NF1 mutation drives neuronal activity-dependent initiation of optic glioma.

Neurons have recently emerged as essential cellular constituents of the tumour microenvironment, and their activity has been shown to increase the growth of a diverse number of solid tumours1. Although the role of neurons in tumour progression has previously been demonstrated2, the importance of neuronal activity to tumour initiation is less clear-particularly in the setting of cancer predisposition syndromes. Fifteen per cent of individuals with the neurofibromatosis 1 (NF1) cancer predisposition syndrome (in which tumours arise in close association with nerves) develop low-grade neoplasms of the optic pathway (known as optic pathway gliomas (OPGs)) during early childhood3,4, raising  the possibility that postnatal light-induced activity of the optic nerve drives tumour initiation. Here we use an authenticated mouse model of OPG driven by mutations in the neurofibromatosis 1 tumour suppressor gene (Nf1)5 to demonstrate that stimulation of optic nerve activity increases optic glioma growth, and that decreasing visual experience via light deprivation prevents tumour formation and maintenance. We show that the initiation of Nf1-driven OPGs (Nf1-OPGs) depends on visual experience during a developmental period in which Nf1-mutant mice are susceptible to tumorigenesis. Germline Nf1 mutation in retinal neurons results in aberrantly increased shedding of neuroligin 3 (NLGN3) within the optic nerve in response to retinal neuronal activity. Moreover, genetic Nlgn3 loss or pharmacological inhibition of NLGN3 shedding blocks the formation and progression of Nf1-OPGs. Collectively, our studies establish an obligate role for neuronal activity in the development of some types of brain tumours, elucidate a therapeutic strategy to reduce OPG incidence or mitigate tumour progression, and underscore the role of Nf1mutation-mediated dysregulation of neuronal signalling pathways in mouse models of the NF1 cancer predisposition syndrome.

Effectiveness of a non-physician community health-care provider-led intensive blood pressure intervention versus usual care on cardiovascular disease (CRHCP): an open-label, blinded-endpoint, cluster-randomised trial.

BACKGROUND: Effectiveness of a non-physician community health-care provider-led intensive blood pressure intervention on cardiovascular disease has not been established. We aimed to test the effectiveness of such an intervention compared with usual care on risk of cardiovascular disease and all-cause death among individuals with hypertension. METHODS: In this open-label, blinded-endpoint, cluster-randomised trial, we recruited individuals aged at least 40 years with an untreated systolic blood pressure of at least 140 mm Hg or a diastolic blood pressure of at least 90 mm Hg (≥130 mm Hg and ≥80 mm Hg for those at high risk for cardiovascular disease or if currently taking antihypertensive medication). We randomly assigned (1:1) 326 villages to a non-physician community health-care provider-led intervention or usual care, stratified by provinces, counties, and townships. In the intervention group, trained non-physician community health-care providers initiated and titrated antihypertensive medications according to a simple stepped-care protocol to achieve a systolic blood pressure goal of less than 130 mm Hg and diastolic blood pressure goal of less than 80 mm Hg with supervision from primary care physicians. They also delivered discounted or free antihypertensive medications and health coaching for patients. The primary effectiveness outcome was a composite outcome of myocardial infarction, stroke, heart failure requiring hospitalisation, and cardiovascular disease death during the 36-month follow-up in the study participants. Safety was assessed every 6 months. This trial is registered with ClinicalTrials.gov, NCT03527719. FINDINGS: Between May 8 and Nov 28, 2018, we enrolled 163 villages per group with 33 995 participants. Over 36 months, the net group difference in systolic blood pressure reduction was -23·1 mm Hg (95% CI -24·4 to -21·9; p<0·0001) and in diastolic blood pressure reduction, it was -9·9 mm Hg (-10·6 to -9·3; p<0·0001). Fewer patients in the intervention group than the usual care group had a primary outcome (1·62% vs 2·40% per year; hazard ratio [HR] 0·67, 95% CI 0·61-0·73; p<0·0001). Secondary outcomes were also reduced in the intervention group: myocardial infarction (HR 0·77, 95% CI 0·60-0·98; p=0·037), stroke (0·66, 0·60-0·73; p<0·0001), heart failure (0·58, 0·42-0·81; p=0·0016), cardiovascular disease death (0·70, 0·58-0·83; p<0·0001), and all-cause death (0·85, 0·76-0·95; p=0·0037). The risk reduction of the primary outcome was consistent across subgroups of age, sex, education, antihypertensive medication use, and baseline cardiovascular disease risk. Hypotension was higher in the intervention than in the usual care group (1·75% vs 0·89%; p<0·0001). INTERPRETATION: The non-physician community health-care provider-led intensive blood pressure intervention is effective in reducing cardiovascular disease and death. FUNDING: The Ministry of Science and Technology of China and the Science and Technology Program of Liaoning Province, China.

