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.

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.

Efficacy of combined low-dose ruxolitinib and cyclosporine in murine immune bone marrow failure.

Not available.

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.

Immunosuppressive Activity of Exosomes from Granulocytic Myeloid-Derived Suppressor Cells in a Murine Model of Immune Bone Marrow Failure.

We previously reported that granulocytic myeloid-derived suppressor cells (G-MDSCs) suppressed T-cell activation and attenuated bone marrow failure (BMF) in a minor histocompatibility (minor-H) antigen mismatched murine aplastic anemia (AA) model. In the current study, we tested the hypothesis that exosomes, a subset of extracellular vesicles, are responsible at least partially for G-MDSCs' therapeutic efficacy. Indeed, exosomes isolated from GMDSCs (G-MDSC-exos) suppressed CD4+ and CD8+ T-cell proliferation in vitro and mildly attenuated immune BMF in the minor-H mismatched AA model. G-MDSC-exos treatment significantly increased red blood cells, hemoglobin, and total bone marrow (BM) cells, and moderately reduced BM CD8+ T cells. G-MDSC-exos' effects were associated with upregulations in an array of lymphocyte-suppression-related miRNAs such as hsa-miR-142-5p, miR-19a-3p, and miR-19b-3p in both BM CD4+ and CD8+ T cells. We concluded that G-MDSC-exos attenuate immune BMF via modulating the delivery of immunosuppressive miRNAs into activated T lymphocytes.

Effects of ruxolitinib on murine regulatory T cells are immune-context dependent.

Aplastic anemia is a bone marrow failure (BMF) disorder characterized by pancytopenia and hypocellular marrow from an immune-mediated etiology. Regulatory T cells (Tregs) prevent autoimmunity by suppressing autoreactive T cells. We recently demonstrated the efficacy of ruxolitinib (RUX), a JAK 1/2 inhibitor, in attenuating murine BMF. Herein, we investigated the changes of Tregs in the context of RUX treatment for murine BMF. Tregs are conventionally identified by surface expression of CD4 and CD25, in addition to intracellular transcription factor FoxP3. RUX promoted the expansion of Tregs in BMF mice defined by increased expression of FoxP3 in CD4 T cells but suppressed expression of activation marker CD25 in CD4 and CD8 T cells. In this context, CD25 is no longer a reliable surface marker for Tregs. We observed strong co-expression of FoxP3 with surface marker GITR instead of CD25 in RUX-treated BMF mice. Fluorescence-activated cell sorting (FACS)-sorted CD4+GITRhi cells showed high FoxP3 expression and intact suppressive function in vitro, suggesting GITR to be a surrogate marker for Tregs. In contrast to its expansive effect on Tregs in BMF, RUX suppressed Tregs in normal and sublethal irradiation conditions, indicating that the effects of RUX on Tregs are immune-context dependent.

Serum metabolomics profiling of improved metabolic syndrome is characterized by decreased pro-inflammatory biomarkers: A longitudinal study in Chinese male adults.

Metabolic syndrome (MetS) is a serious global health concern. The objective of this study is to dynamically investigate the changes of metabolic profiles and metabolites in Chinese male MetS subjects after an 18 months diet and exercise intervention. Fifty male MetS patients defined according to International Diabetes Federation 2005 guidelines were subjected to diet and exercise counseling for 18 months. Serum samples were taken at baseline, 12 months, and 18 months, respectively, for clinical evaluation and metabolomics analyses. Diet and exercise intervention for 18 months achieved significant improvements in the metabolic profiles of all participants. Nineteen subjects (38.0%) exhibited MetS remission at the end of the study. A total of 812 relative features were characterized and 61 were successfully identified. Furthermore, 17 differential metabolites were of significance at both time points (baseline-12 months, baseline-18 months) and presented nonlinear trends through time. Eight metabolites (47.1%) were predominantly converged to inflammation and oxidative stress. Pro-inflammatory biomarkers were remarkably decreased after 18 months of intervention, and prostaglandin E2, neuroprotectin D1, and taxiphyllin in combination were firstly found to demonstrate a fair discriminative power (area under curve = 0.911) to predict the improvement of MetS undergone diet and exercise intervention. The significant shift of metabolomic profiling after 18 months of lifestyle counseling provide a novel insight and reveal that earlier inflammation control may be of potential benefit in MetS management.

