Glycated Hemoglobin Variability Is Associated With Adverse Outcomes in Patients With Heart Failure Irrespective of Diabetic Status.

BACKGROUND: The effect of glycated hemoglobin (HbA1c) variability on adverse outcomes in patients with heart failure (HF) is unclear. We aim to investigate the predictive value of HbA1c variability on the risks of all-cause death and HF rehospitalization in patients with HF irrespective of their diabetic status. METHODS AND RESULTS: Using a previously validated territory-wide clinical data registry, HbA1c variability was assessed by average successive variability (ASV) or SD of all HbA1c measurements after HF diagnosis. Multivariable Cox proportional hazards models were used to estimate the adjusted hazard ratio (HR) and its corresponding 95% CI. A total of 65 950 patients with HF were included in the study. Over a median follow-up of 6.7 (interquartile range, 4.0-10.6) years, 34 508 patients died and 52 446 required HF rehospitalization. Every unit increment of variability in HbA1c was significantly associated with higher HF rehospitalization (HR ASV, 1.20 [95% CI, 1.18-1.23]) and all-cause death (HR ASV, 1.50 [95% CI, 1.47-1.53]). Diabetes significantly modified the association between HbA1c variability and outcomes (Pinteraction<0.001). HbA1c variability in patients with HF without diabetes conferred a higher risk of rehospitalization (HR ASV, 1.92 [95% CI, 1.70-2.17] versus HR ASV, 1.19 [95% CI, 1.17-1.21]), and all-cause death (HR ASV, 3.90 [95% CI, 3.31-4.61] versus HR ASV, 1.47 [95% CI, 1.43-1.50] compared with patients with diabetes). CONCLUSIONS: HbA1c variability is significantly associated with greater risk of rehospitalization and all-cause death in patients with HF, irrespective of their diabetic status. These observations were more pronounced in patients with HF without diabetes.

Statins and risks of dementia among patients with heart failure: a population-based retrospective cohort study in Hong Kong.

Background: Heart failure (HF) and dementia frequently co-exist with shared pathological mechanisms and risk factors. Our study aims to investigate the association between statin therapy and the risks of dementia and its subtypes among patients with HF. Methods: The Hong Kong Clinical Data Analysis and Reporting System database was interrogated to identify patients with incident HF diagnosis from 2004 to 2018, using ICD 9/ICD 10 codes. Inverse probability of treatment weighting (IPTW) was used to balance baseline covariates between statin users (N = 54,004) and non-users (N = 50,291). The primary outcomes were incident all-cause dementia, including subtypes of Alzheimer's disease, vascular dementia, and unspecified dementia. Cox proportional-hazard model with competing risk regression was performed to estimate the sub-distribution hazards ratio (SHR) with corresponding 95% confidence intervals (CI) of the risks of all-cause dementia and its subtypes that are associated with statin use. Findings: Of all eligible patients with HF (N = 104,295), the mean age was 74.2 ± 13.6 years old and 52,511 (50.3%) were male. Over a median follow-up of 9.9 years (interquartile range [IQR]: 6.4-13.0), 10,031 (9.6%) patients were diagnosed with dementia, among which Alzheimer's disease (N = 2250), vascular dementia (N = 1831), and unspecified dementia (N = 5950) were quantified separately. After IPTW, statin use was associated with a 20% lower risk of incident dementia compared with non-use (multivariable-adjusted SHR 0.80, 95% CI 0.76-0.84). Stratified by subtypes of dementia, statin use was associated with a 28% lower risk of Alzheimer's disease (SHR 0.72, 95% CI 0.63-0.82), 18% lower risk of vascular dementia (SHR 0.82, 95% CI 0.70-0.95), and a 20% lower risk of unspecified dementia (SHR 0.80, 95% CI 0.75-0.85). Interpretation: In patients with HF, statin use was associated with a significantly lower risk of all-cause dementia and its subtypes, including Alzheimer's disease, vascular dementia, and unspecified dementia. Both randomized trials and experimental studies to validate the potential neuroprotective effect of statin are warranted. Funding: No funding was provided for this study.

Risk of hyperkalaemia in patients with type 2 diabetes mellitus prescribed with SGLT2 versus DPP-4 inhibitors.

