Epidermal Growth Factor-Like Repeats and Discoidin I-Like Domains 3 Deficiency Attenuates Dilated Cardiomyopathy by Inhibiting Ubiquitin Specific Peptidase 10 Dependent Smad4 Deubiquitination.

BACKGROUND: Dilated cardiomyopathy (DCM) is the leading cause of heart failure with a poor prognosis. Recent studies suggest that endothelial to mesenchymal transition (EndMT) may be involved in the pathogenesis and cardiac remodeling during DCM development. EDIL3 (epidermal growth factor-like repeats and discoidin I-like domains 3) is an extracellular matrix glycoprotein that has been reported to promote EndMT in various diseases. However, the roles of EDIL3 in DCM still remain unclear. METHODS AND RESULTS: A mouse model of DCM and human umbilical vein endothelial cells were used to explore the roles and mechanisms of EDIL3 in DCM. The results indicated that EndMT and EDIL3 were activated in DCM mice. EDIL3 deficiency attenuated cardiac dysfunction and remodeling in DCM mice. EDIL3 knockdown alleviated EndMT by inhibiting USP10 (ubiquitin specific peptidase 10) dependent Smad4 deubiquitination in vivo and in vitro. Recombinant human EDIL3 promoted EndMT via reinforcing deubiquitination of Smad4 in human umbilical vein endothelial cells treated with IL-1ß (interleukin 1ß) and TGF-ß (transforming growth factor beta). Inhibiting USP10 abolished EndMT exacerbated by EDIL3. In addition, recombinant EDIL3 also aggravates doxorubicin-induced EndMT by promoting Smad4 deubiquitination in HUVECs. CONCLUSIONS: Taken together, these results indicate that EDIL3 deficiency attenuated EndMT by inhibiting USP10 dependent Smad4 deubiquitination in DCM mice.

Maresin-1 ameliorates hypertensive vascular remodeling through its receptor LGR6.

Hypertensive vascular remodeling is defined as the changes in vascular function and structure induced by persistent hypertension. Maresin-1 (MaR1), one of metabolites from Omega-3 fatty acids, has been reported to promote inflammation resolution in several inflammatory diseases. This study aims to investigate the effect of MaR1 on hypertensive vascular remodeling. Here, we found serum MaR1 levels were reduced in hypertensive patients and was negatively correlated with systolic blood pressure (SBP). The treatment of MaR1 reduced the elevation of blood pressure and alleviated vascular remodeling in the angiotensin II (AngII)-infused mouse model. In addition, MaR1-treated vascular smooth muscle cells (VSMCs) exhibited reduced excessive proliferation, migration, and phenotype switching, as well as impaired pyroptosis. However, the knockout of the receptor of MaR1, leucine-rich repeat-containing G protein-coupled receptor 6 (LGR6), was seen to aggravate pathological vascular remodeling, which could not be reversed by additional MaR1 treatment. The mechanisms by which MaR1 regulates vascular remodeling through LGR6 involves the Ca2+/calmodulin-dependent protein kinase II/nuclear factor erythroid 2-related factor 2/heme oxygenase-1 signaling pathway. Overall, supplementing MaR1 may be a novel therapeutic strategy for the prevention and treatment of hypertension.

Kielin/chordin-like protein deficiency aggravates pressure overload-induced cardiac dysfunction and remodeling via P53/P21/CCNB1 signaling in mice.

