Reprogramming of DNA methylation patterns mediates perfluorooctane sulfonate-induced fetal cardiac dysplasia.

Prenatal exposure to perfluorooctane sulfonate (PFOS) is associated with adverse health effects, including congenital heart disease, yet the underlying mechanisms remain elusive. Herein, we aimed to evaluate the embryotoxicity of PFOS using C57BL/6 J mice to characterize fetal heart defects after PFOS exposure, with the induction of human embryonic stem cells (hESC) into cardiomyocytes (CMs) as a model of early-stage heart development. We also performed DNA methylation analysis to clarify potential underlying mechanisms and identify targets of PFOS. Our results revealed that PFOS caused septal defects and excessive ventricular trabeculation cardiomyopathy at 5 mg/kg/day in embryonic mice and inhibited the proliferation and pluripotency of ESCs at concentrations >20 µM. Moreover, it decreased the beating rate and the population of CMs during cardiac differentiation. Decreases were observed in the abundances of NPPA+ trabecular and HEY2+ compact CMs. Additionally, DNA methyl transferases and ten-eleven translocation (TET) dioxygenases were regulated dynamically by PFOS, with TETs inhibitor treatment inducing significant decreases similar as PFOS. 850 K DNA methylation analysis combined with expression analysis revealed several potential targets of PFOS, including SORBS2, FHOD1, SLIT2, SLIT3, ADCY9, and HDAC9. In conclusion, PFOS may reprogram DNA methylation, especially demethylation, to induce cardiac toxicity, causing ventricular defects in vivo and abnormal cardiac differentiation in vitro.

Household use of solid fuel and sarcopenia among middle-aged and older adults: The China Health and Retirement Longitudinal Study.

OBJECTIVE: Few studies have examined the effects of air pollution on the risk of sarcopenia, especially pollution in indoor settings. We explored the cross-sectional and longitudinal associations of household use of solid fuel for cooking and heating, separately and simultaneously, with risk of sarcopenia. METHODS: Cross-sectional and follow-up data from the China Health and Retirement Longitudinal Study were used. Multivariable-adjusted generalized linear models and Cox proportional hazards regression models were performed to estimate the odds ratio and hazard ratio for sarcopenia, respectively. RESULTS: 11,494 (median age: 57.0 years; 47.4 % males) and 7483 (median age: 57.0 years; 46.9 % males) participants were included in the cross-sectional and longitudinal study, respectively. After fully adjusting for covariates, including outdoor concentration of particulate matter (PM2.5), both the use of solid fuels for cooking and use for heating were positively associated with incident sarcopenia in the longitudinal analyses, with hazard ratios (95 % confidence interval) of 1.56 (1.28-1.89) and 1.26 (1.04-1.52), respectively. Moreover, significant multiplicative and/or additive interactions were observed between age, smoking and cooking with solid fuel and risk of sarcopenia (all P for interaction <0.05). Similar results were found in the cross-sectional analyses. CONCLUSIONS: Household use of solid fuel was significantly associated with a higher risk of sarcopenia, while ageing and smoking had synergetic effects with burning solid fuels on the risk of sarcopenia. Our results highlight the importance of taking multi-pronged measures with respect to both air pollution and healthy lifestyle to prevent sarcopenia and promote healthy ageing.

Outdoor artificial light at night and incident cardiovascular disease in adults: A national cohort study across China.

Cardiovascular diseases (CVDs) become a major public health concern. Evidence concerning the effects of outdoor artificial light at night (ALAN) on CVD in adults is scarce. We aimed to investigate the extent to which outdoor ALAN could affect the risk of CVD over a exposure range. Data from the China Health and Retirement Longitudinal Study, a population-based longitudinal study, launched in 2011-2012 and follow up till 2018, covering 28 provinces, autonomous regions and municipalities across mainland China. This study included 14,097 adults aged ≥45 years. Outdoor ALAN exposure (in nanowatts per centimeters squared per steradian) within 500 m of each participant's baseline residence was obtained from satellite image data. CVD was defined from medical diagnosis. The population was divided into three groups based on outdoor ALAN exposure from low to high. Cox regression model was used to estimate the association between outdoor ALAN exposure and incident CVD with hazard ratios (HRs) and 95 % confidence intervals (CIs). The mean (SD) age of the cohort was 57.6 (9.1) years old and 49.3 % were males. Outdoor ALAN exposure of study participants ranged from 0.02 to 39.79 nW/cm2/sr. During 83,033 person-years of follow-up, 2190 (15.5 %) cases of CVD were identified. Both low (HR: 1.21; 95 % CI: 1.02-1.43) and high (HR: 1.23; 95 % CI: 1.04-1.46) levels of outdoor ALAN exposure group were associated with higher risk of CVD compared with intermediate levels of outdoor ALAN exposure group. Body mass index was a significant effect modifier in the association between outdoor ALAN and risk of CVD, with stronger effects among those who was overweight or obese. The findings of this study suggest that low and high outdoor ALAN exposure were associated with a higher risk for CVD. More attention should be given to the cardiovascular effects associated with outdoor ALAN exposure.