The Early Impact of the People-centred Integrated Care on the Hypertension Management in Shenzhen.

Objective: To evaluate the impact of the integrated care in Luohu, China on the hypertension management. Methods: Hypertensive patients aged 35-74 years were recruited by the cluster-randomized sampling method from Luohu district which adopted integrated care and another district that remained original routine care during October 2018~January 2020, with 1353 and 583 patients from integrated and routine care communities, respectively. Health information, knowledge, attitude, and practice (KAP) towards cardiovascular diseases, pharmaceutical expenditure on hypertension and its comorbidities, and healthcare-related satisfaction were collected by questionnaires, with the expenditure additionally verified by hospitals' billing records database. Continuous and categorical variables were compared by Wilcoxon test and Chi-square test, respectively. The age-standardized hypertension control rate was calculated by direct standardization. Results: The standardized hypertension management rate in the integrated care communities (45.75%) was significantly higher than that in routine care communities (14.07%) (P < 0.0001), while the age-standardized hypertension control rates were similar (integrated care: 50.3%, routine care: 52.65%, P = 0.518). The pharmaceutical expenditure on hypertension and its comorbidities in the integrated care communities was Ò°264.23 ± 357.38/month/person, lower than that in the routine care communities (Ò°354.56 ± 430.59/month/person). Patients in the integrated care had higher KAP scores (73.48 ± 11.54), compared with routine care (68.89 ± 15.51) (P < 0.0001). Moreover, the integrated care communities had higher satisfaction rates towards the convenience of dual referral (90.15% vs. 77.99%) and service quality (95.18% vs. 87.81%) than routine care communities (P < 0.0001). Conclusion: The practice of the integrated care in Luohu has substantially improved the hypertension management and the healthcare-related satisfaction while with relatively low pharmaceutical expenditure. The investigation of long-term impact of the integrated care on hypertension control and management is warranted.

Sex Differences in Associations Between Socioeconomic Status and Incident Hypertension Among Chinese Adults.

BACKGROUND: With rapid socioeconomic development and transition, associations between socioeconomic status (SES) and hypertension remained uncertain in China. We aimed to examine the health effects of SES on hypertension incidence and explore the sex differences among Chinese adults. METHODS: We included 53 891 participants without hypertension from the China-PAR (Prediction for Atherosclerotic Cardiovascular Disease Risk in China) project. SES was evaluated by education level, occupation prestige, and household monthly per capita income, and categorized into low, medium, and high groups. Hazard ratios and their 95% CIs were calculated using Cox proportional hazards regression models. RESULTS: Compared with high SES, participants with medium SES (hazard ratio, 1.142 [95% CI, 1.068-1.220]) or low SES (hazard ratio, 1.166 [95% CI, 1.096-1.241]) had increased risks of incident hypertension in multivariate analyses. Interactions between SES and sex on hypertension were observed, with more pronounced adverse effects of lower SES among women. The corresponding hazard ratios (95% CIs) for low SES group were 1.270 (1.155-1.397) for women and 1.086 (0.999-1.181) for men. Effects of occupation prestige on hypertension were the strongest among SES factors. CONCLUSIONS: Our study provided the compelling evidence from China that lower SES was associated with incident hypertension and women were more susceptible. These findings will have substantial implications on future hypertension prevention and management, especially among women. Sex-specific approaches are warranted to reduce socioeconomic disparities.

Changes in fasting blood glucose status and incidence of cardiovascular disease: The China-PAR project.

BACKGROUND: The effect of long-standing prediabetes or its transition on incident cardiovascular disease (CVD) is unclear. This study aimed to evaluate the association of changes in fasting blood glucose (FBG) status with the risk of developing CVD. METHODS: This research included 12 145 Chinese adults aged 35-74 years and free from diabetes mellitus (DM) at baseline. Study participants were cross-classified into six categories according to glucose at the first (1998-2001) and the second visit after 8 years: normal fasting glucose (NFG; 50-99 mg/dl), impaired FBG (IFG; 100-125 mg/dl), and DM. Cox proportional hazard regression model was used to estimate the hazard ratio (HR) and 95% confidence interval (CI) for CVD associated with transition of glucose status. RESULTS: During a median follow-up of 5.5 years, 373 incident CVD cases occurred. Compared with participants remaining persistent NFG, a higher risk of developing CVD was identified among those remaining persistent IFG, progressing to DM from NFG or from IFG, with the multivariate-adjusted HR (95% CI) of 1.792 (1.141, 2.816), 1.723 (1.122, 2.645) and 1.946 (1.120, 3.381), respectively. Furthermore, when stratified by glucose status at baseline, persistent IFG and progression from IFG to DM still increased CVD risk in comparison with reversion from IFG to NFG, with the multivariate-adjusted HR (95% CI) of 1.594 (1.003, 2.532) and 1.913 (1.080, 3.389). CONCLUSIONS: Participants with long-standing IFG and progressing to DM had a higher risk of developing CVD. Further well-designed studies are warranted to assess the association of other phenotypes or prediabetes duration with CVD.

