RESUMO
The main objective was to compare the meaning of soluble angiotensin-converting enzyme-2 (sACE2) plasma levels modulation on the prognosis of two cohorts of heart failure (HF) and acute coronary syndrome (ACS). We conducted an observational clinical study where sACE2 was measured in two cohorts of HF or ACS (102 patients each), matched by age and gender. The primary endpoint (cardiac death) and the secondary endpoints (non-fatal myocardial infarction or HF readmission) were registered during a 5-year follow-up period. Association with pharmacotherapy was studied, and the effects of cardiovascular drugs on ACE isoforms expression were analysed in human umbilical vein endothelial cells (HUVEC) in vitro. The levels of sACE2 were significantly higher in the HF than ACS cohort. sACE2 was inversely related with the leukocytes number and directly with urea levels. In the ACS cohort, sACE2 was associated with age and glycaemic parameters, but in the HF cohort, the association was with N-terminal pro-B-type natriuretic peptide. The levels of sACE2 were related to long-term prognosis and confirmed as a non-independent predictor in the HF cohort. Soluble ACE2 was higher in patients treated with angiotensin receptors blockers and ß-blockers, accordingly with losartan and metoprolol upregulation of ACE1 and ACE2 in HUVECs. Plasma levels of sACE2 were higher in HF than in ACS, independently of age and gender, and were related to long-term cardiac death in the HF cohort. Losartan and metoprolol, but not enalapril, upregulated ACE expression in endothelial cells, accordingly with higher levels of sACE2 in patients using these drugs.
Assuntos
Síndrome Coronariana Aguda/sangue , Enzima de Conversão de Angiotensina 2/sangue , Insuficiência Cardíaca/sangue , Proteína ADAM17/genética , Síndrome Coronariana Aguda/mortalidade , Antagonistas Adrenérgicos beta/farmacologia , Idoso , Idoso de 80 Anos ou mais , Angiotensina II/farmacologia , Antagonistas de Receptores de Angiotensina/farmacologia , Enzima de Conversão de Angiotensina 2/genética , Enalapril/farmacologia , Feminino , Insuficiência Cardíaca/mortalidade , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , Estimativa de Kaplan-Meier , Losartan/farmacologia , Masculino , Metoprolol/farmacologia , Pessoa de Meia-Idade , Peptidil Dipeptidase A/genética , PrognósticoRESUMO
Recently the coronavirus disease (COVID-19) outbreak has been declared a pandemic. Despite its aggressive extension and significant morbidity and mortality, risk factors are poorly characterized outside China. We designed a registry, HOPE COVID-19 (NCT04334291), assessing data of 1021 patients discharged (dead or alive) after COVID-19, from 23 hospitals in 4 countries, between 8 February and 1 April. The primary end-point was all-cause mortality aiming to produce a mortality risk score calculator. The median age was 68 years (IQR 52-79), and 59.5% were male. Most frequent comorbidities were hypertension (46.8%) and dyslipidemia (35.8%). A relevant heart or lung disease were depicted in 20%. And renal, neurological, or oncological disease, respectively, were detected in nearly 10%. Most common symptoms were fever, cough, and dyspnea at admission. 311 patients died and 710 were discharged alive. In the death-multivariate analysis, raised as most relevant: age, hypertension, obesity, renal insufficiency, any immunosuppressive disease, 02 saturation < 92% and an elevated C reactive protein (AUC = 0.87; Hosmer-Lemeshow test, p > 0.999; bootstrap-optimist: 0.0018). We provide a simple clinical score to estimate probability of death, dividing patients in four grades (I-IV) of increasing probability. Hydroxychloroquine (79.2%) and antivirals (67.6%) were the specific drugs most commonly used. After a propensity score adjustment, the results suggested a slight improvement in mortality rates (adjusted-ORhydroxychloroquine 0.88; 95% CI 0.81-0.91, p = 0.005; adjusted-ORantiviral 0.94; 95% CI 0.87-1.01; p = 0.115). COVID-19 produces important mortality, mostly in patients with comorbidities with respiratory symptoms. Hydroxychloroquine could be associated with survival benefit, but this data need to be confirmed with further trials. Trial Registration: NCT04334291/EUPAS34399.
Assuntos
COVID-19/mortalidade , Idoso , COVID-19/complicações , COVID-19/terapia , Feminino , Hospitalização , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Sistema de Registros , Medição de Risco , Fatores de Risco , Espanha , Taxa de SobrevidaRESUMO
INTRODUCTION AND OBJECTIVES: The protein cystatin C has a stable plasma concentration and is eliminated exclusively by the kidneys. The aim of this study was to determine the prognostic value of cystatin C in patients with acute coronary syndrome (ACS). METHODS: The prospective study included 203 hospitalized ACS patients. Clinical evaluation during the first 24 hours of hospitalization included a hemogram and measurement of creatinine, cystatin C, total and fractionated cholesterol and markers of myocardial necrosis. The glomerular filtration rate (GFR) was estimated using the MDRD (Modification of Diet in Renal Disease) equation. A comparison was made between two groups of patients divided according to a serum cystatin-C level above or below 0.95 mg/L. The mean follow-up period was 151 days. RESULTS: In total, 90 patients (44.3%) had a cystatin-C level < or =0.95 mg/L and 113 (55.7%) had a level >0.95 mg/L. Those with a cystatin-C level >0.95 mg/L had poorer in-hospital outcomes, including more frequent heart failure (51.3% vs. 13.3%; P=.001) and higher in-hospital mortality (17.6% vs. 3.3%; P=.001), as well as higher mortality throughout follow-up (22.0% vs. 5.6%; P=.001). Multivariate analysis adjusted for age, ejection fraction and troponin-I and high-sensitivity C-reactive protein concentrations showed that cystatin C was the most powerful independent predictor of a cardiovascular event (relative risk=1.91; 95% confidence interval, 1.03-3.53). Patients with a GFR >60 mL/1.73 m(2) and a cystatin-C level >0.95 mg/L had higher in-hospital mortality (10.2% vs. 3.9%; P=.001). CONCLUSIONS: Measurement of cystatin C in high-risk ACS patients may be clinically useful for risk stratification during hospitalization, particularly in those with a normal GFR.