A village doctor-led multifaceted intervention for blood pressure control in rural China: an open, cluster randomised trial.

BACKGROUND: The prevalence of uncontrolled hypertension is high and increasing in low-income and middle-income countries. We tested the effectiveness of a multifaceted intervention for blood pressure control in rural China led by village doctors (community health workers on the front line of primary health care). METHODS: In this open, cluster randomised trial (China Rural Hypertension Control Project), 326 villages that had a regular village doctor and participated in the China New Rural Cooperative Medical Scheme were randomly assigned (1:1) to either village doctor-led multifaceted intervention or enhanced usual care (control), with stratification by provinces, counties, and townships. We recruited individuals aged 40 years or older with an untreated blood pressure of 140/90 mm Hg or higher (≥130/80 mm Hg among those with a history of cardiovascular disease, diabetes, or chronic kidney disease) or a treated blood pressure of 130/80 mm Hg or higher. In the intervention group, trained village doctors initiated and titrated antihypertensive medications according to a standard protocol with supervision from primary care physicians. Village doctors also conducted health coaching on home blood pressure monitoring, lifestyle changes, and medication adherence. The primary outcome (reported here) was the proportion of patients with a blood pressure of less than 130/80 mm Hg at 18 months. The analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, NCT03527719, and is ongoing. FINDINGS: Between May 8 and November 28, 2018, we enrolled 33 995 individuals from 163 intervention and 163 control villages. At 18 months, 8865 (57·0%) of 15 414 patients in the intervention group and 2895 (19·9%) of 14 500 patients in the control group had a blood pressure of less than 130/80 mm Hg, with a group difference of 37·0% (95% CI 34·9 to 39·1%; p<0·0001). Mean systolic blood pressure decreased by -26·3 mm Hg (95% CI -27·1 to -25·4) from baseline to 18 months in the intervention group and by -11·8 mm Hg (-12·6 to -11·0) in the control group, with a group difference of -14·5 mm Hg (95% CI -15·7 to -13·3 mm Hg; p<0·0001). Mean diastolic blood pressure decreased by -14·6 mm Hg (-15·1 to -14·2) from baseline to 18 months in the intervention group and by -7·5 mm Hg (-7·9 to -7·2) in the control group, with a group difference of -7·1 mm Hg (-7·7 to -6·5 mm Hg; p<0·0001). No treatment-related serious adverse events were reported in either group. INTERPRETATION: Compared with enhanced usual care, village doctor-led intervention resulted in statistically significant improvements in blood pressure control among rural residents in China. This feasible, effective, and sustainable implementation strategy could be scaled up in rural China and other low-income and middle-income countries for hypertension control. FUNDING: Ministry of Science and Technology of China.

Mesenchymal stem cells, as glioma exosomal immunosuppressive signal multipliers, enhance MDSCs immunosuppressive activity through the miR-21/SP1/DNMT1 positive feedback loop.

BACKGROUND: The immunosuppressive microenvironment in glioma induces immunotherapy resistance and is associated with poor prognosis. Glioma-associated mesenchymal stem cells (GA-MSCs) play an important role in the formation of the immunosuppressive microenvironment, but the mechanism is still not clear. RESULTS: We found that GA-MSCs promoted the expression of CD73, an ectonucleotidase that drives immunosuppressive microenvironment maintenance by generating adenosine, on myeloid-derived suppressor cells (MDSCs) through immunosuppressive exosomal miR-21 signaling. This process was similar to the immunosuppressive signaling mediated by glioma exosomal miR-21 but more intense. Further study showed that the miR-21/SP1/DNMT1 positive feedback loop in MSCs triggered by glioma exosomal CD44 upregulated MSC exosomal miR-21 expression, amplifying the glioma exosomal immunosuppressive signal. Modified dendritic cell-derived exosomes (Dex) carrying miR-21 inhibitors could target GA-MSCs and reduce CD73 expression on MDSCs, synergizing with anti-PD-1 monoclonal antibody (mAb). CONCLUSIONS: Overall, this work reveals the critical role of MSCs in the glioma microenvironment as signal multipliers to enhance immunosuppressive signaling of glioma exosomes, and disrupting the positive feedback loop in MSCs with modified Dex could improve PD-1 blockade therapy.

Gender-specific effects of soybean consumption on cardiovascular events in elderly individuals from rural Northeast China - a prospective cohort study.

