Antiatherogenic effect of HDL subpopulations in patients with newly diagnosed peripheral artery disease

Česká verzia

Authors: M. Kaško ¹; P. Gavornik ¹; K. Gruber ²; S. Oravec ¹; A. Dukát ¹
Authors place of work: II. interná klinika Lekárskej fakulty UK a UN Bratislava, Slovenská republika, prednosta doc. MUDr. Ľudovít Gašpar, CSc. ¹; Interná klinika Landeskrankenhaus, Thermenregion Baden, Viedeň, Rakúsko, prednosta Univ. Doc. Dr. Med. Johann Pidlich ²
Published in the journal: Vnitř Lék 2012; 58(7 a 8): 37-41
Category: 80th Birthday MUDr. Miroslav Mydlík, DrSc.

Summary

Objective:
To assess the relationship of high-density lipoprotein subfractions to newly diagnosed lower extremity artery disease (LEAD) in individuals without diabetes mellitus (DM).

Background:
The high-density lipoprotein (HDL) family forms a protective part of plasma lipoproteins. It consists of large HDL, intermediate HDL, and small HDL subclasses. The large HDL and intermediate HDL subclasses are widely considered as anti-atherogenic parts of the HDL family. The atherogenicity of the small HDL subclass is currently the subject of wide interest. The association of HDL cholesterol (HDL-C) spectrum abnormality with lower extremity artery disease has not been investigated yet. In the patients with this vascular impairment (LEAD) were identified the HDL subclasses. Patients with peripheral artery disease – lower extremity artery disease as a consequence of atherosclerosis may be often affected by lower extremity pain, worsen ambulation and in addition mutilating wounds. In addition patients with LEAD are affected by normal-to-high HDL atherogenic dyslipidemia. Thus, there is significantly higher risk of cardiovascular morbidity and mortality.

Methods:
This clinical study involving 96 subjects: 48 were newly diagnosed LEAD patients (29 men of average age 56 ± 9, 19 women of average age 61 ± 7) and no DM anamnesis and were not on hypolipidemic therapy; another 48 subjects – control group (24 men of average age 56 ± 12, 24 women of average age 57 ± 13) were without clinical presentation of LEAD and were normolipidemic. Quantitative and qualitative analysis of HDL subclasses were performed by an innovative electrophoresis method on polyacrylamide gel (PAGE), the Lipoprint HDL system, Quantimetrix.

Results:
In LEAD patients, HDL-C levels as well as intermediate HDL subfraction levels were significantly decreased (p < 0.0001 and p < 0.03 respectively). The small HDL particles subfraction was significantly higher (p < 0.01).

Conclusion:
These findings pointed out that the reduction of HDL-C and intermediate HDL subpopulation and even the increase of small HDL subclass may be considered as important predictors of cardiovascular events in newly diagnosed LEAD. There are undisputable advantages of using Lipoprint HDL to identificate HDL subfractions. The presence of a high concentration of small HDL particles in patients with LEAD emphasize that the atherogenic subclass of HDL family is comparable with small HDL.

Keywords:
cardiovascular diseases – peripheral artery disease – lower extremity artery disease – HDL cholesterol – small HDL particles – pro-atherogenic effect of small high-density lipoprotein particles

Zdroje

1. Albers JJ, Aladjem F. Precipitation of 125I-labeled lipoproteins with specific polypeptide antisera: Evidence for two populations with differing polypeptide compositions in human high-density lipoproteins. Biochemistry 1971; 10: 3436–3442.

2. Otvos JD, Jeyarajah EJ, Bennet SW et al. Development of a proton nuclear magnetic resonance spectroscopic method for determining plasma protein concentrations and subspecies distribution from a single, rapid measurement. Clin Chem 1992; 38: 1632–1638.

3. Kostner GM, Laggner P. Chemical and physical properties of lipoproteins. In: Fruchart JC, Shepherd J (eds). Clinical Biochemistry – Human Plasma Lipoproteins. Berlin, New York: Walter de Gruyter 1989: 23–54.

4. Grundy SM. Small LDL, atherogenic dyslipidemia, and the metabolic syndrome. Circulation 1997; 95: 1–4.

5. Ounpuu S, Negassa A, Yusuf S. INTER--HEART: A global study of risk factors for acute myocardial infarction. Am Heart J 2001; 141: 711–721.

6. European cardiovascular disease statistics. British Heart Foundation 2008; http://www.ehnheart.org/cvd-statistics.html

7. Národné centrum zdravotníckych informácií (NCZI). Zdravotnícka ročenka Slovenskej republiky 2010; 27–28.

8. Gordon DJ, Probstfield JL, Garrison RJ et al. High-density lipoprotein cholesterol and cardiovascular disease. Four prospective American studies. Circulation 1989; 79: 8–15.

9. Efrat M, Aviram M. Paraoxonase 1 interactions with HDL, antioxidants and macrophages regulate atherogenesis – a protective role for HDL phospholipids. Adv Exp Med Biol 2010; 660: 153–166.