Single-cell RNA sequencing reveals the role of mitochondrial dysfunction in the cardiogenic toxicity of perfluorooctane sulfonate in human embryonic stem cells.

Perfluorooctane sulfonate (PFOS), an endocrine-disrupting chemical pollutant, affects embryonic heart development; however, the mechanisms underlying its toxicity have not been fully elucidated. Here, Single-cell RNA sequencing (scRNA-seq) was used to investigate the overall effects of PFOS on myocardial differentiation from human embryonic stem cells (hESCs). Additionally, apoptosis, mitochondrial membrane potential, and ATP assays were performed. Downregulated cardiogenesis-related genes and inhibited cardiac differentiation were observed after PFOS exposure in vitro. The percentages of cardiomyocyte and cardiac progenitor cell clusters decreased significantly following exposure to PFOS, while the proportion of primitive endoderm cell was increased in PFOS group. Moreover, PFOS inhibited myocardial differentiation and blocked cellular development at the early- and middle-stage. A Gene Ontology analysis and pseudo-time trajectory illustrated that PFOS disturbed multiple processes related to cardiogenesis and oxidative phosphorylation in the mitochondria. Furthermore, PFOS decreased mitochondrial membrane potential and induced apoptosis. These results offer meaningful insights into the cardiogenic toxicity of PFOS exposure during heart formation as well as the adverse effects of PFOS on mitochondria.

Social Determinants of Health, Cardiovascular Health, and Outcomes in Community-Dwelling Adults Without Cardiovascular Disease.

Background: Limited data exist regarding the prognostic implications of social determinants of health (SDOH) and cardiovascular health (CVH) in Chinese community populations. Objectives: The aim of this study was to evaluate the associations of SDOH and CVH with major adverse cardiovascular events (MACE) and all-cause death. Methods: Individuals without cardiovascular disease were obtained from the China Patient-Centered Evaluative Assessment of Cardiac Events Million Persons Project. SDOH (educational attainment, economic stability, health care access, social support, and neighborhood) and CVH components were extracted. Participants were divided into groups with low and high burden of unfavorable SDOH and groups with poor, intermediate, and ideal CVH. MACE (a composite of coronary heart disease or myocardial infarction, stroke, heart failure, and cardiovascular death) and all-cause death were identified by linking hospital records with resident identity card number. Results: Among the cohort (n = 38,571, median age 54 years, 60.5% women), the proportion of individuals with a high burden of unfavorable SDOH was 68.9%, and that with poor CVH was 30.7%. In reference to the group with a low burden of unfavorable SDOH, the adjusted HRs for MACE and all-cause death in the high burden group were 1.18 (95% CI: 1.08-1.30) and 1.35 (95% CI: 1.09-1.68), respectively. In reference to the group with ideal CVH, poor CVH was associated with higher risks for MACE and all-cause death. A high burden of unfavorable SDOH and poor CVH exerted joint effects on all-cause death (HR: 2.20; 95% CI: 1.08-4.48). Conclusions: A high burden of unfavorable SDOH and poor CVH were associated with increased risks for MACE and mortality. Dedicated efforts are needed to address these health disparities.

Construction of millimeter-scale vascularized engineered myocardial tissue using a mixed gel.

