Artikel
Impact of the apolipoprotein(a) size polymorphism on total mortality in dialysis patients: a 10 year follow-up
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Autoren
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Florian Kronenberg
- Institute of Medical Biology and Human Genetics, University of Innsbruck, Austria and GSF - National Research Center for Environment and Health, Munich-Neuherberg, Germany, Innsbruck und München, Österreich
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Ulrich Neyer
- Feldkirch Hospital, Feldkirch, Österreich
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Paul König
- Innsbruck University Hospital, Department of Clinical Nephrology, Austria, Innsbruck
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Martin Auinger
- Lainz Hospital, Vienna, Austria
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Karl Lhotta
- Innsbruck University Hospital, Department of Clinical Nephrology, Austria, Innsbruck, Österreich
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Martin Wiesholzer
- St. Pölten Hospital, Austria, St. Pölten, Österreich
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Hans Dieplinger
- Institute of Medical Biology and Human Genetics, University of Innsbruck, Austria, Innsbruck, Österreich
| Veröffentlicht: | 14. September 2004 |
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Gliederung
Text
Lipoprotein(a) [Lp(a)] is a genetically determined risk factor for atherosclerosis [Ref. 1], [Ref. 2]. About 30-70% of the Lp(a) plasma concentrations are determined by the apo(a) size polymorphism [Ref. 3]. This polymorphism is caused by a kringle-IV repeat polymorphism in the LPA gene with more than 30 isoforms [Ref. 4]. These isoforms can be grouped in low (LMW) and high molecular weight (HMW) apo(a) isoforms.
Patients with kidney disease have a 10- to 20-fold increased risk for cardiovascular complications [Ref. 5] which can not be explained by traditional atherosclerosis risk factors. Lipoprotein(a) is significantly elevated in these patients [Ref. 6], [Ref. 7], [Ref. 8]. Previous studies, however, demonstrated that the apo(a) size polymorphism is a better predictor for cardiovascular disease than Lp(a) concentrations [Ref. 9], [Ref. 10], [Ref. 11].
We are following a group of more than 600 dialysis patients recruited between 1991 and 1996 in five Austrian dialysis centers [Ref. 7]. Until fall of 2004 we will have finished the follow-up of on average 10 years in these patients. Preliminary results show that about 65% of the patients have already died. A Cox hazard regression model reveals that the following variables contributed significantly to total mortality: [Tab. 1]
From the pathogenetic standpoint the LMW apo(a) phenotype is mainly associated with atherosclerotic complication. Therefore, we conclude that the association of the apo(a) phenotype with atherosclerosis in dialysis patients is so strong that we can even observe an association with total mortality to which cardiovascular events might contribute 50%. The ongoing validation of all fatal and non-fatal cardiovascular events will be of major importance for a deepened analysis of the data.
References
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