Liver steatosis and fibrosis increase the predicted 10-year atherosclerotic cardiovascular disease (ASCVD) risk, though the roles of chronic inflammation and metabolic dysregulation remain unclear. This cross-sectional study quantitatively assesses this association and evaluates the mediating effects of metabolic dysregulation and chronic inflammation.

In this study, we enrolled 6110 adults from ten communities in Canton, China. Hepatic steatosis and fibrosis were assessed using vibration-controlled transient elastography (VCTE) through controlled attenuation parameter (CAP) and liver stiffness measurement (LSM), while predicted 10-year ASCVD risk was calculated using the China-PAR project model. Associations between CAP/LSM values and predicted 10-year ASCVD risk were analyzed. Mediation analysis quantified the effects of high-sensitivity C-reactive protein (hs-CRP), homeostasis model assessment of insulin resistance (HOMA-IR), remnant cholesterol (RC), and non-high-density lipoprotein cholesterol (non-HDL-C). The main statistical methods used included logistic regression, restricted cubic splines (RCS) analysis, interaction calculations, and mediation analysis to examine the relationships and mediators.

The study population had a mean age of 50.1 years (SD = 9.7), with 3927 females (64.3%) and 2183 males (35.7%). Additionally, 808 participants (13.2%) had type 2 diabetes, and 1911 participants (31.3%) had hypertension. Compared to the first CAP quartile (Q1), higher CAP quartiles showed increased odds ratios (OR) for predicted moderate to high 10-year ASCVD risk: 1.14 (0.89, 1.45), 1.37 (1.08, 1.73), and 2.44 (1.93, 3.10). Mediation analysis showed hs-CRP and HOMA-IR mediated CAP's link to ASCVD risk, with mediation proportions of 15.40% and 27.37%. RC and non-HDL-C mediated this association at 7.12% and 6.26%. Among patients with hepatic steatosis (CAP ≥ 248 dB/m), LSM Q4 participants had a significantly higher predicted 10-year ASCVD risk than those in LSM Q1 (OR 2.22, [1.52, 3.25]), with hs-CRP and HOMA-IR mediating 2.62% and 13.75%, respectively.

Liver steatosis and fibrosis were associated with the increased predicted ASCVD risk, with mediation effects from hs-CRP, HOMA-IR, RC, and non-HDL-C.

An overproduction of oxidized low-density lipoprotein (ox-LDL) can lead to vascular endothelial dysfunction. Relaxin-2, a novel peptide hormone, exhibits various biological functions within the cardiovascular system. However, the effects of Relaxin-2 in atherosclerosis (AS) are underreported.

We aimed to investigate the regulatory role of Relaxin-2 in the endothelial function of human aortic endothelial cells (HAECs) upon ox-LDL stimulation.

HAECs were stimulated with ox-LDL (100 mg/l) and rhRelaxin-2 (25, 50 nM) for 24 h. Multiple techniques, including real-time PCR, Western blot analysis, ELISA, and Calcein AM staining, were applied.

Treatment with human recombinant (rh) Relaxin-2 decreased lectin-like ox-LDL receptor 1 (LOX-1), a primary receptor for ox-LDL, in HAECs. rhRelaxin-2 also reduced the ox-LDL-induced expression of pro-inflammatory mediators such as interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), and monocyte chemoattractant protein-1 (MCP-1). Additionally, we observed increased expression of cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), and high mobility group protein B1 (HMGB-1) in ox-LDL-challenged HAECs, which was diminished by rhRelaxin-2. Significantly, the heightened expression of intercellular cell adhesion molecule-1 (ICAM-1) and E-selectin in ox-LDL-stimulated HAECs was mitigated by rhRelaxin-2. Consequently, rhRelaxin-2 alleviated the attachment of THP-1 cells to HAECs in a dose-dependent manner. Mechanistically, we found that rhRelaxin-2 inhibited the expression of Egr-1, a central mediator of endothelial inflammation. Furthermore, overexpression of Egr-1 was found to negate the beneficial effects of rhRelaxin-2, suggesting that these effects are mediated by the suppression of Egr-1.

Our findings propose a novel therapeutic approach with rhRelaxin-2 for patients with atherosclerosis.

The monocyte/macrophage infiltration plays critical roles in the development of atherosclerosis. Arterial stiffness is a cholesterol-independent risk factor for cardiovascular events. The regulation of arterial stiffness on biomechanics of macrophages and its underlying mechanism remains unclear. We prepared polyacrylamide gels with low and high stiffness that corresponded to healthy and diseased blood vessels, respectively. We found that macrophages cultured on stiff matrix had increased rigidity and migration ability compared to those on soft matrix. An actin capping protein, tropomodulin1 (Tmod1) was upregulated in macrophages by stiff matrix and in arteries with high stiffness. Further analyses showed that deficiency of Tmod1 in macrophages completely or partially prevented the changes in actin polymerization, cell adhesion and cell spreading induced by stiff matrix. Overexpression of Tmod1 in macrophages enhanced actin polymerization, cell adhesion and spreading on stiff matrix. Tmod1 was involved in the regulation of vinculin expression and formation of focal adhesion in macrophages on stiff matrix. Finally, the deficiency of Tmod1 in macrophages retarded the formation of atherosclerotic plaques in blood vessels with high matrix stiffness. The results suggest that Tmod1 was a key regulator in macrophage rigidity and migration on stiff substrate. The present work will help us to understand the biomechanical mechanisms for the development of atherosclerosis.

Intracerebral hemorrhage (ICH) is a common and fatal type of stroke, especially in central China. However, recent epidemiologic data are scarce. The study aimed to investigate the latest prevalence of ICH in central China and assess the risk of ICH in the next 10 years based on the Resident Health Records (RHR) data.

First, this cross-sectional study was based on a large-scale face-to-face investigation of ICH, which was launched on residents aged 20 years or older from January 1, 2021, to December 31, 2021, and estimated the prevalence of ICH in Hunan, a representative province in central China. Then, based on the RHR database, we assessed the ICH risk, population attributable fraction (PAF), and effects of ICH prevention under different risk factor control scenarios over the next decade by the China Kadoorie Biobank (CKB)-cardiovascular disease (CVD) model.

