title: Lipoprotein(a) concentrations, apolipoprotein(a) isoforms and clinical endpoints in haemodialysis patients with type 2 diabetes mellitus: results from the 4D Study.
abstract: High lipoprotein(a) [Lp(a)] concentrations and low molecular weight (LMW) apolipoprotein(a) [apo(a)] isoforms are associated with cardiovascular disease and mortality in the general population. We examined the association of both with all-cause mortality and cardiovascular endpoints in haemodialysis patients with diabetes mellitus.
  
  
  
  This is a post hoc analysis of the prospective 4D Study (German Diabetes Dialysis Study) that evaluated atorvastatin compared with placebo in 1255 haemodialysis patients with type 2 diabetes mellitus (median follow-up 4 years). The association of natural logarithm-transformed Lp(a) concentrations (increment one unit) and apo(a) isoforms with outcomes was analysed by Cox proportional hazards regression. The influence of age (median 66 years) was evaluated by stratified survival analyses.
  
  
  
  The median baseline Lp(a) concentration was 11.5 mg/dL (IQR 5.0-41.8). A quarter of patients had at least one LMW apo(a) isoform. Increased Lp(a) concentrations were associated with all-cause mortality in the total group [hazard ratio (HR) 1.09 (95% CI 1.03-1.16), P = 0.004]. LMW apo(a) isoforms were only associated with all-cause mortality in patients ≤ 66 years [HR 1.38 (95% CI 1.05-1.80), P = 0.02]. The strongest association for Lp(a) concentrations and LMW apo(a) isoforms was found for death due to infection in patients ≤ 66 years [HR 1.39 (95% CI 1.14-1.71), P = 0.001; HR 2.17 (95% CI 1.26-3.75), P = 0.005]. Lp(a) concentrations were also associated with fatal stroke in patients ≤66 years of age [HR 1.54 (95% CI 1.05-2.24), P = 0.03]. Neither Lp(a) nor LMW apo(a) isoforms were associated with other atherosclerosis-related events.
  
  
  
  High Lp(a) concentrations and LMW apo(a) isoforms are risk predictors for all-cause mortality and death due to infection in haemodialysis patients with diabetes mellitus. These associations are modified by age.
authors.affiliation: Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Barbara
authors.initials: B
authors.lastname: Kollerits
authors.affiliation: Division of Nephrology, Department of Internal Medicine 1 and Comprehensive Heart Failure Centre, University Hospital of Würzburg, Würzburg, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Drechsler
authors.affiliation: Division of Nephrology, Department of Internal Medicine 1 and Comprehensive Heart Failure Centre, University Hospital of Würzburg, Würzburg, Germany.
authors.forename: Vera
authors.initials: V
authors.lastname: Krane
authors.affiliation: Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Claudia
authors.initials: C
authors.lastname: Lamina
authors.affiliation: Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.|Medical Clinic V (Nephrology, Hypertensiology, Rheumatology, Endocrinology, Diabetology), Mannheim Medical Faculty, University of Heidelberg, Mannheim, Germany.|Synlab Academy, Synlab Services GmbH, Mannheim, Germany.
authors.forename: Winfried
authors.initials: W
authors.lastname: März
authors.affiliation: Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Hans
authors.initials: H
authors.lastname: Dieplinger
authors.affiliation: Department of Nephrology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Eberhard
authors.initials: E
authors.lastname: Ritz
authors.affiliation: Division of Nephrology, Department of Internal Medicine 1 and Comprehensive Heart Failure Centre, University Hospital of Würzburg, Würzburg, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Wanner
authors.affiliation: Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Florian
authors.initials: F
authors.lastname: Kronenberg
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D053241:Apoprotein(a) / Q000097:blood; D000069059:Atorvastatin / Q000008:administration & dosage*; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000209:etiology* / Q000517:prevention & control; D002423:Cause of Death / Q000639:trends; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000628:therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D005858:Germany / Q000453:epidemiology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage; D015994:Incidence; D017270:Lipoprotein(a) / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011446:Prospective Studies; D020033:Protein Isoforms; D006435:Renal Dialysis; D015996:Survival Rate / Q000639:trends; D013997:Time Factors; D055815:Young Adult
chemical_list: D015415:Biomarkers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D017270:Lipoprotein(a); D020033:Protein Isoforms; D000069059:Atorvastatin; D053241:Apoprotein(a)
keywords: all-cause mortality; apolipoprotein(a) isoforms; cardiovascular disease; diabetes mellitus; infection; lipoprotein(a)