Artikel
Apolipoprotein A-IV and its relation to cardiovascular endpoints and all-cause mortality in patients on hemodialysis – the 4D Study
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Veröffentlicht: | 20. September 2011 |
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Background: Apolipoprotein A-IV (apoA-IV) is a 46 kDa glycoprotein almost exclusively produced in intestinal enterocytes. In vitro studies suggest a role for apoA-IV in reverse cholesterol transport. ApoA-IV has been linked to hepatic lipid metabolism, physiological control of food intake, body weight and shows anti-atherogenic and anti-oxidative properties. It is an early marker of kidney impairment and is associated with progression of kidney disease. The aim of this study was to examine the association between apoA-IV, cardiovascular endpoints, all-cause mortality and parameters of protein-energy wasting and nutrition in patients on hemodialysis.
Methods: This post hoc analysis was performed in the 4D Study (German Diabetes Dialysis Study), which evaluates the efficacy and safety of atorvastatin in 1,255 patients with type 2 diabetes mellitus (T2DM) on maintenance hemodialysis treatment during 4 years of follow-up.
Results: Mean apoA-IV concentration at baseline was 49.8±14.2 mg/dL. A significant interaction between BMI, albumin and phosphate concentration and apoA-IV levels was detected. ApoA-IV was strongly associated with the presence of congestive heart failure at baseline (OR 0.78 (0.71-0.86) per 10 mg/dL increase, p=0.0000003). In the total group, patients with lower apoA-IV concentrations had a significantly higher risk for cerebrovascular events and a trend for higher risk for cardiac endpoints (death from cardiac causes and sudden cardiac death) observed during follow-up. The strongest association was found for all-cause mortality (HR 0.89 (0.84-0.95) p=0.0003), which was most pronounced in the BMI group >23 kg/m² (HR 0.87 (0.81-0.93), p=0.00005 (and the albumin group >3.8 g/dL) and remained significant after additionally adjusting for congestive heart failure. For the BMI group >23 kg/m² the same holds true for the cardiac and cerebrovascular events. Phosphate and apoA-IV levels interact in their effect on all cause mortality. For low phosphate levels (<2.4 mmol/L), decreasing apoA-IV levels have a significant impact on all-cause mortality. For high apoA-IV levels (>36.1 mg/dL), increasing phosphate levels have a significant impact on all-cause mortality.
Conclusion: Low apoA-IV levels seem to be a risk predictor for cardiac and cerebrovascular events as well as all-cause mortality in T2DM patients on hemodialysis that might be modified by wasting and nutrition.
References
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