In 2021, 1.78 million participants enrolled in the investigation (mean age = 50.1 years; 51% male). The age-standardized prevalence rate of ICH was 159.2 (95% CI 153.7-164.9) per 100,000. The prevalence rate of ICH in men was 193.6 (95% CI 185.2-202.5) per 100,000, while in women was 124.0 (95% CI 117.1-131.3) per 100,000, and it increased with age. Spatial aggregation was observed, with the peak prevalence rate of ICH at 327.3 (95% CI 293.1-365.5) per 100,000 in Zhuzhou, followed by Changsha was 215.8 (95% CI 190.6-243.9) per 100,000, while Shaoyang had the lowest rate was 62.8 (95% CI 51.2-77.1) per 100,000. For the assessment of 10-year ICH risk, we included a total of 8.36 million participants aged 30-79 with the RHR database into the CKB-CVD model. We found that there will be 354,146 cases (ICH risk: 4.2%) of ICH among the participants in the next decade. Controlling hypertension showed the highest potential for ICH prevention, with a PAF of 8.6%. By controlling hypertension, smoking, waist circumference, and diabetes, 56,673 ICH cases (PAF 19.1%) can be avoided in the next decade.

The ICH prevalence in central China remained high. Strict blood pressure control could significantly reduce the risk of ICH in the next 10 years. It is important to continually improve ICH prevention strategies in the general population.

Electronic health records (EHR) passively generate large datasets on real-world patient populations in easily retrievable form, allowing the cost-efficient and timely execution of epidemiological cohorts on a broad array of topics. However, EHR-based cohorts specialising in mental disorders have not yet been reported. Ningbo has made significant achievements in healthcare data management in China. This study, relying on the Ningbo Mental Health Information System and the Ningbo Regional Health Information Platform, has established the Ningbo Schizophrenia Cohort (NSC), providing an exemplary study for cohort studies on schizophrenia.

This population-based ambispective cohort study included patients with schizophrenia aged 18-65 years at the time of diagnosis who were eligible for healthcare services in Ningbo, China. Participants were identified using the Ningbo Mental Health Information System between 1 January 2010, and 31 December 2023. Once an individual enters the NSC, they are followed up continuously until death or relocation. A total of 26 899 patients with schizophrenia are included in the NSC.

Among 26 899 patients, 55.4% were female and 53.1% had less than 7 years of education. Until 31 December 2023, 4505 deaths occurred, and 97.83% of patients had at least one electronic medical record. The median age at diagnosis for non-survivors (median (IQR): 40 (29-51) years) was higher than that of survivors (median (IQR): 34 (26-45) years).

The NSC will continue to collect longitudinal data to capture the full life cycle of schizophrenia, including pre-onset, diagnosis, follow-up, recovery or death. This will result in a continuous, complete and multidimensional EHR for patients with schizophrenia. Planned future research aims to generate new real-world evidence on the aetiology of schizophrenia, investigate comorbidities to facilitate co-management and develop predictive models for schizophrenia and related cardiovascular diseases.

NCT06370793.

Dinitroaniline herbicides are widely used to control weed resistance, but their effects on atherosclerotic cardiovascular disease (ASCVD) are unknown. Serum trifluralin and pendimethalin, mitochondrial DNA copy number (mtDNAcn), and predictors of 10-year ASCVD risk were measured in participants from the Wuhan-Zhuhai cohort. Linear mixed model, restricted cubic spline (RCS) model, Bayesian kernel machine regression (BKMR) model, and weighted quantile sum (WQS) regression model were used for association analyses. Mediation models were used to estimate the potential role of mtDNAcn in the above associations. Cross-sectionally, each 1-unit increase in ln-transformed serum trifluralin and pendimethalin levels were associated with an increase in 10-year ASCVD risk of 0.272 % and 0.178 %, respectively (all P < 0.05). The BKMR and WQS models showed that trifluralin and pendimethalin co-exposure was associated with the increased 10-year ASCVD risk, with trifluralin being the primary contributor. Longitudinally, each 1-unit increase in ln-transformed serum trifluralin and pendimethalin levels were associated with the annual increase in 10-year ASCVD risk of 0.192 % and 0.156 %, respectively (all P < 0.05). Mediation analysis showed that mtDNAcn mediated 3.8 % of the trifluralin-associated increase in 10-year ASCVD risk. In conclusion, trifluralin and pendimethalin were cross-sectionally and longitudinally associated with the increased 10-year ASCVD risk, and mtDNAcn partially mediated the association.

Existing evidence suggests that elevated 1-hour post-load plasma glucose (1-h PG ≥ 8.6 mmol/L) during an oral glucose tolerance test (OGTT) is associated with atherogenic lipid parameters which are linked to an increased risk of cardiovascular disease (CVD). However, it remains unclear whether normal glucose tolerance (NGT) individuals with elevated 1-h PG (NGT-1hPG-high) should still be considered low-risk. Therefore, this study aims to demonstrate comprehensive lipid characteristics in individuals with different glycemic status stratified by 1-h PG, with a particular focus on those with NGT-1hPG-high.

This cross-sectional study included individuals aged 25-55 years with high-risk of diabetes from the Daqing Diabetes Prevention Study II (Daqing DPS-II). Individuals were categorized into different glycemic status based on the World Health Organization's 1999 criteria and the International Diabetes Federation's 2024 position statement on 1-h PG. Traditional (TC, TG, HDL-C, LDL-C) and non-traditional lipid parameters [ApoA-1, ApoB, sdLDL-C, Lp(a), non-HDL-C, remnant cholesterol (RC), ApoB/ApoA-1, LDL-C/ApoB] were measured. Dyslipidemia was defined according to the 2023 Chinese Guidelines for Lipid Management. The China-PAR equation was used to estimate 10-year CVD risk. Spearman's correlation coefficients were calculated to evaluate the correlation between lipid parameters and 10-year CVD risk. Logistic and multiple linear regression models were performed to assess the association between 1-h PG and dyslipidemia as well as lipid parameters adjusting for covariates.