Engineering myocardium has shown great clinal potential for repairing permanent myocardial injury. However, the lack of perfusing blood vessels and difficulties in preparing a thick-engineered myocardium result in its limited clinical use. We prepared a mixed gel containing fibrin (5 mg/ml) and collagen I (0.2 mg/ml) and verified that human umbilical vein endothelial cells (HUVECs) and human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) could form microvascular lumens and myocardial cell clusters by harnessing the low-hardness and hyperelastic characteristics of fibrin. hiPSC-CMs and HUVECs in the mixed gel formed self-organized cell clusters, which were then cultured in different media using a three-phase approach. The successfully constructed vascularized engineered myocardial tissue had a spherical structure and final diameter of 1-2 mm. The tissue exhibited autonomous beats that occurred at a frequency similar to a normal human heart rate. The internal microvascular lumen could be maintained for 6 weeks and showed good results during preliminary surface re-vascularization in vitro and vascular remodeling in vivo. In summary, we propose a simple method for constructing vascularized engineered myocardial tissue, through phased cultivation that does not rely on high-end manufacturing equipment and cutting-edge preparation techniques. The constructed tissue has potential value for clinical use after preliminary evaluation.

Positive additive interaction effects of age, sex, obesity, and metabolic syndrome on left ventricular dysfunction.

OBJECTIVE: This study aims to explore the association between metabolic syndrome (MetS) and left ventricular diastolic dysfunction (LVDD) and systolic dysfunction (LVSD), defined by impaired global longitudinal strain (GLS), and assess additive and multiplicative interactions among age, sex, obesity, and MetS regarding LVDD and LVSD. METHODS: We prospectively recruited 5503 participants from the China PEACE (Patient-Centered Evaluative Assessment of Cardiac Events) Million Persons Project with complete echocardiography exam. Multivariable logistic models were used to calculate adjusted odds ratios to evaluate both additive and multiplicative interactions. RESULTS: The mean age was 56.59 years; 59.4% were women, 46.7% had MetS, 26.6% had left ventricular hypertrophy, 46.3% had LVDD, and 12.50% had impaired GLS. Compared to the non-MetS, the odds ratio (OR) of LVDD and impaired GLS in MetS were 1.40 (1.20-1.64) and 1.26 (1.03-1.54), respectively. For LVDD, relative excess risk due to additive interaction (RERI) for women and MetS, elderly and MetS, obesity and MetS were 0.76 (0.02-1.50), 35.65 (17.51-53.79), and 2.14 (0.66-3.62), respectively, thus suggesting additive interactions. For impaired GLS, RERI for obesity and MetS was 3.37 (0.50-6.24), thus suggesting additive interactions. CONCLUSIONS: The MetS is independently associated with LVDD and impaired GLS. From the public health implications, prevention of MetS in women, elderly, and obese individuals might result in a greater reduction of LVDD and LVSD risk in cardiovascular high-risk population.

Life's Essential 8 and risk of incident heart failure in community population without cardiovascular disease: Results of the sub-cohort of China PEACE Million Persons Project.

OBJECTIVE: The American Heart Association has introduced the Life's Essential 8 metrics to evaluate and promote cardiovascular health (CVH) and we aimed to evaluate the association of CVH and incident heart failure (HF). METHODS: The China PEACE Million Persons Project is a population-based cardiovascular disease (CVD) screening study. This was a sub-cohort of the project that included individuals free of CVD at baseline. Components and classifications of CVH, including diet, physical activity, smoking status, sleep status, body mass index (BMI), non-high density lipoprotein (non-HDL), blood glucose and blood pressure, were determined based on the Life's Essential 8. CVH status was categorized as poor, intermediate and ideal status. HF cases were identified by linking hospital records. RESULTS: Among the cohort (n = 38,571, median age 54 years and women 60.5%), proportion of individuals with poor, intermediate and ideal CVH was 30.7%, 56.9% and 12.4%. After a median follow-up of 3.56 years, the incidence of HF in individuals with poor, intermediate and ideal CVH was 2.5%, 1.1% and 0.5% respectively. Compared to poor CVH, intermediate (adjusted HR: 0.52 [95% CI: 0.43-0.61]) and ideal CVH (adjusted HR: 0.38 [95% CI: 0.26-0.57]) were associated with a lower HF risk. A gradient of association between CVH and HF risk was observed (P-trend<0.001). Ideal physical activity, ideal smoking status, and intermediate and ideal status of BMI, blood glucose and blood pressure were associated with a lower HF risk. CONCLUSION: Poor CVH was associated with an increased risk of HF, and promotion of CVH may help prevent HF development.