10. Barter PJ, Nicholls S, Rye KA et al. Antiinflammatory properties of HDL. Circ Res 2004; 95: 764–772.

11. Huang Y, von Eckardstein A, Wu S et al. Cholesterol efflux, cholesterol esterification, and cholesteryl ester transfer by LpA-I and LpA-I/A-II in native plasma. Arterioscler Thromb Vasc Biol 1995; 15: 1412–1418.

12. Tailleux A, Duriez P, Fruchart JC et al. Apolipoprotein A-II, HDL metabolism and atherosclerosis. Atherosclerosis 2002; 164: 1–13.

13. Syvänne M, Kahri J, Virtanen KS et al. HDLs containing apolipoproteins A-I and A-II (LpA-I:A-II) as markers of coronary artery disease in men with non-insulin-dependent diabetes mellitus. Circulation 1995; 92: 364–370.

14. Puchois P, Kandoussi A, Fievet P et al. Apolipoprotein A-I containing lipoproteins in coronary artery disease. Atherosclerosis 1987; 68: 35–40.

15. Oravec S, Gruber K, Dostal E et al. Hyper-betalipoproteinemia LDL 1,2: A newly identified nonatherogenic hypercholesterolemia in a group of hypercholesterolemic subjects. Neuro Endocrinol Lett 2011; 32: 322–327.

16. Oravec S, Gavornik P, Čaprnda M et al. Lipoproteínový profil sera pri novozistenej artériovej hypertenzii. Úloha aterogénnych lipoproteínov v patogenéze ochorenia. Vnitř Lék 2010; 56: 967–971.

17. Oravec S. A new laboratory-medical support in the diagnostics of dyslipoproteinemia and cardiovascular diseases. Med Milit Slov 2006; 8: 28–32.

18. Okuda LS, Castilho G, Rocco DDFM et al. HDL loses its anti-inflammatory property and even induces more inflammation in S100B or LPS stimulated macrophages previously exposed to AGE albumin. Atherosclerosis Supplements 2011; 12: 13–14.

19. ESC/EAS Guidelines for the management of dyslipidaemias. The Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). Atherosclerosis 2011; 217S: S1–S44.

20. Shammas NW. Epidemiology, classification, and modifiable risk factors of peripheral arterial disease. Vasc Health Risk Manag 2007; 3: 229–234.

21. Gavorník P. Končatinovocievne ischemické choroby. B 2.1.: 1–92. In: Gavorník P, Hrubiško M, Rozborilová E (eds). Diferenciálna diagnostika kardio-vaskulárnych, respiračných a hematologických ochorení. Bratislava: Dr. Josef Raabe 2010.

22. Gavorník P. Obliterujúce choroby artérií a končatinovocievna ischemická choroba. Nová klinicko-etiologicko-anatomicko-patofyziologická (CEAP) klasifikácia. Cardiology 2010; 19: 201–213.

23. Gavorník P. Základné princípy prevencie a liečby končatinovocievnych ischemických chorôb. Medikom/Medinews 2011; 1: 33–36.

24. Gavorník P. Nevyhnutnosť neustáleho prehodnocovania manažmentu artériovej hypertenzie ako cievnej choroby cievnych chorôb. Medikom/Medinews 2011; 1: 12–13.

25. Tendera M, Aboyans V, Bartelink ML et al. ESC Guidelines on the diagnosis and treatment of peripheral artery diseases: Document covering atherosclerotic disease of extracranial carotid and vertebral, mesenteric, renal, upper and lower extremity arteries. The Task Force on the Diagnosis and Treatment of Peripheral Artery Diseases of the European Society of Cardiology (ESC). Eur Heart J 2011; 32(22): 2851–2906.

26. Morais J, Neyer G, Muniz N. Measurement and Distribution of HDL subclasses with new Lipoprint® HDL Method. Presented at AACC, 55^th Annual meeting. Philadelphia, PA: 2003.

27. Morais J. Quantimetrix shows that all HDL subfractions may not protect against heart disease. ACC international congress of Clinical Chemistry. Orlando, FL: 2005.

28. Morais J, Muniz N. Differences in HDL subfraction distribution in normolipidemic versus dyslipidemic individuals. Presented at AACC, 57^th Annual meeting. Orlando, FL: 2005.

29. Aboyans V, Mcclelland RL, Allison MA et al. Prevalence and risk factors of lower extremity artery disease in subjects without traditional modifiable cardiovascular risk factors. The multi--ethnic study of atherosclerosis. Arch Cardiovasc Dis Supplements 2011; 3: 72–78.

30. Gašpar Ľ, Makovník M, Hlinšťáková S et al. Význam Holter EKG monitorovania v predoperačnej príprave u pacientov s kritickou končatinovou ischémiou. Revue Medicíny v Praxi 2011; 1: 9–10.

31. Gašpar Ľ, Makovník M, Hlinšťáková S et al. Médiokalcinóza – marker zvýšeného kardiovaskulárneho rizika. Vask Med 2011; 3: 29–31.

32. Rosolová H, Petrlová B, Šimon J et al. Makroaskulární a mikrovaskulární komplikace u diabetiků 2 typu. Vnitř Lék 2008; 54: 229–237.

33. Češka R, Krutská L, Zlatohlávek L et al. Komplexní léčba kardiovaskulárního rizika. Vnitř Lék 2010; 59: 839–844.