BACKGROUND: The impact of consuming soybean and its products on cardiovascular events (CVEs), cardiovascular mortality, and all-cause mortality remains unclear. This study aimed to examine the prospective association of soybean consumption with CVEs, cardiovascular mortality, and all-cause mortality among the elderly population in rural China. METHODS: The Northeast China Rural Cardiovascular Health Study included 2477 elderly individuals (mean age 67 ± 6 years, 49.97% men) in the initial phase of the study from 2012 to 2013, with a follow-up period between 2015 and 2017. Soybean consumption was categorized as follows: low-frequency consumption: rare consumption; moderate-frequency consumption: two to three times/week; high-frequency consumption: ≥ four times/week. Cox proportional hazard analysis assessed the potential relationship of soybean consumption with CVEs, cardiovascular mortality, and all-cause mortality. RESULTS: The prevalence of soybean and its product consumption was as follows: 38.3% for low-frequency consumption (43.8% for women; 32.8% for men), 49.7% for moderate-frequency consumption (45.8% for women; 53.7% for men), and 11.9% for high-frequency consumption (10.4% for women; 13.5% for men). After adjusting for possible confounders, Cox proportional hazard analysis revealed that the frequency of soybean consumption was an effective predictor of CVEs [Hazard ratio (HR) high (95% CI): 0.555 (0.348, 0.883)], stroke [HR moderate (95% CI): 0.672 (0.494, 0.913); HR high (95% CI): 0.483 (0.276, 0.842)], and all-cause mortality [HR high (95% CI): 0.540 (0.310, 0.942)] in the overall older population. High-frequency consumption of soybean [HR (95% CI): 0.467 (0.225, 0.968)] and moderate-frequency consumption [HR (95% CI): 0.458 (0.270, 0.779)] were associated with stroke events in older men and women, respectively. In addition, high-frequency consumption of soybean [HR (95% CI): 0.437 (0.197, 0.968)] decreased the risk of CVEs in older women. CONCLUSION: Soybean consumption is closely associated with CVEs and all-cause mortality in older individuals residing in rural areas, with a significant gender discrepancy in this relationship. These findings provide new insights into the impact of soybean consumption on cardiovascular well-being in the elderly rural population, thus enhancing our understanding of this field of interest.

Impact of liver fibrosis score on the incidence of stroke: A cohort study.

PURPOSE: The purpose was to explore the value of liver fibrosis scores (fibrosis-4, BAAT score and BARD score) for incidence risk of stroke in a cohort study. METHODS: A total of 9088 participants without stroke history enrolled the follow-up. Three liver fibrosis scores (LFSs) including FIB-4, BARD score and BAAT score were adopted. The end point was stroke. Cox regression analysis was used to calculate hazard ratios and 95% confidence interval. Kaplan-Meier curve was used to show the probability of stoke in different levels of LFSs. Subgroup analysis showed the association between LFSs and stroke under different stratification. Restricted cubic spline could further explore whether there is a linear relationship between LFSs and stroke. Finally, we used C-statistics, Net Reclassification Index (NRI) and Integrated Discrimination Improvement (IDI) to assess the discriminatory power of each LFS for stroke. RESULTS: During a median follow-up time of 4.66 years, 272 participants had a stroke. Through the baseline characteristics, we observed that the stroke incidence population tends to be male and older. It was shown by Kaplan-Meier that three LFSs were associated with stroke and high levels of LFSs significantly increase the probability of stroke. In the univariate Cox regression analysis, the HR of stroke risk was 6.04 (4.14-8.18) in FIB-4, 2.10 (1.45-3.04) in BAAT score and 1.81 (1.38-2.38) in BARD score by comparing the high level with the low level at each LFSs. The adjusted HRs for three LFSs were 2.05 (1.33-3.15) in FIB-4, 1.61 (1.10-2.35) in BAAT score and 1.54 (1.17-2.04) in BARD score by comparing the high group with low group. We found that multivariable-adjusted HRs of three LFSs still increased for stroke when stratified by various factors in subgroup analysis. Moreover, after adding LFSs to original risk prediction model which consist of age, sex, drinking, smoking, hypertension, diabetes, low-density lipoprotein cholesterol, total cholesterol and triglycerides, we found that new models have higher C-statistics of stroke. Furthermore, we calculated Net Reclassification Index (NRI) and Integrated Discrimination Improvement (IDI) to show the ability of LFSs to predict stroke. CONCLUSIONS: Our study showed that three LFSs were associated with stroke amongst middle-aged populations in rural areas of Northeast China. Furthermore, it suggests that LFSs can be used as a risk stratification tool to predict stroke.

Is waist-to-height ratio the best predictive indicator of cardiovascular disease incidence in hypertensive adults? A cohort study.

