SERUM LEVEL OF LIPOPROTEIN(a)(Lpa) AND LIPIDPROFILESIN HIV POSITIVE PATIENTS ON HIGHLY ACTIVE ANTI-RETROVIRAL THERAPY [HAART] AT THE LAGOS UNIVERSITY TEACHING HOSPITAL IDI-ARABA, LAGOS,NIGERIA
Formerly Published in Vol 6 No. 1 Jan. – Jun., 2021
Abstract
BACKGROUND: Lipoprotein(a) is an emerging biochemical risk factor for cardiovascular disease that has not been widely studied in people of Sub-Saharan African origin. It’s interaction with antiretroviral agents have been less studied than those of traditional lipid parameters. This study therefore assessed the effect of highly active anti-retroviral therapy (HAART) on lipoprotein(a) levels in HIV-positive patients.
METHOD: This was a prospective study of HIV-infected patients on HAART at the HIV Outpatient Clinic of the Lagos University Teaching Hospital. Baseline serum Lp(a)and fasting lipid profiles were determined on sero-positive patients. For sero-positive patients who had immunological indication for HAART, fasting samples were obtained every 2 months for 6 months post commencement of HAART for serum Lp(a) and lipid profile estimation.
RESULTS: The median baseline serum level of Lp(a) in HIV-positive patients with CD4 count ≤ 350 was not significantly different from that of HIV-positive patients with CD4 counts ˃350. Median Lp(a) and mean values of TC, TG and LDL-C were all significantly raised at the end of the study (p<0.001). During the study period significant increase in median Lp(a), mean TC, TG and LDL-C were first noticed by the second month. Lp(a) consistently and significantly correlated positively with LDL-C across the two study groups. A significant association was found between Lp(a) levels and duration of HAART, however no significant association was found between Lp(a) levels and type of HAART regimen.><)
CONCLUSION: HAART is associated with significant increase in Lp(a). This may have clinical implications as high serum level of Lp(a) is a potential risk factor for myocardial infarction and stroke. Therefore routine monitoring of serum Lp(a) levels especially from the second month of ART may be beneficial for HIV-infected patients in order to reduce the risk of cardiovascular incidence.
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1. World Health Organization. HIV/AIDS report (internet) c2013. Available from:http://www.unaids.org/en/res Pioneer Medical Journal Vol. 6, No. 1 Jan-Jun, 2021 16 coronary artery ources/campaign/2014gapreport/pd f (cited22 December,2014). 2. 3. Chaturvedi V, Bhargava B. Health care delivery for coronary Heart Disease in India- where are we Headed? Am Heart Hosp J 2007; 5:32-37. Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol on Adults (ATP III). JAMA 2001; 285:2486-2947 4. 5. 6. 7. Crum NF, Riffenburgh RH, Wegner S, Agan BK, Tasker SA, Spooner KM, et al; Triservice AIDS Clinical Consortium. Comparisons of causes of death and mortality rates among HIV infected persons: Analysis of the pre, early and late HAART eras. J Acquir Immune DeficSyndr 2006; 41(2):194-200. Dahlen G, Ericson C, Furberg C, Lundkrist L, Svardsuddk: Angina of effort and an extra pre-beta lipoprotein fraction. Acta Med Scand 1972; 531:6-7. Papadopoulos NM, Bedynek JL. Serum lipoprotein patterns in patients with coronary atherosclerosis. Clin Chem Acta 1973; 44:153-154. Insull W, Najmi M, Vloedman DA. Plasma pre-beta subfractions in lipoprotein diagnosis of disease. Circulation 1972; 45:170-171. 