AIMS: To investigate the risk of hyperkalaemia in new users of sodium-glucose cotransporter 2 (SGLT2) inhibitors vs. dipeptidyl peptidase-4 (DPP-4) inhibitors among patients with type 2 diabetes mellitus (T2DM). METHODS AND RESULTS: Patients with T2DM who commenced treatment with an SGLT2 or a DPP-4 inhibitor between 2015 and 2019 were collected. A multivariable Cox proportional hazards analysis was applied to compare the risk of central laboratory-determined severe hyperkalaemia, hyperkalaemia, hypokalaemia (serum potassium ≥6.0, ≥5.5, and <3.5 mmol/L, respectively), and initiation of a potassium binder in patients newly prescribed an SGLT2 or a DPP-4 inhibitor. A total of 28 599 patients (mean age 60 ± 11 years, 60.9% male) were included after 1:2 propensity score matching, of whom 10 586 were new users of SGLT2 inhibitors and 18 013 of DPP-4 inhibitors. During a 2-year follow-up, severe hyperkalaemia developed in 122 SGLT2 inhibitor users and 325 DPP-4 inhibitor users. Use of SGLT2 inhibitors was associated with a 29% reduction in incident severe hyperkalaemia [hazard ratio (HR) 0.71, 95% confidence interval (CI) 0.58-0.88] compared with DPP-4 inhibitors. Risk of hyperkalaemia (HR 0.81, 95% CI 0.71-0.92) and prescription of a potassium binder (HR 0.74, 95% CI 0.67-0.82) were likewise decreased with SGLT2 inhibitors compared with DPP-4 inhibitors. Occurrence of incident hypokalaemia was nonetheless similar between those prescribed an SGLT2 inhibitor and those prescribed a DPP-4 inhibitor (HR 0.90, 95% CI 0.81-1.01). CONCLUSION: Our study provides real-world evidence that compared with DPP-4 inhibitors, SGLT2 inhibitors were associated with lower risk of hyperkalaemia and did not increase the incidence of hypokalaemia in patients with T2DM.

Statin Therapy Is Associated With a Lower Risk of Heart Failure in Patients With Atrial Fibrillation: A Population-Based Study.

BACKGROUND: Whether statin use can reduce the risk of heart failure (HF) remains controversial. The present study evaluates the association between statin use and HF in patients with atrial fibrillation. METHODS AND RESULTS: Patients with newly diagnosed atrial fibrillation from 2010 to 2018 were included. An inverse probability of treatment weighting was used to balance baseline covariates between statin users (n=23 239) and statin nonusers (n=29 251). The primary outcome was incident HF. Cox proportional hazard models with competing risk regression were used to evaluate the risk of HF between statin users and nonusers. The median age of the cohort was 74.7 years, and 47.3% were women. Over a median follow-up of 5.1 years, incident HF occurred in 3673 (15.8%) statin users and 5595 (19.1%) statin nonusers. Statin use was associated with a 19% lower risk of HF (adjusted subdistribution hazard ratio, 0.81 [95% CI, 0.78-0.85]). Restricted to the statin users, duration of statin use was measured during follow-up; compared with short-term use (3 months to <2 years), there was a stepwise reduction in the risk of incident HF among those with 2 to <4 years of statin use (subdistribution hazard ratio, 0.86 [95% CI, 0.84-0.88]), 4 to <6 years of statin use (subdistribution hazard ratio, 0.74 [95% CI, 0.72-0.76]), and ≥6 years of statin use (subdistribution hazard ratio, 0.71 [95% CI, 0.69-0.74]). Subgroup analysis showed consistent reductions in the risk of HF with statin use. CONCLUSIONS: Statin use was associated with a decreased risk of incident HF in a duration-dependent manner among patients with atrial fibrillation.

Percutaneous transhepatic cholangial drainage-guided methylene blue for fistulotomy using dual-knife for bile duct intubation: A case report.

BACKGROUND: Difficult bile duct intubation is a big challenge for endoscopists during endoscopic retrograde cholangiopancreatography (ERCP) procedure. We report a case of percutaneous transhepatic cholangial drainage (PTCD)-guided methylene blue for fistulotomy using dual-knife for bile duct intubation. CASE SUMMARY: A 50-year-old male patient had developed obstructive jaundice, and ERCP procedure need to be performed to treat the obstructive jaundice. But intubation cannot be performed if the duodenal papilla cannot be identified because of previous surgery for a perforated descending duodenal diverticulum. We used PTCD-guided methylene blue to identify the intramural common bile duct before dual-knife fistulotomy, and bile duct intubation was successfully completed. CONCLUSION: The method that combing methylene blue and dual-knife fistulotomy to achieve bile duct intubation during difficult ERCP is safe and effective.

Opportunistic screening for asymptomatic left ventricular dysfunction in type 2 diabetes mellitus.

