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Vascular smooth muscle cells (VSMCs) proliferation and migration play a fundamental role during the process of hypertensive angiopathy. Angiotensin-II (Ang-II) is one of the robust phenotype-modulating agents, which changes VSMCs to efficiently proliferate and migrate. The mechanism of the proliferation and migration is not well understood yet. Septin4, as a member of GTP binding protein family, is widely expressed in the eukaryotic cells and considered to be an essential component of the cytoskeleton which is involved in many important physiological processes. We approved that Septin4 expression was upregulated in mouse aorta by continuous infusion of Ang-II and in cultured VSMCs treated with Ang-II. Overexpression of Septin4 led to lower level of autophagy and decreased capacity of proliferation and migration. In order to identify the mechanism by which Septin4 interacts with these processes, we blocked autophagy by chloroquine (CQ). After inhibiting the autophagy, the ability of proliferation and migration was further restrained in the Septin4 overexpression VSMCs. In conclusion, our results indicated that during the process of VSMCs proliferation and migration induced by Ang-II, Septin4 modulated autophagy and thus regulated the activity of proliferation and migration.

Objective:To gain more comprehensive understanding of metabolic syndrome (Mets) among in general Chinese population.Design:Cross-sectional study. Mets was defined by three widely accepted definitions including modified Adults Treatment Panel (ATP) III criteria, International Diabetes Federation (IDF) criteria and harmonized definition. Risk factors were evaluated by using multivariate logistic regression.Setting:Nineteen rural villages in northeast China.Participants:The survey was conducted in September 2017 and May 2018 on 10 926 individuals.Results:According to modified ATP III criteria, IDF criteria and harmonised definition, the overall prevalence of Mets was 41·3 % (95 % CI 40·3, 42·2), 34·2 % (95 % CI 33·2, 35·1) and 44·1 % (95 % CI 43·1, 45·1), respectively. Females had a higher prevalence, and elevated blood pressure was the most frequent. Age, female sex, non-peasant worker, higher BMI and lower-annual income were independent risk factors of Mets in all three definitions (all ps Conclusions:Mets is highly prevalent in rural areas of northeast China. Its independent risk factors include higher age, female sex, non-peasantry worker, higher BMI and lower-annual income. Modified ATP III criteria and harmonised definition may be superior definitions of Mets.

OBJECTIVES The 2017 American College of Cardiology/American Heart Association (ACC/AHA) Guideline for high blood pressure (BP) in adults redefined hypertension as SBP at least 130 mmHg or DBP at least 80 mmHg. However, the optimal BP for different BMI population to reduce stroke incidence is uncertain. METHODS A prospective cohort study was designed by four examinations: baseline (2004-2006), 2008, 2010 and 2017 follow-up. The study group composed of 36 352 individuals, to determine the ideal BP range to reduce stroke incidence of two BMI level, adjusted Cox proportional hazards models were utilized to establish the associations between SBP/DBP and the risk of stroke incident. Then, the restricted cubic spline regression was applied to find the ideal range of SBP/DBP values for two kinds of BMI categories definitions. RESULTS During a median follow-up period of 12.5 years, 2548 (7.0%) nonstroke individuals at baseline developed incident stroke. After fully adjusting confounding factors, SBP (per 20 mmHg increase) and DBP (per 10 mmHg increase) are independently associated with the risk of stroke incidence [SBP, hazard ratio = 1.277, 95% confidence interval (95% CI), 1.217-1.340, P

Background. The 2017 American College of Cardiology and American Heart Association hypertension guideline updated stage 1 hypertension definition as systolic blood pressure range from 130 to 139 mmHg or diastolic blood pressure from 80 to 89 mmHg. However, the association of stage 1 hypertension with stroke and its subtypes among the older population in rural China remains unclear. Methods. This population-based cohort study consisted of 7,503 adults aged ≥60 years with complete data and no cardiovascular disease at baseline from rural areas of Fuxin County, Liaoning province, China. Follow-up for the new cases of stroke was conducted from the end of the baseline survey to the end of the third follow-up survey (January 1, 2007–December 31, 2017). Adjusted Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals with the normal blood pressure as a reference, and calculated population attributable risk was based on prevalence and hazard ratios. Results. During a median follow-up of 12.5 years, we observed 1,159 first-ever incident stroke (774 ischemic, 360 hemorrhagic, and 25 uncategorized). With the blood pressure Conclusion. Among adults aged ≥60 years in rural China, stage 1 hypertension defined by 2017 American College of Cardiology and American Heart Association hypertension guideline was independently associated with the increased risk of all stroke and ischemic stroke, excluding hemorrhagic stroke.

BackgroundThe study was performed to investigate the impact of prehypertension defined by the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC7) on the risk of major adverse cardiovascular events (MACE) in a Chinese rural cohort.MethodsThe epidemiological prospective cohort study included 38,765 participants aged ≥35 years followed for a median of 12.5 years—divided into normal BP (n = 7,366), prehypertension (n = 18,095), and hypertension groups (n = 13,304)—were enrolled for the final analysis. Follow-up for MACE including cardiovascular disease (CVD) death, stroke and myocardial infarction (MI) was conducted. Adjusted Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI).ResultsThe age and sex-adjusted incidence of MACE and its subtypes rose progressively with elevation of BP levels (P < 0.001). After adjusting multivariable Cox proportional hazards, significant increases were observed from the prehypertensive group for incident MACE (HR = 1.337, 95% CI: 1.186–1.508, P < 0.001), CVD mortality (HR = 1.331, 95% CI: 1.109–1.597, P = 0.002), and stroke (HR = 1.424, 95% CI：1.237–1.639, P < 0.001) but not MI (P > 0.05) compared with normal BP.ConclusionPrehypertensive individuals had a greater risk of incident MACE, CVD mortality, and stroke, implying that improvements in BP monitoring and early intervention in individuals with prehypertension in rural China are urgently needed.

Hyperuricemia and Hypertension are two independent risk factors of renal function damage. Our research aimed to investigate the synergistic interaction between hyperuricemia and hypertension toward reduced eGFR.Our analyses included 11,694 participants from a cross-sectional population-based Northeast China Rural Cardiovascular Health Study. Interaction was assessed on both multiplicative and additive scales.The prevalence of reduced estimated glomerular infiltration rate (eGFR) was 2.11% in our population. After adjustment of age, sex, race, education level, family income, current smoking and drinking status, body mass index, total cholesterol, high-density lipoprotein cholesterol, and diabetes, subjects with both hyperuricemia and hypertension suffered from a 11.004 (95% CI: 7.080-17.102) times risk of reduced eGFR than the healthy reference group, greater than that in participants with only hyperuricemia (5.741, 95% CI: 3.045-10.825) or hypertension (1.145, 95% CI: 0.764-1.715). Furthermore, additive interaction between hyperuricemia and hypertension was statistically significant and synergistic (relative excess risk due to interaction: 5.118, 95% CI: 0.611-9.624; the attributable proportion due to interaction: 0.465, 95% CI: 0.151-0.779; Synergy index: 2.047, 95% CI: 1.017-4.120). However, our results revealed no significant interaction on the multiplicative scale.Hyperuricemia and hypertension may have a synergistic interaction toward renal function loss in addition to their independent impacts. Our findings may provide a straightforward illustration which is easy for the public to realize the hazard of coexistent hypertension and hyperuricemia on renal injury.