Early Famine Exposure Results in Left Ventricular Remodeled, Diastolic Dysfunction and Systolic Function Preserved in Adults.

INTRODUCTION: Malnutrition during a critical window of development in a fetus or infant can result in abnormal cardiac remodeling and function. It is uncertain whether the contribution of these effects continues to impact the cardiac remodeling and function of adults over the course of several decades of growth. Our study examined the impact of early Chinese famine exposure on cardiac remodeling, left ventricular (LV) diastolic function, and LV systolic function in adults. METHODS: Participants at high risk of cardiovascular disease from the China Patient-Centered Evaluative Assessment of Cardiac Events Million Persons Project (PEACE MPP) were enrolled. The famine in China lasted from 1959 to 1962. A total of three groups were formed based on the participants' birth dates: pre-famine group, famine exposure group, and post-famine group. Logistic regression and linear mixed models were used to explore the association between famine exposure and cardiac remodeling, LV diastolic function and LV systolic function in adults. RESULTS: The study included 2,758 participants, the mean age was 57.05 years, 62.8% were female, 26.4% had LV hypertrophy (LVH), 59.6% had LV diastolic dysfunction (LVDD), and 10.5% had reduced global longitudinal strain (GLS). Compared to post-famine exposure, participants had independently increased risk of LVH in the famine exposure group (OR: 2.02, 95% CI: 1.60-2.56) and pre-famine exposure (OR: 1.36, 95% CI: 1.06-1.76). Compared to post-famine exposure, the risk of LVDD remarkably increased in the famine exposure group (OR: 3.04, 95% CI: 2.49-3.71) and pre-famine exposure group (OR: 1.87, 95% CI: 1.52-2.31). Famine exposure had no significant impact on GLS but was associated with a significant increase in LV ejection fraction (LVEF) and LV end-diastolic diameter (LVEDD). Significant interactions were observed between the effects of famine exposure and other clinical/sociodemographic variables (gender, systolic blood pressure [SBP] ≥140 mm Hg or not, high school or above or not, and annual income <50,000 RMB or not) on these outcomes. CONCLUSION: Exposure to famine, particularly during fetal and infant stages, increases the risk of LVH and LVDD in adults. However, the LV systolic function remains preserved. These impacts are more pronounced in females, individuals with SBP ≥140 mm Hg, those with low income, or those with high educational status.

Associations of maternal exposure to multiple plasma trace elements with the prevalence of fetal congenital heart defects: A nested case-control study.

BACKGROUND: Scanty knowledge prevails regarding the combined impact of multiple plasma trace elements and main contributors on the prevalence of congenital heart defects (CHDs) in offspring. Thus, we performed a nested case-control analysis in a neonates cohort to investigate this important public health issue. METHODS: We selected 164 pairs of cases and non-malformed controls from live births registered in the parent cohort (n = 11,578) at the same hospital. Plasma levels of 14 trace elements were determined by inductively coupled plasma-mass spectrometry. The odds ratios (ORs) of exposure were compared between cases and controls. Bayesian Kernel Machine Regression (BKMR) and Quantile g-Computation (QgC) models were employed to assess the cumulative effect of exposure to trace elements. RESULTS: We found positive associations and linear dose-response relationships between plasma Pb and Sn and CHD. BKMR models indicated that the overall effect of the trace element mixture was associated with CHDs below the 45th percentile or above the 50th percentile, and the combined effect was primarily attributed to Sn and Pb. The QgC model indicated significantly increased odds of CHD with simultaneous exposure to all studied trace elements (OR: 2.19, 95%CI: 1.44-3.33). CONCLUSIONS: This study is the first to report an association between elevated levels of mixed trace elements in maternal plasma with an increased prevalence of fetal CHDs, particularly in the case of Pb and Sn. Findings from this study provide further evidence of the important of heavy metal pollution to human health, and can help stakeholders prioritize policies and develop interventions to target the leading contributors to human exposure.

Sex difference in incidence and risk factors of hospitalization for heart failure, and subsequent mortality: findings from the China PEACE million persons project.

