RESUMO
BACKGROUND: The risk of sudden death has changed over time among patients with symptomatic heart failure and reduced ejection fraction with the sequential introduction of medications including angiotensin-converting-enzyme inhibitors, angiotensin-receptor blockers, beta-blockers, and mineralocorticoid-receptor antagonists. We sought to examine this trend in detail. METHODS: We analyzed data from 40,195 patients who had heart failure with reduced ejection fraction and were enrolled in any of 12 clinical trials spanning the period from 1995 through 2014. Patients who had an implantable cardioverter-defibrillator at the time of trial enrollment were excluded. Weighted multivariable regression was used to examine trends in rates of sudden death over time. Adjusted hazard ratios for sudden death in each trial group were calculated with the use of Cox regression models. The cumulative incidence rates of sudden death were assessed at different time points after randomization and according to the length of time between the diagnosis of heart failure and randomization. RESULTS: Sudden death was reported in 3583 patients. Such patients were older and were more often male, with an ischemic cause of heart failure and worse cardiac function, than those in whom sudden death did not occur. There was a 44% decline in the rate of sudden death across the trials (P=0.03). The cumulative incidence of sudden death at 90 days after randomization was 2.4% in the earliest trial and 1.0% in the most recent trial. The rate of sudden death was not higher among patients with a recent diagnosis of heart failure than among those with a longer-standing diagnosis. CONCLUSIONS: Rates of sudden death declined substantially over time among ambulatory patients with heart failure with reduced ejection fraction who were enrolled in clinical trials, a finding that is consistent with a cumulative benefit of evidence-based medications on this cause of death. (Funded by the China Scholarship Council and the University of Glasgow.).
Assuntos
Morte Súbita/epidemiologia , Insuficiência Cardíaca/mortalidade , Adulto , Fatores Etários , Idoso , Causas de Morte , Fatores de Confusão Epidemiológicos , Feminino , Seguimentos , Insuficiência Cardíaca/fisiopatologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Análise de Regressão , Risco , Fatores Sexuais , Volume SistólicoRESUMO
Aims: Recent guidelines recommend that patients with heart failure and left ventricular ejection fraction (LVEF) 40-49% should be managed similar to LVEF ≥ 50%. We investigated the effect of beta-blockers according to LVEF in double-blind, randomized, placebo-controlled trials. Methods and results: Individual patient data meta-analysis of 11 trials, stratified by baseline LVEF and heart rhythm (Clinicaltrials.gov: NCT0083244; PROSPERO: CRD42014010012). Primary outcomes were all-cause mortality and cardiovascular death over 1.3 years median follow-up, with an intention-to-treat analysis. For 14 262 patients in sinus rhythm, median LVEF was 27% (interquartile range 21-33%), including 575 patients with LVEF 40-49% and 244 ≥ 50%. Beta-blockers reduced all-cause and cardiovascular mortality compared to placebo in sinus rhythm, an effect that was consistent across LVEF strata, except for those in the small subgroup with LVEF ≥ 50%. For LVEF 40-49%, death occurred in 21/292 [7.2%] randomized to beta-blockers compared to 35/283 [12.4%] with placebo; adjusted hazard ratio (HR) 0.59 [95% confidence interval (CI) 0.34-1.03]. Cardiovascular death occurred in 13/292 [4.5%] with beta-blockers and 26/283 [9.2%] with placebo; adjusted HR 0.48 (95% CI 0.24-0.97). Over a median of 1.0 years following randomization (n = 4601), LVEF increased with beta-blockers in all groups in sinus rhythm except LVEF ≥50%. For patients in atrial fibrillation at baseline (n = 3050), beta-blockers increased LVEF when < 50% at baseline, but did not improve prognosis. Conclusion: Beta-blockers improve LVEF and prognosis for patients with heart failure in sinus rhythm with a reduced LVEF. The data are most robust for LVEF < 40%, but similar benefit was observed in the subgroup of patients with LVEF 40-49%.
Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Insuficiência Cardíaca , Volume Sistólico/fisiologia , Idoso , Fibrilação Atrial , Método Duplo-Cego , Feminino , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Placebos , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: Small studies have suggested that high-intensity interval training (HIIT) is superior to moderate continuous training (MCT) in reversing cardiac remodeling and increasing aerobic capacity in patients with heart failure with reduced ejection fraction. The present multicenter trial compared 12 weeks of supervised interventions of HIIT, MCT, or a recommendation of regular exercise (RRE). METHODS: Two hundred sixty-one patients with left ventricular ejection fraction ≤35% and New York Heart Association class II to III were randomly assigned to HIIT at 90% to 95% of maximal heart rate, MCT at 60% to 70% of maximal heart rate, or RRE. Thereafter, patients were encouraged to continue exercising on their own. Clinical assessments were performed at baseline, after the intervention, and at follow-up after 52 weeks. Primary end point was a between-group comparison of change in left ventricular end-diastolic diameter from baseline to 12 weeks. RESULTS: Groups did not differ in age (median, 60 years), sex (19% women), ischemic pathogenesis (59%), or medication. Change in left ventricular end-diastolic diameter from baseline to 12 weeks was not different between HIIT and MCT (P=0.45); left ventricular end-diastolic diameter changes compared with RRE were -2.8 mm (-5.2 to -0.4 mm; P=0.02) in HIIT and -1.2 mm (-3.6 to 1.2 mm; P=0.34) in MCT. There was also no difference between HIIT and MCT in peak oxygen uptake (P=0.70), but both were superior to RRE. However, none of these changes was maintained at follow-up after 52 weeks. Serious adverse events were not statistically different during supervised intervention or at follow-up at 52 weeks (HIIT, 39%; MCT, 25%; RRE, 34%; P=0.16). Training records showed that 51% of patients exercised below prescribed target during supervised HIIT and 80% above target in MCT. CONCLUSIONS: HIIT was not superior to MCT in changing left ventricular remodeling or aerobic capacity, and its feasibility remains unresolved in patients with heart failure. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00917046.
Assuntos
Insuficiência Cardíaca/diagnóstico , Treinamento Intervalado de Alta Intensidade , Volume Sistólico/fisiologia , Idoso , Ecocardiografia , Teste de Esforço , Tolerância ao Exercício , Feminino , Seguimentos , Insuficiência Cardíaca/fisiopatologia , Frequência Cardíaca/fisiologia , Ventrículos do Coração/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Remodelação VentricularRESUMO
CONTEXT AND OBJECTIVE: To evaluate if YKL-40 can provide prognostic information in patients with ischemic heart failure (HF) and identify patients who may benefit from statin therapy. MATERIALS AND METHODS: The association between serum YKL-40 and predefined outcome was evaluated in 1344 HF patients assigned to rosuvastatin or placebo. RESULTS: YKL-40 was not associated with outcome in adjusted analysis. In YKL-40 tertile 1, an effect on the primary outcome (HR 0.50, p = 0.006) and CV death (HR 0.54, p = 0.040) was seen by rosuvastatin in adjusted analysis. CONCLUSIONS: A beneficial modification of outcome was observed with statin therapy in patients with low YKL-40 levels.
Assuntos
Proteína 1 Semelhante à Quitinase-3/sangue , Insuficiência Cardíaca/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Rosuvastatina Cálcica/uso terapêutico , Idoso , Doença Crônica , Feminino , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/diagnóstico , Humanos , Masculino , Valor Preditivo dos Testes , Prognóstico , Resultado do TratamentoRESUMO
BACKGROUND: International geographic differences in outcomes may exist for clinical trials of heart failure and reduced ejection fraction (HF-REF), but there are few data for those with preserved ejection fraction (HF-PEF). METHODS AND RESULTS: We analyzed outcomes by international geographic region in the Irbesartan in Heart Failure with Preserved systolic function trial (I-Preserve), the Candesartan in Heart failure Assessment of Reduction in Mortality and morbidity (CHARM)-Preserved trial, the CHARM-Alternative and CHARM-Added HF-REF trials, and the Controlled Rosuvastatin Multinational Trial in HF-REF (CORONA). Crude rates of heart failure hospitalization varied by geographic region, and more so for HF-PEF than for HF-REF. Rates in patients with HF-PEF were highest in the United States/Canada (HF hospitalization rate 7.6 per 100 patient-years in I-Preserve; 8.8 in CHARM-Preserved), intermediate in Western Europe (4.8/100 and 4.7/100), and lowest in Eastern Europe/Russia (3.3/100 and 2.8/100). The difference between the United States/Canada versus Eastern Europe/Russia persisted after adjustment for key prognostic variables: adjusted hazard ratios 1.34 (95% confidence interval, 1.01-1.74; P=0.04) in I-Preserve and 1.85 (95% confidence interval, 1.17-2.91; P=0.01) in CHARM-Preserved. In HF-REF, rates of HF hospitalization were slightly lower in Western Europe compared with other regions. For both HF-REF and HF-PEF, there were few regional differences in rates of all-cause or cardiovascular mortality. CONCLUSIONS: The differences in event rates observed suggest there is international geographic variation in 1 or more of the definition and diagnosis of HF-PEF, the risk profile of patients enrolled, and the threshold for hospitalization, which has implications for the conduct of future global trials.
