Wenming Yao

Circulating miR-30d Predicts Survival in Patients with Acute Heart Failure

Background/Aims: Identification of novel biomarkers to identify acute heart failure (AHF) patients at high risk of mortality is an area of unmet clinical need. Recently, we reported that the baseline level of circulating miR-30d was associated with left ventricular remodeling in response to cardiac resynchronization therapy in advanced chronic heart failure patients. However, the role of circulating miR-30d as a prognostic marker of survival in patients with AHF has not been explored. Methods: Patients clinically diagnosed with AHF were enrolled and followed up for 1 year. Quantitative reverse transcription polymerase chain reactions were used to determine serum miR-30d levels. The univariate logistic regression analysis and multivariate logistic regression analysis were used to determine the predictors for all-cause mortality in AHF patients. Kaplan–Meier survival analysis was used to analyze the role of miR-30d in prediction of survival. Results: A total of 96 AHF patients were enrolled and followed up for 1 year. Serum miR-30d was significantly lower in AHF patients who expired in the one year follow-up period compared to those who survived. Univariate logistic regression analysis yielded 18 variables that were associated with all-cause mortality in AHF patients, while the multivariate logistic regression analysis identified 4 variables including heart rate, hemoglobin, serum sodium, and serum miR-30d level associated with mortality. ROC curve analysis showed that hemoglobin, heart rate and serum sodium displayed poor prognostic value for AHF (AUCs not higher than 0.700) compared to miR-30d level (AUC = 0.806). Kaplan–Meier survival analysis confirmed that patients with higher serum miR-30d levels had significantly lower mortality (P=0.001). Conclusion: In conclusion, this study shows evidence for the predictive value of circulating miR-30d as 1-year all-cause mortality in AHF patients. Large multicentre studies are further needed to validate our findings and accelerate the transition to clinical utilization.

Relationship between brachial-ankle pulse wave velocity and metabolic syndrome components in a Chinese population.

Abstract The purpose of this study was to assess the relationship between arterial stiffness, as measured by brachial-ankle pulse wave velocity (baPWV), and the presence of the metabolic syndrome (MS) in a Chinese population. A total of 4,445 subjects were enrolled. The prevalence of MS in our study population was 21.7%, 17.2% and 25.6% for the general population, males and females, respectively. With adjustments for age, gender, cigarette smoking, heart rate, total cholesterol, low-density lipoprotein (LDL) cholesterol, and the use of anti-hypertensive drug, the stepwise regression analysis showed that baPWV had a significant relationship with components of MS, including systolic blood pressure (P < 0.001), diastolic blood pressure (P < 0.001), glucose (P < 0.001), high-density lipoprotein (HDL) cholesterol (P  =  0.04), and triglycerides (P < 0.001), but no relationship with waist circumference (P  =  0.25). With an increase in the number of the MS components, baPWV increased significantly both in women and men. This study indicated that the MS is indeed a risk factor for arterial stiffness. Monitoring of baPWV in patients with MS may help in identifying persons at high risk for cardiovascular disease.

Physical activity modifies the association between CYBA gene polymorphisms and small artery elasticity in a Chinese population

Emerging evidence suggests that increased superoxide production is responsible for a significant proportion of endothelial dysfunction. The relationship between variants of the CYBA gene and cardiovascular diseases is currently debated. In the present study, we investigated the influence of CYBA polymorphisms (rs1049255 and rs7195830) on arterial elasticity in a Chinese population. In the 2178 participants enrolled in the GaoYou study, we measured large artery elasticity (C1) and small artery elasticity (C2) non-invasively, genotyped the CYBA polymorphisms and calculated energy expenditure. The AA genotype of the rs1049255 polymorphism was associated with a lower C2 than were the GG/AG genotypes (5.31±0.11 vs. 5.52±0.06 ml mm Hg−1 × 100; P=0.01). Further analyses revealed an interaction between CYBA polymorphisms and physical activity with respect to C2 (P=0.007 for rs1049255 and P=0.038 for rs7195830). In less physically active participants, the AA genotype of the rs1049255 polymorphism was associated with a significantly lower C2 than the GG/AG genotypes (4.69±0.16 vs. 5.26±0.19 ml mm Hg−1 × 100; P=0.008). In physically active participants, the GG/AG genotypes of rs7195830 polymorphism were correlated with higher C2 values than the AA genotype (5.84±0.08 vs. 5.08±0.32 ml mm Hg−1 × 100; P=0.049). Haplotype analyses revealed higher C2 values in rs1049255G–rs7195830G carriers (P=0.0015). In conclusion, the rs1049255 and rs7195830 polymorphisms of the CYBA gene were associated with C2 in a Chinese population; physical activity could modify this genetic effect.

