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1.
Eur J Nutr ; 63(5): 1513-1528, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38478042

RESUMO

BACKGROUND: While folic acid (FA) is widely used to treat elevated total homocysteine (tHcy), promoting vascular health by reducing vascular oxidative stress and modulating endothelial nitric oxide synthase, the optimal daily dose and individual variation by MTHFR C677T genotypes have not been well studied. Therefore, this study aimed to explore the efficacy of eight different FA dosages on tHcy lowering in the overall sample and by MTHFR C677T genotypes. METHODS: This multicentered, randomized, double-blind, controlled clinical trial included 2697 eligible hypertensive adults with elevated tHcy (≥ 10 mmol/L) and without history of stroke and cardiovascular disease. Participants were randomized into eight dose groups of FA combined with 10 mg enalapril maleate, taken daily for 8 weeks of treatment. RESULTS: The intent to treat analysis included 2163 participants. In the overall sample, increasing FA dosage led to steady tHcy reduction within the FA dosing range of 0-1.2 mg. However, a plateau in tHcy lowering was observed in FA dose range of 1.2-1.6 mg, indicating a ceiling effect. In contrast, FA doses were positively and linearly associated with serum folate levels without signs of plateau. Among MTHFR genotype subgroups, participants with the TT genotype showed greater efficacy of FA in tHcy lowering. CONCLUSIONS: This randomized trial lent further support to the efficacy of FA in lowering tHcy; more importantly, it provided critically needed evidence to inform optimal FA dosage. We found that the efficacy of FA in lowering tHcy reaches a plateau if the daily dosage exceeds 1.2 mg, and only has a small gain by increasing the dosage from 0.8 to 1.2 mg. GOV IDENTIFIER: NCT03472508 (Registration Date: March 21, 2018).


Assuntos
Ácido Fólico , Genótipo , Homocisteína , Metilenotetra-Hidrofolato Redutase (NADPH2) , Humanos , Ácido Fólico/administração & dosagem , Ácido Fólico/sangue , Homocisteína/sangue , Feminino , Masculino , Método Duplo-Cego , Pessoa de Meia-Idade , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Hipertensão/tratamento farmacológico , Relação Dose-Resposta a Droga , Idoso , Enalapril/administração & dosagem , Enalapril/farmacologia , Adulto , Hiper-Homocisteinemia/tratamento farmacológico , Hiper-Homocisteinemia/sangue
2.
Artigo em Inglês | MEDLINE | ID: mdl-38108918

RESUMO

The transient receptor potential melastatin 2 (TRPM2) channel is a nonselective calcium channel that is sensitive to oxidative stress (OS), and is widely expressed in multiple organs, such as the heart, kidney, and brain, which is inextricably related to calcium dyshomeostasis and downstream pathological events. Due to the increasing global burden of kidney or cardiovascular diseases (CVDs), safe and efficient drugs specific to novel targets are imperatively needed. Notably, investigation of the possibility to regard the TRPM2 channel as a new therapeutic target in ROS-related CVDs or renal diseases is urgently required because the roles of the TRPM2 channel in heart or kidney diseases have not received enough attention and thus have not been fully elaborated. Therefore, we aimed to review the involvement of the TRPM2 channel in cardiovascular disorders related to kidney or typical renal diseases and attempted to speculate about TRPM2-mediated mechanisms of cardiorenal syndrome (CRS) to provide representative perspectives for future research about novel and effective therapeutic strategies.

3.
Nutr Metab Cardiovasc Dis ; 32(5): 1210-1217, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35277327

RESUMO

BACKGROUND AND AIMS: As a new simple anthropometric index, the weight-adjusted-waist index (WWI) appears to be superior to body mass index (BMI) and waist circumference (WC) in assessing both muscle and fat mass. We aimed to explore the association of WWI with all-cause and cardiovascular mortality in southern China. METHODS AND RESULTS: A total of 12,447 participants (mean age, 59.0 ± 13.3 years; 40.6% men) in Jiangxi Province from the China Hypertension Survey study were included. WWI was defined as WC divided by the square root of weight. The outcome was all-cause and cardiovascular mortality. During a median follow-up of 5.6 years, 838 all-cause deaths occurred, with 390 cardiovascular deaths. Overall, there was a nonlinear positive relationship of WWI with all-cause and cardiovascular mortality. Accordingly, compared with participants in quartiles 1-3 (<11.2 cm/√kg), a significant higher risk of all-cause mortality (HR: 1.36, 95% CI: 1.17, 1.58) and cardiovascular mortality (HR: 1.43, 95% CI: 1.15, 1.77) were found in quartile 4 (≥11.2 cm/√kg). Further adjustment for BMI and WC did not substantially alter the results. No significant interactions were found in any of the subgroups (sex, age, area, physical activity, current smoking, current alcohol drinking, hypertension, and stroke). CONCLUSION: Higher WWI levels (≥11.2 cm/√kg) were associated with increased the risk of all-cause and cardiovascular mortality in southern China. These findings, if confirmed by further studies, suggested that WWI may serve as a simple and effective anthropometric index in clinical practice.


