RESUMO
BACKGROUND: Elevated uric acid concentration is associated with higher rates of cardiovascular (CV) morbidity and mortality in the general population. It is not known whether hyperuricemia increases the risk for CV death or transplant failure in kidney transplant recipients. STUDY DESIGN: Post hoc cohort analysis of the FAVORIT Study, a randomized controlled trial that examined the effect of homocysteine-lowering vitamins on CV disease in kidney transplantation. SETTING & PARTICIPANTS: Adult recipients of kidney transplants in the United States, Canada, or Brazil participating in the FAVORIT Study, with hyperhomocysteinemia, stable kidney function, and no known history of CV disease. PREDICTOR: Uric acid concentration. OUTCOMES: The primary end point was a composite of CV events. Secondary end points were all-cause mortality and transplant failure. Risk factors included in statistical models were age, sex, race, country, treatment assignment, smoking history, body mass index, presence of diabetes mellitus, history of CV disease, blood pressure, estimated glomerular filtration rate (eGFR), donor type, transplant vintage, lipid concentrations, albumin-creatinine ratio, and uric acid concentration. Cox proportional hazards models were fit to examine the association of uric acid concentration with study end points after risk adjustment. RESULTS: 3,512 of 4,110 FAVORIT participants with baseline uric acid concentrations were studied. Median follow-up was 3.9 (IQR, 3.0-5.3) years. 503 patients had a primary CV event, 401 died, and 287 had transplant failure. In unadjusted analyses, uric acid concentration was significantly related to each outcome. Uric acid concentration was also strongly associated with eGFR. The relationship between uric acid concentration and study end points was no longer significant in fully adjusted multivariable models (P=0.5 for CV events; P=0.09 for death, and P=0.1 for transplant failure). LIMITATIONS: Unknown use of uric acid-lowering agents among study participants. CONCLUSIONS: Following kidney transplantation, uric acid concentrations are not independently associated with CV events, mortality, or transplant failure. The strong association between uric acid concentrations with traditional risk factors and eGFR is a possible explanation.
Assuntos
Doenças Cardiovasculares/mortalidade , Hiper-Homocisteinemia/tratamento farmacológico , Hiperuricemia/epidemiologia , Falência Renal Crônica/epidemiologia , Transplante de Rim , Vitaminas/uso terapêutico , Adulto , Brasil , Canadá , Causas de Morte , Feminino , Taxa de Filtração Glomerular , Humanos , Falência Renal Crônica/cirurgia , Masculino , Pessoa de Meia-Idade , Mortalidade , Análise Multivariada , Modelos de Riscos Proporcionais , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Estados UnidosRESUMO
BACKGROUND: Physical activity (PA) is inversely associated with adverse cardiovascular outcomes in healthy populations, but the impact of physical activity in patients with heart failure (HF) with preserved ejection fraction is less well characterized. METHODS: The baseline self-reported PA of 1751 subjects enrolled in the Americas region of the TOPCAT trial (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) was categorized as poor, intermediate, or ideal PA with American Heart Association criteria. PA was related to the primary composite outcome (HF hospitalization, cardiovascular mortality, or aborted cardiac arrest), its components, and all-cause mortality with the use of multivariable Cox models. RESULTS: The mean age at enrollment was 68.6±9.6 years. Few patients met American Heart Association criteria for ideal activity (11% ideal, 14% intermediate, 75% poor). Over a median follow-up of 2.4 years, the primary composite outcome occurred in 519 patients (397 HF hospitalizations, 222 cardiovascular deaths, and 6 aborted cardiac arrests). Compared with those with ideal baseline PA, poor and intermediate baseline PA was associated with a greater risk of the primary outcome (hazard ratio [HR], 2.05; 95% confidence interval [CI], 1.28-3.28; HR, 1.95; 95% CI, 1.15-3.33, respectively), HF hospitalization (HR, 1.93; 95% CI, 1.16-3.22; HR, 1.84; 95% CI, 1.02-3.31), cardiovascular mortality (HR, 4.36; 95% CI, 1.37-13.83; HR, 4.05; 95% CI, 1.17-14.04), and all-cause mortality (HR, 2.95; 95% CI, 1.44-6.02; HR, 2.05; 95% CI, 0.90-4.67) after multivariable adjustment for potential confounders. CONCLUSIONS: In patients with HF with preserved ejection fraction, both poor and intermediate self-reported PA were associated with higher risk of HF hospitalization and mortality. CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov. Unique identifier: NCT00094302.
