scholarly journals Circulating Neprilysin Level Predicts the Risk of Cardiovascular Events in Hemodialysis Patients

2021 ◽  
Vol 8 ◽  
Author(s):  
Hyeon Seok Hwang ◽  
Jin Sug Kim ◽  
Yang Gyun Kim ◽  
Yu Ho Lee ◽  
Dong-Young Lee ◽  
...  

Background: Neprilysin inhibition has demonstrated impressive benefits in heart failure treatment, and is the current focus of interest in cardiovascular (CV) and kidney diseases. However, the role of circulating neprilysin as a biomarker for CV events is unclear in hemodialysis (HD) patients.Methods: A total of 439 HD patients from the K-cohort were enrolled from June 2016 to April 2019. The plasma neprilysin level and echocardiographic findings at baseline were examined. The patients were prospectively followed up to assess the primary endpoint (composite of CV events and cardiac events).Results: Plasma neprilysin level was positively correlated with left ventricular (LV) mass index, LV end-systolic volume, and LV end-diastolic volume. Multivariate linear regression analysis revealed that neprilysin level was negatively correlated with LV ejection fraction (β = −2.14; p = 0.013). The cumulative event rate of the composite of CV events was significantly greater in neprilysin tertile 3 (p = 0.049). Neprilysin tertile 3 was also associated with an increased cumulative event rate of cardiac events (p = 0.016). In Cox regression analysis, neprilysin tertile 3 was associated with a 2.61-fold risk for the composite of CV events [95% confidence interval (CI), 1.37–4.97] and a 2.72-fold risk for cardiac events (95% CI, 1.33–5.56) after adjustment for multiple variables.Conclusions: Higher circulating neprilysin levels independently predicted the composite of CV events and cardiac events in HD patients. The results of this study suggest the importance of future studies on the effect of neprilysin inhibition in reducing CV events.

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Hyeon Seok Hwang ◽  
Jin Sug Kim ◽  
Yang-Gyun Kim ◽  
So-Young Lee ◽  
Shin Young Ahn ◽  
...  

Abstract Background and Aims Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a promising new target for prevention of cardiovascular (CV) events. However, the clinical significance of circulating PCSK9 is unclear in hemodialysis (HD) patients. Method A total of 353 HD patients were prospectively enrolled from June 2016 to May 2018 in a K-cohort. Plasma PCSK9 level was measured at the time of study enrollment. Patients were classified into three groups based on PCSK9 tertile. The primary endpoint was defined as composite of CV event and death from any cause. Results Plasma PCSK9 level was positively correlated with total cholesterol level in patients with statin treatment. However, PCSK9 was not related to plasma inflammatory (high-sensitivity C-reactive peptide, monocyte chemoattractant protein-1, interleukin-6) or calcification-related markers (osteoprotegerin and receptor activator of nuclear factor kappa-Β ligand). Multivariate linear regression analysis revealed that baseline statin treatment and serum glucose, albumin, and total cholesterol were independent determinants of circulating PCSK9 levels. In Cox-regression analysis, PCSK9 tertile 3 was associated with a 1.99-fold risk for composite events (95% CI, 1.08–3.66), and it was associated with a 2.26-fold risk for CV events (95% CI, 1.11–4.62) after adjustment for multiple variables. PCSK9 tertile 3 provides additional prognostic power to predict composite events in subgroups with higher levels of high-sensitivity C-reactive peptide and LDL. Conclusion In conclusion, higher circulating PCSK9 level independently predicted CV events and death in HD patients. These results suggest the importance of future studies regarding the effect of PCSK9 inhibition on reduction of CV events.


