Prevalence of prediabetes and risk of CVD mortality in individuals with prediabetes alone or plus hypertension in Northeast China: insight from a population based cohort study.

BACKGROUND: To evaluate the current prevalence of prediabetes in northeast China, and further determine the association between prediabetes alone or coexistent with hypertension and cardiovascular disease (CVD) mortality. METHODS: In the prospective study, 15,557 participants without diabetes among aged ≥40 years in northeast China, were followed for a median of 5.5 years. Following the American Diabetes Association, prediabetes was defined as fasting plasma glucose (FPG) range of 5.6-6.9 mmol/L or glycated hemoglobin (HbA1c) range of 5.7-6.4% in people without diabetes. RESULTS: The prevalence of prediabetes was 44.3% among population aged ≥40 years in northeast China. Prediabetes alone did not promote risk of CVD mortality. However, when the subgroups were stratified by hypertension, the CVD mortality risk in prediabetes plus hypertension subjects increased significantly compared with population without prediabetes and hypertension. Multivariate-adjusted hazard ratios for CVD mortality in prediabetes subgroups plus hypertension were 2.28 (95% CI: 1.50, 3.47) for those diagnosed by FPG < 5.6 mmol/L & HbA1c 5.7-6.4%, 2.18 (95% CI: 1.53, 3.10) for those diagnosed by FPG 5.6-6.0 mmol/L & HbA1c < 6.5% and 2.35 (95% CI: 1.65, 3.35) for those diagnosed by FPG 6.1-6.9 & HbA1c < 6.5% compared with the reference group. Moreover, the percentage of hypertension in prediabetes subjects was high (60.4%), but the awareness, treatment and control rates were far from satisfactory (45.3, 35.1 and 4.8%, respectively). CONCLUSIONS: The prevalence of prediabetes remains high in northeast China, and the CVD mortality was elevated significantly in prediabetes coexistent with hypertension. Considering the high percentage and low control rate of hypertension in prediabetes, strategies focused on HbA1c screening, FPG lowering and blood pressure management should be emphasized in northeast China.

Neck circumference as an additional predictor of cardiovascular disease mortality: A multi-center prospective population-based study in northeastern China.

BACKGROUND AND AIMS: This study aimed to assess the potential of neck circumference (NC) and neck-to-height ratio (NHR) as predictors of future cardiovascular disease (CVD) mortality in a general population from Northeastern China. METHODS: A multi-center prospective study was conducted in Northeastern China, involving 18, 796 participants. The associations between NC or NHR and the incidence of overall CVD mortality, stroke mortality, and coronary heart disease (CHD) mortality were examined using multivariate Cox regression models. Hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) were calculated. Reclassification analyses were conducted to determine the incremental predictive value of NC or NHR. RESULTS: NC was significantly associated with the risk of CVD mortality, independent of other anthropometric measurements for obesity. Individuals in the highest quartile of NC had a 1.83-fold (95% CI 1.29 to 2.61) and a 2.40-fold (95% CI 1.45 to 4.00) higher risk of overall CVD mortality and CHD mortality, respectively. Larger NC was significantly related to a heightened risk of ischemic stroke mortality, although no such association was observed with hemorrhagic stroke mortality. Furthermore, the risk of overall CVD mortality, stroke mortality, and CHD mortality increased by approximately 1.21 to 1.25 times per 1-SD change in NC. Similar findings were observed for NHR. The percentages of correct classification of overall CVD mortality improved by 12.1% and 16.3% after the addition of NC or NHR into established models, respectively. CONCLUSIONS: NC and NHR might be promising predictors of CVD mortality, with higher values indicating greater risk.

Common carotid artery diameter and the risk of cardiovascular disease mortality: a prospective cohort study in northeast China.