BACKGROUND: Cardiovascular disease (CVD) brings high mortality and economic burden to patients, especially in rural areas. Simple, low-cost abdominal adiposity measures may help identify individuals with increased CVD risk. It is unclear that which obesity indices is the best to predict CVD in hypertensive people. METHODS: Northeast China Rural Cardiovascular Health Study (NCRCHS) is a prospective cohort study in a general population in Northeast China. The study examined the cardiovascular health from 2013 to 2015, and follow-up captured the CVD incidence in 2018. Baseline waist-to-height ratio (WHtR), waist circumference (WC), waist-to-hip (WHR)and body mass index (BMI) were calculated and analyzed in relation to the CVD incidence. RESULTS: A total of 4244 hypertensive adults without pre-existing CVD at baseline were included in this analysis (age 35-92 years; 2108 men). Over a median follow-up of 4.66 years, a total of 290 CVD cases (6.83%) were documented during the follow-up. Baseline WHtR showed a significant positive association with CVD incidence, even after adjusting for age, sex, diabetes, drinking, smoking, SBP, DBP, Triglyceride, HDL-C, LDL-C, and TC (Hazard Ratios per SD of WHtR ranging from 1.03 to 1.31, p = 0.017). Reclassification and discrimination analyses indicated WHtR addition could improve the conventional model for predicting adverse outcomes within 4 years. Moreover, WHtR predicted the CVD incidence better than other obesity indices (BMI, WC, WHR). CONCLUSION: These findings support a positive association between WHtR and CVD incidence in CVD-free hypertensive adults. WHtR can be used to predict CVD incidence in hypertensive adults.

Exosomal miR-1246 from glioma patient body fluids drives the differentiation and activation of myeloid-derived suppressor cells.

Glioma is a heterogeneous cellular environment in which immune cells play critical roles in tumor progression. Myeloid-derived suppressor cells (MDSCs) contribute to the formation of the immunosuppressive microenvironment of glioma; however, how glioma cells interact with MDSCs and how this interaction affects the function of other immune cells are unclear. Glioma cells can systemically communicate with immune cells via the secretion of exosomes, which contain microRNAs (miRNAs). Leveraging miRNA sequencing of exosomes, we identified enrichment of miR-1246 in glioma-derived exosomes and exosomes isolated from the cerebrospinal fluid (CSF) of glioma patients. We demonstrated that miR-1246 drives the differentiation and activation of MDSCs in a dual specificity phosphatase 3 (DUSP3)/extracellular signal­regulated kinase (ERK)-dependent manner. In addition, postoperative CSF exosomal miR-1246 expression was found to be associated with the glioma recurrence rate. Hypoxia, a well-recognized feature of the glioblastoma microenvironment, increased miR-1246 levels in glioma-derived exosomes by enhancing miR-1246 transcription and selective packaging via upregulation of POU class 5 homeobox 1 (POU5F1) and heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1). Importantly, we identified a mechanism of 2-methoxyestradiol, a microtubule inhibitor currently undergoing clinical trials for glioblastoma. 2-Methoxyestradiol suppresses MDSC activation by inhibiting hypoxia-driven exosomal miR-1246 expression in glioma cells and PD-L1 expression in MDSCs.

Exosomes derived from hypoxic glioma deliver miR-1246 and miR-10b-5p to normoxic glioma cells to promote migration and invasion.

Hypoxia is an important feature of the tumor microenvironment and is associated with glioma progression and patient outcome. Exosomes have been implicated in the intercellular communication in the tumor microenvironment. However, the effects of hypoxic glioma exosomes on glioma migration and invasion and the underlying mechanisms remain poorly understood. In this study, we found that exosomes derived from hypoxic glioma cells (H-GDEs) promoted normoxic glioma migration and invasion in vitro and in vivo. Given that exosomes can regulate recipient cell functions by delivering microRNAs, we further revealed miR-1246 and miR-10b-5p were upregulated significantly in H-GDEs and delivered to normoxic glioma cells by H-GDEs. Moreover, we determined the clinical relevance of miR-1246 and miR-10b-5p in glioma patients. Subsequent investigations indicated that miR-1246 and miR-10b-5p markedly induced glioma migration and invasion in vitro and in vivo. Finally, we demonstrated that miR-1246 and miR-10b-5p induced glioma migration and invasion by directly targeting FRK and TFAP2A respectively. In conclusion, our findings suggest that the hypoxic microenvironment stimulates glioma to generate miR-1246- and miR-10b-5p-rich exosomes that are delivered to normoxic glioma cells to promote their migration and invasion; treatment targeting miR-1246 and miR-10b-5p may impair the motility of gliomas, providing a novel direction for the development of antitumor therapy.