Granulocytic myeloid-derived suppressor cells to prevent and treat murine immune-mediated bone marrow failure.

Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells that originate in the bone marrow (BM) and have immunoregulatory functions. MDSCs have been implicated in the pathogenesis of several autoimmune diseases but have not been investigated in immune aplastic anemia (AA). We examined the roles of granulocytic-MDSCs (G-MDSCs) in murine models of human AA and BM failure (BMF). As both prophylaxis and therapy, BM-derived G-MDSCs improved pancytopenia and BM cellularity and suppressed BM T-cell infiltration in major histocompatibility complex (MHC)-matched C.B10 BMF mice. These effects were not obtained in the MHC-mismatched CByB6F1 AA model, likely because of MHC disparity between G-MDSCs and donor T cells. Single-cell RNA sequencing demonstrated that G-MDSCs downregulated cell cycle-related genes in BM-infiltrated T cells, consistent with suppression of T-cell proliferation by G-MDSCs through reactive oxygen species pathways. Clearance of G-MDSCs in the MHC-mismatched CByB6F1 model using anti-Ly6G antibody facilitated T cell-mediated BM destruction, suggesting an intrinsic immunosuppressive property of G-MDSCs. However, the same anti-Ly6G antibody in the MHC-matched C.B10 AA model mildly mitigated BMF, associated with expansion of an intermediate Ly6G population. Our results demonstrate that G-MDSC eradication and therapeutic efficacy are immune context-dependent.

Efficacy of JAK1/2 inhibition in murine immune bone marrow failure.

Immune aplastic anemia (AA) is a severe blood disease characterized by T-lymphocyte- mediated stem cell destruction. Hematopoietic stem cell transplantation and immunosuppression are effective, but they entail costs and risks, and are not always successful. The Janus kinase (JAK) 1/2 inhibitor ruxolitinib (RUX) suppresses cytotoxic T-cell activation and inhibits cytokine production in models of graft-versus-host disease. We tested RUX in murine immune AA for potential therapeutic benefit. After infusion of lymph node (LN) cells mismatched at the major histocompatibility complex [C67BL/6 (B6)⇒CByB6F1], RUX, administered as a food additive (Rux-chow), attenuated bone marrow hypoplasia, ameliorated peripheral blood pancytopenia, preserved hematopoietic progenitors, and prevented mortality, when used either prophylactically or therapeutically. RUX suppressed the infiltration, proliferation, and activation of effector T cells in the bone marrow and mitigated Fas-mediated apoptotic destruction of target hematopoietic cells. Similar effects were obtained when Rux-chow was fed to C.B10 mice in a minor histocompatibility antigen mismatched (B6⇒C.B10) AA model. RUX only modestly suppressed lymphoid and erythroid hematopoiesis in normal and irradiated CByB6F1 mice. Our data support clinical trials of JAK/STAT inhibitors in human AA and other immune bone marrow failure syndromes.

The association of long-term ambient fine particulate matter exposure with blood pressure among Chinese adults.

