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Abstract Background The 2018/2023 ESC/ESH Guidelines underlined a gap how baseline cardiovascular disease (CVD) risk predicted blood pressure (BP) lowering benefits. Further, 2017 ACC/AHA Guideline and 2021 WHO Guideline recommended implementation studies about intensive BP control. Now, to bridge these guideline gaps, we conducted a post hoc analysis to validate whether the baseline CVD risk influences the effectiveness of the intensive BP control strategy, which was designed by China Rural Hypertension Control Project (CRHCP). Methods This is a post hoc analysis of CRHCP, among which participants were enrolled except those having CVD history, over 80 years old, or missing data. Subjects were stratified into quartiles by baseline estimated CVD risk and then grouped into intervention and usual care group according to original assignment in CRHCP. Participants in the intervention group received an integrated, multi-faceted treatment strategy, executed by trained non-physician community health-care providers, aiming to achieve a BP target of

Abstract Background Metabolic syndrome (MetS) includes a group of metabolic irregularities, including insulin resistance (IR), atherogenic dyslipidemia, central obesity, and hypertension. Consistent evidence supports IR and ongoing low-grade inflammation as the main contributors to MetS pathogenesis. However, the association between the triglyceride-glucose (TyG) index and mortality in people with MetS remains uncertain. The objective of this study was to examine the correlation between the baseline TyG index and all-cause and cardiovascular (CV) mortality in rural Northeast Chinese individuals with MetS. Methods For the Northeast China Rural Cardiovascular Health Study, 3918 participants (mean age, 55 ± 10; 62.4% women) with MetS at baseline were enrolled in 2012–2013 and followed up from 2015 to 2017. The TyG index was calculated using the equation TyG index = ln [fasting TG (mg/dL) × fasting glucose (mg/dL)/2] and subdivided into tertiles [Q1(

Abstract Background Diabetic vascular remodeling is the most important pathological basis of diabetic cardiovascular complications. The accumulation of advanced glycation end products (AGEs) caused by elevated blood glucose promotes the proliferation and migration of vascular smooth muscle cells (VSMCs), leading to arterial wall thickening and ultimately vascular remodeling. Therefore, the excessive proliferation and migration of VSMCs is considered as an important therapeutic target for vascular remodeling in diabetes mellitus. However, due to the lack of breakthrough in experiments, there is currently no effective treatment for the excessive proliferation and migration of VSMCs in diabetic patients. Bcl-2-associated athanogene 3 (BAG3) protein is a multifunctional protein highly expressed in skeletal muscle and myocardium. Previous research has confirmed that BAG3 can not only regulate cell survival and apoptosis, but also affect cell proliferation and migration. Since the excessive proliferation and migration of VSMCs is an important pathogenesis of vascular remodeling in diabetes, the role of BAG3 in the excessive proliferation and migration of VSMCs and its molecular mechanism deserve further investigation. Methods In this study, BAG3 gene was manipulated in smooth muscle to acquire SM22αCre; BAG3 FL/FL mice and streptozotocin (STZ) was used to simulate diabetes. Expression of proteins and aortic thickness of mice were detected by immunofluorescence, ultrasound and hematoxylin-eosin (HE) staining. Using human aorta smooth muscle cell line (HASMC), cell viability was measured by CCK-8 and proliferation was measured by colony formation experiment. Migration was detected by transwell, scratch experiments and Phalloidin staining. Western Blot was used to detect protein expression and Co-Immunoprecipitation (Co-IP) was used to detect protein interaction. Results In diabetic vascular remodeling, AGEs could promote the interaction between BAG3 and signal transducer and activator of transcription 3 (STAT3), leading to the enhanced interaction between STAT3 and Janus kinase 2 (JAK2) and reduced interaction between STAT3 and extracellular signal-regulated kinase 1/2 (ERK1/2), resulting in accumulated p-STAT3(705) and reduced p-STAT3(727). Subsequently, the expression of matrix metallopeptidase 2 (MMP2) is upregulated, thus promoting the migration of VSMCs. Conclusions BAG3 upregulates the expression of MMP2 by increasing p-STAT3(705) and decreasing p-STAT3(727) levels, thereby promoting vascular remodeling in diabetes. This provides a new orientation for the prevention and treatment of diabetic vascular remodeling.

Protein phosphorylation is an important link in a variety of signaling pathways, and most of the important life processes in cells involve protein phosphorylation. Based on the amino acid residues of phosphorylated proteins, protein kinases can be categorized into the following families: serine/threonine protein kinases, tyrosine-specific protein kinases, histidine-specific protein kinases, tryptophan kinases, and aspartate/glutamyl protein kinases. Of all the protein kinases, most are serine/threonine kinases, where serine/threonine protein kinases are protein kinases that catalyze the phosphorylation of serine or threonine residues on target proteins using ATP as a phosphate donor. The current socially accepted classification of serine/threonine kinases is to divide them into seven major groups: protein kinase A, G, C (AGC), CMGC, Calmodulin-dependent protein kinase (CAMK), Casein kinase (CK1), STE, Tyrosine kinase (TKL) and others. After decades of research, a preliminary understanding of the specific classification and respective functions of serine/threonine kinases has entered a new period of exploration. In this paper, we review the literature of the previous years and introduce the specific signaling pathways and related therapeutic modalities played by each of the small protein kinases in the serine/threonine protein kinase family, respectively, in some common cardiovascular system diseases such as heart failure, myocardial infarction, ischemia-reperfusion injury, and diabetic cardiomyopathy. To a certain extent, the current research results, including molecular mechanisms and therapeutic methods, are fully summarized and a systematic report is made for the prevention and treatment of cardiovascular diseases in the future.

Cardiovascular diseases (CVDs) have a complex pathogenesis and pose a major threat to human health. Cardiomyocytes have a low regenerative capacity, and their death is a key factor in the morbidity and mortality of many CVDs. Cardiomyocyte death can be regulated by specific signaling pathways known as programmed cell death (PCD), including apoptosis, necroptosis, autophagy, pyroptosis, and ferroptosis, etc. Abnormalities in PCD can lead to the development of a variety of cardiovascular diseases, and there are also molecular-level interconnections between different PCD pathways under the same cardiovascular disease model. Currently, the link between programmed cell death in cardiomyocytes and cardiovascular disease is not fully understood. This review describes the molecular mechanisms of programmed death and the impact of cardiomyocyte death on cardiovascular disease development. Emphasis is placed on a summary of drugs and potential therapeutic approaches that can be used to treat cardiovascular disease by targeting and blocking programmed cell death in cardiomyocytes.

Summary: Background: The isolated systolic hypertension (ISH) is of high prevalence, with a relatively poor prognosis. However, there is still no direct evidence to demonstrate the benefits of intensive blood pressure (BP) control among these patients. We aimed to evaluate intensive BP control with the target of 0.05 for all interaction test). The incidences of symptomatic hypotension, syncope injurious falls and renal outcomes did not differ between the two groups, even though hypotension was increased in intervention group (RR:1.71; 95% CI: 1.28–2.28; P

Primary aldosteronism (PA), often due to aldosteronoma, commonly causes secondary hypertension and typically requires surgery. We present a case of an elderly man with longstanding hypertension, complicated by cerebral hemorrhage and myocardial infarction. Enhanced CT imaging identified a right-sided aldosteronoma and left adrenal gland fullness. Combined with upright supine aldosterone ratio, captopril challenge test, bilateral adrenal venous sampling, and CYP11B1/CYP11B2 fusion gene testing, the diagnosis of PA was confirmed. Despite the absence of surgical intervention in this patient, pharmacotherapy effectively managed hypertension and enhanced cardiac function, thereby underscoring the advantageous utilization of aldosterone antagonists in non-surgical candidates diagnosed with PA.

