Distributions and trends of the global burden of COPD attributable to risk factors by SDI, age, and sex from 1990 to 2019: a systematic analysis of GBD 2019 data.

BACKGROUND: Global distributions and trends of the risk-attributable burdens of chronic obstructive pulmonary disease (COPD) have rarely been systematically explored. To guide the formulation of targeted and accurate strategies for the management of COPD, we analyzed COPD burdens attributable to known risk factors. METHODS: Using detailed COPD data from the Global Burden of Disease study 2019, we analyzed disability-adjusted life years (DALYs), years lived with disability (YLDs), years of life lost (YLLs), and deaths attributable to each risk factor from 1990 to 2019. Additionally, we calculated estimated annual percentage changes (EAPCs) during the study period. The population attributable fraction (PAF) and summary exposure value (SEV) of each risk factor are also presented. RESULTS: From 1990 to 2019, the age-standardized DALY and death rates of COPD attributable to smoking and household air pollution, occupational particles, secondhand smoke, and low temperature presented consistently declining trends in almost all socio-demographic index (SDI) regions. However, the decline in YLD was not as dramatic as that of the death rate. In contrast, the COPD burden attributable to ambient particulate matter, ozone, and high temperature exposure showed undesirable increasing trends in the low- and low-middle-SDI regions. In addition, the age-standardized DALY and death rates attributable to each risk factor except household air pollution and low temperature were the highest in the low-middle-SDI region. In 2019, the COPD burden attributable to smoking ambient particulate matter, ozone, occupational particles, low and high temperature was obviously greater in males than in females. Meanwhile, the most important risk factors for female varied across regions (low- and low-middle-SDI regions: household air pollution; middle-SDI region: ambient particles; high-middle- and high-SDI region: smoking). CONCLUSIONS: Increasing trends of COPD burden attributable to ambient particulate matter, ozone, and high temperature exposure in the low-middle- and low-SDI regions call for an urgent need to implement specific and effective measures. Moreover, considering the gender differences in COPD burdens attributable to some risk factors such as ambient particulate matter and ozone with similar SEV, further research on biological differences between sexes in COPD and relevant policy-making of disease prevention are required.

Association of Inpatient Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers With Mortality Among Patients With Hypertension Hospitalized With COVID-19.

RATIONALE: Use of ACEIs (angiotensin-converting enzyme inhibitors) and ARBs (angiotensin II receptor blockers) is a major concern for clinicians treating coronavirus disease 2019 (COVID-19) in patients with hypertension. OBJECTIVE: To determine the association between in-hospital use of ACEI/ARB and all-cause mortality in patients with hypertension and hospitalized due to COVID-19. METHODS AND RESULTS: This retrospective, multi-center study included 1128 adult patients with hypertension diagnosed with COVID-19, including 188 taking ACEI/ARB (ACEI/ARB group; median age 64 [interquartile range, 55-68] years; 53.2% men) and 940 without using ACEI/ARB (non-ACEI/ARB group; median age 64 [interquartile range 57-69]; 53.5% men), who were admitted to 9 hospitals in Hubei Province, China from December 31, 2019 to February 20, 2020. In mixed-effect Cox model treating site as a random effect, after adjusting for age, gender, comorbidities, and in-hospital medications, the detected risk for all-cause mortality was lower in the ACEI/ARB group versus the non-ACEI/ARB group (adjusted hazard ratio, 0.42 [95% CI, 0.19-0.92]; P=0.03). In a propensity score-matched analysis followed by adjusting imbalanced variables in mixed-effect Cox model, the results consistently demonstrated lower risk of COVID-19 mortality in patients who received ACEI/ARB versus those who did not receive ACEI/ARB (adjusted hazard ratio, 0.37 [95% CI, 0.15-0.89]; P=0.03). Further subgroup propensity score-matched analysis indicated that, compared with use of other antihypertensive drugs, ACEI/ARB was also associated with decreased mortality (adjusted hazard ratio, 0.30 [95% CI, 0.12-0.70]; P=0.01) in patients with COVID-19 and coexisting hypertension. CONCLUSIONS: Among hospitalized patients with COVID-19 and coexisting hypertension, inpatient use of ACEI/ARB was associated with lower risk of all-cause mortality compared with ACEI/ARB nonusers. While study interpretation needs to consider the potential for residual confounders, it is unlikely that in-hospital use of ACEI/ARB was associated with an increased mortality risk.