Targeting cardiac remodeling is regarded as a key therapeutic strategy for heart failure. Kielin/chordin-like protein (KCP) is a secretory protein with 18 cysteine-rich domains and associated with kidney and liver fibrosis. However, the relationship between KCP and cardiac remodeling remains unclear. Here, we aimed to investigate the role of KCP in cardiac remodeling induced by pressure overload and explore its potential mechanisms. Left ventricular (LV) KCP expression was measured with real-time quantitative PCR, western blotting, and immunofluorescence staining in pressure overload-induced cardiac remodeling in mice. Cardiac function and remodeling were evaluated in wide-type (WT) mice and KCP knockout (KO) mice by echocardiography, which were further confirmed by histological analysis with hematoxylin and eosin and Masson staining. RNA sequence was performed with LV tissue from WT and KO mice to identify differentially expressed genes and related signaling pathways. Primary cardiac fibroblasts (CFs) were used to validate the regulatory role and potential mechanisms of KCP during fibrosis. KCP was down-regulated in the progression of cardiac remodeling induced by pressure overload, and was mainly expressed in fibroblasts. KCP deficiency significantly aggravated pressure overload-induced cardiac dysfunction and remodeling. RNA sequence revealed that the role of KCP deficiency in cardiac remodeling was associated with cell division, cell cycle, and P53 signaling pathway, while cyclin B1 (CCNB1) was the most significantly up-regulated gene. Further investigation in vivo and in vitro suggested that KCP deficiency promoted the proliferation of CFs via P53/P21/CCNB1 pathway. Taken together, these results suggested that KCP deficiency aggravates cardiac dysfunction and remodeling induced by pressure overload via P53/P21/CCNB1 signaling in mice.

Resolvin D1 attenuates Ang II-induced hypertension in mice by inhibiting the proliferation, migration and phenotypic transformation of vascular smooth muscle cells by blocking the RhoA/mitogen-activated protein kinase pathway.

The proliferation, migration and phenotypic transformation of vascular smooth muscle cells contribute to vascular remodeling and hypertension. Resolvin D1 (RvD1) is a specialized pro-resolving lipid mediator that has been shown to have anti-inflammatory effects and can protect against different cardiovascular diseases. However, the role and mechanism of RvD1 in hypertension are not clear. The current study investigated the role of RvD1 in Ang II-induced hypertensive mice and Ang II-stimulated rat vascular smooth muscle cells. The results showed that RvD1 treatment significantly attenuated hypertension and vascular remodeling, as indicated by decreases in blood pressure, aortic media thickness and collagen deposition. In addition, RvD1 inhibited the proliferation, migration and phenotypic transformation of vascular smooth muscle cells (VSMCs) in vivo and in vitro . Notably, the protective effects of RvD1 were mediated by the Ras homolog gene family member A (RhoA)/mitogen-activated protein kinase (MAPK) signaling pathway. In conclusion, our findings demonstrated the potential benefits of RvD1 as a promising therapeutic agent in the treatment of vascular remodeling and hypertension.

DEL-1 deficiency aggravates pressure overload-induced heart failure by promoting neutrophil infiltration and neutrophil extracellular traps formation.

Recent studies have shown that neutrophils play an important role in the development and progression of heart failure. Developmental endothelial locus-1 (DEL-1) is an anti-inflammatory glycoprotein that has been found to have protective effects in various cardiovascular diseases. However, the role of DEL-1 in chronic heart failure is not well understood. In a mouse model of pressure overload-induced non-ischemic cardiac failure, we found that neutrophil infiltration in the heart increased and DEL-1 levels decreased in the early stages of heart failure. DEL-1 deficiency worsened pressure overload-induced cardiac dysfunction and remodeling in mice. Mechanistically, DEL-1 deficiency promotes neutrophil infiltration and the formation of neutrophil extracellular traps (NETs) through the regulation of P38 signaling. In vitro experiments showed that DEL-1 can inhibit P38 signaling and NETs formation in mouse neutrophils in a MAC-1-dependent manner. Depleting neutrophils, inhibiting NETs formation, and inhibiting P38 signaling all reduced the exacerbation of heart failure caused by DEL-1 deletion. Overall, our findings suggest that DEL-1 deficiency worsens pressure overload-induced heart failure by promoting neutrophil infiltration and NETs formation.

The association between outdoor air pollution and body mass index, central obesity, and visceral adiposity index among middle-aged and elderly adults: a nationwide study in China.