Abstract Electrocardiography (ECG) is an accessible diagnostic tool for screening patients with hypertensive left ventricular hypertrophy (LVH). However, its diagnostic sensitivity is low, with a high probability of false‐negatives. Thus, this study aimed to establish a clinically useful nomogram to supplement the assessment of LVH in patients with hypertension and without ECG‐LVH based on Cornell product criteria (low‐risk hypertensive population). A cross‐sectional dataset was used for model construction and divided into development (n = 2906) and verification (n = 1447) datasets. A multivariable logistic regression risk model and nomogram were developed after screening for risk factors. Of the 4353 low‐risk hypertensive patients, 673 (15.4%) had LVH diagnosed by echocardiography (Echo‐LVH). Eleven risk factors were identified: hypertension awareness, duration of hypertension, age, sex, high waist‐hip ratio, education level, tea consumption, hypochloremia, and other ECG‐LVH diagnostic criteria (including Sokolow–Lyon, Sokolow–Lyon products, and Peguero–Lo Presti). For the development and validation datasets, the areas under the curve were 0.724 (sensitivity = 0.606) and 0.700 (sensitivity = 0.663), respectively. After including blood pressure, the areas under the curve were 0.735 (sensitivity = 0.734) and 0.716 (sensitivity = 0.718), respectively. This novel nomogram had a good predictive ability and may be used to assess the Echo‐LVH risk in patients with hypertension and without ECG‐LVH based on Cornell product criteria.

AimsThe body roundness index (BRI) has good predictive ability for both body fat and visceral adipose tissue. Longitudinal BRI trajectories can reveal the potential dynamic patterns of change over time. This prospective study assessed potential associations between BRI trajectories and incident cardiovascular disease (CVD) in rural regions of Northeast China.MethodsIn total, 13,209 participants (mean age: 49.0 ± 10.3 years, 6,856 [51.9%] male) were enrolled with three repeated times of BRI measurements at baseline (2004–2006), 2008, and 2010, and followed up until 2017 in this prospective study. Using latent mixture model, the BRI trajectories were determined based on the data from baseline, 2008 and 2010. Composite CVD events (myocardial infarction, stroke, and CVD death combined) was the primary endpoint. Cox proportional-hazards models were used to analyze the longitudinal associations between BRI trajectories and incident CVD.ResultsThree distinct BRI trajectories were identified: high-stable (n = 538), moderate-stable (n = 1,542), and low-stable (n = 11,129). In total, 1,382 CVD events were recorded during follow-up. After adjustment for confounders, the moderate-stable and high-stable BRI groups had a higher CVD risk than did the low-stable BRI group, and the HR (95%CI) were 1.346 (1.154, 1.571) and 1.751 (1.398, 2.194), respectively. Similar associations were observed between the trajectories of BRI and the risk of stroke and CVD death. The high-stable group was also significantly and independently associated with CVD, myocardial infarction, stroke, and CVD death in participants aged

Abstract 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.

Abstract Background Most adult patients with depression complain about sleep symptoms, including insufficient and excessive sleep. However, previous studies investigating the impact of sleep duration on depression have yielded conflicting results. Therefore, this study aimed to analyse the link between depression and sleep duration, daytime napping, and snoring among rural Chinese adults. Methods A cross-sectional study was conducted with 9104 individuals. Interviews were conducted with the participants regarding their sleep patterns and their daytime napping routines. The individuals were then assessed for depression using the Patient Health Questionnaire-9. The risk of depression was assessed using a multifactor binary logistic regression analysis. A generalized additive model was used to evaluate the nonlinear relationship between depression and sleep duration/nap time. Additionally, subgroup analysis was conducted to investigate the correlation between sleep duration, daytime napping, snoring, and depression. Results Less than 6 h or more than 8 h of nighttime sleep, daytime napping for more than 1 h, and snoring were all significantly associated with an increased risk of depression. A U-shaped relationship was found between the duration of nighttime sleep and depression. In addition, we found that the nighttime duration of sleep, daytime naps, and snoring had a significant combined effect on the risk of depression. The subgroup analysis further revealed that lack of sleep at night significantly increased the risk of depression in all subgroups. However, snoring and excessive nighttime sleep and napping were only associated with the risk of depression in some subgroups. Conclusions Lack of nighttime sleep (short sleep duration), excessive sleep, and napping for more than one hour during the day were associated with a high risk of depression and had a combined effect with snoring.

Abstract Background Accurately predicting the risk of atherosclerotic cardiovascular disease (ASCVD) is crucial for implementing individualized prevention strategies and improving patient outcomes. Our objective is to develop machine learning (ML)-based models for predicting ASCVD risk in a prospective Chinese population and compare their performance with conventional regression models. Methods A hybrid dataset consisting of 551 features was used, including 98 demographic, behavioral, and psychological features, 444 Electrocardiograph (ECG) features, and 9 Echocardiography (Echo) features. Seven machine learning (ML)-based models were trained, validated, and tested after selecting the 30 most informative features. We compared the discrimination, calibration, net benefit, and net reclassification improvement (NRI) of the ML models with those of conventional ASCVD risk calculators, such as the Pooled Cohort Equations (PCE) and Prediction for ASCVD Risk in China (China-PAR). Results The study included 9,609 participants (mean age 53.4 ± 10.4 years, 53.7% female), and during a median follow-up of 4.7 years, 431 (4.5%) participants developed ASCVD. In the testing set, the final ML-based ANN model outperformed PCE, China-PAR, recalibrated PCE, and recalibrated China-PAR in predicting ASCVD. This was demonstrated by the model's higher area under the curve (AUC) of 0.800, compared to 0.777, 0.780, 0.779, and 0.779 for the other models, respectively. Additionally, the model had a lower Hosmer–Lemeshow χ2 of 9.1, compared to 37.3, 67.6, 126.6, and 18.6 for the other models. The net benefit at a threshold of 5% was also higher for the ML-based ANN model at 0.017, compared to 0.016, 0.013, 0.017, and 0.016 for the other models, respectively. Furthermore, the NRI was 0.089 for the ML-based ANN model, while it was 0.355, 0.098, and 0.088 for PCE, China-PAR, and recalibrated PCE, respectively. Conclusions Compared to conventional regression ASCVD risk calculators, such as PCE and China-PAR, the ANN prediction model may help optimize identification of individuals at heightened cardiovascular risk by flexibly incorporating a wider range of potential predictors. The findings may help guide clinical decision-making and ultimately contribute to ASCVD prevention and management.