BACKGROUND: The association between the common carotid artery (CCA) diameter and cardiovascular disease (CVD) is recognized, but the precise nature of this link remains elusive. This study aimed to investigate the potential relationship between CCA diameter and the risk of CVD mortality in a large population in northeast China. METHODS: The current study included 5668 participants (mean age 58.9 ± 10.1 years) from a population-based study conducted in rural areas of northeast China between September 2017 and May 2018. Information on death was collected from baseline until July 31, 2022. The CCA inter-adventitial diameter was measured using ultrasound. Cox proportional-hazard models were employed to explore the relationship between the common carotid artery diameter and cardiovascular mortality. RESULTS: At baseline, the mean CCA diameter (mm) of subjects was 7.30 ± 0.99 and increased significantly with age, ranging from 6.65 ± 0.71 among people 40-49 years to 7.99 ± 1.04 among people ≥ 80 years. CCA diameter was significantly larger in males compared to females (7.51 ± 1.03 versus vs. 7.16 ± 0.94; P < 0.001). A total of 185 participants died of CVD during a median follow-up of 4.48 years. CCA diameters were divided into quartiles, and the highest quartile of carotid diameter (≥ 8.06 mm) had a 2.29 (95% confidence interval [CI]: 1.24, 4.22) times higher risk of CVD mortality than the lowest quartile (≤ 6.65 mm) (P < 0.01) in the fully adjusted model. Each increase in the diameter of the common carotid artery (per SD) raised the risk of cardiovascular death by 36% (hazard ratio [HR]: 1.36; 95% CI: 1.18, 1.57). The subgroup analysis results demonstrated that a per SD increase was associated with a 42% increased risk of CVD mortality in participants aged ≥ 64 years in the fully adjusted model (HR: 1.42; 95%CI: 1.21, 1.66). CONCLUSIONS: Our study indicates the possible incremental value of CCA diameter in optimizing the risk stratification of cardiovascular disease and provides essential insights into reducing the burden of cardiovascular disease.

VEGF-B prevents excessive angiogenesis by inhibiting FGF2/FGFR1 pathway.

Although VEGF-B was discovered as a VEGF-A homolog a long time ago, the angiogenic effect of VEGF-B remains poorly understood with limited and diverse findings from different groups. Notwithstanding, drugs that inhibit VEGF-B together with other VEGF family members are being used to treat patients with various neovascular diseases. It is therefore critical to have a better understanding of the angiogenic effect of VEGF-B and the underlying mechanisms. Using comprehensive in vitro and in vivo methods and models, we reveal here for the first time an unexpected and surprising function of VEGF-B as an endogenous inhibitor of angiogenesis by inhibiting the FGF2/FGFR1 pathway when the latter is abundantly expressed. Mechanistically, we unveil that VEGF-B binds to FGFR1, induces FGFR1/VEGFR1 complex formation, and suppresses FGF2-induced Erk activation, and inhibits FGF2-driven angiogenesis and tumor growth. Our work uncovers a previously unrecognized novel function of VEGF-B in tethering the FGF2/FGFR1 pathway. Given the anti-angiogenic nature of VEGF-B under conditions of high FGF2/FGFR1 levels, caution is warranted when modulating VEGF-B activity to treat neovascular diseases.

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.

Critical role of mitogen-inducible gene 6 in restraining endothelial cell permeability to maintain vascular homeostasis.

Although mitogen-inducible gene 6 (MIG6) is highly expressed in vascular endothelial cells, it remains unknown whether MIG6 affects vascular permeability. Here, we show for the first time a critical role of MIG6 in limiting vascular permeability. We unveil that genetic deletion of Mig6 in mice markedly increased VEGFA-induced vascular permeability, and MIG6 knockdown impaired endothelial barrier function. Mechanistically, we reveal that MIG6 inhibits VEGFR2 phosphorylation by binding to the VEGFR2 kinase domain 2, and MIG6 knockdown increases the downstream signaling of VEGFR2 by enhancing phosphorylation of PLCγ1 and eNOS. Moreover, MIG6 knockdown disrupted the balance between RAC1 and RHOA GTPase activation, leading to endothelial cell barrier breakdown and the elevation of vascular permeability. Our findings demonstrate an essential role of MIG6 in maintaining endothelial cell barrier integrity and point to potential therapeutic implications of MIG6 in the treatment of diseases involving vascular permeability. Xing et al. (2022) investigated the critical role of MIG6 in vascular permeability. MIG6 deficiency promotes VEGFA-induced vascular permeability via activation of PLCγ1-Ca2+-eNOS signaling and perturbation of the balance in RAC1/RHOA activation, resulting in endothelial barrier disruption.

