Endothelial function and cardiovascular events in chronic kidney disease.
BACKGROUND
As patients with chronic kidney disease (CKD) are at high risk of developing coronary artery disease (CAD), it is important to stratify their cardiovascular risk. We investigated whether peripheral endothelial dysfunction is associated with the presence of CAD in patients with CKD and is a predictor of cardiovascular events.


METHODS
We enrolled 383 CKD patients with at least one coronary risk factor. Peripheral endothelial function was assessed by reactive hyperemia peripheral arterial tonometry index (RHI). The presence of CAD was determined by coronary angiography. Cardiovascular events were assessed during follow-up.


RESULTS
Ln-RHI was significantly lower in risk factor-matched CKD patients (n=323) than risk factor-matched non-CKD patients (n=323) (0.527 ± 0.192 vs. 0.580 ± 0.218, p=0.001). In CKD patients (n=383), Ln-RHI was significantly lower in CAD (0.499 ± 0.183, n=262) than non-CAD (0.582 ± 0.206, n=121) (p<0.001) patients. Multivariate logistic regression analysis identified Ln-RHI as an independent factor associated with the presence of CAD (p=0.001). During a mean follow-up period of 30 months, 90 cardiovascular events were recorded in CKD patients. Multivariate Cox hazard analysis identified low-Ln-RHI as an independent predictor of cardiovascular events (hazard ratio=2.70, 95% confidence interval=1.62-4.51, p<0.001). The predictive value of combined Ln-RHI and Framingham risk score (FRS) was evaluated by net reclassification index (NRI) and C-statistics, which showed significant improvement (NRI=22%, p<0.001) (C-statistics: FRS=0.49, FRS+Ln-RHI=0.62, p=0.005).


CONCLUSIONS
Endothelial function was significantly impaired in CKD patients and correlated with the presence of CAD. Severe endothelial dysfunction was an independent and incremental predictor of cardiovascular events in CKD.
Faculty of Life Sciences, Department of Cardiovascular Medicine, Graduate School of Medical Science, Kumamoto University Kumamoto, Japan.
Yoshihiro
Y
Hirata
Faculty of Life Sciences, Department of Cardiovascular Medicine, Graduate School of Medical Science, Kumamoto University Kumamoto, Japan; Cardiovascular Division Diabetes Care Center, Jinnouchi Hospital Kumamoto, Japan. Electronic address: ssugiyam@kumamoto-u.ac.jp.
Seigo
S
Sugiyama
Faculty of Life Sciences, Department of Cardiovascular Medicine, Graduate School of Medical Science, Kumamoto University Kumamoto, Japan.
Eiichiro
E
Yamamoto
Division of Cardiology, Yokohama City University Medical Center Yokohama, Japan.
Yasushi
Y
Matsuzawa
Faculty of Life Sciences, Department of Cardiovascular Medicine, Graduate School of Medical Science, Kumamoto University Kumamoto, Japan; Division of Cardiology, Yokohama City University Medical Center Yokohama, Japan.
Eiichi
E
Akiyama
Faculty of Life Sciences, Department of Cardiovascular Medicine, Graduate School of Medical Science, Kumamoto University Kumamoto, Japan.
Hiroaki
H
Kusaka
Faculty of Life Sciences, Department of Cardiovascular Medicine, Graduate School of Medical Science, Kumamoto University Kumamoto, Japan.
Koichiro
K
Fujisue
Faculty of Life Sciences, Department of Cardiovascular Medicine, Graduate School of Medical Science, Kumamoto University Kumamoto, Japan.
Hirofumi
H
Kurokawa
Faculty of Life Sciences, Department of Cardiovascular Medicine, Graduate School of Medical Science, Kumamoto University Kumamoto, Japan.
Junichi
J
Matsubara
Faculty of Life Sciences, Department of Cardiovascular Medicine, Graduate School of Medical Science, Kumamoto University Kumamoto, Japan.
Koichi
K
Sugamura
Faculty of Life Sciences, Department of Cardiovascular Medicine, Graduate School of Medical Science, Kumamoto University Kumamoto, Japan.
Hirofumi
H
Maeda
Faculty of Life Sciences, Department of Cardiovascular Medicine, Graduate School of Medical Science, Kumamoto University Kumamoto, Japan.
Satomi
S
Iwashita
Diabetes Care Center, Jinnouchi Hospital Kumamoto, Japan; Division of Preventive Cardiology, Department of Cardiovascular Medicine, Kumamoto University Hospital Kumamoto, Japan.
Hideaki
H
Jinnouchi
Department of General Internal Medicine, Yamaguchi University Hospital Ube, Japan.
Kunihiko
K
Matsui
Faculty of Life Sciences, Department of Cardiovascular Medicine, Graduate School of Medical Science, Kumamoto University Kumamoto, Japan.
Hisao
H
Ogawa
D000368:Aged; D000369:Aged, 80 and over; D002318:Cardiovascular Diseases / Q000175:diagnosis / Q000453:epidemiology* / Q000503:physiopathology*; D015331:Cohort Studies; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D051436:Renal Insufficiency, Chronic / Q000175:diagnosis / Q000453:epidemiology* / Q000503:physiopathology*; D012307:Risk Factors
Cardiovascular events; Chronic kidney disease; Cohort study; Coronary artery disease; Endothelial dysfunction