2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Sofia Skampardoni ◽  
Diana Y Y Chiu ◽  
Philip A Kalra ◽  
Darren Green

Abstract Background and Aims Cardiovascular disease is common in chronic and end stage kidney disease. Left ventricular hypertrophy (LVH) has been identified as contributor to cardiovascular risk in this population. The aim of the study was to assess whether the combined use of electrocardiography and echocardiography in assessing LVH in a haemodialysis population can provide improved risk stratification. Method Prospective study of 192 prevalent maintenance haemodialysis ( HD) patients 12 lead ECGs were performed on a mid week non –dialysis day. Electrocardiographic strain was defined as a down slopping convex ST segment with inverted T waves in leads V5 and / or V6. Transthoracic echocardiographic was performed immediately after ECG .LV mass was indexed to body surface area (LVMIBSA). LVH was determined if LVMI >116g/m2 for male patients, and >100g/m2 for female patients. The primary study endpoint was major cardiac events (MACE). A secondary endpoint was all cause mortality. Results 192 patients included in the final analysis, 137 (71.4%) male.. The mean ejection fraction (EF) was 60.6± 11.1 % and the mean LVMI (BSA) was 115.0± 36.8 g/m2. During a mean follow up period of 2.4 ± 1.0 years, 50 patients reached a MACE end point and 62 patients died. On univariate Cox regression analysis, the factors associated with MACE were the presence of ECG strain (HR 2.961, CI: 1.254 – 6.990, p= 0.013)) URR (HR 0.968, CI: 0.942 – 0.994, p=0.015) and history of CAD (HR: 2.397 CI: 1.363 -4.2515, p= 0.002). In multivariate Cox regression analysis adjusting for baseline cardiovascular phenotype and dialysis parameters ECG strain remained significantly associated with MACE. Conclusion The presence of electrocardiographic strain increases the risk for MACE independently of LVH in haemodialysis patients. ECG strain has potential to be a simple bedside prognostic biomarker and even therapeutic target in haemodialysis patients.


Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Yan Liu ◽  
Qiaobing Sun ◽  
Yixiao Zhao ◽  
Yinong Jiang

The Correlation between Left Atrial-Left Ventricular-Arterial Coupling and Circadian Rhythm of Blood Pressure in Hypertension Objective: Hypertension induces left atrial (LA) and left ventricular (LV) dysfunction, and arterial stiffness increased. In this study, we further investigated the association between LA-LV-arterial coupling and circadian rhythm of blood pressure (BP) in essential hypertension (HT). Design and Methods: We enrolled 289 HT patients which were evaluated by 2 dimensional speckle tracking echocardiography (2D-STE), ambulatory 24-hour BP monitoring (ABPM) and carotid-femoral pulse wave velocity (PWV). According to BP patterns, these patients were divided into two groups, which included dippers (n=109), patients with a >10% reduction in BP at nighttime; non-dippers (n=180), patients with a <10% reduction in BP at nighttime. 2D-STE based LA and LV strains were studied and the following parameters were measured, LV global longitudinal strain (GLS), LA reservoir strain (LA S-S ), LA conduit strain (LA S-E ), and LA booster pump strain (LA S-A ). LA stiffness index (LASI) defined as the ratio of E/e' to LA S-S , and PWV-to-GLS ratio (PWV/GLS) were calculated to reflect LA-LV-arterial coupling. Furthermore, we also explored the correlation between LASI (or PWV/GLS) and ambulatory blood pressure indexes. The related factors were evaluated by multivariate linear regression analysis to find the independent factors. Results: LASI was significantly higher in non-dippers (0.35±0.24) than dippers (0.29±0.12) ( p <0.05). PWV/GLS was significantly higher in non-dippers (-90.30±34.13) than dippers (-79.62±25.84) ( p <0.05). LA S-S , LA S-A and LV GLS were significantly lower in non-dippers than dippers ( p <0.05). Multivariate linear regression analysis revealed that LV mass index (LVMI), PWV/GLS, nighttime mean SBP (n-SBP) and nighttime mean DBP (n-DBP) were independently correlated with LASI; LASI and n-SBP were independently correlated with PWV/GLS. Conclusions: LA and LV myocardial mechanics, and LA-LV-arterial coupling were associated with circadian rhythm of BP. Nocturnal systolic BP was the independent risk factor of abnormal LA-LV-arterial coupling in HT.


