RESUMO
BACKGROUND: Experimental and clinical data indicate a major influence of diabetes on atherogenesis. We aimed to assess whether the effect of diabetes on long-term mortality in asymptomatic patient with carotid stenosis is contingent upon the degree of the carotid atherosclerotic burden. METHODS: 1065 patients with neurological asymptomatic carotid atherosclerosis as evaluated by duplex sonography were prospectively followed for cause-specific mortality. RESULTS: During a median of 11.8 years, a total of 549 deaths, including 362 cardiovascular deaths, were recorded. Diabetes and glycohemoglobin A1c (Hba1c) levels were significantly associated with mortality. Diabetes displayed an independent risk for all-cause (adjusted HR 1.62; 95% CI 1.35-1.94) and cardiovascular death (adjusted HR 1.75, 95% CI 1.40-2.19). The adjusted hazard ratio per increase of 1% of Hba1c levels was 1.21 (P < 0.01) for all-cause and 1.31 (P < 0.01) for cardiovascular mortality, respectively. Patients with diabetes mellitus and a higher degree of carotid stenosis and were at great risk of adverse outcome. Only 21% of the asymptomatic diabetic patients with carotid narrowing over 50% survived, whereas 62% of the patients without diabetes and with carotid atherosclerosis below 50% were still alive after 12-years of follow-up. The high risk for all-cause and cardiovascular death of these patients remained significant after adjustment for various established cardiovascular risk factors in multivariable regression analysis (adjusted hazard ratio 2.4, P < 0.001; compared to patients without diabetes and < 50% carotid atherosclerosis). CONCLUSION: Diabetic patients with carotid stenosis ≥ 50% are at exceptional high risk for all-cause and cardiovascular death. Thus, routinely ultrasound investigation of the carotid arteries might be a valuable prognostic tool for patients with diabetes mellitus.
Assuntos
Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/mortalidade , Vasos Coronários/diagnóstico por imagem , Diabetes Mellitus/mortalidade , Ultrassonografia Doppler Dupla , Idoso , Doenças Assintomáticas , Áustria/epidemiologia , Biomarcadores/sangue , Glicemia/metabolismo , Causas de Morte , Diabetes Mellitus/sangue , Diabetes Mellitus/diagnóstico , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Fatores de TempoRESUMO
BACKGROUND AND PURPOSE: Despite extensive research in the last decade, the role of serum amyloid A (SAA) in atherogenesis remains highly controversial. The aim of this study was therefore to assess whether SAA is associated with long-term mortality in patients with subclinical carotid artery disease. METHODS: One thousand sixty-five patients with neurological asymptomatic carotid atherosclerosis as evaluated by duplex sonography were prospectively followed for cause-specific mortality. RESULTS: During a median of 11.8 years, a total of 549 deaths, including 362 cardiovascular deaths, were recorded. Patients who died within the follow-up period had significantly higher baseline SAA serum levels compared to those who survived (12.9 vs 9.5 mg/dL; P < 0.001). In univariable Cox regression analysis, the risk of all-cause and cardiovascular mortality significantly increased in patients with elevated serum levels of SAA (crude hazard ratio for cardiovascular mortality per increase of 1 SD of SAA levels was 1.14, 95% CI 1.08-1.22], P < 0.0001). However, SAA lost its significance after adjusting for high-sensitivity C-reactive protein (hsCRP), suggesting that SAA might not be directly associated with atherogenesis, but rather be a mere reflection of the individual patient's inflammatory status. CONCLUSIONS: Serum amyloid A is not independently associated with (cardiovascular) mortality in patients with subclinical carotid atherosclerosis.
RESUMO
BACKGROUND: Randomized controlled trials have yielded conflicting results regarding the ability of beta-blockers to influence perioperative cardiovascular morbidity and mortality. Thus routine prescription of these drugs in unselected patients remains a controversial issue. OBJECTIVES: The objective of this review was to systematically analyse the effects of perioperatively administered beta-blockers for prevention of surgery-related mortality and morbidity in patients undergoing any type of surgery while under general anaesthesia. SEARCH METHODS: We identified trials by searching the following databases from the date of their inception until June 2013: MEDLINE, Embase , the Cochrane Central Register of Controlled Trials (CENTRAL), Biosis Previews, CAB Abstracts, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Derwent Drug File, Science Citation Index Expanded, Life Sciences Collection, Global Health and PASCAL. In addition, we searched online resources to identify grey literature. SELECTION CRITERIA: We included randomized controlled trials if participants were randomly assigned to a beta-blocker group or a control group (standard care or placebo). Surgery (any type) had to be performed with all or at least a significant proportion of participants under general anaesthesia. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data from all studies. In cases of disagreement, we reassessed the respective studies to reach consensus. We computed summary estimates in the absence of significant clinical heterogeneity. Risk ratios (RRs) were used for dichotomous outcomes, and mean differences (MDs) were used for continuous outcomes. We performed subgroup analyses for various potential effect modifiers. MAIN RESULTS: We included 88 randomized controlled trials with 19,161 participants. Six studies (7%) met the highest methodological quality criteria (studies with overall low risk of bias: adequate sequence generation, adequate allocation concealment, double/triple-blinded design with a placebo group, intention-to-treat analysis), whereas in the remaining trials, some form of bias was present or could not be definitively excluded (studies with overall unclear or high risk of bias). Outcomes were evaluated separately for cardiac and non-cardiac surgery.CARDIAC SURGERY (53 trials)We found no clear evidence of an effect of beta-blockers on the following outcomes.⢠All-cause mortality: RR 0.73, 95% CI 0.35 to 1.52, 3783 participants, moderate quality evidence.⢠Acute myocardial infarction (AMI): RR 1.04, 95% CI 0.71 to 1.51, 3553 participants, moderate quality evidence.