The role of serine/threonine protein kinases in cardiovascular disease and potential therapeutic methods.

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.

Impact of baseline cardiovascular risk on the outcomes of intensive blood pressure intervention: a post hoc analysis of the China rural hypertension control project.

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 < 130/80 mmHg. Cox proportional-hazards models were used to estimate the hazard ratios of outcomes for intervention in each quartile, while interaction effect between intervention and estimated CVD risk quartiles was additionally assessed. The primary outcome comprised myocardial infarction, stroke, hospitalization for heart failure, or CVD deaths. RESULTS: Significant lower rates of primary outcomes for intervention group compared with usual care for each estimated CVD risk quartile were reported. The hazard ratios (95% confidence interval) in the four quartiles (from Q1 to Q4) were 0.59 (0.40, 0.87), 0.54 (0.40, 0.72), 0.72 (0.57, 0.91) and 0.65 (0.53, 0.80), respectively (all Ps < 0.01). There's no significant difference of hazard ratios by intervention across risk quartiles (P for interaction = 0.370). Only the relative risk of hypotension, not symptomatic hypotension, was elevated in the intervention group among upper three quartiles. CONCLUSIONS: Intensive BP lowering strategy designed by CRHCP group was effective and safe in preventing cardiovascular events independent of baseline CVD risk. TRIAL REGISTRATION: The trial is registered with ClinicalTrials.gov, NCT03527719.

Multifaceted Intensive Blood Pressure Control Model in Older and Younger Individuals With Hypertension: A Randomized Clinical Trial.

Importance: The sustainable effectiveness and safety of a nonphysician community health care practitioner-led intensive blood pressure intervention on cardiovascular disease have not, to the authors' knowledge, been studied, especially in the older adult population. Objective: To evaluate such a multifaceted model with a more stringent blood pressure treatment goal (<130/80 mm Hg) among patients aged 60 years and older with hypertension. Design, Setting, and Participants: This was a 48-month follow-up study of the China Rural Hypertension Control Project (CRHCP), an open-cluster randomized clinical trial, conducted from 2018 to 2023. Participants 60 years and older and younger than 60 years with a diagnosis of hypertension from the CRHCP trial were included for analysis. Individuals were recruited from 326 villages in rural China. Interventions: The well-trained, nonphysician, community health care practitioner implemented a multifaceted intervention program (eg, initiation or titration of antihypertensive medications) to achieve a blood pressure level of less than 130/80 mm Hg, supervised by primary care physicians. Main Outcomes and Measures: Cardiovascular disease (a composite of myocardial infarction, stroke, heart failure requiring hospitalization, and cardiovascular disease death). Results: A total of 22 386 individuals 60 years and older with hypertension and 11 609 individuals younger than 60 years with hypertension were included in the analysis. The mean (SD) age of the participants was 63.0 (9.0) years and included 20 825 females (61.3%). Among the older individuals with hypertension, a total of 11 289 patients were randomly assigned to the intervention group and 11 097 to the usual-care group. During a median (IQR) of 4.0 (4.0-4.1) years, there was a significantly lower rate of total cardiovascular disease (1133 [2.7%] vs 1433 [3.5%] per year; hazard ratio [HR], 0.75; 95% CI, 0.69-0.81; P < .001) and all-cause mortality (1111 [2.5%] vs 1210 [2.8%] per year; HR, 0.90; 95% CI, 0.83-0.98; P = .01) in the intervention group than in the usual-care group. For patients younger than 60 years, the risk reductions were also significant for total cardiovascular disease (HR, 0.64; 95% CI, 0.56-0.75; P < .001), stroke (HR, 0.64; 95% CI, 0.55-0.76; P < .001), heart failure (HR, 0.39; 95% CI, 0.18-0.87; P = .02), and cardiovascular death (HR, 0.54; 95% CI, 0.37-0.77; P < .001), with all interaction P values for age groups greater than .05. In both age categories, the incidences of injurious falls, symptomatic hypotension, syncope, and the results for kidney outcomes did not differ significantly between groups. Conclusions and Relevance: In both the aging and younger general population with hypertension, the nonphysician health care practitioner-led, multifaceted, intensive blood pressure intervention model could effectively and safely reduce the risk of cardiovascular disease and all-cause death. Trial Registration: ClinicalTrials.gov Identifier: NCT03527719.