Background: Previous animal studies have suggested that air pollution (AP) exposure may be a potential risk factor for obesity; however, there is limited epidemiological evidence available to describe the association of obesity with AP exposure. Methods: A retrospective cross-sectional study was conducted on 11,766 participants across mainland China in 2015. Obesity was assessed using body mass index (BMI), waist circumference (WC), and visceral adiposity index (VAI). The space-time extremely randomized tree (STET) model was used to estimate the concentration of air pollutants, including SO2, NO2, O3, PM1, PM2.5, and PM10, matched to participants' residential addresses. Logistic regression models were employed to estimate the associations of obesity with outdoor AP exposure. Further stratified analysis was conducted to evaluate whether sociodemographics or lifestyles modified the effects. Results: Increased AP exposure was statistically associated with increased odds of obesity. The odds ratio (ORs) and 95% confidence interval (CI) of BMI-defined obesity were 1.21 (1.17, 1.26) for SO2, 1.33 (1.26, 1.40) for NO2, 1.15 (1.10, 1.21) for O3, 1.38 (1.29, 1.48) for PM1, 1.19 (1.15, 1.22) for PM2.5, and 1.11 (1.09, 1.13) for PM10 per 10 µg/m3 increase in concentration. Similar results were found for central obesity. Stratified analyses suggested that elderly participants experienced more adverse effects from all 6 air pollutants than middle-aged participants. Furthermore, notable multiplicative interactions were found between O3 exposure and females as well as second-hand smokers in BMI-defined obesity. Conclusions: This study suggested that outdoor AP exposure had a significant association with the risk of obesity in the middle-aged and elderly Chinese population. Elderly individuals and women may be more vulnerable to AP exposure.

Resolvin E1/ChemR23 Protects Against Hypertension and Vascular Remodeling in Angiotensin II-Induced Hypertensive Mice.

BACKGROUND: Inflammation plays a critical role in the development of hypertension and vascular remodeling. Resolvin E1 (RvE1), as one of the specialized proresolving lipid mediators, promotes inflammation resolution by binding with a G protein-coupled receptor, ChemR23 (chemerin receptor 23). However, whether RvE1/ChemR23 regulates hypertension and vascular remodeling is unknown. METHODS: Hypertension in mice was induced by Ang II (angiotensin II) infusion (750 ng/kg per minute), and RvE1 (2 µg/kg per day) was administered through intraperitoneal injection. Loss of ChemR23 was achieved by mice receiving intravenous injection of adeno-associated virus 9-encoding shRNA against ChemR23. RESULTS: Aortic ChemR23 expression was increased in Ang II-induced hypertensive mice and that ChemR23 was mainly expressed on vascular smooth muscle cells (VSMCs). RvE1 lowered blood pressure, reduced aortic media thickness, attenuated aortic fibrosis, and mitigated VSMC phenotypic transformation and proliferation in hypertensive mice, which were all reversed by the knockdown of ChemR23. Moreover, RvE1 reduced the aortic infiltration of macrophages and T cells, which was also reversed by ChemR23 knockdown. RvE1 inhibited Ccl5 expression in VSMCs via the AMPKα (AMP-activated protein kinase α)/Nrf2 (nuclear factor E2-related factor 2)/canonical NF-κB (nuclear factor κB) pathway, thereby reducing the infiltration of macrophages and T cells. The AMPKα/Nrf2 pathway also mediated the effects of RvE1 on VSMC phenotypic transformation and proliferation. In patients with hypertension, the serum levels of RvE1 and other eicosapentaenoic acid-derived metabolites were significantly decreased. CONCLUSIONS: RvE1/ChemR23 ameliorated hypertension and vascular remodeling by activating AMPKα/Nrf2 signaling, which mediated immune cell infiltration by inhibiting the canonical NF-κB/Ccl5 pathway, and regulated VSMC proliferation and phenotypic transformation. RvE1/ChemR23 may be a potential therapeutic target for hypertension.

Macrophage neogenin deficiency exacerbates myocardial remodeling and inflammation after acute myocardial infarction through JAK1-STAT1 signaling.

