Angiopoietin-2 as a Prognostic Biomarker of Major Adverse Cardiovascular Events and All-Cause Mortality in Chronic Kidney Disease.
BACKGROUND
Chronic kidney disease (CKD) patients have higher prevalence of major adverse cardiovascular events (MACE) and all-cause mortality. Endothelial damage and dysfunction have been regarded as early portents of MACE in CKD patients. Angiopoietin-2 (Ang-2) impairs endothelial function and promotes aberrant neovascularization. The aim of the study was to assess the relationship between circulating Ang-2 and MACE or all-cause mortality in a CKD cohort.


METHODS
A total of 621 pre-dialysis stage 3-5 CKD patients were enrolled from January 2006 to December 2011 and were followed up till October 2014. Plasma Ang-2 was measured in duplicate using commercial enzyme-linked immunosorbent assays (ELISA). Clinical outcomes included MACE or all-cause mortality.


RESULTS
Of all patients, 122 (19.8%) reached MACE or all-cause mortality. Seventy-two had MACE, 79 died, and 29 had both MACE and all-cause mortality during the follow-up period of 41.5±28.3 months. Ang-2 quintile was divided at 1405.0, 1730.0, 2160.9, and 2829.9 pg/ml. The adjusted HR of MACE or all-cause mortality for every single higher log Ang-2 was 5.69 (95% CI: 2.00-16.20, P = 0.001). The adjusted HR of MACE or all-cause mortality was 2.48 (95% CI: 1.25-4.90) for patients of quintile 5 compared with those of quintile 1. A longitudinal association between MACE or all-cause mortality and stepwise increases in Ang-2 levels was found (P-trend = 0.008).


CONCLUSIONS
Ang-2 is an independent predictor of MACE or all-cause mortality in CKD patients. Additional study is necessary in order to explore the mechanism of the association of Ang-2 with adverse outcomes in patients with CKD.
Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Division of General Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Division of Nephrology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Faculty of Renal Care, Kaohsiung Medical University, Kaohsiung, Taiwan.
Yi-Chun
YC
Tsai
Division of General Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Division of Cardiology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
Chee-Siong
CS
Lee
Division of Nephrology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Faculty of Renal Care, Kaohsiung Medical University, Kaohsiung, Taiwan.
Yi-Wen
YW
Chiu
Division of Nephrology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Faculty of Renal Care, Kaohsiung Medical University, Kaohsiung, Taiwan.
Hung-Tien
HT
Kuo
Division of Nephrology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
Su-Chu
SC
Lee
Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Division of Nephrology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Faculty of Renal Care, Kaohsiung Medical University, Kaohsiung, Taiwan; Institute of Population Sciences, National Health Research Institutes, Miaoli, Taiwan.
Shang-Jyh
SJ
Hwang
Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Division of Nephrology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Faculty of Renal Care, Kaohsiung Medical University, Kaohsiung, Taiwan.
Mei-Chuan
MC
Kuo
Division of Nephrology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Faculty of Renal Care, Kaohsiung Medical University, Kaohsiung, Taiwan.
Hung-Chun
HC
Chen
D000368:Aged; D042702:Angiopoietin-2 / Q000097:blood*; D002318:Cardiovascular Diseases / Q000097:blood* / Q000209:etiology / Q000401:mortality*; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000150:complications / Q000401:mortality* / Q000628:therapy; D015996:Survival Rate
D042702:Angiopoietin-2