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BMC Pulmonary Medicine Jan 2024Klotho is an anti-aging protein that has multiple functions and may play a key role in the pathogenesis and progression of chronic respiratory diseases such as chronic...
BACKGROUND
Klotho is an anti-aging protein that has multiple functions and may play a key role in the pathogenesis and progression of chronic respiratory diseases such as chronic obstructive pulmonary disease (COPD). Fractional Exhaled Nitric Oxide (FeNO) is a non-invasive and novel biomarker that has the advantages of being simple, fast and reproducible. It can effectively assess the degree of airway inflammation in diseases such as asthma and COPD. Despite these insights, the relationship between serum Klotho levels and FeNO has not been explored yet.
METHODS
Leveraging data from the National Health and Nutrition Examination Survey (NHANES) spanning 2007 to 2012, we investigated the correlation between FeNO and serum Klotho levels. This association was scrutinized both as continuous variables and within quartile distributions, utilizing the Kruskal-Wallis H test. The correlation between the two variables was assessed through Spearman rank analysis. Employing survey weight-adjusted linear regression models, we gauged the strength of these associations.
RESULTS
This study included 6,527 participants with a median FeNO level of 14.5 parts per billion (ppb). We found that FeNO levels varied significantly across different quartiles of Klotho protein (H = 7.985, P = 0.046). We also found a significant positive correlation between serum Klotho levels and FeNO levels in the whole population (Spearman's rho = 0.029, P = 0.019). This correlation remained significant after adjusting for covariates such as age, gender, lung function, smoking status, alcohol use, BMI, cardiovascular disease (including hypertension, heart failure, coronary heart disease, and myocardial infarction), diabetes, inflammatory markers, serum vitamin D level and BUN (P < 0.05 for all). Furthermore, this correlation was stronger at the high (K3) and super high (K4) levels of Klotho than at the low (K1) and medium (K2) levels (β = 1.979 ppb and β = 1.993 ppb for K3 and K4 vs. K1, respectively; 95% CI: 0.497 ~ 2.953 and 95% CI: 0.129 ~ 2.827, respectively; P = 0.007 and P = 0.032, respectively). The β coefficient for serum Klotho was 0.002 ppb/pg/ml.
CONCLUSIONS
Our study illuminates a positive correlation between serum Klotho levels and FeNO. Further study is needed to verify the causality of this association and elucidate the underlying mechanisms.
Topics: Humans; Nutrition Surveys; Cross-Sectional Studies; Fractional Exhaled Nitric Oxide Testing; Nitric Oxide; Breath Tests; Pulmonary Disease, Chronic Obstructive; Exhalation
PubMed: 38287280
DOI: 10.1186/s12890-024-02864-7 -
Global Heart 2024To investigate differences in levels of the triglyceride-glucose (TyG) index between individuals with myocardial infarction (MI) and those without MI, as well as the...
OBJECTIVE
To investigate differences in levels of the triglyceride-glucose (TyG) index between individuals with myocardial infarction (MI) and those without MI, as well as the association between TyG index and risk of MI.
METHODS
Data from the National Health and Nutrition Examination Survey (NHANES) for US adults from 2013 to 2018 were included in this study. Using MI as an outcome variable and TyG index as an exposure variable, logistic regression models were employed to analyze relationship between MI and TyG index.
RESULTS
The study included 6,695 participants. Compared to the non-MI group, patients with MI had significantly higher TyG index (8.89 vs. 8.63, = 0.003). Higher TyG index was significantly associated with an increased risk of MI in US adults (OR: 1.69, 95% CI: 1.26-2.26, < 0.001). Race, smoking status, and history of chronic obstructive pulmonary disease (COPD) had significant impacts on the association between TyG index and risk of MI ( for interaction < 0.05). Subgroup analysis demonstrated a significant positive correlation between TyG index and MI risk in non-Hispanic Black individuals, non-smokers, and individuals without COPD across multiple models (OR > 1.0, < 0.05).
CONCLUSION
US adults with higher TyG index were more susceptible to MI, and TyG index may be used to identify individuals at high risk of MI in the US population.