Abstract We aimed to compare the relationship between hypertension and obesity-related anthropometric indices (waist circumference [WC], waist-height ratio, waist-hip ratio [WHR], and body mass index; unconventional: new body shape index [ABSI] and body roundness index [BRI]) to identify best predictors of new-onset hypertension. The study included 4123 adult participants (2377 women). Hazard ratios (HRs) and 95% confidence intervals (CIs) were determined using a Cox regression model to estimate the risk of new-onset hypertension with respect to each obesity index. In addition, we assessed the predictive value of each obesity index for new-onset hypertension using area under the receiver operating characteristic curve (AUC) after adjusting for common risk factors. During the median follow-up of 2.59 years, 818 (19.8%) new hypertension cases were diagnosed. The non-traditional obesity indices BRI and ABSI had predictive value for new-onset hypertension; however, they were not better than the traditional indexes. WHR was the best predictor of new-onset hypertension in women aged ≤ 60 and > 60 years, with HRs of 2.38 and 2.51 and AUCs of 0.793 and 0.716. However, WHR (HR 2.28, AUC = 0.759) and WC (HR 3.24, AUC = 0.788) were the best indexes for predicting new-onset hypertension in men aged ≤ 60 and > 60 years, respectively.

Abstract Background Endothelial injury caused by Type 2 diabetes mellitus (T2DM) is considered as a mainstay in the pathophysiology of diabetic vascular complications (DVCs). However, the molecular mechanism of T2DM-induced endothelial injury remains largely unknown. Here, we found that endothelial WW domain-containing E3 ubiquitin protein ligase 2 (WWP2) act as a novel regulator for T2DM-induced vascular endothelial injury through modulating ubiquitination and degradation of DEAD-box helicase 3 X-linked (DDX3X). Methods Single-cell transcriptome analysis was used to evaluate WWP2 expression in vascular endothelial cells of T2DM patients and healthy controls. Endothelial-specific Wwp2 knockout mice were used to investigate the effect of WWP2 on T2DM-induced vascular endothelial injury. In vitro loss- and gain-of-function studies were performed to assess the function of WWP2 on cell proliferation and apoptosis of human umbilical vein endothelial cells. The substrate protein of WWP2 was verified using mass spectrometry, coimmunoprecipitation assays and immunofluorescence assays. The mechanism of WWP2 regulation on substrate protein was investigated by pulse-chase assay and ubiquitination assay. Results The expression of WWP2 was significantly down-regulated in vascular endothelial cells during T2DM. Endothelial-specific Wwp2 knockout in mice significantly aggravated T2DM-induced vascular endothelial injury and vascular remodeling after endothelial injury. Our in vitro experiments showed that WWP2 protected against endothelial injury by promoting cell proliferation and inhibiting apoptosis in ECs. Mechanically, we found that WWP2 is down-regulated in high glucose and palmitic acid (HG/PA)-induced ECs due to c-Jun N-terminal kinase (JNK) activation, and uncovered that WWP2 suppresses HG/PA-induced endothelial injury by catalyzing K63-linked polyubiquitination of DDX3X and targeting it for proteasomal degradation. Conclusion Our studies revealed the key role of endothelial WWP2 and the fundamental importance of the JNK-WWP2-DDX3X regulatory axis in T2DM-induced vascular endothelial injury, suggesting that WWP2 may serve as a new therapeutic target for DVCs.

Abstract Identifying risk factors for atrial fibrillation (AF) and evaluating their impact are essential to avoid the occurrence of adverse events. However, few studies to date have explored the prevalence, risk factors, and prognosis of AF in hypertensive patients. The objective of this study was to investigate the epidemiology of AF in a hypertensive population and determine the relationship between AF and all‐cause mortality. At baseline, a total of 8541 Chinese patients with hypertension were enrolled from the Northeast Rural Cardiovascular Health Study. A logistic regression model was established to assess the relationship between blood pressure and AF, and Kaplan–Meier survival curve analysis and multivariate Cox regression were used to explore the relationship between AF and all‐cause mortality. Meanwhile, subgroup analyses illustrated the robustness of results. This study found that the overall prevalence rate of AF was 1.4% in its Chinese hypertensive population. After adjusting for the confounding factors, every standard deviation increase in diastolic blood pressure (DBP) was associated with a 37% increase in the prevalence of AF (95% confidence interval: 1.152–1.627, p

AbstractBackground Hypertension has become increasingly prevalent in Chinese children and adolescents in recent decades, which affects growth and development of children, leads to cognitive decline and multiple target organ damage. Here, we assessed the impact of different body mass index (BMI) trajectories on the occurrence of hypertension in children and adolescents using a cohort study in Northeast China.Materials and methods Children and adolescents aged 5–18 years was extracted for physical examination in Fuxin City, Liaoning Province, China during the 2009–2015 period. A latent category growth mixed model (LCGMM) was used to classify BMI changes and analyze the effect of different BMI trajectories on the risk of occurrence of hypertension in these participants within 5 years.Results All participates were divided into five BMI trajectories by LCGMM method: slow increasing group (n = 2616, 30.8%), overweight and obesity (OW/OB) group (n = 1141, 13.4%), normal decreasing group (n = 232, 2.7%), stable normal group (n = 4383, 51.6%), and fast-increasing group (n = 120, 1.4%). Compared with the stable normal group, the slow increasing group [adjusted odds ratio (AOR): 1.610, 95% confidence interval (CI): 1.304–1.989], the OW/OB group (AOR: 3.172, 95% CI: 2.500–4.023) and the fast-increasing group (AOR: 2.708, 95% CI: 1.445–5.074) all increased the risk of developing hypertension in children and adolescents.Conclusion The potential of developing hypertension varies among groups of children aged 5–18 with different BMI trajectories. Children and adolescents in the normal BMI range (the slow growth group) still need to be aware of the change in BMI trajectory to stop or slow down the progression of BP abnormalities.

As a widely used lipid-lowering drug in clinical practice, atorvastatin is widely recognized for its role in protecting vascular endothelium in the cardiovascular system. However, a clear mechanistic understanding of its action is lacking. Here, we found that atorvastatin counteracted angiotensin II-induced vascular endothelial injury in mice with hypertension. Mechanistically, atorvastatin up-regulated WWP2, a E6AP C-terminus (HECT)-type E3 ubiquitin ligase with an essential role in regulating protein ubiquitination and various biological processes, thereby rescuing vascular endothelial injury. By ubiquitinating ATP5A (ATP synthase mitochondrial F1 complex subunit alpha), WWP2 degraded ATP5A via the proteasome pathway, stabilizing Bcl-2/Bax in the mitochondrial pathway of apoptosis. Moreover, atorvastatin further ameliorated death of vascular endothelial cells and improved vascular endothelial functions under WWP2 overexpression, whereas WWP2 knockout abrogated these beneficial effects of atorvastatin. Furthermore, we generated endothelial cell-specific WWP2 knockout mice, and this WWP2-mediated mechanism was faithfully recapitulated in vivo. Thus, we propose that activation of a WWP2-dependent pathway that is pathologically repressed in damaged vascular endothelium under hypertension is a major mechanism of atorvastatin. Our findings are also pertinent to develop novel therapeutic strategies for vascular endothelial injury-related cardiovascular diseases.

