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Hypertension is one of the most common chronic diseases in older people, and the prevalence is on the rise as the global population ages. Hypertension is closely associated with many adverse health outcomes, including cardiovascular disease, chronic kidney disease and mortality, which poses a substantial threat to global public health. Reasonable blood pressure (BP) management is very important for reducing the occurrence of adverse events. Frailty is an age-related geriatric syndrome, characterized by decreased physiological reserves of multiple organs and systems and increased sensitivity to stressors, which increases the risk of falls, hospitalization, fractures, and mortality in older people. With the aging of the global population and the important impact of frailty on clinical practice, frailty has attracted increasing attention in recent years. In older people, frailty and hypertension often coexist. Frailty has a negative impact on BP management and the prognosis of older hypertensive patients, while hypertension may increase the risk of frailty in older people. However, the causal relationship between frailty and hypertension remains unclear, and there is a paucity of research regarding the efficacious management of hypertension in frail elderly patients. The management of hypertension in frail elderly patients still faces significant challenges. The benefits of treatment, the optimal BP target, and the choice of antihypertensive drugs for older hypertensive patients with frailty remain subjects of ongoing debate. This review provides a brief overview of hypertension in frail older adults, especially for the management of BP in this population, which may help in offering valuable ideas for future research in this field.
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Antihipertensivos , Anciano Frágil , Hipertensión , Humanos , Hipertensión/epidemiología , Hipertensión/tratamiento farmacológico , Anciano , Antihipertensivos/uso terapéutico , Fragilidad/epidemiología , Anciano de 80 o más Años , Factores de RiesgoRESUMEN
BACKGROUND: Hypertension and frailty often coexist in older people. The present study aimed to evaluate the association of frailty status with overall survival in elderly hypertensive patients, using data from the Chinese Longitudinal Healthy Longevity Survey. METHODS: A total of 10,493 elderly hypertensive patients were included in the present study (median age 87.0 years, 58.3% male). Frailty status was assessed according to a 36-item frailty index (FI), which divides elderly individuals into four groups: robustness (FI ≤ 0.10), pre-frailty (0.10 < FI ≤ 0.20), mild-frailty (0.20 < FI ≤ 0.30), and moderate-severe frailty (FI > 0.30). The study outcome was overall survival time. Accelerated failure time model was used to evaluate the association of frailty status with overall survival. RESULTS: During a period of 44,616.6 person-years of follow-up, 7327 (69.8%) participants died. The overall survival time was decreased with the deterioration of frailty status. With the robust group as reference, adjusted time ratios (TRs) were 0.84 (95% confidence interval [CI]: 0.80-0.87) for the pre-frailty group, 0.68 (95% CI: 0.64-0.72) for the mild frailty group, and 0.52 (95% CI: 0.48-0.56) for the moderate-severe frailty group, respectively. In addition, restricted cubic spline analysis revealed a nearly linear relationship between FI and overall survival (p for non-linearity = 0.041), which indicated the overall survival time decreased by 17% with per standard deviation increase in FI (TR = 0.83, 95% CI: 0.82-0.85). Stratified and sensitivity analyses suggested the robustness of the results. CONCLUSIONS: The overall survival time of elderly hypertensive patients decreased with the deterioration of frailty status. Given that frailty is a dynamic and even reversible process, early identification of frailty and active intervention may improve the prognosis of elderly hypertensive patients.
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Anciano Frágil , Fragilidad , Hipertensión , Humanos , Masculino , Femenino , Estudios Longitudinales , Hipertensión/mortalidad , Anciano de 80 o más Años , China/epidemiología , Fragilidad/mortalidad , Anciano , Anciano Frágil/estadística & datos numéricos , Longevidad , Evaluación Geriátrica , Análisis de Supervivencia , Encuestas Epidemiológicas , Pueblos del Este de AsiaRESUMEN
BACKGROUND: This study focused on circulating plasma protein profiles to identify mediators of hypertension-driven myocardial remodeling and heart failure. METHODS: A Mendelian randomization design was used to investigate the causal impact of systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure on 82 cardiac magnetic resonance traits and heart failure risk. Mediation analyses were also conducted to identify potential plasma proteins mediating these effects. RESULTS: Genetically proxied higher SBP, DBP, and pulse pressure were causally associated with increased left ventricular myocardial mass and alterations in global myocardial wall thickness at end diastole. Elevated SBP and DBP were linked to increased regional myocardial radial strain of the left ventricle (basal anterior, mid, and apical walls), while higher SBP was associated with reduced circumferential strain in specific left ventricular segments (apical, mid-anteroseptal, mid-inferoseptal, and mid-inferolateral walls). Specific plasma proteins mediated the impact of blood pressure on cardiac remodeling, with FGF5 (fibroblast growth factor 5) contributing 2.96% (P=0.024) and 4.15% (P=0.046) to the total effect of SBP and DBP on myocardial wall thickness at end diastole in the apical anterior segment and leptin explaining 15.21% (P=0.042) and 23.24% (P=0.022) of the total effect of SBP and DBP on radial strain in the mid-anteroseptal segment. Additionally, FGF5 was the only mediator, explaining 4.19% (P=0.013) and 4.54% (P=0.032) of the total effect of SBP and DBP on heart failure susceptibility. CONCLUSIONS: This mediation Mendelian randomization study provides evidence supporting specific circulating plasma proteins as mediators of hypertension-driven cardiac remodeling and heart failure.