Programmed death of cardiomyocytes in cardiovascular disease and new therapeutic approaches.

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.

Altered gut microbiota and metabolite profiles provide clues in understanding resistant hypertension.

BACKGROUND: Resistant hypertension is a severe phenotype in hypertension that may be driven by interactions between genetic and environmental factors. Specific changes in gut microbiota and metabolites have been shown to influence cardiovascular disease progression. However, microbial and metabolomic changes associated with resistant hypertension remain elusive. METHODS: In this study, the gut microbiome of 30 participants with resistant hypertension, 30 with controlled hypertension, and 30 nonhypertension was characterized using 16S rRNA amplicon sequencing. In addition, the serum metabolome of the same population was assessed by untargeted metabolomics. RESULTS: The alpha diversity of microbiome in the resistant hypertension decreased, and changes were also observed in the composition of the gut microbiota. The resistant hypertension group was characterized by elevated levels of Actinobacteitia and Proteobacteria. Twenty-three genera were found to have significantly different abundances between resistant hypertension and controlled hypertension, as well as 55 genera with significantly different abundances between resistant hypertension and nonhypertension. Compared with the controlled hypertension group, the genera Rothia and Sharpea in resistant hypertension were more abundant. Compared with the nonhypertension group, the genera Escherichia-Shigella , Lactobacillus , Enterococcus were more abundant. Untargeted metabolomics provided distinctly different serum metabolic profiles for the three groups and identified a range of differential metabolites. These metabolites were mainly associated with the pathway of glycerophospholipid metabolism. Furthermore, correlation analysis provided evidence of new interactions between gut microbiota and metabolites in the resistant hypertension. CONCLUSION: In conclusion, our study provides a comprehensive understanding of the resistant hypertension gut microbiota and metabolites, suggesting that treatment resistance in resistant hypertension patients may be related to the gut microbiota and serum metabolites.

Triglyceride-glucose index predicts all-cause mortality, but not cardiovascular mortality, in rural Northeast Chinese patients with metabolic syndrome: a community-based retrospective cohort study.

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(< 8.92); Q2 (8.92-9.36); Q3 (≥ 9.36)]. Multivariate Cox proportional hazards models were developed to examine the correlations between mortality and the baseline TyG index. RESULTS: During a median of 4.66 years of follow-up, 196 (5.0%) all-cause deaths and 108 (2.8%) CV disease-related deaths occurred. The incidence of all-cause mortality was significantly different among TyG index tertiles of the overall population (P = 0.045). Kaplan-Meier analysis demonstrated a significantly increased risk of all-cause mortality in rural Chinese patients with a higher TyG index (log-rank P < 0.05). After adjusting for possible confounders, Cox proportional hazard analysis revealed that the TyG index could effectively predict all-cause mortality (HR for the third vs. first tertile of TyG was 1.441 [95% confidence interval, 1.009-2.059]), but not CV mortality, in rural Chinese patients with MetS. CONCLUSIONS: The TyG index is an effective predictor of all-cause mortality in rural Chinese patients with MetS. This indicates that the TyG index may be useful for identifying rural Chinese individuals with MetS at a high risk of death.

WWP2 protects against sepsis-induced cardiac injury through inhibiting cardiomyocyte ferroptosis.

Background and Objectives: Cardiac injury plays a critical role in contributing to the mortality associated with sepsis, a condition marked by various forms of programmed cell deaths. Previous studies hinted at the WW domain-containing E3 ubiquitin protein ligase 2 (WWP2) involving in heart failure and endothelial injury. However, the precise implications of WWP2 in sepsis-induced cardiac injury, along with the underlying mechanisms, remain enigmatic. Methods: Sepsis induced cardiac injury were constructed by intraperitoneal injection of lipopolysaccharide. To discover the function of WWP2 during this process, we designed and performed loss/gain-of-function studies with cardiac-specific vectors and WWP2 knockout mice. Combination experiments were performed to investigate the relationship between WWP2 and downstream signaling in septic myocardium injury. Results: The protein level of WWP2 was downregulated in cardiomyocytes during sepsis. Cardiac-specific overexpression of WWP2 protected heart from sepsis induced mitochondrial oxidative stress, programmed cell death and cardiac injury, while knockdown or knockout of WWP2 exacerbated this process. The protective potency of WWP2 was predominantly linked to its ability to suppress cardiomyocyte ferroptosis rather than apoptosis. Mechanistically, our study revealed a direct interaction between WWP2 and acyl-CoA synthetase long-chain family member 4 (FACL4), through which WWP2 facilitated the ubiquitin-dependent degradation of FACL4. Notably, we observed a notable reduction in ferroptosis and cardiac injury within WWP2 knockout mice after FACL4 knockdown during sepsis. Conclusions: WWP2 assumes a critical role in safeguarding the heart against injury induced by sepsis via regulating FACL4 to inhibit LPS-induced cardiomyocytes ferroptosis.