Objective: To characterize the influence of relative wall thickness (RWT) on Cornell, Sokolow-Lyon and Peguero-Lo Presti voltages and elucidate its potential impacts on their diagnostic accuracy for LVH in a large general Chinese population. Methods: A total of 10,614 permanent residents aged ≥ 35 years were recruited for this study. All the participants were subjected to ECG and echocardiogram during the same visit. Multivariate linear and logistic regression analyzes were conducted to assess the influence of RWT on the voltages and their diagnostic performance for LVH detection. Results: A distinct correlation was identified between RWT and Cornell and Peguero-Lo Presti voltages following adjustments for age, gender and left ventricular mass (LVM) (β = 0.675 and 1.342, respectively; Ps < 0.001). Besides, subjects with RWT > 0.42 exhibited higher rates of LVH diagnosed by Cornell (OR = 1.78, 95% CI: 1.45–2.20), Sokolow-Lyon (OR = 1.30, 95% CI: 1.08–1.56), and Peguero-Lo Presti voltage (OR = 1.48, 95% CI: 1.29–1.70) after adjustments for age, gender and echocardiographic LVH. Furthermore, concentric remodeling or concentric hypertrophy displayed higher rates of LVH diagnoses via Cornell and Peguero-Lo Presti voltage criteria, as compared with normal geometry or eccentric hypertrophy, respectively (all Ps < 0.05), findings of which were independent of age, gender and LVMI. Conclusion: Echocardiographic RWT was independently correlated with electrocardiographic voltage measures of LVH, which influenced their positive rates and contributed to poor diagnostic performance.

SIRT1 and STAT3 are key to human aortic vascular smooth muscle cells (HAVSMCs) proliferation, migration and phenotypic transformation, but the regulatory mechanism of SIRT1-STAT3 in this process is still unclear. Septin4 is a cytoskeleton-related protein that regulates oxidative stress-vascular endothelial injury. However, the role and underlying mechanism of Septin4 in atherosclerosis remains unknown. Here, we revealed the role and mechanism of Septin4 in regulating SIRT1-STAT3 in atherosclerosis. We determined that the expression of Septin4 were markedly increased in Apoe-/- atherosclerosis mice and PDGF-BB-induced HAVSMCs. Knockdown of Septin4 significantly increased PDGF-BB-induced HAVSMCs proliferation, migration and phenotypic transformation, while overexpression of Septin4 had the opposite effects. Mechanically, co-immunoprecipitation results demonstrated that Septin4 was a novel interacting protein of STAT3 and SIRT1. Septin4 formed a complex with SIRT1-STAT3, enhancing the interaction between SIRT1 and STAT3, ensuing promoting SIRT1-regulated STAT3-K685 deacetylation and STAT3-Y705 dephosphorylation, which inhibited PDGF-BB-induced HAVSMCs proliferation, migration and phenotype transformation. Therefore, our findings provide novel insights into the prevention and treatment of atherosclerosis.

This study aimed to investigate the effect of body mass index (BMI) changes on hypertension among rural areas of China. A population-based sample of 13,263 and 5944 rural Chinese people aged ≥35 years and without hypertension at baseline was included in our analysis of BMI changes (from (2004-2006) to 2008) and short- and long-term outcomes of hypertension (from 2008 to 2010 and 2010 to 2017). The participants were divided into four groups by a comprehensive cross-sectional combination according to baseline BMI (18.5-24 vs. ≥24 kg/m2) and follow-up changes (decreased vs. increased). Adjusted Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs). During a median follow-up period of 4.8 (short-term) and 11.7 (long-term) years, 2299 (17.33%) and 2020 (33.98%) participants developed hypertension, respectively. For participants with a baseline BMI ≥ 24 kg/m2, when BMI decreased in follow-ups, the multivariable-adjusted HRs (95% CI) of short-term hypertension were 0.898 (0.857-0.942). For baseline 18.5 kg/m2 ≤ BMI < 24 kg/m2, when BMI increased in follow-ups, the risks of short-term hypertension were 1.103 (1.068-1.139). We detected that BMI changes had a lower impact on the incidence of hypertension in long-term than short-term. Our study indicated that BMI changes were significantly associated with the incidence of hypertension for the short-term, and it had a stronger impact on short-term outcomes than long-term. Managing weight by lifestyle modification was particularly important for the primary prevention of hypertension in rural Chinese population.

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.

ObjectivesThis study aimed to reveal the association between metabolic score for insulin resistance (MetS-IR) and the risk of mildly decreased estimated glomerular filtration rate (eGFR), and explore the evaluation effect of MetS-IR on the progress of eGFR decline.Study designA cross-sectional study.Setting and participantsA total of 11 956 rural participants (aged ≥35 years) from northeastern China were enrolled in the study. After excluding the subjects whose data were not integrated or who met the exclusion criteria, we finally obtained 11 042 participants in the present study.Main outcome measuresMildly decreased eGFR was defined as 60–90 mL/min/1.73 m2.ResultsThe prevalence of mildly decreased eGFR in the general population was 36.9%. After adjustment of covariates, each SD increment of MetS-IR could bring 26.3% additional risk of mildly decreased eGFR (OR: 1.263, 95% CI: 1.066 to 1.497, p=0.007). When MetS-IR was classified into four levels by quartile, we observed participants in the top level had 3.032-fold risk of mildly decreased eGFR (OR: 3.032, 95% CI: 1.841 to 4.991, pConclusionHigh MetS-IR was associated with high risk of mildly reduced eGFR and often accompanied by a high risk of accelerated decline in eGFR. Hence, we believed MetS-IR was a suitable indicator to evaluate the risk of early-stage renal dysfunction.

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.

Zhao Li,1 Yiqing Yang,1 Liqiang Zheng,2 Guozhe Sun,1 Xiaofan Guo,1 Yingxian Sun1 1Department of Cardiology, The First Hospital of China Medical University, Shenyang, 110001, People’s Republic of China; 2Department of Clinical Epidemiology, Library, Department of Health Policy and Hospital Management, Shengjing Hospital of China Medical University, Shenyang, 110004, People’s Republic of ChinaCorrespondence: Yiqing Yang; Yingxian Sun Tel +86 24 83282688Fax +86 24 83282346Email yangyiqing0725@163.com; yingxiansun123@163.comObjective: To develop and validate a new prediction model for the general population based on a large panel of both traditional and novel factors in cardiovascular disease (CVD).Design and Setting: We used a prospective cohort in the Northeast China Rural Cardiovascular Health Study (NCRCHS).Participants: A total of 11,956 participants aged ≥ 35 years were recruited between 2012 and 2013, using a multistage, randomly stratified, cluster-sampling scheme. In 2015 and 2017, the participants were invited to join the follow-up study for incident cardiovascular events. The loss to follow-up number was 351. At the study’s end, we obtained the CVD outcome events for 10,349 participants.Primary and Secondary Outcome Measures: The prediction model was developed using demographic factors, blood biochemical indicators, electrocardiographic (ECG) characteristics, and echocardiography indicators collected at baseline (Model 1). Framingham-related variables, namely age, sex, smoking, total and high-density lipoprotein cholesterol and diabetes status were used to construct the traditional model (Model 2).Results: For the observed population (n = 10,349), the median follow-up time was 4.66 years. The total incidence of CVD was 1.1%/year, including stroke (n = 342) and coronary heart disease (n = 175). The results of Model 1 indicated that in addition to the traditional risk factors, QT interval (p < 0.001), aortic root diameter (p < 0.001), and ventricular septal thickness (p < 0.001) were predictive factors for CVD. Decision curve analysis (DCA) showed that the net benefit with Model 1 was higher than that of Model 2.Conclusion: QT interval from electrocardiography and aortic root diameter and ventricular septal thickness from echocardiography should be included in the CVD risk prediction models.Keywords: CVD, predictive model, general cohort, QT interval, aortic root diameter, ventricular septal thickness