Integrated molecular and clinical analysis of low-grade gliomas in children with neurofibromatosis type 1 (NF1).

Low-grade gliomas (LGGs) are the most common childhood brain tumor in the general population and in individuals with the Neurofibromatosis type 1 (NF1) cancer predisposition syndrome. Surgical biopsy is rarely performed prior to treatment in the setting of NF1, resulting in a paucity of tumor genomic information. To define the molecular landscape of NF1-associated LGGs (NF1-LGG), we integrated clinical data, histological diagnoses, and multi-level genetic/genomic analyses on 70 individuals from 25 centers worldwide. Whereas, most tumors harbored bi-allelic NF1 inactivation as the only genetic abnormality, 11% had additional mutations. Moreover, tumors classified as non-pilocytic astrocytoma based on DNA methylation analysis were significantly more likely to harbor these additional mutations. The most common secondary alteration was FGFR1 mutation, which conferred an additional growth advantage in multiple complementary experimental murine Nf1 models. Taken together, this comprehensive characterization has important implications for the management of children with NF1-LGG, distinct from their sporadic counterparts.

The imaging features of extrapancreatic perineural invasion (EPNI) in pancreatic Cancer：A comparative retrospective study.

BACKGROUND: Extrapancreatic perineural invasion (EPNI) is a risk factor for the prognosis of patients with pancreatic cancer. Few reliable clinical indicators can be used to evaluate EPNI. METHODS: We reviewed clinicopathological information of pancreatic cancer patients received radical surgery in our center from 2014 to 2019. The minimum distance between the tumor boundary and celiac artery (CA), superior mesenteric arteria (SMA) was respectively measured on enhanced-contrast CT images. Receiver Operating Characteristic (ROC) analysis was used to evaluate the diagnostic efficacy, and the optimal cut-off value was determined by Youden index. The latter was used as a diagnostic indicator for imaging perineural invasion (iPNI). K-M method and Cox risk regression model were applied to analyze the prognostic value of iPNI. RESULTS: A total of 384 patients were enrolled in this study. ROC analysis showed the minimum distance is an efficient indicator, and the best cut-off value 6.5 mm provided 71.63% sensitivity and specificity 84.31%. Cox regression model showed that iPNI was an independent risk factor for disease-free survival (DFS) and overall survival (OS). Subgroup analysis indicated that patients with larger tumor size and iPNI positive suggested a worse prognosis. CONCLUSIONS: The minimum distance between tumor boundary and arteries is an efficient imaging indicator for diagnosing EPNI. iPNI is an independent risk factor for DFS and OS. The novel typing method based on plexus pancreaticus capitalis (PLX) potentially invaded may have guiding significance for extent of dissection.

Delta HU is a potential marker to predict chemotherapy response for unresectable pancreatic ductal adenocarcinoma.

BACKGROUND: FOLFIRINOX and gemcitabine plus albumin-bound paclitaxel (AG) regimens are recommended as first-line therapy for both locally advanced and metastatic pancreatic cancer. However, there were no specific markers to conduct personalized regimen choice. The research is to assess delta Housfield unit (delta HU), which is the difference in CT attenuation value (in HU) between enhanced and nonenhanced phase of region of interest, as a marker for predicting chemotherapy response of unresectable pancreatic cancer. METHODS: A total of 179 unresectable pancreatic cancer patients were enrolled in the study. Kaplan-Meier analysis and COX regression analysis were performed for progression-free survival (PFS) and overall survival. The differences of clinical characteristics were analyzed by χ 2test. Microvessel density (MVD) was calculated by immunochemistry staining of CD34. RESULTS: Delta HU was an independent risk factor for unresectable pancreatic cancer (P = 0.017, HR 0.672, 95%CI 0.485-0.930). Patients with higher delta HU were associated with better PFS (P = 0.004). For modified FOLFIRINOX (mFOLFIRINOX) group, delta HU was an independent risk factor (P = 0.045, HR 0.571), but not for AG group (P = 0.473, HR 0.855). Delta HU was correlated with stroma MVD (P = 0.000, R = 0.483), not with parenchyma MVD (P = 0.074, R = 0.199). CONCLUSIONS: Delta HU was a marker predicting chemotherapy response for unresectable pancreatic cancer. Higher delta HU was associated with better survival for patients receiving mFOLFIRINOX rather than AG. The delta HU was positively correlated with stroma MVD, explaining the relationship between delta HU and prognosis.

Risk factor control after ischemic stroke or transient ischemic attack.