BACKGROUND: International guidelines recommend natriuretic peptide biomarker-based screening for patients at high heart failure (HF) risk to allow early detection. There have been few reports about the incorporation of screening procedure to existing clinical practice. OBJECTIVE: To implement screening of left ventricular dysfunction in patients with type 2 diabetes mellitus (DM). METHOD: A prospective screening study at the DM complication screening centre was performed. RESULTS: Between 2018 and 2019, 1043 patients (age: 63.7±12.4 years; male: 56.3%) with mean glycated haemoglobin of 7.25%±1.34% were recruited. 81.8% patients had concomitant hypertension, 31.1% had coronary artery disease, 8.0% had previous stroke, 5.5% had peripheral artery disease and 30.7% had chronic kidney disease (CKD) stages 3-5. 43 patients (4.1%) had an elevated N-terminal prohormone of brain natriuretic peptide (NT-proBNP) concentration above the age-specific diagnostic thresholds for HF, and 43 patients (4.1%) had newly detected atrial fibrillation (AF). The prevalence of elevated NT-proBNP increased with age from 0.85% in patients aged <50 years to 7.14% in those aged 70-79 years and worsening kidney function from 0.43% in patients with CKD stage 1 to 42.86% in CKD stage 5. In multivariate logistic regression, male gender (OR: 3.67 (1.47-9.16), p = 0.005*), prior stroke (OR: 3.26 (1.38-7.69), p = 0.007*), CKD (p<0.001*) and newly detected AF (OR: 7.02 (2.65-18.57), p<0.001*) were significantly associated with elevated NT-proBNP. Among patients with elevated NT-proBNP, their mean left ventricular ejection fraction (LVEF) was 51.4%±14.7%, and 45% patients had an LVEF <50%. CONCLUSION: NT-proBNP and ECG screening could be implemented with relative ease to facilitate early detection of cardiovascular complication and improve long-term outcomes.

Incidence, Clinical Correlates, and Prognostic Impact of Dementia in Heart Failure: A Population-Based Cohort Study.

Background: Heart failure (HF) may increase the risk of dementia via shared risk factors. Objectives: The authors investigated the incidence, types, clinical correlates, and prognostic impact of dementia in a population-based cohort of patients with index HF. Methods: The previously territory-wide database was interrogated to identify eligible patients with HF (N = 202,121) from 1995 to 2018. Clinical correlates of incident dementia and their associations with all-cause mortality were assessed using multivariable Cox/competing risk regression models where appropriate. Results: Among a total cohort aged ≥18 years with HF (mean age 75.3 ± 13.0 years, 51.3% women, median follow-up 4.1 [IQR: 1.2-10.2] years), new-onset dementia occurred in 22,145 (11.0%), with age-standardized incidence rate of 1,297 (95% CI: 1,276-1,318) per 10,000 in women and 744 (723-765) per 10,000 in men. Types of dementia were Alzheimer's disease (26.8%), vascular dementia (18.1%), and unspecified dementia (55.1%). Independent predictors of dementia included: older age (≥75 years, subdistribution hazard ratio [SHR]: 2.22), female sex (SHR: 1.31), Parkinson's disease (SHR: 1.28), peripheral vascular disease (SHR: 1.46), stroke (SHR: 1.24), anemia (SHR: 1.11), and hypertension (SHR: 1.21). The population attributable risk was highest for age ≥75 years (17.4%) and female sex (10.2%). New-onset dementia was independently associated with increased risk of all-cause mortality (adjusted SHR: 4.51; P < 0.001). Conclusions: New-onset dementia affected more than 1 in 10 patients with index HF over the follow-up, and portended a worse prognosis in these patients. Older women were at highest risk and should be targeted for screening and preventive strategies.

Prediabetes Is Associated With Increased Risk of Heart Failure Among Patients With Atrial Fibrillation.

