The relationship between self-compassion, coping style, sleep quality, and depression among college students.

Background: The prevalence of sleep quality problems and depression in the college student population has attracted widespread attention. However, the factors influencing this are still unclear. The objective of this study was to investigate the associations between self-compassion (S-C), sleep quality (SQ), and depression (DEP) among college students and examine the mediating effects of coping style (CS) between the variables. Methods: A total of 1,038 Chinese university students were recruited for the study. The study used the Self-Compassion Scale (SCS), Simplified Coping Style Questionnaire (SCSQ), Depression Anxiety Stress Scale 21 (DASS-21), and Pittsburgh Sleep Quality Index (PSQI) to conduct the survey. Results: The self-compassion and coping style showed significant negative correlations with sleep quality and depression. Coping style partially mediated the relationship between self-compassion and sleep quality. The coping style also fully mediated the relationship between self-compassion and depression. Conclusion: This study reveals the associations between self-compassion and sleep quality and depression, and the mediating role of coping style among college students. This study provides valuable insights for improving sleep quality and alleviating depression problems among college students. It emphasizes the importance of self-compassion and positive coping style.

A combined experimental and computational study of ligand-controlled Chan-Lam coupling of sulfenamides.

The unique features of the sulfenamides' S(II)-N bond lead to interesting stereochemical properties and significant industrial functions. Here we present a chemoselective Chan-Lam coupling of sulfenamides to prepare N-arylated sulfenamides. A tridentate pybox ligand governs the chemoselectivity favoring C-N bond formation, and overrides the competitive C-S bond formation by preventing the S,N-bis-chelation of sulfenamides to copper center. The Cu(II)-derived resting state of catalyst is captured by UV-Vis spectra and EPR technique, and the key intermediate is confirmed by the EPR isotope response using 15N-labeled sulfenamide. A computational mechanistic study reveals that N-arylation is both kinetically and thermodynamically favorable, with deprotonation of the sulfenamide nitrogen atom occurring prior to reductive elimination. The origin of ligand-controlled chemoselectivity is explored, with the interaction between the pybox ligand and the sulfenamide substrate controlling the energy of the S-arylation and the corresponding product distribution, in agreement with the EPR studies and kinetic results.

Kinetic Resolution of P-Chiral Phosphindole Oxides through Rhodium-Catalyzed Asymmetric Arylation.

Highly efficient kinetic resolution of P-chiral phosphindole oxides via rhodium-catalyzed asymmetric arylation under mild conditions is described. Selectivity factors of up to 569 were achieved by employing chiral diene* as a ligand. The transformation of the enantiopure benzophosphole derivative into a useful P-chiral bisphosphine ligand is also demonstrated.

Metabolomics signature of blood pressure salt sensitivity and its link to cardiovascular disease: A dietary salt-intervention trial.

Individuals with a high degree of salt sensitivity (SS) have a greater risk of cardiovascular disease (CVD), but whether SS fosters CVD by influencing metabolomics homeostasis remains unclear. This study aimed to reveal the role of the SS-related metabolomics signature in the development of CVDs, based on the MetaSalt study, which was a dietary salt-intervention trial conducted at four centers in China in 2019. A total of 528 participants were recruited and underwent 3 days of baseline observations, a 10-day low-salt intervention, and a 10-day high-salt intervention. Plasma untargeted metabolomics, lipidomics, and BP measurements were scheduled at each stage. Participants were grouped into extreme SS, moderate SS, and salt-resistant (SR) individuals according to their BP responses to salt. Linear mixed models were used to identify SS-related metabolites and determine the relationship between the SS-related metabolomics signature and arterial stiffness. Mendelian randomization (MR) analyses were applied to establish the causal pathways among the SS-related metabolites, BP, and CVDs. Among the 713 metabolites, 467 were significantly changed after the high-salt intervention. Among them, the changes in 30 metabolites from the low-salt to the high-salt intervention differed among the SS groups. Of the remaining nonsalt-related metabolites, the baseline levels of 11 metabolites were related to SS. These 41 metabolites explained 23% of the variance in SS. Moreover, SS and its metabolomics signature were positively correlated with arterial stiffness. MR analyses demonstrated that the SS-related metabolites may affect CVD risk by altering BP, indicating that the increase in BP was the consequence of the changes in SS-related metabolites rather than the cause. Our study revealed that the metabolomics signature of SS individuals differs from that of SR individuals and that the changes in SS-related metabolites may increase arterial stiffness and foster CVDs. This study provides insight into understanding the biology and targets of SS and its role in CVDs.