Among 2 469 individuals, 22.7% had NGT with normal 1-h PG (NGT-1hPG-normal), 19.9% had NGT-1hPG-high, 2.6% had prediabetes with normal 1-h PG (PDM-1hPG-normal), 34.2% had prediabetes with elevated 1-h PG (PDM-1hPG-high), and 20.6% had newly diagnosed diabetes. The prevalence of dyslipidemia did not significantly differ between NGT-1hPG-high and PDM-1hPG-high (OR = 1.13, 95%CI: 0.88-1.44, P > 0.05). Higher 1-h PG levels were consistently associated with an atherogenic lipid profile, characterized by increased TC, TG, LDL-C, ApoB, sdLDL-C, non-HDL-C, RC and ApoB/ApoA-1, along with decreased ApoA-1, HDL-C and LDL-C/ApoB (all P < 0.05). Among lipid parameters, TG, sdLDL-C, RC, ApoB/ApoA-1, LDL-C/ApoB and HDL-C showed the strongest correlation with 10-year CVD risk, with Spearman's correlation coefficients of 0.41, 0.38, 0.35, 0.31, - 0.37 and - 0.36, respectively. In the NGT-1hPG-high, TG, sdLDL-C, and ApoB/ApoA-1 levels were significantly higher, while HDL-C and LDL-C/ApoB levels were significantly lower compared to counterparts with NGT-1hPG-normal (all P < 0.05). Moreover, except for TG and RC (both P < 0.01), the majority of lipid parameter levels in NGT-1hPG-high did not significantly differ from those in PDM (all P > 0.05).

NGT-1hPG-high exhibited a similar atherogenic lipid profile to that observed in PDM. 1-h PG could serve as a potential indicator for the early identification of at-risk individuals who may otherwise go undetected among NGT population.

Sleep is an important determinant of cardiovascular health. We sought to investigate the longitudinal association between sleep duration and incident carotid plaque in a rural Chinese population.

This population-based prospective cohort study included 1004 rural residents (age ≥40 years) who were free of carotid plaque and had no history of clinical stroke and transient ischemic attack at baseline (2017). Incident carotid plaques were detected by carotid ultrasound images at follow-up (2021). Multivariable Cox regression was used to associate sleep duration with the presence and severity of incident carotid plaques. Restricted cubic splines analyses were conducted to assess dose-response association between sleep duration and incident carotid plaques.

During the mean follow-up of 3.95 (SD=0.14) years, 214 (21.3%) of the 1004 participants were found to have incident carotid plaques. A short sleep duration (<7 versus 7-9 hours) was associated with multivariable-adjusted hazard ratio (95% CI) of 1.58 (1.10-2.28) for carotid plaques, 2.96 (1.38-6.36) for greater carotid plaque thickness, and 2.57 (1.33-4.97) for multiple carotid plaques; those associations remained significant in participants with low-to-intermediate traditional cardiovascular disease risk. Long sleep duration (>9 versus 7-9 hours) was not significantly associated with carotid plaques. Restricted cubic splines supported the association of short, but not long, sleep duration with increased risk of incident carotid plaques.

A short sleep duration is a risk factor for carotid plaques, even among individuals with low-to-intermediate cardiovascular disease risk. This suggests that short sleep duration may be a potential target for early interventions to delay carotid atherosclerosis.

URL: https://www.chictr.org.cn; Unique Identifier: ChiCTR1800017197.

This study evaluates the burden of ischemic stroke attributable to air pollution in China from 1990 to 2021, examines gender and age-specific differences, and projects future disease burden trends from 2022 to 2036. By analyzing the impact of air pollution on ischemic stroke, this study aims to provide insights for public health policies and preventive measures.

Utilizing data from the 2021 Global Burden of Disease (GBD) study, this research examined the ischemic stroke burden associated with air pollution in China. To assess historical trends and project disease burden from 2022 to 2036, Joinpoint regression modeling and decomposition analysis were employed. These methods allow for identifying significant trend changes and disentangling the contributions of various factors.

From 1990 to 2021, China observed a decline in both age-standardized mortality rates (ASMR) and age-standardized disability-adjusted life years (DALY) rates for ischemic stroke attributed to air pollution. However, the decline was slower among men than women, with a higher burden observed in elderly males. Epidemiological transitions, including improved healthcare and lifestyle changes, were the main drivers behind the overall reduction in disease burden. Projections indicate that over the next 15 years, ASMR and age-standardized DALY rates (ASDR) for women will continue to decline, while ASMR for men is expected to rise and ASDR for men will gradually increase before stabilizing.

Elderly males are disproportionately affected by ischemic stroke related to air pollution, highlighting a critical public health issue. To mitigate this burden, it is essential for the government to implement targeted, gender- and age-specific policies aimed at improving air quality, enhancing healthcare access, and promoting preventive measures for vulnerable populations, particularly the elderly and men. These findings underscore the need for integrated strategies to reduce health disparities and address the ongoing challenges posed by air pollution.

Carbohydrates are shown to be crucial to several biological processes. They are essential mediators of cell-cell recognition processes. Among them, Sialyl Lewis X (sLex) is a very significant structure in the human body. It is a critical tetrasaccharide that plays a pivotal role in various biological processes, including cell adhesion, immune response, and cancer metastasis. Known as the blood group antigen, sLex is also referred to as cluster of differentiation 15s (CD15s) or stage-specific embryonic antigen 1 (SSEA-1). sLex is not only a prominent blood group antigen, but also involved in the attraction of sperm to the egg during fertilization, prominently displayed at the terminus of glycolipids on the cell surface. By describing the synthetic methods and biological functions of sLex, this review underscores the importance of sLex in both fundamental and applied sciences and its potential to impact clinical practice.

This study aims to analyse the burden of ischemic heart disease (IHD) in China and other G20 countries from 1990-2021 and predict the burden for the next decade.