Background and objectiveObesity has become a serious public health problem and brings a heavy burden of cardiovascular disease. Metabolically healthy obesity (MHO) is defined as individuals with obesity with no or only minor metabolic complications. Whether individuals with MHO have a lower cardiovascular risk remains controversial. In this study, a new criterion was used to define MHO and assess its predictive value for cardiovascular events and death. At the same time, the new criterion and the traditional criterion are compared to analyze the differences between different diagnostic criteria.MethodsA prospective cohort was established in northeast rural China from 2012 to 2013. Follow-up was conducted in 2015 and 2018 to investigate the incidence of cardiovascular events and survival. Subjects were grouped according to the metabolic health and obesity status. Kaplan-Meier curves were drawn to describe the cumulative risk of endpoint events in the four groups. Cox regression analysis model was constructed to evaluate the risk of endpoint events. Analysis of variance and post hoc analyses were used to calculate and compare differences in metabolic markers between MHO subjects diagnosed by novel and traditional criteria.ResultsA total of 9345 participants 35 years of age or older without a history of cardiovascular disease were included in this study. After a median follow-up of 4.66 years, the data showed that participants in the MHO group had no significant increase in the risk of composite cardiovascular events and stroke, but had a 162% increase in the risk of coronary heart disease (HR: 2.62; 95%CI: 1.21-5.67). However, when using conventional criteria for metabolic health, mMHO group had a 52% increase in combined CVD risk (HR: 1.52; 95%CI: 1.14-2.03). By comparing the differences of metabolic indicators between MHO subjects diagnosed by the two criteria, MHO subjects diagnosed by the new criterion had higher WC, WHR, TG, FPG, and lower HDL-C levels except for lower blood pressure, showing more exposure to cardiovascular risk factors.ConclusionsThe risk of combined CVD and stroke was not increased in MHO subjects. The new metabolic health criterion is superior to the traditional criterion and can effectively identify individuals with obesity with a lower risk of combined CVD. Blood pressure levels may be responsible for the inconsistent risk of combined CVD in MHO subjects diagnosed with both criteria.

Post-translational modifications regulate numerous biochemical reactions and functions through covalent attachment to proteins. Phosphorylation, acetylation and ubiquitination account for over 90% of all reported post-translational modifications. As one of the tyrosine protein kinases, spleen tyrosine kinase (SYK) plays crucial roles in many pathophysiological processes and affects the pathogenesis and progression of various diseases. SYK is expressed in tissues outside the hematopoietic system, especially the heart, and is involved in the progression of various cardio-cerebrovascular diseases, such as atherosclerosis, heart failure, diabetic cardiomyopathy, stroke and others. Knowledge on the role of SYK in the progress of cardio-cerebrovascular diseases is accumulating, and many related mechanisms have been discovered and validated. This review summarizes the role of SYK in the progression of various cardio-cerebrovascular diseases, and aims to provide a theoretical basis for future experimental and clinical research targeting SYK as a therapeutic option for these diseases.

Abstract Background Hypertension and dyslipidemia are considered reversible risk factors for cardiovascular disease. The purpose of this study was to explore the impact of traditional and nontraditional blood lipid profiles on the risk of left ventricular hypertrophy (LVH) and to explore the superposition effect of dyslipidemia combined with hypertension. Methods Data on 9134 participants (53.5 ± 10.3 years old) from the Northeast China Rural Cardiovascular Health Study (NCRCHS) were statistically analyzed. The blood lipid profile was measured by total cholesterol (TC), low‐density lipoprotein cholesterol (LDL‐C), high‐density lipoprotein cholesterol (HDL‐C), total glyceride (TG), and calculated nontraditional blood lipid indices including non‐HDL‐C, atherosclerosis index (AI), TC/HDL‐C, and residual cholesterol (RC). Results After the adjustment of age and gender, the odds ratios (ORs) of LVH in patients with hypertension, high LDL‐C, high non‐HDL‐C, high AI, and high TC/HDL‐C were 3.97 (3.31–4.76), 1.27 (1.02–1.59), 1.21 (1.04–1.39), 1.33 (1.15–1.53), and 1.42 (1.22–1.65), respectively. After full adjustment of potential confounding factors, high AI and TC/HDL‐C were associated with LVH rather than traditional blood lipid indices. The combination of hypertension and nontraditional dyslipidemia (defined by high AI and TC/HDL‐C) was associated with the highest risk of LVH, especially in participants under 45 years of age. The risk was more significant in men, 5.09‐fold and 6.24‐fold, respectively, compared with 3.66‐fold and 4.01‐fold in women. Conclusions People with dyslipidemia defined by nontraditional blood lipid indices (high AI and high TC/HDL‐C) and hypertension were more likely to develop LVH.

Abstract 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.

Abstract Post-translational modifications (PTMs) are a covalent processing process of proteins after translation. Proteins are capable of playing their roles only after being modified, so as to maintain the normal physiological function of cells. As a key modification of protein post-translational modification, ubiquitination is an essential element, which forms an enzyme-linked reaction through ubiquitin-activating enzyme, ubiquitin binding enzyme, and ubiquitin ligase, aiming to regulate the expression level and function of cellular proteins. Nedd4 family is the largest group of ubiquitin ligases, including 9 members, such as Nedd4-1, Nedd4L (Nedd4-2), WWP1, WWP2, ITCH, etc. They could bind to substrate proteins through their WW domain and play a dominant role in the ubiquitination process, and then participate in various pathophysiological processes of cardiovascular diseases (such as hypertension, myocardial hypertrophy, heart failure, etc.). At present, the role of Nedd4L in the cardiovascular field is not fully understood. This review aims to summarize the progress and mechanism of Nedd4L in cardiovascular diseases, and provide potential perspective for the clinical treatment or prevention of related cardiovascular diseases by targeting Nedd4L.

PurposeThis study aimed to clarify the relationship between liver fibrosis scores (Fibrosis-4, BARD score, and BAAT score) and chronic kidney disease (CKD).MethodsWe collected a range of data from 11,503 subjects (5,326 men and 6,177 women) from the rural regions of Northeastern China. Three liver fibrosis scores (LFSs) including fibrosis-4 (FIB-4), BARD score, and BAAT score were adopted. A logistic regression analysis was used to calculate odds ratios and the 95% confidence interval. A subgroup analysis showed the association between LFSs and CKD under different stratifications. Restricted cubic spline could further explore whether there is a linear relationship between LFSs and CKD. Finally, we used C-statistics, Net Reclassification Index (NRI), and Integrated Discrimination Improvement (IDI) to assess the effect of each LFS on CKD.ResultsThrough the baseline characteristics, we observed that LFSs were higher in the CKD population than in non-CKD. The proportion of participants with CKD also increased with LFSs. In a multivariate logistic regression analysis, the ORs of CKD were 6.71 (4.45–10.13) in FIB-4, 1.88 (1.29–2.75) in the BAAT score, and 1.72 (1.28–2.31) in the BARD score by comparing the high level with the low level in each LFSs. Moreover, after adding LFSs to the original risk prediction model, which consisted of age, sex, drinking, smoking, diabetes, low-density lipoprotein cholesterol, total cholesterol, triglycerides, and mean waist circumference, we found the new models have higher C-statistics. Furthermore, NRI and IDI both indicate LFSs had a positive effect on the model.ConclusionsOur study showed that LFSs are associated with CKD among middle-aged populations in rural areas of northeastern China.

