Skip to main content

Advertisement

SpringerLink
Log in

Lipoprotein profile, lipoprotein-associated phospholipase A2 and cardiovascular risk in hemodialysis patients

  • Original Article
  • Published:
Journal of Nephrology Aims and scope Submit manuscript

Abstract

Background

Cardiovascular disease is the leading cause of morbidity and mortality in hemodialysis patients; the increased risk of cardiovascular disease is due to accelerated atherosclerosis, inflammation and impaired lipoprotein metabolism. We aimed to evaluate lipoprotein-associated phospholipase A2 (Lp-PLA2) and some pro-inflammatory aspects of the lipoprotein profile in dialyzed patients in order to evaluate the relationship with the accelerated atherosclerosis and vascular accidents.

Methods

In 102 dialysis patients and 40 non-uremic controls, we investigated the lipoprotein plasma profile, high sensitivity C-reactive protein (CRP), ceruloplasmin and serum amyloid A protein (SAA), and followed patients for 1 year to analyze the risk of acute cardiovascular events.

Results

Total cholesterol, low-density lipoprotein and high-density lipoprotein plasma levels were significantly lower in uremic patients than controls, whereas CRP, SAA, ceruloplasmin, Lp-PLA2 and their ratio with apolipoprotein A1 were significantly higher. Patients with Lp-PLA2 levels >194 nmol/min/ml had more acute cardiovascular events than patients with lower values.

Conclusion

Our results show that in dialysis subjects: (1) low-density lipoproteins show a more atherogenic phenotype than in the general population; (2) high-density lipoproteins are less anti-inflammatory; (3) Lp-PLA2 could potentially be used to evaluate cardiovascular risk.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Abbreviations

HP:

Hemodialysis patients

CVD:

Cardiovascular disease

CRP:

High sensitivity C-reactive protein

LDL:

Low-density lipoprotein

HDL:

High-density lipoprotein

ApoB:

Apolipoprotein B

ApoA1:

Apolipoprotein A1

Lp-PLA2 :

Lipoprotein-associated phospholipase A2

Cp:

Ceruloplasmin

SAA:

Serum amyloid A protein

References

  1. Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY (2004) Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med 351:1296–1305 (Erratum in: N Engl J Med 2008;18:4)

    Article  CAS  PubMed  Google Scholar 

  2. Stenvinkel P (2010) Chronic kidney disease: a public health priority and harbinger of premature cardiovascular disease. J Intern Med 268:456–467

    Article  CAS  PubMed  Google Scholar 

  3. Beattie JN, Soman SS, Sandberg KR, Yee J, Borzak S, Garg M, McCullough PA (2001) Determinants of mortality after myocardial infarction in patients with advanced renal dysfunction. Am J Kidney Dis 37:1191–1200 (Erratum in: Am J Kidney Dis 2001;38:701)

    Article  CAS  PubMed  Google Scholar 

  4. Vanholder R, Massy Z, Argiles A, Spasovski G, Verbeke F, Lameire N, European Uremic Toxin Work Group (2005) Chronic kidney disease as cause of cardiovascular morbidity and mortality. Nephrol Dial Transplant 20:1048–1056

    Article  CAS  PubMed  Google Scholar 

  5. Stenvinkel P, Carrero JJ, Axelsson J, Lindholm B, Heimbürger O, Massy Z (2008) Emerging biomarkers for evaluating cardiovascular risk in the chronic kidney disease patient: how do new pieces fit into the uremic puzzle? Clin J Am Soc Nephrol 3:505–521

    Article  CAS  PubMed  Google Scholar 

  6. Himmelfarb J, Stenvinkel P, Ikizler TA, Hakim RM (2002) The elephant in uremia: oxidant stress as a unifying concept of cardiovascular disease in uremia. Kidney Int 62:1524–1538

    Article  CAS  PubMed  Google Scholar 

  7. Stenvinkel P (2003) Interactions between inflammation, oxidative stress, and endothelial dysfunction in end-stage renal disease. J Ren Nutr 13:144–148

    Article  PubMed  Google Scholar 

  8. Wolfe RA, Ashby VB, Milford EL, Ojo AO, Ettenger RE, Agodoa LY et al (1999) Comparison of mortality in all patients on dialysis, patients on dialysis awaiting transplantation, and recipients of a first cadaveric transplant. N Engl J Med 341:1725–1730

    Article  CAS  PubMed  Google Scholar 

  9. Kushiya F, Wada H, Sakakura M, Mori Y, Gabazza EC, Nishikawa M et al (2003) Effects of lipid abnormalities on arteriosclerosis and hemostatic markers in patients under hemodialysis. Clin Appl Thromb Hemost 9:203–210

    Article  CAS  PubMed  Google Scholar 

  10. Osorio A, Ortega E, de Haro T, Torres JM, Sánchez P, Ruiz-Requena E (2011) Lipid profiles and oxidative stress parameters in male and female hemodialysis patients. Mol Cell Biochem 353:59–63