Predictors of Long-Term Mortality in Patients With Acute Heart Failure

To investigate parameters which were related with long-term mortality in patients hospitalized for acute heart failure (AHF).A total of 287 patients with AHF presenting to the First Affiliated Hospital of Nanjing Medical University were enrolled into the registry from April 2012 to January 2015. The primary endpoint was all-cause mortality within 1 year; the association between variables and prognosis was assessed after 1 year.Among the 287 patients, 17 did not continue follow-up and 47 (17.4%) passed away. Baseline NT-proBNP and sST2 concentrations were higher amongst deceased than among survivors (P < 0.001). Serum sodium concentrations of patients who died were lower (P < 0.001). In receiver operator characteristics (ROC) analyses, the area under the curve (AUC) values for NT-proBNP, sST2, and serum sodium to predict 1-year mortality were 0.699 (95%CI 0.639-0.755), 0.692, (95%CI 0.634-0.747), and 0.694 (95%CI 0.634-0.750), respectively. The optimal cut-off points for NT-proBNP, sST2, and serum sodium were 2137.0 ng/L, 35.711 ng/mL, and 136.6 mmol/L, respectively. In Cox regression analysis, ln-transformed NT-proBNP (HR 1.546, P = 0.039), ln-transformed sST2 (HR1.542, P = 0.049), and serum sodium (HR 0.880, P = 0.000) values reliably predicted long-term mortality after multivariable adjustment.In patients with acute heart failure, NT-proBNP, sST2 and serum sodium are potential predictors of 1-year mortality.

Serum Irisin Predicts Mortality Risk in Acute Heart Failure Patients

Background/Aims: Irisin is a peptide hormone cleaved from a plasma membrane protein fibronectin type III domain containing protein 5 (FNDC5). Emerging studies have indicated association between serum irisin and many major chronic diseases including cardiovascular diseases. However, the role of serum irisin as a predictor for mortality risk in acute heart failure (AHF) patients is not clear. Methods: AHF patients were enrolled and serum was collected at the admission and all patients were followed up for 1 year. Enzyme-linked immunosorbent assay was used to measure serum irisin levels. To explore predictors for AHF mortality, the univariate and multivariate logistic regression analysis, and receiver-operator characteristic (ROC) curve analysis were used. To determine the role of serum irisin levels in predicting survival, Kaplan-Meier survival analysis was used. Results: In this study, 161 AHF patients were enrolled and serum irisin level was found to be significantly higher in patients deceased in 1-year follow-up. The univariate logistic regression analysis identified 18 variables associated with all-cause mortality in AHF patients, while the multivariate logistic regression analysis identified 2 variables namely blood urea nitrogen and serum irisin. ROC curve analysis indicated that blood urea nitrogen and the most commonly used biomarker, NT-pro-BNP, displayed poor prognostic value for AHF (AUCs ≤ 0.700) compared to serum irisin (AUC = 0.753). Kaplan-Meier survival analysis demonstrated that AHF patients with higher serum irisin had significantly higher mortality (P<0.001). Conclusion: Collectively, our study identified serum irisin as a predictive biomarker for 1-year all-cause mortality in AHF patients though large multicenter studies are highly needed.