Assuntos
Benzimidazóis/uso terapêutico , Compostos de Bifenilo/uso terapêutico , Fluorbenzenos/uso terapêutico , Geografia , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/fisiopatologia , Pirimidinas/uso terapêutico , Volume Sistólico/fisiologia , Sulfonamidas/uso terapêutico , Tetrazóis/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Canadá/epidemiologia , Europa (Continente)/epidemiologia , Feminino , Insuficiência Cardíaca/epidemiologia , Hospitalização/estatística & dados numéricos , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Irbesartana , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Rosuvastatina Cálcica , Federação Russa/epidemiologia , Resultado do Tratamento , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: Our aim was to describe the incidence and predictors of stroke in patients who have heart failure without atrial fibrillation (AF). METHODS AND RESULTS: We pooled 2 contemporary heart failure trials, the Controlled Rosuvastatin in Multinational Trial Heart Failure (CORONA) and the Gruppo Italiano per lo Studio della Sopravvivenza nell'Insufficienza cardiaca-Heart Failure trial (GISSI-HF). Of the 9585 total patients, 6054 did not have AF. Stroke occurred in 165 patients (4.7%) with AF and in 206 patients (3.4%) without AF (rates 16.8/1000 patient-years and 11.1/1000 patient-years, respectively). Using Cox proportional-hazards models, we identified the following independent predictors of stroke in patients without AF (ranked by χ(2) value): age (hazard ratio, 1.34; 95% confidence interval, 1.18-1.63 per 10 years), New York Heart Association class (1.60, 1.21-2.12 class III/IV versus II), diabetes mellitus treated with insulin (1.87, 1.22-2.88), body mass index (0.74, 0.60-0.91 per 5 kg/m(2) up to 30), and previous stroke (1.81, 1.19-2.74). N-terminal pro B-type natriuretic peptide (available in 2632 patients) was also an independent predictor of stroke (hazard ratio, 1.31; 1.11-1.57 per log unit) when added to this model. With the use of a risk score formulated from these predictors, we found that patients in the upper third of risk had a rate of stroke that approximated the risk in patients with AF. CONCLUSIONS: A small number of demographic and clinical variables identified a subset of patients who have heart failure without AF at a high risk of stroke.
Assuntos
Ácidos Graxos Ômega-3/uso terapêutico , Fluorbenzenos/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Pirimidinas/uso terapêutico , Acidente Vascular Cerebral/etiologia , Sulfonamidas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/etiologia , Benzimidazóis/uso terapêutico , Biomarcadores/sangue , Compostos de Bifenilo , Fármacos Cardiovasculares/uso terapêutico , Diabetes Mellitus Tipo 1/complicações , Feminino , Seguimentos , Insuficiência Cardíaca/complicações , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Rosuvastatina Cálcica , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/prevenção & controle , Volume Sistólico , Tetrazóis/uso terapêuticoRESUMO
BACKGROUND: The extracellular matrix (ECM) plays an important role in left ventricular remodeling and progression of heart failure (HF). Biglycan and mimecan are ECM proteins that are abundantly expressed in cardiac tissue but have not been evaluated as prognostic markers in HF. We investigated their interaction with statin treatment and association with adverse outcome in chronic HF. METHODS AND RESULTS: The association between serum levels of biglycan and mimecan and the primary end point (cardiovascular [CV] death, nonfatal myocardial infarction, nonfatal stroke), all-cause mortality, CV death, the composite of all-cause mortality/hospitalization for worsening of HF, and the coronary end point was evaluated in 1,390 patients >60 years of age with ischemic systolic HF in the Controlled Rosuvastatin Multinational Trial in HF (CORONA) population, randomly assigned to 10 mg rosuvastatin or placebo. Serum biglycan and mimecan added no prognostic information beyond conventional risk factors, including N-terminal pro-B-type natriuretic peptide. However, statin treatment improved all outcomes except CV death in patients with low biglycan levels (ie, lower tertile), even after full multivariable adjustment. CONCLUSIONS: Although circulating levels of mimecan and biglycan were of limited predictive value in patients with chronic HF, circulating biglycan could be a useful marker for targeting statin therapy in patients with HF.
Assuntos
Biglicano/sangue , Matriz Extracelular/metabolismo , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Feminino , Seguimentos , Humanos , Masculino , Valor Preditivo dos Testes , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoRESUMO
OBJECTIVES: Increased circulating endostatin levels have been demonstrated in progressive cardiovascular (CV) and renal disorders. We investigated the predictive value of endostatin in patients with chronic heart failure (HF) and the association between endostatin and renal function. METHODS: The interaction between serum endostatin, estimated glomerular filtration rate (eGFR) and predefined endpoints, including the primary endpoint (CV death, nonfatal myocardial infarction, nonfatal stroke; n = 397), all-cause mortality (n = 410), CV death (n = 335) or the coronary endpoint (n = 317), was evaluated in 1,390 patients >60 years of age with ischemic systolic HF in the Controlled Rosuvastatin Multinational Trial in HF (CORONA) population, who were randomly assigned to 10 mg rosuvastatin or placebo. RESULTS: In the population as a whole, endostatin added no predictive information after full multivariable adjustment including eGFR and N-terminal pro-brain natriuretic peptide. Serum endostatin was strongly correlated with eGFR (r = 0.59, p < 0.001). After full multivariable adjustment, an association between high serum endostatin and increased risk of all-cause mortality and decreased risk of the primary and coronary endpoints was seen in HF patients with impaired and preserved renal function, respectively. CONCLUSIONS: Endostatin added no predictive information regarding the adverse outcome in patients with chronic systolic HF of ischemic etiology. An increased risk of all-cause mortality was seen in patients with decreased renal function.