Assuntos
Hipertensão , Idoso , Índice de Massa Corporal , China/epidemiologia , Feminino , Humanos , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Circunferência da Cintura
4.
BMC Psychiatry ; 22(1): 504, 2022 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-35897015

RESUMO

PURPOSE: The aim of this study was to evaluate the association of marital status with cognitive function and to examine the potential effect modifiers in Chinese hypertensive populations. METHODS: A total of 9,525 adult Chinese hypertensive patients were enrolled in this cross-sectional study. Cognitive function, as the dependent variable in our study, was assessed by the Chinese version of the Mini-Mental State Examination (MMSE). We adjusted for potential confounding factors in multiple linear regression models to examine the relationship of marital status with cognitive function. In addition, we divided the population according to sex to explore whether there were sex-specific differences. RESULTS: Among the 9,525 study participants, the mean (SD) age for men was 63.5 (10.3) years, and the mean MMSE score was 24.9 ± 5.0, whereas for women, the mean (SD) age was 63.8 (9.3) years, and the mean MMSE score was 19.4 ± 6.4. Unmarried persons had lower scores on the MMSE and lower subscores in each of the cognitive domains. A stronger correlation between marital status and a lower MMSE score was statistically significant in men (unmarried men: ß = -1.55; 95% CI: -1.89, -1.21) but not women (unmarried women: ß = -0.22; 95% CI: -0.56, 0.12; p interaction = 0.006). Compared to men who were widowed or divorced, never married men were more likely to have lower MMSE scores (ß = -2.30, 95% CI -3.10,-1.50; p < 0.001). CONCLUSIONS: Our study demonstrated that being unmarried is an extremely important but neglected social risk factor for cognitive function. Sex was a strong effect modifier: being unmarried was correlated with a higher risk of cognitive decline than being married in Chinese hypertensive men, especially among older men, but this correlation was not observed among women. Moreover, never married men showed poorer cognitive function than those who were divorced or widowed.


Assuntos
Hipertensão , Adulto , Idoso , China , Cognição , Estudos Transversais , Feminino , Humanos , Masculino , Estado Civil , Pessoa de Meia-Idade
5.
Hypertens Res ; 47(6): 1500-1511, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38438721

RESUMO

Plasma total homocysteine (tHcy) and kidney function are both associated with mortality risk, but the degree to which kidney function modifies the impact of tHcy on mortality remains unknown. This prospective cohort study included a total of 14,225 hypertensive adults. Cox proportional hazard regression was used to analyze the separate and combined association of tHcy and estimated glomerular filtration rate (eGFR) with all-cause and cause-specific mortality. Mediation analysis was conducted to explore the mediating effect of eGFR. During a median follow-up of 4.0 years, 805 deaths were identified, including 397 deaths from cardiovascular disease (CVD). There were significant, positive relationships of tHcy with all-cause mortality (per 5 µmol/L; HR: 1.09; 95% CI: 1.07, 1.11), CVD mortality (HR: 1.11; 95% CI: 1.08, 1.13), and non-CVD mortality (HR: 1.07; 95% CI: 1.04, 1.10). The proportions of eGFR mediating these relationships were 39.1%, 35.7%, and 49.7%, respectively. There were additive interactions between tHcy and eGFR. Compared with those with low tHcy (<15 µmol/L) and high eGFR (≥90 mL·min-1·1.73 m-2), participants with high tHcy (≥20 µmol/L) and low eGFR (<60 mL·min-1·1.73 m-2) had the highest risk of all-cause mortality (HR: 4.89; 95% CI: 3.81, 6.28), CVD mortality (HR: 5.80; 95% CI: 4.01, 8.40), and non-CVD mortality (HR: 4.25; 95% CI: 3.02, 5.97). In conclusion, among Chinese hypertensive adults, high tHcy and impaired kidney function were independently and jointly associated with higher risks of all-cause and cause-specific mortality. Importantly, kidney function explained most (nearly 40%) of the increased risk of mortality conferred by high tHcy.