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 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.

Longitudinal Association Between Markers of Liver Injury and Mortality in COVID-19 in China.

BACKGROUND AND AIMS: Coronavirus disease 2019 (COVID-19) is a new infectious disease. To reveal the hepatic injury related to this disease and its clinical significance, we conducted a multicenter retrospective cohort study that included 5,771 adult patients with COVID-19 pneumonia in Hubei Province. APPROACH AND RESULTS: We reported the distributional and temporal patterns of liver injury indicators in these patients and determined their associated factors and death risk. Longitudinal liver function tests were retrospectively analyzed and correlated with the risk factors and death. Liver injury dynamic patterns differed in alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin (TBIL). AST elevated first, followed by ALT, in severe patients. ALP modestly increased during hospitalization and largely remained in the normal range. The fluctuation in TBIL levels was mild in the non-severe and the severe groups. AST abnormality was associated with the highest mortality risk compared with the other indicators of liver injury during hospitalization. Common factors associated with elevated liver injury indicators were lymphocyte count decrease, neutrophil count increase, and male gender. CONCLUSION: The dynamic patterns of liver injury indicators and their potential risk factors may provide an important explanation for the COVID-19-associated liver injury. Because elevated liver injury indicators, particularly AST, are strongly associated with the mortality risk, our study indicates that these parameters should be monitored during hospitalization.

Facilitating Anti-Cancer Combinatorial Drug Discovery by Targeting Epistatic Disease Genes.

Due to synergistic effects, combinatorial drugs are widely used for treating complex diseases. However, combining drugs and making them synergetic remains a challenge. Genetic disease genes are considered a promising source of drug targets with important implications for navigating the drug space. Most diseases are not caused by a single pathogenic factor, but by multiple disease genes, in particular, interacting disease genes. Thus, it is reasonable to consider that targeting epistatic disease genes may enhance the therapeutic effects of combinatorial drugs. In this study, synthetic lethality gene pairs of tumors, similar to epistatic disease genes, were first targeted by combinatorial drugs, resulting in the enrichment of the combinatorial drugs with cancer treatment, which verified our hypothesis. Then, conventional epistasis detection software was used to identify epistatic disease genes from the genome wide association studies (GWAS) dataset. Furthermore, combinatorial drugs were predicted by targeting these epistatic disease genes, and five combinations were proven to have synergistic anti-cancer effects on MCF-7 cells through cell cytotoxicity assay. Combined with the three-dimensional (3D) genome-based method, the epistatic disease genes were filtered and were more closely related to disease. By targeting the filtered gene pairs, the efficiency of combinatorial drug discovery has been further improved.

Orientin regulates the proliferation and migration of hepatocellular carcinoma cells.

Orientin is a flavone isolated from medicinal plants used in traditional Chinese medicine (TCM) that suppresses the growth of cancer cells in vitro. The effects of orientin in hepatoma carcinoma cells remain unknown. The aim of this paper is to investigate the effects of orientin on the viability, proliferation, and migration of hepatocellular carcinoma cells in vitro. In this study, we found that orientin could inhibit the proliferation, migration, and the activation of NF-κB signaling pathway in hepatocellular carcinoma cells. An activator of NF-κB signaling pathway, PMA, could abolish the inhibitory effect of orientin on NF-κB signaling pathway and proliferation and migration of Huh7 cells. These findings raise the possibility that orientin can be used in the treatment of hepatocellular carcinoma.

Gastrodin inhibits prostate cancer proliferation by targeting canonical Wnt/ß-catenin signaling pathway.

Prostate cancer is an epithelial malignant tumor occurring in the prostate and is the most common malignant tumor in the male genitourinary system. In recent years, the incidence of prostate cancer in China has shown a trend of sudden increase. The search for new and effective drugs to treat prostate cancer is therefore extremely important.The canonical Wnt/ß-catenin signaling pathway has been shown to be involved in the regulation of tumor proliferation, migration and differentiation. Activation of the canonical Wnt/ß-Catenin signaling pathway in the prostate has oncogenic effects. Drugs targeting the canonical Wnt/ß-catenin signaling pathway have great potential in the treatment of prostate cancer. In this study, we found that Gastrodin could significantly inhibit the proliferation of prostate cancer cell line PC3 and DU145. Oral administration Gastrodin could significantly inhibit the tumor growth of PC3 cells subcutaneously injected. Gastrodin has an inhibitory effect on canonical Wnt/ß-Catenin signaling pathway in Prostate cancer, and this inhibitory effect can be abolished by Wnt/ß-Catenin agonist LiCl. These findings raise the possibility that Gastrodin can be used in the treatment of Prostate cancer by targeting canonical Wnt/ß-Catenin signaling pathway.