⢠Myocardial ischaemia: RR 0.51, 95% CI 0.25 to 1.05, 166 participants, low quality evidence.⢠Cerebrovascular events: RR 1.52, 95% CI 0.58 to 4.02, 1400 participants, low quality evidence.⢠Hypotension: RR 1.54, 95% CI 0.67 to 3.51, 558 participants, low quality evidence.⢠Bradycardia: RR 1.61, 95% CI 0.97 to 2.66, 660 participants, low quality evidence.⢠Congestive heart failure: RR 0.22, 95% CI 0.04 to 1.34, 311 participants, low quality evidence.Beta-blockers significantly reduced the occurrence of the following endpoints.⢠Ventricular arrhythmias: RR 0.37, 95% CI 0.24 to 0.58, number needed to treat for an additional beneficial outcome (NNTB) 29, 2292 participants, moderate quality evidence.⢠Supraventricular arrhythmias: RR 0.44, 95% CI 0.36 to 0.53, NNTB five, 6420 participants, high quality evidence.⢠On average, beta-blockers reduced length of hospital stay by 0.54 days (95% CI -0.90 to -0.19, 2450 participants, low quality evidence).NON-CARDIAC SURGERY (35 trials)Beta-blockers significantly increased the occurrence of the following adverse events.⢠All-cause mortality: RR 1.25, 95% CI 1.00 to 1.57, 11,413 participants, low quality of evidence, number needed to treat for an additional harmful outcome (NNTH) 167.⢠Hypotension: RR 1.50, 95% CI 1.38 to 1.64, NNTH 16, 10,947 participants, high quality evidence.⢠Bradycardia: RR 2.23, 95% CI 1.48 to 3.36, NNTH 21, 11,033 participants, moderate quality evidence.We found a potential increase in the occurrence of the following outcomes with the use of beta-blockers.⢠Cerebrovascular events: RR 1.59, 95% CI 0.93 to 2.71, 9150 participants, low quality evidence.Whereas no clear evidence of an effect was found when all studies were analysed, restricting the meta-analysis to low risk of bias studies revealed a significant increase in cerebrovascular events with the use of beta-blockers: RR 2.09, 95% CI 1.14 to 3.82, NNTH 265, 8648 participants.Beta-blockers significantly reduced the occurrence of the following endpoints.⢠AMI: RR 0.73, 95% CI 0.61 to 0.87, NNTB 76, 10,958 participants, high quality evidence.⢠Myocardial ischaemia: RR 0.51, 95% CI 0.34 to 0.77, NNTB nine, 978 participants, moderate quality evidence.⢠Supraventricular arrhythmias: RR 0.73, 95% CI 0.57 to 0.94, NNTB 112, 8744 participants, high quality evidence.We found no clear evidence of an effect of beta-blockers on the following outcomes.⢠Ventricular arrhythmias: RR 0.68, 95% CI 0.31 to 1.49, 476 participants, moderate quality evidence.⢠Congestive heart failure: RR 1.18, 95% CI 0.94 to 1.48, 9173 participants, moderate quality evidence.⢠Length of hospital stay: mean difference -0.45 days, 95% CI -1.75 to 0.84, 551 participants, low quality evidence. AUTHORS' CONCLUSIONS: According to our findings, perioperative application of beta-blockers still plays a pivotal role in cardiac surgery, as they can substantially reduce the high burden of supraventricular and ventricular arrhythmias in the aftermath of surgery. Their influence on mortality, AMI, stroke, congestive heart failure, hypotension and bradycardia in this setting remains unclear.In non-cardiac surgery, evidence shows an association of beta-blockers with increased all-cause mortality. Data from low risk of bias trials further suggests an increase in stroke rate with the use of beta-blockers. As the quality of evidence is still low to moderate, more evidence is needed before a definitive conclusion can be drawn. The substantial reduction in supraventricular arrhythmias and AMI in this setting seems to be offset by the potential increase in mortality and stroke.
Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Doenças Cardiovasculares/prevenção & controle , Complicações Pós-Operatórias/prevenção & controle , Procedimentos Cirúrgicos Operatórios/efeitos adversos , Antagonistas Adrenérgicos beta/efeitos adversos , Anestesia Geral , Arritmias Cardíacas/mortalidade , Arritmias Cardíacas/prevenção & controle , Bradicardia/induzido quimicamente , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/mortalidade , Procedimentos Cirúrgicos Cardiovasculares/efeitos adversos , Procedimentos Cirúrgicos Cardiovasculares/mortalidade , Causas de Morte , Transtornos Cerebrovasculares/mortalidade , Transtornos Cerebrovasculares/prevenção & controle , Humanos , Hipotensão/induzido quimicamente , Hipotensão/mortalidade , Hipotensão/prevenção & controle , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/prevenção & controle , Isquemia Miocárdica/mortalidade , Isquemia Miocárdica/prevenção & controle , Complicações Pós-Operatórias/mortalidade , Ensaios Clínicos Controlados Aleatórios como Assunto , Procedimentos Cirúrgicos Operatórios/mortalidadeRESUMO
BACKGROUND AND PURPOSE: Inflammatory responses play a key role in atherogenesis. The aim of this study was to assess the prognostic value of hsCRP (high-sensitivity C-reactive protein) and to evaluate whether degree of carotid stenosis and serum levels of hsCRP jointly predict long-term mortality in asymptomatic patients with carotid atherosclerosis. METHODS: One thousand sixty-five patients with neurological asymptomatic carotid atherosclerosis as evaluated by duplex sonography were prospectively followed for cause-specific mortality. RESULTS: During a median of 11.81 years, a total of 549 deaths, including 362 cardiovascular deaths, were recorded. The risk of all-cause and cardiovascular mortality significantly increased in patients with elevated serum levels of hsCRP (the adjusted hazard ratio for cardiovascular mortality per increase of 1 mg/dL of hsCRP levels was 1.47; P<0.001). Patients with a high degree of carotid stenosis and increased hsCRP levels were particularly at risk of adverse outcome. Patients with carotid narrowing over 50% and hsCRP levels >0.29 mg/dL (=median) had nearly twice as high a risk of cardiovascular mortality compared with patients with carotid stenosis of <50% and hsCRP levels <0.29 mg/dL (adjusted hazard ratio 1.89; P<0.001). Improvement in risk stratification with combined assessment of carotid stenosis and hsCRP was confirmed by an improvement of the continuous net reclassification improvement with 18% for all-cause mortality and 15% for cardiovascular mortality compared with the degree of carotid stenosis alone (P<0.01). CONCLUSIONS: Measurement of hsCRP in combination with ultrasound investigations of the carotid arteries at a single time point provides additional prognostic information for patients with asymptomatic carotid atherosclerosis.