Assuntos
Taxa de Filtração Glomerular , Homocisteína , Hipertensão , Humanos , Homocisteína/sangue , Masculino , Feminino , Pessoa de Meia-Idade , Hipertensão/mortalidade , Hipertensão/fisiopatologia , Hipertensão/sangue , Estudos Prospectivos , Idoso , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/sangue , Adulto , Rim/fisiopatologia , Causas de Morte , Análise de Mediação
6.
J Geriatr Cardiol ; 19(10): 753-760, 2022 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-36338286

RESUMO

BACKGROUND: While studies have suggested the association between triglyceride-glucose (TyG) index, a reliable surrogate for insulin resistance and hypertension data are limited to the correlation of TyG and central blood pressure. This study aims to test the hypothesis that a higher TyG index is associated with elevated central systolic blood pressure (cSBP). METHODS: A total of 9249 Chinese hypertensive adults from the H-type Hypertension and Stroke Prevention and Control Project were analyzed in this study. cSBP was measured noninvasively using an A-Pulse CASPro device. TyG index was calculated as ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. Smoothing curve and multivariate linear regression models [beta coefficient (ß) with 95% CI] were applied to analyze the association between TyG index and cSBP. Subgroup analyses were conducted to explore potential modifications to such a correlation. RESULTS: The overall mean TyG index is 8.8 ± 0.7, and the total mean cSBP is 131.3 ± 12.8 mmHg. TyG index was observed to be independently and positively associated with cSBP among the total population (ß = 0.92, 95% CI: 0.53-1.31, P < 0.001), and participants who do not use antihypertensive drugs (ß = 1.03, 95% CI: 0.46-1.60, P < 0.001), which is in accordance with the result of the smoothing curve. The association between TyG index and cSBP appears robust in all tested subgroups. CONCLUSIONS: TyG index is positively and independently associated with cSBP among hypertensive adults. Our study result suggests that TyG index might serve as an effective marker for vascular function.

7.
Behav Neurol ; 2022: 7566033, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35783996

RESUMO

Objectives: Cognitive decline could be seen as the sign of preclinical phase of dementia, which was found to be sex differentiated. Previous studies had discovered that there might be some link between abnormal sleep duration and cognitive performance. Additionally, hypertension was found to be one of the important risk factors for cognitive decline and abnormal sleep duration was also a significant risk factor for hypertension. Therefore, the purpose of this study was to investigate sex differences in the association of sleep duration with cognitive performance and to further explore potential effect modifiers that may exist. Methods: Data analyzed in this study was from the China H-type Hypertension Registry Study. Sleep duration was assessed with a sleep questionnaire and categorized as <5 hours, 5-8 hours, and ≥8 hours. Cognitive performance was evaluated with the Mini-Mental State Examination (MMSE). Result: A total of 9527 subjects were included. The average age was 63.7 ± 9.8 years. Linear regression analyses showed that the association between long sleep duration (≥8 h) and MMSE score adjusting for pertinent covariables was stronger in female (ß = -0.95, 95% CI: -1.23 to -0.68, P < 0.001) than in male (ß = -0.29, 95% CI: -0.53 to -0.06, P = 0.013). Furthermore, there was a significant interaction between sleep duration and age on cognitive performance only in female. Conclusion: In summary, this study found that long sleep duration (≥8 h) was associated with poorer cognitive performance. Furthermore, this association was more pronounced in female than in male, especially in older female.