BACKGROUND: Epidemiological study of sex differences in incidence and risk factors of heart failure (HF), and subsequent mortality attributed to HF in the Chinese general population is lacking. This study aims to assess the sex differences in the incidence and risk factors of hospitalization for HF and evaluate the sex differences in population attributable fractions (PAFs) for the subsequent mortality among the general population. METHODS: Data were from a sub-cohort of the Patient-Centered Evaluative Assessment of Cardiac Events Million Persons Project in China. Fine and Gray models were conducted to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) accounting for the competing risk of all-cause mortality. Propensity score matching analysis and subgroup analyses were used to verify the robustness of the results. Adjusted PAFs of HF for all-cause and cardiovascular mortality were evaluated by sex. RESULTS: Of the 102,278 participants, 60.5% were women, and the mean age was 54.3 years. After a median follow-up of 3.52 years, 1588 cases of hospitalization for HF were identified. After adjusting for the covariates, women had 31% (95% CI: 0.61-0.79) lower risk for HF than men. The results were consistent in the propensity score matching cohort and across all subgroup analyses (all P sex-subgroups interaction > 0.05). Although women were associated with a lower risk of HF, they had a higher PAF (24.2%, 95% CI: 16.0-31.6) for subsequent cardiovascular mortality than men (16.5%, 95% CI: 11.3-21.5). Several significant differences in risk factors for HF were noted between sexes. CONCLUSION: In the southern Chinese population, women had a lower risk of HF but had a higher cardiovascular mortality fraction attributed to HF than men. Sex-specific preventative strategies and management for HF should be warranted.

System analysis based on the lysosome-related genes identifies HPS4 as a novel therapy target for liver hepatocellular carcinoma.

Background: Liver cancer is a leading cause of cancer-related deaths worldwide. Lysosomal dysfunction is implicated in cancer progression; however, prognostic prediction models based on lysosome-related genes (LRGs) are lacking in liver cancer. This study aimed to establish an LRG-based model to improve prognosis prediction and explore potential therapeutic targets in liver cancer. Methods: Expression profiles of 61 LRGs were analyzed in The Cancer Genome Atlas liver cancer cohorts. There were 14 LRGs identified, and their association with clinical outcomes was evaluated. Unsupervised clustering, Cox regression, and functional assays were performed. Results: Patients were classified into high-risk and low-risk subgroups based on the 14 LRGs. The high-risk group had significantly worse overall survival. Aberrant immune infiltration and checkpoint expression were observed in the high-risk group. Furthermore, HPS4 was identified as an independent prognostic indicator. Knockdown of HPS4 suppressed liver cancer cell proliferation and induced apoptosis. Conclusion: This study developed an LRG-based prognostic model to improve risk stratification in liver cancer. The potential value of HPS4 as a therapeutic target and biomarker was demonstrated. Regulation of HPS4 may offer novel strategies for precision treatment in liver cancer patients.

Stage 1 hypertension defined by the 2017 ACC/AHA blood pressure guideline and cardiometabolic multimorbidity in Chinese adults.

The association of blood pressure (BP) classification defined by the 2017 American College of Cardiology/American Heart Association (ACC/AHA) guideline with cardiometabolic multimorbidity (CMM) remains unclear. The present study aimed to investigate this research gap in the Chinese adults. Cross-sectional data were collected from a population-based cohort conducted in Southern China. Participants were categorized as having normal BP, elevated BP, stage 1 hypertension, and stage 2 hypertension according to the 2017 ACC/AHA guideline. CMM was defined as having two or more of the following diseases: coronary heart disease, stroke, and diabetes. The relationship between the BP classifications and CMM was examined by multivariate logistic regression. A total of 95 649 participants (mean age: 54.3 ± 10.2 years, 60.7% were women) were enrolled in this study. Multivariable-adjusted logistic regression models revealed that stage 1 hypertension (odds ratio [OR], 1.35; 95% confidence interval [CI], 1.03-1.78) and stage 2 hypertension (OR, 3.53; 95% CI, 2.82-4.47) were significantly associated with a higher prevalence of CMM compared with normal BP. The association between stage 1 hypertension and CMM were profound in women (OR, 1.76; 95% CI, 1.17-2.67) and in the middle-aged group (OR, 1.53; 95% CI, 1.02-2.35) compared with men and older individuals, respectively. Our study showed that among Chinese adults, stage 1 hypertension defined by the 2017 ACC/AHA guideline was already associated with higher odds of CMM compared with normal BP, particularly in women and middle-aged participants. Managing stage 1 hypertension may be an important measure to prevent CMM in Chinese adults.