8. 9. 10. 11. 12. 13. 14. Dahlen G, Berg K, Gillnas T, Ericson C. Lipoprotein (a)/pre-beta lipoprotein in Swedish middle aged males and in Patients with coronary heart disease. Clin Genet 1975; 7:334-336. Berg K: A new serum type system in man– the Lp system. Acta PatholMicrobiolScand1963; 59:369-382. Nordestgaard BG, Chapman MJ, Ray K, Boren J, Andreotti F, Watts GF et al. Lipoprotein (a) as a cardiovascular risk factor: current status. Eur Heart J 2010; 31:2844 2853. Kamstrup PR, Tybaerg-Hansen A, Nordestgaard BG. Lipoprotein (a) and risk of myocardial infarction genetic epidemiologic evidence of causality. Scand J Clin Lab Invest 2011; 71:87-93. Danesh J, Collins R, Peto R. lipoprotein(a) and coronary heart disease; meta-analysis of prospective studies. Circulation 2000; 102:1082-1085. Smolders B, Lemmens R, Thijs V. Lipoprotein(a) and stroke: a meta analysis of observational studies. Stroke 2007; 38:1959-1966. Schreiner PJ, Morrisett JD, Sharrett AR, Patsch W, Tyroler HA, Wu K et al. Lipoprotein(a) as a risk factor for preclinical atherosclerosis. Pioneer Medical Journal Vol. 6, No. 1 Jan-Jun, 2021 17 ArteriosclerThromb 1993; 13:826 833. 15. 16. 17. 18. 19. 20. Djurovic S, Berg K, Epidemiology of Lipoprotein (a): it’s role in atherosclerosis/thrombotic disease. Clin Genet 1997; 52:281-292. Lesi OA, Soyebi KS, Eboh CN. Fatty liver and hyperlipidemia in a cohort of HIV-positive Africans on highly active antiretroviral therapy. J Natl Med. 2009;101(2):151-155. Assoc Salami AK, Akande AA, Olokoba AB. Serum lipids and glucose abnormalities in HIV/AIDS patients on antiretroviral therapies. West Africa J Med 2009; 28(1):10 15. Adewole OO, Eze S, Betiku YE, Anteyi E, Wada I, Ajuwon Z et al. Lipid profile in HIV/IADS patients in Nigeria. Afr Health Sci 2010; 10:144-149. Triant VA, Lee H, Hadigan C, Grinspoon SK, Increased acute myocardial infarction rates and cardiovascular risk factors among patients with human immunodeficiency virus diseases. J Clin Endocrinol Metab2007;92:2506-2512. Fontas E, Vanleth F, Sabin A, Friis– Meller N, Rickenbach M, d’Arminio Monforte A, et al. Lipid profile in HIV– infected patients receiving combination antiretroviral therapy: Are different antiretroviral drugs associated with different lipid profiles? J Infect Dis 2004; 189:1056-1074. 21. 22. 23. 24. 25. 26. Ogbera A O, Azenabor A O. Lipoprotein(a), C-reactive protein and some metabolic cardiovascular risk factors in type 2 DM. Diabetology and syndrome 2010;2:51-55. Metabolic Armin I, Wolfgang K. Alcohol inflammation and coronary heart disease. J Addiction Biology 2006; 8:1293-1299. DAD study group, Friis-Moller N, Reiss P, Sabin CA, Weber R, Moufork A, et al. Class of antiretroviral drugs and the risk of myocardial infarction. N Engl J Med 2007; 356:1723-1735. Friis-Moller N, Weber R, Reiss P, Thiebaut R, Kirk O, d’Armimio Monforte, et al; DAD study group. Cardiovascular disease risk factors in HIV patients- association with antiretroviral therapy. AIDS 2003; 17(8):1179-1193. Manuthu EM, Joshi MD, Lule GN, Karari E. Prevalence of Dyslipidemia and dysglycaemia in HIV infected patients. East African Medical Journal 2008; 85(1):10-17. Armstrong C, Liu E, Okuma J, Spiegelman D, Guerino C, Njelekela M, et al. Dyslipidemia in an HIV- positive antiretroviral treatment- naive population in Dares Salaam, Tanzanian. J Acquir Immune Deficiency Syndrome 2011; 57(2):141-145. Pioneer Medical Journal Vol. 6, No. 1 Jan-Jun, 2021 18 27. 