Risultati per: Le cause della polmonite nei bambini

Circulation, Volume 150, Issue Suppl_1, Page A4145632-A4145632, November 12, 2024. Background:High circulating levels of galectin-3 are associated with all-cause and cardiovascular (CV) mortality in patients with coronary artery disease (CAD). However, the impact of anemia on the prediction of galectin-3 with cause-specific mortality in patients with suspected or known CAD is unknown.Methods:Serum levels of galectin-3 were measured in 2,418 patients with suspected or known CAD undergoing elective coronary angiography. The outcomes were all-cause death, CV death, and non-CV death. Patients were divided into 2 groups according to the presence (n=882) or absence (n=1,536) of anemia, and followed up over a 6-year period.Results:During the follow-up, 329 anemic and 207 non-anemic patients died of any cause, 116 anemic and 50 non-anemic patients died of CV diseases, and 187 anemic and 139 non-anemic patients died of non-CV diseases. After adjustment for potential clinical confounders and established CV biomarkers, log-transformed (Ln-) galectin-3 levels were significantly associated with all-cause death (hazard ratio [HR] for 1-SD increase, 1.23; 95% confidence interval [CI], 1.10–1.37) and non-CV death (HR, 1.30; 95% CI, 1.13–1.50), but not with CV death (HR, 1.16; 95% CI, 0.95–1.41) in the entire cohort; significantly associated with all-cause death (HR, 1.20; 95% CI, 1.03–1.41) and non-CV death (HR, 1.49; 95% CI, 1.20–1.85), but not with CV death (HR, 0.95; 95% CI, 0.72–1.24), in anemic patients; and significantly associated with all-cause death (HR, 1.33; 95% CI, 1.13–1.57) and CV death (HR, 1.19; 95% CI, 1.00–1.42), but not with non-CV death (HR, 1.17; 95% CI, 0.95–1.43), in non-anemic patients. We also evaluated the incremental predictive performance of galectin-3 by calculating continuous net reclassification improvement, and integrated discrimination improvement metrics. The addition of Ln-galectin-3 levels to the model with potential clinical confounders and established CV biomarkers further improved the prediction of all-cause death and non-CV death, but not that of CV death, in the entire cohort and in anemic patients, and the prediction of all-cause death and CV death, but not that of non-CV death, in non-anemic patients.Conclusions:In patients with suspected or known CAD, distinct differences were observed between anemic and non-anemic patients, in the prediction for cause-specific mortality by galectin-3 levels, which independently predicted non-CV mortality in anemic patients and CV mortality in non-anemic patients.

Circulation, Volume 150, Issue Suppl_1, Page A4143662-A4143662, November 12, 2024. Background:Hypoxia-inducible factor-1 (HIF-1) is a heterodimeric transcription factor composed of a constitutively expressed β subunit (HIF-1β) and an oxygen-dependent α subunit (HIF-1α). HIF-1α has an important protective effect on the pathophysiology underlying coronary artery disease (CAD). However, the association between serum HIF-1α levels and mortality in patients with suspected or known CAD is unknown.Methods and Results:Serum levels of HIF-1α were measured in 2,418 patients with suspected or known CAD using a commercially available enzyme-linked immunosorbent assay kit (sensitivity, 30 pg/mL). The outcomes were all-cause death, cardiovascular (CV) death, and non-CV death. Patients were divided into 5 groups according to HIF-1α levels; below the sensitivity (Q0,