Dietary intake changes the associations between long-term exposure to fine particulate matter and the surrogate indicators of insulin resistance.

The relationship of fine particulate matter (PM2.5) exposure and insulin resistance remains inclusive. Our study aimed to investigate this association in the project of Prediction for Atherosclerotic Cardiovascular Disease Risk in China (China-PAR). Specifically, we examined the associations between long-term PM2.5 exposure and three surrogate indicators of insulin resistance: the triglyceride-glucose index (TyG), TyG with waist circumference (TyG-WC) and metabolic score for insulin resistance (METS-IR). Additionally, we explored potential effect modification of dietary intake and components. Generalized estimating equations were used to evaluate the associations between PM2.5 and the indicators with an unbalanced repeated measurement design. Our analysis incorporated a total of 162,060 observations from 99,329 participants. Each 10 µg/m3 increment of PM2.5 was associated with an increase of 0.22 % [95 % confidence interval (CI): 0.20 %, 0.25 %], 1.60 % (95 % CI: 1.53 %, 1.67 %), and 2.05 % (95 % CI: 1.96 %, 2.14 %) in TyG, TyG-WC, and METS-IR, respectively. These associations were attenuated among participants with a healthy diet, particularly those with sufficient intake of fruit and vegetable, fish or tea (pinteraction < 0.0028). For instance, among participants with a healthy diet, TyG increased by 0.11 % (95 % CI: 0.08 %, 0.15 %) per 10 µg/m3 PM2.5 increment, significantly lower than the association observed in those with an unhealthy diet. The findings of this study emphasize the potential of a healthy diet to mitigate these associations, highlighting the urgency for improving air quality and implementing dietary interventions among susceptible populations in China.

Rhodium-Catalyzed Asymmetric Addition to 4- or 5-Carbonyl-cycloenones through Dynamic Kinetic Resolution: Enantioselective Synthesis of (-)-Cannabidiol.

The reaction of 4/5-carbonyl-cycloalkenone 1 or its achiral isomer 1' with organoboronic acid 2 in the presence of a chiral diene (S,S)-Fc-tfb-rhodium catalyst gave disubstituted trans-cycloalkanone 3 with high diastereo- and enantioselectivity. This highly efficient dynamic kinetic resolution is achieved by fast racemization of 1 through the formation of a dienolate followed by kinetic resolution with the chiral catalyst. The utility is demonstrated by the synthesis of key intermediates en route to (-)-cannabidiol.

Somatic and Germline Variants and Coronary Heart Disease in a Chinese Population.