Folia Medica ◽  
2013 ◽  
Vol 55 (3-4) ◽  
pp. 26-32 ◽  
Author(s):  
Christos Tsalikidis ◽  
Fotini Papachristou ◽  
Michael Pitiakoudis ◽  
Byron Asimakopoulos ◽  
Grigorios Trypsianis ◽  
...  

ABSTRACT OBJECTIVE: Modifications in E-cadherin (E-Cad) expression are associated with dedifferentiation, progression, metastases and poor prognosis in many types of tumors. The aim of the present study was to identify a potential association of the pre- and post-operative soluble E-Cad levels (sE-Cad) with the clinicopathological parameters of patients with gastric cancer. PATIENTS AND METHODS: Serum sE-Cad levels were determined in 99 gastric cancer patients and 78 healthy volunteers using ELISA. RESULTS: Levels of sE-Cad were significantly increased in gastric cancer patients compared with these levels in healthy controls (p < 0.001). For the evaluation of the diagnostic significance of sE-Cad the area under the receiver operating characteristic (ROC) curve (AUC) was 0.835, while the optimal cut-off point of 9.9 μg/mL was determined to classify gastric cancer patients, which yielded sensitivity of 72.7%, specificity of 80.8% and accuracy of 76.3%. Poor differentiation (p = 0.009) and the presence of distant metastases (p < 0.001) were the two significant independent prognostic determinants for high sE-Cad levels in multivariate linear regression analysis. The preoperative levels of sE-Cad also proved helpful in classifying patients according to the choice treatment (curative versus palliative) (AUC, 0.656); when the optimal cut-off point was set at 17.60 μg/mL, the sensitivity was 57%, the specificity was 83% and accuracy was 75%. Survival was shorter in patients with increased sE-Cad (median, 7 months vs 39 months, p = 0.0002), although multivariate Cox regression analysis demonstrated a marginal prognostic significance of sE-Cad for survival (adjusted HR = 1.68, 95% CI = 0.93 to 3.02, p = 0.072). CONCLUSIONS: Serum sE-Cad levels could be considered as a diagnostic and prognostic marker in gastric cancer patients as well as a tool to select a treatment approach. The prognostic value of sE-Cad on overall survival requires further study.


2020 ◽  
Vol 9 (1) ◽  
pp. 244 ◽  
Author(s):  
Hyeon Seok Hwang ◽  
Jin Sug Kim ◽  
Yang Gyun Kim ◽  
So-Young Lee ◽  
Shin Young Ahn ◽  
...  

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a promising new target for the prevention of cardiovascular (CV) events. However, the clinical significance of circulating PCSK9 is unclear in hemodialysis (HD) patients. A total of 353 HD patients were prospectively enrolled from June 2016 to August 2019 in a K-cohort. Plasma PCSK9 level was measured at the time of study enrollment. The primary endpoint was defined as a composite of CV event and death. Plasma PCSK9 level was positively correlated with total cholesterol level in patients with statin treatment. Multivariate linear regression analysis revealed that baseline serum glucose, albumin, total cholesterol, and statin treatment were independent determinants of circulating PCSK9 levels. Cumulative rates of composite and CV events were significantly higher in patients with tertile 3 PCSK9 (p = 0.017 and p = 0.010, respectively). In multivariate Cox-regression analysis, PCSK9 tertile 3 was associated with a 1.97-fold risk of composite events (95% CI, 1.13–3.45), and it was associated with a 2.31-fold risk of CV events (95% CI, 1.17–4.59). In conclusion, a higher circulating PCSK9 level was independently associated with incident CV events and death in HD patients. These results suggest the importance of future studies regarding the effect of PCSK9 inhibition.


Cardiology ◽  
2015 ◽  
Vol 133 (3) ◽  
pp. 135-140 ◽  
Author(s):  
Qiong Yao ◽  
Xi-hong Hu ◽  
Quan-li Shen ◽  
Zhong-wei Qiao ◽  
Mi-er Pa ◽  
...  