Assuntos
Endostatinas/sangue , Insuficiência Cardíaca Sistólica/sangue , Nefropatias/sangue , Idoso , Idoso de 80 Anos ou mais , Proteína C-Reativa/metabolismo , Feminino , Fluorbenzenos/uso terapêutico , Taxa de Filtração Glomerular/fisiologia , Insuficiência Cardíaca Sistólica/tratamento farmacológico , Insuficiência Cardíaca Sistólica/mortalidade , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Técnicas Imunoenzimáticas , Nefropatias/tratamento farmacológico , Nefropatias/mortalidade , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Pirimidinas/uso terapêutico , Rosuvastatina Cálcica , Sulfonamidas/uso terapêuticoRESUMO
OBJECTIVES: Reduced arterial vasodilatatory capacity is a marker of coronary heart disease. The aim was to investigate if the difference between the vasodilatory response before and after exercise, as assessed by non-invasive methodology, is related to endothelial and inflammatory biomarkers. DESIGN: Post-ischemic hyperemia after 5 min of arterial occlusion was examined before and after a bicycle test with strain-gauge plethysmography (measuring peak reactive hyperemia in the forearm) and peripheral arterial tonometry (PAT hyperemia ratio: measuring pulse waves in the index finger relative to the contra-lateral index finger) in 30 healthy males. A low PAT hyperemia ratio or a low peak reactive hyperemia reflects endothelial dysfunction. Inflammatory and endothelial biomarkers were assessed. RESULTS: A low peak reactive hyperemia and a low PAT hyperemia ratio before the bicycle test was associated with a high percentage increase in peak reactive hyperemia after exercise (r = - 0.68, p < 0.001; r = - 0.35, p = 0.06, respectively). Asymmetric dimethylarginine and interleukin-10 were associated with the percentage increase in peak reactive hyperemia in multiple linear regression analyses (ß: 165 (confidence interval [CI], 34-296), p = 0.02; ß: 19 (CI, - 0.5-39), p = 0.06, respectively). CONCLUSIONS: The difference in the vasodilatory response before and after exercise, as assessed by non-invasive methodology, is related to endothelial and inflammatory biomarkers in healthy males.
Assuntos
Arginina/análogos & derivados , Endotélio Vascular , Exercício Físico/fisiologia , Hiperemia , Interleucina-10/metabolismo , Vasodilatação/fisiologia , Adulto , Idoso , Arginina/metabolismo , Biomarcadores/metabolismo , Endotélio Vascular/metabolismo , Endotélio Vascular/fisiopatologia , Teste de Esforço/métodos , Humanos , Hiperemia/etiologia , Hiperemia/metabolismo , Hiperemia/fisiopatologia , Inflamação/metabolismo , Masculino , Pessoa de Meia-Idade , Pletismografia de Impedância/métodos , Estatística como AssuntoRESUMO
AIM: Angina pectoris is common in patients with heart failure and reduced ejection fraction (HF-REF) but its relationship with outcomes has not been well defined. This relationship was investigated further in a retrospective analysis of the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA). METHODS AND RESULTS: Four thousand, eight hundred and seventy-eight patients were divided into three categories: no history of angina and no chest pain at baseline (Group A; n = 1240), past history of angina but no chest pain at baseline (Group B; n = 1353) and both a history of angina and chest pain at baseline (Group C; n = 2285). Outcomes were examined using Kaplan-Meier and Cox regression survival analysis. Compared with Group A, Group C had a higher risk of non-fatal myocardial infarction or unstable angina (HR: 2.36, 1.54-3.61; P < 0.001), this composite plus coronary revascularization (HR: 2.54, 1.76-3.68; P < 0.001), as well as HF hospitalization (HR: 1.35, 1.13-1.63; P = 0.001), over a median follow-up period of 33 months. There was no difference in cardiovascular or all-cause mortality. Group B had a smaller increase in risk of coronary events but not of heart failure hospitalization. CONCLUSION: Patients with HF-REF and ongoing angina are at an increased risk of acute coronary syndrome and HF hospitalization. Whether these patients would benefit from more aggressive medical therapy or percutaneous revascularization is not known and merits further investigation.