33. Constans J, Pellegrin J, Peuchant E. Plasma lipids in HIV– infected patients: A prospective study in 95 patients. Eur J Clin Invest 1994; 24:416-420. 28. 29. 30. 31. 32. Bernal E, Masia M, Padilla S, Gutierrez F. High density lipoprotein cholesterol in HIV infected patients: Evidence for an Association with HIV-I viral load, Antiretroviral Therapy status and Regimen composition. AIDS patient care and STDs article published May 15 2008. Lichtenstein KA, Ward DJ, Moorman AC, Delaney KM, Young B, Palella FJ, et al. Clinical assessment of HIV- associated lipodystrophy in an ambulatory population. AIDS 2001; 15:1389 1398. Carr A, Samaras K, Chisholm DJ, Cooper DA. Pathogenesis of HIV protease inhibitor– associated syndrome of peripheral lipodystrophy, hyperlipidemia and insulin resistance. Lancet 1998; 351: 1881– 1883. Carr A. Samaras K, Burton S, Law M, Freund J, Chisholm DJ, et al. A syndrome of peripheral lipodystrophy, hyperlipidemia and insulin resistance in patients receiving HIV protease inhibitors. AIDS 1998; 12:F51-F58. Carr A, Cooper DA. Adverse effects of antiretroviral therapy. Lancet 2000; 356:1423-1430. Mallal SA, John M, Moore CB, James IR, Contribution analogue Mckinnon of EJ. nucleoside reverse transcriptase inhibitors to subcutaneous fat wasting in patients with HIV infection. AIDS 2000; 14:1309-16. 34. 35. 36. 37. 38. 39. Murata H, Hruz P, Mueckler M. The mechanism of insulin resistance caused by HIV protease inhibitor therapy. J Biol Chem 2000; 275:20251-20254. Gazzaruso C, Bruno R, Garzaniti A, Giordanetti S, Fratino P, Sacchi P et al. Hypertension among HIV patients: prevalence and relationships to insulin resistance and metabolic syndrome. J Hypertens 2003; 21:1377-1382. Chow D, Souza S, Richmond Crum S, Epidemiological Shikuma evidence C. of increasing blood pressure in HIV 1 infected individuals in the era of HAART. AntivirTher 2000; 5:31 32. Barbaro G. Cardiovascular manifestations of HIV infection. Circulation 2002; 106:1420-1425. Gisselbrecht M. Vasculitis during human acquired immunodeficiency virus infection. Pathol Biol (Paris) 1999; 47(3): 245-247. Chi D, Henry J, Kelley J, Thorpe R, Smith JK, Krishnaswamy G. The effects of HIV infection on endothelial function. Endothelium 2000; 7(4): 223-242. Pioneer Medical Journal Vol. 6, No. 1 Jan-Jun, 2021 19 PioneerMedicalJournalVol.6,No.1Jan-Jun,2021 20 40. Berger O, Gan X, Gujuluva C, BurnsAR,SulurG,StinsM,etal. CXCandCCchemokinereceptors oncoronaryandbrainendothelia. MolMed1999;5(12):795-805. 41. Grahame–ClarkeC, AlberDG, Lucas SB,Miller R, Vallance P. Association between kaposi’s sarcoma and atherosclerosis:Implications for gammaherpesviruses and vascular disease.AIDS2001;15:1902-1905. 42. SteinJH,KleinMA,Bellehumeur JL,McBridePE,WiebeDA,Otvos JD, et al. Use of human immunodeficiency virus–1 protease inhibitors is associated with atherogenic lipoprotein changes and endothelial dysfunction. Circulation 2001; 104:257-267. 