OBJECTIVE: To evaluate the association between prediabetes and heart failure (HF) and the association of HF with changes in glycemic status. RESEARCH DESIGN AND METHODS: Patients newly diagnosed with atrial fibrillation (AF) between 2015 and 2018 were divided into three groups (normoglycemia, prediabetes, and type 2 diabetes) according to their baseline glycemic status. The primary outcome was incident HF. The Fine and Gray competing risks model was applied, with death defined as the competing event. RESULTS: Among 17,943 patients with AF (mean age 75.5 years, 47% female), 3,711 (20.7%) had prediabetes, and 10,127 (56.4%) had diabetes at baseline. Over a median follow-up of 4.7 years, HF developed in 518 (14%) patients with normoglycemia, 646 (15.7%) with prediabetes, and 1,795 (17.7%) with diabetes. Prediabetes was associated with an increased risk of HF compared with normoglycemia (subdistribution hazard ratio [SHR] 1.12, 95% CI 1.03-1.22). In patients with prediabetes at baseline, 403 (11.1%) progressed to diabetes, and 311 (8.6%) reversed to normoglycemia at 2 years. Compared with remaining prediabetic, progression to diabetes was associated with an increased risk of HF (SHR 1.50, 95% CI 1.13-1.97), whereas reversion to normoglycemia was associated with a decreased risk (SHR 0.61, 95% CI 0.42-0.94). CONCLUSIONS: Prediabetes was associated with an increased risk of HF in patients with AF. Compared with patients who remained prediabetic, those who progressed to diabetes at 2 years experienced an increased risk of HF, whereas those who reversed to normoglycemia incurred a lower risk of HF.

Chronic kidney disease begets heart failure and vice versa: temporal associations between heart failure events in relation to incident chronic kidney disease in type 2 diabetes.

AIM: To investigate the interplay of incident chronic kidney disease (CKD) and/or heart failure (HF) and their associations with prognosis in a large, population-based cohort with type 2 diabetes (T2DM). METHODS: Patients aged ≥18 years with new-onset T2DM, without renal disease or HF at baseline, were identified from the territory-wide Clinical Data Analysis Reporting System between 2000 and 2015. Patients were followed up until December 31, 2020 for incident CKD and/or HF and all-cause mortality. RESULTS: Among 102 488 patients (median age 66 years, 45.7% women, median follow-up 7.5 years), new-onset CKD occurred in 14 798 patients (14.4%), in whom 21.7% had HF. In contrast, among 9258 patients (9.0%) with new-onset HF, 34.6% had CKD. The median time from baseline to incident CKD or HF (4.4 vs. 4.1 years) did not differ. However, the median (interquartile range) time until incident HF after CKD diagnosis was 1.7 (0.5-3.6) years and was 1.2 (0.2-3.4) years for incident CKD after HF diagnosis (P < 0.001). The crude incidence of CKD was higher than that of HF: 17.6 (95% confidence interval [CI] 17.3-17.9) vs. 10.6 (95% CI 10.4-10.9)/1000 person-years, respectively, but incident HF was associated with a higher adjusted-mortality than incident CKD. The presence of either condition (vs. CKD/HF-free status) was associated with a three-fold hazard of death, whereas concomitant HF and CKD conferred a six to seven-fold adjusted hazard of mortality. CONCLUSION: Cardiorenal complications are common and are associated with high mortality risk among patients with new-onset T2DM. Close surveillance of these dual complications is crucial to reduce the burden of disease.

Concomitant Hepatorenal Dysfunction and Malnutrition in Valvular Heart Surgery: Long-Term Prognostic Implications for Death and Heart Failure.

Background Strategies to improve long-term prediction of heart failure and death in valvular surgery are urgently needed because of an increasing number of procedures globally. This study sought to report the prevalence, changes, and prognostic implications of concomitant hepatorenal dysfunction and malnutrition in valvular surgery. Methods and Results In 909 patients undergoing valvular surgery, 3 groups were defined based on hepatorenal function (the modified model for end-stage liver disease excluding international normalized ratio score) and nutritional status (Controlling Nutritional Status score): normal hepatorenal function and nutrition (normal), hepatorenal dysfunction or malnutrition alone (mild), and concomitant hepatorenal dysfunction and malnutrition (severe). Overall, 32%, 46%, and 19% of patients were classified into normal, mild, and severe groups, respectively. Over a 4.1-year median follow-up, mild and severe groups incurred a higher risk of mortality (hazard ratio [HR], 3.17 [95% CI, 1.40-7.17] and HR, 9.30 [95% CI, 4.09-21.16], respectively), cardiovascular death (subdistribution HR, 3.29 [95% CI, 1.14-9.52] and subdistribution HR, 9.29 [95% CI, 3.09-27.99]), heart failure hospitalization (subdistribution HR, 2.11 [95% CI, 1.25-3.55] and subdistribution HR, 3.55 [95% CI, 2.04-6.16]), and adverse outcomes (HR, 2.11 [95% CI, 1.25-3.55] and HR, 3.55 [95% CI, 2.04-6.16]). Modified model for end-stage liver disease excluding international normalized ratio and controlling nutritional status scores improved the predictive ability of European System for Cardiac Operative Risk Evaluation (area under the curve: 0.80 versus 0.73, P<0.001) and Society of Thoracic Surgeons score (area under the curve: 0.79 versus 0.72, P=0.004) for all-cause mortality. One year following surgery (n=707), patients with persistent concomitant hepatorenal dysfunction and malnutrition (severe) experienced worse outcomes than those without. Conclusions Concomitant hepatorenal dysfunction and malnutrition was frequent and strongly linked to heart failure and mortality in valvular surgery.