OBJECTIVE: We aimed to estimate the status of risk factor control after ischemic stroke or transient ischemic attack (IS/TIA), and the influence on recurrent stroke in rural communities of northeastern China. METHODS: This population-based, prospective cohort study enrolled adults aged ≥35 years residing in rural northeastern China. We conducted cardiovascular health examinations in 2012-2015 and followed up in 2018 to record any cardiovascular event. Control of risk factors after IS/TIA was determined through a baseline survey. The Cox proportional hazard model was used to evaluate the relationship between uncontrolled risk factors and stroke recurrence. RESULTS: Of the 10,700 participants, 575 were diagnosed with IS/TIA and were included in the analysis. At baseline, the rates of control of risk factors were as follows: fasting plasma glucose (FPG), 81.6%; not currently smoking, 65.7%; and achieving physical activity targets, 61%. Blood pressure (BP), low-density lipoprotein cholesterol (LDL-C), and body mass index (BMI) were poorly controlled (28.3%, 26.3%, and 37.4%, respectively). The rate of stroke recurrence was 12% during a median follow-up of 4.43 years. After adjusting for age, sex, ethnicity, family history of stroke, and current drinking, uncontrolled BP and not achieving physical exercise targets were associated with an increased risk of recurrence (hazard ratios: 2.081, 1.685, respectively; p < .05). Uncontrolled FPG, BMI, or LDL-C and current smoking did not significantly influence recurrent risk (p > .05). CONCLUSIONS: Control of risk factors after IS/TIA needs to be improved in rural communities of northeastern China to prevent recurrence and thus alleviate the public health and economic burden of stroke.

Echocardiographic left ventricular geometry profiles for prediction of stroke, coronary heart disease and all-cause mortality in the Chinese community: a rural cohort population study.

BACKGROUND: The utility of echocardiographic left ventricular (LV) geometry in the prediction of stroke/coronary heart disease (CHD) and all-cause mortality is not well characterized. This study aimed to evaluate the overall and sex-specific prognostic value of different geometric patterns on the incidence of stroke/CHD and all-cause mortality in a Chinese population-based cohort. METHODS: We conducted a prospective study in the general population in Northeast China, and a total of 9940 participants aged ≥ 35 years underwent echocardiography for LV geometry and were successfully followed up for incident stroke/CHD and all-cause death. Cox proportional hazards models were utilized to estimate the association of baseline LV geometry with adverse outcomes. RESULTS: Over a median follow-up of 4.66 years, abnormal LV geometric patterns had increased crude incident rates of stroke/CHD and all-cause mortality compared with normal geometry in overall population and each sex group (all P < 0.05). Multivariable Cox analysis reported that LV concentric and eccentric hypertrophy were associated with incident stroke/CHD (concentric hypertrophy: hazard ratio (HR) = 1.39, 95% confidence interval (CI) = 1.04-1.86; eccentric hypertrophy: HR = 1.42, 95% CI = 1.11-1.82) and all-cause mortality (concentric hypertrophy: HR = 1.50, 95% CI = 1.07-2.12; eccentric hypertrophy: HR = 1.58, 95% CI = 1.19-2.10), and LV concentric remodeling was related to stroke/CHD incidence (HR = 1.42, 95% CI = 1.09-1.84) in total population compared to normal geometry after the adjustment for potential confounders. In men, a significant increase was observed from LV eccentric hypertrophy for incident stroke/CHD, whereas in women, LV concentric hypertrophy was associated with elevated incidence of both stroke/CHD and all-cause death, and eccentric hypertrophy was correlated with increased all-cause mortality (all P < 0.05). CONCLUSIONS: Our prospective cohort supports that abnormal LV geometry by echocardiography has a prognostic significance for incident stroke/CHD and all-cause mortality, implying that early detection and intervention of LV structural remodeling in rural China are urgently needed to prevent adverse outcomes.

Gender discrepancy in the predictive effect of metabolic syndrome and its components on newly onset cardiovascular disease in elderly from rural China.