Immune response plays a crucial role in post-myocardial infarction (MI) myocardial remodeling. Neogenin (Neo1), a multifunctional transmembrane receptor, plays a critical role in the immune response; however, whether Neo1 participates in pathological myocardial remodeling after MI is unclear. Our study found that Neo1 expression changed significantly after MI in vivo and after LPS + IFN-γ stimulation in bone marrow-derived macrophages (BMDMs) in vitro. Neo1 functional deficiency (using a neutralizing antibody) and macrophage-specific Neo1 deficiency (induced by Neo1flox/flox;Cx3cr1cre mice) increased infarction size, enhanced cardiac fibrosis and cardiomyocyte apoptosis, and exacerbated left ventricular dysfunction post-MI in mice. Mechanistically, Neo1 deficiency promoted macrophage infiltration into the ischemic myocardium and transformation to a proinflammatory phenotype, subsequently exacerbating the inflammatory response and impairing inflammation resolution post-MI. Neo1 deficiency regulated macrophage phenotype and function, possibly through the JAK1-STAT1 pathway, as confirmed in BMDMs in vitro. Blocking the JAK1-STAT1 pathway with fludarabine phosphate abolished the impact of Neo1 on macrophage phenotype and function, inflammatory response, inflammation resolution, cardiomyocyte apoptosis, cardiac fibrosis, infarction size and cardiac function. In conclusion, Neo1 deficiency aggravates inflammation and left ventricular remodeling post-MI by modulating macrophage phenotypes and functions via the JAK1-STAT1 signaling pathway. These findings highlight the anti-inflammatory potential of Neo1, offering new perspectives for therapeutic targets in MI treatment. Neo1 deficiency aggravated inflammation and left ventricular remodeling after MI by modulating macrophage phenotypes and functions via the JAK1-STAT1 signaling pathway.

Prevalence and trend of atrial fibrillation and its associated risk factors among the population from nationwide health check-up centers in China, 2012-2017.

Background: Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia, which poses huge disease burdens in China. A study was conducted to systematically analyze the recent prevalence trend of AF and age-related disparities in AF risk among the nationwide healthy check-up population. Method: We conducted a nationwide cross-sectional study involving 3,049,178 individuals ≥35 years from health check-up centers to explore the prevalence and trend of AF by age, sex, and region from 2012 to 2017. Additionally, we analyzed risk factors associated with AF among the overall population and different age groups via the Boruta algorithm, the LASSO regression, and the Logistic regression. Result: The age-, sex-. and regional-standardized prevalence of AF kept stable between 0.4%-0.45% among national physical examination individuals from 2012 to 2017. However, the prevalence of AF showed an undesirable upward trend in the 35-44-year age group (annual percentage changes (APC): 15.16 [95%CI: 6.42,24.62]). With increasing age, the risk of AF associated with the overweight or obesity gradually exceeds that associated with diabetes and hypertension. In addition to traditional leading risk factors such as age≥65 and coronary heart disease, elevated uric acid and impaired renal function were tightly correlated with AF in the population. Conclusion: The significant rise in the prevalence of AF in the 35-44 age group reminds us that in addition to the elderly (the high-risk group), younger people seem to be in more urgent need of attention. Age-related disparities in AF risk also exist. This updated information may provide references for the national prevention and control of AF.

Lipoprotein(a) distribution and its association with carotid arteriopathy in the Chinese population.

BACKGROUND AND AIMS: The distribution of lipoprotein(a) [Lp(a)] has not been well-studied in a large population in China. The relationship between Lp(a) and carotid atherosclerosis remains undefined. In this study, we aimed to investigate the distribution of Lp(a) levels and to assess their association with carotid arteriopathy in China. METHODS: In this cross-sectional study, 411,634 adults with Lp(a) measurements from 22 health check-up centers were used to investigate Lp(a) distribution in China. Among participants with Lp(a) data, carotid ultrasound was performed routinely at seven health check-up centers covering 75,305 subjects. Carotid intima-media thickness (cIMT) and carotid plaque were used as surrogate biomarkers of carotid arteriopathy. The multivariate logistic regression model was applied to evaluate the association of increased Lp(a) levels with carotid arteriopathy. RESULTS: The distribution of Lp(a) concentrations was right-skewed, with a median concentration of 10.60 mg/dL. The proportions of Lp(a) levels ≥30 mg/dL and ≥50 mg/dL were 16.75% and 7.10%, respectively. The median Lp(a) level was higher in females individuals in northern China, and increased with age. Spearman's analysis revealed weak correlations between the Lp(a) concentration as a continuous variable and other lipid profiles. The multiple logistic regression analysis showed that participants with Lp(a) levels ≥50 mg/dL had an increased risk of cIMT ≥1.0 mm (OR = 1.138, 95% CI, 1.071-1.208) and carotid plaque (OR = 1.296, 95% CI, 1.219-1.377) compared with those with Lp(a) levels <50 mg/dL. CONCLUSIONS: This is the first study of the Lp(a) distribution in a large population in China. Our findings revealed a positive association between elevated Lp(a) levels (≥50 mg/dL) and increased prevalence of carotid atherosclerosis, which implies an increased risk of cardiovascular disease in the future.