Topics: Adult; Humans; Nutrition Surveys; Glucose; Myocardial Infarction; Pulmonary Disease, Chronic Obstructive; Triglycerides; Blood Glucose; Biomarkers
PubMed: 38404616
DOI: 10.5334/gh.1303 -
Diabetes Care Oct 2023To develop a risk assessment tool to identify patients with type 2 diabetes (T2D) at higher risk for kidney disease progression and who might benefit more from...
OBJECTIVE
To develop a risk assessment tool to identify patients with type 2 diabetes (T2D) at higher risk for kidney disease progression and who might benefit more from sodium-glucose cotransporter 2 (SGLT2) inhibition.
RESEARCH DESIGN AND METHODS
A total of 41,204 patients with T2D from four Thrombolysis In Myocardial Infarction (TIMI) clinical trials were divided into derivation (70%) and validation cohorts (30%). Candidate predictors of kidney disease progression (composite of sustained ≥40% decline in estimated glomerular filtration rate [eGFR], end-stage kidney disease, or kidney death) were selected with multivariable Cox regression. Efficacy of dapagliflozin was assessed by risk categories (low: <0.5%; intermediate: 0.5 to <2%; high: ≥2%) in Dapagliflozin Effect on Cardiovascular Events (DECLARE)-TIMI 58.
RESULTS
There were 695 events over a median follow-up of 2.4 years. The final model comprised eight independent predictors of kidney disease progression: atherosclerotic cardiovascular disease, heart failure, systolic blood pressure, T2D duration, glycated hemoglobin, eGFR, urine albumin-to-creatinine ratio, and hemoglobin. The c-indices were 0.798 (95% CI, 0.774-0.821) and 0.798 (95% CI, 0.765-0.831) in the derivation and validation cohort, respectively. The calibration plot slope (deciles of predicted vs. observed risk) was 0.98 (95% CI, 0.93-1.04) in the validation cohort. Whereas relative risk reductions with dapagliflozin did not differ across risk categories, there was greater absolute risk reduction in patients with higher baseline risk, with a 3.5% absolute risk reduction in kidney disease progression at 4 years in the highest risk group (≥1%/year). Results were similar with the 2022 Chronic Kidney Disease Prognosis Consortium risk prediction model.
CONCLUSIONS
Risk models for kidney disease progression can be applied in patients with T2D to stratify risk and identify those who experience a greater magnitude of benefit from SGLT2 inhibition.
Topics: Humans; Benzhydryl Compounds; Diabetes Mellitus, Type 2; Disease Progression; Glomerular Filtration Rate; Kidney; Myocardial Infarction; Renal Insufficiency, Chronic; Risk Assessment; Sodium-Glucose Transporter 2; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 37556796
DOI: 10.2337/dc23-0492 -
Translational Neuroscience Jan 2023Endovascular therapy (EVT) was the standard treatment for acute ischemic stroke with large vessel occlusion. Prognosis after EVT is always a major concern. Here, we...
BACKGROUND
Endovascular therapy (EVT) was the standard treatment for acute ischemic stroke with large vessel occlusion. Prognosis after EVT is always a major concern. Here, we aimed to explore a predictive model for patients after EVT.
METHOD
A total of 156 patients were retrospectively enrolled. The primary outcome was functional dependence (defined as a 90-day modified Rankin Scale score ≤ 2). Least absolute shrinkage and selection operator and univariate logistic regression were used to select predictive factors. Various machine learning algorithms, including multivariate logistic regression, linear discriminant analysis, support vector machine, -nearest neighbors, and decision tree algorithms, were applied to construct prognostic models.
RESULT
Six predictive factors were selected, namely, age, baseline National Institute of Health Stroke Scale (NIHSS) score, Alberta Stroke Program Early CT (ASPECT) score, modified thrombolysis in cerebral infarction score, symptomatic intracerebral hemorrhage (sICH), and complications (pulmonary infection, gastrointestinal bleeding, and cardiovascular events). Based on these variables, various models were constructed and showed good discrimination. Finally, a nomogram was constructed by multivariate logistic regression and showed a good performance.
CONCLUSION
Our nomogram, which was composed of age, baseline NIHSS score, ASPECT score, recanalization status, sICH, and complications, showed a very good performance in predicting outcome after EVT.
