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Lipoprotein(a) is not elevated in non-diabetic microalbuminuric subjects

A longitudinal study of lipoprotein(a) concentrations and apolipoprotein(a) size isoforms

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International Journal of Clinical and Laboratory Research

Abstract

Microalbuminuric non-diabetic subjects have an increased risk of cardiovascular disease which is not explained by standard risk factors. In diabetic patients, microalbuminuria is associated with increased lipoprotein(a) concentrations. We have determined lipoprotein(a) concentrations and duplicate measures of albumin excretion rate, on two occasions separated by around 3 years, in 125 Europid subjects aged 40–75 years without hypertension or glucose intolerance and in 49 offspring aged 15–40 years. The apolipoprotein(a) isoform size, the major genetic determinant of lipoprotein(a) concentration, was also determined. There were no differences in lipoprotein(a) concentration between the 42 subjects who were microalbuminuric on either or both samples at screening (median 9.4 mg/dl, 20th and 80th percentiles 2.6 and 46.3 mg/dl) and the 79 who had been normoalbuminuric at both collections (median 10.9 mg/dl, 20th and 80th percentiles 2.9 and 53.0 mg/dl;P=0.58). Lipoprotein(a) concentrations were not significantly different between subjects with or without microalbuminuria at recell (P=0.55) or between those with or without microalbuminuria classified by mean albumin excretion rate in either collection (P=0.24 andP=0.73, respectively). There were no significant relationships between albumin excretion rate as a continuous variable and lipoprotein(a) concentration, or between changes in the two variables over 3 years. The microalbuminuric and normoalbuminuric subjects had similar distributions of size isoforms. There were also no differences in lipoprotein(a) concentration or isoform distribution between offspring of microalbuminuric and of normoalbuminuric subjects. In conclusion, we found no evidence that micro-albuminuric subjects with normal blood pressure and normal glucose tolerance have elevated concentrations of lipoprotein(a) to explain their increased cardiovascular risk.

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References

  1. Yudkin JS, Forrest RD, Jackson CA. Microalbuminuria as predictor of vascular disease in non-diabetic subjects: Islington Diabetes Survey. Lancet 1988; II:530.

    Article  Google Scholar 

  2. Damsgaard EM, Frøland A, Jørgensen OD, Mogensen CE. Eight to nine year mortality in known non-insulin dependent diabetics and controls. Kidney Int 1992; 41:731.

    Article  PubMed  CAS  Google Scholar 

  3. Winocour PH, Harland JOE, Millar JP, Laker MF, Alberti KGMM. Microalbuminuria and associated cardiovascular risk factors in the community. Atherosclerosis 1992; 93:71.

    Article  PubMed  CAS  Google Scholar 

  4. Yudkin JS. Microalbuminuria in non-diabetic individuals: a prognostic index of cardiovascular disease. In: Andreucci VE, Fine LG, eds. International Yearbook of Nephrology Dialysis Transplantation. Oxford: Oxford University Press; 1994:59–74.

    Google Scholar 

  5. Woo J, Cockram CS, Swaminathan R, Lau E, Chan A, Cheung R. Microalbuminuria and other cardiovascular risk factors in nondiabetic subjects. Int J Cardiol 1992; 37:345.

    Article  PubMed  CAS  Google Scholar 

  6. Metcalf P, Baker J, Scott A, Wild C, Scragg R, Dryson E. Albuminuria in people at least 40 years old: effect of obesity, hypertension and hyperlipidaemia. Clin Chem 1992; 38:1802.

    PubMed  CAS  Google Scholar 

  7. Foyle W-J, Carstensen E, Fernandez M, Yudkin JS. A longitudinal study of associations of microalbuminuria with the insulin resistance syndrome and sodium-lithium countertransport in nondiabetic subjects. Arterioscler Thromb Vasc Biol 1995; 15:1330.