Previous studies indicated that long-term exposure to high level of fine particulate matter (PM2.5) was associated with elevated blood pressure (BP) and hypertension, but most of them were conducted in high-income countries with low PM2.5 level. Therefore, we aimed to evaluate the adverse impacts of long-term exposure to PM2.5 on BP and hypertension in China with high concentration. A total of 99,084 adults aged ≥18 years old were included from three cohorts among the project of Prediction for Atherosclerotic Cardiovascular Disease Risk in China. PM2.5 concentrations during 2000-2015 at 1 × 1 km spatial resolution were evaluated using satellite-based spatiotemporal models. Generalized estimating equation was applied to assess the impact of three-year average PM2.5 concentrations on BP level and hypertension. We also examined whether health status and lifestyles modified the effects of PM2.5 on BP and hypertension. Generally, high concentration of PM2.5 was associated with increased BP level and higher risk of hypertension. With each 10 µg/m3 increment in PM2.5 concentration, systolic BP (SBP) and diastolic BP (DBP) increased by 1.67 [95% confidence interval (CI): 1.48, 1.86] mmHg and 0.45 (95% CI: 0.35, 0.56) mmHg, and the prevalence of hypertension increased by 29% [odds ratio (OR): 1.29, 95% CI: 1.26, 1.32]. In comparison with the first quartile of PM2.5 concentration, SBP, DBP and prevalence of hypertension in the fourth quartile were increased by 8.26 (95% CI: 7.73, 8.80) mmHg, 2.85 (95% CI: 2.55, 3.15) mmHg, and 133% (OR: 2.33, 95% CI: 2.21, 2.47), respectively, in the fully adjusted model. However, the relationships of PM2.5 with BP might be non-linear, as BP level started to decline when PM2.5 exceeded 75 µg/m3. In conclusion, long-term PM2.5 exposure could elevate BP level and prevalence of hypertension. People living in high-polluted areas should strengthen their awareness of prevention.

The association of dietary resistance starch intake with all-cause and cause-specific mortality.

Background: Several studies have estimated daily intake of resistant starch (RS), but no studies have investigated the relationship of RS intake with mortality. Objective: We aimed to examine associations between RS intake and all-cause and cause-specific mortality. Methods: Data from US National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018 with 24-h dietary recall data was used in current study. The main exposure in this study was RS intake, and the main outcome was the mortality status of participants until December 31, 2019. The multivariable Cox proportional hazards regression models were developed to evaluate the hazard ratios (HRs) and 95% confidence interval (95% CI) of cardiovascular disease (CVD), cancer, and all-cause mortality associated with RS intake. Results: A total of 42,586 US adults [mean (SD) age, 46.91 (16.88) years; 22,328 (52.43%) female] were included in the present analysis. During the 454,252 person-years of follow-up, 7,043 all-cause deaths occurred, including 1,809 deaths from CVD and 1,574 deaths from cancer. The multivariable-adjusted HRs for CVD, cancer, and all-cause mortality per quintile increase in RS intake were 1 (95%CI, 0.97-1.04), 0.96 (95%CI, 0.93-1), and 0.96 (95%CI, 0.95-0.98), respectively. The associations remained similar in the subgroup and sensitivity analyses. Conclusion: Higher RS intake is significantly associated with lower cancer and all-cause mortality, but not significantly with CVD mortality. Future studies focusing on other populations with different food sources of RS and RS subtypes are needed to access the dose-response relationship and to improve global dietary recommendations.

Changes in dendritic complexity and spine morphology following BCG immunization in APP/PS1 mice.

Bacillus Calmette - Guerin (BCG) is an immune regulator that can enhance hippocampal synaptic plasticity in rats; however, it is unclear whether it can improve synaptic function in a mouse model with Alzheimer's disease (AD). We hypothesized that BCG plays a protective role in AD mice and investigated its effect on dendritic morphology. The results obtained show that BCG immunization significantly increases dendritic complexity, as indicated by the increased number of dendritic intersections and branch points, as well as the increase in the fractal dimension. Furthermore, the number of primary neurites and dendritic length also increased following BCG immunization, which increased the number of spines and promoted maturation. IFN-γ and IL-4 levels increased, while TNF-α levels decreased following BCG immunization; expression levels of p-JAK2, P-STAT3, SYN, and PSD-95 also increased. Therefore, this study demonstrates that BCG immunization in APP/PS1 mice mitigated hippocampal dendritic spine pathology, especially after the third round of immunization. This effect could possibly be attributed to; changes in dendritic arborization and spine morphology or increases in SYN and PSD-95 expression levels. It could also be related to mechanisms of BCG-induced increases in IFN-γ or IL-4/JAK2/STAT3 levels.

BCG immunization in a mouse model for Alzheimer's disease significantly increased dendritic complexity, as indicated by an increase in the number of dendritic intersections and branch points, as well as an increase in the fractal dimension of hippocampal CA1 neurons.

A Pooled Analysis of the PCR for the Detection of Candida Auris.