Abstract Tyrosine phosphorylation by protein tyrosine kinases (PTKs) is a type of post-translational modification. Tec kinases, which are a subfamily of non-receptor PTKs, were originally discovered in the hematopoietic system and include five members: Tec, Btk, Itk/Emt/Tsk, Etk/Bmx, and Txk/Rlk. With the progression of modern research, certain members of the Tec family of kinases have been found to be expressed outside the hematopoietic system and are involved in the development and progression of a variety of diseases. The role of Tec family kinases in cardiovascular disease is receiving increasing attention. Tec kinases are involved in the occurrence and progression of ischemic heart disease, atherosclerosis, cardiac dysfunction associated with sepsis, atrial fibrillation, myocardial hypertrophy, coronary atherosclerotic heart disease, and myocardial infarction and post-myocardial. However, no reviews have comprehensively clarified the role of Tec kinases in the cardiovascular system. Therefore, this review summarizes research on the role of Tec kinases in cardiovascular disease, providing new insights into the prevention and treatment of cardiovascular disease.

Abstract Background Hyperlipidemia (HLP) and hypertension (HTN) are both independent risk factors for ischemic stroke. This study aimed to assess whether HTN and HLP have a synergistic effect on the risk of ischemic stroke. Methods Between January and August 2013, 11,695 subjects in rural areas of northeastern China were enrolled. The additive and multiplicative scales were used to evaluate the interaction. Results The prevalence of ischemic stroke was 5.7%. Using the healthy group (without HTN or HLP) as the reference group, subjects with both HTN and HLP had a higher risk of ischemic stroke (odds ratio [OR]: 3.369, 95% confidence interval [CI]: 2.579–4.402), and this OR was greater than that of subjects with only HTN (OR: 1.995, 95% CI 1.526–2.610) or HLP (OR: 1.321, 95% CI 0.937–1.862) (adjusting for age, sex, race, education level, family income, current smoking and drinking status, physical activity, body mass index, diabetes, family history of stroke, and atrial fibrillation). Regarding the additive scale, the relative excess risk due to interaction (OR: 1.053, 95% CI 0.458–1.648) was positive after adjusting for confounders. Moreover, the attributable proportion was 31.3%, which means that 31.3% of the total risk of ischemic stroke was due to the synergistic interaction between HTN and HLP. Furthermore, the synergistic index (S) of ischemic stroke was 1.8 (95% CI 1.157–2.801), which also indicates a synergistic interaction between HTN and HLP. Regarding the multiplicative scale, the interaction effect was also significant after adjusting for confounders (OR: 2.163, 95% CI 1.817–2.575). Conclusion The results suggest that the synergistic effect of HTN and HLP on ischemic stroke is significantly higher than the sum of their independent effects. The quantification of the combined effect should help to promote healthy blood pressure and blood lipid levels among the general population.

Objective: Previous studies have investigated the relationships between alcohol and ventricular structure, but few studies have evaluated the relation between alcohol consumption and the atrium size. This study aims to test the association between alcohol consumption and left atrium (LA) size in a general population. Methods: A population-based sample of 10 211 subjects aged ≥ 35 years and free from hypertension at baseline were followed from January 2012 to August 2013. Left atrial enlargement (LAE) was defined as the ratio of LA diameter to body surface area exceeding 2.4 cm/m2 in both genders. Independent factors for LAE were estimated by multiple logistic regression analyses. Results：The study included 10 211 participants (4 751 men and 5 460 women). Left atrium diameter / body surface area (LAD/BSA) was higher in the moderate and heavy alcohol consumption groups compared with the non-drinker group (non-drinker, 20.5+-0.03 cm/m2; moderate, 20.8+-0.09 cm/m2; and heavy, 20.6+-0.06 cm/m2; P

Abstract Many assessments have been used to predict cardiovascular risks in the general population, but their applicability in patients with hypertension needs to be further evaluated. In the current study, a cardiovascular risk assessment model was constructed in a hypertensive population. This prospective cohort study was conducted with cardiovascular examinations in rural northeast China in 2012 and 2013, and followed up to collect cardiovascular events in 2015 and 2018. Data were derived from 4763 hypertensive patients who were free of cardiovascular disease (CVD) at baseline and completed follow‐up. After lasso regression was used to screen for risk factors of CVD at baseline, a multivariate Cox regression risk model was established and a nomogram was developed. The model was validated using an independent test set (one third of data not used for model building). Among 4763 patients, 354 (7.43%) had a cardiovascular event during a median follow‐up of 4.66 years. Nine risk factors were screened by lasso regression, including sex, age, current smoking, body mass index (BMI), history of transient ischemic attack (TIA), family history of hypertension, family history of stroke, physical labor intensity, and high low‐density lipoprotein cholesterol (LDL‐C). The c‐index of the CVD model was 0.707, and that of an updated model with baseline blood pressure was 0.732. In the validated cohort the respective c‐indexes were 0.665 and 0.714. An assessment model of CVD risk was established in a hypertensive population which may provide an original prevention strategy for hypertensive populations in rural China, and further reduce the CVD burden.

Abstract The 2017 American College of Cardiology/American Heart Association (ACC/AHA) guideline lowered the threshold (systolic blood pressure [SBP]

ObjectiveThe study aimed to estimate the possible predictors of cardiovascular events (CVEs) in elderly patients with metabolic syndrome (MetS) from rural China. Moreover, we also attempted to find the potential risk factors for newly diagnosed MetS.MethodsThe Northeast China Rural Cardiovascular Health Study (NCRCHS) is a community-based prospective cohort study carried out in rural areas of northeast China. Approximately 1,059 elderly patients with MetS but no cardiovascular diseases and 1,565 elderly patients without MetS at baseline were enrolled in this study. They underwent a physical examination, completed a questionnaire in 2012–2013, and were followed up during 2015–2017. Cox proportional hazard analysis was conducted to assess the possible predictors of newly developed CVEs, and multivariate analysis was used to estimate the risk factors of newly diagnosed MetS.ResultsThe common predictors of newly developed CVEs in both men and women were family history of stroke (HR [hazard ratios] female: 1.696; HR male: 2.504) and soybean consumption (HR female: 0.253; HR male: 0.130). Moreover, minority race (HR: 0.109), systolic blood pressure (SBP) (HR: 1.021), current drinking habits (HR: 2.551), family history of hypertension (HR: 2.297), LDL-C (HR: 1.669), 5,000–20,000 CNY/year annual income (HR: 0.290), and strenuous physical activity (HR: 0.397) were predictors of CVEs only in male elderly patients. For newly diagnosed MetS, body mass index (OR female: 1.212; OR male: 1.207) and fasting blood glucose (OR female: 1.305; OR male: 1.217) were common risk factors in both genders, whereas age (OR:0.958) was a protective factor in men and > 9-h/day sleep duration (OR:0.212) was a protective factor in women. In addition, SBP (OR:1.014) ≥4 times/day, bean consumption (OR:1.955), and uric acid (OR:1.005) increased the risk of MetS in men but not in women.ConclusionOur study identified many effective predictors of CVEs in rural elderly patients with MetS and confirmed the presence of a gender-based discrepancy. Moreover, we also identified additional risk factors, along with the traditional ones, for newly diagnosed MetS in rural elderly patients.