Importance: The genetic basis of coronary heart disease (CHD) has expanded from a germline to somatic genome, including clonal hematopoiesis of indeterminate potential (CHIP). How CHIP confers CHD risk in East Asian individuals, especially those with small clones (variant allele fraction [VAF] 0.5%-2%) and different genetic backgrounds, was completely unknown. Objective: To investigate the CHIP profile in a general Chinese cohort by deep sequencing and further explore the association between CHIP and incident CHD considering germline predisposition. Design, Setting, and Participants: This cohort study used data from 3 prospective cohorts in the project Prediction for Atherosclerotic Cardiovascular Disease Risk in China. Participants without cardiovascular disease or cancer at baseline were enrolled in 2001 and 2008 and had a median follow-up of 12.17 years extending into 2021. Exposures: CHIP mutations were detected by targeted sequencing (mean depth, 916×). A predefined CHD polygenic risk score (PRS) comprising 531 variants was used to evaluate germline predisposition. Main Outcomes and Measures: The main outcome was first incident CHD. Results: Among 6181 participants, the median (IQR) age was 53.83 years (45.35-62.39 years); 3082 participants (49.9%) were female, and 3099 (50.1%) were male. A total of 1100 individuals (17.80%) harbored 1372 CHIP mutations at baseline. CHIP was independently associated with incident CHD (hazard ratio [HR], 1.42; 95% CI, 1.18-1.72; P = 2.82 × 10-4) and presented a risk gradient with increasing VAF (P = 3.98 × 10-3 for trend). Notably, individuals with small clones, nearly half of CHIP carriers, also demonstrated a higher CHD risk compared with non-CHIP carriers (HR, 1.33; 95% CI, 1.02-1.74; P = .03) and were 4 years younger than those with VAF of 2% or greater (median age, 58.52 vs 62.70 years). Heightened CHD risk was not observed among CHIP carriers with low PRS (HR, 1.02; 95% CI, 0.64-1.64; P = .92), while high PRS and CHIP jointly contributed a 2.23-fold increase in risk (95% CI, 1.51-3.29; P = 6.29 × 10-5) compared with non-CHIP carriers with low PRS. Interestingly, the diversity in CHIP-related CHD risk within each PRS group was substantially diminished when removing variants in the inflammatory pathway from the PRS. Conclusions: This study revealed that elevated CHD risk attributed to CHIP was nonnegligible even for small clones. Inflammation genes involved in CHD could aggravate or abrogate CHIP-related CHD risk.

Regio- and Stereoselective Iodoamination of Ferrocene-Containing Allenylphosphonates: Synthesis of Multifunctional Tetrasubstituted Allylic Amines and Allylic Azides.

A general and practical methodology for the regio- and stereoselective synthesis of multifunctional tetrasubstituted allylic amines and azides based on iodoamination of ferrocene-containing allenylphosphonates with anilines and sodium azide is described. A tetrasubstituted olefin moiety, as well as an iodine atom, a phosphonate, and a ferrocene group, are installed to the allylic amine motif simultaneously in moderate to good yields.

Genetic Predisposition, Sedentary Behavior, and Incident Coronary Artery Disease: A Prospective Chinese Cohort Study.

PURPOSE: Whether the association of sedentary behaviors with coronary artery disease (CAD) can be influenced by genetic susceptibility remains unclear. We aimed to investigate the joint and interplay effects between genetic risk and sedentary time (ST) and to further explore the extent to which the risk for CAD can be counteracted by reducing ST in different genetic groups. METHODS: This prospective cohort study included 39,164 Chinese adults without CAD history. Genetic susceptibility was quantified by a predefined polygenic risk score (PRS) with 540 genetic variants, and daily ST was assessed by questionnaire. We analyzed the modification effect of genetic risk on the association of ST with CAD using the Cox proportional hazards models. RESULTS: During a median follow-up of 11.60 yr, 1156 CAD events were documented. Higher ST and PRS were separately related to elevated CAD risk. Significant additive interaction was also observed (relative excess risk due to interaction: 0.77; 95% confidence interval [CI] = 0.27-1.28). Compared with participants with low genetic risk and low ST (<6 h·d -1 ), those with high genetic risk and high ST (≥10 h·d -1 ) had the highest CAD risk, with the hazard ratio (HR) and 95% CI of 4.22 (2.65-6.71). When stratified by genetic risks, participants with high ST had gradient increment of CAD risks across low, intermediate, and high genetic risk groups, with HR (95% CI) values of 1.21 (0.61-2.40), 1.57 (1.14-2.16), and 2.15 (1.40-3.31), respectively. For the absolute risk reduction, individuals with high genetic risk achieved the greatest benefit from low ST ( Ptrend = 0.024). CONCLUSIONS: Genetic susceptibility may synergistically interact with ST to increase CAD risk. Reducing ST could attenuate the CAD risk, especially among individuals with high genetic risk.