Quality control of the blood pressure phenotype in the Gaoyou population study.

Abstract The Korotkoff approach is the only blood pressure (BP) measurement technique that allows contemporary data to be compared with decades of research. We randomly recruited 4483 people (53.3% women; mean age 52.1 years) from Gaoyou County, Jiangsu Province, China. Nine observers recorded the participants™ BP three times consecutively following Chinese Society of Hypertension guidelines. We assessed the BP phenotype based on five criteria: completeness of readings, percentage of identical BP readings, odd BP readings, end-digit preference and trends in BP from the first to the third reading. The proportion of participants with identical readings were 2.0% and 3.1% for systolic (SBP) and diastolic blood pressure (DBP), respectively. Among 26,898 BP values, 0.3% ended in an odd number. Among observers, the prevalence of identical readings varied from 0% to 5.3% for SBP and from 0% to 6.8% for DBP. Compared with the expected frequency of 20%, those ending in 0 had a lower frequency (17.2%; p < 0.001), whereas those ending in 8 had a higher frequency (22.4%; p < 0.001). From the first to the third measurement, SBP and DBP decreased (p < 0.001) by 0.87 and 0.55 mmHg, respectively. In conclusion, the procedures set up in the Gaoyou study produced a high-quality BP phenotype.

Traditional Chinese Medication Qiliqiangxin Protects Against Cardiac Remodeling and Dysfunction in Spontaneously Hypertensive Rats

Qiliqiangxin (QLQX), a traditional Chinese herbs medication, exerted protective effect in chronic heart failure patients in a multicenter randomized double-blind study. QLQX has also been found to improve cardiac function and reduce cardiac fibrosis in spontaneously hypertension animal model. However, the effect of longterm treatment with QLQX in such a condition and the related molecular mechanisms remain largely unknown. In the present study, thirteen-week-old spontaneously hypertensive rats (SHRs) were treated by daily intragastric administration of QLQX or saline for one year. Echocardiography, electron microscopy, and Massons trichrome staining were used to determine cardiac function, mitochondria ultrastructure, and cardiac fibrosis, respectively. Quantitative reverse transcription polymerase chain reactions (qRT-PCRs) and Western blotting were used to determine gene expressions. We found that QLQX significantly improved cardiac function and reduced gene markers of pathological hypertrophy including ANP, BNP, and Myh7. QLQX also attenuated cardiac fibrosis and apoptosis in SHRs as evidenced by downregulation of α-SMA, collagen I, collagen III, and TGF-β expressions and reduction of Bax to Bcl-2 ratio. Moreover, the damage of mitochondrial ultrastructure was greatly improved and the reduction of PPAR-α, PPAR-γ, and PGC-1α expression levels was significantly restored in SHRs by treatment with QLQX. In conclusion, longterm treatment with QLQX protects against cardiac remodeling and dysfunction in hypertension by increasing PPARs and PGC-1α.

Qiliqiangxin Attenuates Adverse Cardiac Remodeling after Myocardial Infarction in Ovariectomized Mice via Activation of PPARγ

Background/Aims: This study was designed to investigate the therapeutic effect of traditional Chinese medication Qiliqiangxin (QLQX) on adverse cardiac remodeling after myocardial infarction (MI) in bilateral ovariectomized (OVX) female mice. Methods: Eight-week old female C57BL/6 mice were operated to ligate the left anterior descending coronary artery seven days after bilateral ovariectomy and were orally administered either QLQX or vehicle. 21 days after ligation, echocardiography was performed to evaluate the heart function of all mice. Massons Trichrome staining was applied to evaluate myocardial fibrosis. Collagen deposition was determined by the mRNA level of Collagen I, Collagen III and α-SMA using real-time quantitative polymerase chain reaction (qPCR). Myocardial apoptosis was examined by the protein level of Bax, Bcl2 and the Bcl2/Bax ratio using western blotting. Results: These mice displayed a significant reduction in heart function, increased myocardial fibrosis and apoptosis, and decreased expression of peroxisome proliferator activated receptor γ (PPARγ) in the heart tissue, which could be reversed by QLQX treatment. Inhibition of PPAR reduced QLQX-mediated cardio-protective effects, while PPARγ activation did not further enhance the beneficial effect of QLQX. Furthermore, QLQX upregulated 9 genes (Cd36, Fatp, Pdk4, Acadm, Acadl, Acadvl, Cpt1a, Cpt1b and Cpt2) facilitating energy metabolism in the MI hearts of the OVX mice and 5 (Acadm, Acadl, Cpt1a, Cpt1b, Cpt2) of the 9 genes were the downstream targets of PPARγ. Conclusion: The present study indicates that QLQX has a treatment effect on pathological remodeling post MI in bilateral OVX female mice via activation of PPARγ, suggesting that QLQX may be a promising prescription for the treatment of postmenopausal women suffering from MI.