BAG3 promotes proliferation and migration of arterial smooth muscle cells by regulating STAT3 phosphorylation in diabetic vascular remodeling.

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; BAG3FL/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.

Regulation of lipid metabolism by E3 ubiquitin ligases in lipid-associated metabolic diseases.

Previous studies have progressively elucidated the involvement of E3 ubiquitin (Ub) ligases in regulating lipid metabolism. Ubiquitination, facilitated by E3 Ub ligases, modifies critical enzymes in lipid metabolism, enabling them to respond to specific signals. In this review, we aim to present a comprehensive analysis of the role of E3 Ub ligases in lipid metabolism, which includes lipid synthesis and lipolysis, and their influence on cellular lipid homeostasis through the modulation of lipid uptake and efflux. Furthermore, it explores how the ubiquitination process governs the degradation or activation of pivotal enzymes, thereby regulating lipid metabolism at the transcriptional level. Perturbations in lipid metabolism have been implicated in various diseases, including hepatic lipid metabolism disorders, atherosclerosis, diabetes, and cancer. Therefore, this review focuses on the association between E3 Ub ligases and lipid metabolism in lipid-related diseases, highlighting enzymes critically involved in lipid synthesis and catabolism, transcriptional regulators, lipid uptake translocators, and transporters. Overall, this review aims to identify gaps in current knowledge, highlight areas requiring further research, offer potential targeted therapeutic approaches, and provide a comprehensive outlook on clinical conditions associated with lipid metabolic diseases.

Associations of trajectories in body roundness index with incident cardiovascular disease: a prospective cohort study in rural China.

Aims: The 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. Methods: In 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. Results: Three 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 <50 years. Conclusion: BRI trajectory was positively associated with incident CVD, providing a novel possibility for the primary prevention of CVD in rural regions of China.

E3 ubiquitin ligase WWP2 as a promising therapeutic target for diverse human diseases.

Mammalian E3 ubiquitin ligases have emerged in recent years as critical regulators of cellular homeostasis due to their roles in targeting substrate proteins for ubiquitination and triggering subsequent downstream signals. In this review, we describe the multiple roles of WWP2, an E3 ubiquitin ligase with unique and important functions in regulating a wide range of biological processes, including DNA repair, gene expression, signal transduction, and cell-fate decisions. As such, WWP2 has evolved to play a key role in normal physiology and diseases, such as tumorigenesis, skeletal development and diseases, immune regulation, cardiovascular disease, and others. We attempt to provide an overview of the biochemical, physiological, and pathophysiological roles of WWP2, as well as open questions for future research, particularly in the context of putative therapeutic opportunities.

Construction and validation of a nomogram to predict left ventricular hypertrophy in low-risk patients with hypertension.

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.

Advances in the study of exosomes in cardiovascular diseases.