Circulation, Volume 150, Issue Suppl_1, Page A4141127-A4141127, November 12, 2024. Introduction:Cardioprotective glucose-lowering drugs including sodium glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists, and lipid-lowering statins are both aimed at preventing morbidity and mortality in individuals with type 2 diabetes. The importance of combining cardioprotective glucose-lowering drugs and statins in a real-world setting is unknown, and this was never tested in a 2-by-2 randomized trial.Hypotheses:We tested the hypothesis that combination of cardioprotective glucose-lowering drug and statin is associated with lower risk of all-cause mortality than using either drug alone.Aims:We investigated the association with all-cause mortality of combined treatment of cardioprotective glucose-lowering drug with statin versus either drug alone versus no drugs, in a nationwide real-world setting.Methods:From January 2013 through December 2021, we identified all individuals with type 2 diabetes living in Denmark. We categorized four groups according to treatment status: i) both cardioprotective glucose-lowering drug and statin, ii) cardioprotective glucose-lowering drug alone, iii) statin alone, and iv) neither cardioprotective glucose-lowering drug nor statin. First, using a simple cohort design, we followed 197,507 individuals with type 2 diabetes from January 2015 through December 2021. Second, using a time-varying cohort design, we followed all 354,979 individuals with type 2 diabetes and updated their treatment and covariate status annually from 2013 through 2021. All-cause mortality was assessed from the nationwide Danish Central Person Registry, which is 100% complete.Results:During mean follow-ups of 6.1 and 6.0 years, 50,571 and 80,712 individuals died in the simple and time-varying cohorts. Compared with nonusers of cardioprotective glucose-lowering drug or statin, the multivariable adjusted hazard ratios of all-cause mortality were 0.60 (95% confidence interval: 0.57–0.63) for combined use of cardioprotective glucose-lowering drug and statin, 0.76 (0.74–0.77) for treatment with statin alone, and 0.76 (0.70–0.82) for treatment with cardioprotective glucose-lowering drug alone. Corresponding values in the time-varying cohort were 0.43 (0.42-0.45), 0.63 (0.62-0.64), and 0.61 (0.58-0.64), respectively.Conclusions:In individuals with type 2 diabetes, treatment with a cardioprotective glucose-lowering drug and statin in combination was associated with a lower risk of all-cause mortality than using either drug alone.

Circulation, Volume 150, Issue Suppl_1, Page A4143511-A4143511, November 12, 2024. Background:The Triglyceride-glucose (TyG) index , a novel indicator of insulin resistance, has been associated with mortality from non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease (CVD). However, the association between the TyG index and the derived index of TyG (TyG-WHtR) and CVD in NAFLD patients remains unclear.Methods:This study enrolled 6627 adults aged 18 and above diagnosed NAFLD from the National Health and Nutrition Examination Survey (NHANES, 1999-2018). Binary weighted logistic regression analyses, cox proportional hazards model, restricted cubic spline (RCS), and receiver operating characteristic (ROC) were used to analyze the relationship between TyG and TyG-WHtR and all-cause mortality, CVD mortality and CVD related diseases. Mediation analysis explored the mediating role of glycohemoglobin (HbA1c), insulin and hypertension in the above relationships.Results:Except for no significant association between TyG and all-cause mortality and chronic heart failure (CHF), both TyG and TyG-WHtR exhibited significant positive correlations or trends of positive correlation with all-cause mortality, CVD mortality, total-CVD, CHF, coronary heart disease (CHD) and angina pectoris. For all-cause mortality, CVD mortality and CHF, TyG-WHtR was a better predictor than TyG (HR 1.31, 95%CI 1.03-1.66; HR 2.22, 95%CI 1.42-3.47; OR 3.99, 95%CI 1.79-8.93). However, TyG index demonstrated a stronger association with total-CVD, CHD and angina pectoris (OR 2.00, 95%CI 1.26-3.18; OR 1.85, 95%CI 1.19-2.91; OR 2.93, 95%CI 1.23-7.00). Otherwise, the ROC curve illustrated that, for all-cause mortality, CVD mortality, CHD and angina pectoris, TyG had a higher diagnostic efficacy. For CHF, the diagnostic efficacy of TyG-WHtR is higher. For total-CVD, TyG and TyG-WHtR had approximately equal diagnostic efficacy. RCS analysis showed that after adjusting for covariates, most of the above relationships were linearly correlated (P-overall < 0.0001, P-nonlinear > 0.05), while TyG and TyG-WHtR were non-linearly associated with all-cause mortality and CHF (P-overall < 0.0001, P-nonlinear< 0.05) in NAFLD patients.Conclusions:The predictive value of TyG or TyG-WHtR for mortality and cardiovascular risk in NAFLD patients was significant. The TyG index and TyG-WHtR might be a valid predictor of cardiovascular outcomes of patients with NAFLD.