Assuntos
Angina Pectoris/complicações , Insuficiência Cardíaca/complicações , Idoso , Angina Pectoris/mortalidade , Angina Pectoris/fisiopatologia , Feminino , Fluorbenzenos/administração & dosagem , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/mortalidade , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Pirimidinas/administração & dosagem , Estudos Retrospectivos , Rosuvastatina Cálcica , Volume Sistólico/fisiologia , Sulfonamidas/administração & dosagem , Resultado do Tratamento , Disfunção Ventricular Esquerda/complicações , Disfunção Ventricular Esquerda/mortalidade , Disfunção Ventricular Esquerda/fisiopatologiaRESUMO
BACKGROUND: Recent genome-wide association studies have identified multiple loci that are associated with an increased risk of developing coronary artery disease (CAD). The impact of these loci on the disease severity and prognosis of ischemic heart failure due to CAD is currently unknown. METHODS: We undertook association analysis of 7 single nucleotide polymorphism (rs599839, rs17465637, rs2972147, rs6922269, rs1333049, rs501120, and rs17228212) at 7 well established CAD risk loci (1p13.3, 1q41, 2q36.3, 6q25.1, 9p21.3, 10q11.21, and 15q22.33, respectively) in 3,320 subjects diagnosed with systolic heart failure of ischemic aetiology and participating in the COntrolled ROsuvastatin multiNAtional Trial in Heart Failure (CORONA) trial. The primary outcome was the composite of time to first event of cardiovascular death, non-fatal myocardial infarction and non-fatal stroke, secondary outcomes included mortality and hospitalization due to worsening heart failure. RESULTS: None of the 7 loci were significantly associated with the primary composite endpoint of the CORONA trial (death from cardiovascular cases, nonfatal myocardial infarction, and nonfatal stroke). However, the 1p13.3 locus (rs599839) showed evidence for association with all-cause mortality (after adjustment for covariates; HR 0.74, 95%CI [0.61 to 0.90]; P = 0.0025) and we confirmed the 1p13.3 locus (rs599839) to be associated with lipid parameters (total cholesterol (P = 1.1x10(-4)), low-density lipoprotein levels (P = 3.5 × 10(-7)) and apolipoprotein B (P = 2.2 × 10(-10))). CONCLUSION: Genetic variants strongly associated with CAD risk are not associated with the severity and outcome of ischemic heart failure. The observed association of the 1p13.3 locus with all-cause mortality requires confirmation in further studies.
Assuntos
Doença da Artéria Coronariana/genética , Insuficiência Cardíaca Sistólica/genética , Polimorfismo de Nucleotídeo Único , Idoso , Idoso de 80 Anos ou mais , Ensaios Clínicos como Assunto , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/mortalidade , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , PrognósticoRESUMO
Sleep apnoea is a common, yet underestimated, chronic disorder with a major impact on morbidity and mortality in the general population. It is quickly becoming recognized as an independent risk factor for cardiovascular impairment. Hypertension, coronary artery disease, diabetes, cardiovascular rhythm and conduction abnormalities, cerebrovascular disease, and heart failure have all been linked to this syndrome. This review will explore the critical connection between sleep apnoea and chronic cardiovascular diseases while highlighting established and emerging diagnostic and treatment strategies.
Assuntos
Doenças Cardiovasculares/etiologia , Síndromes da Apneia do Sono/terapia , Síndrome Coronariana Aguda/etiologia , Arritmias Cardíacas/etiologia , Doença Crônica , Doença da Artéria Coronariana/etiologia , Insuficiência Cardíaca/etiologia , Humanos , Hipertensão Pulmonar/etiologia , Síndromes da Apneia do Sono/complicações , Síndromes da Apneia do Sono/diagnósticoRESUMO
BACKGROUND: Sensitive troponin assays have substantially improved early diagnosis of myocardial infarction. However, the role of sensitive cardiac troponin (cTn) assays in prediction of significant coronary lesions and long-term prognosis in non-ST-elevation acute coronary syndrome (NSTE-ACS) remains unresolved. METHODS: This prospective study includes 458 consecutive patients with NSTE-ACS admitted for coronary angiography. Serum levels of 4 commercial available sensitive troponin assays were analyzed (Roche high-sensitive cTnT [hs-cTnT; Roche Diagnostics, Basel, Switzerland], Siemens cTnI Ultra [Siemens, Munich, Germany], Abbott-Architect cTnI [Abbott, Abbott Park, IL], Access Accu-cTnI [Beckman Coulter, Nyon, Switzerland]), as well as a standard assay (Roche cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP), before coronary angiography. RESULTS: The relationship between the analyzed biomarkers and significant coronary lesions on coronary angiography, as quantified by area under the receiver operating characteristic curve, was significantly higher with Roche hs-cTnT, Siemens cTnI Ultra, and Access Accu-cTnI as compared with standard troponin T assay (P < .001 for all comparisons). This difference was mainly caused by increased sensitivity below the 99th percentile. Also, NT-proBNP was associated with the presence of significant coronary lesions. Cardiac troponin values were correlated with cardiac death (primary end point) during 1373 (1257-1478) days of follow-up. In both univariate and multivariate Cox regression analyses, NT-proBNP was superior to both hs-cTnT and cTnI in prediction of cardiovascular mortality. Troponin values with all assays were correlated with the need for repeated revascularization (secondary end point) during follow-up. CONCLUSIONS: Sensitive cTn assays are superior to standard cTnT assay in prediction of significant coronary lesions in patients with NSTE-ACS. However, this improvement is primary caused by increased sensitivity below the 99th percentile. N-terminal pro-B-type natriuretic peptide is superior to cTns in prediction of long-term mortality.