Assuntos
Exercício Físico/fisiologia , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/mortalidade , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Volume Sistólico/fisiologia , Idoso , Argentina/epidemiologia , Brasil/epidemiologia , Canadá/epidemiologia , Feminino , Seguimentos , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Antagonistas de Receptores de Mineralocorticoides/farmacologia , Mortalidade/tendências , Prognóstico , Volume Sistólico/efeitos dos fármacos , Resultado do Tratamento , Estados Unidos/epidemiologiaRESUMO
OBJECTIVES: This study examined the relationship between baseline QRS duration and clinical outcomes in subjects enrolled in the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) trial. BACKGROUND: Heart failure with preserved ejection fraction (HFPEF) is a heterogeneous clinical syndrome. Whether QRS duration identifies HFPEF subjects at an increased risk of adverse outcomes has not been well studied. METHODS: QRS duration was analyzed as a dichotomous variable (≥120 ms or <120 ms) and as a continuous variable to determine its relation to the primary outcome (composite of cardiovascular death, aborted cardiac arrest, or HF hospitalization [HFH]) and to each component of the primary outcome. Multivariate analyses were conducted in the entire study cohort as well as in separate analyses for subjects enrolled only from North and South America, or from Russia and Georgia. RESULTS: The QRS duration of ≥120 ms was independently associated with an increased risk of the primary outcome (p = 0.009) and HFH (p = 0.003) in the entire study cohort and in the subset enrolled in the Americas. There was a linear relation of QRS duration with risk of the primary outcome and HFH. No interaction was observed between treatment with spironolactone and QRS duration. The risk of adverse outcomes was increased independently of the type of conduction abnormality underlying prolonged QRS duration. CONCLUSIONS: This post hoc analysis demonstrated that prolonged QRS duration identifies HFPEF subjects at a higher risk of adverse clinical outcomes and that spironolactone had a similar effect on outcomes independent of QRS duration. (Aldosterone Antagonist Therapy for Adults With Heart Failure and Preserved Systolic Function [TOPCAT]; NCT00094302).
Assuntos
Arritmias Cardíacas/fisiopatologia , Insuficiência Cardíaca/fisiopatologia , Volume Sistólico , Idoso , Idoso de 80 Anos ou mais , Arritmias Cardíacas/complicações , Doenças Cardiovasculares/mortalidade , Estudos de Coortes , Eletrocardiografia , Feminino , República da Geórgia , Parada Cardíaca/epidemiologia , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/tratamento farmacológico , Hospitalização/estatística & dados numéricos , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Análise Multivariada , América do Norte , Prognóstico , Federação Russa , América do Sul , Espironolactona/uso terapêuticoRESUMO
BACKGROUND: Heart failure (HF) with preserved ejection fraction patients have equally impaired health-related quality of life (HRQL) compared with those with HF with reduced ejection fraction, but limited studies have evaluated the impact of therapies on changes in HRQL. METHODS AND RESULTS: Patients ≥50 years of age, with symptomatic HF and left ventricular ejection fraction ≥45%, were enrolled in Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) and randomized to spironolactone or placebo. Patients completed the Kansas City Cardiomyopathy Questionnaire (KCCQ), which was the primary HRQL instrument, and EQ5D visual analog scale at baseline, 4 months, 12 months, and annually thereafter. McMaster Overall Treatment Evaluation was assessed at 4 and 12 months to assess global change scores. Change scores (+SD) were calculated to determine between-group differences, and multivariable repeated-measures models were created to identify other factors associated with change scores. Paired KCCQ data were available for 91.7% of 3445 TOPCAT patients. By 4 months, the mean change in KCCQ was 7.7±16 and mean change in EQ5D visual analog scale was 4.7±16. Adjusted mean changes in KCCQ for the spironolactone group were significantly better than those for the placebo group at 4-month (1.54 better; P=0.002), 12-month (1.35 better; P=0.02), and 36-month (1.86 better; P=0.02) visits. No between-group differences in EQ5D visual analog scale change scores or McMaster Overall Treatment Evaluation were noted. Older age, obesity, current smoking, New York Heart Association class III/IV, and comorbid illnesses were associated with declines in KCCQ scores. Use of spironolactone was an independent predictor of improved KCCQ scores. CONCLUSIONS: In symptomatic HF with preserved ejection fraction patients, use of spironolactone was associated with an improvement in HF-specific HRQL. Several modifiable risk factors were associated with HRQL deterioration. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00094302.