Metabolic dysfunction-associated fatty liver disease increased the risk of subclinical carotid atherosclerosis in China.

Background and aims: Metabolic dysfunction-associated fatty liver disease (MAFLD) was proposed to substitute NAFLD in 2020. This new term highlights the systematic metabolic disturbances that accompany fatty liver. We evaluated the correlations between MAFLD and subclinical carotid atherosclerosis (SCA) based on a nationwide health examination population in China. Methods: We performed a nationwide cross-sectional population and a Beijing retrospective cohort from 2009 to 2017. SCA was defined as elevated carotid intima-media thickness. The multivariable logistic and Cox models were used to analyze the association between MAFLD and SCA. Results: 153,482 participants were included in the cross-sectional study. MAFLD was significantly associated with SCA in fully adjusted models, with an odds ratio of 1.66; 95% confidence interval (CI): 1.62-1.70. This association was consistent in the cohort, with a hazard ratio (HR) of 1.31. The association between baseline MAFLD and incident SCA increased with hepatic steatosis severity. Subgroup analysis showed an interaction between age and MAFLD, with a higher risk in younger groups (HR:1.67, 95% CI: 1.17-2.40). Conclusion: In this large cross-section and cohort study, MAFLD was significantly associated with the presence and development of SCA. Further, the risk was higher among MAFLD individuals with high hepatic steatosis index and young adults.

Association of insulin resistance with bone mineral density in a nationwide health check-up population in China.

INTRODUCTION: Insulin resistance (IR) is closely associated with cardio-metabolic diseases. However, the impact of IR on bone mass remains obscure. The present study is to evaluate the association between the triglyceride-glucose (TyG) indicated IR and bone mass in a nationwide health check-up population in China. METHODS: We conducted a retrospective cross-sectional study including 788,247 participants and a longitudinal cohort study in 8770 participants who had repeated measurements of TyG index and bone mass in at least a 2-year follow-up period. The restricted cubic splines and logistic models were used to analyze the association between IR and bone mass in the cross-sectional study. The Cox model was applied to evaluate the relationship between baseline IR and the subsequent incidence of low bone mass and osteoporosis in the longitudinal study. RESULTS: In the cross-sectional study, the TyG index had positive correlations with low bone mass, osteoporosis, or both after adjusting for confounding factors (all P < 0.001). In the longitudinal cohort study, the baseline TyG index was significantly associated with the incidence of low bone mass, osteoporosis, or both during the follow-up period, with hazard ratios (HRs) of 1.56 (95 % confidence interval [CI]: 1.25, 1.93, P < 0.05), 1.66 (95%CI: 1.06, 2.59, P < 0.05), and 1.55 (95%CI: 1.27, 1.88, P < 0.05) after adjusting for confounding factors, respectively. CONCLUSIONS: These results suggest that IR indicated by TyG is significantly associated with an increased risk of low bone mass and osteoporosis. Therefore, bone mass monitoring and early prevention strategies may be needed in individuals with IR to prevent the occurrence of low bone mass and osteoporosis.

The rising death burden of atrial fibrillation and flutter in low-income regions and younger populations.