Assuntos
Proteína C-Reativa/análise , Doenças das Artérias Carótidas/sangue , Doenças das Artérias Carótidas/mortalidade , Estenose das Carótidas/sangue , Estenose das Carótidas/mortalidade , Idoso , Doenças das Artérias Carótidas/diagnóstico por imagem , Estenose das Carótidas/diagnóstico por imagem , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Red cell distribution width (RDW) is associated with morbidity and mortality in chronic cardiac disease. The aim of the present study was to investigate the role of RDW as a predictor of adverse outcome in patients with carotid atherosclerosis. MATERIALS AND METHODS: We prospectively studied 1065 of 1286 consecutive patients with neurological asymptomatic carotid artery stenosis as assessed by duplex Doppler sonography. The study end points were all-cause mortality and cardiovascular mortality respectively. RESULTS: During a median follow-up time of 6·2 years (interquartile range 5·9-6·6), corresponding to 5551 overall person-years, 275 patients (25·8%) died. Of them, 182 patients (66·2%) died due to cardiovascular causes. RDW was significantly associated with adverse outcome. In a continuous multivariate Cox regression analysis, the adjusted hazard ratio for each per cent increase in RDW was 1·39 (95% CI 1·27-1·53; P < 0·001) for all-cause and 1·43 (95% CI 1·28-1·60; P < 0·001) for cardiovascular mortality respectively. Kaplan-Meier estimates showed a gradual relationship between increasing quartiles of RDW and death (log rank P < 0·001). Adjusted hazard ratios for all-cause death ranged from 0·89 to 1·94 for the highest vs. the lowest quartile (P < 0·001 for trend) and for cardiovascular death from 1·08 to 2·34 for the highest vs. the lowest quartile (P < 0·001 for trend) respectively. CONCLUSIONS: Red cell distribution width was significantly and independently associated with all-cause and cardiovascular death in patients with asymptomatic carotid atherosclerosis.
Assuntos
Estenose das Carótidas/sangue , Índices de Eritrócitos , Fatores Etários , Idoso , Doenças Assintomáticas , Doenças das Artérias Carótidas/sangue , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/mortalidade , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/mortalidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Ultrassonografia Doppler DuplaRESUMO
BACKGROUND: Inflammatory responses are pivotal in the initiation and development of premature atherosclerotic lesions. Galectin-3 represents a valuable biomarker for both progression and destabilization of atherosclerotic lesions. This study aims to assess the involvement of galectin-3 in premature myocardial infarction. DESIGN: In this multicentre case-control study, we assessed circulating galectin-3 levels in 144 patients comprising 72 consecutive survivors of acute myocardial infarction (≤ 40 years) and 72 hospital controls frequency matched for age, gender and centre. RESULTS: Patients with acute myocardial infarction showed significantly higher galectin-3 levels as compared to controls in the acute phase of acute myocardial infarction (2552 ± 1992 vs. 1666 ± 829 pg/mL; P < 0·001) as well as in the stable phase 1 year after the index event (3692 ± 1774 vs. 1666 ± 829 pg/mL; P < 0·001). Circulating galectin-3 was significantly and independently associated with premature myocardial infarction in the logistic regression analysis (acute phase: adj. OR per 1-SD change 2·03, 95% CI 1·30-3·19; P = 0·002; stable phase: adj. OR of 6·54 (95% CI 2·56-16·68; P < 0·001). Moreover, we observed a significant correlation between circulating galectin-3 and leucocyte count (r = 0·35, P < 0·001), non-HDL cholesterol (r = 0·23, P = 0·014) and HDL cholesterol (r = -0·29, P = 0·002). CONCLUSION: We demonstrated that elevated levels of circulating galectin-3 are strongly associated with premature myocardial infarction. Galectin-3 might serve as link between dyslipidaemia as driving force of plaque formation with inflammation as initiator of plaque rupture in patients with premature acute myocardial infarction.
Assuntos
Dislipidemias/sangue , Galectina 3/sangue , Infarto do Miocárdio/sangue , Placa Aterosclerótica/sangue , Adulto , Biomarcadores , Proteínas Sanguíneas , Estudos de Casos e Controles , Colesterol/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Comorbidade , Diabetes Mellitus/epidemiologia , Dislipidemias/epidemiologia , Feminino , Galectinas , Humanos , Hipertensão/epidemiologia , Contagem de Leucócitos , Lipase/sangue , Modelos Logísticos , Masculino , Infarto do Miocárdio/epidemiologia , Fumar/epidemiologiaRESUMO
BACKGROUND: There is growing evidence that the predictive value of HDL cholesterol levels for cardiovascular risk stratification is limited in patients with coronary artery disease (CAD). HDL function seems to be a more sensitive surrogate of cardiovascular risk estimation than simple serum levels. Therefore, we aimed to assess whether impaired antioxidant HDL function is involved in the development of premature acute myocardial infarction (AMI). METHODS: In this multicentre case-control study, we compared the antioxidant function of HDL, measured by the HDL inflammatory index (HII), and HDL particle size in 184 patients comprising 92 patients with AMI at a very young age (≤40 years of age) and 92 age- and gender-matched controls. RESULTS: Antioxidant capacities of HDL were significantly impaired in the acute phase of AMI (HII of 1·50 [IQR 1·10-1·74] vs. 0·56 [IQR 0·41-0·86] in controls, P < 0·001 as well as in the chronic stable phase 1 year after the event (HII of 0·85 [IQR 0·72-1·03] vs. 0·56 [IQR 0·41-0·86], P < 0·001) compared to controls. Moreover, HDL function in the stable phase remained significantly associated with premature MI in adjusted logistic regression analysis with an OR of 2·24 per SD increase of HII (95% CI 1·28-3·91; P = 0·005). Analyses of HDL size revealed a significant correlation between all HDL subfractions and HDL function in controls, whereas this correlation was lost for large and intermediate HDL in AMI patients. CONCLUSION: Impaired antioxidant function of HDL is independently associated with the development of premature AMI. The maintenance of HDL function might evolve into a significant therapeutic target, especially in patients with premature CAD.
