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


METHODS
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.
Krane
Vera
V
University Hospital Würzburg, Department of Internal Medicine I, Division of Nephrology, Oberdürrbacher Strasse 6, D-97080 Würzburg, Germany. krane_v@medizin.uni-wuerzburg.de
Berger
Mario
M
Lilienthal
Jürgen
J
Winkler
Karl
K
Schambeck
Christian
C
Wanner
Christoph
C
D000368:Aged; D000906:Antibodies / Q000097:blood*; D001241:Aspirin / Q000009:adverse effects; D000069059:Atorvastatin; D002423:Cause of Death; D016009:Chi-Square Distribution; D003645:Death, Sudden / Q000209:etiology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000276:immunology / Q000401:mortality / Q000628:therapy; D004311:Double-Blind Method; D005260:Female; D005858:Germany; D006493:Heparin / Q000276:immunology*; D006538:Heptanoic Acids / Q000627:therapeutic use; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D053208:Kaplan-Meier Estimate; D007674:Kidney Diseases / Q000150:complications / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000276:immunology / Q000401:mortality; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects; D010978:Platelet Factor 4 / Q000276:immunology*; D016016:Proportional Hazards Models; D011446:Prospective Studies; D011758:Pyrroles / Q000627:therapeutic use; D006435:Renal Dialysis / Q000009:adverse effects / Q000401:mortality; D018570:Risk Assessment; D012307:Risk Factors; D020521:Stroke / Q000276:immunology / Q000401:mortality; D013997:Time Factors; D016896:Treatment Outcome
D000906:Antibodies; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010975:Platelet Aggregation Inhibitors; D011758:Pyrroles; D010978:Platelet Factor 4; D006493:Heparin; D000069059:Atorvastatin; D001241:Aspirin