PubMed: 38035150
DOI: 10.1515/tnsci-2022-0324 -
Circulation. Arrhythmia and... May 2024The risk factor (RF) burden, clinical course, and long-term outcome among patients with atrial fibrillation (AF) aged <65 years is unclear.
BACKGROUND
The risk factor (RF) burden, clinical course, and long-term outcome among patients with atrial fibrillation (AF) aged <65 years is unclear.
METHODS
Adult (n=67 221; mean age, 72.4±12.3 years; and 45% women) patients with AF evaluated at the University of Pittsburgh Medical Center between January 2010 and December 2019 were studied. Hospital system-wide electronic health records and administrative data were utilized to ascertain RFs, comorbidities, and subsequent hospitalization and cardiac interventions. The association of AF with all-cause mortality among those aged <65 years was analyzed using an internal contemporary cohort of patients without AF (n=918 073).
RESULTS
Nearly one-quarter (n=17 335) of the cohort was aged <65 years (32% women) with considerable cardiovascular RFs (current smoker, 16%; mean body mass index, 33.0±8.3; hypertension, 55%; diabetes, 21%; heart failure, 20%; coronary artery disease, 19%; and prior ischemic stroke, 6%) and comorbidity burden (chronic obstructive pulmonary disease, 11%; obstructive sleep apnea, 18%; and chronic kidney disease, 1.3%). Over mean follow-up of >5 years, 2084 (6.7%, <50 years; 13%, 50-65 years) patients died. The proportion of patients with >1 hospitalization for myocardial infarction, heart failure, and stroke was 1.3%, 4.8%, and 1.1% for those aged <50 years and 2.2%, 7.4%, and 1.1% for the 50- to 65-year subgroup, respectively. Multiple cardiac and noncardiac RFs were associated with increased mortality in younger patients with AF with heart failure and hypertension demonstrating significant age-related interaction (=0.007 and =0.013, respectively). Patients with AF aged <65 years experienced significantly worse survival compared with comorbidity-adjusted patients without AF (men aged <50 years and hazard ratio, 1.5 [95% CI, 1.24-1.79]; 50-65 years and hazard ratio, 1.3 [95% CI, 1.26-1.43]; women aged <50 years and hazard ratio, 2.4 [95% CI, 1.82-3.16]; 50-65 years and hazard ratio, 1.7 [95% CI, 1.6-1.92]).
CONCLUSIONS
Patients with AF aged <65 years have significant comorbidity burden and considerable long-term mortality. They are also at a significantly increased risk of hospitalization for heart failure, stroke, and myocardial infarction. These patients warrant an aggressive focus on RF and comorbidity evaluation and management.
Topics: Humans; Atrial Fibrillation; Female; Male; Aged; Hospitalization; Middle Aged; Risk Factors; Comorbidity; Risk Assessment; Age Factors; Retrospective Studies; Time Factors; Aged, 80 and over; Pennsylvania; Cause of Death
PubMed: 38646831
DOI: 10.1161/CIRCEP.123.012143 -
Vaccine Jul 2023Our near-real-time safety monitoring of 16 adverse events (AEs) following COVID-19 mRNA vaccination identified potential elevation in risk for six AEs following primary...
BACKGROUND
Our near-real-time safety monitoring of 16 adverse events (AEs) following COVID-19 mRNA vaccination identified potential elevation in risk for six AEs following primary series and monovalent booster dose administration. The crude association with AEs does not imply causality. Accordingly, we conducted robust evaluation of potential associations.
METHODS
We conducted two self-controlled case series studies of COVID-19 mRNA vaccines (BNT162b2 and mRNA-1273) in U.S. Medicare beneficiaries aged ≥ 65 years. Adjusted incidence rate ratio (IRRs) and 95 % confidence intervals (CIs) were estimated following primary series doses for acute myocardial infarction (AMI), pulmonary embolism (PE), immune thrombocytopenia (ITP), disseminated intravascular coagulation (DIC); and following monovalent booster doses for AMI, PE, ITP, Bell's Palsy (BP) and Myocarditis/Pericarditis (Myo/Peri).