Assuntos
Hipertensão , Transtornos do Sono-Vigília , Idoso , Cognição , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Sono , Transtornos do Sono-Vigília/complicações
8.
Front Endocrinol (Lausanne) ; 13: 1007557, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36277696

RESUMO

Background and aims: The relationship between the new obesity index weight-adjusted-waist index (WWI) and hyperuricemia is unclear. We aimed to explore the association of the WWI and hyperuricemia among the hypertensive population. Methods: A total of 14,078 hypertension participants with complete data were included in our study. WWI was calculated by waist circumference divided by the square root of weight. Specifically, men with 420 µmol/L and women with 360 µmol/L were considered to have hyperuricemia. Results: The prevalence of hyperuricemia was 61.1% in men and 51.4% in women. On the whole, multivariate logistic regression analyses found that there was a linear positive correlation of WWI with hyperuricemia in both men (OR: 1.37; 95%CI: 1.25, 1.49) and women (OR: 1.35; 95%CI: 1.26, 1.45). Subgroup analysis found that the relationship between WWI and hyperuricemia was stable in stratified subgroups (all P-interactions >.05). Conclusion: WWI showed a positive association with hyperuricemia among hypertension patients.


Assuntos
Hipertensão , Hiperuricemia , Masculino , Humanos , Feminino , Hiperuricemia/complicações , Hiperuricemia/epidemiologia , Fatores de Risco , Estudos Transversais , Hipertensão/epidemiologia , Hipertensão/complicações , China/epidemiologia , Sistema de Registros
9.
Front Neurol ; 13: 890499, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36061998

RESUMO

Background: Increased plasma total homocysteine (tHcy) is an influencing factor of cognitive impairment in the general population. However, studies on the relationship between the risk of cognitive impairment and plasma tHcy levels in patients with hypertension are limited. This study aimed to explore the association between plasma tHcy levels and cognitive function assessed by MMSE scores among hypertensive patients in China. Methods: A total of 9,527 subjects from the Chinese Hypertension Registry Study participated in this study. Plasma tHcy levels were quantified by high-performance liquid chromatography using a fluorescence detector. Cognitive assessment was performed using the Mini-Mental State Examination (MMSE). Linear regression models, two piecewise linear regression models, and smoothing curve fitting were applied to determine the relationship between plasma tHcy levels and cognitive function. Results: This analysis included 9,527 Chinese hypertensive adults. Based on the results of linear regression models, a negative relationship was identified between plasma tHcy levels and MMSE scores [beta coefficient (ß) per standard deviation (SD) increase: -0.26, 95% confidence interval (CI) -0.35, -0.16, P < 0.001]. The fully adjusted smooth curve fitting presented a nonlinear between plasma tHcy levels and MMSE scores. The threshold effect analysis showed that the inflection point of tHcy was about 27.1 µmol/L. The effect size [ß (95% CI)] per SD increase in plasma tHcy concentrations on MMSE scores was -0.93 (-1.24, -0.6) on the left side and -0.07 (-0.24, 0.10) on the right side of the inflection point (P-value for log-likelihood ratio (LLR) test was <0.001). Moreover, subgroup analyses revealed that sex could influence the negative association between plasma tHcy levels and MMSE scores up to a specific threshold (P-value for interaction <0.001). Linear regression models indicated that there was an enhanced inverse association between tHcy levels and MMSE scores in female patients with tHcy concentrations less than 26.9 µmol/L compared to male patients with tHcy concentrations less than 32.0 µmol/L. Conclusions: Plasma tHcy levels had a threshold effect on MMSE scores among hypertensive patients in China. Increased plasma tHcy levels were independently inversely associated with cognitive decline among hypertensive patients with tHcy concentrations <27.1 µmol/L.

10.
Adipocyte ; 11(1): 1-10, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-34964707

RESUMO

Obesity is a complex medical condition that affects multiple organs in the body. However, the underlying mechanisms of obesity, as well as its treatment, are largely unexplored. The focus of this research was to use bioinformatics to discover possible treatment targets for obesity. To begin, the GSE133099 database was used to identify 364 differentially expressed genes (DEGs). Then, DEGs were subjected to tissue-specific analyses and enrichment analyses, followed by the creation of a protein-protein interaction (PPI) network and generation of a drug-gene interaction database to screen key genes and potential future drugs targeting obesity. Findings have illustrated that the tissue-specific expression of neurologic markers varied significantly (34.7%, 52/150). Among these genes, Lep, ApoE, Fyn, and FN1 were the key genes observed in the adipocyte samples from obese patients relative to the controls. Furthermore, nine potential therapeutic drugs (dasatinib, ocriplasmin, risperidone, gemfibrozil, ritonavir, fluvastatin, pravastatin, warfarin, atorvastatin) that target the key genes were also screened and selected. To conclude the key genes discovered (Lep, ApoE, Fyn, and FN1), as well as 9 candidate drugs, could be used as therapeutic targets in treating obesity.