BACKGROUND: Cardiovascular disease (CVD) has been the leading cause of death worldwide for many years. In recent years, exosomes have gained extensive attention in the cardiovascular system due to their excellent biocompatibility. Studies have extensively researched miRNAs in exosomes and found that they play critical roles in various physiological and pathological processes in the cardiovascular system. These processes include promoting or inhibiting inflammatory responses, promoting angiogenesis, participating in cell proliferation and migration, and promoting pathological progression such as fibrosis. AIM OF REVIEW: This systematic review examines the role of exosomes in various cardiovascular diseases such as atherosclerosis, myocardial infarction, ischemia-reperfusion injury, heart failure and cardiomyopathy. It also presents the latest treatment and prevention methods utilizing exosomes. The study aims to provide new insights and approaches for preventing and treating cardiovascular diseases by exploring the relationship between exosomes and these conditions. Furthermore, the review emphasizes the potential clinical use of exosomes as biomarkers for diagnosing cardiovascular diseases. KEY SCIENTIFIC CONCEPTS OF REVIEW: Exosomes are nanoscale vesicles surrounded by lipid bilayers that are secreted by most cells in the body. They are heterogeneous, varying in size and composition, with a diameter typically ranging from 40 to 160 nm. Exosomes serve as a means of information communication between cells, carrying various biologically active substances, including lipids, proteins, and small RNAs such as miRNAs and lncRNAs. As a result, they participate in both physiological and pathological processes within the body.

The role of glycolytic metabolic pathways in cardiovascular disease and potential therapeutic approaches.

Cardiovascular disease (CVD) is a major threat to human health, accounting for 46% of non-communicable disease deaths. Glycolysis is a conserved and rigorous biological process that breaks down glucose into pyruvate, and its primary function is to provide the body with the energy and intermediate products needed for life activities. The non-glycolytic actions of enzymes associated with the glycolytic pathway have long been found to be associated with the development of CVD, typically exemplified by metabolic remodeling in heart failure, which is a condition in which the heart exhibits a rapid adaptive response to hypoxic and hypoxic conditions, occurring early in the course of heart failure. It is mainly characterized by a decrease in oxidative phosphorylation and a rise in the glycolytic pathway, and the rise in glycolysis is considered a hallmark of metabolic remodeling. In addition to this, the glycolytic metabolic pathway is the main source of energy for cardiomyocytes during ischemia-reperfusion. Not only that, the auxiliary pathways of glycolysis, such as the polyol pathway, hexosamine pathway, and pentose phosphate pathway, are also closely related to CVD. Therefore, targeting glycolysis is very attractive for therapeutic intervention in CVD. However, the relationship between glycolytic pathway and CVD is very complex, and some preclinical studies have confirmed that targeting glycolysis does have a certain degree of efficacy, but its specific role in the development of CVD has yet to be explored. This article aims to summarize the current knowledge regarding the glycolytic pathway and its key enzymes (including hexokinase (HK), phosphoglucose isomerase (PGI), phosphofructokinase-1 (PFK1), aldolase (Aldolase), phosphoglycerate metatase (PGAM), enolase (ENO) pyruvate kinase (PKM) lactate dehydrogenase (LDH)) for their role in cardiovascular diseases (e.g., heart failure, myocardial infarction, atherosclerosis) and possible emerging therapeutic targets.

Influence of hypertension and global or abdominal obesity on left ventricular hypertrophy: A cross-sectional study.

Although hypertension and obesity are both risk factors for left ventricular hypertrophy (LVH), the extent of their impact on LVH in the general population is still unclear, and the predictive value of obesity indicators for LVH remains to be elucidated. In this study, obesity-related indicators, including waist circumference (WC), waist-height ratio (WHTR), and waist-hip ratio (WHR), were used to define abdominal obesity (AO), whereas body mass index (BMI) was used to measure general obesity (GO). The effects of hypertension and obesity on LVH were estimated using logistic regression analysis, as was the relative risk of LVH based on the presence of obesity, hypertension, or both. Subgroup analyses were performed based on sex and age. Of the 9134 participants (≥35 years old), 915 (10.0%) developed LVH. After adjusting for covariates, the odds ratios (95% confidence intervals) for LVH were 3.94 (3.27-4.75) in patients with hypertension, 1.90 (1.60-2.26) in those with GO, and 1.45 (1.25-1.69), 1.69 (1.43-2.00), and 1.54 (1.33-4.75) in individuals with AO defined based on WC, WHTR, and WHR, respectively. Analysis by sex showed similar values in women, but AO based on WC and WHR were not significantly associated with LVH in men. Further, after adjusting for potential confounding factors, concomitant hypertension and obesity had an increased risk of developing LVH in all age ranges, particularly in patients aged 35-45 years (risk increased 14.14-fold, 10.84-fold, 7.97-fold, and 9.95-fold for BMI-based GO and WC-, WHTR-, and WHR-based AO, respectively), and in both men and women but particularly in men (risk increased 7.71-fold, 4.67-fold, 5.83-fold, and 5.58-fold, respectively). In summary, all obesity indicators (BMI, WC, WHTR, and WHR) had predictive value for LVH in women; however, only BMI and WHTR should be considered for men. Furthermore, monitoring for the occurrence and progression of LVH is imperative for rural Chinese patients with concomitant hypertension and obesity, especially men and those aged 35-45 years.