43. Sattler FR, Qian D, Louie S, JohnsonD,BriggsW,DeQuattroV, et al. Elevated blood pressure in subjectswithlipodystrophy. AIDS 2001;15:2001-2010. 44. ZaeraMG,MiroO,PedrolE,Soler A, PiconnM,CardellachF, et al. Mitochondrial involvement in antiretroviral therapy related lipodystrophy. AIDS 2001; 15:1643-1651. 45. Health KV, Hogg R, Chan KJ, Harris M, Montessori V, O’shaughnessy MV, et al. Lipodystrophy–associated morphological, cholesterol and triglyceride abnormalities in a population–based HIV/AIDS treatment data base. AIDS 2001; 15:231-239. 46. TsiodrasS,MantzorosC,Hammer S, SamoreM. Effects of protease inhibitors on hyperglycemia, hyperlipidemia and lipodystrophy: A 5–year cohort study. Arch InternMed2000;160:2050-2056. 47. VanLethF,PhanuphakP,StroesE, GazzardB,CahnP,RaffiF, etal. Nevirapine and efavirenz elicit different changes in lipidprofiles in antiretroviral therapy–naive patients infected with HIV–1. PLOSMed2004;1:64-74. 48. Marcovina SM, KoschinskyML, Albers JJ, Skarlatos S. Report of theNationalHeart,Lungandblood instituteworkshop on lipoprotein (a) and cardiovascular disease; recent advances and future directions. Clin Chem 2003; 49:1785-1796. 49. Nader R, Russel W, Alan TR. Lipids, lipoproteins, apolipoproteins and other cardiovascular risk factors. In:BurtisCA,AshwoodER,Bruns DE, eds. Tietz fundamentals of clinical chemistry. 6th ed. New Delhi: Saunders Elsevier, 2008:411-426. 50. Kostner GM, Lp(a) Lipoproteins and the genetic polymorphismof lipoprotein. In:DayCE,LevyRS, eds. Lowdensity lipoproteins. 2nd ed. New York: Plenum press, 1976:229-269. 51. atherogenicity. CurrOpinLipidol Kronenberg F, Trenkwalder E, Lingenhel A, Friedrich G, Lhotta K, Schober M, et al. Renovascular arteriovenous difference in Lp(a) plasma concentrations suggest removal of Lp(a) from the renal circulation. J. Lipid Res 1997; 38:1755-1763. 52. 53. 54. 55. 56. 57. Albers JJ, Koschinsky ML, Marcovina SM. Evidence mounts for a role of the kidney in lipoprotein(a) catabolism .Kidney Int 2007; 71:961-962. Eaton DL, Fless GL, Kohr WJ, McLean JW, Xu QT, Miller CG, et al. Partial amino acid sequence of apolipoprotein(a) shows that it is homologous to plasminogen. Proc Natl Acad Sci USA 1987; 84:3224 3228. Miles LA, Fless GM, Levin EG, Scanu AM, Plow EF. A potential basis for the thrombotic risks associated with lipoprotein (a). Nature 1989; 339:301-303. Hajjar KA, Gavish D, Breslow JL, Nachman RL. Lipoprotein (a) modulation of endothelial cell surface fibrinolysis and it’s potential role in atherosclerosis. Nature 1989; 339:301-305. Gouni– Berthold I, Berthold HK. Lipoprotein(a): current perspective. CurrVascpharmacol2011; 9:682 692 Tsimikas S, Witztem JL. The role of oxidized phospholipids in mediating lipoprotein(a) 2008; 19:369-377 58. 59. Ichikawa T, Unoki H, Sun H, Shimoyamada H, Marcovina S, Shikama H, et al. Lipoprotein(a) promotes smooth muscle cell proliferation and differentiation in atherosclerotic lesions of human apo(a) transgenic rabbits. Am J Pathol 2002; 160:227-236. Takagi H, Atorvastatin Umemoto T. decreases lipoprotein(a): A meta-analysis of randomized trials. Int J Cardiol 2012; 154:183-186. 60. 61. 62. 