Assuntos
Síndrome Coronariana Aguda/sangue , Diagnóstico Precoce , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Troponina I/sangue , Troponina T/sangue , Síndrome Coronariana Aguda/diagnóstico , Idoso , Biomarcadores/sangue , Angiografia Coronária , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Precursores de Proteínas , Curva ROC , Fatores de TempoRESUMO
AIMS: To investigate whether plasma galectin-3, a mediator of fibrogenesis, can identify patients with chronic heart failure (HF) for whom statins are effective. METHODS AND RESULTS: Patients with ischaemic systolic HF enrolled in the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA) were randomly assigned to 10 mg/day of rosuvastatin or placebo. Galectin-3 was measured in plasma. The primary outcome was cardiovascular death, myocardial infarction, or stroke. Of 1492 patients, 411 had a primary event during a median follow-up of 32.8 months. There was an interaction between baseline galectin-3 and rosuvastatin on the primary endpoint (P-value for interaction = 0.036). Among patients with below the median plasma concentrations of galectin-3 (≤ 19.0 ng/mL), those assigned to rosuvastatin had a lower primary event rate [hazard ratio (HR) 0.65; 95% confidence interval (CI), 0.46-0.92; P= 0.014], lower total mortality (HR 0.70; 95% CI, 0.50-0.98; P= 0.038), and lower event rate of all-cause mortality and HF hospitalizations (HR 0.72; 95% CI, 0.54-0.98; P= 0.017) compared with placebo, but no benefit was observed in patients with higher levels of galectin-3. The combination of concurrently low concentrations of galectin-3 and N-terminal pro-B-type natriuretic peptide (<102.7 pmol/L) identified patients with a large benefit with rosuvastatin (HR 0.33; 95% CI, 0.16-0.67; P= 0.002). CONCLUSION: Patients with systolic HF of ischaemic aetiology who have galectin-3 values <19.0 ng/mL may benefit from rosuvastatin treatment. However, the data from this post hoc analysis should be interpreted with caution since the overall results of the CORONA study did not show a significant effect on the primary endpoint.
Assuntos
Fluorbenzenos/uso terapêutico , Galectina 3/sangue , Insuficiência Cardíaca Sistólica/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Pirimidinas/uso terapêutico , Sulfonamidas/uso terapêutico , Idoso , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Feminino , Insuficiência Cardíaca Sistólica/sangue , Humanos , Estimativa de Kaplan-Meier , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Infarto do Miocárdio/etiologia , Peptídeo Natriurético Encefálico/metabolismo , Fragmentos de Peptídeos/metabolismo , Rosuvastatina Cálcica , Acidente Vascular Cerebral/etiologia , Resultado do TratamentoRESUMO
BACKGROUND: Galectin-3 is a new biomarker involved in inflammation and fibrogenesis and could therefore contribute to myocardial remodeling. We examined the prognostic value of baseline galectin-3 in a substudy involving approximately 30% of participants in the CORONA study. METHODS: Patients (n = 1462) aged >60 years with systolic, ischemic heart failure (HF) were randomized to 10 mg/d rosuvastatin or placebo. The primary composite end point was cardiovascular death, nonfatal myocardial infarction, or stroke (n = 408). RESULTS: In the unadjusted analysis, galectin-3 was associated with all end points considered, except hospitalization for worsening of HF. In multivariable analyses, adjusting for other clinical and biochemical predictor variables, galectin-3 was significantly associated with the primary end point (hazard ratio [HR] 1.53 [1.10-2.12], P = .011) as well as all-cause (HR 1.61 [1.20-2.29], P = .002) and cardiovascular mortality (HR 1.70 [1.19-2.42], P = .003), sudden death (HR 1.83 [1.14-2.94], P = .012), and the coronary end point (HR 1.48 [1.03-2.12], P = .035). However, when N-terminal pro-brain natriuretic peptide was added to the model, galectin-3 association with the end points was markedly attenuated and no longer significant. CONCLUSIONS: Galectin-3 is not associated with outcome in older patients with advanced chronic systolic HF of ischemic etiology when adjusting for N-terminal pro-brain natriuretic peptide and may therefore have limited use in the prognostication of elderly patients with systolic HF in clinical practice.