    Article  CAS  PubMed  Google Scholar 

  11. Krauss RM (2010) Lipoprotein subfractions and cardiovascular disease risk. Curr Opin Lipidol 21:305–311

    Article  CAS  PubMed  Google Scholar 

  12. Hoogeveen RC, Gaubatz JW, Sun W, Dodge RC, Crosby JR, Jiang J et al (2014) Small dense low-density lipoprotein-cholesterol concentrations predict risk for coronary heart disease: the Atherosclerosis Risk In Communities (ARIC) study. Arterioscler Thromb Vasc Biol 34:1069–1077

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  13. Rizzo M, Pernice V, Frasheri A, Di Lorenzo G, Rini GB, Spinas GA, Berneis K (2009) Small, dense low-density lipoproteins (LDL) are predictors of cardio- and cerebro-vascular events in subjects with the metabolic syndrome. Clin Endocrinol (Oxf) 70:870–875

    Article  CAS  Google Scholar 

  14. Jang EH, Park YM, Hur J, Kim MK, Ko SH, Baek KH et al (2013) Higher levels of small dense low-density lipoprotein (LDL) are associated with cardiac autonomic neuropathy in patients with type 2 diabetes. Diabet Med 30:694–701

    Article  CAS  PubMed  Google Scholar 

  15. Barter PJ, Nicholls S, Rye KA, Anantharamaiah GM, Navab M, Fogelman AM (2004) Antiinflammatory properties of HDL. Circ Res 95:764–772

    Article  CAS  PubMed  Google Scholar 

  16. Tall AR (2008) Cholesterol efflux pathways and other potential mechanisms involved in the athero-protective effect of high density lipoproteins. J Intern Med 263:256–273

    Article  CAS  PubMed  Google Scholar 

  17. Navab M, Reddy ST, Van Lenten BJ, Fogelman AM (2011) HDL and cardiovascular disease: atherogenic and atheroprotective mechanisms. Nat Rev Cardiol 8:222–232

    Article  CAS  PubMed  Google Scholar 

  18. Vaziri ND, Moradi H, Pahl MV, Fogelman AM, Navab M (2009) In vitro stimulation of HDL anti-inflammatory activity and inhibition of LDL pro-inflammatory activity in the plasma of patients with end-stage renal disease by an apoA-1 mimetic peptide. Kidney Int 76:437–444

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Kalantar-Zadeh K, Kopple JD, Kamranpour N, Fogelman AM, Navab M (2007) HDL-inflammatory index correlates with poor outcome in hemodialysis patients. Kidney Int 72:1149–1156

    Article  CAS  PubMed  Google Scholar 

  20. Pencak P, Czerwieńska B, Ficek R, Wyskida K, Kujawa-Szewieczek A, Olszanecka-Glinianowicz M et al (2013) Calcification of coronary arteries and abdominal aorta in relation to traditional and novel risk factors of atherosclerosis in hemodialysis patients. BMC Nephrol 14:10

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  21. Zalewski A, Macphee C (2005) Role of lipoprotein-associated phospholipase A2 in atherosclerosis: biology, epidemiology, and possible therapeutic target. Arterioscler Thromb Vasc Biol 25:923–931

    Article  CAS  PubMed  Google Scholar 

  22. Cai A, Zheng D, Qiu R, Mai W, Zhou Y (2013) Lipoprotein-associated phospholipase A2 (Lp-PLA2): a novel and promising biomarker for cardiovascular risks assessment. Dis Markers 34:323–331

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  23. Davidson MH, Corson MA, Alberts MJ, Anderson JL, Gorelick PB, Jones PH, Lerman A, McConnell JP, Weintraub HS (2008) Consensus panel recommendation for incorporating lipoprotein-associated phospholipase A2 testing into cardiovascular disease risk assessment guidelines. Am J Cardiol 101(12A):51F–57F

    Article  CAS  PubMed  Google Scholar 

  24. Thompson A, Gao P, Orfei L, Watson S, Di Angelantonio E, Kaptoge S et al (2010) Lipoprotein-associated phospholipase A(2) and risk of coronary disease, stroke, and mortality: collaborative analysis of 32 prospective studies. Lancet 375:1536–1544

    Article  CAS  PubMed  Google Scholar 

  25. Holzer M, Birner-Gruenberger R, Stojakovic T, El-Gamal D, Binder V, Wadsack C et al (2011) Uremia alters HDL composition and function. J Am Soc Nephrol 22:1631–1641

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  26. McGillicuddy FC, de la Llera Moya M, Hinkle CC, Joshi MR, Chiquoine EH, Billheimer JT et al (2009) Inflammation impairs reverse cholesterol transport in vivo. Circulation 119:1135–1145