Assuntos
Antioxidantes/fisiologia , HDL-Colesterol/fisiologia , Doença da Artéria Coronariana/complicações , Infarto do Miocárdio/etiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antioxidantes/metabolismo , Estudos de Casos e Controles , HDL-Colesterol/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Adulto JovemRESUMO
BACKGROUND: Serum uric acid (SUA) has been discussed to be related to cardiovascular (CV) disease and outcome. We investigated whether levels of SUA predict long-term mortality in neurologically asymptomatic patients with carotid atherosclerotic disease. METHODS: We prospectively studied 959 consecutive patients with carotid atherosclerosis as evaluated by duplex Doppler sonography for all-cause and CV death, respectively. RESULTS: During a median follow-up time of 6.3 years (interquartile range [IQR], 5.4-7.1 years), 246 deaths (25.7%), including 160 CV deaths (16.7%), were recorded. Median baseline SUA levels were 5.9 mg/dL (IQR, 5.0-7.0 mg/dL). SUA was significantly associated with all-cause death and CV death. Adjusted hazard ratios (HRs) for an increase of 1 mg/dL of SUA levels were 1.12 (95% confidence interval [CI], 1.04-1.21; P = .003) and 1.20 (95% CI, 1.11-1.30; P < .001) for all-cause and CV death, respectively. Quartiles of SUA levels showed a significant association with CV mortality (log-rank P = .002). For CV death, adjusted HRs for quartiles of increasing SUA levels were 1.45 (95% CI, .87-2.43), 1.44 (95% CI, .85-2.46), and 2.26 (95% CI, 1.36-3.76; P < .01), compared with the lowest quartile, respectively. Patients with baseline carotid stenosis of more than 50% and/or increased levels of SUA (≥median) had an approximately 2-fold increase in risk of (CV) death, compared with patients with carotid narrowing of less than 50% and/or SUA levels less than the median (P < .001). CONCLUSIONS: Levels of SUA represent independent predictors for CV mortality in a cohort of patients with asymptomatic carotid atherosclerosis.
Assuntos
Aterosclerose/sangue , Aterosclerose/mortalidade , Doenças das Artérias Carótidas/sangue , Doenças das Artérias Carótidas/mortalidade , Ácido Úrico/sangue , Idoso , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de RiscoRESUMO
BACKGROUND AND OBJECTIVE: Platelets play a pivotal role in atherothrombosis and are potentially involved in the pathogenesis of atherosclerosis. We investigated whether mean platelet volume (MPV) predicts clinical outcome and progression of atherosclerosis in patients with asymptomatic carotid artery disease. METHODS: We studied 1006 of 1268 prospectively collected consecutive patients with asymptomatic carotid atherosclerosis who were evaluated by duplex sonography. Patients were followed up clinically for the occurrence of a major adverse cardiovascular event (MACE), a composite of myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft, stroke and death. RESULTS: During a median follow-up of 3.1 years (interquartile range, 2.5-3.5), a total of 316 (31.5%) MACEs were recorded. Increased levels of MPV were significantly associated with increased risk of the occurrence of MACEs (adjusted hazard ratio [HR] for an increase in one standard deviation [SD] of MPV 1.22, confidence interval [CI] 1.05-1.35, P < 0.01). Patients with MPV levels above 11.8 femtolitre (= fifth quintile) had a significantly higher event rate (41.3% vs. 29.3%, P < 0.001) with an adjusted HR for MACEs of 1.65 (95% CI 1.26-2.16, P < 0.001) compared with patients with MPV levels in the first to fourth quintile. No significant association was found between baseline MPV levels with either baseline degree or progression during a 6-month follow-up of carotid stenosis. CONCLUSION: Mean platelet volume was independently and significantly associated with adverse cardiovascular outcome in patients with asymptomatic carotid atherosclerosis.
Assuntos
Doenças Assintomáticas , Aterosclerose/sangue , Artéria Carótida Interna/diagnóstico por imagem , Estenose das Carótidas/sangue , Volume Plaquetário Médio , Idoso , Aterosclerose/complicações , Aterosclerose/mortalidade , Doenças das Artérias Carótidas/sangue , Doenças das Artérias Carótidas/complicações , Doenças das Artérias Carótidas/mortalidade , Estenose das Carótidas/complicações , Estenose das Carótidas/mortalidade , Estudos de Coortes , Ponte de Artéria Coronária/estatística & dados numéricos , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/complicações , Infarto do Miocárdio/mortalidade , Intervenção Coronária Percutânea/estatística & dados numéricos , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/mortalidade , UltrassonografiaRESUMO
BACKGROUND: Randomized controlled trials have yielded conflicting results regarding the ability of beta-blockers to influence perioperative cardiovascular morbidity and mortality. Thus routine prescription of these drugs in unselected patients remains a controversial issue. OBJECTIVES: The objective of this review was to systematically analyse the effects of perioperatively administered beta-blockers for prevention of surgery-related mortality and morbidity in patients undergoing any type of surgery while under general anaesthesia. SEARCH METHODS: We identified trials by searching the following databases from the date of their inception until June 2013: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), Biosis Previews, CAB Abstracts, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Derwent Drug File, Science Citation Index Expanded, Life Sciences Collection, Global Health and PASCAL. In addition, we searched online resources to identify grey literature. SELECTION CRITERIA: We included randomized controlled trials if participants were randomly assigned to a beta-blocker group or a control group (standard care or placebo). Surgery (any type) had to be performed with all or at least a significant proportion of participants under general anaesthesia. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data from all studies. In cases of disagreement, we reassessed the respective studies to reach consensus. We computed summary estimates in the absence of significant clinical heterogeneity. Risk ratios (RRs) were used for dichotomous outcomes, and mean differences (MDs) were used for continuous outcomes. We performed subgroup analyses for various potential effect modifiers. MAIN RESULTS: We included 89 randomized controlled trials with 19,211 participants. Six studies (7%) met the highest methodological quality criteria (studies with overall low risk of bias: adequate sequence generation, adequate allocation concealment, double/triple-blinded design with a placebo group, intention-to-treat analysis), whereas in the remaining trials, some form of bias was present or could not be definitively excluded (studies with overall unclear or high risk of bias). Outcomes were evaluated separately for cardiac and non-cardiac surgery. CARDIAC SURGERY (53 trials)We found no clear evidence of an effect of beta-blockers on the following outcomes.