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Insuficiencia Cardíaca , Hipertensión , Humanos , Análisis de la Aleatorización Mendeliana , Remodelación Ventricular , Corazón , Presión Sanguínea/fisiologíaRESUMEN
OBJECTIVE: A new inflammatory marker, namely monocyte-to-high-density lipoprotein cholesterol ratio (MHR), has emerged as a useful indicator for adverse outcomes in several cardiovascular diseases; however, the relationship between MHR and the prognosis of hypertrophic cardiomyopathy (HCM) remains to be evaluated. We examined the relationship between MHR and all-cause mortality (ACM) in Chinese adult patients with HCM. METHODS: We retrospectively performed clinical evaluation in 305 patients with HCM (median age: 52.0 years, male: 54.10%). RESULTS: During a median follow-up of 4.9 years, ACM occurred in 57 (18.7%) patients. Based on the tertiles of baseline MHR, ACM increased with higher tertile. With tertile 1 as reference, adjusted ACM hazard ratios (HRs) were 2.68 for tertile 2 (95% confidence interval [CI]: 1.18-6.11, p = 0.019) and 4.85 for tertile 3 (95% CI: 2.16-10.89, p < 0.001). Stratified analysis and E-value analysis suggested the robustness of the above-mentioned results. Furthermore, adjusted smooth curve fitting exhibited a non-linear relationship between MHR and ACM (inflection point: 0.5), and the risk of ACM increased significantly with higher MHR only the value below the inflection point (HR: 4.37 per one standard deviation, 95% CI: 1.81-10.6, p = 0.001). Finally, sensitivity analysis was similar to the main findings. CONCLUSION: In Chinese adult patients with HCM, higher MHR is a strong independent predictor of ACM, and a non-linear relationship is also observed between MHR and ACM.
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Cardiomiopatía Hipertrófica , Monocitos , Adulto , Humanos , Masculino , Persona de Mediana Edad , HDL-Colesterol , Estudios Retrospectivos , Pronóstico , Cardiomiopatía Hipertrófica/complicacionesRESUMEN
Garlic (Allium sativum) is a functional food containing multiple bioactive compounds that find widespread applications in culinary and medicinal practices. It consists of multiple chemical components, including allicin and alliin. This article offers a comprehensive review of the protective effects of garlic extracts and their active constituents on the vascular system. In vitro and in vivo experiments have shown that garlic extracts and their active ingredients possess various bioactive properties. These substances demonstrate beneficial effects on blood vessels by demonstrating anti-inflammatory and antioxidant activities, inhibiting lipid accumulation and migration, preventing lipid peroxidation, promoting angiogenesis, reducing platelet aggregation, enhancing endothelial function, and inhibiting endothelial cell apoptosis. In clinical studies, garlic and its extracts have demonstrated their efficacy in managing vascular system diseases, including atherosclerosis, diabetes, and high cholesterol levels. In summary, these studies highlight the potential therapeutic roles and underlying mechanisms of garlic and its constituents in managing conditions like diabetes, atherosclerosis, ischemic diseases, and other vascular disorders.