BACKGROUND: This study aimed to estimate whether metabolic syndrome (MetS) and its components could be used to predict cardiovascular disease (CVD) in a longitudinal analysis in a rural elderly Chinese population. METHOD: At baseline during 2012-2013, a total of 2486 elderly from rural Chinese were enrolled and were followed up during 2015-2017. Stroke and coronary heart disease (CHD) were included in CVD and were diagnosed by clinicians. The National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III), the American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI) and the International Diabetes Federation (IDF) criteria were used to define MetS separately. RESULT: Hazard ratios adjusting for CHD, stroke and CVD in those with MetS using the NCEP ATP III criteria in females were 1.27 (95 % CI 0.73, 2.21), 1.54 (95 % CI 0.99, 2.40) and 1.45 (95 % CI 1.00, 2.10), respectively; 1.33 (95 % CI 0.77, 2.32), 1.44 (95 % CI 0.92, 2.25) and 1.36 (95 % CI 0.94, 1.97), respectively, with the AHA/NHLBI criteria; and 1.10 (95 % CI 0.89,1.36), 1.62 (95 % CI 1.03, 2.55) and 1.36 (95 % CI 0.93, 1.97), respectively, with the IDF criteria. Additionally, abdominal obesity using the AHA/NHLBI criteria was significantly associated with the incidence of stroke (HR: 1.60; 95 % CI 1.01, 2.52). However, among rural elderly males, neither MetS nor its components predicted new-onset CVD. CONCLUSIONS: MetS is correlated with high incidence of CVD among rural elderly female, and only using the NCEP ATP III criteria to define MetS could make the incidence of CVD obvious difference. In order to reduce rural elderly CVD, effective measures to prevent, diagnose, and treat MetS should be enacted in a timely manner, especially among females.

Combined effect of hypertension and hyperuricemia on ischemic stroke in a rural Chinese population.

BACKGROUND: To investigate the combined effect of hypertension and hyperuricemia to the risk of ischemic stroke in a rural Chinese population. METHODS: The cross-sectional study was conducted from 2012 to 2013 in a rural area of China. After exclusion for missing data, we finally included 11,731 participants into analysis. RESULTS: After adjusting for age, current smoking, current drinking, BMI, TG, HDL-C and eGFR, hypertension was significantly associated with ischemic stroke in men (OR: 2.783, 95% CI: 1.793, 4.320) and in women (OR: 4.800, 95% CI: 2.945, 7.822). However, hyperuricemia was significantly associated with ischemic stroke only in women (OR: 1.888, 95% CI: 1.244, 2.864). After full adjustment, participants with both hypertension and hyperuricemia had 8.9 times higher risk than those without them. Finally, the interaction between hypertension and hyperuricemia was statistically significant only in women rather than in men after full adjustment. CONCLUSIONS: This study demonstrated the positive correlations between hypertension, hyperuricemia and ischemic stroke. Our study also demonstrated the joint effect between hypertension and hyperuricemia towards ischemic stroke only in women, not in men.

Hyperhomocysteinemia accompany with metabolic syndrome increase the risk of left ventricular hypertrophy in rural Chinese.

BACKGROUND: To investigate the influence of hyperhomocysteinemia (HHcy) and metabolic syndrome (MetS) on left ventricular hypertrophy (LVH) in residents in rural Northeast China. METHODS: We performed a cross-sectional baseline data analysis of 6837 subjects (mean age: 54 ± 10 years) recruited from a rural area of China. Anthropometric indicators were measured according to standard methods. MetS was defined by the modified ATP III criteria. HHcy was defined according to the WHO standard: an Hcy level > 15 µmol/L representing HHcy. Four groups were defined: non-HHcy & non-MetS, HHcy & non-MetS, MetS & non-HHcy and HHcy & MetS. RESULTS: The left ventricular mass index for height2.7 (LVMH2.7) in both sexes was significantly higher in the HHcy & MetS group than in the non-HHcy & non-MetS group (females: 51.23 ± 16.34 vs. 40.09 ± 10.55 g-2.7, P < 0.001; males: 48.67 ± 12.24 g-2.7 vs. 42.42 ± 11.38 g-2.7, P < 0.001). A similar result was observed in those groups when using the left ventricular mass index (LVMI) for body surface area to define LVH (females: 103.58 ± 31.92 g- 2 vs. 86.63 ± 20.47 g- 2, P < 0.001; males: 106.10 ± 24.69 g- 2 vs. 98.16 ± 23.29 g- 2, P < 0.001). The results of multiple regression analysis indicated that the HHcy & MetS group had a higher risk of LVH than the other three groups (OR: 1.628 for LVMI, P < 0.001, OR: 2.433 for LVMH2.7, P < 0.001). Moreover, subjects in the HHcy & non-MetS group [OR (95% CI): 1.297 (1.058, 1.591) for LVMI, P < 0.05; OR (95% CI): 1.248 (1.044, 1.492) for LVMH2.7, P < 0.05] also had a statistically greater risk of LVH than subjects in the non-HHcy & non-MetS group. The HHcy & non-MetS group was also found to be significantly and independently associated with LVH. CONCLUSION: Hyperhomocysteinemia has an independent effect on LVH. The combined effect of MetS and hyperhomocysteinemia might increase the strength of the abovementioned effects.

Potential impacts of the 2017 American College of Cardiology/American Heart Association high blood pressure guideline on Chinese adults and how to address them.