Objective: The aim of the study was to depict the global death burden of atrial fibrillation and/or flutter (AFF) between 1990 and 2019 and predict this burden in the next decade. Methods: We retrieved annual death data on cases and rates of AFF between 1990 and 2019 from the Global Burden of Disease (GBD) Study 2019 and projected the trends for 2020-2029 by developing the Bayesian age-period-cohort model. Results: The global number of deaths from AFF increased from 117,038.00 in 1990 to 315,336.80 in 2019. This number is projected to reach 404,593.40 by 2029. The age-standardized mortality rates (ASMRs) of AFF have increased significantly in low- to middle-sociodemographic index (SDI) regions, which will surpass that in high SDI regions and reach above 4.60 per 100,000 by 2029. Globally, women have a higher ASMR than men, which is largely attributed to disproportionately higher mortality in women than men in lower SDI regions. Notably, AFF-related premature mortality continues to worsen worldwide. A pandemic of high systolic blood pressure and high body mass index (BMI) largely contributes to AFF-associated death. In particular, low- to middle-SDI regions and younger populations are increasingly affected by the rapidly growing current and future risk of high BMI. Conclusion: The global death burden of AFF in low-income countries and younger generations have not been sufficiently controlled in the past and will continue growing in the future, which is largely attributed to metabolic risks, particularly for high BMI. There is an urgent need to implement effective measures to control AFF-related mortality.

Global and Regional Trends and Projections of Infective Endocarditis-Associated Disease Burden and Attributable Risk Factors from 1990 to 2030.

Objective To forecast the future burden and its attributable risk factors of infective endocarditis (IE). Method We analyzed the disease burden of IE and its risk factors from 1990 to 2019 using the Global Burden of Disease 2019 database and projected the disease burden from 2020 to 2030 using a Bayesian age-period-cohort model. Results By 2030, the incidence of IE will increase uncontrollably on a global scale, with developed countries having the largest number of cases and developing countries experiencing the fastest growth. The affected population will be predominantly males, but the gender gap will narrow. The elderly in high-income countries will bear the greatest burden, with a gradual shift to middle-income countries. The incidence of IE in countries with middle/high-middle social-demographic indicators (SDI) will surpass that of high SDI countries. In China, the incidence rate and the number of IE will reach 18.07 per 100,000 and 451,596 in 2030, respectively. IE-associated deaths and heart failure will continue to impose a significant burden on society, the burden on women will increase and surpass that on men, and the elderly in high-SDI countries will bear the heaviest burden. High systolic blood pressure has become the primary risk factor for IE-related death. Conclusions This study provides comprehensive analyses of the disease burden and risk factors of IE worldwide over the next decade. The IE-associated incidence will increase in the future and the death and heart failure burden will not be appropriately controlled. Gender, age, regional, and country heterogeneity should be taken seriously to facilitate in making effective strategies for lowering the IE disease burden.

The projections of global and regional rheumatic heart disease burden from 2020 to 2030.

Background: Rheumatic heart disease (RHD) remains the leading cause of preventable death and disability in children and young adults, killing an estimated 320,000 individuals worldwide yearly. Materials and methods: We utilized the Bayesian age-period cohort (BAPC) model to project the change in disease burden from 2020 to 2030 using the data from the Global Burden of Disease (GBD) Study 2019. Then we described the projected epidemiological characteristics of RHD by region, sex, and age. Results: The global age-standardized prevalence rate (ASPR) and age-standardized incidence rate (ASIR) of RHD increased from 1990 to 2019, and ASPR will increase to 559.88 per 100,000 population by 2030. The global age-standardized mortality rate (ASMR) of RHD will continue declining, while the projected death cases will increase. Furthermore, ASPR and cases of RHD-associated HF will continue rising, and there will be 2,922,840 heart failure (HF) cases in 2030 globally. Female subjects will still be the dominant population compared to male subjects, and the ASPR of RHD and the ASPR of RHD-associated HF in female subjects will continue to increase from 2020 to 2030. Young people will have the highest ASPR of RHD among all age groups globally, while the elderly will bear a greater death and HF burden. Conclusion: In the following decade, the RHD burden will remain severe. There are large variations in the trend of RHD burden by region, sex, and age. Targeted and effective strategies are needed for the management of RHD, particularly in female subjects and young people in developing regions.