Assuntos
Biomarcadores/sangue , Fluorbenzenos/uso terapêutico , Galectina 3/sangue , Insuficiência Cardíaca Sistólica/mortalidade , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Pirimidinas/uso terapêutico , Sulfonamidas/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Feminino , Insuficiência Cardíaca Sistólica/sangue , Insuficiência Cardíaca Sistólica/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/mortalidade , Prognóstico , Rosuvastatina Cálcica , Acidente Vascular Cerebral/mortalidadeRESUMO
Cardiovascular disease (CVD) due to atherosclerosis of the arterial vessel wall and to thrombosis is the foremost cause of premature mortality and of disability-adjusted life years (DALYs) in Europe, and is also increasingly common in developing countries.1 In the European Union, the economic cost of CVD represents annually E192 billion1 in direct and indirect healthcare costs. The main clinical entities are coronary artery disease (CAD), ischaemic stroke, and peripheral arterial disease (PAD). The causes of these CVDs are multifactorial. Some of these factors relate to lifestyles, such as tobacco smoking, lack of physical activity, and dietary habits, and are thus modifiable. Other risk factors are also modifiable, such as elevated blood pressure, type 2 diabetes, and dyslipidaemias, or non-modifiable, such as age and male gender. These guidelines deal with the management of dyslipidaemias as an essential and integral part of CVD prevention. Prevention and treatment of dyslipidaemias should always be considered within the broader framework of CVD prevention, which is addressed in guidelines of the Joint European Societies' Task forces on CVD prevention in clinical practice.2 5 The latest version of these guidelines was published in 20075; an update will become available in 2012. These Joint ESC/European Atherosclerosis Society (EAS) guidelines on the management of dyslipidaemias are complementary to the guidelines on CVD prevention in clinical practice and address not only physicians [e.g. general practitioners (GPs) and cardiologists] interested in CVD prevention, but also specialists from lipid clinics or metabolic units who are dealing with dyslipidaemias that are more difficult to classify and treat.
Assuntos
Doenças Cardiovasculares/prevenção & controle , Dislipidemias/prevenção & controle , Adulto , Criança , Dieta , Gorduras na Dieta/administração & dosagem , Suplementos Nutricionais , Dislipidemias/dietoterapia , Dislipidemias/tratamento farmacológico , Diagnóstico Precoce , Ingestão de Energia/fisiologia , Exercício Físico , Feminino , Humanos , Hipolipemiantes/uso terapêutico , Falência Renal Crônica/complicações , Estilo de Vida , Metabolismo dos Lipídeos , Masculino , Cooperação do Paciente , Prevenção Primária/métodos , Medição de Risco , Fatores de Risco , Prevenção Secundária/métodos , Manejo de Espécimes/métodos , Transplante/efeitos adversos , Redução de PesoRESUMO
CONTEXT: Statin therapy has been associated with pancreatitis in observational studies. Although lipid guidelines recommend fibrate therapy to reduce pancreatitis risk in persons with hypertriglyceridemia, fibrates may lead to the development of gallstones, a risk factor for pancreatitis. OBJECTIVE: To investigate associations between statin or fibrate therapy and incident pancreatitis in large randomized trials. DATA SOURCES: Relevant trials were identified in literature searches of MEDLINE, EMBASE, and Web of Science (January 1, 1994, for statin trials and January 1, 1972, for fibrate trials, through June 9, 2012). Published pancreatitis data were tabulated where available (6 trials). Unpublished data were obtained from investigators (22 trials). STUDY SELECTION: We included randomized controlled cardiovascular end-point trials investigating effects of statin therapy or fibrate therapy. Studies with more than 1000 participants followed up for more than 1 year were included. DATA EXTRACTION: Trial-specific data described numbers of participants developing pancreatitis and change in triglyceride levels at 1 year. Trial-specific risk ratios (RRs) were calculated and combined using random-effects model meta-analysis. Between-study heterogeneity was assessed using the I2 statistic. RESULTS: In 16 placebo- and standard care-controlled statin trials with 113,800 participants conducted over a weighted mean follow-up of 4.1 (SD, 1.5) years, 309 participants developed pancreatitis (134 assigned to statin, 175 assigned to control) (RR, 0.77 [95% CI, 0.62-0.97; P = .03; I2 = 0%]). In 5 dose-comparison statin trials with 39,614 participants conducted over 4.8 (SD, 1.7) years, 156 participants developed pancreatitis (70 assigned to intensive dose, 86 assigned to moderate dose) (RR, 0.82 [95% CI, 0.59-1.12; P = .21; I2 = 0%]). Combined results for all 21 statin trials provided RR 0.79 (95% CI, 0.65-0.95; P = .01; I2 = 0%). In 7 fibrate trials with 40,162 participants conducted over 5.3 (SD, 0.5) years, 144 participants developed pancreatitis (84 assigned to fibrate therapy, 60 assigned to placebo) (RR, 1.39 [95% CI, 1.00-1.95; P = .053; I2 = 0%]). CONCLUSION: In a pooled analysis of randomized trial data, use of statin therapy was associated with a lower risk of pancreatitis in patients with normal or mildly elevated triglyceride levels.
