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Plasma Lipoprotein(a) Levels in Polycystic Ovary Syndrome: A Systematic Review and Meta-analysis

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Abstract

Introduction

The polycystic ovary syndrome (PCOS) may represent an important model of lipid alterations. Lipoprotein(a) [Lp(a)] has emerged as a new marker of cardiovascular risk.

Aim

The main objective of this meta-analysis was to analyze the available evidence on Lp(a) levels in patients with PCOS compared to a control group.

Methods

This meta-analysis was performed according to PRISMA guidelines. A literature search was performed to detect studies that have quantified Lp(a) levels in women with PCOS compared to a control group. The primary outcome was Lp(a) levels expressed in mg/dL. Random effects models were used.

Results

Twenty-three observational studies including 2,337 patients were identified and considered eligible for this meta-analysis. In the overall analysis, the quantitative analysis showed that patients with PCOS have a higher Lp(a) levels (SMD: 1.1 [95% CI: 0.7 to 1.4]; I2=93%) compared to the control group. The results were similar in the analysis of the subgroups of patients according to body mass index (normal weight group: SMD: 1.2 [95% CI: 0.5 to 1.9], I2=95%; overweight group: SMD: 1.2 [95% CI: 0.5 to 1.8], I2=89%). Sensitivity analysis showed that the results were robust.

Conclusions

This meta-analysis shows that women with PCOS had higher levels of Lp(a) compared to healthy women used as a control group. These findings were observed in both overweight and non-overweight women.

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References

  1. Liu J, Wu Q, Hao Y, Jiao M, Wang X, Jiang S, Han L. Measuring the global disease burden of polycystic ovary syndrome in 194 countries: Global Burden of Disease Study 2017. Hum Reprod. 2021;36:1108–19.

    Article  PubMed  PubMed Central  Google Scholar 

  2. El Hayek S, Bitar L, Hamdar LH, Mirza FG, Daoud G. Poly cystic ovarian syndrome: an updated overview. Front Physiol. 2016;5(7):124. https://doi.org/10.3389/fphys.2016.00124.

    Article  Google Scholar 

  3. Singh S, Pal N, Shubham S, Sarma DK, Verma V, Marotta F, Kumar M. Polycystic ovary syndrome: etiology, current management, and future therapeutics. J Clin Med. 2023;12(4):1454. https://doi.org/10.3390/jcm12041454.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Wild RA, Rizzo M, Clifton S, Carmina E. Lipid levels in polycystic ovary syndrome: systematic review and meta-analysis. Fertil Steril. 2011;95(3):1073-9.e1-11. https://doi.org/10.1016/j.fertnstert.2010.12.027.

    Article  CAS  PubMed  Google Scholar 

  5. Kronenberg F, Mora S, Stroes ESG, Ference BA, Arsenault BJ, Berglund L, Dweck MR, Koschinsky M, Lambert G, Mach F, McNeal CJ, Moriarty PM, Natarajan P, Nordestgaard BG, Parhofer KG, Virani SS, von Eckardstein A, Watts GF, Stock JK, Ray KK, Tokgözoğlu LS, Catapano AL. Lipoprotein(a) in atherosclerotic cardiovascular disease and aortic stenosis: a European Atherosclerosis Society consensus statement. Eur Heart J. 2022;43(39):3925–46. https://doi.org/10.1093/eurheartj/ehac361.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Bhatia HS, Wilkinson MJ. Lipoprotein(a): evidence for role as a causal risk factor in cardiovascular disease and emerging therapies. J Clin Med. 2022;11(20):6040. https://doi.org/10.3390/jcm11206040.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Velazquez EM, Mendoza SG, Wang P, Glueck CJ. Metformin therapy is associated with a decrease in plasma plasminogen activator inhibitor-1, lipoprotein(a), and immunoreactive insulin levels in patients with the polycystic ovary syndrome. Metabolism. 1997;46(4):454–7. https://doi.org/10.1016/s0026-0495(97)90066-4.

    Article  CAS  PubMed  Google Scholar 

  8. Dejager S, Pichard C, Giral P, Bruckert E, Federspield MC, Beucler I, Turpin G. Smaller LDL particle size in women with polycystic ovary syndrome compared to controls. Clin Endocrinol (Oxf). 2001;54(4):455–62. https://doi.org/10.1046/j.1365-2265.2001.01245.x.