Fine Particulate Matter Exposure, Genetic Susceptibility, and the Risk of Incident Stroke: A Prospective Cohort Study.

BACKGROUND: Both genetic factors and environmental air pollution contribute to the risk of stroke. However, it is unknown whether the association between air pollution and stroke risk is influenced by the genetic susceptibilities of stroke and its risk factors. METHODS: This prospective cohort study included 40 827 Chinese adults without stroke history. Satellite-based monthly fine particulate matter (PM2.5) estimation at 1-km resolution was used for exposure assessment. Based on 534 identified genetic variants from genome-wide association studies in East Asians, we constructed 6 polygenic risk scores for stroke and its risk factors, including atrial fibrillation, blood pressure, type 2 diabetes, body mass index, and triglyceride. The Cox proportional hazards model was applied to evaluate the hazard ratios and 95% CIs for the associations of PM2.5 and polygenic risk score with incident stroke and the potential effect modifications. RESULTS: Over a median follow-up of 12.06 years, 3147 incident stroke cases were documented. Compared with the lowest quartile of PM2.5 exposure, the hazard ratio (95% CI) for stroke in the highest quartile group was 2.72 (2.42-3.06). Among individuals at high genetic risk, the relative risk of stroke was 57% (1.57; 1.40-1.76) higher than those at low genetic risk. Although no statistically significant interaction was found, participants with both the highest PM2.5 and high genetic risk showed the highest risk of stroke, with ≈4× that of the lowest PM2.5 and low genetic risk group (hazard ratio, 3.55 [95% CI, 2.84-4.44]). Similar upward gradients were observed in the risk of stroke when assessing the joint effects of PM2.5 and genetic risks of blood pressure, type 2 diabetes, body mass index, atrial fibrillation, and triglyceride. CONCLUSIONS: Long-term exposure to PM2.5 was associated with a higher risk of incident stroke across different genetic susceptibilities. Our findings highlighted the great importance of comprehensive assessment of air pollution and genetic risk in the prevention of stroke.

Lifestyle improvement and the reduced risk of cardiovascular disease: the China-PAR project.

BACKGROUND: The benefits of healthy lifestyles are well recognized. However, the extent to which improving unhealthy lifestyles reduces cardiovascular disease (CVD) risk needs to be discussed. We evaluated the impact of lifestyle improvement on CVD incidence using data from the China-PAR project (Prediction for Atherosclerotic Cardiovascular Disease Risk in China). METHODS: A total of 12,588 participants free of CVD were followed up for three visits after the baseline examination. Changes in four lifestyle factors (LFs) (smoking, diet, physical activity, and alcohol consumption) were assessed through questionnaires from the baseline to the first follow-up visit. Cox proportional hazard models were used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs). The risk advancement periods (RAPs: the age difference between exposed and unexposed participants reaching the same incident CVD risk) and population-attributable risk percentage (PAR%) were also calculated. RESULTS: A total of 909 incident CVD cases occurred over a median follow-up of 11.14 years. Compared with maintaining 0-1 healthy LFs, maintaining 3-4 healthy LFs was associated with a 40% risk reduction of incident CVD (HR = 0.60, 95% CI: 0.45-0.79) and delayed CVD risk by 6.31 years (RAP: -6.31 [-9.92, -2.70] years). The PAR% of maintaining 3-4 unhealthy LFs was 22.0% compared to maintaining 0-1 unhealthy LFs. Besides, compared with maintaining two healthy LFs, improving healthy LFs from 2 to 3-4 was associated with a 23% lower risk of CVD (HR = 0.77, 95% CI: 0.60-0.98). CONCLUSIONS: Long-term sustenance of healthy lifestyles or improving unhealthy lifestyles can reduce and delay CVD risk.