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Aterosclerosis , Diabetes Mellitus , Ajo , Humanos , Ajo/química , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Aterosclerosis/tratamiento farmacológico , Aterosclerosis/prevención & control , Diabetes Mellitus/tratamiento farmacológicoRESUMEN
BACKGROUND: Albumin to fibrinogen ratio (AFR), a new inflammatory marker, has emerged as a useful indicator to predict adverse outcomes for several diseases. However, whether AFR could be a new useful indicator to predict mortality in HCM patients remains to be evaluated. The study explored the predictive value of AFR for HCM-related death in adult HCM patients. METHODS: A total of 404 HCM patients were eventually enrolled in the study according to the inclusion criteria. Patients were divided into two groups based on the median of baseline AFR. The association between AFR and HCM-related death was analyzed. RESULTS: During a median follow-up of 4.75 years, HCM-related death was observed in 45 patients (11.1%). The incidence of HCM-related death was significantly higher in the low AFR group (log-rank p < 0.001). With the high AFR group as reference, the unadjusted hazard ratio (HR) for HCM-related death was 2.97 (95% confidence interval [CI]: 1.53-5.75, p = 0.001) in the low AFR group, and after adjusting for potentially confounding variables, the adjusted HR for low AFR group was 3.15 (95% CI: 1.56-6.37, p = 0.001). No significant interactions between AFR and other variables were observed in subgroup analysis. Sensitivity analyses in patients with normal albumin and fibrinogen showed similar results. CONCLUSION: AFR is an independent prognostic factor for HCM-related death, adult HCM patients with a lower AFR have a higher risk of HCM-related death.
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Cardiomiopatía Hipertrófica , Fibrinógeno , Adulto , Humanos , Pronóstico , Fibrinógeno/análisis , Albúminas , Modelos de Riesgos Proporcionales , Cardiomiopatía Hipertrófica/diagnóstico , Estudios RetrospectivosRESUMEN
Background: Astragaloside IV (ASIV) is the primary pharmacologically active compound found in Astragalus propinquus Schischkin, which has potential protective effects on cardiac function. However, there are almost no systematic evaluations of ASIV for the treatment of heart failure (HF). Methods: Preclinical studies published before 27 December 2022, were retrieved from PubMed, Web of Science, MEDLINE, SinoMed, Chinese National Knowledge Infrastructure (CNKI), VIP information database, and Wanfang Data information site. The quality of included research was evaluated using SYRCLE's RoB tool. Review Manager 5.4.1 was used to perform meta-analyses of the cardiac function parameters and other indicators. Regression analysis was conducted to observe the dose-efficacy relationship. Results: Nineteen studies involving 489 animals were included. Results indicated that compared with the control group, ASIV could enhance cardiac function indicators, including left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), left ventricular pressure change rate (±dp/dtmax), left ventricular end-diastolic pressure (LVEDP), left ventricular systolic pressure (LVSP), heart weight/body weight (HW/BW) and left ventricular weight/body weight (LVW/BW). Furthermore, the regression analysis showed that the treatment of HF with ASIV was dose-dependent. Conclusion: Findings suggest that ASIV can inhibit cardiac hypertrophy by reducing cardiac preload and afterload, thereby protecting cardiac function.
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Osteoporosis (OP) is a systemic skeletal disease prevalent in older adults, characterized by substantial bone loss and deterioration of microstructure, resulting in heightened bone fragility and risk of fracture. Traditional Chinese Medicine (TCM) herbs have been widely employed in OP treatment owing to their advantages, such as good tolerance, low toxicity, high efficiency, and minimal adverse reactions. Increasing evidence also reveals that many plant-based compounds (or secondary metabolites) from these TCM formulas, such as resveratrol, naringin, and ginsenoside, have demonstrated beneficial effects in reducing the risk of OP. Nonetheless, the comprehensive roles of these natural products in OP have not been thoroughly clarified, impeding the development of synergistic formulas for optimal OP treatment. In this review, we sum up the pathological mechanisms of OP based on evidence from basic and clinical research; emphasis is placed on the in vitro and preclinical in vivo evidence-based anti-OP mechanisms of TCM formulas and their chemically active plant constituents, especially their effects on imbalanced bone homeostasis regulated by osteoblasts (responsible for bone formation), osteoclasts (responsible for bone resorption), bone marrow mesenchymal stem cells as well as bone microstructure, angiogenesis, and immune system. Furthermore, we prospectively discuss the combinatory ingredients from natural products from these TCM formulas. Our goal is to improve comprehension of the pharmacological mechanisms of TCM formulas and their chemically active constituents, which could inform the development of new strategies for managing OP.