Prevalence of isolated diastolic hypertension and the risk of cardiovascular mortality among adults aged 40 years and older in northeast China: a prospective cohort study.

OBJECTIVES: Little is known about the prevalence and impact of isolated diastolic hypertension (IDH) in northeast China. We aimed to investigate the current epidemiology of IDH and to illustrate whether IDH accounted for cardiovascular disease (CVD) mortality. DESIGN: A prospective cohort study. SETTING: A population-based study carried out in northeast China. PARTICIPANTS: We built a community-based study of 18 796 residents aged ≥40 years who were living in northeast China with blood pressure measurements between September 2017 and March 2019. OUTCOME MEASURES: Information on CVD death was obtained from baseline until 31 July 2021. IDH was defined as a diastolic blood pressure ≥90 mm Hg together with systolic blood pressure <140 mm Hg among hypertensive population. RESULTS: The overall prevalence of IDH was 3.9%, which decreased significantly with advancing age (p<0.001) and ranged from 7.2% (95% CI: 6.3% to 8.2%) among participants 40-49 years to 1.5% (95% CI: 1.1% to 2.0%) among participants ≥70 years. Moreover, the IDH prevalence was higher in men than in women (5.2% vs 3.1%, p<0.001). The awareness and treatment rates of IDH were 25.7% and 17.7%, respectively, which were significantly lower than those of patients with non-IDH (50.1% and 21.7%, p=0.009, respectively). During a median follow-up of 3.2 years, 314 subjects died due to CVD (rate 4.84/1000 person-years). IDH and non-IDH were both significantly associated with an increased risk of CVD death (HR: 2.55, 95% CI: 1.35 to 4.82; HR: 2.48, 95% CI: 1.81 to 3.38) when compared with participants with non-hypertension. CONCLUSIONS: IDH was mainly prevalent among young and middle-aged populations, and the awareness and treatment rates in IDH were lower than those in non-IDH hypertension. Additionally, IDH and non-IDH were significantly related to an increased risk of CVD mortality. Early management of IDH is urgently required in northeast China.

Epidemiology of atrial fibrillation and risk of CVD mortality among hypertensive population: A prospective cohort study in Northeast China.

Background: Determining risk factors of cardiovascular disease (CVD)-related mortality and evaluating their influence are important for effectively reducing corresponding mortality. However, few research findings have estimated the relationship between atrial fibrillation (AF) and CVD-related mortality among hypertension individuals. Objective: The objective of this study was to investigate the epidemiology of AF in a hypertension population and determine the relationship between AF and CVD-related mortality. Methods: Using a multistage, stratified, and cluster random sampling method, the prospective cohort study with a median follow-up of 3.51 years enrolled 10,678 hypertensive participants at baseline. The prevalence, awareness, and anticoagulation data of AF in this focal population were carefully assessed. Stepwise logistic regression and Cox regression analysis were respectively performed to evaluate the determinants of AF and the association between AF and CVD-related mortality. Results: The overall prevalence of AF was 1.3% (95% CI, 1.1%-1.6%) in the hypertensive population, and it was higher in men than in women (1.8% vs. 1.0%, respectively; p=0.001). The awareness of AF was 53.1%, and the rate of oral anticoagulant (OAC) therapy was only 4.2%, although all AF participants should have required according to the European Society of Cardiology guidelines. The determinants of AF included elder, male, and history of coronary heart disease in the hypertensive population. Besides, compared with individuals without AF, the risk of CVD-related mortality significantly increased in the hypertensive population with AF (HR 3.37, 95% CI 2.10-5.40). Conclusion: Our results indicated a huge burden of AF and underuse of OAC therapy for them in a community-based hypertensive population. Considering that most of the risk factors of AF were unmodifiable in hypertensive individuals, as well as its high risk of mortality, long-term interventions including AF education, timely screening, and widespread use of OACs should be emphasized in the focal populations.

An Efficient UPLC-MS/MS Method Established to Detect Relugolix Concentration in Rat Plasma.