RESULTS
The primary series study included 3,360,981 individuals who received 6,388,542 primary series doses; the booster study included 6,156,100 individuals with one monovalent booster dose. The AMI IRR following BNT162b2 primary series and booster was 1.04 (95 % CI: 0.91 to 1.18) and 1.06 (95 % CI: 1.003 to 1.12), respectively; for mRNA-1273 primary series and booster, 1.01 (95 % CI: 0.82 to 1.26) and 1.05 (95 % CI: 0.998 to 1.11), respectively. The hospital inpatient PE IRR following BNT162b2 primary series and booster was 1.19 (95 % CI: 1.03 to 1.38) and 0.86 (95 % CI: 0.78 to 0.95), respectively; for mRNA-1273 primary series and booster, 1.15 (95 % CI: 0.94 to 1.41) and 0.87 (95 % CI: 0.79 to 0.96), respectively. The studies' results do not support that exposure to COVID-19 mRNA vaccines elevate the risk of ITP, DIC, Myo/Peri, and BP.
CONCLUSION
We did not find an increased risk for AMI, ITP, DIC, BP, and Myo/Peri and there was not consistent evidence for PE after exposure to COVID-19 mRNA primary series or monovalent booster vaccines. These results support the favorable safety profile of COVID-19 mRNA vaccines administered in the U.S. elderly population.
Topics: United States; Humans; Adult; Aged; 2019-nCoV Vaccine mRNA-1273; BNT162 Vaccine; COVID-19; Medicare; Purpura, Thrombocytopenic, Idiopathic; Thrombocytopenia; Vaccination; Bell Palsy; Facial Paralysis; Myocardial Infarction; Myocarditis; Pericarditis; Pulmonary Embolism; RNA, Messenger
PubMed: 37344261
DOI: 10.1016/j.vaccine.2023.06.014 -
Diagnostics (Basel, Switzerland) Mar 2024Although classical gross features are known in hypothermia victims, they lack specific diagnosis features. The aim of our study was to reveal specific brain and lung...
BACKGROUND AND OBJECTIVES
Although classical gross features are known in hypothermia victims, they lack specific diagnosis features. The aim of our study was to reveal specific brain and lung pathological features in a group of hypothermia-related fatalities.
MATERIALS AND METHODS
The study group comprised 107 cases from our files associated with hypothermia. Routine hematoxylin-eosin (H&E) staining and postmortem immunohistochemistry were performed.
RESULTS
The microscopic cerebral exam revealed diffuse perineuronal and perivascular edema, gliosis, mononuclear cell infiltration, acute brain injuries, focal neuronal ischemia, lacunar infarction, and variable hemorrhages. Variable alveolar edema, pulmonary emphysema, intra-alveolar and/or pleural hemorrhage, and bronchopneumonia, as well as other pre-existing lesions, were identified in lung tissue samples. Glial cells displayed S100β expression, while neurons showed moderate Hsp70 immunopositivity. Alveolar basal membranes exhibited diffuse ICAM-1 positive expression, while ICAM-1 and AQP-1 positivity was observed in the alveolar septum vascular endothelium. Statistical analysis revealed a significant correlation between S100β and Hps70 immunoexpression and cerebral pathological features, between ICAM-1 immunoexpression and alveolar edema and pulmonary emphysema, and between AQP-1 immunoexpression and pulmonary emphysema.
CONCLUSIONS
Our results add supplementary data to brain and lung pathological findings in hypothermia-related fatalities, with potential therapeutic value in hypothermia patients.
PubMed: 38611652
DOI: 10.3390/diagnostics14070739 -
Diagnostics (Basel, Switzerland) Aug 2023Cardiovascular disease (CVD) is a major cause of morbidity and mortality in patients with chronic kidney disease (CKD), especially in end-stage renal disease (ESRD)... (Review)
Review
Cardiovascular disease (CVD) is a major cause of morbidity and mortality in patients with chronic kidney disease (CKD), especially in end-stage renal disease (ESRD) patients and during the first year after transplantation. For these reasons, and due to the shortage of organs available for transplant, it is of utmost importance to identify patients with a good life expectancy after transplant and minimize the transplant peri-operative risk. Various conditions, such as severe pulmonary diseases, recent myocardial infarction or stroke, and severe aorto-iliac atherosclerosis, need to be ruled out before adding a patient to the transplant waiting list. The effectiveness of systematic coronary artery disease (CAD) treatment before kidney transplant is still debated, and there is no universal screening protocol, not to mention that a nontailored screening could lead to unnecessary invasive procedures and delay or exclude some patients from transplantation. Despite the different clinical guidelines on CAD screening in kidney transplant candidates that exist, up to today, there is no worldwide universal protocol. This review summarizes the key points of cardiovascular risk assessment in renal transplant candidates and faces the role of noninvasive cardiovascular imaging tools and the impact of coronary revascularization versus best medical therapy before kidney transplant on a patient's cardiovascular outcome.