Assuntos
Biologia Computacional , Preparações Farmacêuticas , Tecido Adiposo , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Obesidade/tratamento farmacológico , Obesidade/genética
11.
Front Cardiovasc Med ; 9: 901240, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35600480

RESUMO

Background: Stroke is a major global health burden, and risk prediction is essential for the primary prevention of stroke. However, uncertainty remains about the optimal prediction model for analyzing stroke risk. In this study, we aim to determine the most effective stroke prediction method in a Chinese hypertensive population using machine learning and establish a general methodological pipeline for future analysis. Methods: The training set included 70% of data (n = 14,491) from the China Stroke Primary Prevention Trial (CSPPT). Internal validation was processed with the rest 30% of CSPPT data (n = 6,211), and external validation was conducted using a nested case-control (NCC) dataset (n = 2,568). The primary outcome was the first stroke. Four received analysis methods were processed and compared: logistic regression (LR), stepwise logistic regression (SLR), extreme gradient boosting (XGBoost), and random forest (RF). Population characteristic data with inclusion and exclusion of laboratory variables were separately analyzed. Accuracy, sensitivity, specificity, kappa, and area under receiver operating characteristic curves (AUCs) were used to make model assessments with AUCs the top concern. Data balancing techniques, including random under-sampling (RUS) and synthetic minority over-sampling technique (SMOTE), were applied to process this unbalanced training set. Results: The best model performance was observed in RUS-applied RF model with laboratory variables. Compared with null models (sensitivity = 0, specificity = 100, and mean AUCs = 0.643), data balancing techniques improved overall performance with RUS, demonstrating a more satisfactory effect in the current study (RUS: sensitivity = 63.9; specificity = 53.7; and mean AUCs = 0.624. Adding laboratory variables improved the performance of analysis methods. All results were reconfirmed in validation sets. The top 10 important variables were determined by the analysis method with the best performance. Conclusion: Among the tested methods, the most effective stroke prediction model in targeted population is RUS-applied RF. From the insights, the current study revealed, we provided general frameworks for building machine learning-based prediction models.

12.
J Geriatr Cardiol ; 19(7): 522-530, 2022 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-35975022

RESUMO

BACKGROUND: The cardiovascular hazards of total homocysteine (tHcy) are long known. In addition, despite the acknowledgment on the importance of low ankle-brachial index (ABI) (< 0.9), borderline ABI (0.91-0.99) was once commonly overlooked. This study aims to explore the independent and joint effect of tHcy level and borderline ABI on all-cause death in hypertensive population. METHODS: This study included 10,538 participants from China H-type Hypertension Registry Study. ABI was described into two groups: normal ABI (1.00-1.40) and borderline ABI. tHcy level was also divided into two groups: < 15.02 and ≥ 15.02 µmo/L. Four groups were analyzed, using COX proportional hazard regression model, separately and pairwise to observe the independent and joint effect on all-cause death. RESULTS: A total of 126 (1.2%) deaths were observed in the 1.7 years follow-up time. Borderline ABI has a higher predicted risk of death than normal ABI (HR = 1.87, 95%CI: 1.17-3.00) after adjusting for potential covariates. Compare with tHcy level < 15.02 µmo/L (low tHcy), those with tHcy ≥ 15.02 µmo/L (high tHcy) had higher risk to event outcome (HR = 1.99, 95% CI: 1.30-3.05). According to the cumulative hazard curve, group with borderline ABI and high tHcy level has significantly higher altitude and larger increasing rate over follow-up period compare to other groups. Among those with borderline ABI, participants with high tHcy had higher death risk than those with low tHcy, nevertheless, no significant different between borderline and normal ABI among those with low tHcy levels. CONCLUSIONS: Borderline ABI and tHcy level both have independent predictive value on all-cause death. The combined group of borderline ABI and high tHcy has highest risk factor of outcomes, which suggested the mutual additive value of borderline ABI and tHcy. More attention should be given to the importance of borderline ABI in hypertensive population, especially with elevated tHcy level.

