Circulating Vascular Adhesion Protein-1 Level Predicts Risk of Cardiovascular Events and Mortality in Hemodialysis Patients

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Circulating Neprilysin Level Predicts the Risk of Cardiovascular Events in Hemodialysis Patients
Hyeon Seok Hwang, 1 Jin sug Kim, 1 Yang gyun Kim, 1 Yu ho Lee, 2 Dong-Young Lee, 3 Shin-Young Ahn, 4 Ju young Moon, 1 Sangho Lee, 1 Kyung hwan Jeong. 1 1 Kyung Hee University Medical Center, Seoul, Republic of Korea; 2 CHA Bundang Medical Center, Seongnam, Gyeonggi-do, Republic of  Korea; 3 Korea Veterans Health Service, Seoul, Republic of Korea; 4 Korea  University Medical Center, Seoul, Republic of Korea.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.

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Hypertension and CVD: Clinical, Outcomes, and Trials

Serum Cathepsin-S Concentration Is Not Related to Arterial Calcification Severity Among Hemodialysis Patients
Hao-Wei Ma, Chih-Ching Lin, Szu-Yuan Li.Taipei Veterans General Hospital, Taipei, Taiwan.
Background: Vascular calcification is prevalent among hemodialysis patients and is strongly correlated to their cardiovascular and total mortality.Cathepsin S, a lysosomal cysteine protease that is elevated in CKD patients, has shown its critical role of vascular calcification in cell culture experiments and in uremic animal model.To validate the relationship of Cathepsin S and vascular calcification in clinical practice, we conducted the current cross sectional study.
Methods: 88 patients on maintenance hemodialysis were enrolled and their serum Cathepsin S and its natural inhibitor Cystatin C were measured.Severity of vascular calcification was semi-quantified by aortic arch calcification (AAC) score on chest X-rays.Patients were divided into groups according to their AAC score, and the serum Cathepsin S level, Cathepsin S / Cystatin C ratio and other factors were compared between groups.
Results: There was no significant difference in the level of Cathepsin S (p=0.778) or Cathepsin S to Cystatin C ratio (p=0.417) between patients with different aortic arch calcification score.Only age was associated with the severity of AAC score (p=0.014).Increasing serum triglyceride level is significantly associated with higher serum Cathepsin S level (Pearson Correlation p=0.001,R square=0.133).
Conclusions: Despite a pre-clinical study supporting the role of Cathepsin S in the development of vascular calcification under uremic and phosphate-rich conditions, serum Cathepsin S was not found to be associated with vascular calcification severity among hemodialysis patients in this study.Serum triglyceride is the strongest predicting factor for higher Cathepsin S levels in these patients.Further study is needed to confirm these findings using a different grading system.