63. Riche DM, East HE, Preist HM. Practical management dyslipidemia with of elevated lipoprotein(a). J Am Pharm Assoc 2008;48(6):803-807. Periard D, Telenti A, Sudre P, Cheseaux J, Halfon P, Marianne JR, et al. Atherogenic dyslipidemia in HIV– infected individuals treated with protease inhibitors. The Swiss HIV cohort study. Circulation 1999; 100:700-705. Enkhmaa B, Annurad E, Zhang W, Abbuthalha A, Li XD, Dotterwelch W, et al. HIV disease activity as a modulator of lipoprotein(a) and allele– specific apolipoprotein(a) levels. ArteriosclerThrombVascBiol 2013; 33(2):387-392. Araoye MO. Research Methodology with Statistics for Health and Social Sciences. Pioneer Medical Journal Vol. 6, No. 1 Jan-Jun, 2021 21 Nathadex publishers. 2004; 117 120. 64. 65. 66. 67. 68. 69. 70. Allain CC, Poon LS, Chan CSG, Richmond W, FU PC. Enzymatic determination of total serum cholesterol. Clin Chem 1974; 20:470-475. Lopes– Virella ME, Stone P, Elliss S. Cholesterol determination in high density lipoprotein separated by three different methods. Clin Chem 1977; 23:882. Buccolo G, David H. Quantitative determination of serum triglycerides by use of enzymes. Clin Chem 1973; 19:476-482 Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low density lipoprotein in plasma without the use of the preparative ultracentrifuge. Clin Chem 1972; 18:499-502. Votila M, Ruoslanti E, EnguallE .J Immunol methods 1981; 42: 11-5. Caplice NM, Panetta C, Peterson TE, Kleppe LS, Mueske CS, Kostner GM, et al. Lipoprotein (a) binds and inactivates tissue factor pathway inhibitor: a novel link between lipoproteins thrombosis. Blood 98(10):2980-2987. and 2001; Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (Adult treatment Panel III) final report. Circulation 2002; 106:3143-3421. 71. 72. 73. 74. 75. 76. Dube N, Voorbij R, Lens F, Gomo Z A. Lipoprotein(a) concentrations and apolipoprotein(a) isoform distribution in a Zimbabwean population. Cent Afr J Med 2002; 48: 83-87. Mauss S, Berger F, Schmutz G, Henke J, Richter W O. Lipoprotein(a) in patients initiating antiretroviral therapy. Medicine 2008; 9: 415-420. HIV Denue B A, Muazu J, Gashau W, Mbo D N, Ajayi N A. Effects of highly active antiretroviral therapy [HAART] on blood pressure changes and it’s associated factors in HAART naïve HIV–infected patients in North eastern Nigeria. Arch Appl Sci Res 2012; 4(3): 1447-1452. Tagoe E A, Osei J K, Asare G, Otu-Nyarko S, Asare-Anane H. HIV-1 infection and highly active anti-retroviral therapy effect on lipid metabolism in Ghanaian patients. Int J Bioassays 2014; 3(4) : 1994-1998. Riddler S A, Li X, Chu H, Kingsley L A, Dobs A, Evans R, et al. Longitudinal changes in serum lipids among HIV- infected men on highly active antiretroviral therapy. HIV Medicine 2007; 8(5): 280-287. Berthold H K, Parhofer K G, Ritter M M, Addo M, Wasmuth J C, Pioneer Medical Journal Vol. 6, No. 1 Jan-Jun, 2021 22 Schliefer K, et al. Influence of protease inhibitor therapy on lipoprotein metabolism. J Intern Med 1999; 246: 567-575. 77. 78. Mulligan K, Grunfeld C, Tai V W, Algren H, Pang M, Chernoff D N, et al. Hyperlipidemia and insulin resistance are induced by protease inhibitors independent of changes in body composition in patients with HIV infection. J Acquir Immune DeficSyndr2000; 23: 35 43. Haubrich R H, Riddler S A, Di Rienzo A G, Komarow L, Powderly W G, Klingman K, et al. Metabolic outcomes in a randomized trial of nucleoside , non-nucleoside and protease inhibitor sparing regimens for initial HIV treatment . AIDS 2009.