Circulation, Volume 150, Issue Suppl_1, Page A4145549-A4145549, November 12, 2024. Background:There is an increasing prevalence of type 2 diabetes (T2D) and systolic heart failure. Glucagon-like peptide-1 receptor agonists (GLP-1 RA) are becoming popular in the management of T2D. Previous studies have demonstrated that GLP-1 RAs reduce major adverse cardiovascular events (MACE) in T2D patients compared to placebo. However, the impact of GLP-1 RAs on mortality and cardiovascular outcomes in patients with T2D and systolic heart failure remains uncertain.AimThis study examines the effects of GLP-1 RA on individuals with T2D and systolic heart failure, focusing on all-cause mortality, cardiovascular outcomes (including ischemic heart disease, acute myocardial infarction, heart failure exacerbations, stroke, peripheral vascular disease, chronic kidney disease), and all-cause hospitalization.Methods:The TriNetX research database was utilized to identify patients aged 18 years and older with T2D and systolic heart failure. Patients were classified into two groups: GLP-1 RA users and non-users. Propensity score matching (1:1) was conducted based on demographics, body mass index, comorbidities, glycated hemoglobin levels, and medications, resulting in a matched cohort of 23,873 patients. Outcomes analyzed included all-cause mortality, cardiovascular outcomes and all cause hospitalization. Survival analysis was performed using TriNetX software, estimating the probability of outcomes over 5 years from the index event and generating hazard ratios (HR), log-rank tests, and Kaplan-Meier survival curves.Results:The GLP-1 RA user group demonstrated a reduced hazard ratio (HR, 95% confidence interval) over 5 years compared with the control group for all-cause mortality (0.705, 0.675-0.736, P

Circulation, Volume 150, Issue Suppl_1, Page A4126304-A4126304, November 12, 2024. Background:About one in five adults at age 40 will develop heart failure (HF) during their lifetime. Risk factors for HF (e.g., hypertension, etc.) alter cardiomyocytes structure and function resulting in HF. At the cellular level, these changes consist of mis/over-expression of genes that regulate cardiac identity (e.g., CamK2d, PKC, etc). The current paradigm for treating HF is pharmacological intervention or surgery; however, with few exceptions, the condition worsens with time. We are proposing a paradigm-shift for treating HF from a drug-centric system to a molecular approach that would reverse hypertrophy and adverse remodeling.Methods:A cardiac targeting peptide (CTP) was generated and linked by disulfide bond to miRNA106a, which was then introduced into a HF mouse model to measure its ability to reverse multiple heart failure parameters. CTP-miRNA106a was also introduced into a human cardiac cell line, followed by multiple analyses including Western Blot, qPCR, FACS, immunofluorescence all used to identify mechanism(s) utilized by CTP-miRNA106a to reverse HF characteristics.Results:Bio-distribution studies showed CTP delivered its miRNA106a cargo specifically to the heart within 30 mins, followed by clearance of CTP from the heart to the kidneys and liver by 3-5hrs post systemic drug injection. MiRNA106a persisted in cardiomyocytes until day 7 (latest tested time-point). CTP-miRNA106a reversed Ang2/Iso induced hypertrophy in 90% of the experimental mice (Fig1). We also identified two potential HF intracellular signaling mechanisms (PLCb1/PKC/IP3 and NfkB) targeted by CTP-miRNA106a that could benefit both types of HF, HFrEF and HFpEF. PLCβ1 is a direct target for miRNA106a while the Nfkb pathway is indirectly targeted by decreased Camk2d (an miRNA106a target) signaling to IκBα. NfkB activity is quelled by miRNA106a.Conclusions:Our approach utilizes the function of miRNA106a to downregulate genes involved in cardiac hypertrophy and inflammation through the PLCb1 and CamKIId/Nfkb pathways. Most importantly, using a CTP-miRNA106a, we show delivery of miRNA106a cargo is specific to cardiomyocytes bothin vitroandin vivoand that once delivered, many HF parameters including hypertrophy are reversed.

New England Journal of Medicine, Ahead of Print.

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