⢠All-cause mortality: RR 0.73, 95% CI 0.35 to 1.52, 3783 participants, moderate quality of evidence.⢠Acute myocardial infarction (AMI): RR 1.04, 95% CI 0.71 to 1.51, 3553 participants, moderate quality of evidence.⢠Myocardial ischaemia: RR 0.51, 95% CI 0.25 to 1.05, 166 participants, low quality of evidence.⢠Cerebrovascular events: RR 1.52, 95% CI 0.58 to 4.02, 1400 participants, low quality of evidence.⢠Hypotension: RR 1.54, 95% CI 0.67 to 3.51, 558 participants, low quality of evidence.⢠Bradycardia: RR 1.61, 95% CI 0.97 to 2.66, 660 participants, low quality of evidence.⢠Congestive heart failure: RR 0.22, 95% CI 0.04 to 1.34, 311 participants, low quality of evidence.Beta-blockers significantly reduced the occurrence of the following endpoints.⢠Ventricular arrhythmias: RR 0.37, 95% CI 0.24 to 0.58, number needed to treat for an additional beneficial outcome (NNTB) 29, 2292 participants, moderate quality of evidence.⢠Supraventricular arrhythmias: RR 0.44, 95% CI 0.36 to 0.53, NNTB six, 6420 participants, high quality of evidence.⢠On average, beta-blockers reduced length of hospital stay by 0.54 days (95% CI -0.90 to -0.19, 2450 participants, low quality of evidence). NON-CARDIAC SURGERY (36 trials)We found a potential increase in the occurrence of the following outcomes with the use of beta-blockers.⢠All-cause mortality: RR 1.24, 95% CI 0.99 to 1.54, 11,463 participants, low quality of evidence.Whereas no clear evidence of an effect was noted when all studies were analysed, restricting the meta-analysis to low risk of bias studies revealed a significant increase in all-cause mortality with the use of beta-blockers: RR 1.27, 95% CI 1.01 to 1.59, number needed to treat for an additional harmful outcome (NNTH) 189, 10,845 participants.⢠Cerebrovascular events: RR 1.59, 95% CI 0.93 to 2.71, 9150 participants, low quality of evidence.Whereas no clear evidence of an effect was found when all studies were analysed, restricting the meta-analysis to low risk of bias studies revealed a significant increase in cerebrovascular events with the use of beta-blockers: RR 2.09, 95% CI 1.14 to 3.82, NNTH 255, 8648 participants.Beta-blockers significantly reduced the occurrence of the following endpoints.⢠AMI: RR 0.73, 95% CI 0.61 to 0.87, NNTB 72, 10,958 participants, high quality of evidence.⢠Myocardial ischaemia: RR 0.43, 95% CI 0.27 to 0.70, NNTB seven, 1028 participants, moderate quality of evidence.⢠Supraventricular arrhythmias: RR 0.72, 95% CI 0.56 to 0.92, NNTB 111, 8794 participants, high quality of evidence.Beta-blockers significantly increased the occurrence of the following adverse events.⢠Hypotension: RR 1.50, 95% CI 1.38 to 1.64, NNTH 15, 10,947 participants, high quality of evidence.⢠Bradycardia: RR 2.24, 95% CI 1.49 to 3.35, NNTH 18, 11,083 participants, moderate quality of evidence.We found no clear evidence of an effect of beta-blockers on the following outcomes.⢠Ventricular arrhythmias: RR 0.64, 95% CI 0.30 to 1.33, 526 participants, moderate quality of evidence.⢠Congestive heart failure: RR 1.17, 95% CI 0.93 to 1.47, 9223 participants, moderate quality of evidence.⢠Length of hospital stay: mean difference -0.27 days, 95% CI -1.29 to 0.75, 601 participants, low quality of evidence. AUTHORS' CONCLUSIONS: According to our findings, perioperative application of beta-blockers still plays a pivotal role in cardiac surgery , as they can substantially reduce the high burden of supraventricular and ventricular arrhythmias in the aftermath of surgery. Their influence on mortality, AMI, stroke, congestive heart failure, hypotension and bradycardia in this setting remains unclear.In non-cardiac surgery, evidence from low risk of bias trials shows an increase in all-cause mortality and stroke with the use of beta-blockers. As the quality of evidence is still low to moderate, more evidence is needed before a definitive conclusion can be drawn. The substantial reduction in supraventricular arrhythmias and AMI in this setting seems to be offset by the potential increase in mortality and stroke.
Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Doenças Cardiovasculares/prevenção & controle , Complicações Pós-Operatórias/prevenção & controle , Procedimentos Cirúrgicos Operatórios/efeitos adversos , Antagonistas Adrenérgicos beta/efeitos adversos , Anestesia Geral , Arritmias Cardíacas/mortalidade , Arritmias Cardíacas/prevenção & controle , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/mortalidade , Procedimentos Cirúrgicos Cardiovasculares/efeitos adversos , Procedimentos Cirúrgicos Cardiovasculares/mortalidade , Causas de Morte , Transtornos Cerebrovasculares/mortalidade , Transtornos Cerebrovasculares/prevenção & controle , Humanos , Hipotensão/induzido quimicamente , Hipotensão/mortalidade , Hipotensão/prevenção & controle , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/prevenção & controle , Isquemia Miocárdica/mortalidade , Isquemia Miocárdica/prevenção & controle , Complicações Pós-Operatórias/mortalidade , Ensaios Clínicos Controlados Aleatórios como Assunto , Procedimentos Cirúrgicos Operatórios/mortalidadeRESUMO
Atherosclerosis is a chronic disease of the vascular wall driven by lipid accumulation and inflammation in the intimal layer of arteries, and its main complications, myocardial infarction and stroke, are the leading cause of mortality worldwide [1], [2]. Recent studies have identified Triggering receptor expressed on myeloid cells 2 (TREM2), a lipid-sensing receptor regulating myeloid cell functions [3], to be highly expressed in macrophage foam cells in experimental and human atherosclerosis [4]. However, the role of TREM2 in atherosclerosis is not fully known. Here, we show that hematopoietic or global TREM2 deficiency increased, whereas TREM2 agonism decreased necrotic core formation in early atherosclerosis. We demonstrate that TREM2 is essential for the efferocytosis capacities of macrophages, and to the survival of lipid-laden macrophages, indicating a crucial role of TREM2 in maintaining the balance between foam cell death and clearance of dead cells in atherosclerotic lesions, thereby controlling plaque necrosis.
