Apolipoprotein A- IV concentrations and clinical outcomes in haemodialysis patients with type 2 diabetes mellitus - a post hoc analysis of the 4 D Study.

Background Apolipoprotein A- IV (apo A- IV) is an anti-atherogenic and anti-oxidative plasma glycoprotein involved in reverse cholesterol transport. The aim of this study was to examine the association between apo A- IV and all-cause mortality, cardiovascular endpoints and parameters of protein-energy wasting and nutrition in haemodialysis patients. Methods This post hoc analysis was performed in the German Diabetes Dialysis Study (4 D Study) evaluating atorvastatin in 1255 haemodialysis patients with type 2 diabetes mellitus, followed for a median of 4 years. The association between apo A- IV and relevant outcomes was analysed using Cox proportional hazards regression analyses. Body mass index ( BMI) was used as a marker of protein-energy wasting. In addition, a definition of extended wasting was applied, combining median values of BMI, serum albumin, creatinine and sensitive C-reactive protein, to classify patients. Results Mean (±SD) apo A- IV concentration was 49.8 ± 14.2 mg dL⁻¹. Age- and gender-adjusted apo A- IV concentrations were strongly associated with the presence of congestive heart failure at baseline [odds ratio = 0.81, 95% confidence interval (CI) 0.74-0.88 per 10 mg dL⁻¹ increase; P < 0.001). During the prospective follow-up, the strongest association was found for all-cause mortality [hazard ratio ( HR) = 0.89, 95% CI 0.85-0.95, P = 0.001), which was mainly because of patients with BMI > 23 kg m⁻² ( HR = 0.87, 95% CI 0.82-0.94, P < 0.001) and those in the nonwasting group according to the extended definition ( HR = 0.89, 95% CI 0.84-0.96, P = 0.001). This association remained significant after additionally adjusting for parameters associated with apo A- IV at baseline. Further associations were observed for sudden cardiac death. Apo A- IV was less strongly associated with atherogenic events such as myocardial infarction. Conclusions Low apo A- IV levels seem to be a risk predictor of all-cause mortality and sudden cardiac death. This association might be modified by nutritional status. [ABSTRACT FROM AUTHOR]