BackgroundVarious anthropometric indices have been proved to be useful to predict metabolic syndrome(MetS), but the association between changes in anthropometric indices and the onset of MetS is unclear. This study selected six indices that are easy to measure and calculate in daily life and evaluated the relationships.MethodsWe established a prospective cohort in rural China during 2012-2013 and involved 5,221 participants without MetS. The follow-up visit was conducted in 2015 to repeat anthropometric indices measurements and assess MetS onset. Binary logistic regression model was used to calculate the association between changes in anthropometric indices and MetS onset. Receiver operating characteristic (ROC) curve was drawn to compare their abilities in MetS prediction.ResultsOver a median follow-up time of 2.42 years, 1,367 participants (26.2%) developed MetS. The increase in all the six indices is associated with an increased risk of MetS. Changes in WC and WHtR are the strongest predictors, with a 5 cm increase in WC and a 0.025 increase in WHtR giving the best prediction of MetS onset.ConclusionsPeople should be aware of changes in these six anthropometric indices in daily life, as their increase is closely related to an increased risk of MetS, especially WC and WHtR. We recommend an increase of 5 cm in WC and 0.025 in WHtR as the optimal cut-off for the MetS prediction.

BackgroundTraditional risk estimations for cardiovascular disease (CVD) are based on current blood pressure (BP); however, whether cumulative exposure to elevated BP among rural individuals has additional prognostic value is unclear. We aimed to validate the association of cumulative BP with CVD occurrence and assess the prognostic value of cumulative BP in CVD risk prediction.MethodsA total of 13,057 participants who underwent three examinations from 2004 to 2010 were included in this rural epidemiological study and followed up until 2017. Cumulative BP was defined as the sum of the product of the average BP values between consecutive examinations and the time interval for each pair of successive tests prior to the follow-up period. CVD incidents that occurred during the follow-up period were noted and verified by qualified researchers. We used multivariate Cox models to assess the association of cumulative BP with CVD risk. The receiver operating characteristic curve was constructed to determine the predictive differentiation of single baseline BP measurements and cumulative BP values for CVD outcomes.ResultsDuring the follow-up period, 1,312 participants underwent CVD incidents. We found that cumulative systolic BP (hazard ratio = 1.334, 95% confidence interval: 1.245, 1.430) and cumulative diastolic BP (hazard ratio = 1.253, 95% confidence interval: 1.168, 1.343) were associated with CVD incidence above and beyond that of the current BP. These stronger associations persisted for stroke, myocardial infarction, and CVD mortality. The area under the curve for the model increased significantly (p < 0.001) from 0.735 (0.720, 0.750) to 0.742 (0.728, 0.757) when integrating cumulative systolic BP instead of baseline systolic BP.ConclusionCumulative BP in Chinese rural adults showed a stronger association with CVD incidence than that of current BP. Furthermore, cumulative BP slightly improved the predictive performance for CVD. Our findings underline the incremental predictive value of cumulative BP in CVD risk assessment among Chinese rural adults.

Background Ischemic stroke is likely caused by interactions of multiple genes and environmental determinants. However, large‐scale sequencing studies to discern functional genetic variants and their interactions with clinical and lifestyle risk factors on ischemic stroke are limited. Methods and Results We sequenced functional regions of 740 previously identified genes associated with atherosclerotic disease among 999 ischemic stroke cases and 1001 controls of Chinese ancestry. Multiple logistic regression models were used to examine the associations between variants and ischemic stroke and test interactions between variants and clinical and lifestyle risk factors. Functional variants achieving suggestive significance were replicated in an independent sample of 4724 ischemic stroke cases and 5029 controls. Driven by variant main effects, each minor allele of the correlated rs174535, rs174545, and rs3834458 variants at MYRF‐FADS1‐FADS2 conferred an average 0.83‐fold (95% CI, 0.78–0.88) decreased odds of stroke. Significant main effects of MTHFR rs1801133 missense variant were also observed, with each copy of the A allele associated with a 1.20‐fold (95% CI, 1.13–1.27) higher odds of ischemic stroke. The functional ALDH2 rs671 variant was identified in interaction analyses with alcohol drinking (Meta‐P=3.39×10−17). Each minor allele conferred a 0.54‐fold (95% CI, 0.45–0.64) decreased odds of stroke among drinkers and a 0.89‐fold (95% CI, 0.83–0.97) decreased odds among nondrinkers. Conclusions Significant associations at MYRF‐FADS1‐FADS2 indicate that genetically elevated polyunsaturated fatty acids may decrease ischemic stroke risk in East Asians. Significant associations at MTHFR and ALDH2 robustly confirm deleterious effects of genetically elevated homocysteine and alcohol intake, respectively, on ischemic stroke.

Abstract 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.

Abstract Septin4, a protein localized at mitochondrion, can promote cells apoptosis mainly by binding XIAP (X-linked inhibitors of apoptosis), however, nothing is known about the role and mechanism of Septin4 in cardiomyocytes apoptosis. Here in the current study, we report that HIF-1α (hypoxia-inducible factor 1 alpha) is a novel interacting protein with Septin4 at Septin4-GTPase domain. In addition, Septin4 enhances the binding between HIF-1α and the E3 ubiquitin ligase VHL (von Hippel-Lindau protein) to down-regulate HIF-1α, and by reducing cardio-protective factor HIF-1α levels, Septin4 aggravated the hypoxia-induced cardiomyocytes apoptosis. We believe these findings will be beneficial to provide effective strategies for clinical treatment of myocardial ischemia and the subsequent injury caused by myocardial hypoxia.

BackgroundThe present study aimed to clarify the effects of four inflammatory indicators (monocyte-to-high-density lipoprotein ratio [MHR], neutrophil-to-lymphocyte ratio [NLR], systematic immune-inflammation index [SII], and systemic inflammation response index [SIRI]) in evaluating the risk of metabolic diseases and cardiovascular disease (CVD), filling the gap of inflammation-metabolism system research in epidemiology.MethodsWe conducted a cross-sectional study and multivariable logistic regression analysis to elucidate the association between inflammatory indicators and metabolic diseases and CVD risk. Metabolic diseases were defined as metabolic disorders (MetDs) or their components, such as metabolic syndrome (MetS), dyslipidemia, and central obesity. We calculated the Framingham risk score (FRS) to evaluate 10-year CVD risk.ResultsOdds ratios for the third vs. the first tertile of MHR were 2.653 (95% confidence interval [CI], 2.142–3.286) for MetD, 2.091 (95% CI, 1.620–2.698) for MetS, 1.547 (95% CI, 1.287–1.859) for dyslipidemia, and 1.515 (95% CI, 1.389–1.652) for central obesity. Odds ratios for the third vs. the first tertile of SIRI were 2.092 (95% CI, 1.622–2.699) for MetD, 3.441 (95% CI, 2.917–4.058) for MetS, 1.417 (95% CI, 1.218–1.649) for dyslipidemia, and 2.080 (95% CI, 1.613–2.683) for central obesity. The odds ratio of a 10-year CVD risk of >30% for the third vs. the first tertile of MHR was 4.607 (95% CI, 2.648–8.017) and 3.397 (95% CI, 1.958–5.849) for SIRI.ConclusionsMHR and SIRI had a significant association with MetD and its components, in which a higher level of MHR or SIRI tended to accompany a higher risk of metabolic diseases. Furthermore, they also correlated with CVD, and the increment of these indicators caused a gradually evaluated risk of 10-year CVD risk.