    Article  CAS  PubMed  Google Scholar 

  9. Yildiz BO, Haznedaroğlu IC, Kirazli S, Bayraktar M. Global fibrinolytic capacity is decreased in polycystic ovary syndrome, suggesting a prothrombotic state. J Clin Endocrinol Metab. 2002;87(8):3871–5. https://doi.org/10.1210/jcem.87.8.8716.

    Article  CAS  PubMed  Google Scholar 

  10. Yilmaz M, Biri A, Bukan N, Karakoç A, Sancak B, Törüner F, Paşaoğlu H. Levels of lipoprotein and homocysteine in non-obese and obese patients with polycystic ovary syndrome. Gynecol Endocrinol. 2005;20(5):258–63. https://doi.org/10.1080/09513590400027265.

    Article  CAS  PubMed  Google Scholar 

  11. Yilmaz M, Bukan N, Ayvaz G, Karakoç A, Törüner F, Cakir N, Arslan M. The effects of rosiglitazone and metformin on oxidative stress and homocysteine levels in lean patients with polycystic ovary syndrome. Hum Reprod. 2005;20(12):3333–40. https://doi.org/10.1093/humrep/dei258.

    Article  CAS  PubMed  Google Scholar 

  12. Bickerton AST, Clark N, Meeking D, Shaw KM, Crook M, Lumb P, Turner C, Cummings MH. Cardiovascular risk in women with polycystic ovarian syndrome (PCOS). J Clin Pathol. 2005;58(2):151–4. https://doi.org/10.1136/jcp.2003.015271.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Macut D, Damjanovic S, Panidis D, Spanos N, Glisic B, Petakov M, Rousso D, Kourtis A, Bjekic J, Milic N. Oxidised low-density lipoprotein concentration—early marker of an altered lipid metabolism in young women with PCOS. Eur J Endocrinol. 2006;155(1):131–6. https://doi.org/10.1530/eje.1.02187.

    Article  CAS  PubMed  Google Scholar 

  14. Hu WH, Qiao J, Zhao SY, Zhang XW, Li MZ. Monocyte chemoattractant protein-1 and its correlation with lipoprotein in polycystic ovary syndrome. Beijing Da Xue Xue Bao Yi Xue Ban. 2006;38(5):487–91.

    CAS  PubMed  Google Scholar 

  15. Yilmaz S, Kursad U, Ayse Y, Ali Y, Ercan A, Fahrettin K. The effects of metformin on metabolic and cardiovascular risk factors in nonobese women with polycystic ovary syndrome. Clin Endocrinol (Oxf). 2007;67(6):904–8. https://doi.org/10.1111/j.1365-2265.2007.02985.x.

    Article  CAS  Google Scholar 

  16. Berneis K, Rizzo M, Hersberger M, Rini GB, Di Fede G, Pepe I, Spinas GA, Carmina E. Atherogenic forms of dyslipidaemia in women with polycystic ovary syndrome. Int J Clin Pract. 2009;63(1):56–62. https://doi.org/10.1111/j.1742-1241.2008.01897.x.

    Article  CAS  PubMed  Google Scholar 

  17. Rizzo M, Berneis K, Hersberger M, Pepe I, Di Fede G, Rini GB, Spinas GA, Carmina E. Milder forms of atherogenic dyslipidemia in ovulatory versus anovulatory polycystic ovary syndrome phenotype. Hum Reprod. 2009;24(9):2286–92. https://doi.org/10.1093/humrep/dep121.

    Article  CAS  PubMed  Google Scholar 

  18. Yilmaz M, Bukan N, Demirci H, Oztürk C, Kan E, Ayvaz G, Arslan M. Serum resistin and adiponectin levels in women with polycystic ovary syndrome. Gynecol Endocrinol. 2009;25(4):246–52. https://doi.org/10.1080/09513590802653833.

    Article  CAS  PubMed  Google Scholar 

  19. Arikan S, Bahceci M, Tuzcu A, Kale E, Gökalp D. Serum resistin and adiponectin levels in young non-obese women with polycystic ovary syndrome. Gynecol Endocrinol. 2010;26(3):161–6. https://doi.org/10.3109/09513590903247816.