The prevalence of MAFLD and its association with atrial fibrillation in a nationwide health check-up population in China.

Background and aims: The epidemiological characteristics of MAFLD and its relationship with atrial fibrillation (AF) are limited in China. Therefore, we explored the epidemiological characteristics of MAFLD from adults along with the association of MAFLD and 12-ECG diagnosed AF in a nationwide population from health check-up centers. Methods: This observational study used cross-sectional and longitudinal studies with 2,083,984 subjects from 2009 to 2017. Age-, sex-, and regional-standardized prevalence of MAFLD was estimated. Latent class analysis (LCA) was used to identify subclusters of MAFLD. Multivariable logistic regression and mixed-effects Cox regression models were used to analyze the relationship between MAFLD and AF. Results: The prevalence of MAFLD increased from 22.75% to 35.58% during the study period, with higher rates in males and populations with high BMI or resided in northern regions. The MAFLD population was clustered into three classes with different metabolic features by LCA. Notably, a high proportion of MAFLD patients in all clusters had overweight and prediabetes or diabetes. The MAFLD was significantly associated with a higher risk of AF in the cross-sectional study and in the longitudinal study. In addition, the coexistence of prediabetes or diabetes had the largest impact on subsequent AF. Conclusion: Our findings suggested a high prevalence of MAFLD and a high prevalence of other metabolic diseases in the MAFLD population, particularly overweight and glucose dysregulation. Moreover, MAFLD was associated with a significantly higher risk for existing and subsequent subclinical AF in the Chinese population.

The global disease burden attributable to a diet low in fibre in 204 countries and territories from 1990 to 2019.

OBJECTIVE: The relationship of a diet low in fibre with mortality has not been evaluated. This study aims to assess the burden of non-communicable chronic diseases (NCD) attributable to a diet low in fibre globally from 1990 to 2019. DESIGN: All data were from the Global Burden of Disease (GBD) Study 2019, in which the mortality, disability-adjusted life-years (DALY) and years lived with disability (YLD) were estimated with Bayesian geospatial regression using data at global, regional and country level acquired from an extensively systematic review. SETTING: All data sourced from the GBD Study 2019. PARTICIPANTS: All age groups for both sexes. RESULTS: The age-standardised mortality rates (ASMR) declined in most GBD regions; however, in Southern sub-Saharan Africa, the ASMR increased from 4·07 (95 % uncertainty interval (UI) (2·08, 6·34)) to 4·60 (95 % UI (2·59, 6·90)), and in Central sub-Saharan Africa, the ASMR increased from 7·46 (95 % UI (3·64, 11·90)) to 9·34 (95 % UI (4·69, 15·25)). Uptrends were observed in the age-standardised YLD rates attributable to a diet low in fibre in a number of GBD regions. The burden caused by diabetes mellitus increased in Central Asia, Southern sub-Saharan Africa and Eastern Europe. CONCLUSIONS: The burdens of disease attributable to a diet low in fibre in Southern sub-Saharan Africa and Central sub-Saharan Africa and the age-standardised YLD rates in a number of GBD regions increased from 1990 to 2019. Therefore, greater efforts are needed to reduce the disease burden caused by a diet low in fibre.

Global disease burden of stroke attributable to high fasting plasma glucose in 204 countries and territories from 1990 to 2019: An analysis of the Global Burden of Disease Study.