Elevated plasma levels of osteoglycin in cardiovascular patients: a systematic review and meta-analysis.

BACKGROUND: To evaluate the levels of osteoglycin (OGN) in patients with cardiovascular disease. METHODS: A meta-analysis was conducted on retrospective studies that compared patients with and without cardiovascular disease. Data including the levels of OGN, low density lipoprotein (LDL), and high density lipoprotein (HDL) were analyzed and expressed as mean differences (MD) with a 95% confidence interval (CI). RESULTS: This meta-analysis included 6 studies with a total of 1,443 patients. The results showed that the concentration of OGN in the blood of patients with cardiovascular disease was significantly elevated compared to that observed in control patients. There were no significant differences in LDL and HDL expression between cardiovascular patients and control patients. Sensitivity analysis and funnel plots showed that this investigation was robust and had low publication bias. DISCUSSION: This report demonstrated that the blood concentration of OGN in patients with cardiovascular disease is significantly elevated compared to that in control patients. Furthermore, the elevated levels of OGN suggests that OGN may be a biomarker/or therapeutic target for patients with cardiovascular disease. Although the structure of OGN is simple, it is indispensable in many important life processes. It plays a protective role in the occurrence of cardiovascular and cerebrovascular diseases through antioxidant, anti-inflammatory, anti-apoptosis and increasing tolerance to hypoxia.

Body volume is the major determinant of worsening renal function in acutely decompensated heart failure with reduced left ventricular ejection fraction.

AIMS: Little is known about the relative importance of body volume and haemodynamic parameters in the development of worsening of renal function in acutely decompensated heart failure (ADHF). To study the relationship between haemodynamic parameters, body water content and worsening of renal function in patients with heart failure with reduced ejection fraction (HFrEF) hospitalised for ADHF. METHODS AND RESULTS: This prospective observational study involved 51 consecutive patients with HFrEF (age: 73±14 years, male: 60%, left ventricular ejection fraction: 33.3%±9.9%) hospitalised for ADHF. Echocardiographic-determined haemodynamic parameters and body volume determined using a bioelectric impedance analyser were serially obtained. All patients received intravenous furosemide 160 mg/day for 3 days. There was a mean weight loss of 3.95±2.82 kg (p<0.01), and brain natriuretic peptide (BNP) reduced from 1380±901 pg/mL to 797±738 pg/mL (p<0.01). Nonetheless serum creatinine (SCr) increased from 134±46 µmol/L to 151±53 µmol/L (p<0.01), and 35% of patients developed worsening of renal function. The change in SCr was positively correlated with age (r=0.34, p=0.017); and negatively with the ratio of extracellular water to total body water, a parameter of body volume status (r=-0.58, p<0.001); E:E' ratio (r=-0.36, p=0.01); right ventricular systolic pressure (r=-0.40, p=0.009); and BNP (r=-0.40, p=0.004). Counterintuitively, no correlation was observed between SCr and cardiac output, or total peripheral vascular resistance. Regression analysis revealed that normal body volume and lower BNP independently predicted worsening of renal function. CONCLUSIONS: Normal body volume and lower serum BNP on admission were associated with worsening of renal function in patients with HFrEF hospitalised for ADHF.

Prebiotic-like effects of chitosan on the intestinal microflora in mice.

Food supplements can modulate the composition of human intestinal microflora due to the potential capacity of improving the host health. Chitosan (CS) possesses diverse biological and pharmacological effects and has been used as a new source of prebiotic. In this study, ERIC (Enterobacterial Repetitive Intergenic Consensus)-PCR and viable counts methods were combined to explore the prebiotic-like effects of CS on the intestinal microflora in mice. Mice were divided into 3 groups randomly, and treated with water, 1g/kg of CS, 0.25g/kg of CS, respectively for 24 days. Subsequently, they were treated with levofloxacin (65mg/kg) for 6 days. Viable counts method indicated the growth of Lactobacillus was promoted with CS treatment while at the same time Enterobacteria and Enterococcus were inhibited. ERIC-PCR fingerprint, UPGMA dendrogram, PCA and diversity analysis showed that the intestinal microflora composition was changed with antibiotics treatment, and that samples were significantly separated from those of the control and long-term CS-treated groups. Together, our results demonstrated that CS could be regarded as a potential food supplement for protecting intestinal microflora and regulate imbalance.

