Assuntos
Amiloidose/diagnóstico , Cardiomiopatias/diagnóstico , Idoso de 80 Anos ou mais , Amiloidose/fisiopatologia , Amiloidose/terapia , Fibrilação Atrial/fisiopatologia , Cardiomiopatias/fisiopatologia , Cardiomiopatias/terapia , Diagnóstico Diferencial , Diagnóstico por Imagem , Progressão da Doença , Dispneia/fisiopatologia , Humanos , Masculino , Esforço FísicoRESUMO
OBJECTIVES: We hypothesized that obstructive sleep apnea(OSA) has a dose-dependent impact on mortality in those with ischemic heart disease or previous myocardial injury. METHODS: We performed a retrospective cohort study of 281 consecutive OSA patients with a history of myocardial injury as determined by elevated troponin levels or with known existing ischemic heart disease. We compared survival between those with severe OSA [apneahypopneaindex (AHI) ≥30] and those with mild to moderate OSA(AHI >5 and <30). RESULTS: Of the 281 patients (mean age 65 years, mean BMI34, 98% male, 58% with diabetes), 151 patients had mild moderate OSA and 130 had severe OSA. During a mean follow-up of 4.1 years, there were significantly greater deaths in the severe OSA group compared to the mild moderate OSA group [53 deaths (41%) vs. 44 deaths(29%), respectively, p00.04]. The adjusted hazard ratio for mortality with severe OSA was 1.72 (95% confidence interval1.012.91, p00.04). CONCLUSIONS: The severity of obstructive sleep apnea is associated with increased risk of death, and risk stratification based on OSA severity is relevant even in the diseased cardiac patient.
Assuntos
Angina Instável/mortalidade , Insuficiência Cardíaca/mortalidade , Infarto do Miocárdio/mortalidade , Isquemia Miocárdica/mortalidade , Apneia Obstrutiva do Sono/mortalidade , Troponina I/sangue , Idoso , Angina Instável/diagnóstico , Índice de Massa Corporal , Causas de Morte , Estudos de Coortes , Comorbidade , Pressão Positiva Contínua nas Vias Aéreas/estatística & dados numéricos , Ecocardiografia , Feminino , Seguimentos , Insuficiência Cardíaca/diagnóstico , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico , Isquemia Miocárdica/diagnóstico , Cooperação do Paciente , Polissonografia , Prognóstico , Risco , Fatores de Risco , Apneia Obstrutiva do Sono/classificação , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/terapia , Análise de SobrevidaRESUMO
OBJECTIVE: The G-protein-coupled receptor APJ and its ligand apelin are highly expressed in the pulmonary vasculature, but their function in this vascular bed is unclear. We hypothesized that disruption of apelin signaling would lead to worsening of the vascular remodeling associated with pulmonary hypertension (PH). METHODS AND RESULTS: We found that apelin-null mice developed more severe PH compared with wild-type mice when exposed to chronic hypoxia. Micro-computed tomography of the pulmonary arteries demonstrated significant pruning of the microvasculature in the apelin-null mice. Apelin-null mice had a significant reduction of serum nitrate levels. This was secondary to downregulation of endothelial nitric oxide synthase (eNOS), which was associated with reduced expression of Kruppel-like factor 2 (KLF2), a known regulator of eNOS expression. In vitro knockdown studies targeting apelin in human pulmonary artery endothelial cells demonstrated decreased eNOS and KLF2 expression, as well as impaired phosphorylation of AMP-activated kinase and eNOS. Moreover, serum apelin levels of patients with PH were significantly lower than those of controls. CONCLUSIONS: These data demonstrate that disruption of apelin signaling can exacerbate PH mediated by decreased activation of AMP-activated kinase and eNOS, and they identify this pathway as a potentially important therapeutic target for treatment of this refractory human disease.