RESUMO
BACKGROUND: Myeloperoxidase (MPO) is involved in a multitude of inflammatory processes involving oxidative modification of soluble components and cellular surfaces. Thus, MPO plays a key role in promoting atherosclerosis via oxidative stress by modification of both high- and low-density lipoprotein and production of other bioactive molecules. A polymorphism (MPO 463G>A, rs2333227) results in different expression rates of MPO. We aimed to assess whether MPO could be of clinical use as a risk marker for vascular disease in a high-risk group. MATERIAL AND METHODS: Plasma MPO levels of 406 patients suffering from peripheral arterial disease (PAD) were measured on an Abbott Architect i2000sr and grouped into patients with high (>115 ng/mL) and low (< 115 ng/mL) MPO levels. Genotyping of rs2333227 was performed on an ABI TaqMan 7900HT RT-PCR thermocycler. RESULTS: The relative risk of major adverse cardiovascular events (MACE) for patients with high plasma MPO is 1.2 (95%CI: 1.038-1.377, P < 0.05), initial event-free periods in male patients are significantly longer in patients with MPO <115 ng/mL (mean = 875 days compared with mean = 734 days, P < 0.05) In smokers, an increased hazard ratio was computed for patients with high MPO levels (HR = 3.127, 95%CI: 1.258-7.772, P < 0.05). Effects of MPO [-463A] allele on initial MACE-free intervals did not persist after multivariate analysis. CONCLUSIONS: Hence, we suggest consideration of plasma MPO for risk stratification of MACE in patients with PAD. In contrast, MPO-463G>A is not an independent risk factor for MACE in patients suffering from PAD.
Assuntos
Biomarcadores/sangue , Doença Arterial Periférica/enzimologia , Peroxidase/sangue , Idoso , Aterosclerose/enzimologia , Aterosclerose/genética , Doenças Cardiovasculares/enzimologia , Doenças Cardiovasculares/genética , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/genética , Peroxidase/genética , Polimorfismo de Nucleotídeo Único , Valor Preditivo dos Testes , Fatores de RiscoRESUMO
BACKGROUND: Humoral mediators of inflammation, in particular the complement system, have been described to play an important role in atherogenesis. Previously, we found a single-nucleotide polymorphism (SNP) in the complement 5 gene (C5 rs17611, A>G) independently associated with stroke. Up to now, the impact of C5 rs17611 on the progression of atherosclerosis and cardiovascular outcome in patients with asymptomatic atherosclerosis was unclear. MATERIALS AND METHODS: We investigated C5 rs17611 in a cohort of 1065 consecutive patients with asymptomatic carotid atherosclerosis. All patients were prospectively followed for the progression of carotid atherosclerosis and the development of a first major cardiovascular event (MACE), respectively. RESULTS: Three hundred and thirty-seven patients (31·6%) experienced a MACE during a median follow-up of 3·0 years. The homozygous GG genotype of the C5 rs17611 was significantly associated with adverse cardiovascular outcome (adjusted HR: 1·36 [95% CI, 1·07-1·73]; P = 0·01). After stratification for sex, C5 rs17611 CC was found to be an independent risk factor for MACE in men (HR 1·50 [95% CI, 1·12-1·83]). No association of C5 rs17611 with progression of carotid stenosis, observed in 93 (8·7%) patients, was detectable. Performance of ELISA indicated a significant association of the C5 rs17611 variant with C5a plasma levels. CONCLUSION: The C5 rs17611 GG genotype is associated with increased C5a plasma levels and represents a risk factor for adverse cardiovascular outcome in male patients with carotid atherosclerosis.
Assuntos
Aterosclerose/genética , Complemento C5/genética , Infarto do Miocárdio/genética , Polimorfismo de Nucleotídeo Único , Idoso , Doenças Cardiovasculares/genética , Estudos de Coortes , Ensaio de Imunoadsorção Enzimática , Feminino , Seguimentos , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Fatores SexuaisRESUMO
BACKGROUND: Low-density lipoprotein (LDL) cholesterol lowering has been established as one of the principal targets in preventive cardiology. Recently, assessment of LDL particle size and number as well as other lipid moieties has been presented as a more reliable method to quantify atherogenicity of the lipoprotein fractions. Thus, it was our aim to assess the influence of different lipoprotein fractions on premature myocardial infarction (≤ 40 years of age). METHODS AND RESULTS: We enrolled 302 patients into our multicentre case-control study, including 102 patients with myocardial infarction and 200 age-, gender- and centre-matched controls. The LDL and HDL Lipoprint System were used for lipid subfraction quantification. The lipid risk factors most strongly associated with premature acute myocardial infarction (AMI) in the adjusted model were non-HDL C (OR 5·02, 95% CI 2·75-9·15, P-value = 0·001), LDL-C (OR 4·35, 95% CI 2·5-7·57, P-value = 0·001), VLDL-C (OR 3·66, 95% CI 2·14-6·28, P-value = 0·001), large IDL-C (OR 3·15, 95% CI 1·94-5·12, P-value = 0·001), large LDL-C (OR 3·67, 95% CI 2·19-6·15, P-value = 0·001) and intermediate LDL-C (OR 1·96, 95% CI 1·25-3·06, P-value = 0·003). In contrast, small dense LDL was not significantly associated with premature myocardial infarction. CONCLUSION: Non-HDL cholesterol is most strongly associated with premature coronary artery disease and could serve as preferred risk predictor and therapeutic target in this young patient population (≤ 40 years). Besides, VLDL, LDL-C, large LDL, intermediate LDL and large IDL were significantly associated with premature myocardial infarction. Furthermore, our data suggest that risk prediction using small dense LDL particles might not be useful in young AMI survivors.