Objectives The possible predictive effect of echocardiographic aortic root diameter (ARD) on the incidence of cardiovascular events (CVEs) in a large, general population is limited. In addition, there is a lack of data about rural participants. We intend to figure out the possible relationship between ARD and the incidence of CVEs among the general population from rural China.Design Population-based cohort study.Setting Rural areas in Liaoning Province, Northeast China.Participants At baseline, 9810 participants (mean age 53±10, 49.1% male) were enrolled in the Northeast China Rural Cardiovascular Health Study between 2012 and 2017.Main outcome measures Cardiac ultrasonography, lifestyle, medical history, laboratory testing, blood pressure, weight and height. ARD measurement was conducted at the level of the sinuses of Valsalva. Furthermore, the ARD was indexed to height or body surface area.Results During a median follow-up of 4.66 years, 550 non-fatal or fatal CVEs were recorded. Adjusting for blood pressure, age, total cholesterol, fasting blood glucose, estimated glomerular filtration rate, current smoking and drinking, previous cardiovascular diseases and antihypertensive treatment; ARD/height (HR per 1-unit increase=1.781, 95% CI: 1.160 to 2.736, p=0.008) was associated with an increased risk of CVEs in men only. The combination of left ventricular hypertrophy (LVH) and aortic dilation was an independent and powerful predictor for cardiovascular prognosis compared with aortic dilation alone in men but not in women.Conclusions Our study enrols a large sample of rural Chinese residents, and first confirms that ARD/height has a predictive effect on the incidence of CVEs among rural Chinese residents. The combination of LVH and aortic dilation is synergistic, which increases its predictive effect on CVEs in men only, suggesting that aortic dilatation predicts cardiovascular prognosis better than LVH does in men but not in women.

ObjectiveCumulative evidence indicates that education plays a major role in predicting cardiovascular risk factors. In this study, we intend to examine the possible relationship between education status and mortality in a large general subject from rural China.MethodsAdult hypertensive subjects (n = 5,227, age = 57.22 ± 10.18 years; 49.1% men) were recruited from general population surveys (Northeast China Rural Cardiovascular Health Study). Their educational status was categorized into two groups as follows: (1) Low education (illiterate or lower than primary school) and (2) medium-high education (higher than primary school). Cardiometabolic comorbidities, related cardiovascular risk factors, and echocardiographic measurements were analyzed in both groups.ResultsLess educated hypertensive subjects had significantly higher prevalence of obesity, diabetes, dyslipidemia, and left ventricular hypertrophy than medium-high educated hypertensive subjects. In the medium-high educated subjects, a significant increase in left ventricular ejection fraction and lower rate of antihypertensive medication was found. Cox proportional hazards analysis indicated that medium-high education was independently associated with all-cause mortality (hazard ratio = 0.76; 95% confidence interval, 0.58, 0.99; P = 0.043) and cardiovascular mortality (hazard ratio = 0.65; 95% confidence interval, 0.44, 0.96; P = 0.028).ConclusionEducation may act as the best predictor of all-cause and cardiovascular mortality in rural hypertensive subjects. This finding suggests that in rural areas, education is likely to represent a cardiovascular specific risk factor and should be evaluated in the strategies of hypertension.

Abstract 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.

Abstract 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

Abstract 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.

Oxidative stress-associated endothelial damage is the initiation factor of cardiovascular disease, and protein posttranslational modifications play critical roles in this process. Bcl-2-associated athanogene 3 (BAG3) is a molecular chaperone regulator of the BAG family, which interacts with various proteins and influences cell survival by activating multiple pathways. BAG3 undergoes posttranslational modifications; however, research evaluating BAG3 acetylation and its regulatory mechanism is lacking. In addition, the interacting protein and regulatory mechanism of BAG3 in oxidative stress-associated endothelial damage remain unclear. Here, key molecular interactions and protein modifications of BAG3 were identified in oxidative stress-associated endothelial damage. Endothelial-specific BAG3 knockout in the mouse model starkly enhances oxidative stress-associated endothelial damage and vascular remodeling, while BAG3 overexpression in mice significantly relieves this process. Mechanistically, poly(ADP-ribose) polymerase 1 (PARP1), causing oxidative stress, was identified as a novel physiological substrate of BAG3. Indeed, BAG3 binds to PARP1's BRCT domain to promote its ubiquitination (K249 residue) by enhancing the E3 ubiquitin ligase WWP2, which leads to proteasome-induced PARP1 degradation. Furthermore, we surprisingly found that BAG3 represents a new substrate of the acetyltransferase CREB-binding protein (CBP) and the deacetylase Sirtuin 2 (SIRT2) under physiological conditions. CBP/SIRT2 interacted with BAG3 and acetylated/deacetylated BAG3's K431 residue. Finally, deacetylated BAG3 promoted the ubiquitination of PARP1. This work reveals a novel regulatory system, with deacetylation-dependent regulation of BAG3 promoting PARP1 ubiquitination and degradation via enhancing WWP2, which is one possible mechanism to decrease vulnerability of oxidative stress in endothelial cells.

The relationship between serum spermidine levels and future cardiovascular disease risk has not yet been well elucidated in the general population based on community studies. Using a nested case-control study, we estimated the association between serum spermidine level and future stroke. New stroke cases had higher baseline levels of spermidine than controls [182.8 (141.8–231.5) vs. 152.0 (124.3–193.0), P < 0.001]. After multivariable adjustment, individuals with spermidine ≥ 205.9 nmol/L (T3) higher risks of stroke (HR 5.02, 95% CI 1.58–16.02) with the lowest quartile (< 136.9 nmol/L) as reference. The association between serum spermidine levels and risk of stroke seemed to be consistent and was reproducible in our cross-sectional studies. In addition, comparisons of the areas under receiver operator characteristics curves confirmed that a model including spermidine had better discrimination than without (0.755 vs. 0.715, P = 0.04). Here we report a close relationship exists between serum spermidine levels and risk of stroke.