    Article  CAS  PubMed  Google Scholar 

  20. Güdücü N, İşçi H, Görmüş U, Yiğiter AB, Dünder I. Serum visfatin levels in women with polycystic ovary syndrome. Gynecol Endocrinol. 2012;28(8):619–23. https://doi.org/10.3109/09513590.2011.650749.

    Article  CAS  PubMed  Google Scholar 

  21. Güdücü N, Işçi H, Yiğiter AB, Dünder I. C-reactive protein and lipoprotein-a as markers of coronary heart disease in polycystic ovary syndrome. J Turk Ger Gynecol Assoc. 2012;13(4):227–32. https://doi.org/10.5152/jtgga.2012.35.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Kim JJ, Chae SJ, Choi YM, Hwang KR, Song SH, Yoon SH, Kim SM, Ku SY, Kim SH, Kim JG, Moon SY. Atherogenic changes in low-density lipoprotein particle profiles were not observed in non-obese women with polycystic ovary syndrome. Hum Reprod. 2013;28(5):1354–60. https://doi.org/10.1093/humrep/det057.

    Article  CAS  PubMed  Google Scholar 

  23. Tsouma I, Kouskouni E, Gennimata V, Demeridou S, Boutsikou M, Grigoriou V, Chasiakou A, Hassiakou S, Baka S. Leptin levels in women with polycystic ovaries undergoing ovarian stimulation: relation to lipoprotein profiles. In Vivo. 2014;28(5):989–92.

    CAS  PubMed  Google Scholar 

  24. Tsouma I, Kouskouni E, Demeridou S, Boutsikou M, Hassiakos D, Chasiakou A, Hassiakou S, Gennimata V, Baka S. Lipid lipoprotein profile alterations in Greek infertile women with polycystic ovaries: influence of adipocytokines levels. In Vivo. 2014;28(5):935–9.

    CAS  PubMed  Google Scholar 

  25. Kumar PS, Ananthanarayanan PH, Rajendiran S. Cardiovascular risk markers and thyroid status in young Indian women with polycystic ovarian syndrome: a case-control study. J Obstet Gynaecol Res. 2014;40(5):1361–7. https://doi.org/10.1111/jog.12346.

    Article  CAS  Google Scholar 

  26. Tsouma I, Kouskouni E, Demeridou S, Boutsikou M, Hassiakos D, Chasiakou A, Hassiakou S, Baka S. Correlation of visfatin levels and lipoprotein lipid profiles in women with polycystic ovary syndrome undergoing ovarian stimulation. Gynecol Endocrinol. 2014;30(7):516–9. https://doi.org/10.3109/09513590.2014.896896.

    Article  CAS  PubMed  Google Scholar 

  27. Tu AS, Zhong Y, Mao XG. Changes of serum TOS and TAS levels and their association with apolipoprotein(a) in patients with polycystic ovary syndrome and infertility. Nan Fang Yi Ke Da Xue Xue Bao. 2016;36(3):405–9.

    CAS  PubMed  Google Scholar 

  28. Bousmpoula A, Kouskouni E, Benidis E, Demeridou S, Kapeta-Kourkouli R, Chasiakou A, Baka S. Adropin levels in women with polycystic ovaries undergoing ovarian stimulation: correlation with lipoprotein lipid profiles. Gynecol Endocrinol. 2018;34(2):153–6. https://doi.org/10.1080/09513590.2017.1379498.

    Article  CAS  PubMed  Google Scholar 

  29. Shah AK, Yadav BK, Suri A, Shah AK. A study on lipoprotein-a and PAI-1 in women with polycystic ovary syndrome. Horm Mol Biol Clin Investig. 2022;43(3):357–61. https://doi.org/10.1515/hmbci-2021-0044.

    Article  CAS  PubMed  Google Scholar 

  30. Toulis KA, Goulis DG, Mintziori G, Kintiraki E, Eukarpidis E, Mouratoglou SA, Pavlaki A, Stergianos S, Poulasouchidou M, Tzellos TG, Makedos A, Chourdakis M, Tarlatzis BC. Meta-analysis of cardiovascular disease risk markers in women with polycystic ovary syndrome. Hum Reprod Update. 2011;17(6):741–60. https://doi.org/10.1093/humupd/dmr025.

    Article  CAS  PubMed  Google Scholar 

  31. Arya S, Kaji AH, Boermeester MA. PRISMA reporting guidelines for meta-analyses and systematic reviews. JAMA Surg. 2021;156(8):789–90. https://doi.org/10.1001/jamasurg.2021.0546.