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Salvia miltiorrhiza Bunge is a natural drug for treating myocardial infarction (MI). However, the targets and mechanisms of S. miltiorrhiza Bunge in the treatment of MI are yet to be elucidated. Traditional Chinese medicine systems pharmacology (TCMSP) data were used to screen out chemical constituents, and UniProt was used to predict relevant targets. Disease targets were obtained from the Online Mendelian Inheritance in Man and GeneCards databases. We used the STRING platform to build a protein-protein interaction network and used Cytoscape_v3.8.1 software to make a Drug-Ingredients-Gene Symbols-Disease network map. The Metascape database was used to perform gene ontology and Kyoto Encyclopaedia of Genes and Genomes (KEGG) enrichment analyses for drug-disease overlapping gene symbols. The targets identified by network pharmacology were further verified by in vitro and in vivo experiments. Seventy-five active components of S. miltiorrhiza Bunge were obtained from the TCMSP database, while 370 disease targets and 29 cross-targets were obtained from the Genecards database. The KEGG pathway enrichment results suggested that the mechanism of S. miltiorrhiza Bunge in the treatment of MI was significantly related to the VEGF signalling pathway. In vitro and in vivo experiments were used to evaluate the reliability of some important active ingredients and targets. S. miltiorrhiza Bunge alleviated the damage to cardiac function, attenuated myocardial fibrosis and protected endothelial cell function by increasing the expression of TGF-ß and VEGFA. S. miltiorrhiza Bunge showed the therapeutic effect of MI by promoting the expression of VEGFA signalling pathway, providing a reliable basis for exploring herbal treatment of MI.
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Medicamentos Herbarios Chinos , Infarto del Miocardio , Salvia miltiorrhiza , Humanos , Farmacología en Red , Reproducibilidad de los Resultados , Infarto del Miocardio/tratamiento farmacológico , Infarto del Miocardio/genética , Bases de Datos Genéticas , Medicina Tradicional China , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Simulación del Acoplamiento MolecularRESUMEN
We report on the successful development of a magnetic molecularly imprinted polymer (MMIP) for the separation and detection of catalpol in Rehmannia glutinosa extract and biological samples. Catalpol was used as the template molecule for the MMIPs, which were synthesized using the reverse prediction approach and differential UV-visible spectra to optimize the synthesis conditions. The resulting MMIPs were characterized using techniques including scanning electron microscopy, transmission electron microscopy, Fourier transform infrared spectroscopy, and vibrating sample magnetometry, which confirmed their excellent nuclear shell construction and simple rapid magnetic separation. Static and dynamic adsorption experiments were performed to assess the sensitivity, repeatability, and adsorption capacity of the MMIPs. Adsorption capacity was found to be high (59.09 µg/mg). The MMIPs also exhibited strong identification specificity for catalpol analogs (IFâ =â 2.41). Magnetic solid phase extraction (MSPE) was optimized to establish an MSPE-HPLC approach based on the MMIPs. Under ideal conditions, the new method showed excellent determination coefficient (R2â > 0.99) in the ranges of 0.1-1.0 mg/mL and 0.03-0.18 mg/mL for R. glutinosa extract and biological material, respectively, with limits of detection of 5.4 ng/mL and 1.7 ng/mL. The novelty of this research lies in the preparation of magnetic surface MMIPs using a magnetic carrier. These MMIPs exhibit excellent magnetic properties and possess specific adsorption capability for catalpol, enabling rapid separation. They offer advantages such as low cost, high specificity, chemical stability, physical robustness, and recyclability (97.09%-106.53%, 91.32%-100.99%). The application of these polymers in the pretreatment method for determining the catalpol content in R. glutinosa extract and biological samples enhances the extraction efficiency and detection accuracy for catalpol. It eliminates interference and influences from other components in catalpol determination while exhibiting high sensitivity, good enrichment effects, excellent reusability, and a high recovery rate.
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Impresión Molecular , Rehmannia , Impresión Molecular/métodos , Microesferas , Adsorción , Fenómenos Magnéticos , Extracción en Fase Sólida/métodos , Cromatografía Líquida de Alta PresiónRESUMEN
Hawthorn belongs to the rose family and is a type of functional food. It contains various chemicals, including flavonoids, terpenoids, and organic acid compounds. This study aimed to review the vascular protective effects and molecular mechanisms of hawthorn and its extracts on cardiovascular diseases (CVDs). Hawthorn has a wide range of biological functions. Evidence suggests that the active components of HE reduce oxidative stress and inflammation, regulate lipid levels to prevent lipid accumulation, and inhibit free cholesterol accumulation in macrophages and foam cell formation. Additionally, hawthorn extract (HE) can protect vascular endothelial function, regulate endothelial dysfunction, and promote vascular endothelial relaxation. It has also been reported that the effective components of hawthorn can prevent age-related endothelial dysfunction, increase cellular calcium levels, cause antiplatelet aggregation, and promote antithrombosis. In clinical trials, HE has been proved to reduce the adverse effects of CVDs on blood lipids, blood pressure, left ventricular ejection fraction, heart rate, and exercise tolerance. Previous studies have pointed to the benefits of hawthorn and its extracts in treating atherosclerosis and other vascular diseases. Therefore, as both medicine and food, hawthorn can be used as a new drug source for treating cardiovascular diseases.