BACKGROUND: Candida auris is an opportunistic pathogen with multiple drug resistance. Therefore, researchers conducted a meta-analysis to review PCR's ability to diagnose Candida auris to promote the development of accurate Candida auris diagnosis. METHODS: Researchers systematically retrieved relevant articles from PubMed, Cochrane Library, Embase, and Web of Science. Then, researchers extracted the key data required for the study from the selected articles. Meta-DiSc 1.4 was used for the statistical analysis. RevMan 5.3 was employed to assess the quality of the included literature. A funnel plot can appraise whether the included articles have publication bias. RESULTS: Five articles were included in the study. The results suggest that the pooled sensitivity and pooled specificity were 0.94 (95% CI: 0.92 - 0.95) and 0.99 (95% CI: 0.99 - 0.99), respectively. The positive and negative likelyhood ratios were 100.94 (95% CI: 47.51 - 214.47) and 0.07 (95% CI: 0.05 - 0.10), respectively. The diagnostic odds ratio was 1,814.70 (95% CI: 717.30 - 4,591.04), and the area under the SROC curve was 0.9935. Deek's funnel plot indicated that there was no publication bias. CONCLUSIONS: The results of the analysis indicate that PCR can become a valuable technique for the clinical diagnosis of Candida auris due to its excellent performance.

Metabolomics study of blood pressure salt-sensitivity and hypertension.

BACKGROUND AND AIMS: Identify novel metabolite associations with blood pressure (BP) salt-sensitivity and hypertension. METHODS AND RESULTS: The Genetic Epidemiology Network of Salt Sensitivity (GenSalt) Replication study includes 698 Chinese participants who underwent a 3-day baseline examination followed by a 7-day low-sodium feeding and 7-day high-sodium feeding. Latent mixture models identified three trajectories of blood pressure (BP) responses to the sodium interventions. We selected 50 most highly salt-sensitive and 50 most salt-resistant participants for untargeted metabolomics profiling. Multivariable adjusted mixed logistic regression models tested the associations of baseline metabolites with BP salt-sensitivity. Multivariable adjusted mixed linear regression models tested the associations of BP salt-sensitivity with metabolite changes during the sodium interventions. Identified metabolites were tested for associations with hypertension among 1249 Bogalusa Heart Study (BHS) participants using multiple logistic regression. Fifteen salt-sensitivity metabolites were associated with hypertension in the BHS. Baseline values of serine, 2-methylbutyrylcarnitine and isoleucine directly associated with high salt-sensitivity. Among them, serine indirectly associated with hypertension while 2-methylbutyrylcarnitine and isoleucine directly associated with hypertension. Baseline salt-sensitivity status predicted changes in 14 metabolites when switching to low-sodium or high-sodium interventions. Among them, glutamate, 1-carboxyethylvaline, 2-methylbutyrylcarnitine, 3-methoxytyramine sulfate, glucose, alpha-ketoglutarate, hexanoylcarnitine, gamma-glutamylisoleucine, gamma-glutamylleucine, and gamma-glutamylphenylalanine directly associated with hypertension. Conversely, serine, histidine, threonate and 5-methyluridine indirectly associated with hypertension. Together, these metabolites explained an additional 7% of hypertension susceptibility when added to a model including traditional risk factors. CONCLUSIONS: Our findings contribute to the molecular characterization of BP response to sodium and provide novel biological insights into salt-sensitive hypertension.

A polygenic risk score improves risk stratification of coronary artery disease: a large-scale prospective Chinese cohort study.

AIMS: To construct a polygenic risk score (PRS) for coronary artery disease (CAD) and comprehensively evaluate its potential in clinical utility for primary prevention in Chinese populations. METHODS AND RESULTS: Using meta-analytic approach and large genome-wide association results for CAD and CAD-related traits in East Asians, a PRS comprising 540 genetic variants was developed in a training set of 2800 patients with CAD and 2055 controls, and was further assessed for risk stratification for CAD integrating with the guideline-recommended clinical risk score in large prospective cohorts comprising 41 271 individuals. During a mean follow-up of 13.0 years, 1303 incident CAD cases were identified. Individuals with high PRS (the highest 20%) had about three-fold higher risk of CAD than the lowest 20% (hazard ratio 2.91, 95% confidence interval 2.43-3.49), with the lifetime risk of 15.9 and 5.8%, respectively. The addition of PRS to the clinical risk score yielded a modest yet significant improvement in C-statistic (1%) and net reclassification improvement (3.5%). We observed significant gradients in both 10-year and lifetime risk of CAD according to the PRS within each clinical risk strata. Particularly, when integrating high PRS, intermediate clinical risk individuals with uncertain clinical decision for intervention would reach the risk levels (10-year of 4.6 vs. 4.8%, lifetime of 17.9 vs. 16.6%) of high clinical risk individuals with intermediate (20-80%) PRS. CONCLUSION: The PRS could stratify individuals into different trajectories of CAD risk, and further refine risk stratification for CAD within each clinical risk strata, demonstrating a great potential to identify high-risk individuals for targeted intervention in clinical utility.