Using data from the Global Burden of Disease (GBD) 2021 study, we evaluated the age-standardised rates (ASRs) of incidence, prevalence, mortality and disability-adjusted life years (DALYs) by estimated annual percentage change (EAPC). The Bayesian age-period-cohort (BAPC) model was used to forecast the incidence, mortality and DALY rates of IHD in China from 2021-2040.

The ASRs of incidence, mortality and DALYs of IHD in China increased with EAPCs of 0.66 (95% CI: 0.50, 0.82), 0.97 (95% CI: 0.63, 1.31) and 0.51 (95% CI: 0.24, 0.78), respectively. Compared with other G20 countries, China was ranked 14th for the ASR of incidence in 1990 and then rose to 7th in 2021. The ASR of prevalence for IHD in China jumped from 8th in 1990 to 5th in 2021, and both the ASR of mortality and DALYs for IHD in China ranked 7th in 2021. The top five risk factors affecting mortality in China in 2021 were high systolic blood pressure, dietary risk, air pollution, high LDL cholesterol and tobacco. Over the next 20 years, the ASR of incidence, mortality and DALYs for IHD will increase continuously in males.

The burden of IHD is expected to increase steadily in China, highlighting the urgency for early monitoring and preventative strategies, particularly focusing on the elderly and male populations.

Asia faces a rapidly rising burden of cardiovascular disease (CVD). Preventive cardiology efforts may help address the CVD epidemic.

Solutions to address the CVD burden include a cardiovascular risk assessment framework, improving health screening efforts, better cardiovascular risk factor management, novel innovation strategies encompassing targeted lifestyle measures, and strengthening governmental efforts. With the region's wide socioeconomic and other disparities, contextualizing and practical adaptation of various strategies into local practices, especially in low-middle-income countries, will determine the success of CVD prevention efforts.

A differential approach addressing cardiovascular risk factor screening, prevention, and management that considers the context-specific socioeconomic, governmental, and cultural aspects in diverse Asian populations may help reduce the rapidly rising CVD trajectory in Asia.

The association of mortality with resting heart rate (RHR) and predicted risk of incident cardiovascular disease (CVD) has not been comprehensively elucidated.

The purpose of this study was to evaluate the individual and combined impacts of RHR and predicted CVD risk on mortality among Chinese adults.

A total of 108,257 Chinese adults underwent follow-up during 1992 to 2015. The Cox proportional hazards model was used to assess the hazard ratio (HR) and 95% confidence interval (CI) of mortality associated with RHR and the predicted risk of incident CVD.

During an average of 8.53 years of follow-up, we identified 6267 nonaccidental deaths, including 2324 CVD deaths. High-RHR participants had higher HRs of nonaccidental (HR 1.58; 95% CI 1.47-1.70), CVD (HR 1.71; 95% CI 1.53-1.92), and non-CVD mortality (HR 1.50; 95% CI 1.37-1.64) than low-RHR participants. Compared to individuals with low CVD risk, those with high CVD risk demonstrated HRs of 1.67 (95% CI 1.51-1.83) and 3.90 (95% CI 3.29-4.61) for nonaccidental and CVD mortality, respectively. Mortality risk gradually increased with elevation of CVD risk and RHR, showing the greatest HRs of nonaccidental (HR 2.57; 95% CI 2.24-2.94) and CVD mortality (HR 7.16; 95% CI 5.52-9.29) among participants with both high CVD risk and high RHR.

Our findings demonstrated that RHR and CVD risk are independently associated with mortality, and integrating them potentially could refine risk stratification of mortality. The study highlighted their important role in personalized strategies for primordial and primary prevention.

Hypertension is a prevalent chronic disease affecting over 1.2 billion people worldwide, representing a major modifiable risk factor for cardiovascular diseases. The Waist-to-Height Ratio (WHtR) and Triglyceride to High-Density Lipoprotein Cholesterol (TG/HDL-C) ratio are established metabolic indicators linked to the risk of cardiovascular and metabolic diseases. Recently, a Cardiometabolic Index (CMI), combining WHtR and TG/HDL-C ratios, has been proposed to provide a comprehensive assessment of metabolic health. This study investigates the association between CMI and hypertension using data from the National Health and Nutrition Examination Survey (NHANES).

The study utilized NHANES data from nine cycles spanning 2001 to 2018, encompassing 20,049 participants aged over 20. Exclusions were made for individuals with incomplete CMI or hypertension data, and pregnant women. CMI was calculated by multiplying the WHtR by the TG/HDL-C ratio. Hypertension was defined according to American Heart Association guidelines. The relationship between CMI and hypertension was evaluated using multivariate logistic regression analyses, with additional subgroup analyses conducted based on demographic factors. Nonlinear relationships were analyzed using smoothing curve fitting techniques.

The study identified a significant positive correlation between CMI and hypertension risk, with an increase of one unit in CMI associated with a 9% heightened risk of hypertension (OR: 1.09, 95% CI: 1.05, 1.13). The association remained significant across various demographic subgroups. A nonlinear relationship was observed, with a critical CMI threshold of 2.64. Below this threshold, higher CMI values were associated with a progressively higher prevalence of hypertension, whereas beyond this threshold, further increases in CMI did not significantly correlate with an elevated risk of hypertension.

The study demonstrates that CMI is significantly associated with hypertension risk and may serve as a valuable tool for early screening and risk assessment, particularly in identifying individuals at higher risk before reaching the critical CMI threshold. These results underscore the importance of addressing metabolic health in the prevention and management of hypertension. Future research should focus on longitudinal studies to establish causality, explore the clinical utility of CMI in hypertension screening, and examine its applicability in diverse populations.

Cardiovascular health is influenced by various factors, including not only physiological and behavioural ones but also psychological well-being. However, when developing comprehensive preventive approaches, psychological interventions often receive less attention, despite their possible multiple mechanisms on cardiovascular health. Incorporating both healthy behaviour and psychological well-being promotion would be a more efficacious preventive approach. This study aims to investigate the effects of a community-based multicomponent intervention combining positive psychological intervention and lifestyle intervention on improving cardiovascular health among older adults with risk factors of cardiovascular diseases.

