Wiener klinische Wochenschrift

, Volume 122, Issue 5–6, pp 159–164 | Cite as

Lipoprotein(a) predicts progression of carotid artery intima-media thickening in patients with type 2 diabetes: A four-year follow-up

  • Jozo Boras
  • Spomenka Ljubic
  • Nikica Car
  • Zeljko Metelko
  • Mladen Petrovecki
  • Marijana Vucic Lovrencic
  • Zeljko Reiner
Original article
Received:
Accepted:

Summary

BACKGROUND: The aim of the study was to establish whether increased levels of serum lipoprotein(a) significantly contribute to an increase in intima-media thickness and the number of carotid artery plaques, and consequently to cardiovascular risk in patients with type 2 diabetes mellitus. METHODS: Lipoprotein(a) levels, intima-media thickness and the number of carotid artery plaques were determined at the beginning of the study in 146 patients with type 2 diabetes. Patients were divided into two groups according to serum lipoprotein(a) levels (> or ≤30 mg/dl). Intima-media thickness and the number of plaques were again determined after four years of follow-up. Intima-media thickness was assessed using high-resolution B-mode ultrasound. RESULTS: The two groups of patients revealed no significant differences in baseline intima-media thickness (P = 0.112) in relation to lipoprotein(a) level. After follow-up, intima-media thickness was significantly greater in patients with higher lipoprotein(a) levels (1.24 + 0.22 vs. 1.15 + 0.17 mm, respectively; P = 0.005). The mean increase in thickness over four years was 0.12 mm (0.030 mm/year) in the group with low lipoprotein(a) levels and 0.17 mm (0.043 mm/year) in the group with high lipoprotein(a). Multivariate analysis indicated that intima-media thickness depended on lipoprotein(a), and not on triglyceride, HDL-cholesterol levels or waist-to-hip ratio. No significant difference in baseline and follow-up number of plaques was observed between the study groups (P = 0.276 vs. P = 0.355, respectively). Although the group with lipoprotein(a) >30 mg/dl had more cardiovascular events, the difference was not statistically significant. CONCLUSIONS: These results indicate that lipoprotein(a) is an independent, genetically determined risk factor closely associated with progression of intima-media thickness in type 2 diabetes.

Keywords

Lipoprotein(a) intima-media thickness diabetes mellitus carotid artery plaque cardiovascular risk 

Lipoprotein(a) als Einflussfaktor auf die Intima-Media-Dicke bei Patienten mit Diabetes mellitus Typ 2

Zusammenfassung

HINTERGRUND: Ziel dieser Studie war es, herauszufinden ob erhöhtes Serum Lipoprotein(a) (Lpa) bei Patienten mit Diabetes mellitus Typ 2 signifikant zu einem Anstieg der Intima-Media-Dicke und der Zahl der Plaques der Carotiden beiträgt und so das kardiovaskuläre Risiko dieser Patienten erhöht. METHODEN: Bei 146 Patienten mit Diabetes mellitus Typ 2 wurden die Lipoprotein(a)-Spiegel, die Intima-Media-Dicke und die Zahl der Plaques in den Carotiden erhoben. Die Intima-Media-Dicke und die Anzahl der Plaques wurde nach 4 Jahren Follow-up kontrolliert. Die Patienten wurden entsprechend ihrem Serum-Lipoprotein(a)-Spiegel in 2 Gruppen (> oder ≤30 mg/dl) eingeteilt. Die Intima-Media-Dicke wurde mit hochauflösendem B-Mode Ultraschall erhoben. ERGEBNISSE: Anfangs bestand kein signifikanter Unterschied in der Intima-Media Dicke der Carotiden der beiden Gruppen. Bei der Kontrolle waren die Intima-Media-Dicken der Gruppe mit höherem Lipoprotein(a)-Spiegel signifkant höher als jene der Gruppe mit niedrigem Lipoprotein(a) Spiegel (1,24 + 0,22 vs. 1,15 + 0,17 mm; p = 0.005), Die mittlere Zunahme der Intima-Media Dicke betrug in der Gruppe mit niedrigem Lipoprotein(a) Spiegel nach 4 Jahren 0,12 mm (0,030 mm/Jahr) und in der Gruppe mit höherem Lipoprotein(a) Spiegel 0,17 mm (0,043 mm/Jahr). Die Multivarianzanalyse ergab, dass die Intima-Media Dicke nur vom Lipoprotein(a)- und nicht vom Triglyzerid- beziehungsweise vom HDL-Cholesterin-Spiegel oder dem Taille-Hüfte Quotienten abhing. Die Anzahl der Plaques unterschied sich weder bei der Erstuntersuchung noch bei der Kontrolle zwischen den beiden Gruppen signifikant (p = 0,276 respektive p = 0,355). In der Gruppe mit höherem Lipoprotein(a)-Spiegel traten mehr kardiovaskuläre Ereignisse ein als in der anderen Gruppe – der Unterschied war allerdings statistisch nicht signifikant. SCHLUSSFOLGERUNGEN: Unsere Ergebnisse weisen daraufhin, dass Lipoprotein(a) ein unabhängiger, genetisch determinierter Risikofaktor ist, der eng mit der Zunahme der Intima-Media-Dicke bei Diabetes mellitus Typ 2 assoziiert ist.