Assuntos
Insuficiência Cardíaca/tratamento farmacológico , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Espironolactona/uso terapêutico , Volume Sistólico , Função Ventricular Esquerda , Argentina , Brasil , Canadá , Método Duplo-Cego , Feminino , República da Geórgia , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/psicologia , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Qualidade de Vida , Fatores de Risco , Federação Russa , Inquéritos e Questionários , Fatores de Tempo , Resultado do Tratamento , Estados UnidosRESUMO
BACKGROUND: Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) patients with heart failure and preserved left ventricular ejection fraction assigned to spironolactone did not achieve a significant reduction in the primary composite outcome (time to cardiovascular death, aborted cardiac arrest, or hospitalization for management of heart failure) compared with patients receiving placebo. In a post hoc analysis, an ≈4-fold difference was identified in this composite event rate between the 1678 patients randomized from Russia and Georgia compared with the 1767 enrolled from the United States, Canada, Brazil, and Argentina (the Americas). METHODS AND RESULTS: To better understand this regional difference in clinical outcomes, demographic characteristics of these populations and their responses to spironolactone were explored. Patients from Russia/Georgia were younger, had less atrial fibrillation and diabetes mellitus, but were more likely to have had prior myocardial infarction or a hospitalization for heart failure. Russia/Georgia patients also had lower left ventricular ejection fraction and creatinine but higher diastolic blood pressure (all P<0.001). Hyperkalemia and doubling of creatinine were more likely and hypokalemia was less likely in patients receiving spironolactone in the Americas with no significant treatment effects in Russia/Georgia. All clinical event rates were markedly lower in Russia/Georgia, and there was no detectable impact of spironolactone on any outcomes. In contrast, in the Americas, the rates of the primary outcome, cardiovascular death, and hospitalization for heart failure were significantly reduced by spironolactone. CONCLUSIONS: This post hoc analysis demonstrated greater potassium and creatinine changes and possible clinical benefits with spironolactone in patients with heart failure and preserved ejection fraction from the Americas. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00094302.
Assuntos
Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/fisiopatologia , Internacionalidade , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Pacientes , Espironolactona/uso terapêutico , Volume Sistólico/fisiologia , Idoso , Creatinina/sangue , Método Duplo-Cego , Feminino , República da Geórgia , Insuficiência Cardíaca/mortalidade , Humanos , Hiperpotassemia/epidemiologia , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , América do Norte , Fatores de Risco , Federação Russa , América do Sul , Resultado do TratamentoRESUMO
BACKGROUND: Treatment of Preserved Cardiac Function with an Aldosterone Antagonist (TOPCAT) is an ongoing randomized controlled trial of spironolactone versus placebo for heart failure with preserved ejection fraction (HFpEF). We sought to describe the baseline clinical characteristics of subjects enrolled in TOPCAT relative to other contemporary observational studies and randomized clinical trials of HFpEF. METHODS AND RESULTS: Between August 2006 and January 2012, 3445 patients with symptomatic HFpEF from 270 sites in 6 countries were enrolled in TOPCAT. At the baseline study visit, all subjects provided a detailed medical history and underwent physical examination, electrocardiography, quality of life, and laboratory assessment. Key parameters were compared with other large, contemporary HFpEF studies. The mean age was 68.6±9.6 years with a slight female predominance (52%); mean body mass index was 32 kg/m2; and comorbidities were common. History of hypertension (91% prevalence in TOPCAT) exceeded all other major HFpEF clinical trials. However, baseline blood pressure was well controlled (129/76 mm Hg; systolic blood pressure 7-16 mm Hg lower than other similar trials). Other common comorbidities included coronary artery disease (57%), atrial fibrillation (35%), chronic kidney disease (38%) and diabetes mellitus (32%). Self-reported activity levels were low, quality of life scores were comparable with those reported for patients with end-stage renal disease, and the prevalence of moderate or greater depression was 27%. CONCLUSIONS: TOPCAT subjects share many common characteristics with contemporary HFpEF cohorts. Low activity level, significantly decreased quality of life, and depression were common at baseline in TOPCAT, underscoring the continued unmet need for evidence-based treatment strategies in HFpEF. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. UNIQUE IDENTIFIER: NCT00094302.