Poly(ADP-ribose) polymerase 1 (PARP1) has a major regulatory role in cardiovascular disease. However, inhibiting PARP1 activity does not significantly improve clinical outcomes of cardiovascular disease, which suggests that the regulatory mechanism of PARP1 in cardiovascular disease is unclear. Here, we focused on deacetylation regulatory mechanisms of PARP1 and crosstalk of PARP1 post-translational modifications. We uncovered the crucial molecular interactions and protein modifications of deacetylase Sirtuin 2 (SIRT2) and PARP1 in vascular damage. The results showed that SIRT2 was involved in this process and oxidative stress damage factor PARP1 was a novel physiological substrate of SIRT2. SIRT2 interacted with PARP1 at the PARP-A-helical domain and deacetylated the K249 residue of PARP1. Furthermore, SIRT2 promoted ubiquitination of the K249 residue of PARP1 via mobilization of the E3 ubiquitin ligase WW domain-containing protein 2 (WWP2), which led to proteasome-mediated degradation of PARP1. Knockout of SIRT2 in mice and cells increased PARP1 acetylation and decreased PARP1 ubiquitination, which in turn aggravated oxidative stress-induced vascular injury and remodeling. Conversely, overexpression of SIRT2 in mice and cells decreased PARP1 acetylation, increased PARP1 ubiquitination, and relieved oxidative stress-induced vascular injury and remodeling. Overall, this study revealed a previously unrecognized mechanistic link between SIRT2 and PARP1 in the regulation of oxidative stress-induced vascular injury., Graphical abstract Image 1, Highlights • SIRT2 is the key in Sirtuin family involved in oxidative stress vascular injury. • SIRT2-KO/SIRT2-TG mice aggravates/relieves oxidative stress vascular injury. • Oxidative stress injury factor PARP1 is a novel physiological substrate of SIRT2. • Lysine 249 is of critical importance of PARP1 deacetylation by SIRT2. • SIRT2 promotes ubiquitination of the K249 residue of PARP1 by mobilization of WWP2.

Hypertension is a major modifiable risk factor that affects the global health burden. Despite the availability of multiple antihypertensive drugs, blood pressure is often not optimally controlled. The prevalence of true resistant hypertension in treated hypertensive patients is ~2-20%, and these patients are at higher risk for adverse events and poor clinical outcomes. Therefore, an in-depth dissection of the pathophysiological mechanisms of hypertension and resistant hypertension is needed to identify more effective targets for regulating blood pressure. Omics technologies, such as genomics, transcriptomics, proteomics, metabolomics, and microbiomics, can accurately present the characteristics of organisms at varying molecular levels. Integrative omics can further reveal the network of interactions between molecular levels and provide a complete dynamic view of the organism. In this review, we describe the applications, progress, and challenges of omics technologies in hypertension. Specifically, we discuss the application of omics in resistant hypertension. We believe that omics approaches will produce a better understanding of the pathogenesis of hypertension and resistant hypertension and improve diagnostic and therapeutic strategies, thus increasing rates of blood pressure control and reducing the public health burden of hypertension.

Background: The recent American College of Cardiology/American Heart Association (ACC/AHA) guidelines redefined blood pressure levels 130-139/80-89 mmHg as stage 1 hypertension. However, the association of stage 1 hypertension with cardiovascular disease (CVD) and its age-specific differences among the rural women in Liaoning province remains unclear. It needs to be quantified in considering guideline adoption in China.Methods: In total, 19,374 women aged ≥35 years with complete data and no cardiovascular disease at baseline were followed in a rural community-based prospective cohort study of Liaoning province, China. Follow-up for the new cases of CVD was conducted from the end of the baseline survey to the end of the third follow-up survey (January 1, 2008–December 31, 2017). Adjusted Cox proportional hazards models were applied to estimate the Hazard Ratios (HR) and 95% Confidence Intervals (CI) with the normal blood pressure as a reference.Results: During the median follow-up period of 12.5 years, 1,419 subjects suffered all-cause death, 748 developed CVD, 1,224 participants suffered stroke and 241 had Myocardial Infarction (MI). Compared with normal BP, Stage 1 hypertension had a HR (95% CI) of 1.694 (1.202–2.387) in CVD mortality, 1.575 (1.244–1.994) in the incidence of stroke. The results obtained that the risk of CVD mortality and incidence of stroke was significantly associated with stage 1 hypertension in rural women aged ≥45 years after adjusting for other potential factors. However, in participants aged 35–44 years, stage 1 hypertension was not associated with an increased risk of cardiovascular disease.Conclusions: The newly defined stage 1 hypertension is associated with an increased risk of CVD mortality and also incidence of stroke in the rural women aged ≥45 years population of Liaoning province. This study can be a good reference for health policy makers and clinicians workers to make evidence-based decisions toward lowering burden of cardiovascular disease more efficient, timely measures on prevention and control of stage 1 hypertension in China.

Hypertensive nephropathy (HN), mainly caused by chronic hypertension, is one of the major causes of end-stage renal disease. However, the pathogenesis of HN remains unclarified, and there is an urgent need for improved treatments. Gene expression profiles for HN and normal tissue were obtained from the Gene Expression Omnibus database. A total of 229 differentially co-expressed genes were identified by weighted gene co-expression network analysis and differential gene expression analysis. These genes were used to construct protein–protein interaction networks to search for hub genes. Following validation in an independent external dataset and in a clinical database, POLR2I, one of the hub genes, was identified as a key gene related to the pathogenesis of HN. The expression level of POLR2I is upregulated in HN, and the up-regulation of POLR2I is positively correlated with renal function in HN. Finally, we verified the protein levels of POLR2I in vivo to confirm the accuracy of our analysis. In conclusion, our study identified POLR2I as a key gene related to the pathogenesis of HN, providing new insights into the molecular mechanisms underlying HN.