Assuntos
Ácidos Fíbricos/efeitos adversos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Hipertrigliceridemia , Pancreatite/induzido quimicamente , Pancreatite/prevenção & controle , Ácidos Fíbricos/uso terapêutico , Cálculos Biliares/induzido quimicamente , Cálculos Biliares/complicações , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hiperlipidemias/tratamento farmacológico , Hipertrigliceridemia/complicações , Hipertrigliceridemia/tratamento farmacológico , Incidência , Pancreatite/epidemiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Risco , Triglicerídeos/sangueRESUMO
INTRODUCTION: Helicopter pilots are exposed to whole body vibration and noise in their working environment. Some researchers have found that kinetic energy from both noise and vibration is believed to affect pericardial thickness and lead to pulmonary fibrosis, known as vibroacoustic disease. The aim of this project was to determine whether we could discover similar findings in a selection of helicopter pilots. METHODS: A case control study where 27 helicopter pilots were compared to an age-matched control group of typical office workers was conducted. High resolution CT scanning of the thorax was used as the diagnostic method. Two medical radiologists interpreted the images independently, blinded to whether the subjects were pilots or from the control group. RESULTS: There were no signs of pericardial thickening or significant lung fibrosis formations in either of the groups. The average pericardium thickness for the helicopter group was 1.38 mm, SD = 0.54 mm, and for the control group: 1.37 mm, SD = 0.33 mm. There was no significant correlation between pericardium thickness and flight hours or age. DISCUSSION: The average pericardial thickness values for the helicopter and the age-matched control groups were almost identical. The results are within normal limits and comparable to an American study where 21 normal individuals were measured to 1.2 mm +/- 0.8 mm in an average of 26 different points by using trans-esophageal echocardiography. CONCLUSION: On the basis of the CT scans, our findings do not support the existence of vibroacoustic disease, where pericardial thickening is the most prominent sign.
Assuntos
Pulmão/diagnóstico por imagem , Ruído Ocupacional , Exposição Ocupacional , Pericárdio/diagnóstico por imagem , Vibração , Adulto , Medicina Aeroespacial , Estudos de Casos e Controles , Humanos , Masculino , Pessoa de Meia-Idade , Fibrose Pulmonar/diagnóstico por imagem , Tomografia Computadorizada por Raios XAssuntos
Ácidos Graxos Ômega-3/uso terapêutico , Fluorbenzenos/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Pirimidinas/uso terapêutico , Acidente Vascular Cerebral/etiologia , Sulfonamidas/uso terapêutico , Feminino , Humanos , MasculinoRESUMO
BACKGROUND: Trials of statin therapy have had conflicting findings on the risk of development of diabetes mellitus in patients given statins. We aimed to establish by a meta-analysis of published and unpublished data whether any relation exists between statin use and development of diabetes. METHODS: We searched Medline, Embase, and the Cochrane Central Register of Controlled Trials from 1994 to 2009, for randomised controlled endpoint trials of statins. We included only trials with more than 1000 patients, with identical follow-up in both groups and duration of more than 1 year. We excluded trials of patients with organ transplants or who needed haemodialysis. We used the I(2) statistic to measure heterogeneity between trials and calculated risk estimates for incident diabetes with random-effect meta-analysis. FINDINGS: We identified 13 statin trials with 91 140 participants, of whom 4278 (2226 assigned statins and 2052 assigned control treatment) developed diabetes during a mean of 4 years. Statin therapy was associated with a 9% increased risk for incident diabetes (odds ratio [OR] 1.09; 95% CI 1.02-1.17), with little heterogeneity (I(2)=11%) between trials. Meta-regression showed that risk of development of diabetes with statins was highest in trials with older participants, but neither baseline body-mass index nor change in LDL-cholesterol concentrations accounted for residual variation in risk. Treatment of 255 (95% CI 150-852) patients with statins for 4 years resulted in one extra case of diabetes. INTERPRETATION: Statin therapy is associated with a slightly increased risk of development of diabetes, but the risk is low both in absolute terms and when compared with the reduction in coronary events. Clinical practice in patients with moderate or high cardiovascular risk or existing cardiovascular disease should not change. FUNDING: None.