    Article  PubMed  Google Scholar 

  32. Sterne JA, Hernán MA, Reeves BC, Savović J, Berkman ND, Viswanathan M, Henry D, Altman DG, Ansari MT, Boutron I, Carpenter JR, Chan AW, Churchill R, Deeks JJ, Hróbjartsson A, Kirkham J, Jüni P, Loke YK, Pigott TD, Ramsay CR, Regidor D, Rothstein HR, Sandhu L, Santaguida PL, Schünemann HJ, Shea B, Shrier I, Tugwell P, Turner L, Valentine JC, Waddington H, Waters E, Wells GA, Whiting PF, Higgins J. ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ. 2016;355: i4919.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Wan X, Wang W, Liu J, Tong T. Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range. BMC Med Res Methodol. 2014;14:135.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Viechtbauer W. Conducting meta-analyses in R with the metaphor package. J Stat Softw. 2010;36:1–48.

    Article  Google Scholar 

  35. Pustejovsky JE, Rodgers MA. Testing for funnel plot asymmetry of standardized mean differences. Res Synth Methods. 2019;10(1):57–71. https://doi.org/10.1002/jrsm.1332.

    Article  PubMed  Google Scholar 

  36. Shrivastava S, Conigliaro RL. Polycystic ovarian syndrome. Med Clin N Am. 2023;107(2):227–34. https://doi.org/10.1016/j.mcna.2022.10.004.

    Article  PubMed  Google Scholar 

  37. Berni TR, Morgan CL, Rees DA. Women with polycystic ovary syndrome have an increased risk of major cardiovascular events: a population study. J Clin Endocrinol Metab. 2021;106(9):e3369–80. https://doi.org/10.1210/clinem/dgab392.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Anagnostis P, Paparodis RD, Bosdou JK, Bothou C, Macut D, Goulis DG, Livadas S. Risk of type 2 diabetes mellitus in polycystic ovary syndrome is associated with obesity: a meta-analysis of observational studies. Endocrine. 2021;74(2):245–53. https://doi.org/10.1007/s12020-021-02801-2.

    Article  CAS  PubMed  Google Scholar 

  39. Tehrani FR, Amiri M, Behboudi-Gandevani S, Bidhendi-Yarandi R, Carmina E. Cardiovascular events among reproductive and menopausal age women with polycystic ovary syndrome: a systematic review and meta-analysis. Gynecol Endocrinol. 2020;36(1):12–23. https://doi.org/10.1080/09513590.2019.1650337.

    Article  Google Scholar 

  40. Vekic J, Zeljkovic A, Al Rasadi K, Cesur M, Silva Nunes J, Stoian AP, Rizzo M. A new look at novel cardiovascular risk biomarkers: the role of atherogenic lipoproteins and innovative antidiabetic therapies. Metabolites. 2022;12(2):108. https://doi.org/10.3390/metabo12020108.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Kronenberg F, Utermann G. Lipoprotein(a): resurrected by genetics. J Intern Med. 2013;273(1):6–30. https://doi.org/10.1111/j.1365-2796.2012.02592.x.

    Article  CAS  PubMed  Google Scholar 

  42. Tatsumi Y, Nakao YM, Masuda I, Higashiyama A, Takegami M, Nishimura K, Watanabe M, Ohkubo T, Okamura T, Miyamoto Y. Risk for metabolic diseases in normal weight individuals with visceral fat accumulation: a cross-sectional study in Japan. BMJ Open. 2017;7(1):e013831. https://doi.org/10.1136/bmjopen-2016-013831.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Gaeta G, Lanero S, Barra S, Silvestri N, Cuomo V, Materazzi C, Vitagliano G. Sex hormones and lipoprotein(a) concentration. Expert Opin Investig Drugs. 2011;20(2):221–38. https://doi.org/10.1517/13543784.2011.548804.

    Article  CAS  PubMed  Google Scholar 

  44. Enkhmaa B, Berglund L. Non-genetic influences on lipoprotein(a) concentrations. Atherosclerosis. 2022;349:53–62. https://doi.org/10.1016/j.atherosclerosis.2022.04.006.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Guzik TJ, Skiba DS, Touyz RM, Harrison DG. The role of infiltrating immune cells in dysfunctional adipose tissue. Cardiovasc Res. 2017;113:1009–23. https://doi.org/10.1093/cvr/cvx108.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Inal HA, Yilmaz N, Gorkem U, Oruc AS, Timur H. The impact of follicular fluid adiponectin and ghrelin levels based on BMI on IVF outcomes in PCOS. J Endocrinol Invest. 2016;39(4):431–7. https://doi.org/10.1007/s40618-015-0392-6.