Relugolix, a gonadotropin-releasing hormone (GnRH) receptor antagonist, has been well studied in the treatment of endometriosis symptomatic. It is mainly metabolized by the CYP3A subfamily of P450 enzymes, while minorly metabolized by CYP2C8. Daidzein in different dose groups exhibited a certain induction on the mRNA expression level of CYP3A4 and resulted in the potent induction of CYP3A4. However, it is still unknown whether daidzein and relugolix interact. We developed an effective ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method to study the effect of daidzein on the pharmacokinetics of relugolix in rats after oral administration of 12 mg/kg relugolix in a single or mixed of 50 mg/kg daidzein. The results showed that the method had respectable linearity (r 2 > 0.999) on the scale of 0.7-1000 ng/mL. The intra-day precision was between 3.0% and 8.4% in this assay, and the inter-day was between 4.0% and 11.7%. The intra-day accuracy was from -4.3% to 6.1%, and the inter-day was 2.9% to 12.1%. Another three key indicators, including the stability, the recovery rate of extraction and the new technique's matrix effect, were perfectly in accord with the test verification rule in the biological medium by the United States Food and Drug Administration. Meanwhile, treatment with daidzein led to a decrease in Cmax and AUC0-t of relugolix by about 15.56% and 21.36%, respectively. Although there was no statistical difference in pharmacokinetic parameters, it reflected the induction trend of daidzein on relugolix metabolism for food-drug interaction. It would provide reference and improvement value for subsequent experiments.

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.

Study on Microwave Absorption Performance Enhancement of Metamaterial/Honeycomb Sandwich Composites in the Low Frequency Band.

With the rapid development of electronic technology and modern radar detection system, there is increasingly urgent demand for microwave absorbing composites working efficiently in the low frequency range (e.g., 1−2 GHz). In this work, a type of metamaterial/honeycomb sandwich composite (MHSC) was proposed and fabricated, which exhibited a light weight structure and excellent wave-absorbing performance in the low frequency band. The relationship between the wave-absorbing properties and the design parameters of the composite, such as the thickness of the wave-transmitting skin, the thickness and dielectric properties of the wave-absorbing honeycomb, was systematically investigated. The electromagnetic coupling interference between the honeycomb absorber and metamaterial resonator proved to be a crucial factor that affects synergistic wave-absorbing performance in the low-frequency band. Under the rational design, the incorporation of subwavelength-sized phase-gradient metamaterial units in the composite can significantly improve low-frequency wave-absorbing performance for greater than 5 dB (an increment larger than 100%); and the obtained MHSC exhibits averaged reflectivity (Ra) less than −10 dB in the low frequency band of 1−2 GHz as well as outstanding performance (Ra < −14.6 dB) over an extremely wide frequency range (1−18 GHz). The MHSC reported in this study could be a promising candidate for the key material in high-performance radar stealth and other related applications.

Incremental significance and sex discrepancies of neck circumference on the odds of ischaemic stroke: a multistage, population-based, cross-sectional study from Northeast China.

OBJECTIVES: Accumulated evidence suggests that neck circumference (NC) is associated with cardiometabolic risk factors. However, limited studies are available regarding the association between NC or height normalised NC (neck-to-height ratio (NHR)) and risk of ischaemic stroke (IS) in the Chinese population. Therefore, we aimed at examining the associations between NC or NHR and odds of IS and exploring the discrepancies between men and women. DESIGN: A multistage cluster cross-sectional study. SETTING: A population-based study carried out in Northeast China. METHODS: A cross-sectional study was undertaken in Northeast China between September 2017 and March 2019, involving 7236 men and 11 352 women, respectively. The median age of participants was 60.30 years, ranging from 40 to 97 years. The associations between NC or NHR and odds of IS were calculated using multiple logistic regression models. Dose-response relationships were depicted using restricted cubic spline functions. Reclassification analyses were carried out to determine the incremental significance of NC or NHR on the odds of IS. RESULTS: In women, NC and NHR were significantly associated with the odds of IS, independent of traditional risk factors and other anthropometric parameters for obesity. The highest quartile of NC and NHR had a 1.60 (95% CI 1.16 to 2.22)-and 1.72 (95% CI 1.23 to 2.41) times higher odds of IS compared with the lowest quartile. Furthermore, the odds of IS increased by 1.10 (95% CI 1.01 to 1.20) and 1.12 (95% CI 1.02 to 1.22) times per 1 SD increase in NC and NHR, respectively. Reclassification analyses showed that the proportion of correct classification increased by 11.5% (95% CI 2.2% to 20.7%) and 22.8% (95% CI 13.5% to 32.0%) after the addition of NC or NHR into established models, respectively. However, the findings could not be replicated in men. CONCLUSION: NC and NHR might be promising independent indicators for women IS. Their incremental value in the risk stratification of IS enables the individualised prevention of IS in women.