In middle-aged and elderly individuals, the relationship between tea consumption and incident metabolic syndrome (MetS) is still unclear. Therefore, this study intends to figure out the relationship between tea-drinking frequency and MetS in rural middle-aged and older Chinese residents. In the Northeast China Rural Cardiovascular Health Study, 3632 middle-aged or older individuals (mean age 57 ± 8, 55.2% men) without MetS were included at baseline during 2012–2013 and were followed up on between 2015–2017. Participants showing differential tea consumption frequency were divided into the following classes: non-habitual tea drinkers, occasional tea drinkers, 1–2 times/day drinkers, and ≥3 times/day drinkers. Data showed that non-habitual tea drinking was more common among women. The frequency of tea consumption was higher in ethnic groups other than Han and among singles, as well as in concurrent smokers and drinkers and individuals with primary or lower educational status. The increasing tea consumption was in line with baseline elevations in body mass index, systolic and diastolic blood pressure, high-density lipoprotein cholesterol (HDL-C), and AST/ALT ratio. Multivariate logistic regression analysis confirmed that occasional tea drinking increased the incidence of low HDL-C [OR (95% CI): 1.268 (1.015, 1.584)], high waist circumference [OR (95% CI): 1.336 (1.102, 1.621)], and MetS [OR (95% CI): 1.284 (1.050, 1.570)]. In addition, 1–2 times/day tea drinking increased the cumulative incidence of high TG [OR (95% CI): 1.296 (1.040, 1.616)], high waist circumference [OR (95% CI): 1.296 (1.044, 1.609)] and MetS [OR (95% CI): 1.376 (1.030, 1.760)]. We demonstrated that regular tea consumption is correlated with a greater incidence of metabolic disorders and MetS. Our findings may help clarify the contradictory association reported between tea drinking and MetS development in middle-aged and older residents of rural China.

The relationship between the weight-adjusted waist index (WWI) and newly diagnosed type 2 diabetes (T2D) remains uncertain. This study intended to explore the association between the WWI and the incidence of newly diagnosed T2D among participants in rural areas of China. In the Northeast China Rural Cardiovascular Health Study, 9205 non-diabetic individuals (mean age 53 ± 10, 53.1% women) without T2D were included at baseline during 2012–2013. They were followed up from 2015 to 2017. WWI was calculated as waist circumference (cm) divided by the square root of weight (kg). We used multivariate logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the probability of new diagnoses across three WWI categories. A total of 358 participants had been diagnosed with T2D during a median follow-up of 4.6 years. After adjusting for potential confounders, compared with the lowest WWI category (

In recent years, there has been an increase in the incidence of metabolic syndrome (MetS) in rural China. Thus, for better intervention, it is necessary to identify the possible risk factors of MetS. This community-based prospective cohort study was performed to evaluate the relationship between the snoring status and incidence of MetS. In this Northeast China rural cardiovascular health study, 4980 residents aged ≥35 years (2586 men and 2394 women; follow-up proportion: 87.5%) at baseline were recruited between 2012 and 2013 and were followed up between 2015 and 2017. The primary outcome was the incidence of MetS, as defined by the unified criteria for MetS defined in 2009. The residents were classified based on their snoring status, and the outcomes were compared between the two groups. The odds ratio (OR) for MetS incidence was estimated using a logistic regression model and adjusted for confounding factors. With a median follow-up duration of 4.6 years, the MetS incidence was higher among the snorers (men, 26.2%; women, 33.5%) than in the non-snorers (men, 19.7%; women, 23.2%). The participants’ diastolic blood pressure was increased at follow-up as compared with the baseline values among the male snorers; however, a decrease was noted among the male non-snorers. Similarly, the female snorers had higher blood glucose levels during the follow-up, whereas the non-snorers had lower blood sugar levels. A significant association was noted between snoring and the incidence of MetS (adjusted OR = 1.51; 95% confidence interval = 1.32–1.74). Moreover, the incidence of severe snoring increased with increased levels of snoring, with severe snorers having an OR twice as high as that of the non-snorers (adjusted OR = 2.10; 95% confidence interval = 1.38–3.20). Overall, snoring was independently associated with a higher incidence of newly diagnosed MetS in rural Northeast China. Thus, more attention should be paid to residents with snoring problems.

Abstract Background To investigate the relationship between triglyceride glucose-body mass index (TyG-BMI) and ischemic stroke. Methods Leveraging two Chinese general population surveys, the Northeast China Rural Cardiovascular Health Study (NCRCHS, N = 11,097) and the National Stroke Screening and Intervention Program in Liaoning (NSSIPL, N = 10,862), we evaluated the relationship between TyG-BMI and ischemic stroke by a restricted cubic spline and multivariate logistic regression after adjusting age, sex, level of education, exercise regularly, current smoking, current drinking, atrial fibrillation, hypertension, coronary artery disease, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. The category-free analysis was used to determine whether TyG-BMI enhanced the capacity of estimating ischemic stroke. Results A total of 596 and 347 subjects, respectively, from NSSIPL and NCRCHS were survivors of ischemic stroke. In NSSIPL, the relationship between TyG-BMI and ischemic stroke was linear and did not have a threshold or saturation effect according to the results of the restricted cubic spline. The regression analysis indicated that the risk of ischemic stroke increased 20% for per SD increase of TyG-BMI after multivariate adjustment [odds ratio (OR): 1.20, 95% confidence interval (CI): 1.10–1.32]. Compared with those in the lowest tertile, the risk of ischemic stroke in subjects with intermediate and high TyG-BMI was significantly higher [OR (95% CI): 1.39 (1.10–1.74); OR (95% CI) 1.72 (1.37–2.17), respectively]. Category-free analysis indicated that TyG-BMI had a remarkable improvement in the ability to estimate prevalent ischemic stroke [NRI (95% CI): 0.188 (0.105–0.270)]. These abovementioned relationships were confirmed in NCRCHS. Conclusions The present study found the robust correlation between TyG-BMI and ischemic stroke, independently of a host of conventional risk factors. Meanwhile, our findings also suggested the potential usefulness of TyG-BMI to improve the risk stratification of ischemic stroke.

Abstract 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.

Abstract Background We reported a relatively high rate of MetS in rural Northeast residents in 2012–2013. Many strategies like health knowledge propagation and lifestyle modification have been taken to help rural residents decrease metabolic disorders. Hence, we held the present follow-up study in order to figure the changes of metabolic parameters and the possible reasons together with the evaluation of MetS incidence and associated risk factors. Methods A population-based sample of 8147 rural Northeast Chinese residents aged ≥ 35 years at baseline were followed up from 2012–2013 to 2015–2017. MetS was diagnosed following the unify criteria in 2009 using the Asian specific criteria. Results Among residents with MetS at baseline, value of systolic, diastolic blood pressure, total cholesterol, HDL-C decreased while waist circumference increased in both genders in follow-up. Discrepancy of trend in body mass index, LDL-C and estimated GFR existed between male and female. Besides, triglyceride increased, and fast glucose decreased in female only. The alterations of dietary pattern might be accountable for those changes. Among residents without MetS at baseline, the cumulative incidence of newly diagnosed MetS was 24.0% (25.8% for male; 22.3% for female). As the number of metabolic disorders increased at baseline, the incidence of MetS also increased (zero metabolic disorder: 8.3%; one metabolic disorder: 17.1%; two metabolic disorders: 35.4%). In male residents, bad living habits like smoking and drinking were associated with increasing risk of Mets while in female, higher risk of MetS was more likely relevant to dietary pattern. Conclusion Metabolic parameters changes during the past years and seem to be associated with alteration of diet pattern. Incidence of MetS still high among rural Northeast Chinese. The risk factors of higher incidence of MetS show gender discrepancy which make the prophylaxis and control of MetS more effective and directive in rural residents.