This study is a multicentre, community-based, randomised controlled trial with 18 months of intervention and follow-up for community-dwelling older adults aged 60 years and above with risk factors for cardiovascular health. Intervention activities last 6 months and are composed of in-person group training sessions of 60-80 min led by trained group instructors and weekly self-monitoring homework. Participants are randomly assigned to a multicomponent intervention 'Harmony' group (24 sessions of positive psychology and lifestyle intervention delivered weekly), an active control 'Lifestyle' group (eight sessions of lifestyle intervention delivered every 3-4 weeks) or a waitlist control group (no intervention activities). Positive psychological training sessions are designed using well-known techniques derived from positive psychology theories with adaptations to Chinese culture, and lifestyle training sessions are developed according to national guidelines. The primary outcome includes the change of a composite score of systolic blood pressure, total cholesterol, high-density lipoprotein and low-density lipoprotein levels, as well as psychological well-being measured from three perspectives, including hedonic, eudaimonic and evaluative well-being. Secondary assessments include other measures for physical and biological indicators, psychological well-being, health behaviours, social connection factors and overall cognitive functions. Primary data analyses will follow the intention-to-treat principle. To examine the effects of intervention, multilevel mixed models will be performed. In case of any differences in baseline participant characteristics, they will be adjusted for as covariates.

A centralised ethics review process was conducted, and the study protocol was approved by the ethics committee of the Institutional Review Board of the Institute of Psychology, Chinese Academy of Sciences in April 2022. A signed written informed consent form will be obtained from all participants. On completion, the trial results will be disseminated through published manuscripts and presentations at scientific conferences.

ChiCTR2200062929.

Polygenic risk score (PRS) quantifies the cumulative effects of common genetic variants across the genome, including both coding and non-coding regions, to predict the risk of developing common diseases. In cardiovascular medicine, PRS enhances risk stratification beyond traditional clinical risk factors, offering a precision medicine approach to coronary artery disease (CAD) prevention. This study evaluates the predictive performance of a multi-ancestry PRS framework for cardiovascular risk assessment using the All of Us (AoU) short-read whole-genome sequencing dataset comprising over 225,000 participants.

We developed PRSs for lipid traits (LDL-C, HDL-C, triglycerides) and cardiometabolic conditions (type 2 diabetes, hypertension, atrial fibrillation) and constructed two metaPRSs: one integrating lipid and cardiometabolic PRSs (risk factor metaPRS) and another incorporating CAD PRSs in addition to these risk factors (risk factor + CAD metaPRS). Predictive performance was evaluated separately for each trait-specific PRS and for both metaPRSs to assess their effectiveness in CAD risk prediction across diverse ancestries. Model predictive performance, including calibration, was assessed separately for each ancestry group, ensuring that all metrics were ancestry-specific and that PRSs remain generalizable across diverse populations Results: PRSs for lipids and cardiometabolic conditions demonstrated strong predictive performance across ancestries. The risk factors metaPRS predicted CAD risk across multiple ancestries. The addition of a CAD-specific PRS to the risk factors metaPRS improved predictive performance, highlighting a genetic component in CAD etiopathology that is not fully captured by traditional risk factors, whether clinically measured or genetically inferred. Model calibration and validation across ancestries confirmed the broad applicability of PRS-based approaches in multi-ethnic populations.

PRS-based risk stratification provides a reliable, ancestry-inclusive framework for personalized cardiovascular disease prevention, enabling better targeted interventions such as pharmacological therapy and lifestyle modifications. By incorporating genetic information from both coding and non-coding regions, PRSs refine risk prediction across diverse populations, advancing the integration of genomics into precision medicine for common diseases.

Recent studies link pesticide exposures to cardiovascular disease risk factors. However, research on the combined effects of multiple pesticides on atherosclerotic cardiovascular disease (ASCVD) is limited, particularly in rural areas. Despite advances in toxicogenomics, the mechanisms underlying these effects remain unclear. This study aims to investigate the combined effects and mechanisms of pesticide exposures on ASCVD.

In the cross-sectional study section, 2291 participants were included. Variables were filtered using machine learning models, and associations between mixed exposure to multiple pesticides and ASCVD were explored using environmental mixed exposure models (weighted quartile sum (WQS) regression and quantile-based g-computation (QGC)). In the bioinformatics analysis section, the GEO, CTD, Malacards, and GeneCards databases were used to retrieve target genes for pesticide exposure and atherosclerotic diseases. Enrichment analysis was then performed to identify the biological pathways associated with these genes.

Three machine models screened 34 pesticides. Single pesticide exposures, such as atrazine, oxadiazon, p,p'-DDE, α-BHC, β-BHC, fenitrothion, malathion, fenitrothion, cypermethrin, cypermethrin, and cypermethrin might increase the 10-year ASCVD risk (all P < 0.05). Total mixed pesticide exposure was positively associated with 10-year ASCVD risk in both the QGC (3.223(2.196, 4.730)) and WQS models (4.642(3.070, 7.020)). Notably, there was a linear relationship between totalQGC (P_overal < 0.001; P_nonlinearity = 0.864) and high 10-year ASCVD risk. In toxicogenomic bioinformatics analysis, we identified 112 potential atherosclerosis target genes affected by pesticide exposure. Pathway enrichment analysis suggests pesticide-induced atherosclerosis is linked to pathways such as metabolic pathways, lipid metabolism, MAPK, AMPK, FoxO signaling, apoptosis, fluid shear stress, endocrine resistance, TNF, and PI3K-Akt. Key genes were identified based on maximal clique centrality, including AKT1, TP53, IL6, BCL2, TNF, JUN, PTGS2, CASP3, MAPK3, and CASP9.

Individual and combined exposure to pesticides increased the 10-year ASCVD risk, especially in patients with T2DM. Mixed levels of pesticide exposure were linearly and positively associated with high 10-year ASCVD risk. The mechanism of atherogenesis by mixed pesticide exposure may involve pathways such as lipid metabolism, MAPK, AMPK, FoxO signaling, apoptosis, fluid shear stress, endocrine resistance, TNF, and PI3K-Akt.