Sex-specific prediction value of common carotid artery diameter for stroke risk in a hypertensive population: a cross-sectional study.

BACKGROUND: The importance of sex as a risk factor for stroke has been established. This study aimed to assess sex-related disparities in carotid artery diameter and stroke in a hypertensive population. METHODS: The cross-sectional survey was conducted in rural areas of northeast China. A multistage cluster sampling method was employed to select a representative population. The study comprised 3,245 individuals with hypertension. The common carotid artery (CCA) interadventitial diameter was measured by ultrasound. A linear model of restricted cubic spline function was used to characterize the concentration-response (C-R) relationship between CCA diameter and stroke. RESULTS: The overall prevalence of stroke was 8.9% among hypertensive individuals, with a higher rate in men than in women (10.8% vs. 7.6%). When the women's CCA diameters were divided into quartiles, the top quartile (>8.10 mm) had a 2.49 (95% CI: 1.36-4.56) times greater risk of stroke compared to the bottom quartile (≤6.80 mm) after adjustment was made for other variables. The C-R relationship further confirmed a positive association between CCA diameter and stroke prevalence in women. Moreover, a category-free net reclassification index (0.325; 95% CI: 0.173-0.476; P<0.001) and an integrated discrimination index (0.008; 95% CI: 0.004-0.012, P<0.001) showed improvement in predicting the probability of stroke from CCA diameter. However, no significant relationship between CCA diameter and prevalence of stroke was found in men. CONCLUSIONS: The risk of stroke increased proportionally with the enlargement of the CCA diameter in women, supporting the sex-specific value of CCA diameter in optimizing the risk stratification of stroke.

Sex difference in the correlation between carotid artery diameter and prevalence of stroke: Insights from a Chinese population.

BACKGROUND: The atherosclerotic process can cause compensatory enlargement of artery diameter. However, the association between common carotid artery (CCA) diameter and stroke remains unclear. METHODS: This cross-sectional study included 5668 participants ≥40 years of age residing in rural northeast China, in whom the inter-adventitial diameter of CCA was measured. The association between CCA diameter and stroke prevalence was explored using multivariate logistic regression and concentration-response relationship in females and males, respectively. RESULTS: CCA diameter (mm) was greater in stroke than in non-stroke populations in both males (7.73 versus [vs.] 7.49; P < 0.05) and females (7.69 vs. 7.13; P < 0.001). Among males, when dividing CCA diameters into quartiles, the second quartile (6.86-7.5 mm) had a 1.64 times higher risk for stroke than the bottom quartile (≤6.85 mm) (P < 0.05) in the adjusted model. In females, the top quartile (>7.95 mm) had a 2.08 (1.07-4.04) times higher risk than the bottom quartile (≤6.50 mm) (P < 0.01) (overall trend 1.19 [1.00-1.43]). Moreover, dose-response relationship confirmed correlations between CCA diameter and stroke in females (P < 0.05). The net reclassification index (NRI) and integrated discrimination index (IDI) confirmed the incremental value of CCA diameter in predicting probability of stroke in females (NRI 0.353 [95% confidence interval (CI) 0.198-0.497], P < 0.001; IDI 0.004 [95% CI 0.001-0.006], P < 0.01) and males (NRI 0.201 [95% CI 0.158-0.241], P < 0.001; IDI 0.005 [95% CI 0.001-0.009], P < 0.01). CONCLUSIONS: This study highlighted the incremental value of CCA diameter in optimizing risk classification and stroke prevention in a Chinese population.

Epidemiological features of hypertension among ischemic survivors in Northeast China: insights from a population-based study, 2017-2019.

