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Antibodies to platelet factor 4-heparin complex and outcome in hemodialysis patients with diabetes

Clin J Am Soc Nephrol. 2010 May;5(5):874-81. doi: 10.2215/CJN.01170209. Epub 2010 Feb 25.

Abstract

Background and objectives: Hemodialysis patients with type 2 diabetes exhibit an excessive cardiovascular risk and regularly receive heparin. We tested whether antibodies to the platelet factor 4-heparin complex (PF4-H-AB) contribute to outcome.

Design, setting, participants, & measurements: In 1255 hemodialysis patients with type 2 diabetes, the German Diabetes Dialysis Study evaluated the effect of atorvastatin (20 mg/d) versus placebo. In a post hoc analysis, the association among PF4-H-ABs, biochemistry, and prespecified, centrally adjudicated end points (combined cardiovascular end point [CVE], all-cause mortality, sudden death, myocardial infarction, stroke) was investigated.

Results: During 4 years, 460 patients reached the CVE; 605 died, 159 of sudden death. Myocardial infarction and stroke occurred in 199 and 97 patients, respectively. Positive PF4-H-AB status was found in 231 (18.7%) of 1236 tested patients and was associated with lower albumin, higher C-reactive protein, and arrhythmia. In a multivariate model adjusted for demographics, comorbidities, and biochemistry, PF4-H-ABs were associated with sudden death. No significant association between PF4-H-ABs and all-cause mortality, myocardial infarction, stroke, or the CVE was observed. Detecting an interaction between acetylsalicylic acid and PF4-H-ABs regarding sudden death and mortality, we found that the association between PF4-H-ABs and outcomes was restricted to patients with acetylsalicylic acid use, most likely because of indication bias.

Conclusions: In hemodialysis patients who have type 2 diabetes and are treated with acetylsalicylic acid, PF4-H-ABs are associated with sudden and all-cause death. Further studies are needed to elucidate this association.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Antibodies / blood*
  • Aspirin / adverse effects
  • Atorvastatin
  • Cause of Death
  • Chi-Square Distribution
  • Death, Sudden / etiology
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetes Mellitus, Type 2 / immunology
  • Diabetes Mellitus, Type 2 / mortality
  • Diabetes Mellitus, Type 2 / therapy
  • Double-Blind Method
  • Female
  • Germany
  • Heparin / immunology*
  • Heptanoic Acids / therapeutic use
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Kaplan-Meier Estimate
  • Kidney Diseases / complications
  • Kidney Diseases / immunology
  • Kidney Diseases / mortality
  • Kidney Diseases / therapy*
  • Logistic Models
  • Male
  • Middle Aged
  • Myocardial Infarction / immunology
  • Myocardial Infarction / mortality
  • Platelet Aggregation Inhibitors / adverse effects
  • Platelet Factor 4 / immunology*
  • Proportional Hazards Models
  • Prospective Studies
  • Pyrroles / therapeutic use
  • Renal Dialysis* / adverse effects
  • Renal Dialysis* / mortality
  • Risk Assessment
  • Risk Factors
  • Stroke / immunology
  • Stroke / mortality
  • Time Factors
  • Treatment Outcome

Substances

  • Antibodies
  • Heptanoic Acids
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Platelet Aggregation Inhibitors
  • Pyrroles
  • Platelet Factor 4
  • Heparin
  • Atorvastatin
  • Aspirin