BACKGROUND: The current analysis was performed to estimate the percentage and number of Chinese adults with hypertension and the percentage and number of Chinese adults recommended to receive pharmacological antihypertensive treatment according to the 2017 American College of Cardiology/American Heart Association (ACC/AHA) guideline compared with the same parameters according to the 2010 Chinese guideline. METHODS: We used 2011 data from the China Health and Nutrition Survey (CHNS). A total of 12,499 Chinese adults aged ≥18 years with complete blood pressure (BP) values were selected for the present analysis. RESULTS: The crude prevalence rates (95% CI) of hypertension according to the definitions from the 2017 ACC/AHA guideline and the 2010 Chinese guideline were 58.0% (57.2 to 58.9%) and 25.4% (24.7 to 26.2%), respectively. Moreover, the percentage of the participants recommended to take antihypertensive medications were 31.5 and 28.8%, respectively. Among adults who took antihypertensive medications, 88.8% had above-goal BP levels compared to 53.3%. Overall, 613.3 million Chinese adults (aged ≥18 years) met the criteria for hypertension according to the 2017 ACC/AHA guideline, and 267.7 million met the criteria according to 2010 Chinese guideline. An additional 28.4 million (2.7%) Chinese adults were recommended to take antihypertensive medication. CONCLUSIONS: The present analysis revealed that the 2017 ACC/AHA hypertension guideline will result in a substantial increase in the percentage and number of Chinese adults defined as having hypertension and a small increase in the percentage of adults who are recommended to take antihypertensive medications compared to the same parameters based on the 2010 Chinese guideline. More intensive management and antihypertensive medications use are suggested to improve the control rate of hypertension among Chinese adults.

Metabolic syndrome associated with the onset of depressive symptoms among women but not men in rural Northeast China.

BACKGROUND: The present study aimed to assess the cumulative incidence of major depressive disorder (MDD) among rural Chinese residents. Furthermore, we intended to estimate whether metabolic syndrome (MetS) was associated with MDD by both cross-sectional and prospective analysis. METHOD: Data of 11,675 residents (46.3% men) was used for cross-sectional analysis. The residents were followed up with median 4.66 years. MDD was diagnosed using the Patient Health Questionnaire-9 (PHQ-9). The data of 2796 individuals without any depressive symptoms was used for prospective analysis. RESULT: With median of 4.66 years follow-up, the cumulative incidence of MDD among rural residents was 3.9%. Women had significantly higher cumulative incidence of MDD than men (5.3% for women and 2.9% for men, P < 0.01). The incidence of MDD was significantly higher among women with MetS (7.3% vs. 3.8%, P < 0.001), hypertriglyceridemia (7.0% vs. 4.5%, P < 0.001) or elevated blood pressure (6.4% vs. 3.4%, P < 0.001) at baseline compared with those without them. There was no incidence difference of MDD among men with or without baseline metabolic disorders. In prospective study, after adjusting possible confounders, baseline MetS was associated with higher incidence of MDD (OR: 1.82, 95%CI: 1.01, 3.27, P = 0.045) in women but not men (OR: 1.84, 95%CI: 0.88, 3.83, P = 0.104). CONCLUSION: Cumulative incidence of MDD in rural China was higher among women than among men. Baseline MetS was associated with higher cumulative incidence of MDD in women but not men. More concern should be put on women with MetS in case of onset depressive symptom in future.

Lower or higher HDL-C levels are associated with cardiovascular events in the general population in rural China.

BACKGROUND: The present study aims to estimate whether high-density lipoprotein cholesterol (HDL-C) is correlated with cardiovascular events (CVEs) and cardiovascular mortality (CVM) in a large sample of the general population in rural areas of China. METHODS: Adult participants (n = 10,266, age = 53.79 ± 10.49 years; 46.5% men) were enrolled from the Northeast China Rural Cardiovascular Health Study (NCRCHS). Laboratory testing, blood pressure, weight, height, and questionnaires about socioeconomic status were collected. RESULTS: In all, 585 nonfatal or fatal CVEs and 212 cardiovascular deaths were documented during a 4.66-year follow-up. Compared to the reference groups (HDL-C between 1.5 and 1.99 mmol/L), either lower or higher levels of HDL-C were correlated with an increased incidence of CVEs but not CVM [hazard ratio (HR) the lowest = 1.369, 95% confidence interval, 1.007-1.861; HR the highest = 1.044, 0.509-2.231]. Elevated CVM was seen in the lowest HDL-C category (1.840; 1.121-3.021). CONCLUSIONS: Lower or higher HDL-C was associated with a higher incidence of CVEs but not CVM in the general population of rural China. Perhaps if an appropriate level of HDL-C is maintained, CVEs can be effectively prevented.