The prevalence, predictors, and prognosis of tricuspid regurgitation in stage B and C heart failure with preserved ejection fraction.

AIMS: Previous studies have demonstrated that moderate/severe tricuspid regurgitation (TR) is associated with adverse outcome in patients with heart failure (HF) with reduced ejection fraction. Little is known about the prevalence and prognostic value of TR in patients of stage B HF and those with stage C HF with preserved ejection fraction (HFpEF). We aimed to investigate the prevalence and prognosis of TR in patients with HFpEF. METHODS AND RESULTS: From 2013 to 2017, 2014 patients with stage B (n = 1341) or C (n = 673) HFpEF were enrolled in the study. Detailed transthoracic echocardiogram was performed, and the severity of TR was graded as no, mild, moderate, and severe. The mean age of the study population was 66.7 ± 14.1 years old, and 46% were men. Mean left ventricular ejection fraction was 62.2 ± 5.5%. The prevalence of moderate/severe TR increased from stage B to C HF (8% to 16%, respectively, P < 0.01). Older age, hyperlipidaemia, atrial fibrillation, left ventricular mass, and right ventricular systolic pressure were independently associated with moderate/severe TR (P < 0.05 for all). With a median follow-up of 3.8 (2.9-4.7) years, 346 patients died and 234 developed HF requiring hospitalization. Kaplan-Meier curve revealed that the presence of moderate/severe TR was associated with all-cause mortality, HF requiring hospitalization and cardiovascular death (log-rank test P < 0.01). Multivariable analysis demonstrated that moderate (hazard ratio = 1.5; 95% confidence interval: 1.1-2.2; P < 0.05) and severe TR (hazard ratio = 2.1; 95% confidence interval: 1.3-3.3; P < 0.01) were independently associated with mortality, HF requiring hospitalization and cardiovascular death. CONCLUSIONS: The presence of moderate/severe TR is not uncommon in patients with stage B HF and stage C HFpEF. Importantly, moderate/severe TR was independently associated with mortality and HF requiring hospitalization.

Growth differentiation factor-15 combined with N-terminal prohormone of brain natriuretic peptide increase 1-year prognosis prediction value for patients with acute heart failure: a prospective cohort study.

BACKGROUND: Clinical assessment and treatment guidance for heart failure depends on a variety of biomarkers. The objective of this study was to investigate the prognostic predictive value of growth differentiation factor-15 (GDF-15) and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) in assessing hospitalized patients with acute heart failure (AHF). METHODS: In total, 260 patients who were admitted for AHF in the First Affiliated Hospital of Nanjing Medical University were enrolled from April 2012 to May 2016. Medical history and blood samples were collected within 24 h after the admission. The primary endpoint was the all-cause mortality within 1 year. The patients were divided into survival group and death group based on the endpoint. With established mortality risk factors and serum GDF-15 level, receiver-operator characteristic (ROC) analyses were performed. Cox regression analyses were used to further analyze the combination values of NT-proBNP and GDF-15. RESULTS: Baseline GDF-15 and NT-proBNP were significantly higher amongst deceased than those in survivors (P < 0.001). In ROC analyses, area under curve (AUC) for GDF-15 to predict 1-year mortality was 0.707 (95% confidence interval [CI]: 0.648-0.762, P < 0.001), and for NT-proBNP was 0.682 (95% CI: 0.622-0.738, P < 0.001). No statistically significant difference was found between the two markers (P = 0.650). Based on the optimal cut-offs (GDF-15: 4526.0 ng/L; NT-proBNP: 1978.0 ng/L), the combination of GDF-15 and NT-proBNP increased AUC for 1-year mortality prediction (AUC = 0.743, 95% CI: 0.685-0.795, P < 0.001). CONCLUSIONS: GDF-15, as a prognostic marker in patients with AHF, is not inferior to NT-proBNP. Combining the two markers could provide an early recognition of high-risk patients and improve the prediction values of AHF long-term prognosis. CLINICAL TRIAL REGISTRATION: ChiCTR-ONC-12001944, http://www.chictr.org.cn.

[Evaluation of Left Atrial Structure and Function with Two-dimensional Speckle Tracking Imaging and Real-time Three-dimensional Imaging in Patients with Paroxysmal Atrial Fibrillation After Radiofrequency Catheter Ablation].