    Article  CAS  PubMed  Google Scholar 

  47. Guler E, Guler GB, Kizilirmak F, Batgerel U, Demir GG, Gunes HM, Özcan Ö, Barutcu I, Turkmen MM, Esen AM. Evaluation of adiponectin and lipoprotein(a) levels in cardiac syndrome X. Herz. 2015;40(Suppl 3):291–7. https://doi.org/10.1007/s00059-014-4191-1.

    Article  PubMed  Google Scholar 

  48. Simantiris S, Antonopoulos AS, Papastamos C, Benetos G, Koumallos N, Tsioufis K, Tousoulis D. Lipoprotein(a) and inflammation- pathophysiological links and clinical implications for cardiovascular disease. J Clin Lipidol. 2023;17(1):55–63. https://doi.org/10.1016/j.jacl.2022.10.004.

    Article  PubMed  Google Scholar 

  49. Gleicher N, Darmon S, Patrizio P, Barad DH. Reconsidering the polycystic ovary syndrome (PCOS). Biomedicines. 2022;10(7):1505. https://doi.org/10.3390/biomedicines10071505.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Bjornstad P, Eckel RH. Pathogenesis of lipid disorders in insulin resistance: a brief review. Curr Diab Rep. 2018;18(12):127. https://doi.org/10.1007/s11892-018-1101-6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Cardoso-Saldaña GC, González-Salazar MDC, Posadas-Sánchez R, Vargas-Alarcón G. Metabolic syndrome, lipoprotein(a) and subclinical atherosclerosis in Mexican population. Arch Cardiol Mex. 2021;91(3):307–14. https://doi.org/10.24875/ACM.20000276.

    Article  PubMed  Google Scholar 

  52. Bozbas H, Yildirir A, Pirat B, Eroğlu S, Korkmaz ME, Atar I, Ulus T, Aydinalp A, Ozin B, Müderrisoğlu H. Increased lipoprotein(a) in metabolic syndrome: is it a contributing factor to premature atherosclerosis? Anadolu Kardiyol Derg. 2008;8:111–5.

    PubMed  Google Scholar 

  53. Wu XY, Lin L, Qi HY, Du R, Hu CY, Ma LN, Peng K, Li M, Xu Y, Xu M, Chen YH, Lu JL, Bi YF, Wang WQ, Ning G. Association between lipoprotein(a) levels and metabolic syndrome in a middle-aged and elderly Chinese cohort. Biomed Environ Sci. 2019;32(7):477–85. https://doi.org/10.3967/bes2019.065.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Servicio de Cardiología, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina

    Walter Masson & Leandro Barbagelata

  2. Servicio de Cardiología, Hospital Militar Campo de Mayo, Buenos Aires, Argentina

    Martín Lobo

  3. Servicio de Cardiología, Sanatorio Finochieto, Buenos Aires, Argentina

    Augusto Lavalle-Cobo

  4. Facultad Medicina, Universidad FASTA, Mar del Plata, Argentina

    Pablo Corral

  5. Centro de Investigación en EndocrinologíaNutrición y Metabolismo (CIENM), Facultad de Ciencias de la Salud, Universidad Nacional de Formosa, Formosa, Argentina

    Juan Patricio Nogueira

  6. Universidad Internacional de las Américas, San José, Costa Rica

    Juan Patricio Nogueira

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WM and LB participated in the conception and design of the research. WM, LB and JPN participated in the data collection. The interpretation of the data and the statistical analysis was done by WM and ML. WM, ALC, PC and LB drafted the manuscript. All authors performed a critical review of the final document. All authors have read and agreed to the published version of the manuscript.

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Masson, W., Barbagelata, L., Lobo, M. et al. Plasma Lipoprotein(a) Levels in Polycystic Ovary Syndrome: A Systematic Review and Meta-analysis. High Blood Press Cardiovasc Prev 30, 305–317 (2023). https://doi.org/10.1007/s40292-023-00585-2

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