Digital, Background Guidelines recommend nonstatin lipid-lowering agents in patients at very high risk for major adverse cardiovascular events (MACE) if low-density lipoprotein cholesterol (LDL-C) remains ≥70 mg/dL on maximum tolerated statin treatment. It is uncertain if this approach benefits patients with LDL-C near 70 mg/dL. Lipoprotein(a) levels may influence residual risk. Objectives In a post hoc analysis of the ODYSSEY Outcomes (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) trial, the authors evaluated the benefit of adding the proprotein subtilisin/kexin type 9 inhibitor alirocumab to optimized statin treatment in patients with LDL-C levels near 70 mg/dL. Effects were evaluated according to concurrent lipoprotein(a) levels. Methods ODYSSEY Outcomes compared alirocumab with placebo in 18,924 patients with recent acute coronary syndromes receiving optimized statin treatment. In 4,351 patients (23.0%), screening or randomization LDL-C was 13.7 mg/dL or ≤13.7 mg/dL; corresponding adjusted treatment hazard ratios were 0.82 (95% CI: 0.72-0.92) and 0.89 (95% CI: 0.75-1.06), with Pinteraction = 0.43. Conclusions In patients with recent acute coronary syndromes and LDL-C near 70 mg/dL on optimized statin therapy, proprotein subtilisin/kexin type 9 inhibition provides incremental clinical benefit only when lipoprotein(a) concentration is at least mildly elevated. (ODYSSEY Outcomes: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; NCT01663402), Ciencias Médicas y de la Salud

Background: The triglyceride glucose index (TyG) has been proposed as a marker of insulin resistance or type 2 diabetes mellitus (T2DM). Risk of serum alanine aminotransferase (ALT) levels is increased in T2DM patients. We aimed to evaluate the association between TyG index and elevated ALT. Methods: A multicenter, cross-sectional study was conducted in China from Northeast China Rural Cardiovascular Health Study (NCRCHS), and 11,573 adults with complete data were included in our final analysis.Results: TyG index was positively associated with the prevalence of elevated ALT. Frequency of elevated ALT increased from the lowest to the top quartile of TyG in both sexes (p for trend Conclusions: TyG index is effective to identify individuals at risk for elevated ALT. TyG thresholds of 8.69 for men and 8.96 for women was highly sensitive for detecting elevated ALT subjects. Findings from this study underscore that TyG index may be suitable as a surrogate marker for abnormal liver enzymes in Chinese adults.

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 indice is the best to predict CVD in hypertensive people. Methods NCRCHS is a prospective cohort study in a general population in Northeast China. The study examined the cardiovascular health from 2013–2015, and follow-up captured the CVD incidence in 2018. Baseline waist-to-height ratio (WHtR), body mass index (BMI),waist-to-hip(WHR)and waist circumference (WC) 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 may be useful in predicting CVD incidence in hypertensive adults.

ObjectivesFew studies have explored whether the risk of myocardial infarction (MI) or stroke varies among patients with degenerative aortic valve disease (DAVD) with different severity of aortic regurgitation (AR) or not. Thus, a prospective study was conducted to elucidate the causal relationship between AR severity and risk of incident MI and stroke among patients with DAVD recruited from a general population in Northeast China.DesignProspective cohort study.SettingCommunity-based study carried out in rural areas of Northeast China.MethodsThere were 3675 patients with DAVD aged ≥45 years eligible for the prospective study. During a median follow-up time of 4.64 years, 99 participants lost to follow-up. Cox regression analyses were used to investigate the association between baseline AR severity and the risk of incident MI or stroke.ResultsIn the final cohort of 3576 patients with DAVD, there were 3153 patients without AR (88.2%), 386 patients with mild AR (10.8%) and 37 patients with moderate or severe AR (1.0%). Multivariate analyses showed that, compared with participants without AR, those with moderate/severe AR were associated with 8.33 and 6.22-fold increased risk of MI and MI mortality, respectively. However, no significant associations between AR and the risk of stroke or stroke mortality were observed.ConclusionsAs compared with no AR, moderate/severe AR but not mild AR was an independent predictor for the risk of MI and MI mortality. AR was not significantly associated with stroke or stroke mortality, irrespective of AR severity. Secondary prevention strategies should be taken to delay the progression of DAVD and thus reduce the incidence of MI.

Background Several ECG criteria have been widely used for diagnosis of left ventricular hypertrophy (LVH) in clinical practice. However, their performance in a general Chinese population is limited. Methods and results A multi‐stage, stratified cluster sampling across China was performed and 7415 representative Chinese adults aged 18–85 years were analyzed. ECG was collected by using GE MAC 5500 machine. The association between five ECG‐LVH criteria (i.e., Peguero–Lo Presti, Cornell, Cornell product, Sokolow–Lyon and Sokolow–Lyon product) and echocardiographic LVH (Echo‐LVH) was assessed by Pearson's correlation, diagnostic statistics like predictive values, and receiver operating characteristics (ROC) curve. We found that the prevalence of the Echo‐LVH was 11% while ECG‐LVH ranged from 3% to 27%. All ECG‐LVH criteria had high negative predictive value (NPV) (89%) and specificity (73–96%) but low positive predictive value (PPV) (12–24%) and sensitivity (4–29%). The newly Peguero–Lo Presti criteria had higher sensitivity (29%) but lower specificity (73%) and accuracy (68%) compared with other criteria. Cornell product had the best diagnostic performance (AUC: 0.59), as well as the highest specificity (96%) and accuracy (86%) but lowest sensitivity (4%). Among single‐lead components of ECG criteria, RaVL voltage and QRS duration performed relatively better than others. Hypertensive and older individuals had higher sensitivity but lower specificity and accuracy than their counterparts. Conclusion ECG‐LVH criteria had high NPV to detect Echo‐LVH. Though with higher sensitivity, Peguero–Lo Presti criteria did not have better diagnostic performance to detect Echo‐LVH. RaVL and QRS duration had stronger association with Echo‐LVH among all single‐lead components.

DNA polymerase gamma (PolG) is the major polymerase of mitochondrial DNA (mtDNA) and essential for stabilizing mitochondrial function. Vascular calcification (VC) is common senescence related degenerative pathology phenomenon in the end-stage of multiple chronic diseases. Mitochondrial dysfunction was often observed in calcified vessels, but the function and mechanism of PolG in the calcification process was still unknown. The present study found PolGD257A/D257A mice presented more severe calcification of aortas than wild type (WT) mice with vitamin D3 (Vit D3) treatment, and this phenomenon was also confirmed in vitro. Mechanistically, PolG could enhance the recruitment and interaction of p53 in calcification condition to recover mitochondrial function and eventually to resist calcification. Meanwhile, we found the mutant PolG (D257A) failed to achieve the same rescue effects, suggesting the 3'-5' exonuclease activity guarantee the enhanced interaction of p53 and PolG in response to calcification stimulation. Thus, we believed that it was PolG, not mutant PolG, could maintain mitochondrial function and attenuate calcification in vitro and in vivo. And PolG could be a novel potential therapeutic target against calcification, providing a novel insight to clinical treatment.

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.

Background: Prolonged heart rate-corrected QT (QTc) interval has been associated with incident cardiovascular diseases (CVD) in general Western populations. However, this association is unclear in Asian population. We aim to estimate the association between QTc interval and incident CVD in a general Chinese population.Methods: We analyzed 8,867 participants age ≥35 years and free of CVD at baseline in the Northeast China Rural Cardiovascular Health Study. A resting 12-lead electrocardiogram was performed on all participants, and QTc interval computed using the Framingham formula. Cox proportional hazards models were used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) for associations between QTc interval and incident stroke, coronary heart disease, and combined CVD events.Results: Over a median follow-up of 4.66 years, a total of 439 CVD events occurred (298 stroke cases and 152 CHD cases). After full adjustment, prolonged QTc defined by a sex-specific cutoff was associated with increased risk of developing stroke (HR: 1.82, 95% CI 1.20–2.75, P = 0.004) and combined CVD (HR: 1.52, 95% CI 1.05–2.19, P = 0.026). Spline analyses demonstrated no clear thresholds; when modeled as a linear relationship, each 10 ms increase of QTc interval was associated with an HR of 1.12 (95% CI 1.06–1.19, P < 0.001) for stroke and an HR of 1.10 (95% CI 1.05–1.15, P < 0.001) for combined CVD. Baseline QTc interval was not associated with incident CHD with either modeling strategy.Conclusions: Baseline QTc interval is associated with incident stroke and CVD in adults without prior CVD from a general Chinese population.

