title: The reverse epidemiology of plasma total homocysteine as a mortality risk factor is related to the impact of wasting and inflammation.
abstract: BACKGROUND
  The reason(s) for the apparently paradoxical 'reverse' association in end-stage renal disease (ESRD) patients in whom a low, rather than a high, total plasma total homocysteine (tHcy) level is an indicator of poor outcome remains unclear. The aim of this study was to examine whether the inverse association maintains, mitigates or reverses after comprehensive multivariate adjustment for the presence of wasting and inflammation as well as other potential confounders.
  
  
  METHODS
  We studied 317 ESRD patients starting dialysis therapy. Fasting blood samples were taken for the analyses of tHcy, serum albumin, C-reactive protein (CRP), serum creatinine and plasma folate. Nutritional status was assessed by subjective global assessment (SGA). Survival was followed for up to 66 months; 105 patients died.
  
  
  RESULTS
  Using Kaplan-Meier analysis, a low tHcy concentration (< or =30 micromol/l) was associated with higher all-cause and cardiovascular (CV) mortality (P < 0.05). Using Cox proportional analysis adjusting for age, gender, glomerular filtration rate = GFR, cardiovascular disease = CVD, plasma folate, total cholesterol and diabetes mellitus, the all-cause and CV mortality still tended to be high for patients with low tHcy. Adding nutritional and inflammation markers (Body mass index = BMI, SGA, serum creatinine, serum albumin and CRP), a low tHcy level was no longer associated with higher mortality but a trend for high tHcy was observed.
  
  
  CONCLUSIONS
  The link between wasting inflammation and a low tHcy appears to be responsible for the reverse association between plasma tHcy and clinical outcome in ESRD patients. After adjustment for confounders including nutritional and inflammation markers, a trend towards increased death risk for high, rather than low, tHcy levels was apparent after adjustment.
authors.affiliation: Renal Medicine and Baxter Novum, K56, Karolinska University Hospital Huddinge, Karolinska Institutet, S-141 86 Stockholm, Sweden.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Suliman
authors.forename: Peter
authors.initials: P
authors.lastname: Stenvinkel
authors.forename: Abdul Rashid
authors.initials: AR
authors.lastname: Qureshi
authors.forename: Kamyar
authors.initials: K
authors.lastname: Kalantar-Zadeh
authors.forename: Peter
authors.initials: P
authors.lastname: Bárány
authors.forename: Olof
authors.initials: O
authors.lastname: Heimbürger
authors.forename: Edward F
authors.initials: EF
authors.lastname: Vonesh
authors.forename: Bengt
authors.initials: B
authors.lastname: Lindholm
mesh_terms: D000328:Adult; D000368:Aged; D002097:C-Reactive Protein / Q000378:metabolism; D005260:Female; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D007249:Inflammation; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000453:epidemiology / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D052756:Nutritional Sciences; D016016:Proportional Hazards Models; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D006710:Homocysteine; D002097:C-Reactive Protein