13.
Front Neurol ; 12: 732757, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35185745

RESUMO

BACKGROUND: Hypertension is a major cardiovascular risk factor for cognitive impairment. Lipid accumulation product (LAP), an index that represents fat overaccumulation in the body, has been shown to be associated with cardiovascular disease. Nevertheless, the relationship between LAP and cognitive function in hypertensive patients with normal weight has been infrequently studied. OBJECTIVE: This study aimed to assess the relationship between LAP and cognitive function in hypertensive patients with normal weight. METHODS: This study included 5,542 Chinese hypertensive patients with normal weight. Cognitive function was evaluated using the Mini-Mental State Examination (MMSE). The relationship between LAP and MMSE scores was evaluated using multiple linear regression. RESULTS: The mean age of the participants was 64.8 ± 9.3 years, and 2,700 were men (48.7%). The mean MMSE score was 24.5 ± 5.1 in men and 19.2 ± 6.5 in women. The mean LAP was 26.2 ± 25.5 in men and 42.5 ± 34 in women. Log10-LAP showed a significant positive association with MMSE score (men: ß = 0.69, 95% CI 0.14-1.24, p = 0.015; women: ß = 1.03, 95% CI 0.16-1.90, p = 0.020). When LAP was divided into 3 groups according to tertiles, participants in the third LAP tertile had higher MMSE scores for both men (p for trend = 0.04) and women (p for trend = 0.015). CONCLUSION: LAP showed an independent positive association with MMSE in Chinese hypertensive patients with normal weight.

14.
Int J Gen Med ; 14: 3627-3634, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34321908

RESUMO

BACKGROUND: High body mass index (BMI) is a well-recognized risk factor for cardiovascular diseases. But its role in peripheral artery disease (PAD) remains perplexing. Our study aims to evaluate the association of BMI with PAD in the Chinese hypertensive population. METHODS: This is a cross-sectional study with enrollment data from the Chinese H-type Hypertension Registry.10896 hypertensive patients aged ≥18 years were included in the final analysis. RESULTS: The prevalence of PAD diagnosed by ABI in this study was 3.2% (n=351). A U-shaped association between BMI and PAD was found. Per SD increment (3.6 kg/m2) on the left side of the BMI threshold (BMI < 25.7 kg/m2) was associated with a 27% decrease in the adjusted risk of PAD [OR, 0.73; 95% confidence interval (CI) 0.60, 0.89; P=0.002]; BMI was significantly positively associated with the risk of PAD (OR, 1.52; 95% CI 1.52, 1.93; P=0.001) in those with BMI ≥25.7 kg/m2. CONCLUSION: In summary, a U-shaped association between BMI and the risk of PAD in the Chinese hypertensive population was found. BMI with the lowest risk of PAD was estimated to be 25.7 kg/m2.

15.
Bioengineered ; 12(2): 12544-12554, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34839787

RESUMO

Sepsis-induced myocardial dysfunction (SIMD) is ubiquitous in septic shock patients and is associated with high morbidity and mortality rates. Heat shock protein 22 (Hsp22), which belongs to the small HSP family of proteins, is involved in several biological functions. However, the function of Hsp22 in lipopolysaccharide (LPS)-induced myocardial injury is not yet established. This study was aimed at investigating the underlying mechanistic aspects of Hsp22 in myocardial injury induced by LPS. In this study, following the random assignment of male C57BL/6 mice into control, LPS-treated, and LPS + Hsp22 treated groups, relevant echocardiograms and staining were performed to scrutinize the cardiac pathology. Plausible mechanisms were proposed based on the findings of the enzyme-linked immunosorbent assay and Western blotting assay. A protective role of Hsp22 against LPS-induced myocardial injury emerged, as evidenced from decreased levels of creatinine kinase-MB (CK-MB), lactate dehydrogenase (LDH), and enhanced cardiac function. The post-LPS administration-caused spike in inflammatory cytokines (IL-1ß, IL-6, TNF-α and NLRP3) was attenuated by the Hsp22 pre-treatment. In addition, superoxide dismutase (SOD) activity and B-cell lymphoma-2 (Bcl2) levels were augmented by Hsp22 treatment resulting in lowering of LPS-induced oxidative stress and cardiomyocyte apoptosis. In summary, the suppression of LPS-induced myocardial injury by Hsp22 overexpression via targeting of inflammation, oxidative stress, and apoptosis in cardiomyocytes paves the way for this protein to be employed in the therapy of SIMD.


