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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]

Background: Chronic kidney disease (CKD) represents a chronic proinflammatory state and is associated with very high cardiovascular risk. Apolipoprotein A-IV (apoA-IV) has antiatherogenic, antioxidative, anti-inflammatory and antithrombotic properties and levels increase significantly during the course of CKD., Objectives: We aimed to investigate the association between apoA-IV and all-cause mortality and cardiovascular outcomes in the German Chronic Kidney Disease study., Methods: This was a prospective cohort study including 5141 Caucasian patients with available apoA-IV measurements and CKD. The majority of the patients had an estimated glomerular filtration rate (eGFR) of 30-60 ml/min/1.73m 2 or an eGFR >60 ml/min/1.73m 2 in the presence of overt proteinuria. Median follow-up was 6.5 years. The association of apoA-IV with comorbidities at baseline and endpoints during follow-up was modelled adjusting for major confounders., Results: Mean apoA-IV concentrations of the entire cohort were 28.9 ± 9.8 mg/dl. Patients in the highest apoA-IV quartile had the lowest high-sensitivity C-reactive protein values despite the highest prevalence of diabetes, albuminuria and the lowest eGFR. Each 10 mg/dl higher apoA-IV translated into lower odds of prevalent cardiovascular disease (1289 cases, odds ratio = 0.80, 95% confidence interval [CI] 0.72-0.86, p = 0.0000003). During follow-up, each 10 mg/dl higher apoA-IV was significantly associated with a lower risk for all-cause mortality (600 cases, hazard ratio [HR] = 0.81, 95% CI 0.73-0.89, p = 0.00004), incident major adverse cardiovascular events (506 cases, HR = 0.88, 95% CI 0.79-0.99, p = 0.03) and death or hospitalizations due to heart failure (346 cases, HR = 0.84, 95% CI 0.73-0.96, p = 0.01)., Conclusions: These data support a link between elevated apoA-IV concentrations and reduced inflammation in moderate CKD. ApoA-IV appears to be an independent risk marker for reduced all-cause mortality, cardiovascular events and heart failure in a large cohort of patients with CKD., (© 2021 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.)