PubMed: 37627968
DOI: 10.3390/diagnostics13162709 -
Frontiers in Immunology 2024Juvenile Systemic Connective Tissue Diseases (JSCTD) are a heterogeneous group of chronic autoimmune diseases, associated with dyslipidemia and increased cardiovascular... (Review)
Review
Juvenile Systemic Connective Tissue Diseases (JSCTD) are a heterogeneous group of chronic autoimmune diseases, associated with dyslipidemia and increased cardiovascular risk are related. Studies from the last 10 years, from 2013 to 2022, on lipid profiles in JSCTD were collected. Different studies on lipid profiles in children affected by JSCTD were selected, because the aim is to analyze the cardiovascular risk and the possibility of atherosclerosis in these patients in whom, sometimes, corticosteroid therapies and immunosuppressants increase the state of dyslipidemia. Several studies have shown that autoimmune diseases with an inflammatory substrate also share abnormalities in lipid profile and increased cardiovascular risk. Specifically, associations have been found between Juvenile Systemic Connective Tissue Diseases and elevated triglycerides, TC-C (Total Cholesterol), LDL-C (Low-Density Lipoprotein), low HDL-C (High-Density Lipoprotein), and increased risk of developing diseases such as myocardial infarction, peripheral vascular disease, pulmonary and arterial hypertension, and atrial fibrillation. Supplementation with alpha-linolenic acid (ALA) on the other hand has also been analyzed with positive results in reducing inflammatory parameters, such as IL-6 (Interleukin-6), CRP (C-reactive protein), and fasting glucose, in subjects with dyslipidemia. These observations suggest that supplementation with ALA, an omega-3 precursor, may positively modulate both the inflammatory status and dyslipidemic conditions in patients with autoimmune disorders.
Topics: Child; Humans; Risk Factors; Cardiovascular Diseases; Inflammation; Lipoproteins, LDL; Heart Disease Risk Factors; Dyslipidemias; Connective Tissue Diseases
PubMed: 38605945
DOI: 10.3389/fimmu.2024.1380372 -
Cureus Aug 2023Asthma is a common pathology worldwide that occurs due to chronic inflammation of the respiratory airways. Persistent pulmonary inflammation leads to low-grade systemic... (Review)
Review
Asthma is a common pathology worldwide that occurs due to chronic inflammation of the respiratory airways. Persistent pulmonary inflammation leads to low-grade systemic inflammation, influencing blood vessels and triggering coronary artery disease (CAD) events. This review's objectives include discussing the susceptible population for CAD, the mechanism underlying CAD creation in asthma patients, the characteristics of asthma, and the influence of anti-asthmatic medications on CAD development. Adult-onset asthma is strongly linked to CAD and stroke. Future research may shed light on these disparities. Atherosclerosis and asthma are linked through both intrinsic and extrinsic pathways, with inflammation being the intrinsic pathway and hypoxia and tachyarrhythmia being the extrinsic pathways. The most probable mechanisms for increased coronary vasospastic angina (CVsA) incidence in asthmatic patients are vascular smooth muscle cell hypercontraction and endothelial dysfunction. Studies have shown a dose-response relationship between asthma control and myocardial infarction (MI) risk, with uncontrolled asthma at the highest risk. Impairment of ventilatory function is a distinct risk factor for lethal MI and cardiovascular death (CVD). The use of beta-2-agonists and chronic oral glucocorticoid therapy in severe asthmatics has been linked to increasing the risk for CAD. However, some studies have shown that the risk of MI among patients with active asthma is not related to the use of asthma medications. Further research is needed to determine the involvement of adult asthma features and their treatments in the development of CAD.
PubMed: 37719576
DOI: 10.7759/cureus.43621