Fruit and vegetable intake and the risk of arterial hypertension in China: A prospective cohort study.

Background: Population-based epidemiological evidence regarding the association between fruit and vegetable intake and the incidence of hypertension is inconsistent. This prospective cohort study aimed to investigate the association between fruit and vegetable intake and the risk of new-onset hypertension. Methods: Based on the project of Prediction for Atherosclerotic Cardiovascular Disease Risk in China (China-PAR), 58,981 Chinese adults without hypertension at baseline were included. Information on fruit and vegetable intake was collected using a food-frequency questionnaire. Cox proportional hazards models were performed to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of incident hypertension. Results: During 640,795 person-years of follow-up, 21,008 new cases of hypertension were recorded. Compared with participants in the lowest quintile (Q1) of total fruit and vegetable (TFV) intake, the HRs (95% CIs) of incident hypertension were 0.90 (0.86-0.95), 0.85 (0.81-0.90), 0.82 (0.78-0.86), and 0.83 (0.78-0.88) for the Q2 to Q5 group (p trend < 0.001), respectively. In further analyses categorizing participants according to the recommended intake level (500 g/day), we found that increasing the intake of TFV, even though it was still insufficient for the recommendation, also had a protective effect against the incident hypertension. When considering the intake of fruit or vegetable separately, we found similar trends as the TFV intake. Conclusion: These results suggest that a higher intake of fruit and vegetable is beneficial for preventing hypertension in Chinese adults.

Egg consumption and risk of coronary artery disease, potential amplification by high genetic susceptibility: a prospective cohort study.

BACKGROUND: Remarkable heterogeneity has been observed among population-based studies on egg consumption and risk of coronary artery disease (CAD). Whether genetic susceptibility serves as a potential explanation for this inconsistency remains unknown. OBJECTIVES: We performed a prospective cohort study to investigate the association of egg consumption with incident CAD at different genetic susceptibilities. METHODS: We included 34,111 participants without CAD at baseline from the project of Prediction for Atherosclerotic Cardiovascular Disease Risk in China. Egg consumption was assessed with food frequency questionnaires. Genetic susceptibility was quantified by a predefined polygenic risk score (PRS) with 540 genetic variants. The hazard ratio (HR) and 95% confidence interval (95% CI) of incident CAD associated with egg consumption and PRS were estimated using the Cox proportional hazards models. RESULTS: Over a median 11.7 y of follow-up, 1,128 incident cases of CAD were recorded. Both higher egg consumption and increased PRS were related to higher risk of CAD. When stratified by genetic risk, each increment of 3 eggs/wk was associated with a 5% higher risk of CAD for participants at low to intermediate genetic risk (HR: 1.05; 95% CI: 1.01, 1.09), whereas risk increased to HR 1.10 (95% CI: 1.05, 1.16) for those at high genetic risk; a significant synergistic interaction was also indicated at both multiplicative (Pinteraction = 0.007) and additive (relative excess risk: 0.73; 95% CI: 0.24, 1.22) scales. When the joint effect was examined, in comparison with those at low to intermediate genetic risk and consuming <1 egg/wk, the HR (95% CI) was 2.95 (2.41, 3.62) for participants with high genetic risk and consumption of ≥10 eggs/wk, and the corresponding standardized 10-y CAD rates increased from 1.37% to 4.24%. CONCLUSIONS: Genetic predisposition may synergistically interact with egg consumption in relation to increased CAD risk. PRS-stratified recommendations on egg consumption may help formulate personalized nutrition policies.

Shear Strength Behaviors of Aeolian Sand Solidified by Microbially Induced Calcite Precipitation and Basalt Fiber Reinforcement.