    Article  CAS  PubMed  Google Scholar 

  27. Milionis HJ, Elisaf MS, Karabina SA, Bairaktari E, Tselepis AD, Siamopoulos KC (1999) Plasma and Lp(a)-associated PAF-acetylhydrolase activity in uremic patients undergoing different dialysis procedures. Kidney Int. 56(6):2276–2285

    Article  CAS  PubMed  Google Scholar 

  28. Vaziri ND, Bai Y, Yuan J, Said HL, Sigala W, Ni Z (2010) ApoA-1 mimetic peptide reverses uremia-induced upregulation of pro-atherogenic pathways in the aorta. Am J Nephrol 32(3):201–211

    Article  CAS  PubMed  Google Scholar 

  29. Pedersen TX, Bro S, Andersen MH, Etzerodt M, Jauhiainen M, Moestrup S, Nielsen LB (2009) Effect of treatment with human apolipoprotein A-I on atherosclerosis in uremic apolipoprotein-E deficient mice. Atherosclerosis 202(2):372–381

    Article  CAS  PubMed  Google Scholar 

  30. Caslake MJ, Packard CJ, Suckling KE, Holmes SD, Chamberlain P, Macphee CH (2000) Lipoprotein-associated phospholipase A(2), platelet-activating factor acetylhydrolase: a potential new risk factor for coronary artery disease. Atherosclerosis 150:413–419

    Article  CAS  PubMed  Google Scholar 

  31. Kolodgie FD, Burke AP, Skorija KS, Ladich E, Kutys R, Makuria AT, Virmani R (2006) Lipoprotein-associated phospholipase A2 protein expression in the natural progression of human coronary atherosclerosis. Arterioscler Thromb Vasc Biol 26:2523–2529

    Article  CAS  PubMed  Google Scholar 

  32. Libby P, Ridker PM, Hansson GK (2009) Leducq Transatlantic Network on Atherothrombosis. Inflammation in atherosclerosis: from pathophysiology to practice. J Am Coll Cardiol 54:2129–2138

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  33. Chisolm GM, Steinberg D (2000) The oxidative modification hypothesis of atherogenesis: an overview. Free Radic Biol Med 28:1815–1826

    Article  CAS  PubMed  Google Scholar 

  34. Ryu SK, Mallat Z, Benessiano J, Tedgui A, Olsson AG, Bao W, Schwartz GG, Tsimikas S, Myocardial Ischemia Reduction With Aggressive Cholesterol Lowering (MIRACL) Trial Investigators (2012) Phospholipase A2 enzymes, high-dose atorvastatin, and prediction of ischemic events after acute coronary syndromes. Circulation 14(125):757–766

    Article  Google Scholar 

Download references

Conflict of interest

All Authors disclose that there are no financial or personal relationships with other people or organizations that could inappropriately influence this work. All Authors participated in the study design, in the collection, analysis, and interpretation of data, in the writing of the manuscript and in the decision to submit the manuscript for publication. No study sponsors had involvement in this manuscript.

Ethical approval

All procedures were approved by the Italian ethics committees (981/CE) and were in accordance with the Helsinki declaration.

Informed consent

As approved by the institutional review board for research involving human subjects, the residual plasma used in this study was considered discarded and no informed consent was necessary. Nevertheless, at the moment of commencing hemodialysis in our center, all patients signed an informed consent allowing the use of their clinical data in anonymous form for scientific publications.

Author information

Author notes

    Authors and Affiliations

    1. Clinical Chemistry Laboratory, Department of Health Sciences, Amedeo Avogadro University of Eastern Piedmont, Novara, Italy

      Roberta Rolla, Ambra Valsesia, Matteo Vidali & Giorgio Bellomo

    2. Nephrology and Dialysis Unit, University Hospital ‘Maggiore della Carità’, Corso Mazzini, 18, 28100, Novara, Italy

      Andreana De Mauri & Doriana Chiarinotti

    Authors
    1. Roberta Rolla
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Andreana De Mauri
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Ambra Valsesia
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. Matteo Vidali
      View author publications

      You can also search for this author in PubMed Google Scholar

    5. Doriana Chiarinotti
      View author publications

      You can also search for this author in PubMed Google Scholar

    6. Giorgio Bellomo
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding author

    Correspondence to Andreana De Mauri.

    Additional information

    R. Rolla and A. De Mauri equally contributed to the work.

    Rights and permissions

    Reprints and permissions

    About this article

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this article

    Rolla, R., De Mauri, A., Valsesia, A. et al. Lipoprotein profile, lipoprotein-associated phospholipase A2 and cardiovascular risk in hemodialysis patients. J Nephrol 28, 749–755 (2015). https://doi.org/10.1007/s40620-015-0194-0

    Download citation

    • Received:

    • Accepted:

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1007/s40620-015-0194-0

    Keywords

    Search

    Navigation