Assuntos
HDL-Colesterol/sangue , LDL-Colesterol/sangue , Infarto do Miocárdio/sangue , Adolescente , Adulto , Fatores Etários , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Estudos Prospectivos , Fatores de Risco , Adulto JovemRESUMO
BACKGROUND AND PURPOSE: Atherosclerosis is a chronic inflammatory disease. Ongoing inflammation is associated with elevated levels of beta 2 microglobulin (B2M). We investigated B2M levels in a large cohort of patients with carotid atherosclerosis for the occurrence of major adverse cardiovascular events. METHODS: One thousand five of 1286 consecutive, neurologically asymptomatic patients with carotid atherosclerosis were followed for a median of 3 years (interquartile range, 2.5 to 3.5) for the occurrence of major adverse cardiovascular events, a composite of myocardial infarction, percutaneous coronary intervention, coronary bypass graft, stroke, and death. RESULTS: We recorded 359 major cardiovascular events in 271 (27%) patients. B2M was significantly associated with the occurrence of major adverse cardiovascular events. With increasing quartiles of B2M, the adjusted hazard ratios were 1.19 (95% CI, 0.81 to 1.73), 1.51 (95% CI, 1.05 to 2.18), and 1.88 (95% CI, 1.26 to 2.79) compared with the lowest quartile, respectively (P<0.001). Adjusted hazard ratios for the occurrence of death, myocardial infarction, and stroke for increasing quartiles of B2M were 1.25 (95% CI, 0.92 to 1.70), 1.52 (95% CI, 1.12 to 2.06), and 1.62 (95% CI, 1.16 to 2.67) compared with the lowest quartile, respectively (P<0.001). Through statistical estimation of improvement in risk stratification, addition of B2M to baseline risk factors improved the risk stratification for major cardiovascular events, at least as much as high-sensitivity C-reactive protein or even better. CONCLUSIONS: B2M was independently and significantly associated with adverse cardiovascular outcome in patients with prevalent asymptomatic carotid atherosclerosis.
Assuntos
Doenças Cardiovasculares/complicações , Doenças das Artérias Carótidas/complicações , Placa Aterosclerótica/complicações , Microglobulina beta-2/biossíntese , Idoso , Biomarcadores/metabolismo , Doenças Cardiovasculares/diagnóstico , Doenças das Artérias Carótidas/sangue , Estudos de Coortes , Feminino , Humanos , Hipertensão , Inflamação , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/metabolismo , Placa Aterosclerótica/sangue , Modelos de Riscos ProporcionaisRESUMO
BACKGROUND AND PURPOSE: Markers of apoptosis are associated with cardiovascular disease. The soluble apoptosis-stimulating fragment (sFAS) was found to be a predictor for outcome in patients with heart failure, but its importance in patients with atherosclerotic disease has not been fully understood as yet. The aim of the present study was to investigate the impact of sFAS on all-cause and cardiovascular mortality in patients with atherosclerosis in the carotid arteries. METHODS: We studied 981 of 1286 consecutive patients with neurological asymptomatic carotid atherosclerosis as evaluated by duplex Doppler sonography. Patients were prospectively followed for long-term all-cause and cardiovascular mortality. RESULTS: During a median follow-up of 6.2 years (interquartile range, 5.9 to 6.6 years), a total of 250 deaths (25.5%), including 165 (66%) cardiovascular deaths, were recorded. The risk for all-cause and for cardiovascular mortality, respectively, increased significantly with sFAS concentrations (P<0.001). The hazard ratio for all-cause death was elevated by 2.3-fold (P<0.001) and for cardiovascular death by 2.4-fold (P<0.001) in patients within the highest quintile of sFAS compared with patients within the lowest quintile, respectively. Results remained significant after adjustment for potential confounders and established cardiovascular risk factors, including high-sensitivity C-reactive protein. Patients with high sFAS but low high-sensitivity C-reactive protein had a comparable survival rate with those with elevated high-sensitivity C-reactive protein only (P=0.50). CONCLUSIONS: Markers of apoptosis, as measured by sFAS, were found to be independent risk predictors for death in patients with atherosclerotic disease in the carotid arteries.
Assuntos
Doenças das Artérias Carótidas/sangue , Doenças das Artérias Carótidas/mortalidade , Receptor fas/sangue , Idoso , Biomarcadores/sangue , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Taxa de Sobrevida , Fatores de TempoRESUMO
BACKGROUND: A novel self-expanding drug-eluting stent was designed to slowly release everolimus to prevent restenosis following peripheral arterial intervention. The purpose of the first-in-human Superficial Femoral Artery Treatment with Drug-Eluting Stents (STRIDES) trial was to evaluate the safety and efficacy of this device for the treatment of symptomatic superficial femoral and proximal popliteal arterial occlusive disease. METHODS AND RESULTS: One hundred four patients were enrolled at 11 European investigative centers in a prospective, nonrandomized, single-arm trial. The patients had severe symptomatic vascular disease, including a significant proportion of patients with critical limb ischemia (17%), diabetes (39%), and single-vessel outflow (26%). The mean lesion length was 9.0 ± 4.3 cm. Ninety-nine percent of patients were available for 12-month follow-up, including duplex imaging in 90% and arteriography in 83%. Clinical improvement, defined as a sustained decrease in Rutherford-Becker clinical category, was achieved in 80% of patients. Primary patency (freedom from ≥50% in-stent restenosis) was 94 ± 2.3% and 68 ± 4.6% at 6 and 12 months, respectively. Plain radiographic examination of 122 implanted devices at 12 months revealed no evidence for stent fracture. CONCLUSIONS: The everolimus-eluting self-expanding nitinol stent can be successfully implanted in patients with severe peripheral arterial disease with favorable outcomes and clinical improvements observed in the majority of patients.