    PubMed  CAS  Google Scholar 

  8. Mogensen CE. Microalbuminuria predicts clinical proteinuria and early mortality in maturity-onset diabetes. N Engl J Med 1984; 310:356.

    Article  PubMed  CAS  Google Scholar 

  9. Messent JWC, Elliott TG, Hill RD, Jarrett J, Keen H, Viberti G. Prognostic significance of microalbuminuria in insulin-dependent diabetes mellitus: a twenty-three year follow-up study. Kidney Int 1992; 41:836.

    Article  PubMed  CAS  Google Scholar 

  10. Mogensen CE, Christensen CK. Predicting diabetic nephropathy in insulin-dependent patients. N Engl J Med 1984; 311:89.

    Article  PubMed  CAS  Google Scholar 

  11. Andersen AR, Christiansen JS, Andersen JK, Kreiner S, Deckert T. Diabetic nephropathy in type 1 (insulin-dependent) diabetes: an epidemiological study. Diabetologia 1983; 25:496.

    Article  PubMed  CAS  Google Scholar 

  12. Earle K, Walker J, Hill C, Viberti GC. Familial clustering of cardiovascular disease in patients with insulin-dependent diabetes and nephropathy. N Engl J Med 1992; 326:673.

    Article  PubMed  CAS  Google Scholar 

  13. Viberti GC, Keen H, Wiseman MJ. Raised arterial pressure in parents of proteinuric insulin dependent diabetics. BMJ 1987; 295:515.

    PubMed  CAS  Google Scholar 

  14. Seaquist ER, Goetz FC, Rich S, Barbosa J. Familial clustering of diabetic kidney disease: evidence for genetic susceptibility to diabetic nephropathy. N Engl J Med 1989; 320:1161.

    Article  PubMed  CAS  Google Scholar 

  15. Kaperlrud H, Bangstad H-J, Dahl-Jørgensen K, Berg K, Hanssen KF. Serum Lp(a) lipoprotein concentrations in insulin dependent diabetic patients with microalbuminuria. BMJ 1991; 303:675.

    Google Scholar 

  16. Scott J. Lipoprotein(a): thrombotic and atherogenic. BMJ 1991; 303:663.

    PubMed  CAS  Google Scholar 

  17. Boerwinkle E, Leffert CC, Lin J, Lackner C, Chiesa G, Hobbs HH. Apolipoprotein(a) gene accounts for greater than 90% of the variation in plasma lipoprotein(a) concentrations. J Clin Invest 1992; 90:52.

    PubMed  CAS  Google Scholar 

  18. Utermann G, Menzel HJ, Kraft HG, Duba HC, Kemmler HG, Seitz C. Lp(a) glycoprotein phenotypes: inheritance and relation to Lp(a)-lipoprotein concentrations in plasma. J Clin Invest 1987; 80:458.

    PubMed  CAS  Google Scholar 

  19. Lindahl G, Gersdorf E, Menzel HJ, Seed M, Humphries S, Utermann G. VAriation in the size of human apolipoprotein(a) is due to a hypervariable region in the gene. Hum Genet 1990; 84:563.

    Article  PubMed  CAS  Google Scholar 

  20. Lackner C, Boerwinkle E, Leffert CC, Rahmig T, Hobbs HH. Molecular basis of apolipoprotein(a) isoform size heterogeneity as revealed by pulsed-field gel electrophoresis. J Clin Invest 1991; 87:2153.

    PubMed  CAS  Google Scholar 

  21. Rhoads GG, Dahlen G, Berg K, Morton NE, Dannenberg AL. Lp(a) lipoprotein as a risk factor for myocardial infarction. JAMA 1986; 256:2540.

    Article  PubMed  CAS  Google Scholar 

  22. Winocour PH, Bhatnagar D, Ishola M, Arrol S, Durrington PN. Lipoprotein(a) and microvascular disease in type 1 (insulin-dependent) diabetes. Diabetic Med 1991; 8:922.