ObjectivesThe 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.DesignPopulation-based cohort study.SettingRural areas in Liaoning Province, Northeast China.ParticipantsAt 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 measuresCardiac 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.ResultsDuring 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.ConclusionsOur 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.

Background Growing evidence suggests that remnant cholesterol (RC) may contribute to residual atherosclerotic cardiovascular disease (ASCVD) risk. But the cut-off point to treat RC for reducing ASCVD is still not known. This study was aimed to investigate the relationships between RC and combined cardiovascular diseases (CVDs) in a general China cohort, with 11,956 subjects aged ≥ 35 years. Methods Baseline RC was estimated with the Friedewald formula for 8782 subjects. The outcome was the incidence of combined CVD, including fatal and nonfatal stroke and coronary heart disease (CHD). Cox proportional hazards model was used to calculate hazard ratios (HRs) with 95% confidence intervals. Restricted cubic spline model was used to evaluate dose-response relationship between continuous RC and the natural log of HRs. Results After a mean follow-up of 4.66 years, 431 CVD events occurred. In the cox proportional models, participants with high level of categorial RC had significantly higher risk for combined CVD (HR: 1.37; 95% CI: 1.07–1.74) and CHD (HR: 1.63; 95% CI: 1.06–2.53), compared to those with medium level of RC. In the stratification analyses, high level of RC significantly increased combined CVD risk for subgroups females, age

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 P Conclusions Our prospective cohort supports that abnormal LV geometry by echocardiography has a prognostic significance for incident stroke/CHD and all-cause mortality, implying that early detection and intervention of LV structural remodeling in rural China are urgently needed to prevent adverse outcomes.

Funding Acknowledgements Type of funding sources: None. Background Cardiometabolic index (CMI) defines adiposity based on triglycerides (TG) to high-density lipoprotein cholesterol (HDL-C) ratio and waist-to-height ratio (WHtR). This newly proposed metric has been used to detect multiple cardiovascular risk factors, but data relative to diabetes in the general population are lacking. This study aims to validate CMI’s utility of discriminating diabetes and compares it with other indexes among general Chinese population. Methods Analyses were based on a cross-sectional study of 11,478 participants that underwent assessment of metabolic and anthropometric parameters in rural areas of northeastern China in 2013. CMI was calculated by TG/HDL-C × WHtR. Multivariate logistic regressions were performed to clarify CMI’s association with diabetes, ROC analyses were engaged to investigate CMI’s discriminating ability for diabetes. Results The prevalence of diabetes was 9.93% in males while 10.76% in females, and increased with CMI’s increment. After full adjustment, each SD increment of CMI had odds ratios (ORs) for diabetes of 1.471 (1.367–1.584) and 1.422 (1.315–1.539) in females and males, respectively. Compared with bottom categories of CMI, the top quartiles had ORs of 3.736 (2.783–5.015) in females and 3.697 (2.757–4.958) in males. The ROC results showed an excellent discriminating power of CMI (AUC: 0.702 for females, 0.664 for males). Conclusions An increasing CMI was correlated with higher odds of diabetes, supporting CMI as a useful and economic measure to screen and quantify diabetes in general Chinese population. Monitoring and promoting achievement of dyslipidemia and abdominal obesity based on CMI may improve subclinical and cardiovascular outcomes. Abstract Figure.

Funding Acknowledgements Type of funding sources: None. Background AHA"s Life"s Simple 7 cardiovascular health score is recommended for use in primary prevention. Simpler tools not requiring laboratory tests, such as the Fuster-BEWAT score (FBS) (blood pressure [B], exercise [E], weight [W], alimentation [A], and tobacco [T]), are also available. Purpose This study sought to compare the effectiveness of Life"s Simple 7 and FBS in predicting the newly proposed 4-tiered left ventricular hypertrophy (LVH) classification based on LV dilatation (high LV end-diastolic volume [EDV] index) and concentricity (mass/end-diastolic volume [M/EDV]0.67) in the general Chinese population. Methods Participants from Northeast China Rural Cardiovascular Health study who underwent cardiac echocardiography (n = 11,261) were enrolled. Patients with LVH were divided into 4 groups—eccentric nondilated (normal M/EDV and EDV), eccentric dilated (increased EDV, normal M/EDV), concentric nondilated (increased M/EDV, normal EDV), and concentric dilated (increased M/EDV and EDV)—and compared with patients with normal LVM. Results With poor Life"s Simple 7 and FBS as references, individuals with ideal Life"s Simple 7 and FBS showed lower adjusted odds of having eccentric nondilated (Life"s Simple 7, odds ratio [OR]: 0.26; 95% confidence interval [CI]: 0.20 to 0.34 vs. FBS, OR: 0.28; 95% CI: 0.20 to 0.38), eccentric dilated (OR: 0.73 [0.57-0.94] vs. OR: 0.57 [0.43-0.76]), concentric nondilated (OR: 0.12 [0.04-0.38] vs. OR: 0.19 [0.07-0.52]), and concentric dilated LVH (OR: 0.12 [0.03-0.37] vs. OR: 0.26 [0.10-0.72]). Taken together, the odds for these 4 LV geometric phenotypes decreased in a graded manner in subjects with intermediate and ideal ICHS and FBS compared with subjects with poor ICHS and FBS (p for trend Conclusions Our findings demonstrate that the FBS appears capable of performing just as well as does the Life"s Simple 7 in predicting the novel 4-group classification of LVH, making the FBS particularly suited as a reliable low-cost indicator of CV health in settings where access to laboratory analysis is limited and health care resources are constrained. Abstract Figure.

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.

Hypertension and hyperhomocysteinemia are two independent risk factors of chronic kidney disease (CKD). Our study aimed to evaluate whether hypertension and hyperhomocysteinemia act synergistically toward renal injury. Our analysis included 13 693 subjects from the National Health and Nutritional Survey (NHANES) 1999-2006. Association was assessed by multivariate logistic regressions. The interaction was investigated on both additive and multiplicative scales. CKD had a prevalence of 17.62% in the NHANES population. After adjusting for age, sex, race, education, physical activity, drinking frequency, current smoking status, poverty-to-income ratio, Total cholesterol, high-density lipoprotein cholesterol, serum folate, vitamin B12, body mass index, waist circumference, and diabetes mellitus, patients with both hypertension and hyperhomocysteinemia had a 5.072 (3.967-6.486) times risk of CKD than their healthy compartments, higher than that in patients with only hypertension or hyperhomocysteinemia. Moreover, additive interaction of hypertension and hyperhomocysteinemia was significant (relative excess risk due to interaction: 2.107, 95% CI: 1.071-3.143; the attributable proportion due to interaction: 0.415, 95% CI: 0.270-0.561; synergy index: 2.072, 95% CI: 1.449-2.962). Finally, subgroup analyses elucidated the interaction was robust in those with only reduced estimated glomerular filtration rate or albuminuria, and stratification analyses based on gender showed consistency with the main results. Hypertension and hyperhomocysteinemia may act synergistically toward a greater renal injury than the sum of their independent effects. Our findings suggest the coexistence itself also correlates with a deteriorative impact on renal function in addition to the effects of hypertension and diabetes themselves. The results may support the rationality and value of simultaneous tight control of hypertension and hyperhomocysteinemia to prevent CKD.