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References

  1. Libby P (2008) The pathogenesis, prevention, and treatment of atherosclerosis. In: Fauci AS, et al (eds) Harrison's principles of internal medicine, 17th edn. McGraw-Hill, New York, pp 1501–9Google Scholar
  2. Erbel R, Möhlenkamp S, Lehmann N, Schmermund A, Moebus S, Stang A, et al (2008) Cardiovascular risk factors and signs of subclinical atherosclerosis in the Heinz Nixdorf Recall Study. Dtsch Arztebl 105: 1–8Google Scholar
  3. Kuulasmaa K, Tunstall-Pedoe H, Dobson A, Fortmann S, Sans S, Tolonen H, et al (2000) Estimation of contribution of changes in classic risk factors to trends in coronary-event rates across the WHO MONICA Project populations. Lancet 355: 675–87CrossRefPubMedGoogle Scholar
  4. Gaubatz JW, Heideman C, Gotto AM Jr, Morrisett JD, Dahlen GH (1983) Human plasma lipoprotein[a]. Structural properties. J Biol Chem 258: 4582–9PubMedGoogle Scholar
  5. McLean JW, Tomlinson JE, Kuang WJ, Eaton DL, Chen EY, Fless GM, et al (1987) cDNA sequence of human apolipoprotein(a) is homologous to plasminogen. Nature 330: 132–7CrossRefPubMedGoogle Scholar
  6. Beekman M, Heijmans BT, Martin NG, Pedersen NL, Whitfield JB, DeFaire U, et al (2002) Heritabilities of apolipoprotein and lipid levels in three countries. Twin Res 5: 87–97CrossRefPubMedGoogle Scholar
  7. Dieplinger H, Kronenberg F (1999) Genetics and metabolism of lipoprotein(a) and their clinical implications (Part 1). Wien Klin Wochenschr 111: 5–20PubMedGoogle Scholar
  8. Dangas G, Mehran R, Harpel PC, Sharma SK, Marcovina SM, Dube G, et al (1998) Lipoprotein(a) and inflammation in human coronary atheroma: association with the severity of clinical presentation. J Am Coll Cardiol 32: 2035–42CrossRefPubMedGoogle Scholar
  9. Zhao S, Xu DY (2000) Oxidized lipoprotein(a) enhanced the expression of P-selectin in cultured human umbilical vein endothelial cells. Thromb Res 100: 501–10CrossRefPubMedGoogle Scholar
  10. Niskanen L, Rauramaa R, Miettinen H, Haffner SM, Mercuri M, Uusitupa M (1996) Carotid artery intima-media thickness in elderly patients with NIDDM and in nondiabetic subjects. Stroke 27: 1986–92PubMedGoogle Scholar
  11. World Health Organization (1995) Diabetes mellitus: report of a WHO study group. World Health Organization, Geneva, pp 9–20Google Scholar
  12. Lippi G, Veraldi GF, Dorucci V, Dusi R, Ruzzenente O, Brentegani C, et al (1998) Usefulness of lipids, lipoprotein(a) and fibrinogen measurements in identifying subjects at risk of occlusive complications following vascular and endovascular surgery. Scand J Clin Lab Invest 58: 497–504CrossRefPubMedGoogle Scholar
  13. Pignoli P (1984) Ultrasound B-mode imaging for arterial wall thickness measurements. Atherosclerosis Rev 12: 177–84Google Scholar
  14. Salonen J, Salonen R (1991) Ultrasonographically assessed carotid morphology and the risk of coronary heart disease. Atheroscler Thromb 11: 1245–9Google Scholar
  15. Dahlen GH, Ericson C, Furberg C, Lundvist L, Svardsudd K (1972) Angina of effort and an extra pre-beta lipoprotein fraction. Acta Med Scand 531: 11–24Google Scholar
  16. Danesh J, Collins R, Peto R (2000) Lipoprotein(a) and coronary heart disease. Meta-analysis of prospective studies. Circulation 102: 1082–5PubMedGoogle Scholar
  17. Seman LJ, DeLuca C, Jenner JL, Cupples LA, McNamara JR, Wilson PW, et al (1999) Lipoprotein(a)-cholesterol and coronary heart disease in the Framingham Heart Study. Clin Chem 45: 1039–46PubMedGoogle Scholar
  18. Milionis HJ, Winder AF, Mikhailidis DP (2000) Lipoprotein(a) and stroke. J Clin Pathol 53: 487–96CrossRefPubMedGoogle Scholar