Assuntos
Insuficiência Cardíaca/tratamento farmacológico , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Espironolactona/uso terapêutico , Volume Sistólico , Idoso , Argentina/epidemiologia , Comorbidade , Depressão/epidemiologia , Método Duplo-Cego , Eletrocardiografia , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/fisiopatologia , Humanos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Exame Físico , Valor Preditivo dos Testes , Qualidade de Vida , Inquéritos e Questionários , Fatores de Tempo , Resultado do Tratamento , U.R.S.S./epidemiologia , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: Hyperhomocysteinemia may be a modifiable risk factor for the prevention of arteriosclerotic outcomes in patients with chronic kidney disease (CKD). Few clinical trials of homocysteine lowering have been conducted in persons with CKD before reaching end-stage renal disease. Kidney transplant recipients are considered individuals with CKD. OBJECTIVES: To describe the baseline characteristics of renal transplant recipients enrolled in a clinical trial of homocysteine lowering with a standard multivitamin containing high doses of folic acid and vitamins B(6) and B(12) aimed at reducing arteriosclerotic outcomes. Factors considered were level of kidney function, total homocysteine concentration, and prevalence of diabetes and previous cardiovascular disease (CVD). STUDY DESIGN: Cross-sectional survey within a randomized controlled trial cohort. SETTING & PARTICIPANTS: Participants were recruited from kidney transplant clinics in the United States, Canada, and Brazil. Eligible participants had increased levels of homocysteine (> or =12.0 micromol/L in men and > or =11.0 micromol/L in women) and kidney function measured by means of Cockroft-Gault estimated creatinine clearance of 30 mL/min or greater. RESULTS: Of 4,110 randomly assigned participants, 38.9% had diabetes and 19.5% had previous CVD. Mean total homocysteine concentration was 17.1 +/- 6.3 (SD) micromol/L, whereas mean creatinine clearance was 66.4 +/- 23.2 mL/min. Approximately 90% of the trial cohort had an estimated glomerular filtration rate consistent with stages 2 to 3 CKD (i.e., 30 to 89 mL/min). LIMITATIONS: Analysis is based on cross-sectional data from a randomized controlled trial, self-report of comorbid illnesses, and level of kidney function was estimated. CONCLUSIONS: A large population of stable renal transplant recipients who are at high risk of the development of CVD (both de novo and recurrent) has been recruited into the Folic Acid for Vascular Outcome Reduction in Transplantation Trial and are likely to experience a sufficient number of events to address the primary hypothesis of the trial.
Assuntos
Doenças Cardiovasculares/prevenção & controle , Ácido Fólico/uso terapêutico , Nefropatias/cirurgia , Transplante de Rim , Complexo Vitamínico B/uso terapêutico , Adulto , Brasil , Canadá , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/etiologia , Doença Crônica , Estudos de Coortes , Creatinina/sangue , Estudos Transversais , Relação Dose-Resposta a Droga , Feminino , Taxa de Filtração Glomerular/fisiologia , Homocisteína/sangue , Humanos , Rim/fisiopatologia , Nefropatias/sangue , Nefropatias/complicações , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Resultado do Tratamento , Estados UnidosRESUMO
Realizamos estudo duplo-cego, comparativo com placebo para determinar se a dilataçäo ventricular continua durante a fase de convalescença após infarto do miocárdio e se a terapêutica com captopril altera esse processo. Cinqüenta e nove pacientes com primeiro infarto do miocárdio anterior e fraçäo de ejeçäo de 45 por cento ou menos se submeteram a cateterismo 11 e 31 dias depois do infarto, se näo estivessem em insuficiência cardiáca congestiva evidente. Foram entäo randomicamente alocados para placebo ou captopril e acompanhados por um ano. Repetiu-se a cateterizaçäo para avaliar as mudanças intervalares na funçäo hemodinâmica e volume ventricular esquerdo. Trinta e oito pacientes masculinos foram avaliados, a cada três meses, para prova de exercício máximo em esteira. Näo foram detectadas diferenças na situaçäo basal em relaçäo às variáveis clínicas, hemodinâmicas ou de ventriculografia quantitativa. Durante um ano de acompanhamento o volume distólico final do ventrículo esquerdo aumentou em média (ñ DP) de 21 ñ 8ml (P < 0,02) no grupo placebo, mas somente 10 ñ 6ml (P näo significante) no grupo captopril. A pressäo de enchimento ventricular esquerda permaneceu elevada com placebo mas diminuiu (P < 0,01) de 36 pacientes que era de alto risco para dilataçäo ventricular, por terem uma oclusäo persistente da artéria coronária anterior esquerda, captopril preveniu dilataçöes ventriculares futuras (P < 0,05). Pacientes que receberam captopril tambem tiveram aumento na capacidade de exercício (P < 0,05). Este estudo preliminar indica que após infarto anterior do miocárdio, a dilataçäo ventricular é progressiva e captopril pode atenuar esse processo, reduzir as pressöes de enchimento, e melhorar a tolerância ao exercício