This study was performed to investigate the association between stage 1 hypertension defined by the 2017 ACC/AHA guidelines and the risk of adverse events among adults aged 35 to 49 years. A total of 20,072 adults aged 35–49 years, without a history of cardiovascular disease (CVD) at baseline were included in the present study. Adjusted Cox proportional hazards models were applied to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). During a median follow-up period of 12.5 years, the results indicated that 777 subjects suffered all-cause death and 299 subjects developed CVD. A total of 830 subjects were involved in incident stroke and 141 subjects had a myocardial infarction (MI). Stage 1 hypertension had a HR (95% CI) of 1.38 (1.13–1.70) for all-cause mortality, 1.74 (1.20–2.53) for CVD mortality, 1.78 for (1.40–2.26) for stroke incidence, and 1.64 (0.99–2.71) for MI incidence, respectively, compared with blood pressure (BP)

Background Elevated blood pressure (BP) is closely related to stroke and its subtypes. However, different time periods changes in BP may result in differential risk of stroke. Hypothesis Short‐term blood pressure changes have a more strong impact on stroke and its subtypes than long‐term blood pressure changes. Methods We designed the study on the effects of short‐ (2008‐2010) and long‐term (2004‐2010) BP changes on stroke events (2011‐2017), including 22 842 and 28 456 subjects, respectively. The difference in β coefficients between short‐ and long‐term BP changes on the effects of stroke were examined using the Fisher Z test. Results During a median 12.5‐year follow‐up period, 1014 and 1505 strokes occurred in short‐ and long‐term groups. In short‐term group, going from prehypertension to hypertension, the risk of stroke events increased (stroke: hazard ratio [HR] = 1.537 [1.248‐1.894], ischemic stroke: 1.456 [1.134‐1.870] and hemorrhagic stroke: 1.630 [1.099‐2.415]); going from hypertension to prehypertension, the risk of stroke events decreased (stroke:0.757 [0.619‐0.927] and hemorrhagic stroke:0.569 [0.388‐0.835]). Similarly, in long‐term group, going from prehypertension to hypertension, individuals had an increased risk of stroke (1.291, 1.062‐1.569) and hemorrhagic stroke (1.818, 1.261‐2.623); going from hypertension to prehypertension, participants had a decreased risk of stroke (0.825, 0.707‐0.963) and hemorrhagic stroke (0.777, 0.575‐0.949). Furthermore, the effects of BP changes during short‐term period on stroke events were greater than that in long‐term period. Conclusions Short‐ and long‐terms BP changes were both associated with the risk of stroke events. Furthermore, short‐term BP changes had a stronger impact than did long‐term changes on risk of stroke events.

Purpose: The increased level of saturated fatty acids (SFAs) is found in patients with diabetes, obesity, and other metabolic disorders. SFAs can induce lipotoxic damage to cardiomyocytes, but the mechanism is unclear. The long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) acts as a key regulator in palmitic acid (PA)-induced hepatic steatosis, but its role in PA-induced myocardial lipotoxic injury is still unknown. The aim of this study was to explore the role and underlying mechanism of MALAT1 in PA-induced myocardial lipotoxic injury. Methods: MALAT1 expression in PA-treated human cardiomyocytes (AC16 cells) was detected by RT-qPCR. The effect of MALAT1 on PA-induced myocardial injury was measured by Cell Counting Kit-8, lactate dehydrogenase (LDH), and creatine kinase-MB (CK-MB) assays. Apoptosis was detected by flow cytometry. The activities of cytokines and nuclear factor (NF)-κB were detected by enzyme-linked immunosorbent assay. The interaction between MALAT1 and miR-26a was evaluated by a luciferase reporter assay and RT-qPCR. The regulatory effects of MALAT1 on high mobility group box 1 (HMGB1) expression were evaluated by RT-qPCR and western blotting. Results: MALAT1 was significantly upregulated in cardiomyocytes after PA treatment. Knockdown of MALAT1 increased the viability of PA-treated cardiomyocytes, decreased apoptosis, and reduced the levels of LDH, CK-MB, TNF-α, and IL-1β. Moreover, we found that MALAT1 specifically binds to miR-26a and observed a reciprocal negative regulatory relationship between these factors. We further found that the downregulation of MALAT1 represses HMGB1 expression, thereby inhibiting the activation of the Toll-like receptor 4 (TLR4)/NF-κB-mediated inflammatory response. These repressive effects were rescued by an miR-26a inhibitor. Conclusion: We demonstrate that MALAT1 is induced by SFAs and its downregulation alleviates SFA-induced myocardial inflammatory injury via the miR-26a/HMGB1/TLR4/NF-κB axis. Our findings provide new insight into the mechanism underlying myocardial lipotoxic injury.

PURPOSE Coronary artery disease is the top cause of death among the Chinese population. With the establishment of a Chinese prediction model, it is urgent to assess factors related to the prognosis of patients with acute coronary syndrome at extremely high risk. METHODS In this retrospective study, we enrolled 601 patients assessed as being of extremely high risk, according to specific criteria from the China-PAR (Prediction for Atherosclerotic Cardiovascular Disease Risk) project, and investigated various clinical parameters using Cox multivariate analysis to establish a risk nomogram. C-index and calibration curves were involved to assess the internal identification. By using the all-cause death risk model, we stratified patients by risk level and compared the effects of clopidogrel and ticagrelor on end points. FINDINGS We identified several factors, including body mass index, angiopathy, smoking status, β-blocker usage, history of myocardial infarction, total number of stents, and usage of antiplatelet agents, related to ischemic end points, all-cause death, cardiovascular events, and cardiac death. A C-index of >0.7 and the calibration curve demonstrated good concordance. In a subsequent analysis, we used the all-cause death model to stratify patients by risk level, and compared the effects of clopidogrel and ticagrelor. In the subgroup with a 2-year death rate of >50%, ticagrelor showed a positive effect (P = 0.045), but in the subgroup with a 2-year death rate of

ObjectiveThe present epidemiological study aimed to evaluate the association of serum electrolyte levels with hypertension in a population with a high-salt diet.DesignSecondary analysis of epidemiology data from the Northeast China Rural Cardiovascular Health Study conducted in 2012–2013. Blood pressure and hypertension status were analysed for association with serum sodium, potassium, chloride, total calcium, phosphate and magnesium levels using regression models.SettingHigh-salt diet, rural China.ParticipantsAdult residents in Liaoning, China.ResultsIn total 10 555 participants were included, of whom 3287 had incident hypertension (IH) and 1655 had previously diagnosed hypertension (PDH). Fifty-six per cent of participants had electrolyte disturbance. Sixty-two per cent of hypercalcaemic participants had hypertension, followed by hypokalaemia (56 %) and hypernatraemia (54 %). Only hypercalcaemia showed significant associations with both IH (OR=1·70) and PDH (OR=2·25). Highest serum calcium quartile had higher odds of IH (OR=1·58) and PDH (OR=1·64) than the lowest quartile. Serum sodium had no significant correlation with hypertension. Serum potassium had a U-shaped trend with PDH. Highest chloride quartile had lower odds of PDH than the lowest chloride quartile (OR=0·65). Highest phosphate quartile was only associated with lower odds of IH (OR=0·75), and the higher magnesium group had significantly lower odds of IH (OR=0·86) and PDH (OR=0·77).ConclusionsWe have shown the association of serum calcium, magnesium and chloride levels with IH and/or PDH. In the clinical setting, patients with IH may have concurrent electrolyte disturbances, such as hypercalcaemia, that may indicate other underlying aetiologies.