Lipoprotein(a) as a Higher Residual Risk for Coronary Artery Disease in Patients with Type 2 Diabetes Mellitus than without.

Purpose: Lipoprotein(a) (Lp[a]) is well-known as a residual risk factor for coronary artery disease (CAD). However, the different adverse effects of Lp(a) about CAD in patients with or without type 2 diabetes mellitus (T2DM) are unclear. This study aimed to investigate the Lp(a) thresholds for CAD diagnosis in T2DM and non-T2DM patients, and further compare the Lp(a) alarm values along with optimal low-density lipoprotein cholesterol (LDL-C) level. Methods: This retrospective study consecutively enrolled patients with suspected CAD who underwent coronary angiography in Guangdong Provincial People's Hospital between September 2014 and July 2015. A logistic regression model was established to explore the association of Lp(a) and CAD in patients. Restricted cubic splines were used to compare the threshold values of Lp(a) for CAD in patients with and without T2DM, and further in optimal LDL-C level situation. Results: There were 1522 patients enrolled finally. After multivariable adjustment, Lp(a) was an independent risk factor for CAD in patients with T2DM (odds ratio [OR]: 1.98, 95% CI]: 1.12-3.49, p = 0.019) and without T2DM (OR: 3.42, 95% CI: 2.36-4.95, p < 0.001). In the whole population, the Lp(a) threshold of CAD was 155, while 145 mg/L for T2DM and 162 mg/L for non-T2DM ones, respectively. In patients with LDL-C<1.8 mmol/l, the alarm value of Lp(a) was even lower in T2DM than non-T2DM patients (155 vs 174 mg/L). Conclusion: Lp(a) was a significant residual risk for CAD in patients whether with T2DM or not. And Lp(a) had a lower alarm value in T2DM patients, especially in optimal LDL-C level.

Time to Benefit of Sodium-Glucose Cotransporter-2 Inhibitors Among Patients With Heart Failure.

Importance: Emerging evidence has consistently demonstrated that sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of heart failure (HF) hospitalization and cardiovascular (CV) death among patients with HF. However, it remains unclear how long a patient needs to live to potentially benefit from SGLT2 inhibitors in this population. Objectives: To estimate the time to benefit from SGLT2 inhibitors among patients with HF. Design, Setting, and Participants: This comparative effectiveness study systematically searched PubMed for completed randomized clinical trials about SGLT2 inhibitors and patients with HF published until September 5, 2022; 5 trials with the year of publication ranging from 2019 to 2022 were eventually included. Statistical analysis was performed from April to October 2022. Intervention: Addition of SGLT2 inhibitors or placebo to guideline-recommended therapy. Main Outcomes and Measures: The primary outcome was the time to first event of CV death or worsening HF, which was broadly comparable across the included trials. Results: Five trials consisting of 21 947 patients with HF (7837 [35.7%] were female; mean or median age older than 65 years within each trial) were included. SGLT2 inhibitors significantly reduced the risk of worsening HF or CV death (hazard ratio [HR], 0.77 [95% CI, 0.73-0.82]). Time to first nominal statistical significance (P < .05) was 26 days (0.86 months), and statistical significance was sustained from day 118 (3.93 months) onwards. A mean of 0.19 (95% CI, 0.12-0.35) months were needed to prevent 1 worsening HF or CV death per 500 patients with SGLT2 inhibitors (absolute risk reduction [ARR], 0.002). Likewise, 0.66 (95% CI, 0.43-1.13) months was estimated to avoid 1 event per 200 patients with SGLT2 inhibitors (ARR, 0.005), 1.74 (95% CI, 1.07-2.61) months to avoid 1 event per 100 patients (ARR, 0.010), and 4.96 (95% CI, 3.18-7.26) months to avoid 1 event per 50 patients (ARR, 0.020). Further analyses indicated a shorter time to benefit for HF hospitalization and among patients with diabetes or HF with reduced ejection fraction. Conclusions and Relevance: In this comparative effectiveness research study of estimating the time to benefit from SGLT2 inhibitors among patients with HF, a rapid clinical benefit in reducing CV death or worsening HF was found, suggesting that their use may be beneficial for most individuals with HF.