Although existing evidence suggests that arterial stiffness and obesity impact cardiovascular health, limited studies have been conducted to explore the association between brachial-ankle pulse wave velocity (baPWV), obesity-related indices, and the risk of atherosclerotic cardiovascular disease (ASCVD).

The study participants were among those who completed the baPWV measurement at the second follow-up examination (during 2018-2020) of the Rural Chinese Cohort Study. Logistic regression models were employed to calculate odds ratios (ORs) and 95 % confidence intervals (CIs) of the 10-year incident risk score of ASCVD associated with baPWV and obesity-related indices. Mediation analysis was applied to investigate the role of baPWV in the obesity-induced 10-year incident risk score of ASCVD. A total of 1589 individuals, including 573 men and 1016 women, were included in the study. In logistic regression analyses, the highest quartile levels of baPWV and obesity-related indices all significantly increased the 10-year incident risk score of ASCVD compared to their corresponding lowest quartiles. The ORs (95%CIs) of ASCVD 10-year incident risk score risk were 4.21(2.55-6.94) for baPWV, 4.43(2.69-7.29) for METS-VF, 7.20(4.09-12.66) for CVAI, 3.38(2.12-5.38) for CI, and 2.40(1.54-3.75) for ABSI. The indirect effect of baPWV accounted for 5.85 %, 7.92 %, 14.56 %, and 5.08 % of the total effects for METS-VF, CVAI, CI, and ABSI, respectively.

This study found that elevated levels of both baPWV and obesity-related indices were associated with a higher 10-year incident risk score of ASCVD. Additionally, baPWV partially mediated the obesity-related increase in 10-year incident risk score of ASCVD.

Diabetic macrovascular and microvascular complications often coexist and may share similar risk factors and pathological pathways. We aimed to investigate whether 10-year atherosclerotic cardiovascular disease (ASCVD) risk, which is commonly assessed in diabetes management, can predict incident diabetic nephropathy (DN) and retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM).

This prospective cohort study enrolled 2,891 patients with clinically diagnosed T2DM who were free of ASCVD, nephropathy, or retinopathy at baseline in the Guangzhou (2017-2022) and Shaoguan (2019-2021) Diabetic Eye Study in southern China. The 10-year ASCVD risk was calculated by the Prediction for ASCVD Risk in China (China-PAR) equations. Multivariable- adjusted Cox proportional hazard models were developed to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). The area under the receiver operating characteristic curve (AUC) was used to evaluate predictive capability.

During follow-up, a total of 171 cases of DN and 532 cases of DR were documented. Each 1% increment in 10-year ASCVD risk was associated with increased risk of DN (pooled HR, 1.122; 95% CI, 1.094 to 1.150) but not DR (pooled HR, 0.996; 95% CI, 0.979 to 1.013). The model demonstrated acceptable performance in predicting new-onset DN (pooled AUC, 0.670; 95% CI, 0.628 to 0.715). These results were consistent across cohorts and subgroups, with the association appearing to be more pronounced in women.

Ten-year ASCVD risk predicts incident DN but not DR in our study population with T2DM. Regular monitoring of ASCVD risk in routine diabetes practice may add to the ability to enhance population-based prevention for both macrovascular and microvascular diseases, particularly among women.

Whether the new standard of metabolic dysfunction-associated fatty liver disease (MAFLD) has more pronounced clinical and population screening diagnostic value than nonalcoholic fatty liver disease (NAFLD) is unclear. This study evaluated the utility of MAFLD and NAFLD for predicting major cardiovascular disease (CVD) risk.

A prospective cohort study approach was utilized to collect 19,399 study participants without CVD at baseline who completed follow-up from the Jinchang cohort platform during 2011-2017. According to clinical ultrasonic diagnosis results and disease diagnosis criteria, the baseline population was divided into MAFLD, NAFLD, Both-FLD and No-FLD groups. Based on the multifactorial Cox proportional risk model to analyze the relationship between three kinds of patients and CVD, the score prediction model of CVD was constructed with reference to the Framingham Risk Score (FRS) and the model was evaluated. Compared with No-FLD, the HRs and 95 % CIs for the risk of CVD development in patients with NAFLD, MAFLD, and Both-FLD were 1.54 (1.34-1.76), 1.57 (1.37-1.79), and 1.62 (1.41-1.87), in that order. The scoring model showed a range of 5.90%-84.59 % risk of CVD in the three groups. As the risk score increased, the risk of developing CVD gradually increased. Evaluation metrics of all three models in the training set and validation set showed that the models have good prediction efficacy.

In terms of CVD risk and prognosis, MAFLD had no advantage over NAFLD. However, Both-FLD was found to predict a higher risk of CVD and to have superior predictive efficacy.

Circulating metabolic profiles have shown promising potential in identifying high-risk populations for various diseases, while metabolic perturbation plays an important role in gastric cancer. In this study, we conducted a cross-sectional study with 1800 participants to identify plasma metabolite signatures associated with environmental risk factors of gastric cancer. Subsequently, we evaluated the association between these signatures and gastric cancer risk in a nested case-control study involving 326 gastric cancer cases and 326 matched cancer-free controls. We conducted mediation analyses to elucidate the potential impact of metabolites on the association between environmental factors and gastric cancer. In the cross-sectional study, we identified 46 metabolites associated with Helicobacter pylori (H. pylori) infection, 365 with alcohol drinking, and 154 with smoking status. In the nested case-control study, 60 plasma metabolites, comprising 30 lipids, 15 amino acids, 6 xenobiotics, 3 nucleotides, 2 cofactors and vitamins, 2 carbohydrate, 1 energy, and 1 peptide, were associated with gastric cancer risk. A one-standard deviation increment in the H. pylori infection-related metabolomic signature was associated with an increased risk of gastric cancer (OR = 1.66, 95% CI: 1.32-2.09, p = 1.62 × 10-5). Furthermore, the effect of H. pylori infection on gastric cancer was partially mediated by the metabolomic signature (23.28%, 95% CI: 0.09-0.56) or adenine (13.69%, 95% CI: 0.05-0.31). In conclusion, we have identified metabolites associated with environmental factors and demonstrated the association between the H. pylori infection signature and gastric cancer risk. The findings provide novel insights into characterizing high-risk population for gastric cancer.