The Association Between Metabolic Dysfunction-Associated Fatty Liver Disease and Peripheral Arterial Disease in the Chinese Population.

Purpose: Emerging evidence suggested that metabolic dysfunction-associated fatty liver disease (MAFLD) was significantly associated with atherosclerotic diseases. Atherosclerosis in the peripheral arteries is the most common cause of peripheral arterial disease (PAD), which has not been substantially controlled in the past. We aimed to investigate the association between MAFLD and PAD in the Chinese population. Patients and Methods: This observational study covered 102,115 participants who underwent health checkups with detailed examinations for PAD and MAFLD. PAD was measured by ankle-brachial index, and MAFLD was diagnosed by abdominal ultrasound. The generalized linear mixed models and random-effects Cox proportional hazards models were used to analyze the relationship between MAFLD and PAD. Results: The baseline characteristics showed that patients with MAFLD had higher prevalence of PAD compared with those without MAFLD (2.7% vs 2.2%). Compared to non-MAFLD, the individuals with MAFLD were associated with a higher risk of the presence of PAD (adjusted odds ratio: 1.30, 95% confidence interval (CI): 1.19-1.42, P < 0.001). In the prospective cohort study, 6833 participants underwent a follow-up of 2.76 (standard deviation: 1.36) years, and MAFLD at baseline was a higher risk of associated with incident PAD (adjusted hazards ratio: 1.67, 95% CI: 1.17-2.38, P = 0.005). Moreover, with the accumulation of metabolic abnormalities, the risk of the PAD was increased in the individuals with MAFLD. Furthermore, MAFLD attributed risk of PAD was more evident in participants without metabolic comorbidities. Conclusion: MAFLD was associated with a significantly higher risk for the prevalence and incidence of PAD in the Chinese population. The finding suggested that individuals with MAFLD are not only have a higher risk of coronary heart diseases but also have an increased risk of atherosclerosis in peripheral arteries.

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.

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.

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 between questionnaire-based and accelerometer-based physical activity and the incidence of chronic kidney disease using data from UK Biobank: a prospective cohort study.

Background: Prior studies on the relationship between chronic kidney disease (CKD) and physical activity (PA) mainly relied on subjective PA data and rarely considered the genetic risk. This study aims to thoroughly investigate this relationship by utilizing both accelerometer-measured and questionnaire-measured PA data. Methods: This prospective cohort study encompasses two cohorts from the UK Biobank. The questionnaire-based cohort involves 448,444 CKD-free participants who completed an International Physical Activity Questionnaire between 2006 and 2010 and had genetic data. PA was categorized into distinct activities: leisure, housework, job-related, and transportation. The accelerometer-based cohort involves 89,296 CKD-free participants who provided a full week of accelerometer-based physical activity data between 2013 and 2015 and had genetic data. PA was classified as light-intensity, moderate-intensity, vigorous-intensity, moderate to vigorous-intensity PA (LPA, MPA, VPA, MVPA), and total PA. Incident CKD was ascertained from linked hospital inpatient and death records. Genetic risk was assessed using polygenic risk scores. Cox proportional hazard models with restricted cubic splines were used for the analysis. Findings: In the questionnaire-based cohort, 18,184 (4.05%) participants developed CKD during 13.6 years of follow-up. Engaging in strenuous sports, other exercises, walking for pleasure, stair climbing, and heavy DIY were associated with a reduced risk of CKD. In the accelerometer-based cohort, 2297 (2.57%) participants developed CKD during 7.9 years of follow-up. Higher levels [highest quartile vs lowest quartile] of MPA (HR 0.639, 95% CI 0.554-0.737), VPA (HR 0.639, 95% CI 0.549-0.745), MVPA (HR 0.630, 95% CI 0.545-0.729), and total PA (HR 0.649, 95% CI 0.563-0.750) were associated with a lower CKD risk. There were significant interactions between MPA and genetic risk on the risk of CKD incidence (P for interaction = 0.025). A linear dose-response relationship was observed between MPA, total PA, and the risk of CKD incidence with no minimal or maximal threshold. These associations are robust in different subgroups and a series of sensitivity analyses. Interpretation: Engaging in multiple types of PA and higher levels of total PA, MPA, VPA, and MVPA may be associated with a lower risk of developing CKD, regardless of genetic risk. This finding holds substantial implications for clinical approaches to CKD prevention and provides evidence to inform future PA guideline development. Funding: Medical Science Advancement Program of Wuhan University, and the National Science Foundation of China.