Sex-specific population attributable risk factors for cardiovascular and all-cause mortality in the general population: Findings from the China PEACE million persons project.

Little evidence exists regarding the sex-specific population attributable risk factors for cardiovascular and all-cause mortality in the Chinese general population. We used a sub-cohort of the China Patient-Centered Evaluative Assessment of Cardiac Events million persons project to evaluate the overall and sex-specific associations and population attributable fractions (PAFs) of twelve risk factors for cardiovascular and all-cause mortality. 95,469 participants were included between January 2016 and December 2020. The twelve risk factors (including four socioeconomic status and eight modifiable risk factors) were collected or measured at baseline. The outcomes of the study were all-cause mortality and cardiovascular mortality. Overall, 60.7% (N = 57,971) were women, and the mean age was 54.3 ± 10.2 years. After a median of 3.52 years of follow-up, 1311 (1.4%) people died, and 362 (0.4%) people died of cardiovascular causes. Majorities of risk factors were significantly associated with all-cause and cardiovascular mortality, and suboptimal blood pressure and low educational attainment were the two leading attributable risk factors for all-cause and cardiovascular mortality. The twelve risk factors collectively explained 72.4% (95% confidence interval (CI): 63.5, 79.2) and 84.0% (95% CI: 71.1, 91.1) of PAFs for all-cause and cardiovascular mortality. When stratified by sex, men had more risk factors that were significantly attributable to mortality than women, whereas low educational attainment had a more pronounced impact on female cardiovascular health. This study found that the twelve risk factors collectively explained a significant proportion of PAFs for all-cause and cardiovascular mortality. Several sex-related disparities in the associations between risk factors and mortality were noted.

Prognostic implications of machine learning-derived echocardiographic phenotypes in community hypertensive patients.

BACKGROUND: Echocardiogram is commonly used to evaluate cardiac remodeling in hypertension (HTN). However, study on echocardiographic phenotypes and their prognostic implications in HTN is limited. OBJECTIVE: We aimed to evaluate the prognostic implications echocardiographic phenotypes in community hypertensive patients. METHOD: A total of 1881 community hypertensive patients without overt cardiovascular disease and severe renal disease (mean age 62.8 years, women 57.9%) were included. Using Two-Step cluster analysis with four conventional echocardiographic variables, two clusters with distinct echocardiographic phenotypes were identified. RESULT: The Cluster 1 (namely "mild-remodeling" HTN; n = 1492) had low prevalence of enlarged left atrium (LA; 0.9%) and left ventricular hypertrophy (LVH; 16.2%) and better LV diastolic function. They were younger and more likely to be men and had lower comorbid burden. The Cluster 2 (namely "severe-remodeling" HTN; n = 389) had higher prevalence of enlarged LA (26.0%) and LVH (83.0%) and worse LV diastolic function. They were older and more likely to be women and had higher comorbid burden. After a median follow-up of 4.2 years, compared to the Cluster 1, the Cluster 2 had higher incidence of cardiovascular (4.1% vs 1.7%; P = .006) and all-cause (9.8% vs 4.8%; P < .001) death, with adjusted hazard ratio of 2.80 (95% CI 1.39-5.62; P = .004) and 2.04 (95% CI 1.32-3.14; P < .001) respectively. CONCLUSION: These findings indicate that the conventional echocardiographic variables-based algorithm could help identify asymptomatic community hypertensive patients at risk for cardiovascular and all-cause death. Further studies are needed to develop and validate phenotype-specific prevention and intervention strategies in HTN.

Longitudinal Study of Left Ventricular Mass Index Trajectories and Risk of Mortality in Hypertension: A Cohort Study.