    PubMed  CAS  Google Scholar 

  23. Jenkins AJ, Steele JS, Janus ED, Santamaria JD, Best JD. Plasma apolipoprotein(a) is increased in type 2 (non-insulin-dependent) diabetic patients with microalbuminuria. Diabetologia 1992; 35:1055.

    Article  PubMed  CAS  Google Scholar 

  24. Gould MM, Mohamed-Ali V, Goubet SA, Yudkin JS, Haines AP. Microalbuminuria: associations with height and sex in non-diabetic subjects. BMJ 1993; 306:240.

    PubMed  CAS  Google Scholar 

  25. Gould MM, Mohamed-Ali V, Goubet SA, Yudkin JS, Haines AP. Associations of urinary albumin excretion rate with vascular disease in Europid nondiabetic subjects. J Diabetic Complications 1994; 8:180.

    Article  CAS  Google Scholar 

  26. Chesham J, Anderton SW, Kingdon CFM. Rapid competitive enzymoimmunoassay for albumin in urine. Clin Chem 1986; 32:669.

    PubMed  CAS  Google Scholar 

  27. Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein-cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1992; 18:499.

    Google Scholar 

  28. Marcovina SM, Albers JJ, Gabel B, Koschinsky ML, Gaur VP. The effect of the number of apo(a) kringle 4 domains on the immunochemical measurement of Lp(a). Clin Chem 1995; 41:246.

    PubMed  CAS  Google Scholar 

  29. Marcovina SM, Zhang ZH, Gaur VP, Albers JJ. Identification of 34 apolipoprotein(a) isoforms: differential expression of apolipoprotein(a) alleles between American Blacks and Whites. Biochem Biophys Res Commun 1993; 191:1192.

    Article  PubMed  CAS  Google Scholar 

  30. Mogensen CE, Chachati A, Christensen CK, Close CF, Deckert T, Hommel E, Kastrup J, Lefebvre P, Mathiesen ER, Feldt-Rasmussen B, Schmitz A, Viberti GC. Microalbuminuria: an early marker of renal involvement in diabetes. Uremia Invest 1985-86; 9:85.

    PubMed  Google Scholar 

  31. Borch-Johnsen K, Kreiner S. Proteinuria: value as predictor of cardiovascular mortality in insulin-dependent diabetes mellitus. BMJ 1987; 294:1651.

    PubMed  CAS  Google Scholar 

  32. Jarrett RJ, Viberti GC, Argyropoulos A, Hill RD, Mahmud U, Murrells TJ. Microalbuminuria predicts mortality in non-insulin-dependent diabetes. Diabetic Med 1984; 1:17.

    Article  PubMed  CAS  Google Scholar 

  33. Pettitt DJ, Saad MF, Bennett PH, Nelson RG, Knowler WC. Familial predisposition to renal disease in two generations of Pima Indians with type 2 (non-insulin-dependent) diabetes mellitus. Diabetologia 1990; 33:438.

    Article  PubMed  CAS  Google Scholar 

  34. Haffner S, Morales PA, Gruber MK, Hazuda HP, Stern MP. Cardiovascular risk factors in non-insulin dependent diabetic subjects with microalbuminuria. Arterioscler Thromb 1993; 13:205.

    PubMed  CAS  Google Scholar 

  35. Schnack C, Pietschmann P, Knöbl P, Schuller E, Prager R, Schernthaner G. Apolipoprotein(a) levels and artherogenic lipid fractions in relation to the degree of urinary albumin excretion in type 2 diabetes mellitus. Nephron 1994; 66:273.

    PubMed  CAS  Google Scholar 

  36. Rosengren A, Wilhelmsen L, Eriksson E, Risberg B, Wedel H. Lipoprotein(a) and coronary heart disease: a prospective case-control study in a general population sample of middle aged men. BMJ 1990; 301:1248.