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Enfermedades Cardiovasculares , Crataegus , Enfermedades Vasculares , Humanos , Crataegus/química , Enfermedades Cardiovasculares/tratamiento farmacológico , Enfermedades Cardiovasculares/prevención & control , Enfermedades Cardiovasculares/inducido químicamente , Volumen Sistólico , Función Ventricular Izquierda , Extractos Vegetales/química , LípidosRESUMEN
INTRODUCTION: This study aims to explore the mortality risk in older people who drank alcohol in the past by varying the duration of alcohol abstention. METHODS: In total, 31,999 participants aged ≥65 years from the Chinese Longitudinal Healthy Longevity Survey (Waves 1998, 2000, 2002, 2005, 2008, 2011, 2014) were included. Duration of alcohol abstention was assessed by designed questions, and the study outcome was all-cause mortality. Cox proportional hazard models were used to examine the association. Analyses occurred from 2022 to 2023. RESULTS: During a follow-up of 140,974.8 person-years, all-cause mortality occurred in 24,257 participants. Mortality significantly increased by 23% (adjusted hazard ratio=1.23, 95% CI=1.14, 1.33, p<0.001), by 17% (adjusted hazard ratio=1.17, 95% CI=1.06, 1.31, p=0.003), and by 17% (adjusted hazard ratio=1.17, 95% CI=1.07, 1.28, p=0.001) in people who drank alcohol in the past with ≤5 years, 5-10 years, 10-20 years of alcohol abstention, respectively, compared with that among those who drink alcohol at present. After 20 years of alcohol abstention, the increased mortality risk disappeared (adjusted hazard ratio=1.06, 95% CI=0.97, 1.15, p=0.204). Stratified and sensitivity analysis revealed similar results. In addition, compared with the risk of all-cause mortality among people who never drink alcohol, the risk of all-cause mortality in those who drank alcohol in the past also significantly increased in the following 20 years after they stop drinking, and then the increased risk disappeared afterward. CONCLUSIONS: An increased risk of all-cause mortality in older people who drank alcohol in the past was observed, which disappeared after 20 years of alcohol abstention.
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Consumo de Bebidas Alcohólicas , Mortalidad , Anciano , Humanos , Consumo de Bebidas Alcohólicas/epidemiología , Estado de SaludRESUMEN
Background: Hypertrophic cardiomyopathy (HCM) and hypertension coexist fairly frequently in clinical practice. However, the evidence about the impact of hypertension on the prognosis of HCM is limited. The present study aims to investigate the impact of hypertension on the prognosis of HCM patients. Methods: A total of 468 HCM patients were enrolled, and patients were divided into hypertension group (31.8%) and non-hypertension group (68.2%). The primary study endpoint was HCM-related death, consisting of heart failure (HF)-related death, stroke-related death and sudden cardiac death (SCD). Associations between hypertension and HCM-related death were analyzed by Cox regression models with the use of propensity score matching (PSM) as primary analysis. Results: There were 55 HCM-related death during a median follow-up time of 4.6 years, and the mortality rate was 2.53 per 100 person years. Kaplan-Meier analysis based on the crude cohort or PSM cohort revealed no significant difference regarding the HCM-related death between the two groups. In the crude cohort, both univariable and multivariable Cox regression analysis indicated that hypertension was not significantly associated with HCM-related death with hazard ratios (HR) at 0.74 (95% CI [0.40-1.36], p value: 0.329) and 0.77 (95% CI [0.35-1.71], p value: 0.521), respectively. Similarly, no strong evidence for an association was observed between hypertension and HCM-related death in the PSM cohort with unadjusted HR at 0.90 (95% CI [0.34-2.41]; p value: 0.838) and adjusted HR at 0.77 (95% CI [0.35-1.71]; p value: 0.521), respectively. Other propensity score methods, including overlap weighting and inverse probability treatment weighting demonstrated similar results. Sensitivity analysis also indicated that the concomitant hypertension did not significantly increase the risk of HF-related death, stroke-related death or SCD in HCM patients. Conclusion: HCM-related death did not significantly differ between hypertension and non-hypertension groups, suggesting a negative impact of hypertension on the clinical prognosis of HCM patients.