25-hydroxyvitamin D levels are inversely related to metabolic syndrome risk profile in northern Chinese subjects without vitamin D supplementation.

BACKGROUND: The comparatively low 25 hydroxyvitamin D [25(OH)D] levels have been reported in patients with metabolic syndrome (MetS). Herein we investigated the cross-sectional and longitudinal relationships between serum 25(OH)D levels and MetS risk profile in northern middle-aged Chinese subjects without vitamin D supplementation. METHODS: A cohort of 211 participants including 151 MetS patients and 60 controls at 20-69 years of age were enrolled from suburban Beijing, China. The recruited MetS patients were subjected to diet and exercise counselling for 1-year. All subjects at baseline and MetS patients after intervention underwent clinical evaluations. RESULTS: Serum 25(OH)D levels were significantly decreased in MetS patients. 25(OH)D levels were inversely related to MetS score, fasting blood glucose (FBG) and triglyceride-glucose index (TyG) after adjusting for cofounders (all P < 0.05). Participants in the lowest tertile of 25(OH)D levels had increased odds for MetS (P = 0.045), elevated FBG (P = 0.004) in all subjects, and one MetS score gain in MetS patients (P = 0.005). Longitudinally, the metabolic statuses as well as 25(OH)D levels of MetS patients were significantly improved (all P < 0.05), and the increase of 25(OH)D levels were inversely related to MetS scores, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), FBG, and TyG, while positively related to high-density lipoprotein cholesterol (HDL-C) after adjusting for confounders. CONCLUSIONS: 25(OH)D levels were significantly decreased in MetS patients, and it was negatively associated with metabolic dysfunctions at baseline and 1-year after. Metabolic aberrations of MetS patients were significantly ameliorated with 1-year follow-up counselling accompanying by notably elevated 25(OH)D levels.

Long-term exposure to fine particulate matter modifies the association between physical activity and hypertension incidence.

BACKGROUND: The trade-off between the benefits of regular physical activity (PA) and the potentially detrimental effects of augmented exposure to air pollution in highly polluted regions remains unclear. This study aimed to examine whether ambient fine particulate matter (PM2.5) exposure modified the impacts of PA volume and intensity on hypertension risk. METHODS: We included 54,797 participants without hypertension at baseline in a nationwide cohort of the Prediction for Atherosclerotic Cardiovascular Disease Risk in China (China-PAR) project. PA volume and intensity were assessed by questionnaire, and high-resolution (1 km ×1 km) PM2.5 estimates were generated using a satellite-based model. RESULTS: During 413,516 person-years of follow-up, 12,100 incident hypertension cases were identified. PM2.5 significantly modified the relationship between PA and hypertension incidence (pinteraction < 0.001). Increased PA volume was negatively associated with incident hypertension in the low PM2.5 stratum (<59.8 µg/m3, ptrend < 0.001), with a hazard ratio of 0.81 (95% confidence interval (95%CI): 0.74-0.88) when comparing the fourth with the first quartile of PA volume. However, the health benefits were not observed in the high PM2.5 stratum (≥59.8 µg/m3, ptrend = 0.370). Moreover, compared with light PA intensity, vigorous intensity was related to a 20% (95%CI: 9%-29%) decreased risk of hypertension for participants exposed to low PM2.5, but a 17% (95%CI: 4%-33%) increased risk for those with high PM2.5 levels. CONCLUSION: PA was associated with a reduced risk of hypertension only among participants with low PM2.5 exposure. Our findings recommended regular PA to prevent hypertension in less polluted regions and reinforced the importance of air quality improvement.