59/1134) of those with a lower admission glucose level. CONCLUSION: In a high risk ICCU population, both high admission glucose levels as well as high average glucose levels during hospitalization were independently associated with increased mortality, even when accounting for other risk factors and parameters of disease severity.

Long-term outcome of the unrestricted use of everolimus-eluting stents compared to sirolimus-eluting stents and paclitaxel-eluting stents in diabetic patients: the Bern-Rotterdam diabetes cohort study.

BACKGROUND: Newer generation everolimus-eluting stents (EES) improve clinical outcome compared to early generation sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES). We investigated whether the advantage in safety and efficacy also holds among the high-risk population of diabetic patients during long-term follow-up. METHODS: Between 2002 and 2009, a total of 1963 consecutive diabetic patients treated with the unrestricted use of EES (n=804), SES (n=612) and PES (n=547) were followed throughout three years for the occurrence of cardiac events at two academic institutions. The primary end point was the occurrence of definite stent thrombosis. RESULTS: The primary outcome occurred in 1.0% of EES, 3.7% of SES and 3.8% of PES treated patients ([EES vs. SES] adjusted HR=0.58, 95% CI 0.39-0.88; [EES vs. PES] adjusted HR=0.29, 95% CI 0.13-0.67). Similarly, patients treated with EES had a lower risk of target-lesion revascularization (TLR) compared to patients treated with SES and PES ([EES vs. SES], 5.6% vs. 11.5%, adjusted HR=0.68, 95% CI: 0.55-0.83; [EES vs. PES], 5.6% vs. 11.3%, adjusted HR=0.51, 95% CI: 0.33-0.77). There were no differences in other safety end points, such as all-cause mortality, cardiac mortality, myocardial infarction (MI) and MACE. CONCLUSION: In diabetic patients, the unrestricted use of EES appears to be associated with improved outcomes, specifically a significant decrease in the need for TLR and ST compared to early generation SES and PES throughout 3-year follow-up.

OPTImal CArdiac REhabilitation (OPTICARE) following Acute Coronary Syndromes: Rationale and design of a randomised, controlled trial to investigate the benefits of expanded educational and behavioural intervention programs.

The majority of cardiac rehabilitation (CR) referrals consist of patients who have survived an acute coronary syndrome (ACS). Although major changes have been implemented in ACS treatment since the 1980s, which highly influenced mortality and morbidity, CR programs have barely changed and only few data are available on the optimal CR format in these patients. We postulated that standard CR programs followed by relatively brief maintenance programs and booster sessions, including behavioural techniques and focusing on incorporating lifestyle changes into daily life, can improve long-term adherence to lifestyle modifications. These strategies might result in improved (cardiac) mortality and morbidity in a cost-effective fashion. In the OPTImal CArdiac REhabilitation (OPTICARE) trial we will assess the effects of two advanced and extended CR programs that are designed to stimulate permanent adaption of a heart-healthy lifestyle, compared with current standard CR, in ACS patients. We will study the effects in terms of cardiac risk profile, levels of daily physical activity, quality of life and health care consumption.

First-line evaluation of coronary artery disease with coronary calcium scanning or exercise electrocardiography.

BACKGROUND: Although conventional (CAG) and computed tomography angiography (CTA) are reliable diagnostic modalities for exclusion of obstructive coronary artery disease (CAD), they are costly and with considerable exposure to radiation and contrast media. We compared the accuracy of coronary calcium scanning (CCS) and exercise electrocardiography (X-ECG) as less expensive and non-invasive means to rule out obstructive CAD. METHODS: In a rapid-access chest pain clinic, 791 consecutive patients with stable chest pain were planned to undergo X-ECG and dual-source CTA with CCS. According to the Duke pre-test probability of CAD patients were classified as low (<30%), intermediate (30-70%) or high risk (>70%). Angiographic obstructive CAD (>50% stenosis by CAG or CTA) was found in 210/791 (27%) patients, CAG overruling any CTA results. RESULTS: Obstructive CAD was found in 12/281 (4%) patients with no coronary calcium and in 73/319 (23%) with a normal X-ECG (p<0.001). No coronary calcium was associated with a substantially lower likelihood ratio compared to X-ECG; 0.11, 0.13 and 0.13 vs. 0.93, 0.55 and 0.46 in the low, intermediate and high risk group. In low risk patients a negative calcium score reduced the likelihood of obstructive CAD to less than 5%, removing the need for further diagnostic work-up. CCS could be performed in 754/756 (100%) patients, while X-ECG was diagnostic in 448/756 (59%) patients (p<0.001). CONCLUSIONS: In real-world patients with stable chest pain CCS is a reliable initial test to rule out obstructive CAD and can be performed in virtually all patients.