Assuntos
Apoptose/fisiologia , Proteínas de Choque Térmico/metabolismo , Inflamação/metabolismo , Chaperonas Moleculares/metabolismo , Isquemia Miocárdica/metabolismo , Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , Estresse Oxidativo/fisiologia , Animais , Cardiomiopatias/induzido quimicamente , Cardiomiopatias/metabolismo , Citocinas/metabolismo , Inflamação/induzido quimicamente , Lipopolissacarídeos/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Isquemia Miocárdica/induzido quimicamente , Miócitos Cardíacos/efeitos dos fármacos
16.
Front Aging Neurosci ; 13: 706928, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35250530

RESUMO

BACKGROUND: Increasing studies have focused on the predictive value of high estimated glomerular filtration rate (eGFR) on cardiovascular diseases and mortality; however, the association between high eGFR with cognitive function is still not established. Thus, this study aimed to determine the co-relationship between high eGFR and cognitive performance in the hypertensive population. METHODS: We conducted a baseline cross-sectional study using data from the China H-type Hypertension Registry study. Mini-Mental State Examination (MMSE) assessment was performed to evaluate the cognitive function scale, and serum creatinine was collected to estimate eGFR level. Different MMSE cutoff values were applied in participants with the various educational background to define dementia: <24 in participants with secondary school and above education setting, <20 in those with primary school, and <17 in illiterate participants. RESULTS: A total of 9,527 hypertensive adults with mean age 63.7 ± 9.8 years and 67% female gender were analyzed. The eGFR cutoff value of 71.52 ml/min/1.73 m2 was found after adjusting for potential covariates in a threshold effect analysis. The MMSE increased significantly with the increment of eGFR (ß, 0.27; 95% CI: 0.12-0.41) in participants with eGFR < 71.52 ml/min/1.73 m2 and decreased (ß, -0.28; 95% CI: -0.39 to -0.17) in participants with eGFR ≥ 71.52 ml/min/1.73 m2. Individuals with eGFR ≥ 85 ml/min/1.73 m2 have an elevated risk of cognitive impairment than those with eGFR of 65-75 ml/min/1.73 m2. Subgroup analysis showed that a greater reduction degree of MMSE was observed in female individuals and those who had body mass index (BMI) ≥ 24 kg/m2 among participants with eGFR ≥ 71.52 ml/min/1.73 m2. CONCLUSION: Our findings observed an inverted U-shaped relationship between eGFR and cognitive function. Both the low and high levels of eGFR were independently associated with worse cognitive assessment in the hypertensive population.

17.
Nutr Metab (Lond) ; 18(1): 90, 2021 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-34627312

RESUMO

BACKGROUND: Limited information is available on arterial stiffness risk among hypertensive patients with metabolically abnormal but normal weight. Visceral adiposity index (VAI) is a novel indicator for visceral fat mass and metabolism, however, whether can be used to assessed arterial stiffness in a normal-weight population remains unclear. The goal of this study was to examine the independent association of VAI with arterial stiffness in normal-weight hypertensive patients. METHODS: 3258 participants recruited from the China H-type Hypertension Registry Study. VAI value was calculated using sex-specific equations. High arterial stiffness was defined as baPWV ≥ 18 m/s. Multivariable regression analysis was used to identify the association of VAI with baPWV and high arterial stiffness. RESULTS: Of participants, 50.5% (1644) were males, the mean age was 65.5 (SD, 9.1) years. Mean VAI and baPWV were 2.0 (SD, 2.3) and 18.2 (SD, 3.9) m/s, respectively. For each unit increase of lg VAI in multivariable regression analysis, there was a 1.05 m/s increase in baPWV (95% CI 0.67, 1.43) and a 2.13-fold increase in the risk of high arterial stiffness (95% CI 1.59, 2.86). In all models, the VAI was consistently and significantly associated with baPWV after adjustment for different confounders. High VAI levels were stably associated with baPWV in all subgroups. CONCLUSIONS: We found positive association of VAI with baPWV and high arterial stiffness in normal-weight adults with hypertension. The establishment of this association could help the arterial stiffness risk stratification in normal-weight hypertensive populations, who are frequently overlooked in preventing cardiovascular disease.

18.
Bioengineered ; 12(1): 2810-2819, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34180358

RESUMO

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease involving multiple organs. However, the underlying etiology and mechanisms remain unclear. This study was performed to identify potential therapeutic targets for SLE using bioinformatics methods. First, 584 differentially expressed genes were identified based on the GSE61635 dataset. Tissue-specific analyses, enrichment analyses, and Protein-Protein interaction network were successively conducted. Furthermore, ELISA was performed to confirm the expression levels of key genes in the control and SLE blood samples. The findings revealed that tissue-specific expression of markers of the hematological system (25.5%, 28/110) varied significantly. CCL2, MMP9, and RSAD2 expression was markedly increased in the SLE samples compared with controls. In conclusion, the identified key genes (CCL2, MMP9, and RSAD2) may act as possible therapeutic targets for the treatment of SLE.