We aimed to compare the diagnostic value of indexed right ventricular end-diastolic volume (RVEDVi) and the ratio of right ventricle volume to left ventricle volume (RV/LV ratio) in prediction of the severity of pulmonary regurgitation (PR) expressed as the PR fraction (PRF) after surgery of tetralogy of Fallot (TOF). Forty-one patients with repaired TOF were included in the study. RVEDVi, LVEDVi, RV/LV ratio, PRF and ejection fraction were measured with magnetic resonance imaging. A PRF of more than 20% was considered significant. The predictive capability of two markers (RVEDVi and RV/LV ratio) for significant PR was compared using multivariate linear regression analysis and receiver operating characteristic (ROC) analysis. Both the RV/LV ratio and RVEDVi showed a correlation with PRF (r = 0.526/0.321, p = 0.001/0.041) in the correlation analysis, but in multivariate regression analysis the only independent predictor of PRF was the RV/LV ratio (F = 14.890, p = 0.001). ROC analysis revealed that a better discrimination of significant PR (>20%) from slight types (=20%) PR can be reached with the RV/LV ratio than RVEDVi (AUC = 0.805/0.709, p = 0.01). The RV/LV ratio was better than RVEDVi at differentiating mild from moderate PR (p = 0.006 vs. p = 0.153), and proved superior over RVEDVi in predicting PR based on the PRF criterion.


Biomechanics ◽  
2021 ◽  
Vol 1 (2) ◽  
pp. 190-201
Author(s):  
Pathmanathan Cinthuja ◽  
Graham Arnold ◽  
Rami J. Abboud ◽  
Weijie Wang

There is a lack of evidence about the ways in which balance ability influences the kinematic and kinetic parameters and muscle activities during gait among healthy individuals. The hypothesis is that balance ability would be associated with the lower limb kinematics, kinetics and muscle activities during gait. Twenty-nine healthy volunteers (Age 32.8 ± 9.1; 18 males and 11 females) performed a Star Excursion Balance test to measure their dynamic balance and walked for at least three trials in order to obtain a good quality of data. A Vicon® 3D motion capture system and AMTI® force plates were used for the collection of the movement data. The selected muscle activities were recorded using Delsys® Electromyography (EMG). The EMG activities were compared using the maximum values and root mean squared (RMS) values within the participants. The joint angle, moment, force and power were calculated using a Vicon Plug-in-Gait model. Descriptive analysis, correlation analysis and multivariate linear regression analysis were performed using SPSS version 23. In the muscle activities, positive linear correlations were found between the walking and balance test in all muscles, e.g., in the multifidus (RMS) (r = 0.800 p < 0.0001), vastus lateralis (RMS) (r = 0.639, p < 0.0001) and tibialis anterior (RMS) (r = 0.539, p < 0.0001). The regression analysis models showed that there was a strong association between balance ability (i.e., reaching distance) and the lower limb muscle activities (i.e., vastus medialis–RMS) (R = 0.885, p < 0.0001), and also between balance ability (i.e., reaching distance) and the lower limb kinematics and kinetics during gait (R = 0.906, p < 0.0001). In conclusion, the results showed that vastus medialis (RMS) muscle activity mainly contributes to balance ability, and that balance ability influences the lower limb kinetics and kinematics during gait.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
K Sopova ◽  
C Park ◽  
A Al-Atta ◽  
K Bennaceur ◽  
A Mohammad ◽  
...  