BACKGROUND: High fasting plasma glucose (HFPG) is the leading risk factor contributing to the increase of stroke burden in the past three decades. However, the global distribution of stroke burden specifically attributable to HFPG was not studied in depth. Therefore, we analyzed the HFPG-attributable burden in stroke and its subtypes in 204 countries and territories from 1990 to 2019. METHODS: Detailed data on stroke burden attributable to HFPG were obtained from the Global Burden of Disease Study 2019. The numbers and age-standardized rates of stroke disability-adjusted life years (DALYs), deaths, years lived with disability, and years of life lost between 1990 and 2019 were estimated by age, sex, and region. RESULTS: In 2019, the age-standardized rate of DALYs (ASDR) of HFPG-attributable stroke was 354.95 per 100 000 population, among which 49.0% was from ischemic stroke, 44.3% from intracerebral hemorrhage, and 6.6% from subarachnoid hemorrhage. The ASDRs of HFPG-attributable stroke in lower sociodemographic index (SDI) regions surpassed those in higher SDI regions in the past three decades. Generally, the population aged over 50 years old accounted for 92% of stroke DALYs attributable to HFPG, and males are more susceptible to HFPG-attributable stroke than females across their lifetime. CONCLUSIONS: Successful key population initiatives targeting HFPG may mitigate the stroke disease burden. Given the soaring population-attributable fractions of HFPG for stroke burden worldwide, each country should assess its disease burden and determine targeted prevention and control strategies.

Global death burden and attributable risk factors of peripheral artery disease by age, sex, SDI regions, and countries from 1990 to 2030: Results from the Global Burden of Disease study 2019.

BACKGROUND AND AIMS: Peripheral artery disease (PAD) is a prevalent cardiovascular disease. Understanding current and future disease burden of PAD and its attributable risk factors is critical for developing prevention measures targeting PAD and associated complications. METHODS: We analyzed the death burden of PAD and the trends of six risk factors from 1990 to 2019 using the updated 2019 Global Burden of Disease study database, and projected the next decade death burden using a Bayesian age-period-cohort (BAPC) model. RESULTS: The global age-standardized mortality rate (ASMR) of PAD has a modest downward trend from 1990 to 2019. Regionally, ASMRs in higher-sociodemographic index (SDI) areas remained more remarkable than in lower-SDI areas by 2019, while the rate of increase in death burden in the lower-SDI regions increased rapidly over time. ASMR in males was greater than in females. In the population aged older than 40 years, the sex difference in PAD-associated mortality decreased with age. High fasting plasma glucose (FPG) became the primary risk factor for PAD-related death. The contributions of risk factors to PAD-related death varied by age group. Kidney dysfunction was the primary contributor to PAD-related death in people aged 40-59 years, particularly in women. CONCLUSIONS: The global death burden of PAD has not substantially decreased over the three decades. There are large variations in the trend of PAD mortality and its attributable risk factors by SDI regions, sex, and age group. Targeted and effective strategies are needed for the management of PAD-related mortality in specific subgroups.

A Bidirectional Relationship Between Hyperuricemia and Metabolic Dysfunction-Associated Fatty Liver Disease.

BACKGROUND AND AIMS: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a newly emerged term that is suggested to better reflect the pathogenesis of nonalcoholic fatty liver disease (NAFLD); however, the association between hyperuricemia and MAFLD has not been explored in the Chinese population. Meantime, this study also examined the temporal relationship between the two entities in a longitudinal cohort. METHODS: We conducted a retrospective cross-sectional study including 1,587,962 individuals from 19 health check-up centers in China from 2009-2017 and a longitudinal study with 16,112 individuals. A logistic regression model was applied to determine the association between hyperuricemia and MAFLD in a cross-sectional study. The Cox regression model was used to explore the association between hyperuricemia at baseline and subsequent onset of MAFLD or the association between the presence of MAFLD at baseline and the subsequent incidence of hyperuricemia. The cross-lagged analysis was applied to exam the temporal relationship between hyperuricemia and MAFLD. RESULTS: In the cross-sectional study, hyperuricemia showed a strong positive association with MAFLD after controlled potential confounders. In the longitudinal cohorts, hyperuricemia at baseline was associated with the new-onset of MAFLD, with a hazard ratio (HR) of 1.765 (95% CI: 1.512, 2.060). Interestingly, baseline MAFLD was also associated with the subsequent incidence of hyperuricemia, with an HR of 1.245 (95% CI: 1.106, 1.400). The cross-lagged path analysis revealed a bidirectional relationship between hyperuricemia and MAFLD. CONCLUSIONS: The results suggested that hyperuricemia and MAFLD form a vicious cycle, resulting in more deterioration of metabolic status.