OBJECTIVE: To observe the changes of left atrial structure and function in patients with paroxysmal atrial fibrillation (PAF) after radiofrequency catheter ablation by two-dimensional speckle tracking imaging (STI) and real-time three-dimensional imaging technology (RT-3D) in order to provide basis for clinical evaluation of surgery. METHODS: Thirty two (32) cases of PAF patients with catheter ablation from October 2016 to December 2017 in our hospital were enrolled. According to sinus rhythm whether or not be restored after operation, the patients were divided into sinus rhythm group (SR group, 24 cases) and atrial brillation group (AF group, 8 cases). All PAF patients received echocardiography before and 1, 6 months after surgery. Left atrial structure and functional parameters were measured by STI and RT-3D, including left atrial diameter, volume, left ventricular systole, early diastolic, left atrial systolic peak strain rate and ejection fraction. RESULTS: All parameters in AF group were not changed significantly after surgery ( P>0.05). In SR group, at 6 month after surgery, the levels of Left atrial anteroposterior diameter (LAAPD), Left atrial up and down diameter (LAUDD), Left atrial left and right diameter (LALRD), minimum volume of left atrium (LAV min), Left atrial presystolic volume (LAV p) and max volume of left atrium (LAV max) were significantly decreased, the levels of Left atrial ejection fraction (LAEF), Left atrial active ejection fraction (LAAEF), Left atrial passive ejection fraction (LAPEF) were significantly increased, the strain rates (SRS, SRE, SRA) in the lateral wall base segment, interval middle segment and middle segment of the lateral wall and overall strain parameters (GLSR S, GLSR E, GLSR A) were significantly increased (all P<0.05); and the other segment strain rates were not significantly changed ( P>0.05). In AF group, at 6 month after surgery, the levels of LAV min, LAV p and LAV max were significantly decreased at 6 month after operation, the levels of LAEF, LAAEF were significantly increased, all above had statistical difference ( P<0.05); and the other parameters were not significantly changed ( P>0.05). CONCLUSION: STI and RT-3D could quantitatively analyze the structure and function of left atrium before and after radiofrequency ablation in PAF patients. After ablation, the diameter of LA decreases and the ejection fraction increases in the patients with sinus rhythm; the volume of LA increases and the function reduces in the patients with atrial fibrillation recurrence.

Effect of oral L-citrulline on brachial and aortic blood pressure defined by resting status: evidence from randomized controlled trials.

BACKGROUND: Experimental evidence indicates that oral L-citrulline (L-Cit) may reduce resting blood pressure (BP) as well as BP responses to exercise and cold exposure (non-resting). However, results from human intervention trials are inconsistent. This study aims to summarize the clinical evidence regarding the effects of L-Cit supplementation on brachial systolic blood pressure (SBP), brachial diastolic blood pressure (DBP), in addition to aortic SBP and aortic DBP at rest and non-resting conditions. METHODS: Multiple databases including PubMed, Embase, Cochrane library, Web of Science, and Clinical Trials were searched systematically. Randomized controlled trials of human participants were quantitatively meta-analyzed. RESULTS: Fourteen trials contained in eight studies were available for quantitative syntheses for brachial BP. Results showed that L-Cit supplementation significantly reduced both brachial SBP (- 4.490 mmHg, 95% CI: - 7.332 to - 1.648, P = 0.002) and brachial DBP (- 3.629 mmHg, 95% CI: - 5.825 to - 1.434, P = 0.001). Nine of the trials were meta-analyzed for aortic BP which showed that L-Cit intervention significantly reduced aortic SBP (- 6.763 mmHg, 95% CI: - 10.991 to - 2.534, P = 0.002), but not aortic DBP (- 3.396 mmHg, 95% CI: - 7.418 to 0.627, P = 0.098). The observed reducing effects of L-Cit appeared stronger for non-resting than for resting brachial SBP (P for difference = 0.044). CONCLUSION: L-Cit supplementation significantly decreased non-resting brachial and aortic SBP. Brachial DBP was significantly lowered by L-Cit regardless of resting status. Given the relatively small number of available trials in the stratified analyses and the potential limitations of these trials, the present findings should be interpreted cautiously and need to be confirmed in future well-designed trials with a larger sample size.

Traditional Chinese medicine Qiliqiangxin attenuates phenylephrine-induced cardiac hypertrophy via upregulating PPARγ and PGC-1α.

