The potential therapeutic roles of dental pulp stem cells in spinal cord injury.

Spinal cord injury (SCI) can lead to serious functional disorders, which have serious impacts on patients and society. The current traditional treatments of SCI are not effective the injured spinal cord is difficult to repair and regenerate. In recent years, stem cell transplantation for the treatment of SCI has been a hot research topic. Dental pulp stem cells have strong abilities of self-renewal and multi-directional differentiation, and have been applied for tissue engineering and regenerative medicine. And dental pulp stem cells have certain advantages in neuro-regenetation, bringing new hope to biotherapy for SCI. This article reviews the characteristics of dental pulp stem cells and their research progress in the treatment of SCI.

Cardiometabolic factors and population risks of cardiovascular disease in community-dwelling adults with varied blood pressure statuses.

AIMS: To examine the differential associations between cardiometabolic risk factors and cardiovascular disease (CVD), and to evaluate the population-attributable fractions (PAFs) for CVD among community-dwelling adults with varied blood pressure (BP) statuses. METHODS: This prospective cohort study included participants without prevalent CVD from a subcohort of the China Patient-Centred Evaluative Assessment of Cardiac Events Million Persons Project. Participants were divided into four BP groups according to the American College of Cardiology/American Heart Association guidelines. The study exposure comprised the selected cardiometabolic risk factors, including waist circumference (WC), body mass index, (BMI) heart rate, fasting blood glucose (FBG), low-density lipoprotein cholesterol, and remnant cholesterol. The outcome was hospitalizations for CVD. Cox proportional hazard models were conducted, and the PAFs were calculated in the analysis. RESULTS: Among the 94 183 participants (39.0% were men, mean age: 54.2 years), 26.6% had Stage 1 hypertension and 30.8% had Stage 2 hypertension. A total of 6065 hospitalizations for CVD were captured after a median follow-up of 3.5 years. BP (per 1-standard deviation [SD]: hazard ratio [HR] 1.34, 95% confidence interval [CI] 1.29, 1.40), FBG (per 1-SD: HR 1.16, 95% CI 1.14, 1.19) and WC (per 1-SD: HR 1.41, 95% CI 1.36, 1.47) were three major contributors to CVD events. BP status significantly modified the associations of abdominal obesity, suboptimal BMI, suboptimal heart rate and abnormal FBG with CVD, with stronger associations with CVD observed in optimal BP groups compared to hypertensive groups (p for risk factor-by-BP group interaction <0.05). Participants with all cardiometabolic risk factors were at the highest risk for CVD, accounting for 35.6% (95% CI 30.0, 40.8) of the PAF for CVD. Among the risk factors, BP control explained the highest PAF for CVD (15.1%, 95% CI 8.2, 21.4) The overall PAFs of cardiometabolic risk factors for CVD were higher among the normotensive participants compared to the hypertensive participants. CONCLUSIONS: The awareness and control rates of hypertension were extremely low among Southern Chinese adults. BP status significantly modified the associations between cardiometabolic risk factors and CVD, and the overall PAFs for CVD were higher among people with normal BP. Dedicated efforts are needed to improve the management of cardiometabolic factors.

Sex Differences in the Associations of Traditional Risk Factors and Incident Heart Failure Hospitalization: A Prospective Cohort Study of 102 278 Chinese General Adults.

BACKGROUND: Evidence regarding sex differences in the associations of traditional risk factors with incident heart failure (HF) hospitalization among Chinese general adults is insufficient. This study aimed to evaluate the potential sex differences in the associations of traditional risk factors with HF among Chinese general adults. METHODS AND RESULTS: Data were from a subcohort of the China PEACE (Patient-Centered Evaluative Assessment of Cardiac Events) Million Persons Project. The traditional risk factors were collected at baseline, and the study outcome was HF-related hospitalization identified from the Inpatients Registry. A total of 102 278 participants (mean age, 54.3 years; 39.5% men) without prevalent HF were recruited. A total of 1588 cases of HF-related hospitalization were captured after a median follow-up of 3.52 years. The incidence rates were significantly higher in men (2.1%) than in women (1.2%). However, the observed lower risk of HF in women was significantly attenuated or even vanished when several traditional risk factors were poorly controlled (P for sex-by-risk factors <0.05). The selected 11 risk factors collectively explained 62.5% (95% CI, 55.1-68.8) of population attributable fraction for HF in women, which is much higher than in men (population attributable fraction, 39.6% [95% CI, 28.5-48.9]). CONCLUSIONS: Although women had a lower incidence rate of hospitalization for HF than men in this study, the risk for HF increased more remarkably in women than in men when several traditional risk factors were poorly controlled. This study suggests that intensive preventative strategies are immediately needed in China.

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.

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.

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.

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.

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.

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.

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.

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.