Health care utilisation after defibrillator implantation for primary prevention according to the guidelines in 2 Dutch academic medical centres.

BACKGROUND: The benefit of implantable defibrillators (ICDs) for primary prevention remains debated. We analysed the implications of prophylactic ICD implantation according to the guidelines in 2 tertiary hospitals, and made a healthcare utilisation inventory. METHODS: The cohort consisted of all consecutive patients with coronary artery disease (CAD) or dilated cardiomyopathy (DCM) receiving a primary prophylactic ICD in a contemporary setting (2004-2008). Follow-up was obtained from hospital databases, and mortality checked at the civil registry. Additional data came from questionnaires sent to general practitioners. RESULTS: There were no demographic differences between the 2 centres; one had proportionally more CAD patients and more resynchronisation therapy (CRT-D). The 587 patients were followed over a median of 28 months, and 50 (8.5%) patients died. Appropriate ICD intervention occurred in 123 patients (21%). There was a small difference in intervention-free survival between the 2 centres. The questionnaires revealed 338 hospital admissions in 52% of the responders. Device-related admissions happened on 68 occasions, in 49/276 responders. The most frequently reported ICD-related admission was due to shocks (20/49 patients); for other cardiac problems it was mainly heart failure (52/99). Additional outpatient visits occurred in 19%. CONCLUSION: Over a median follow-up of 2 years, one fifth of prophylactic ICD patients receive appropriate interventions. A substantial group undergoes readmission and additional visits. The high number of admissions points to a very ill population. Overall mortality was 8.5%. The 2 centres employed a similar procedure with respect to patient selection. One centre used more CRT-D, and observed more appropriate ICD interventions.

Encouraging survival rates in patients with acute myocardial infarction treated with an intra-aortic balloon pump.

OBJECTIVE: To evaluate a 30-day and long-term outcome of patients with acute myocardial infarction (AMI) treated with intra-aortic balloon pump (IABP) counterpulsation and to identify predictors of a 30-day and long-term all-cause mortality. METHODS: Retrospective cohort study of 437 consecutive AMI patients treated with IABP between January 1990 and June 2004. A Cox proportional hazards model was used to identify predictors of a 30-day and long-term all-cause mortality. RESULTS: Mean age of the study population was 61 ± 11 years, 80% of the patients were male, and 68% had cardiogenic shock. Survival until IABP removal after successful haemodynamic stabilisation was 78% (n = 341). Cumulative 30-day survival was 68%. Median follow-up was 2.9 years (range, 6 months to 15 years). In patients who survived until IABP removal, cumulative 1-, 5-, and 10-year survival was 75%, 61%, and 39%, respectively. Independent predictors of higher long-term mortality were prior cerebrovascular accident (hazard ratio (HR), 1.8; 95% confidence interval (CI), 1.0-3.4), need for antiarrhythmic drugs (HR, 2.3; 95% CI, 1.5-3.3), and need for renal replacement therapy (HR, 2.3; 95% CI, 1.2-4.3). Independent predictors of lower long-term mortality were primary percutaneous coronary intervention (PCI; HR, 0.6; 95% CI, 0.4-1.0), failed thrombolysis with rescue PCI (HR, 0.5; 95% CI, 0.3-0.9), and coronary artery bypass grafting (HR, 0.3; 95% CI, 0.1-0.5). CONCLUSIONS: Despite high in-hospital mortality in patients with AMI treated with IABP, a favourable number of patients survived in the long-term. These results underscore the value of aggressive haemodynamic support of patients throughout the acute phase of AMI.

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.

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.

Prognosis of patients with peripheral arterial disease.

The incidence of peripheral arterial disease (PAD) is on the increase and is associated with a major health concern in current practical care. The most common disease process underlying PAD is atherosclerosis. Atherosclerosis is a complex generalized disease affecting several arterial beds, including the peripheral and coronary circulation. Especially in patients with PAD, high incidences of coronary artery disease (CAD) have been observed, which may be asymptomatic or symptomatic. The prognosis of patients with PAD is related to the presence and extent of underlying CAD. In patients with PAD undergoing major vascular surgery, cardiac complications are the major cause of perioperative morbidity and mortality and indicate a high-risk for adverse long-term cardiac outcome. In order to improve outcome for PAD patients, assessment and aggressive therapy of atherosclerotic risk factors and usage of cardio-protective medications is recommended. Unfortunately, substantial differences in risk factor management and treatment and long-term outcome have been reported between PAD and CAD patients.

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.

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.