gms | German Medical Science

49. Jahrestagung der Deutschen Gesellschaft für Medizinische Informatik, Biometrie und Epidemiologie (gmds)
19. Jahrestagung der Schweizerischen Gesellschaft für Medizinische Informatik (SGMI)
Jahrestagung 2004 des Arbeitskreises Medizinische Informatik (ÖAKMI)

Deutsche Gesellschaft für Medizinische Informatik, Biometrie und Epidemiologie
Schweizerische Gesellschaft für Medizinische Informatik (SGMI)

26. bis 30.09.2004, Innsbruck/Tirol

Lipoprotein(a) and LDL cholesterol in nephrotic syndrome

Meeting Abstract (gmds2004)

  • corresponding author presenting/speaker Barbara Rantner - Institut für Medizinische Biologie und Humangenetik, Universität Innsbruck, Innsbruck, Österreich
  • Arno Lingenhel - Institut für Medizinische Biologie und Humangenetik, Universität Innsbruck, Innsbruck, Österreich
  • Karl Lhotta - Klinische Abteilung für Nephrologie, Universitätsklinik für Innere Medizin, Innsbruck, Österreich
  • Martina Kronenberg - Institut für Medizinische Biologie und Humangenetik, Universität Innsbruck, Innsbruck, Österreich
  • Paul König - Klinische Abteilung für Nephrologie, Universitätsklinik für Innere Medizin, Innsbruck, Österreich
  • Joachim Thiery - Institut für Labormedizin, klinische Chemie und Molekulardiagnostik, Universitätsspital Leipzig, Leipzig, Deutschland
  • Michael Koch - Klinische Abteilung für Nephrologie und Rheumatologie, Universität Düsseldorf, Düsseldorf, Deutschland
  • Arnold Eckardstein - Institut für klinische Chemie, Universität und Universitätsspital Zürich, Zürich, Schweiz
  • Hans Dieplinger - Institut für Medizinische Biologie und Humangenetik, Universität Innsbruck, Innsbruck, Österreich
  • Florian Kronenberg - Institut für Medizinische Biologie und Humangenetik, Innsbruck, Österreich; Institut für Epidemiologie GSF-National Research Center for Environment and Health, Neuherberg, Deutschland

Kooperative Versorgung - Vernetzte Forschung - Ubiquitäre Information. 49. Jahrestagung der Deutschen Gesellschaft für Medizinische Informatik, Biometrie und Epidemiologie (gmds), 19. Jahrestagung der Schweizerischen Gesellschaft für Medizinische Informatik (SGMI) und Jahrestagung 2004 des Arbeitskreises Medizinische Informatik (ÖAKMI) der Österreichischen Computer Gesellschaft (OCG) und der Österreichischen Gesellschaft für Biomedizinische Technik (ÖGBMT). Innsbruck, 26.-30.09.2004. Düsseldorf, Köln: German Medical Science; 2004. Doc04gmds160

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Veröffentlicht: 14. September 2004

© 2004 Rantner et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielf&aauml;ltigt, verbreitet und &oauml;ffentlich zug&aauml;nglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

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Background

Patients with nephrotic syndrome have the highest Lp(a) concentrations known. The underlying mechanism for this elevation is poorly understood. Furthermore, Lp(a) is an LDL-like particle consisting of 45% cholesterol. The usual methods to determine LDL-cholesterol (LDL-C) do not distinguish between cholesterol derived from LDL and Lp(a) and are thus the net result of cholesterol levels from both lipoproteins. High Lp(a) concentrations therefore significantly contribute to the measured or calculated LDL-C levels. Since statins have no influence on Lp(a) levels, it can be expected that the LDL-C-lowering effect of statins may be diminished in patients who have a pronounced elevation of Lp(a) levels accompanied by only moderate elevations of LDL-C.

Aims of the study

Our study had two goals. First, to investigate whether primary or secondary causes are responsible for the high Lp(a) concentrations. Second, to investigate the Lp(a)-corrected LDL-C concentrations in nephrotic patients.

Methods

We investigated 207 patients with non-diabetic nephrotic syndrome and 274 controls. We measured LDL-C and Lp(a) and analyzed the genetically determined apolipoprotein(a) isoforms.

Results

Patients showed a tremendous elevation of Lp(a) concentrations when compared to controls (mean 60.4 vs. 20.0 mg/dL and median 29.8 vs. 6.4 mg/dL, p<0.0001). Primary and secondary causes contributed to this elevation. The primary causes became apparent by a markedly elevated number of low molecular weight apo(a) phenotypes which are usually associated with high Lp(a) levels. This frequency was 35.7% in patients compared to only 24.8% in controls (P=0.009). In addition, secondary causes by the pathogenetic mechanisms of the nephrotic syndrome itself resulted in a different increase of Lp(a) in the various apo(a) isoform groups. Low molecular weight isoforms were associated with 40-75% elevated Lp(a) concentrations when compared to matched isoforms from controls. High molecular weight apo(a) isoforms showed 100-500% elevated Lp(a) levels compared to matched isoforms from controls. The severity of the nephrotic syndrome as well as the degree of renal impairment did not influence the Lp(a) concentrations.

In the second part of the study, we observed significantly higher LDL-C concentrations in patients when compared to controls (208±82 vs. 132±37 mg/dL, p<0.0001). According to K/DOQI Clinical Practice Guidelines for Managing Dyslipidemias, almost 95% of these patients are candidates for a therapeutic intervention to lower LDL-C. LDL-C levels corrected for Lp(a)-derived cholesterol, however, were 27 mg/dL lower than uncorrected concentrations (compared to only 9 mg/dL in controls). If Lp(a)-corrected instead of total LDL-C levels were used, 25.7% of patients with LMW apo(a) isoforms were classified no longer to be in need of LDL-C-lowering therapeutic intervention compared to only 2.3% of patients with HMW apo(a) phenotypes (p<0.00001). This ("pseudo")pharmacogenetic effect results in incorrect determination of LDL-C.

Discussion

Our observation has an impact on the indication for, and assessment of efficacy of an LDL-C-lowering intervention. This potential artifact should be investigated in ongoing large trials in renal patients as well as in non-renal African-American subjects who have on average markedly higher Lp(a) levels. In non-renal Caucasian subjects with much lower Lp(a) concentrations, this issue will be less relevant.