Aeolian sand flow is identified as the main factor in the formation of sandstorms. However, conventional sand fixation methods cannot meet the current development requirements of environmental protection. In this paper, the method using Microbially Induced Calcite Precipitation (MICP) combined with basalt fiber reinforcement (BFR) was adopted to solidify the aeolian sand. Consolidated undrained triaxial shear tests were carried out to analyze the influence of fiber content, fiber length, confining pressure, and other factors on stress-strain characteristics, peak strength, brittleness index, and shear strength of aeolian sand. A shear strength model of aeolian sand solidification using MICP-BFR and considering the effect of fiber length and fiber content is established according to the test results. The results show that the peak strength of aeolian sand solidified by MICP-BFR is remarkably higher than that of aeolian sand solidified by MICP alone, and the peak strength rises with the increasing fiber length, fiber content, and confining pressure. The application of fiber can effectively reduce the brittleness index of aeolian sand solidified by MICP and improve the sample ductility. As fiber content and fiber length increase, the cohesion of solidified aeolian sand increases while the internal friction angle changes relatively little. In the limited range set by the test, the fiber length of 12 mm and the fiber content of 1.0% constitute the optimum reinforcement condition. The test results coincide with the model prediction results, indicating that the new model is fitting for predicting the shear strength of aeolian sand solidified by MICP-BFR. The research results provide an important reference value for guiding the practice of wind prevention and sand fixation in desert areas.

Construction of Conjugated 1,3-Enynes via Pd-Catalyzed Cascade Alkynylation of Aryl Phenol-Tethered Alkynes with Alkynyl Bromides.

An efficient Pd-catalyzed cascade alkynylation of aryl phenol-tethered alkynes with alkynyl bromides is described. This protocol could provide various conjugated 1,3-enynes possessing a polysubstituted spirocyclohexadienone, as well as an all-carbon tetrasubstituted alkene moiety. The products could also undergo ring-expansion and cyclization transformations under different conditions to convert to diverse fused cyclic scaffolds.

Effect of Air Pollution on Heart Failure: Systematic Review and Meta-Analysis.

BACKGROUND: Heart failure (HF) poses a significant global disease burden. The current evidence on the impact of air pollution on HF remains inconsistent. OBJECTIVES: We aimed to conduct a systematic review of the literature and meta-analysis to provide a more comprehensive and multiperspective assessment of the associations between short- and long-term air pollution exposure and HF from epidemiological evidences. METHODS: Three databases were searched up to 31 August 2022 for studies investigating the association between air pollutants (PM2.5, PM10, NO2, SO2, CO, O3) and HF hospitalization, incidence, or mortality. A random effects model was used to derive the risk estimations. Subgroup analysis was conducted by geographical location, age of participants, outcome, study design, covered area, the methods of exposure assessment, and the length of exposure window. Sensitivity analysis and adjustment for publication bias were performed to test the robustness of the results. RESULTS: Of 100 studies covering 20 countries worldwide, 81 were for short-term and 19 were for long-term exposure. Almost all air pollutants were adversely associated with the risk of HF in both short- and long-term exposure studies. For short-term exposures, we found the risk of HF increased by 1.8% [relative risk (RR)=1.018, 95% confidence interval (CI): 1.011, 1.025] and 1.6% (RR=1.016, 95% CI: 1.011, 1.020) per 10-µg/m3 increment of PM2.5 and PM10, respectively. HF was also significantly associated with NO2, SO2, and CO, but not O3. Positive associations were stronger when exposure was considered over the previous 2 d (lag 0-1) rather than on the day of exposure only (lag 0). For long-term exposures, there were significant associations between several air pollutants and HF with RR (95% CI) of 1.748 (1.112, 2.747) per 10-µg/m3 increment in PM2.5, 1.212 (1.010, 1.454) per 10-µg/m3 increment in PM10, and 1.204 (1.069, 1.356) per 10-ppb increment in NO2, respectively. The adverse associations of most pollutants with HF were greater in low- and middle-income countries than in high-income countries. Sensitivity analysis demonstrated the robustness of our results. DISCUSSION: Available evidence highlighted adverse associations between air pollution and HF regardless of short- and long-term exposure. Air pollution is still a prevalent public health issue globally and sustained policies and actions are called for to reduce the burden of HF. https://doi.org/10.1289/EHP11506.