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Cardiomiopatía Hipertrófica , Insuficiencia Cardíaca , Hipertensión , Accidente Cerebrovascular , Humanos , Estudios Retrospectivos , Factores de Riesgo , Cardiomiopatía Hipertrófica/complicaciones , Muerte Súbita Cardíaca , Insuficiencia Cardíaca/complicaciones , Hipertensión/epidemiología , Pronóstico , Accidente Cerebrovascular/complicacionesRESUMEN
BACKGROUND: Single self-reported measures of daily sleep duration are associated with adverse health outcomes; however, the association between changes in daily sleep duration and all-cause mortality has not been thoroughly evaluated among a large group of older people. METHODS: Using data from the Chinese Longitudinal Healthy Longevity Surveys, a total of 8588 older participants were included in the present study. Changes in daily sleep duration were assessed using annual changes, and Cox regression analysis examined the association of the annual changes with mortality. RESULTS: The median age of the study population was 82.00 (IQR: 72.00, 90.00) years, and 3974 (46.27%) participants were men. During a median follow-up period of 3.81 (IQR: 2.03, 6.74) years, 5100 (59.39%) deaths were recorded. After adjusting for initial daily sleep duration and other confounders, there was a non-linear relationship between annual changes in daily sleep duration and all-cause mortality. Annual changes were not associated with mortality before 0.0 h/year, and mortality risk increased after 0.0 h/year, specially after 1 h/year (adjusted HR: 1.32 per 1-hour/year increment, 95% CI: 1.18-1.47). Compared to the stable group (annual changes between -1 and 1 h), adjusted HRs for mortality were 0.98 (95% CI: 0.89-1.08) for the shorter group (annual decline more than 1 h) and 1.29 (95% CI: 1.19-1.41) for the longer group (annual increase greater than 1 h), respectively. Stratified and sensitivity analyses suggested robustness of the results. CONCLUSIONS: The present study suggested there was a non-linear relationship between annual changes in daily sleep duration and all-cause mortality among older people: longer changes were associated with higher mortality; while, shorter changes were not associated with mortality. Specially, mortality risk increased significantly with longer than 1 h of annual changes. The findings highlight the importance of closely monitoring the changes in daily sleep duration among older people.
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Duración del Sueño , Sueño , Masculino , Humanos , Anciano , Femenino , Estudios Longitudinales , Estado de Salud , Autoinforme , Factores de Riesgo , MortalidadRESUMEN
Cadmium (Cd) is a ubiquitous toxic metal and environmental pollutant. Increasing studies have shown that Cd exposure increases the incidence of various endocrine system diseases, including thyrotoxicity reflected by thyroid structural damage and endocrine toxicity. However, the observed outcomes are complex and conflicting, leading to the mechanism of Cd-induced thyrotoxicity remaining obscure. In this study, 4-week-old male C57BL/6 mice were given 2 or 7 mg/kg Cadmium Chloride (CdCl2) intragastrically for 4 and 8 weeks, and the Cd-mediated thyrotoxicity was evaluated by determining alterations in thyroid structure and endocrine function, and alterations of oxidant stress, apoptosis, and pyroptosis. Our data showed that Cd exposure could reduce body weight and induce thyrotoxicity by impairing thyroid follicular morphology and endocrine function, accompanied by elevated oxidative stress and apoptosis, macrophage infiltration, and inflammatory cytokine secretion. Importantly, Cd significantly promoted thyroid follicular cell pyroptosis by increasing Nlrp3, Asc, Caspase-1, Gsdmd, IL-1ß, and IL-18 expression. Mechanistical analysis suggested that Cd treatment could inhibit antioxidant pathway by downregulating antioxidant response protein, Nrf2, and upregulating its negative feedback regulator, Keap1. Collectively, our in vivo findings suggest that Cd exposure could facilitate thyroid follicular cell pyroptosis by inhibiting Nrf2/Keap1 signaling, thereby disrupting thyroid tissue structure and endocrine function, which offers novel insights into the Cd-mediated detrimental consequences on thyroid homeostasis.