The management of atherosclerotic cardiovascular disease (ASCVD) in the United States is currently based upon large epidemiological studies in primarily non-Hispanic White subjects. Although this strategy provides a uniform approach that is simpler to implement, it may result in inappropriately targeting certain Asian populations for treatment based on inaccurate ASCVD risk estimation. In this state-of-the-art review, we detail the similarities and differences in the prevalence of ASCVD and its risk factors among Chinese, Japanese, and Korean people living in the United States and in their native countries. We highlight the limitations of current risk calculators when applied to East Asian immigrants and summarize risk stratification approaches in China, Japan, and Korea. Our review underscores the need to disaggregate registry, cohort, and clinical trial data by East Asian subgroups, to actively engage these populations in research, and to initiate studies to better define ASCVD risk in East Asian people living in the United States.

It remains unclear whether the cardiovascular benefits of physical activity (PA) vary across populations with different predicted atherosclerotic cardiovascular disease (ASCVD) risks. This study aimed to determine the modification of predicted cardiovascular risk on the association between PA and ASCVD incidence.

A total of 94,734 participants without ASCVD in the Prediction for Atherosclerotic Cardiovascular Disease Risk in China (China-PAR) project were included, with a median follow-up of 6.0 years. PA volume (metabolic equivalent of task (MET)-h/day) and intensity (%, percentage of moderate-to-vigorous PA (MVPA)) were assessed by questionnaires. Based on the ASCVD 10-year and lifetime risk prediction scores, participants were classified into low-to-medium-risk and high-risk groups. Hazard ratios (HRs) and 95% confidence intervals (95%CIs) for ASCVD were calculated using Cox proportional hazards models.

During 679,438 person-years of follow-up, 3470 ASCVD events occurred. Higher PA volume was associated with lower ASCVD incidence, which was more pronounced among high-predicted-risk individuals than their low-to-medium-risk counterparts, with HRs (95%CIs) of 0.58 (0.50-0.67) and 0.62 (0.53-0.71) for the highest vs. lowest quartiles of PA volume, respectively. Additionally, analyses for PA intensity showed similar results. Compared with inactive individuals, there was a 32% (95%CI: 25%-38%) and 23% (95%CI: 13%-32%) risk reduction in high- and low-to-medium-risk groups, respectively, when over half of the PA volume was from MVPA. Furthermore, the additive interactions between PA and predicted risk indicated a further risk reduction by increasing PA, especially MVPA, in high-risk individuals.

Engaging in more PA, especially MVPA, reduced the risk of ASCVD incidence, with greater benefits among high-risk individuals. These findings emphasize the imperative for personalized PA recommendations tailored to distinct risk populations-in particular, reinforcing PA guidance for high-risk individuals.

Antiretroviral therapy (ART) is transforming human immunodeficiency virus (HIV) infection into a chronic condition, leading to an altered disease spectrum in patients. The risk of cardiovascular disease (CVD) in HIV-infected individuals are twice that of the general population.

This study demonstrates elevated cardiovascular risk among the HIV population. The findings reveal that traditional CVD risk factors are prevalent among people living with HIV but remain inadequately addressed in clinical practice.

These findings underscore both the necessity and urgency of implementing systematic CVD risk screening and intervention programs for HIV population. Furthermore, the study emphasizes the critical need to develop CVD screening tools specifically calibrated for the HIV population in China.

To improve upon the estimation of 10-year cardiovascular disease (CVD) event risk for individuals without prior CVD or diabetes mellitus in the Asia-Pacific region by systematic recalibration of the SCORE2 risk algorithm.

The sex-specific and competing risk-adjusted SCORE2 algorithms were systematically recalibrated to reflect CVD incidence observed in four Asia-Pacific risk regions, defined according to country-level World Health Organization age- and sex-standardized CVD mortality rates. Using the same approach as applied for the original SCORE2 models, recalibration to each risk region was completed using expected CVD incidence and risk factor distributions from each region.

Risk region-specific CVD incidence was estimated using CVD mortality and incidence data on 8 405 574 individuals (556 421 CVD events). For external validation, data from 9 560 266 individuals without previous CVD or diabetes were analysed in 13 prospective studies from 12 countries (350 550 incident CVD events). The pooled C-index of the SCORE2 Asia-Pacific algorithms in the external validation datasets was .710 [95% confidence interval (CI) .677-.744]. Cohort-specific C-indices ranged from .605 (95% CI .597-.613) to .840 (95% CI .771-.909). Estimated CVD risk varied several-fold across Asia-Pacific risk regions. For example, the estimated 10-year CVD risk for a 50-year-old non-smoker, with a systolic blood pressure of 140 mmHg, total cholesterol of 5.5 mmol/L, and high-density lipoprotein cholesterol of 1.3 mmol/L, ranged from 7% for men in low-risk countries to 14% for men in very-high-risk countries, and from 3% for women in low-risk countries to 13% for women in very-high-risk countries.

The SCORE2 Asia-Pacific algorithms have been calibrated to estimate 10-year risk of CVD for apparently healthy people in Asia and Oceania, thereby enhancing the identification of individuals at higher risk of developing CVD across the Asia-Pacific region.

It is well established that increased lipoprotein(a) [Lp(a)] is a significant risk factor for coronary artery disease (CAD). Plasma Lp(a) levels are genetically determined and vary widely between different races, regions and individuals. However, most studies on Lp(a) associated genetic variants have focused on the Caucasian population currently. Our study aimed to test the associations among LPA genetic variants, Lp(a) concentrations, and CAD in a Han Chinese cohort.

A total of 3779 patients undergoing coronary angiography were recruited from Tongji Hospital. LPA Kringle IV type 2 (KIV-2) copies were detected using TaqMan probe real-time quantitative polymerase chain reaction (qPCR) analysis and fifteen single nucleotide polymorphisms (SNPs) within the LPA gene were detected using TaqMan probe genotyping analysis. LPA genetic risk score (GRS) was computed based on seven SNPs associated with Lp(a). Associations of LPA genetic variants with Lp(a) and CAD were evaluated using linear regression analyses and Logistic regression analyses, respectively.