ObjectiveTo investigate the prognostic significance of first-degree atrioventricular block (AVB) in Asian populations.Design and settingParticipants (N=9634) from the Northeast China Rural Cardiovascular Health Study were included. The first-degree AVB was defined as PR (from the beginning of the P wave to the beginning of the QRS complex on an electrocardiogram) interval >200 ms, and primary composite outcome (all events) included new onset cardiovascular disease (CVD) and mortality. Cox regression and restricted cubic spline were used to identify the associations of PR interval or first-degree AVB with end points. Furthermore, the relationship between new-onset CVD and mortality and first-degree AVB was separately evaluated. The value of first-degree AVB for predicting adverse events was evaluated by reclassification and discrimination analyses.ResultsDuring a median of 4.65 years follow-up, 524 participants developed CVD and 371 died. Compared with participants with PR ≤200 ms, those with first-degree AVB had an increased risk of all events (HR: 1.84; 95% CI 1.18 to 2.88). Furthermore, first-degree AVB was predictive of incident CVD (1.96, 1.18 to 3.23) and stroke (2.22, 1.27 to 3.90) after adjusting for conventional risk. These statistically significant associations remained unchanged after further stratification by potential confounding factors. Discrimination and reclassification analyses suggested that first-degree AVB addition could improve the conventional model for predicting adverse outcomes within 4 years.ConclusionsOur results indicated that first-degree AVB was an independent risk factor for adverse events, suggesting that it should not be considered as inconsequential factor in general population. These results have potential clinical value for identifying individuals at high risk for adverse outcomes.

Background Atherosclerosis is a chronic inflammatory disease. Accumulating evidence suggests that long non-coding RNAs (lncRNAs) and microRNAs have emerged as critical regulators of atherosclerosis; however, whether they have crosstalk on this issue remains elusive. Here, we investigated the potential associations between lncRNA-MALAT1 and miR-155 on the regulation of atherosclerosis. Methods Quantitative real-time PCR was employed to assess the expression of MALAT1, IL-6 and IL-8. ELISA was performed to measure the secretion of IL-6 and IL-8. MTT assay was used to determine the proliferation of Human Coronary Artery Endothelial Cells (HCAECs). Flow cytometry was used to measure the cell apoptosis. Western blot was used to assess the expression of apoptosis-related proteins and the phosphorylation of STAT1 and STAT3. Results We found that the pro-inflammatory cytokine release and the apoptosis of HCAECs were elevated upon ox-LDL treatment, while MALAT1 expression was also up regulated. Knocking down of MALAT1 boosted ox-LDL-induced cytokine release and apoptosis of HCAECs. The binding site of miR-155 in MALAT1 sequence was confirmed by dual luciferase assay. Furthermore, miR-155 inhibition significantly repressed ox-LDL mediated inflammation and apoptosis of HCAECs via SOCS1. At last, we found that MALAT1 could suppress the inflammatory cytokine release and cell apoptosis via sponging miR-155 to increase SOCS1 level, which in turn restrained JAK-STAT pathway. Conclusion In summary, this study revealed the mechanisms by which MALAT1 worked as a putative atherosclerosis suppressor via miR-155 and SOCS1. Therefore, modulation of MALAT1/miR-155/SOCS1 axis might alleviate the inflammation persisted in atherosclerosis.

Background Recent studies have suggested that cardiometabolic index (CMI), a novel estimate of visceral adipose tissue, could be of use in the evaluation of cardiovascular risk factors. However, the potential utility and clinical significance of CMI in the detection of reduced estimated glomerular filtration rate (eGFR) remains uncertain. The purpose of this study was to investigate the usefulness of CMI in assessing reduced eGFR in the general Chinese population. Methods This cross-sectional analysis included 11,578 participants (mean age: 53.8 years, 53.7% females) from Northeast China Rural Cardiovascular Health Study (NCRCHS) of general Chinese population (data collected from January 2013 to August 2013). CMI was calculated by triglyceride to high density lipoprotein cholesterol ratio multiply waist-to-height ratio. Reduced eGFR was defined as eGFR

ObjectivesTo investigate the associations between echocardiographic left atrial (LA) size and incident stoke and stroke cause mortality among a rural population in China.DesignA prospective study.Setting and participantsBased on the Northeast China Rural Cardiovascular Health Study, we selected a total of 10 041 participants aged ≥35 years who agreed to have transthoracic echocardiography at baseline and were successfully followed up for incident stoke and stroke cause mortality.Primary outcome measureThe outcomes were stroke and stroke cause death according to medical records and death certificates during the follow-up period.ResultsLA enlargement (LAE) group had a higher prevalence of cardiovascular disease than normal LA diameter (LAD) group. After excluding individuals who had a prior stroke, subjects with LAE showed higher incident rates of stroke and its mortality in the overall and specific stratified analyses (all pConclusionsOur population-based study implied that LA size, especially LAD and LAD/BSA, might be useful echocardiographic biomarkers that had the potential to predict incident stroke and stroke cause mortality.

Background: This study intended to use two novel inflammatory indicators: lymphocyte to high-density lipoprotein cholesterol ratio (LHR) and platelet to lymphocyte ratio (PLR), to predict newly diagnosed metabolic syndrome (MetS) among subjects from rural Northeast China.Methods: Adult participants without MetS at baseline (n = 4,980, age = 52.65 ± 10.21 years; 51.9% men) were originated from the Northeast China Rural Cardiovascular Health Study (NCRCHS). LHR (Q1: ≤1.04; Q2: 1.04–1.35; Q3: 1.35–1.79; Q4: ≥1.79) and PLR (Q1: ≤78.50; Q2: 78.50–107.27; Q3: 107.27–140.00; Q4: ≥140.00) were divided in quartile.Results: After 4.66-year follow-up, 1,194 subjects were diagnosed MetS (cumulative incidence 24.0; 25.8% for female and 22.3% for male, P = 0.002). Newly diagnosed MetS had higher value of hemoglobin and platelet count compared to those without MetS. As for LHR, from Q1 to Q4, there were increasing value of waist circumference (WC), serum triglycerides (TG), rates of current smoking and drinking whereas decreasing value of HDL-C. However, for PLR, rates of current smoking and drinking significantly decreased from Q1 to Q4. Similarly, the value of WC and TG showed a decreasing trend. In a logistic regression analysis, after adjusted for possible confounders, LHR [OR (95% CI) Q2: 1.13 (0.86, 1.48); OR (95% CI) Q3: 1.23 (0.94, 1.61); OR (95% CI) Q4: 1.57(1.20, 2.06)] but not PLR was effective predictor of newly diagnosed MetS among rural Chinese.Conclusion: MetS had closed relationship with inflammation among subjects from rural China. As a novel marker of inflammation, LHR but not PLR might be an effective predictor of newly diagnosed MetS and should be widely used in the epidemiological study.