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Antioxidantes , Cadmio , Exposición a Riesgos Ambientales , Proteína 1 Asociada A ECH Tipo Kelch , Factor 2 Relacionado con NF-E2 , Piroptosis , Glándula Tiroides , Animales , Masculino , Ratones , Antioxidantes/metabolismo , Cadmio/toxicidad , Proteína 1 Asociada A ECH Tipo Kelch/antagonistas & inhibidores , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Ratones Endogámicos C57BL , Factor 2 Relacionado con NF-E2/antagonistas & inhibidores , Factor 2 Relacionado con NF-E2/metabolismo , Piroptosis/efectos de los fármacos , Glándula Tiroides/efectos de los fármacos , Glándula Tiroides/patologíaRESUMEN
Background: There is no information about the clinical significance of the albumin-bilirubin (ALBI) score in patients with hypertrophic cardiomyopathy (HCM). Objective: We retrospectively performed clinical evaluations in 462 patients with HCM to estimate whether the ALBI score could be a new tool to predict mortality in HCM. Methods and Results: During a median follow-up of 4.7 years, HCM-related death occurred in 52 (11.3%) patients. Overall, there was a significant positive association between ALBI score and HCM-related death (adjusted hazard ratio [HR]: 1.79 per one standard deviation [SD] increment, 95% confidence interval [CI]: 1.36-2.35). When the score was assessed as tertiles, the adjusted HRs of HCM-related death were 1.30 (95% CI: 0.42-3.99) for the tertile 2 and 4.43 (95% CI: 1.65-11.89) for the tertile 3, compared with the tertile 1. Stratified analysis and E-value analysis suggested the robustness of the above-mentioned results. Meanwhile, time-dependent ROC analysis showed ALBI score could discriminate HCM-related death at various time points (AUC ranges: 0.725-0.850). Furthermore, exploratory analysis indicated the dynamic changes of ALBI score also could predict HCM-related death. Finally, multiple linear regression analysis suggested some pathogenetic pathways associated with HCM-related adverse outcomes significantly correlated with ALBI score, and the pathways included inflammation, myocardial injury, nutritional status and some clinical characteristics, but not abnormal cardiac structure and function itself. Conclusions: Higher ALBI score is a strong independent predictor of HCM-related death in patients with HCM.
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Bilirrubina , Cardiomiopatía Hipertrófica , Humanos , Estudios Retrospectivos , Pronóstico , Cardiomiopatía Hipertrófica/diagnóstico , AlbúminasRESUMEN
OBJECTIVE: Long-term cumulative blood pressure (BP) was associated with cardiovascular mortality in middle-aged to older people. Whether cumulative BP was associated with cardiovascular mortality is uncertain in Chinese older people. DESIGN: Data were obtained from the Chinese Longitudinal Healthy Longevity Survey (CLHLS), a nationwide, ongoing, prospective cohort study of community-dwelling Chinese older people. SETTING, AND PARTICIPANTS: A total of 3361 older participants from the CLHLS study were included (men: 46.68 %, age: ≥65 years, median age: 78.00 years [IQR: 71.0-86.00 years]). METHODS: Cumulative BP, including systolic BP (SBP), diastolic BP (DBP) and pulse pressure (PP), was determined by the area under the curve based on three measurements of BP (waves 2008, 2011, and 2014). The outcome was cardiovascular mortality, which was followed from wave 2014 to wave 2018. RESULTS: During a median follow-up period of 3.98 years, 211 cardiovascular death were recorded. The higher cumulative SBP and PP tended to be positively linearly associated with an elevated risk of cardiovascular mortality. For each SD increment, the adjusted HRs of mortality risk was 1.28 (95 % CI: 1.11-1.47; p = 0.001) and 1.24 (95 % CI, 1.09-1.43; p = 0.002) for cumulative SBP and PP, respectively. While there was no association between cumulative DBP and cardiovascular mortality. In addition, multiple sensitivity analyses suggested robustness of the results. CONCLUSIONS/IMPLICATIONS: Our results indicate that cumulative SBP and PP were associated with cardiovascular mortality in Chinese older people; however, there was no such association between cumulative DBP and mortality. Therefore, control of long-term SBP and PP may be required in those people.
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Enfermedades Cardiovasculares , Hipertensión , Anciano , Presión Sanguínea/fisiología , China/epidemiología , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de RiesgoRESUMEN
Objective: Because of rapid economic growth and followed urban expansion in China, many people drinking natural water had to change their water sources to tap water. We aimed to test the unknown association that whether continued use of natural water for drinking is different from switching to tap water in all-cause mortality risks in elderly people. Methods: In total, based on Chinese Longitudinal Healthy Longevity Survey, 26,688 elderly participants drinking natural water from childhood to young-old were included in the final analyses. Associations between whether changing drinking water sources or not and all-cause mortality risk were then estimated by Cox regression models with the use of multiple propensity score methods, and the primary analysis used propensity score matching, with other propensity score methods confirming the robustness of the results. Results: Baseline characteristics were fairly well balanced by the three post-randomization methods. During a median follow-up period of 3.00 (IQR: 1.52, 5.73) years, 21,379 deaths were recorded. The primary analysis showed people using natural water unchangeably was associated with a lower risk of all-cause mortality than those switching to tap water in later life (HR: 0.94, 95% CI: 0.91-0.97, p < 0.001). Other propensity score methods, as well as Cox regression analysis without using propensity score methods, showed similar results. Conclusions: Among elderly people depending on natural water for drinking from their childhood to young-old in China, continued use of natural water was associated with a lower all-cause mortality risk than conversion to tap water later. Further studies in different countries and populations are needed to verify our conclusions.