Association of Long-Term Exposure to Ambient Fine Particulate Matter with Atherosclerotic Cardiovascular Disease Incidence Varies across Populations with Different Predicted Risks: The China-PAR Project.

Previous studies have established a significant link between ambient fine particulate matter (PM2.5) exposure and atherosclerotic cardiovascular disease (ASCVD) incidence, but whether this association varies across populations with different predicted ASCVD risks was uncertain previously. We included 109,374 Chinese adults without ASCVD at baseline from the Prediction for Atherosclerotic Cardiovascular Disease Risk in China (China-PAR) project. We obtained PM2.5 data of participants' residential address from 2000 to 2015 using a satellite-based spatiotemporal model. Participants were classified into low-to-medium and high-risk groups according to the ASCVD 10-year and lifetime risk prediction scores. Hazard ratios (HRs) and 95% confidence intervals (CIs) for PM2.5 exposure-related incident ASCVD, as well as the multiplication and additive interaction, were calculated using stratified Cox proportional hazard models. The additive interaction between risk stratification and PM2.5 exposure was estimated by the synergy index (SI), the attributable proportion due to the interaction (API), and the relative excess risk due to interaction (RERI). Over the follow-up of 833,067 person-years, a total of 4230 incident ASCVD cases were identified. Each 10 µg/m3 increment of PM2.5 concentration was associated with 18% (HR: 1.18; 95% CI: 1.14-1.23) increased risk of ASCVD in the total population, and the association was more pronounced among individuals having a high predicted ASCVD risk than those having a low-to-medium risk, with the HR (95% CI) of 1.24 (1.19-1.30) and 1.11 (1.02-1.20) per 10 µg/m3 increment in PM2.5 concentration, respectively. The RERI, API, and SI were 1.22 (95% CI: 0.62-1.81), 0.22 (95% CI: 0.12-0.32), and 1.37 (95% CI: 1.16-1.63), respectively. Our findings demonstrate a significant synergistic effect on ASCVD between ASCVD risk stratification and PM2.5 exposure and highlight the potential health benefits of reducing PM2.5 exposure in Chinese, especially among those with high ASCVD risk.

Prevalence of familial hypercholesterolemia and its association with coronary artery disease: A Chinese cohort study.

Background: Familial hypercholesterolemia (FH) is underrecognized, and its association with coronary artery disease (CAD) remains limited, especially in China. We aimed to investigate the prevalence of FH and its relationship with CAD in a large Chinese cohort. Methods: FH was defined using the Make Early Diagnosis to Prevent Early Death (MEDPED) criteria. The crude and age-sex standardized prevalence of FH were calculated based on surveys of the Prediction for Atherosclerotic Cardiovascular Disease Risk in China (China-PAR) project during 2007-2008. The associations of FH with incident CAD and its major subtypes were estimated with the cohort-stratified multivariate Cox proportional hazard models based on the data from the baseline to the last follow-up (2018-2020). Results: Among 98,885 included participants, 190 participants were defined as FH. Crude and age-sex standardized prevalence and 95% confidence interval (CI) of FH were 0.19% (0.17%-0.22%) and 0.13% (0.10%-0.16%), respectively. The prevalence varied across age groups and peaked in the group of 60-<70 years (0.28%), and the peak prevalence (0.18%) in males was earlier, yet lower than the peak crude prevalence in females (0.41%). During a mean follow-up of 10.7 years, 2493 cases of incident CAD were identified. After multivariate adjustment, FH patients had a 2.03-fold greater risk of developing CAD compared to non-FH participants. Conclusions: The prevalence of FH was estimated to be 0.19% in the participants, and it was associated with an elevated risk of incident CAD. Our study suggests that early screening of FH has certain public health significance for the prevention of CAD.