Assuntos
Lúpus Eritematoso Sistêmico , Mapas de Interação de Proteínas/genética , Transcriptoma/genética , Biomarcadores/metabolismo , Biologia Computacional , Bases de Dados Genéticas , Humanos , Lúpus Eritematoso Sistêmico/genética , Lúpus Eritematoso Sistêmico/metabolismo , Especificidade de Órgãos/genética
19.
Hypertens Res ; 44(11): 1505-1514, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34493836

RESUMO

The current study aimed to explore the association between carotid intima-media thickness (CIMT) and cognitive function assessed by the Mini-Mental State Examination (MMSE) and to examine possible effect modifiers in hypertensive patients. A total of 14,322 hypertensive participants (mean age 64.2 ± 7.4 years; 40.9% male) from the China Stroke Primary Prevention Trial (CSPPT) were included in the final analysis. CIMT was measured by ultrasound, and data were collected at the last follow-up visit; MMSE was used to evaluate cognitive function. Nonparametric smoothing plots, multivariate linear regression analysis, subgroup analyses and interaction testing were performed to examine the relationship between the CIMI and cognitive function and effect modification. The mean CIMT was 0.74 ± 0.11 mm, and the mean MMSE score was 23.5 ± 4.8. There was a significant interaction (P interaction < 0.05) in both male and female populations stratified by age (<60 vs. ≥60 years), and higher CIMT was significantly associated with decreased MMSE scores only in participants aged ≥60 years (male: ß = -2.29, 95% CI -3.23 to -1.36; female: ß = -1.96, 95% CI -2.97 to -0.95). Males with abnormal HDL-C showed a stronger negative association (ß = -3.16, 95% CI -4.85 to -1.47) than those with normal HDL-C (normal vs. abnormal, P for interaction = 0.004). We observed that increased CIMT was significantly associated with cognitive impairment in the hypertensive population, especially among individuals with an age greater than 60 years and HDL-C deficiency. Overall, upon diagnosis of hypertension, treatment should start at the earliest opportunity to prevent end-organ damage and cognitive decline.


Assuntos
Disfunção Cognitiva , Hipertensão , Acidente Vascular Cerebral , Idoso , Espessura Intima-Media Carotídea , China , Disfunção Cognitiva/prevenção & controle , Feminino , Humanos , Hipertensão/complicações , Masculino , Pessoa de Meia-Idade , Prevenção Primária , Fatores de Risco
20.
Dis Markers ; 2021: 6258865, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34422136

RESUMO

While the received traditional predictors are still the mainstay in the diagnosis and prognosis of CVD events, increasing studies have focused on exploring the ancillary effect of biomarkers for the aspiring of precision. Under which circumstances, soluble ST2 (sST2), lipoprotein-associated phospholipase A2 (Lp-PLA2), myeloperoxidase (MPO), and procalcitonin (PCT) have recently emerged as promising markers in the field of both acute and chronic cardiovascular diseases. Existent clinical studies have demonstrated the significant associations between these markers with various CVD outcomes, which further verified the potentiality of markers in helping risk stratification and diagnostic and therapeutic work-up of patients. The current review article is aimed at illuminating the applicability of these four novels and often neglected cardiac biomarkers in common clinical scenarios, including acute myocardial infarction, acute heart failure, and chronic heart failure, especially in the emergency department. By thorough classification, combination, and discussion of biomarkers with clinical and instrumental evaluation, we hope the current study can provide insights into biomarkers and draw more attention to their importance.


Assuntos
Biomarcadores/metabolismo , Doenças Cardiovasculares/diagnóstico , 1-Alquil-2-acetilglicerofosfocolina Esterase/metabolismo , Doenças Cardiovasculares/metabolismo , Diagnóstico Precoce , Regulação da Expressão Gênica , Humanos , Proteína 1 Semelhante a Receptor de Interleucina-1/metabolismo , Peroxidase/metabolismo , Pró-Calcitonina/metabolismo , Prognóstico
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