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Agua Potable , Anciano , Pueblo Asiatico , Niño , China/epidemiología , Humanos , Estudios Longitudinales , Estudios ProspectivosRESUMEN
BACKGROUND: Recently, a new metabolic health (MH) definition was developed from NHANES-III. In the origin study, the definition may stratify mortality risks in people who are overweight or normal weight. We aimed to investigate the association between the new MH definition and all-cause mortality in a nonobese Chinese population. METHODS: The data were collected in 1992 and then again in 2007 from the same group of 1157 participants. The association between the new MH definition and all-cause mortality were analyzed by Cox regression models with overlap weighting according to propensity score (PS) as primary analysis. RESULTS: At baseline in 1992, 920 (79.5%) participants were categorized as MH, and 237 (20.5%) participants were categorized as metabolically unhealthy (MUH) based on this new definition. During a median follow-up of 15 years, all-cause mortality occurred in 17 (1.85%) participants in MH group and 13 (5.49%) in MUH group, respectively. In the crude sample, Kaplan-Meier analysis demonstrated a significantly higher all-cause mortality in MUH group when compared to MH group (log-rank p = 0.002), and MUH was significantly associated with increased all-cause mortality when compared to MH with HR at 3.04 (95% CI: 1.47-6.25, p = 0.003). However, Kaplan-Meier analysis with overlap weighting showed that the cumulative incidence of all-cause mortality was not significantly different between MH and MUH groups (adjusted p = 0.589). Furthermore, in the primary multivariable Cox analysis with overlap weighting, adjusted HR for all-cause mortality was 1.42 (95% CI: 0.49-4.17, p = 0.519) in MUH group in reference to MH group. Other additional PS analyses also showed the incidence of all-cause mortality was not significantly different between the two groups. CONCLUSION: The new MH definition may be not appropriate for mortality risk stratification in non-obese Chinese people. Further investigations are needed.
Asunto(s)
Obesidad , Sobrepeso , Índice de Masa Corporal , China/epidemiología , Humanos , Encuestas Nutricionales , Obesidad/epidemiología , Sobrepeso/epidemiología , Factores de RiesgoRESUMEN
A novel magnetic adsorption nanomaterial was synthesized by the copolymerization of a deep eutectic solvent (DES) and chitosan (CS)-modified Fe3O4 particles. This material was proposed for the magnetic solid-phase extraction (MSPE) of flavonoids from an aqueous extract solution of herbal Epimedium folium without pretreatment. Coupled with high-performance liquid chromatography (HPLC), a rapid, environmentally friendly, and efficacious method was established and successfully applied for the enrichment, separation, and quantification of five quality marker flavonoids (viz. icariin, epimedin A, epimedin B, epimedin C, and baohuoside â , respectively) in herbal E. folium collected from four species and 18 habitats. In addition, the physicochemical properties and morphology of Fe3O4-CS-DES were characterized by Fourier transform infrared spectroscopy, transmission electron microscopy, scanning electron microscopy, thermogravimetric analysis, X-ray diffraction, and vibrating sample magnetometry. Furthermore, key parameters, including adsorbent amount, elution solvent, and desorption factor, were optimized. Under the optimal experimental conditions, the five flavonoids were adsorbed rapidly on MSPE, which were released easily using methanol-acidified formic acid. A reversed-phase C18 column with gradient mobile phases comprising acetonitrile and formic acid water was used for analyte separation and elution. Limits of detection for the five analytes ranged from 0.5 to 2.1 ng mL-1. Coefficients of determination in analyses ranged from 0.99994 to 0.99999. Intra-day and inter-day precision ranged from 0.75 to 5.18% (n = 6) and from 2.88 to 7.52% (n = 3), respectively. Recoveries of the five analytes ranged from 80 to 110%, with relative standard deviation values of less than 10%. To the best of our knowledge, as a new adsorbent, Fe3O4-CS-DES nanoparticles were synthesized and used for the first time for the preconcentration and separation of flavonoids. This study provided a new approach for the enrichment and detection of Epimedium flavonoids in real samples.