OS 14-07 PULSE WAVE VELOCITY COMPARED WITH MEAN ARTERIAL PRESSURE AND PULSE PRESSURE PROGNOSTIC IN THE POPULATION OF GAOYOU COUNTY, CHINA.

Objective: To evaluate the predictive value for cardiovascular disease incidence (CVD) of brachial-ankle pulse wave velocity (baPWV) based on a general Chinese population. Design and Method: The study group included 4251 participants with an average age of 52.1 ± 12.1 years and a mean baPWV of 14.8 ± 3.3 m/s. Cox regression was used to investigate the prognostic value of baPWV and forced the appropriate interaction term into the regression models to test the absolute risk associated with baPWV at different levels of mean arterial pressure. Results: Over a median follow-up of 4.4 years, the incidence of cardiovascular mortality, stroke and composite cardiovascular endpoints amounted to 21, 48 and 74. We adjusted for sex, age, body mass index, mean arterial pressure, waist-to-hip ratio, total cholesterol, current smoking, alcohol intake, blood glucose and use of antihypertensive drugs. With these adjustments, for each 1-SD increment in baPWV (3.23 m/s), the hazard ratios for an all-cause mortality, cardiovascular mortality, stroke or composite cardiovascular outcomes were 1.41(1.13–1.75), 1.68 (95% CI:1.20–2.35), 1.51 (95% CI:1.27–1.80), 1.57 (95% CI: 1.28–1.93), respectively. At any given level of mean arterial pressure (MAP), a higher baPWV was associated with a higher death rate. The area under curve (AUC) of baPWV was larger than pulse pressure in predicting composite cardiovascular events (Z = 2.45,P = 0.014). Conclusions: In conclusion, baPWV predicted a composite of cardiovascular outcomes above and beyond pulse pressure in a general Chinese population.

Hypertension related knowledge and behaviour associated with awareness, treatment and control of hypertension in a rural hypertensive population: a community based, cross-sectional survey

Abstract Background and objective: Hypertension-related knowledge and behaviour have been identified as influential factors associated with awareness, treatment and control of hypertension in urban regions. However, there were few studies on rural areas. This study aims to investigate whether hypertension related knowledge and behaviour were associated with hypertension awareness, treatment and control in Gaoyou, a rural area of Jiangsu province, China. Methods: A cross-sectional, population-based survey was conducted among hypertensive individuals in rural areas of Gaoyou, the south-eastern of China in 2010. We identified 1943 subjects with hypertension among 4536 subjects participated in this study and collected information about medical history, use of medication, hypertension related knowledge and behaviour by a standardized questionnaire. Results: This study showed that 41.07% of subjects were aware of their disease, 30.01% of subjects were taking antihypertensive medication and 5.04% of subjects controlled their blood pressure. Multivariate logistic regression analysis showed that subjects who knew the threshold, the lifelong treatment of hypertension and measured blood pressure at least once a year had better detection, treatment or control of hypertension. Conclusion: Hypertension related knowledge and behaviour were associated with awareness, treatment and control rate of hypertension in the rural areas of south-eastern China.