    Article  PubMed  CAS  Google Scholar 

  37. Jauhiainen M, Koskinen P, Ehnholm C, Frick MH, Mänttäri M, Manninen V, Huttunen JK. Lipoprotein(a) and coronary heart disease risk: a nested case-control study of the Helsinki Heart Study participants. Atherosclerosis 1991; 89:59.

    Article  PubMed  CAS  Google Scholar 

  38. Ridker PM, Hennekens CH, Stampfer MJ. A prospective study of lipoprotein(a) and the risk of myocardial infarction. JAMA 1993; 270:2195.

    Article  PubMed  CAS  Google Scholar 

  39. Loscalzo J, Weinfeld M, Fless GM, Scanu AM. Lipoprotein(a), fibrin binding, and plasminogen activation. Arteriosclerosis 1990; 10:240.

    PubMed  CAS  Google Scholar 

  40. Hasstedt SJ, Williams RR. Three alleles for quantitative Lp(a). Genet Epidemiol 1986; 3:53.

    Article  PubMed  CAS  Google Scholar 

  41. Haffner SM, Stern MP, Gruber MKK, Hazuda HP, Mitchell BD, Patterson JK. Microalbuminuria. Potential marker for increased cardiovascular risk factors in non-diabetic subjects? Arteriosclerosis 1990; 10:727.

    PubMed  CAS  Google Scholar 

  42. Black IW, Wilcken DEL. Decreases in apolipoprotein(a) after renal transplantation: implications for lipoprotein(a) metabolism. Clin Chem 1992; 38:353.

    PubMed  CAS  Google Scholar 

  43. Hirata K, Kikuchi S, Saku K, Jimi S, Zhang B, Naito S, Hamaguchi H, Arakawa K. Apolipoprotein(a) phenotypes and serum lipoprotein(a) levels in maintenance haemodialysis patients with/without diabetes mellitus. Kidney Int 1993; 44:1062.

    Article  PubMed  CAS  Google Scholar 

  44. Dieplinger H, Lackner C, Kronenberg F, Sandholzer C, Lhotta K, Hoppichler F, Graf H, König P. Elevated plasma concentrations of lipoprotein(a) in patients with end-stage renal disease are not related to the size polymorphism of apolipoprotein(a). J Clin Invest 1993; 91:397.

    Article  PubMed  CAS  Google Scholar 

  45. Jerums G, Allen TJ, Tsalamandris C, Akdeniz A, Sinha A, Gilbert R, Cooper ME. Relationship of progressively increasing albuminuria to apoprotein(a) and blood pressure in type 2 (non-insulin-dependent) and type 1 (insulin-dependent) diabetic patients. Diabetologia 1993; 36:1037.

    Article  PubMed  CAS  Google Scholar 

  46. Bianchi S, Bigazzi R, Valtriani C, Chiapponi I, Sgherri G, Baldari G, Natali A, Ferrannini E, Campese VM. Elevated serum insulin levels in patients with essential hypertension and micro-albuminuria. Hypertension 1994; 6:681.

    Google Scholar 

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Authors and Affiliations

  1. Department of Medicine, University College London Medical School, G Block, Archway Wing, Whittington Hospital, Archway Road, N19 3UA, London, UK

    J. S. Yudkin, W. -J. Foyle & M. Fernandez

  2. Department of Medicine, Northwest Lipid Research Laboratories, University of Washington, Seattle, Washington, USA

    S. M. Marcovina

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  1. J. S. Yudkin
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  2. S. M. Marcovina
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  3. W. -J. Foyle
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  4. M. Fernandez
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Yudkin, J.S., Marcovina, S.M., Foyle, W.J. et al. Lipoprotein(a) is not elevated in non-diabetic microalbuminuric subjects. Int J Clin Lab Res 26, 43–50 (1996). https://doi.org/10.1007/BF02644773

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  • DOI: https://doi.org/10.1007/BF02644773

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