Effect of body mass index trajectory on hypertension among children and adolescents aged 5-18 years: a retrospective cohort study.

BACKGROUND: 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.

Five body mass index trajectories from ages 5­18 years were determined using the LCGMM method, which labeled as the slow increasing group, overweight and obesity (OW/OB) group, normal decreasing group, stable normal group, and fast-increasing group.Different BMI trajectories in children and adolescents aged 5­18 years are differentially associated with the development of hypertension.Increased BMI levels in children and adolescents increase the risk of hypertension. Moreover, even within the normal BMI range, a modest growth might raise the risk of high-normal BP.

Prevalence and Risk Factors of Mitral, Tricuspid, and Aortic Regurgitation: A Population-Based Study from Rural Northeast China.

The population-based studies on the epidemiologic features of valvular regurgitation in Northeast China are scarce. We aim to estimate the prevalence and risk factors of mitral regurgitation (MR), tricuspid regurgitation (TR), and aortic regurgitation (AR) in a general population from rural Northeast China. Valvular regurgitation was assessed by color flow Doppler echocardiography in a population-based survey of 11,278 participants aged ≥35 years in rural areas of Liaoning Province during 2012 to 2013. The prevalence of mild or greater MR and TR were 1.6% and 1.5%, respectively. Trace or greater AR was present in 4.1% of the participants. In the multivariable regression model, older age, left atrial dimension, low left ventricular (LV) ejection fraction, and fasting plasma glucose were associated with higher risk of MR in men, whereas only older age and left atrial dimension increased the risk in women. Body mass index was found to be a protective factor for MR in women (odds ratio 0.847, 95% confidence interval 0.741 to 0.969). TR was independently associated with age, heart rate, low LV ejection fraction, current drinking status, and high-density lipoprotein cholesterol. The risk for AR significantly increased with age in both genders. LV mass index and aortic dimension increased the risk of AR in males, and females with higher LV mass index and high-density lipoprotein cholesterol had an increased risk for AR. In both genders, systolic blood pressure presented as a risk factor for AR, while diastolic blood pressure as a protective factor. In this large Chinese population-based study, we found remarkably low prevalence of valvular regurgitation, adding evidence for estimating disease burden and making policy strategies in Northeast China.

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

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

Efficacy and Safety Comparative of Sacubitril/Valsartan vs. Olmesartan in the Treatment of hypertension: A Meta-analysis of RCTs.

BACKGROUND: Sacubitril/valsartan (LCZ696) is a widely used drug for hypertension in Asia, popular for its efficacy and safety. However, there has been no comprehensive literature review comparing it with olmesartan. This meta-analysis compared the antihypertensive and adverse effects of sacubitril/valsartan and olmesartan. METHODS: We conducted a comprehensive search of Pubmed, Web of Science, Embase, Cochrane Library, and ClinicalTrials.gov databases to identify eligible randomized controlled trials (RCTs). The data were then analyzed and processed using Revman 5.4 and Stata SE14 software. RESULTS: Six RCTs with 4,127 patients were identified, showing that LCZ696 had better blood pressure control than olmesartan; mean sitting systolic and diastolic blood pressure, sitting pulse pressure, 24-hour ambulatory systolic blood pressure, and 24-hour ambulatory diastolic blood pressure were significantly decreased with LCZ696 compared with olmesartan. No significant difference between LCZ696 and olmesartan was observed in the occurrence of the majority of adverse events, with a decreased probability of headache in patients with sacubitril/valsartan compared with olmesartan. The subgroup analysis showed treatment with 400 mg/d LCZ696 was better than olmesartan in reducing serious adverse events. CONCLUSIONS: Sacubitril/valsartan was better than olmesartan in controlling blood pressure in patients with hypertension, with relatively higher safety.

Associations of sleep duration, daytime napping, and snoring with depression in rural China: a cross-sectional study.

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.