Assuntos
Angioplastia/instrumentação , Fármacos Cardiovasculares/administração & dosagem , Stents Farmacológicos , Artéria Femoral , Doença Arterial Periférica/terapia , Artéria Poplítea , Sirolimo/análogos & derivados , Idoso , Angioplastia/efeitos adversos , Índice Tornozelo-Braço , Constrição Patológica , Europa (Continente) , Everolimo , Feminino , Artéria Femoral/diagnóstico por imagem , Artéria Femoral/fisiopatologia , Humanos , Estimativa de Kaplan-Meier , Salvamento de Membro , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/fisiopatologia , Artéria Poplítea/diagnóstico por imagem , Artéria Poplítea/fisiopatologia , Estudos Prospectivos , Desenho de Prótese , Radiografia , Índice de Gravidade de Doença , Sirolimo/administração & dosagem , Fatores de Tempo , Resultado do Tratamento , Ultrassonografia Doppler Dupla , Grau de Desobstrução VascularRESUMO
BACKGROUND: A single-nucleotide polymorphism (SNP) in the palladin gene (PALLD, rs7439293) has recently been reported to be associated with coronary heart disease (CHD) in two case-control studies as well as in a large population-based cohort (Atherosclerosis Risk in Communities study, ARIC). Its clinical relevance, however, has not been evaluated prospectively. We investigated whether the risk allele (A) of PALLD rs7439293 (G>A) is associated with the occurrence of future major cardiovascular events (MACE) in a cohort of patients with prevalent carotid atherosclerosis. MATERIALS AND METHODS: A total of 1283 consecutive patients with neurologically asymptomatic carotid atherosclerosis were included in the study and prospectively followed for a median of 3·5 years (interquartile range 3-4 years). We analysed whether the risk allele is associated with progression of carotid atherosclerosis after a 6-9-month period as measured by duplex Doppler sonography. Patients were then followed for the occurrence of a first MACE, a composite of myocardial infarction, stroke, coronary revascularization and death. RESULTS: After a median of 7·5 months (interquartile range 6-9 months), progression of carotid stenosis was observed in 103 (8·1%) patients. Cardiovascular events occurred in 337 (30%) patients after a median follow-up of 3·5 years. The risk allele of PALLD was neither associated with progressive carotid atherosclerosis (P = 0·21) nor with MACE (P = 0·58). Adjusted hazard ratios for a first MACE in heterozygous and homozygous carriers were 0·83 (95% CI 0·58-1·18) and 0·94 (95% CI 0·65-1·35) compared to wild type, respectively. CONCLUSIONS: The A-allele of PALLD rs7439293 was not associated with progressive carotid atherosclerosis as measured by duplex Doppler sonography nor did it represent a risk factor for adverse cardiovascular outcome among patients with prevalent carotid atherosclerosis.
Assuntos
Aterosclerose/complicações , Doenças das Artérias Carótidas/genética , Doença das Coronárias/genética , Proteínas do Citoesqueleto/genética , Fosfoproteínas/genética , Polimorfismo de Nucleotídeo Único/genética , Idoso , Alelos , Aterosclerose/genética , Áustria , Estudos de Coortes , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , População BrancaRESUMO
OBJECTIVE: The aim of this study was to assess whether visualisation of in-stent changes can be improved with high-resolution, steady-state, blood pool contrast-enhanced MR angiography compared with first-pass MR angiography. Intra-arterial digital subtraction angiography (DSA) served as the reference standard. METHODS: Twenty patients after stent placement in the superficial femoral artery (SFA) underwent MRA prior to reintervention. MRA of the SFA includes first-pass MRA as well as 3D high-resolution MRA in the steady state (SS-MRA) after injection of Gadofosveset trisodium. Sensitivity and specificity values for the detection of significant in-stent lesions by means of SS-MRA were calculated at the proximal, middle and distal stent segments in comparison to DSA. Kappa statistics were used to determine agreement between the two techniques. RESULTS: Sensitivity and specificity values for the detection of significant stenosis with SS-MRA reached 95% in the proximal, 100% in the middle and 100% in the distal stent segment. Kappa coefficients between SS-MRA and DSA were 0.789, 0.797 and 0.859 for the proximal, middle and distal segments, whereas the Kappa coefficients for FP-MRA were 0,211, 0,200 and 0,594 in these segments, respectively. CONCLUSION: Detection of in stent stenosis is significantly improved using SS MRA, in comparison to state-of-the-art FP-MRA.
Assuntos
Angiografia por Ressonância Magnética/métodos , Doença Arterial Periférica/patologia , Idoso , Idoso de 80 Anos ou mais , Constrição Patológica , Meios de Contraste/farmacologia , Feminino , Gadolínio/farmacologia , Imagem do Acúmulo Cardíaco de Comporta/métodos , Humanos , Imageamento Tridimensional/métodos , Masculino , Pessoa de Meia-Idade , Compostos Organometálicos/farmacologia , Sensibilidade e Especificidade , StentsRESUMO
The second generation BCR/ABL kinase inhibitor nilotinib is increasingly used for the treatment of imatinib-resistant chronic myeloid leukemia (CML). So far, nilotinib is considered a well-tolerated drug with little if any side effects, although an increase in the fasting glucose level has been reported. We examined a series of 24 consecutive CML patients treated with nilotinib in our center for the development of non-hematologic adverse events. Three of these 24 CML patients developed a rapidly progressive peripheral arterial occlusive disease (PAOD) during treatment with nilotinib. In all three cases, PAOD required repeated angioplasty and/or multiple surgeries within a few months. No PAOD was known before nilotinib-therapy in these patients, although all three had received imatinib. In two patients, pre-existing risk factors predisposing for PAOD were known, and one of them had developed diabetes mellitus during nilotinib. In the other 21 patients treated with nilotinib in our center, one less severe PAOD, one myocardial infarction, one spinal infarction, one subdural hematoma, and one sudden death of unknown etiology were recorded. In summary, treatment with nilotinib may be associated with an increased risk of vascular adverse events, including PAOD development. In a subgroup of patients, these events are severe or even life-threatening. Although the exact mechanisms remain unknown, we recommend screening for pre-existing PAOD and for vascular risk factors such as diabetes mellitus in all patients before starting nilotinib and in the follow up during nilotinib-therapy.