High Lp(a) predicts death from infection in younger dialysis patients with diabetes, the 4D Study post hoc analysis of 1255 patients (Nephrol Dial Transplant 2016)

Original title: Lipoprotein(a) concentrations, apolipoprotein(a) isoforms and clinical endpoints in haemodialysis patients with type 2 diabetes mellitus: results from the 4D Study

Nephrol Dial Transplant · 10 January 2016 · 8

Kollerits B, Drechsler C, Krane V, Lamina C, März W, Dieplinger H, Ritz E, Wanner C, Kronenberg F, German Diabetes and Dialysis Study Investigators

This post hoc analysis of the 4D Study (German Diabetes Dialysis Study), which compared atorvastatin with placebo in 1255 haemodialysis patients with type 2 diabetes (median follow-up 4 years, median age 66 years), examined Lp(a) and low molecular weight (LMW) apolipoprotein(a) isoforms as predictors of mortality. Median baseline Lp(a) was 11.5 mg/dL. Higher Lp(a) was associated with all-cause mortality overall (hazard ratio 1.09, P=0.004), while LMW apo(a) isoforms predicted mortality only in patients aged 66 or younger (hazard ratio 1.38, P=0.02). The strongest association was for death due to infection in patients 66 or younger, for both Lp(a) (hazard ratio 1.39, P=0.001) and LMW apo(a) isoforms (hazard ratio 2.17, P=0.005), and Lp(a) also predicted fatal stroke in this younger group (hazard ratio 1.54, P=0.03). Neither Lp(a) nor LMW apo(a) isoforms were associated with other atherosclerosis-related events, and the findings show their mortality effects are modified by age.

Original abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.