Compared with the first quartile of Lp(a), the fourth quartile exhibited a significant association with CAD [odds ratio (OR): 2.08, 95% confidence interval (CI): 1.67-2.59, p < 0.001], multivessel CAD [OR: 2.54, 95% CI: 2.06-3.12, p < 0.001], and high Gensini scores [OR: 2.17, 95% CI: 1.77-2.66, p < 0.001] after multivariable adjustment for cardiovascular risk factors. Both LPA GRS and KIV-2 quartiles were associated with Lp(a) concentrations (both p for trend < 0.001). However, after false discovery rate (FDR) correction, there were no significant associations of LPA genetic variants with CAD, multivessel CAD or high Gensini scores.

Our findings indicate LPA genetic variants can affect Lp(a) levels, but do not exceed Lp(a) molar concentrations to predict CAD incidence and severity usefully, highlighting the importance of Lp(a) detection and management.

Cardiovascular disease (CVD) remains a significant public health challenge in China. This study aimed to project the burden of CVD from 2020 to 2030 using a nationwide cohort and to simulate the potential impact of various control measures on morbidity and mortality.

An agent-based model was employed to simulate annual CVD incidence and mortality from 2021 to 2030. The effects of different prevention and treatment interventions, modelled on international strategies, were also explored.

The study included 106 259 participants. The annual CVD incidence rate is projected to increase from 0.74% in 2021 to 0.97% by 2030, with age-standardised and sex-standardised rates rising from 0.71% to 0.96%. CVD mortality is expected to rise from 0.39% in 2021 to 0.46% in 2024, after which it will stabilise at 0.44% by 2030. Community-based interventions and improved access to inpatient care are predicted to reduce the projected burden of CVD significantly.

The incidence of CVD in China is projected to increase steadily over the next decade, while mortality will plateau after 2024. Comprehensive interventions, including community-based screenings and enhanced healthcare access, could significantly mitigate the CVD burden.

NCT02536456.

With the global aging of the population, menopausal women face higher cardiovascular disease (CVD) risks, with carotid atherosclerosis as the primary pathological basis. However, no effective tools exist for assessing carotid atherosclerosis risk, and this study fills the gap in predictive tools in this field. Using data from 4,446 menopausal women in Shenzhen, we developed and validated a Nomogram model for carotid atherosclerosis risk. The sample was divided into training (2,178), internal validation (934), and external validation (1,334) sets. Variables were selected using logistic regression and LASSO, including age, systolic blood pressure (SBP), lipoprotein a (LPa), non-HDL cholesterol (Non-HDL-C), TC/HDL-C ratio, glycosylated hemoglobin (HbA1c), and blood glucose (GLU). Random Forest validation confirmed the model's robustness. The Nomogram's C-index was 0.706 (training), 0.664 (internal), and 0.668 (external), with Random Forest results of 0.721, 0.662, and 0.661, respectively. Calibration and decision curve analyses demonstrated the model's accuracy and clinical utility. Additionally, a slight negative correlation between age and GLU (OR = 0.689, P = 0.068) suggested reduced glycemic risk with age. This model provides a scientific basis for early risk assessment and personalized interventions for menopausal women, guiding future research on related biological mechanisms.

Atherosclerosis, with its complex pathogenesis, is a leading underlying cause of many cardiovascular diseases, which are increasingly prevalent in the population. Sphingolipids play an important role in the development of atherosclerosis. Key metabolites and enzymes in sphingolipid metabolism influence the pathogenesis of atherosclerosis in a variety of ways, including inflammatory responses and oxidative stress. Thus, an investigation of sphingolipid metabolism-related metabolites and key enzymes may provide novel insights and treatment targets for atherosclerosis. This review discusses various mechanisms and research progress on the relationship between various sphingolipid metabolites, related enzymes, and atherosclerosis. Finally, we look into the future research direction of phytosphingolipids.

Cardiovascular complications are major concerns for Chinese patients with type 2 diabetes. Accurately predicting these risks remains challenging due to limitations in traditional risk models. We aimed to develop a dynamic prediction model using machine learning and longitudinal trajectories of cardiovascular risk factors to improve prediction accuracy.

We included 16,378 patients from the Kailuan cohort, splitting them into training and testing datasets. Using baseline characteristics and changes over a four-year observation period, we developed the ML-CVD-C (Machine Learning Cardiovascular Disease in Chinese) score to predict 10-year cardiovascular risk, including cardiovascular death, nonfatal myocardial infarction, and stroke. We compared the discrimination and calibration of ML-CVD-C with models using only baseline variables (ML-CVD-C [base]), China-PAR (Prediction for ASCVD Risk in China), and PREVENT (Predict Risk of cardiovascular disease EVENTs). Risk stratification improvements were assessed through net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Transition analysis examined the changes in risk stratification over time.

The ML-CVD-C score achieved a C-index of 0.80 (95% CI: 0.78-0.82) in the testing cohort, significantly outperforming the ML-CVD-C (base) score, China-PAR, and PREVENT, which had C-index values of 0.62-0.65. ML-CVD-C also provided more accurate cardiovascular risk estimates, though all models tended to overestimate the prevalence of high-risk cases. Stratification by the ML-CVD-C score showed substantial improvement, with NRI gains of 57.7%, 44.1%, and 47.3%, and IDI gains of 10.1%, 7.9%, and 8.4% compared to the other three scores. Both the trajectory and machine learning algorithm contributed significantly to the enhancement of model performance. Transition analysis revealed that participants who remained in the same risk category or were reclassified to a lower category exhibited 22% and 86% reductions in cardiovascular risk compared to those reclassified to a higher risk category during the observation period.

The ML-CVD-C model, incorporating dynamic cardiovascular risk trajectories and a machine learning algorithm, significantly improves risk prediction accuracy for Chinese patients with diabetes. This model may serve as a valuable tool for more personalized cardiovascular risk management in type 2 diabetes.