Background Left ventricular mass index (LVMI) has been extensively studied for its relationship with mortality but has been typically assessed at a single time point. We, therefore, describe the trajectory of LVMI in a population with hypertension over 6 years to study the subsequent risk of mortality. Methods and Results We assessed LVMI that was collected during annual health examinations in round 1 (2010-2012), round 2 (2013-2014), and round 3 (2015-2016) with 2 allometric scalings, height2.7, and body surface area, in a cohort of participants with hypertension to identify 6-year trajectories of LVMI by latent class trajectory modeling. We followed up with participants for mortality by latent trajectory from the last echocardiographic examination (September 17, 2014-December 8, 2016) to December 31, 2018. We calculated mortality hazard ratios by assigned trajectory using Cox proportional hazards models. We obtained data for LVMI from 2453 participants (mean age, 61.80 [SD, 12.14] years, 1428 [58.2%] female). We identified 3 trajectories of LVM/H2.7, characterized by maintained low stable (1298 [52.9%]); moderate stable (935 [38.1%]); high stable (220 [9.0%]), as well as 3 trajectories by LVM/body surface area. During a median follow-up of 2.15 years, 167 participants developed all-cause mortality, and 71 were cardiovascular mortality. Only the high stable trajectory was associated with a higher risk of all-cause mortality compared with the low stable trajectory by LVM/H2.7 or LVM/body surface area (all P<0.05). In Kaplan-Meier survival analysis, the trajectory with high stable LVM/body surface area had significantly lower survival probability. Conclusions In community hypertension, the individuals with high stable LVMI trajectory had the highest risk of all-cause mortality. The individuals in the moderate stable trajectory had a similar risk for mortality as those in the low stable trajectory.

Temporal Trends in the Incidence and Mortality of Major Reproductive-Related Cancers in Women in Guangzhou From 2010 to 2020: A Joinpoint and Age-Period-Cohort Study.

Objective: To understand the temporal trends of cancer incidence and mortality in women in Guangzhou during the past 11 years and provide clues for future research. Methods: Data were obtained from the Guangzhou Cancer and Death Registry. Average annual percentage changes (AAPCs) in age-standardized incidence rates (ASIRs) and age-standardized mortality rates (ASMRs) were obtained by joinpoint regression. The age-period-cohort (APC) model was generated to quantify the effects of age, period, and cohort. Results: The ASIRs for cervical (AAPC = -4.3%) and ovarian (AAPC = -3.2%) cancers showed a downward trend during 2010-2020, and that for uterine cancer showed an upward trend. The ASMRs of breast (APC = 5.0%) and cervical (APC = 8.8%) cancers increased. The APC model highlights different age, period, and birth cohort effects depending on the cancer site. Conclusion: The ASIRs for cervical and ovarian cancers among women in Guangzhou showed a decreasing trend during the period. The APC model showed mortality for 4 cancers increased with age. Incidence and mortality decreased with increasing birth cohort. Annual reproductive cancer screening is recommended for women of appropriate age to reduce the disease burden.

Long-term exposure to ambient air pollution, circadian syndrome and cardiovascular disease: A nationwide study in China.

OBJECTIVES: Epidemiological evidence suggests associations between ambient air pollution and cardiovascular disease (CVD), while circadian rhythm dysregulation, presented by circadian syndrome (CircS), is emerging as a new proxy to cardiovascular disorder that could provide a bridge between them. The present study aims to clarify the effect of high levels ambient air pollution exposure on CircS and CVD in China. METHODS: From the China Health and Retirement Longitudinal Study, we recruited 9116 Chinese participants in 2011 and followed them to 2015. A spatiotemporal model was applied to estimate exposure to particles with diameters ≤2.5 µm (PM2.5). The variable CircS was defined based on 7 components, including the 5 components used to define metabolic syndrome as well as other two components, lack of sleep and depression. The associations between PM2.5 exposure and prevalent CircS as well as incident CVD were modeled via logistic regression analysis displaying odds ratios (ORs) and 95 % CIs (confidence intervals). A mediation analysis was undertaken to identify the potential mediating role of CircS between PM2.5 exposure and CVD. RESULTS: The mean age (standard deviation) was 59 (9) and 48.22 % were male. The OR (95 % CI) between the highest (Q4) and the lowest (Q1) quartile of PM2.5 exposure for CircS was 1.13 (1.01-1.28) in 2011 and 1.44 (1.22-1.72) in 2015. The cumulative effect of the components of CircS became more obvious with the increase of the PM2.5 quartile exposure. For the Q4 versus Q1 of PM2.5 increment, the multivariate-adjusted OR (95 % CI) was 1.66 (1.20-2.29) for CVD incidence. CircS partially mediated the association between PM2.5 exposure and CVD. CONCLUSIONS: Exposure to PM2.5 is a risk factor for CircS and CVD, and the effect of PM2.5 on CVD may be explained by CircS. Improving air quality would have high value in preventing CircS as well as CVD in public health.