Abstract Background Adverse left ventricular (LV) remodelling is associated with development of heart failure and poor outcomes in patients with acute myocardial infarction (AMI). Understanding the immunomodulatory mechanisms of LV remodelling is an essential step for the development of novel therapies. Interferon-γ-inducible protein-10 (IP-10)/CXCL10 is a chemokine involved in the recruitment of activated T cells into sites of tissue inflammation. Although IP-10 was reported to reduce adverse LV remodeling in a preclinical myocardial infarction model, its role in LV remodeling in humans with AMI remains unknown. Purpose To determine the clinical predictive value of serum IP-10 in LV remodeling in patients with ST-segment elevation myocardial infarction (STEMI). Methods This is a substudy of the double-blind, randomised controlled trial “Evaluating the effectiveness of intravenous ciclosporin on reducing reperfusion injury in patients undergoing primary percutaneous coronary intervention” (CAPRI; ClinicalTrials.gov registry number NCT02390674), which enrolled 52 acute STEMI patients. LV remodeling was assessed by cardiovascular magnetic resonance (CMR) imaging and was defined as the 12-week vs. the 3-day post-myocardial infarction change of the left ventricular ejection fraction (ΔLVEF), LV end-diastolic volume (ΔEDV) or LV end-systolic volume (ΔESV). Serum IP-10 was measured before and 5min, 15min, 30min, 90min and 24h after reperfusion by ELISA. Linear regression analysis was used to determine the independent association of IP-10 with the endpoints of the study. Results Serum IP-10 concentration peaked at 30min after reperfusion followed by a 2-fold decrease at the 24h post reperfusion compared to pre-reperfusion levels (P&lt;0.001 for all). Comparison of the 12-week CMR to the baseline CMR imaging revealed that baseline pre-reperfusion as well as 5min, 15min, 30min and 90min, but not 24h, post-reperfusion IP-10 serum levels associated with increased LVEF and decreased ESV at 12-weeks (range correlation coefficient r=[0.35–0.41], P&lt;0.05 with ΔLVEF and r=[−0.33 to −0.44], P&lt;0.05 with ΔESV) indicating that the increase of IP-10 at the acute phase of myocardial infarction confers a cardioprotective role. Multivariable linear regression analysis for ΔLVEF showed that in a model including baseline pre-reperfusion or 5min or 15min or 30min or 90min post-reperfusion IP-10 and age, gender, traditional risk factors (arterial hypertension, body-mass index, hyperlipoproteinemia, diabetes mellitus, smoking, family history of CAD), infarct location, admission high-sensitivity troponin T, door-to-balloon time and ciclosporin treatment, only IP-10 was the independent determinant of ΔLVEF. Conclusions Increased serum IP-10 levels early after reperfusion are associated with reverse LV remodeling in patients with STEMI undergoing primary PCI. The clinical application of IP-10 as a novel biomarker of LV remodeling post-AMI should be further explored and validated. Funding Acknowledgement Type of funding source: None


2021 ◽  
Vol 49 (6) ◽  
pp. 030006052110161
Author(s):  
Zhenhong Zhang ◽  
Shunyin Wang ◽  
Junru Yan ◽  
Zhiwen Xu ◽  
Dongliang Liang ◽  
...  

Objective We assessed differences and correlations between 24-hour ambulatory blood pressure (ABP) and office blood pressure (OBP) monitoring. Methods We conducted an observational study among 85 untreated patients with essential hypertension and measured 24-hour ABP, OBP, target organ damage (TOD) markers, and metabolism indexes. Variance analysis and the Pearson method were used to compare differences and correlation between the two methods. The Spearman or Pearson method was applied to compare the correlation between TOD markers, blood pressure index, and metabolism index. Linear regression analysis was applied to estimate the quantitative relationship between the blood pressure index and TOD markers. Results There were significant differences in the mean and variance of systolic blood pressure (SBP) and diastolic blood pressure and a positive correlation between ABP and OBP. Correlations between the left ventricular mass index (LVMI) and average ambulatory SBP, daytime ambulatory SBP, nighttime ambulatory SBP, and fasting blood glucose were significant. Correlations between left intima-media thickness (IMT) and average ambulatory SBP, nighttime ambulatory SBP, right IMT, and nighttime ambulatory SBP were significant. In linear regression analysis of the LVMI (y) and ambulatory SBP (x), the equation was expressed as y = 0.637*x. Conclusion Nighttime ambulatory SBP may be an optimal predictor of TOD.


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