Efficacy and safety of low levels of low-density lipoprotein cholesterol: trans-ancestry linear and non-linear Mendelian randomization analyses.

AIMS: LDL cholesterol (LDL-C) is a well-established risk factor for coronary artery disease (CAD). However, the optimal LDL-C level with regard to efficacy and safety remains unclear. We aimed to investigate the causal relationships between LDL-C and efficacy and safety outcomes. METHODS AND RESULTS: We analyzed 353 232 British from the UK Biobank and 41 271 Chinese from the China-PAR project. Linear and non-linear Mendelian randomization (MR) analyses were performed to evaluate the causal relation between genetically proxied LDL-C and CAD, all-cause mortality, and safety outcomes (including haemorrhagic stroke, diabetes mellitus, overall cancer, non-cardiovascular death, and dementia). No significant non-linear associations were observed for CAD, all-cause mortality, and safety outcomes (Cochran Q P > 0.25 in British and Chinese) with LDL-C levels above the minimum values of 50 and 20 mg/dL in British and Chinese, respectively. Linear MR analyses demonstrated a positive association of LDL-C with CAD [British: odds ratio (OR) per unit mmol/L increase, 1.75, P = 7.57 × 10-52; Chinese: OR, 2.06, P = 9.10 × 10-3]. Furthermore, stratified analyses restricted to individuals with LDL-C levels less than the guideline-recommended 70 mg/dL demonstrated lower LDL-C levels were associated with a higher risk of adverse events, including haemorrhagic stroke (British: OR, 0.72, P = 0.03) and dementia (British: OR, 0.75, P = 0.03). CONCLUSION: In British and Chinese populations, we confirmed a linear dose-response relationship of LDL-C with CAD and found potential safety concerns at low LDL-C levels, providing recommendations for monitoring adverse events in people with low LDL-C in the prevention of cardiovascular disease.

We used the Mendelian randomization method to estimate the causal relationships between LDL-C and efficacy and safety outcomes in the UK Biobank and the China-PAR project.We found a linear rather than a non-linear relationship between genetically proxied LDL cholesterol and coronary artery disease.There are potential safety concerns (including haemorrhagic stroke and dementia) for people who have low LDL-C levels.

Integrating polygenic and clinical risks to improve stroke risk stratification in prospective Chinese cohorts.

The utility of the polygenic risk score (PRS) to identify individuals at higher risk of stroke beyond clinical risk remains unclear, and we clarified this using Chinese population-based prospective cohorts. Cox proportional hazards models were used to estimate the 10-year risk, and Fine and Gray's models were used for hazard ratios (HRs), their 95% confidence intervals (CIs), and the lifetime risk according to PRS and clinical risk categories. A total of 41,006 individuals aged 30-75 years with a mean follow-up of 9.0 years were included. Comparing the top versus bottom 5% of the PRS, the HR was 3.01 (95%CI 2.03-4.45) in the total population, and similar findings were observed within clinical risk strata. Marked gradients in the 10-year and lifetime risk across PRS categories were also found within clinical risk categories. Notably, among individuals with intermediate clinical risk, the 10-year risk for those in the top 5% of the PRS (7.3%, 95%CI 7.1%-7.5%) reached the threshold of high clinical risk (⩾7.0%) for initiating preventive treatment, and this effect of the PRS on refining risk stratification was evident for ischemic stroke. Even among those in the top 10% and 20% of the PRS, the 10-year risk would also exceed this level when aged ⩾50 and ⩾60 years, respectively. Overall, the combination of the PRS with the clinical risk score improved the risk stratification within clinical risk strata and distinguished actual high-risk individuals with intermediate clinical risk.