BACKGROUND: Hypertension remains the major modifiable risk factor of stroke recurrence. The study aimed to determine the up-to-date epidemiological features of hypertension among the survivors of ischemic stroke. METHODS: Our cross-sectional study included 18,796 adults aged ≥40 years and residing in northeast China. Ischemic stroke was diagnosed according to the World Health Organization's criteria, which requires the clinical record, computed tomography (CT) and/or magnetic resonance imaging (MRI) during the hospital stay. Hypertension was defined according to the Chinese hypertension guidelines (mean SBP ≥140 mmHg and/or mean DBP ≥90 mmHg, and/or self-reported use of anti-hypertensive medication in the past 2 weeks). RESULTS: Of the 986 survivors of ischemic stroke, 819 (83.1%) were identified with hypertension (535 were pre-stroke hypertension and 284 were post-stroke hypertension). Among hypertensive patients, the awareness and treatment rates were 76.8 and 66.7% respectively. Only 11.0% achieved an appropriate blood pressure (< 140 mmHg and < 90 mmHg) among those who took hypertensive medications. 16.8% of treated hypertensive patients received combination therapy, and calcium channel blockers were the most frequently used anti-hypertensive medication as monotherapy. The mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) of the stroke population was 155.3 ± 22.9 mmHg and 89.2 ± 12.3 mmHg. Both SBP and DBP were higher in rural patients than in urban patients (158.5 ± 23.8 mmHg vs. 146.4 ± 17.5 mmHg and 90.3 ± 12.9 mmHg vs. 85.9 ± 10.1 mmHg, respectively; p < 0.001). The rates of stage 2 and above hypertension in the ischemic stroke population were 32.5 and 18.7%, and was significantly higher in rural areas than in urban areas. CONCLUSIONS: The prevalence of poorly-controlled hypertension and the high rates of blood pressures at stages 2 and above in patients with prior ischemic stroke demonstrated an alarming situation in northeast China.

Mitogen-Inducible Gene 6 Inhibits Angiogenesis by Binding to SHC1 and Suppressing Its Phosphorylation.

The mitogen-inducible gene 6 (MIG6) is an adaptor protein widely expressed in vascular endothelial cells. However, it remains unknown thus far whether it plays a role in angiogenesis. Here, using comprehensive in vitro and in vivo model systems, we unveil a potent anti-angiogenic effect of MIG6 in retinal development and neovascularization and the underlying molecular and cellular mechanisms. Loss of function assays using genetic deletion of Mig6 or siRNA knockdown increased angiogenesis in vivo and in vitro, while MIG6 overexpression suppressed pathological angiogenesis. Moreover, we identified the cellular target of MIG6 by revealing its direct inhibitory effect on vascular endothelial cells (ECs). Mechanistically, we found that the anti-angiogenic effect of MIG6 is fulfilled by binding to SHC1 and inhibiting its phosphorylation. Indeed, SHC1 knockdown markedly diminished the effect of MIG6 on ECs. Thus, our findings show that MIG6 is a potent endogenous inhibitor of angiogenesis that may have therapeutic value in anti-angiogenic therapy.

High Burden of Carotid Atherosclerosis in Rural Northeast China: A Population-Based Study.

Objective: Carotid atherosclerosis is a known marker of increased cardiovascular risk. We aimed to assess the current epidemiology of carotid atherosclerosis, carotid plaque and related risk factors in rural northeast China. Methods: The population-based, cross-sectional study was conducted in 5,838 adults aged ≥40 years residing in rural northeast China in 2017-2018. A multi-stage cluster sampling method was used to select the representative sample. Carotid atherosclerosis was defined as carotid intima-media thickness (CIMT) ≥1.0 mm or presence of plaque. Results: The mean CIMT was 0.72 ± 0.13 mm and increased with age in this population. Among 2,457 individuals with carotid atherosclerosis, 2,333 were diagnosed with carotid plaque, and 210 individuals were moderate or severe carotid stenosis. Crude prevalence of carotid atherosclerosis and plaque were 42.1 and 40.0%, significantly higher in men than in women (p < 0.001). The age-standardized prevalence of carotid atherosclerosis and carotid plaque were 33.1 and 31.5%, respectively. Advancing age, men, hypertension, diabetes, current smoking, ever-smoking and lack of exercise were risk factors for carotid atherosclerosis. Hypertension (69.1%), dyslipidemia (26.0%) and diabetes (16.1%) were highly prevalent in participants with carotid atherosclerosis. However, the control rates of those comorbidities were frustratingly low (4.7, 8.2, and 14.2%, respectively). Conclusions: The high prevalence of carotid atherosclerosis, carotid plaque, carotid stenosis and uncontrolled risk factors indicated the high burden of cardiovascular disease in rural northeast China, particularly in men. Strategies of prevention and management of atherosclerosis and related risk factors were urgently needed in rural northeast China.