  19. Von Depka M, Nowak-Göttl U, Eisert R, Dieterich C, Barthels M, Scharrer I, et al (2000) Increased lipoprotein(a) levels as an independent risk factor for venous thromboembolism. Blood 96: 3364–8PubMedGoogle Scholar
  20. O'Leary DH, Polak JF, Kronmal RA, Manolio TA, Burme GL, Wolfson SK Jr (1999) Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults. Cardiovascular Health Study Collaborative Research Group. N Engl J Med 340: 14–22CrossRefPubMedGoogle Scholar
  21. Mudrikova T, Szabova E, Tkac I (2000) Carotid intima-media thickness in relation to macrovascular disease in patients with type 2 diabetes mellitus. Wien Klin Wochenschr 112: 887–91PubMedGoogle Scholar
  22. Yamamoto M, Egusa G, Yamakido M (1997) Carotid atherosclerosis and serum lipoprotein(a) concentrations in patients with diabetes. Diabetes Care 20: 829–31CrossRefPubMedGoogle Scholar
  23. Boras J, Car N, Pavlić-Renar I, Metelko Ž, Duvnjak L (2001) Intima media thickness in patients with type 2 diabetes mellitus. Diabetes 50[Suppl 2]: A91Google Scholar
  24. Yamasaki Y, Kodama M, Nishizawa H, Sakamoto K, Matsuhisa M, Kajimoto Y, et al (2000) Carotid intima-media thickness in Japanese type 2 diabetic subjects: predictors of progression and relationship with incident coronary heart disease. Diabetes Care 23: 1310–5CrossRefPubMedGoogle Scholar
  25. Salonen R, Salonen JT (1990) Progression of carotid atherosclerosis and its determinants: a population-based ultrasonography study. Atherosclerosis 81: 33–40CrossRefPubMedGoogle Scholar
  26. Yamasaki Y, Kawamori R, Matsuchima H, Nishizawa H, Kodama M, Kajimoto Y, et al (1994) Atherosclerosis in carotid artery of young IDDM patients monitored by ultrasound high-resolution B-mode imaging. Diabetes 43: 634–9CrossRefPubMedGoogle Scholar
  27. Visona A, Luisiani L, Bonanome A, Beltramello G, Confortin L, Papesso B, et al (1995) Wall thickening of common carotid arteries in patients affected by noninsulin-dependent diabetes mellitus: relationship to microvascular complications. Angiology 46: 793–9CrossRefPubMedGoogle Scholar
  28. Chambless LE, Heiss G, Folsom AR, Rosamond W, Szklo M, Sharrett AR, et al (1997) Association of coronary heart disease incidence with carotid arterial wall thickness and major risk factors: the Atherosclerosis Risk in Communities (ARIC) Study, 1987–1993. Am J Epidemiol 146: 483–94PubMedGoogle Scholar
  29. Haffner SM (1993) Lipoprotein(a) and diabetes: an update. Diabetes Care 16: 835–40CrossRefPubMedGoogle Scholar
  30. Hiraga T, Kobayashi T, Okubo M, Nakanishi K, Sugimoto T, Ohashi Y, et al (1995) Prospective study of lipoprotein(a) as a risk factor for atherosclerotic cardiovascular disease in patients with diabetes. Diabetes Care 18: 241–4CrossRefPubMedGoogle Scholar
  31. Tenenbaum A, Fisman EZ, Motro M, Adler Y (2006) Atherogenic dyslipidemia in metabolic syndrome and type 2 diabetes: therapeutic options beyond statins. Cardiovasc Diabetol 5: 20CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Jozo Boras
    • 1
  • Spomenka Ljubic
    • 2
  • Nikica Car
    • 3
  • Zeljko Metelko
    • 3
  • Mladen Petrovecki
    • 4
  • Marijana Vucic Lovrencic
    • 5
  • Zeljko Reiner
    • 6
  1. 1.Department of CardiologyVuk Vrhovac University HospitalZagrebCroatia
  2. 2.Department for Metabolic MedicineVuk Vrhovac University HospitalZagrebCroatia
  3. 3.Clinical DepartmentVuk Vrhovac University HospitalZagrebCroatia
  4. 4.Rijeka University School of Medicine and Dubrava Clinical HospitalZagrebCroatia
  5. 5.Department of Laboratory MedicineVuk Vrhovac University HospitalZagrebCroatia
  6. 6.Department of Internal MedicineZagreb University Hospital CenterZagrebCroatia

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