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.

New avenues for NASH therapy by targeting ACC.

Acetyl-CoA carboxylase (ACC) is one of the more promising therapeutic targets for non-alcoholic steatohepatitis (NASH), but current ACC inhibitors already tested in clinical trials also exert the unwanted adverse side effect of hypertriglyceridemia. In two recent studies by Calle et al. in Nature Medicine and Zhang et al. in Science Translational Medicine, new strategies for ACC targeting were explored for NASH therapy that successfully resolved the adverse effect of hyperlipidemia while maintaining potent anti-NASH efficacy. These findings bring encouraging new momentum to the clinical application of ACC inhibition for NASH therapy.

Projection of global burden and risk factors for aortic aneurysm - timely warning for greater emphasis on managing blood pressure.

RATIONALE: Aortic aneurysm (AA) is a serious condition that largely increases the risk of aortic dissection and sudden death. Exploring the global burden of disease and changes in risk factors for AA is essential for public health policy development. OBJECTIVE: To project the death burden from AA and its attributable risk factors in the following decade based on the epidemiological data over the past 30 years. METHODS AND RESULTS: We analysed the death burden of AA and trends of four risk factors from 1990-2019 using the updated 2019 Global Burden of Disease study database by Joinpoint regression analysis. Furthermore, we project the AA-related death burden for the next decade using the Bayesian age-period-cohort model. This study discovered that the global burden of death attributable to AA began to increase after decreasing for two decades. This upward trend will continue in the subsequent decade (average annual percent change: 0.318%, 95% CI: 0.288 to 0.348). Meanwhile, the disease burdens in all economic regions except high-middle socio-demographic index (SDI) regions will continuously increase in the next decade, with the fastest acceleration in the low-middle SDI region (average annual percent change: 1.183%, 95% CI: 1.166 to 1.200). Notably, high systolic blood pressure will surpass the contribution of smoking to become the most important risk factor for mortality due to AA. CONCLUSION: This study discovered a rebounding trend in the aortic aneurysm-related death burden globally. High systolic blood pressure will be the top risk factor attributed to death from AA. Therefore, it should be considered as the first-degree risk factor in the guidance of AA management and criteria for population-based screening programs.Key messagesThe death burden of aortic aneurysms is beginning to rebound globally, and the trend will continue for the next decade.High systolic blood pressure will replace smoking as the most important risk factor associated with aortic aneurysm death.

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.

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.

High Remnant Cholesterol Level Potentiates the Development of Hypertension.

Background: Emerging evidence suggests an association between remnant cholesterol (RC) and vascular damage and hypertension. However, this association has not been explored in a large-scale population in China, and a temporal relationship between RC and hypertension also needs to be investigated. Methods: We conducted a retrospective cross-sectional study in 2,199,366 individuals and a longitudinal study in 24,252 individuals with repeated measurements of lipid profile and blood pressure in at least a 3-year follow-up. The logistic model was used to explore the association between lipid components and hypertension in the cross-sectional analysis. The Cox model was used to analyze the association between high RC (HRC) at baseline and the subsequent incidence of hypertension or the association between hypertension at baseline and incidence of HRC. The cross-lagged panel model was applied to analyze the temporal relationship between RC and hypertension. Results: RC level as a continuous variable had the highest correlation with hypertension among lipid profiles, including RC, low-density lipoprotein cholesterol, total cholesterol, non-high-density lipoprotein cholesterol, and triglycerides, with an odds ratio of 1.59 (95% confidence interval: 1.58-1.59). In the longitudinal cohort, HRC at baseline was associated with incident hypertension. We further explored the temporal relationship between RC and hypertension using the cross-lagged analysis, and the results showed that RC increase preceded the development of hypertension, rather than vice versa. Conclusions: RC had an unexpected high correlation with the prevalence and incidence of hypertension. Moreover, RC increase might precede the development of hypertension, suggesting the potential role of RC in the development of hypertension.