BACKGROUND: Clinical study has demonstrated that the traditional Chinese medicine Qiliqiangxin (QLQX) has protective effects on heart failure. Phenylephrine (PE) is an important inducing factor for cardiac hypertrophy and our previous studies have showed that QLQX attenuates PE-induced cardiac hypertrophy. Besides, QLQX protects against cardiac remodeling after myocardial infarction via activating PPARγ. However, whether QLQX prevents PE-induced cardiac hypertrophy through PPARγ and its coactivator PGC-1α is still unknown. METHODS: The effects of QLQX were investigated based on PE induced cardiac hypertrophy mouse models. Echocardiography and hematoxylin-eosin (HE) staining were used to determine cardiac function and cross-sectional area, respectively. Quantitative real time PCR (qRT-PCR) was used to determine ANP and BNP expressions. Based on primary neonatal rat ventricular cardiomyocytes (NRVMs) treated with PE, the cell size and expressions of ANP and BNP were determined by immunofluorescent staining and qRT-PCR, respectively. In addition, western blot was used to determine PPARγ and PGC-1α expressions. RESULTS: In present study, we confirmed that QLQX could significantly attenuate cardiac hypertrophy in mice treated with PE. Then we showed that PPARγ and PGC-1α were downregulated in PE-induced cardiac hypertrophy, and QLQX could block the decrease of PPARγ and PGC-1α both in vitro and in vivo. Importantly, we found that PPARγ inhibitors or PGC-1α siRNAs eliminated the protective effects of QLQX on PE-induced cardiac hypertrophy. CONCLUSIONS: Our study suggested that QLQX prevents from PE-induced cardiac hypertrophy by activating PPARγ and its coactivator PGC-1α.

Brachial-ankle pulse wave velocity compared with mean arterial pressure and pulse pressure in risk stratification in a Chinese population.

BACKGROUND: Brachial-ankle pulse wave velocity (baPWV) can be easily measured in an observer-independent way, but lacks robust population-based validation in terms of fatal combined with nonfatal outcomes. METHOD: To address this issue, we studied 4251 Chinese randomly recruited Gaoyou County (54.1% women; mean age, 52.1). RESULTS: In the whole study population, mean values were 102.4 mmHg for mean arterial pressure (MAP), 51.1 mmHg for pulse pressure, and 14.8 m/s for baPWV. Over 4.4 years (median), 74 participants experienced a fatal or nonfatal cardiovascular event and 44 a stroke. In multivariable-adjusted Cox regression, standardized hazard ratios expressing the risk of a composite cardiovascular endpoint were 1.77 (95% confidence interval, 1.43-2.20), 1.37 (1.14-1.64) and 1.50 (1.26-1.78) for MAP, PP and baPWV, respectively; the corresponding hazard ratios for stroke were 1.82 (1.39-2.38), 1.39 (1.12-1.74) and 1.53 (1.25-1.89). baPWV did not add to the prediction of cardiovascular events or stroke by MAP (hazard ratios for baPWV, 1.25 and 1.27, respectively; P ≥ 0.053) but refined models including PP (hazard ratios, 1.42 and 1.45; P ≤ 0.0033). The optimized baPWV threshold, obtained by maximizing Youden's index (16.7 m/s), increased the integrated discrimination improvement over and beyond MAP (+1.27%; P = 0.021) and PP (+1.37%; P = 0.038) for the cardiovascular outcome, but not stroke, and increased the net reclassification improvement for both endpoints (≥42.2%; P ≤ 0.004). CONCLUSION: With fatal and nonfatal cardiovascular and cerebrovascular endpoints as outcome, baPWV marginally increases risk stratification over and beyond MAP, but is a better predictor than PP. A threshold of 16.7 m/s might be used in Chinese populations.

[A clinical study on blood pressure changes before and after tooth extraction in 649 elderly patients].

PURPOSE: To investigate the safety of tooth extraction under ECG monitoring in 649 senile patients with hypertension by observing the blood pressure changes during operation. METHODS: The patients were divided into hypertension group and non-hypertension group. ECG monitoring was carried out during extraction. Blood pressure changes were monitored and recorded. The data was statistically analyzed with SPSS 18.0 software package. RESULTS: The patients' blood pressure in the two groups increased as a result of tooth extraction, and the change was more obvious in patients with hypertension. When blood pressure was controlled to normal range, there was no significant difference in blood pressure between the hypertension group and non-hypertension group. The increase of blood pressure of patients taking ß-receptor blockers was minimal. CONCLUSIONS: Preoperative blood pressure control is important for reducing surgical risk in patients with hypertension during ECG monitoring extraction.