Advanced oxidation protein products as risk factors for atherosclerotic cardiovascular events in nondiabetic predialysis patients.
BACKGROUND
Inflammation and oxidative stress are established risk factors for atherosclerosis, but whether they contribute to the accelerated atherogenesis associated with chronic kidney disease (CKD) remains to be assessed at the predialysis stage.


METHODS
We prospectively examined the relationship between plasma levels of C-reactive protein (CRP), fibrinogen, and advanced oxidation protein products (AOPPs), as selected markers of inflammation and oxidative stress, and incident first occlusive atherosclerotic cardiovascular (CV) events (ASCVEs) in a single-center cohort of 80 uremic predialysis patients without diabetes with a creatinine clearance ranging from 20 to 40 mL/min/1.73 m2 .


RESULTS
During follow-up (median, 7 years), 21 patients developed coronary, cerebral, or peripheral artery occlusive accidents, an incidence of 44/1,000 patient-years. Except for older age, their conventional risk factors did not differ compared with the 59 patients who remained free of such accidents. Conversely, plasma levels of CRP (4.3 +/- 2.7 versus 2.3 +/- 2 mg/L; P = 0.005), fibrinogen (5.6 +/- 1.4 versus 4.4 +/- 1.2 mg/L; P = 0.0009), and AOPPs (58 +/- 20 versus 42 +/- 14 micromol/L; P = 0.0002) were significantly greater at baseline, although serum creatinine levels did not differ between the 2 groups. By multivariate Cox regression analysis, age and CRP, fibrinogen, and AOPP levels were significant independent predictors of ASCVEs. Risk factor-adjusted hazard ratios were as follows: age, 1.13 (95% confidence interval, 1.04 to 1.22; P = 0.002); CRP level, 1.37 (95% confidence interval, 1.05 to 1.79; P = 0.02); fibrinogen level, 2.23 (95% confidence interval, 1.20 to 4.13; P = 0.011); and AOPP level, 1.68 (95% confidence interval, 1.12 to 2.51; P = 0.011).


CONCLUSIONS
CRP, fibrinogen, and AOPP levels independently predict ASCVEs in patients with CKD in the predialysis phase and might directly contribute to the uremia-associated accelerated atherogenesis.
Descamps-Latscha
Béatrice
B
INSERM U507, Necker Hospital, Paris, France. b.descamps@necker.fr
Witko-Sarsat
Véronique
V
Nguyen-Khoa
Thao
T
Nguyen
Anh Thu
AT
Gausson
Valérie
V
Mothu
Nadya
N
London
Gérard M
GM
Jungers
Paul
P
D001161:Arteriosclerosis / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D001798:Blood Proteins / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000097:blood*; D002908:Chronic Disease; D015331:Cohort Studies; D003920:Diabetes Mellitus / Q000097:blood*; D003956:Dialysis / Q000379:methods*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology; D011446:Prospective Studies; D051437:Renal Insufficiency / Q000097:blood; D012307:Risk Factors
D015415:Biomarkers; D001798:Blood Proteins