Objective To investigate whether ECG left ventricular hypertrophy (ECG-LVH) has prognostic value independent of echocardiography LVH (Echo-LVH). Methods Participants (N = 9744, mean age, 53.81 ± 10.49 years and 45.5% male) from the Northeast China Rural Cardiovascular Health Study were included. Associations between Echo-LVH (sex-specific left ventricular mass normalized to BSA) and ECG-LVH (diagnosed using the Cornell-voltage duration product) and adverse outcomes were evaluated using Cox regression. The value of ECG-LVH for predicting adverse events was evaluated by reclassification and discrimination analyses. Results Median follow-up was 4.65 years; 563 participants developed incident stroke or coronary heart disease (CHD) and 402 died. Compared with participants without either condition, those with both Echo-LVH and ECG-LVH had a significantly increased risk of incident stroke or CHD (hazard ratio, 2.42; 95% confidence interval, 1.82-3.22) and mortality (2.58; 1.85-3.60). ECG-LVH remained an independent risk factors for both outcomes when ECG-LVH and Echo-LVH were included in the model as separate variables [incident stroke or CHD (1.43; 1.14-1.79); mortality (1.41; 1.08-1.84)]. Reclassification and discrimination analyses indicated ECG-LVH addition could improve the conventional model for predicting adverse outcomes within 4 years. These relationships persisted after excluding participants with cardiovascular disease history or taking antihypertension drugs or upon applying other ECG-LVH and Echo-LVH diagnostic criteria. Conclusion Our study provides strong evidence that ECG-LVH is associated with adverse outcomes, independent of Echo-LVH. Clinically, ECG-LVH could be considered as a consequential factor, especially in those with Echo-LVH. These findings have potential clinical relevance for risk stratification.

BACKGROUND In China, hypertension prevalence is high and increasing while the control rate is low, especially in rural areas. Traditionally, village doctors play an important role in infectious disease control and delivering essential health services to rural residents. We aim to test the effectiveness of a village doctor-led multifaceted intervention compared with usual care on blood pressure (BP) control and cardiovascular disease (CVD) among rural residents with hypertension in China. METHODS In the China Rural Hypertension Control Project (CRHCP), a cluster randomized trial, 163 villages were randomly assigned to the village doctor-led intervention and 163 villages to control. A total of 33,995 individuals aged ≥40 years with an untreated BP ≥140/90 mm Hg or treated BP ≥130/80 mm Hg or with an untreated BP ≥130/80 mm Hg and a history of clinical CVD were recruited into the study. The village doctor-led multifaceted intervention is designed to overcome barriers at the healthcare system, provider, patient, and community levels. Village doctors receive training on standard BP measurement, protocol-based hypertension treatment, and health coaching. They also receive technical support and supervision from hypertension specialists/primary care physicians and performance-based financial incentives. Study participants receive health coaching on home BP monitoring, lifestyle changes, and adherence to medications. The primary outcome is BP control ( CONCLUSIONS The CRHCP will provide critically important data on the effectiveness, implementation, and sustainability of a hypertension control strategy in rural China for reducing the BP-related CVD burden. CLINICAL TRIALS REGISTRATION Trial Number NCT03527719.

Additional file 1: Supplemental Table 1. Clinical and echocardiographic characteristics of the included participants.

Meng-Qi Chen,1 Wen-Rui Shi,1 Hao-Yu Wang,2 Zhao Li,1 Xiao-Fan Guo,1 Ying-Xian Sun1 1Department of Cardiology, The First Hospital of China Medical University, Shenyang, 110001, People’s Republic of China; 2Department of Cardiology, Coronary Heart Disease Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100037, People’s Republic of ChinaCorrespondence: Ying-Xian SunDepartment of Cardiology, The First Hospital of China Medical University, 155 Nanjing, North Street, Heping District, Shenyang, 110001, People’s Republic of ChinaEmail yxsun_cmu@outlook.comPurpose: Some studies have established an association between hypertension or obesity and the risk of diabetes. This study aimed to examine the interaction of hypertension and obesity on diabetes.Participants and Methods: The data of 11,731 Chinese men and women were analyzed from the 2012– 2013 Northeast China Rural Cardiovascular Health Study. The interaction was examined by both additive and multiplicative scales. General obesity was measured by body mass index (BMI); central obesity was defined by waist circumference (WC), waist-to-height ratio (WHtR) and waist-to-hip ratio (WHpR).Results: After controlling for potential confounders, the odds ratios for diabetes were 3.864 (3.205– 4.660), 4.500 (3.673– 5.514), 4.932 (3.888– 6.255) and 4.701 (3.817– 5.788) for the combinations of hypertension and BMI, WC, WHtR or WHpR, respectively, which had the highest risk of diabetes among the four combinations. Notwithstanding the multiplicative interactions showed statistically significant in all analyses, the results of additive interactions were not consistent, suggesting the diabetes risk from female BMI (relative excess risk due to interaction (RERI): 1.136, 95% CI: 0.127– 2.146, attributable proportion due to interaction (AP): 0.267, 95% CI: 0.057– 0.477, synergy index (S):1.536, 95% CI: 1.017– 2.321) or female WHpR (RERI: 1.076, 95% CI: 0.150– 2.002, AP:0.205, 95% CI: 0.037– 0.374, S:1.340, 95% CI: 1.012– 1.775) was additive to the risk from hypertension.Conclusion: The findings suggest that high BMI and high WHpR have synergistic interactions with hypertension on the risk of diabetes for females. The results of this study also suggest that BMI and WHpR, rather than WC, should be used for the diagnosis of metabolic syndrome in Chinese population.Keywords: interaction, diabetes, hypertension, general obesity, central obesity

Background Cumulative evidence indicates that normal weight with central obesity (NWCO) is associated with cardiovascular diseases risk factors like hypertension, diabetes, dyslipidemia. However, the possible predictive effect of NWCO on newly onset cardiovascular diseases (CVD) including coronary heart disease (CHD) and stroke has not been studied in detail. Methods Participants underwent physical examination at 2012–2013 and followed-up at 2015–2017 who previously diagnosed CVD were excluded. Body mass index (BMI) ≥ 25 kg/m2 defined obesity, waist-to-height ratio ≥ 0.5 defined central obesity. Four groups: Normal weight without (NW) or NWCO, obesity without (OB) or with central obesity (OBCO). Results In total, 9439 participants (5006 men and 4433 women). The prevalence of different types of obesity were 39.6% for NW, 16.1% for NWCO, 4.1% for OB and 40.2% for OBCO. NWCO [HR = 1.565, 95%CI = 1.195, 2.051] and OBCO [HR = 1.845, 95%CI = 1.480, 2.300] were significantly associated with increasing risk of newly onset CVD. Besides, NWCO [HR = 2.337, 95%CI = 1.257, 4.344], OB [HR = 3.22, 95%CI = 1.166, 8.905] and OBCO [HR = 2.449, 95%CI = 1.386, 4.326] were all correlated with newly onset CHD but none of them had relationship with newly onset stroke. Conclusions We found that NWCO and OBCO were associated with newly onset CVD in rural Northeast Chinese adults. This underscored the effect of central obesity on CVD and suggested that even in individual with normal BMI, it is still necessary to prevent, monitor and control of central obesity.

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.