title: Strong association between malnutrition, inflammation, and atherosclerosis in chronic renal failure.
abstract: BACKGROUND
  Atherosclerotic cardiovascular disease and malnutrition are widely recognized as leading causes of the increased morbidity and mortality observed in uremic patients. C-reactive protein (CRP), an acute-phase protein, is a predictor of cardiovascular mortality in nonrenal patient populations. In chronic renal failure (CRF), the prevalence of an acute-phase response has been associated with an increased mortality.
  
  
  METHODS
  One hundred and nine predialysis patients (age 52 +/- 1 years) with terminal CRF (glomerular filtration rate 7 +/- 1 ml/min) were studied. By using noninvasive B-mode ultrasonography, the cross-sectional carotid intima-media area was calculated, and the presence or absence of carotid plaques was determined. Nutritional status was assessed by subjective global assessment (SGA), dual-energy x-ray absorptiometry (DXA), serum albumin, serum creatinine, serum urea, and 24-hour urine urea excretion. The presence of an inflammatory reaction was assessed by CRP, fibrinogen (N = 46), and tumor necrosis factor-alpha (TNF-alpha; N = 87). Lipid parameters, including Lp(a) and apo(a)-isoforms, as well as markers of oxidative stress (autoantibodies against oxidized low-density lipoprotein and vitamin E), were also determined.
  
  
  RESULTS
  Compared with healthy controls, CRF patients had an increased mean carotid intima-media area (18.3 +/- 0.6 vs. 13.2 +/- 0.7 mm2, P < 0.0001) and a higher prevalence of carotid plaques (72 vs. 32%, P = 0.001). The prevalence of malnutrition (SGA 2 to 4) was 44%, and 32% of all patients had an acute-phase response (CRP > or = 10 mg/liter). Malnourished patients had higher CRP levels (23 +/- 3 vs. 13 +/- 2 mg/liter, P < 0.01), elevated calculated intima-media area (20.2 +/- 0.8 vs. 16.9 +/- 0.7 mm2, P < 0.01) and a higher prevalence of carotid plaques (90 vs. 60%, P < 0.0001) compared with well-nourished patients. During stepwise multivariate analysis adjusting for age and gender, vitamin E (P < 0.05) and CRP (P < 0.05) remained associated with an increased intima-media area. The presence of carotid plaques was significantly associated with age (P < 0.001), log oxidized low-density lipoprotein (oxLDL; P < 0.01), and small apo(a) isoform size (P < 0.05) in a multivariate logistic regression model.
  
  
  CONCLUSIONS
  These results indicate that the rapidly developing atherosclerosis in advanced CRF appears to be caused by a synergism of different mechanisms, such as malnutrition, inflammation, oxidative stress, and genetic components. Apart from classic risk factors, low vitamin E levels and elevated CRP levels are associated with an increased intima-media area, whereas small molecular weight apo(a) isoforms and increased levels of oxLDL are associated with the presence of carotid plaques.
authors.affiliation: Department of Clinical Science, Karolinska Institutet, Huddinge University Hospital, Sweden. peter.stenvinkel@klinvet.ki.se
authors.forename: P
authors.initials: P
authors.lastname: Stenvinkel
authors.forename: O
authors.initials: O
authors.lastname: Heimbürger
authors.forename: F
authors.initials: F
authors.lastname: Paultre
authors.forename: U
authors.initials: U
authors.lastname: Diczfalusy
authors.forename: T
authors.initials: T
authors.lastname: Wang
authors.forename: L
authors.initials: L
authors.lastname: Berglund
authors.forename: T
authors.initials: T
authors.lastname: Jogestrand
mesh_terms: D015502:Absorptiometry, Photon; D000368:Aged; D001054:Apolipoproteins A / Q000097:blood; D001161:Arteriosclerosis / Q000000981:diagnostic imaging / Q000453:epidemiology* / Q000276:immunology; D001323:Autoantibodies / Q000097:blood; D015415:Biomarkers; D002097:C-Reactive Protein / Q000032:analysis; D002339:Carotid Arteries / Q000000981:diagnostic imaging / Q000473:pathology; D003430:Cross-Sectional Studies; D005260:Female; D005340:Fibrinogen / Q000032:analysis; D006801:Humans; D006949:Hyperlipidemias / Q000453:epidemiology / Q000276:immunology; D007249:Inflammation / Q000453:epidemiology* / Q000276:immunology; D007676:Kidney Failure, Chronic / Q000453:epidemiology* / Q000276:immunology; D017270:Lipoprotein(a) / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D008875:Middle Aged; D015596:Nutrition Assessment; D018384:Oxidative Stress; D015995:Prevalence; D011502:Protein-Energy Malnutrition / Q000453:epidemiology* / Q000276:immunology; D012044:Regression Analysis; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D017539:Tunica Intima / Q000473:pathology; D014463:Ultrasonography; D014810:Vitamin E / Q000097:blood
chemical_list: D001054:Apolipoproteins A; D001323:Autoantibodies; D015415:Biomarkers; D017270:Lipoprotein(a); D008077:Lipoproteins, LDL; D014409:Tumor Necrosis Factor-alpha; C099252:oxidized low density lipoprotein; D014810:Vitamin E; D005340:Fibrinogen; D002097:C-Reactive Protein