Trajectories of body mass index and risk of incident hypertension among a normal body mass index population: A prospective cohort study.

It is unclear whether there are different body mass index (BMI) trajectories among a population with normal BMI levels, and the association between BMI patterns and incident hypertension is not well characterized. This prospective cohort study includes surveys conducted at baseline and three follow-ups. 3939 participants who are free of hypertension at baseline or first two follow-ups were enrolled. At baseline, the age of participants ranged from 35 to 82 years and the mean age was 45.9 years. The BMI trajectories were identified using latent mixture modeling with data from the baseline and first two follow-ups. The effects of different BMI trajectories on the development of hypertension were analyzed using a Cox proportional hazard model. Four distinct BMI trajectories were identified over the study period (2004-2010): normal-stable (n = 1456), normal-increasing (n = 2159), normal-fluctuated (n = 166), and normal-sharp-increasing (n = 158). Relative to the normal-stable BMI group, the hazard ratios (HRs) and 95% confidence intervals (CIs) after adjustment for confounding factors of the normal-increasing, normal-fluctuated, and normal-sharp-increasing groups were 1.244 (1.103-1.402), 1.331 (1.008-1.756), and 1.641 (1.257-2.142), respectively. Additionally, subgroup analysis showed that the normal-fluctuated BMI trajectory was associated with a significantly higher risk of hypertension only in women (HR = 1.362; 95% CI = 1.151-1.611). The BMI trajectories were significant predictors of hypertension incidence, and increasing BMI trajectories within the currently designated normal range were associated with an increased hypertension risk, especially in women.

Complementary value of ECG and echocardiographic left ventricular hypertrophy for prediction of adverse outcomes in the general population.

OBJECTIVE: To investigate whether ECG left ventricular hypertrophy (ECG-LVH) has prognostic value independent of echocardiography LVH (Echo-LVH). METHODS: Participants (N = 9744, mean age, 53.81 ±â€Š10.49 years and 45.5% male) from the Northeast China Rural Cardiovascular Health Study were included. Associations between Echo-LVH (sex-specific left ventricular mass normalized to BSA) and ECG-LVH (diagnosed using the Cornell-voltage duration product) and adverse outcomes were evaluated using Cox regression. The value of ECG-LVH for predicting adverse events was evaluated by reclassification and discrimination analyses. RESULTS: Median follow-up was 4.65 years; 563 participants developed incident stroke or coronary heart disease (CHD) and 402 died. Compared with participants without either condition, those with both Echo-LVH and ECG-LVH had a significantly increased risk of incident stroke or CHD (hazard ratio, 2.42; 95% confidence interval, 1.82-3.22) and mortality (2.58; 1.85-3.60). ECG-LVH remained an independent risk factors for both outcomes when ECG-LVH and Echo-LVH were included in the model as separate variables [incident stroke or CHD (1.43; 1.14-1.79); mortality (1.41; 1.08-1.84)]. Reclassification and discrimination analyses indicated ECG-LVH addition could improve the conventional model for predicting adverse outcomes within 4 years. These relationships persisted after excluding participants with cardiovascular disease history or taking antihypertension drugs or upon applying other ECG-LVH and Echo-LVH diagnostic criteria. CONCLUSION: Our study provides strong evidence that ECG-LVH is associated with adverse outcomes, independent of Echo-LVH. Clinically, ECG-LVH could be considered as a consequential factor, especially in those with Echo-LVH. These findings have potential clinical relevance for risk stratification.