Download PDF
CC BY 4.0 · TH Open 2021; 05(03): e295-e302
DOI: 10.1055/s-0041-1732803
Review Article

Role of Increased Lipoprotein (a) in Retinal Vein Occlusion: A Systematic Review and Meta-analysis

Francesco Paciullo
1   Division of Internal and Cardiovascular Medicine, Department of Medicine and Surgery, University of Perugia, Perugia, Italy
,
David Giannandrea 
2   Division of Neurology and Stroke Unit, Department of Neurology, Gubbio and Città di Castello Hospital, Perugia, Italy
,
Gianni Virgili
3   Department of Neurosciences, Psychology, Drug Research and Child Health (NEUROFARBA), Ophthalmology Clinic, University of Firenze and AOU Careggi, Florence, Italy
,
Carlo Cagini
4   Section of Ophthalmology, Department of Medicine and Surgery, University of Perugia, Perugia, Italy
,
Paolo Gresele 
1   Division of Internal and Cardiovascular Medicine, Department of Medicine and Surgery, University of Perugia, Perugia, Italy
› Author Affiliations Funding This work was supported in part by a grant from Fondazione CARIPLO (#2018-0483) to P.G.
› Further Information
   Permissions and Reprints

Abstract

Background Increased lipoprotein (a) [Lp(a)] has been associated with enhanced risk of cardiovascular events and more recently with venous thromboembolism. However, there is inconclusive data on the association between enhanced Lp(a) and retinal vein occlusion (RVO). We aimed to assess the role of Lp(a) in RVO.

Methods We performed a systematic review and meta-analysis of the studies addressing the role of Lp(a) in RVO. A systematic literature search was performed to identify all published papers reporting Lp(a) levels. Main outcome measures consisted of Lp(a) levels in patients with (cases) or without (controls) RVO.

Results We included 13 studies for a total of 1,040 cases and 16,648 controls. Lp(a) levels above normal limits were associated with RVO (OR 2.38, 95% CI 1.7–3.34) and patients with RVO had higher Lp(a) levels than controls (weighted mean difference: 13.4 mg/dL, 95% CI 8.2–18.6).

Conclusion Increased Lp(a) levels associate with RVO and should be included among diagnostic and prognostic indexes for this unusual-site vein thrombosis. Therapeutic interventions aimed to lower Lp(a) should be tested in RVO patients.

Keywords

cardiovascular risk - retinal vein occlusion - unusual site vein thrombosis

Supplementary Material



Publication History

Received: 17 November 2020

Accepted: 26 February 2021

Article published online:
06 July 2021

© 2021. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Sivaprasad S, Amoaku WM, Hykin P. RVO Guideline Group. The Royal College of Ophthalmologists Guidelines on retinal vein occlusions: executive summary. Eye (Lond) 2015; 29 (12) 1633-1638
    CrossrefPubMedGoogle Scholar
  • 2 Garcia-Horton A, Al-Ani F, Lazo-Langner A. Retinal vein thrombosis: the Internist's role in the etiologic and therapeutic management. Thromb Res 2016; 148: 118-124
    CrossrefPubMedGoogle Scholar
  • 3 Romiti GF, Corica B, Borgi M. et al. Inherited and acquired thrombophilia in adults with retinal vascular occlusion: a systematic review and meta-analysis. J Thromb Haemost 2020; 18 (12) 3249-3266
    CrossrefPubMedGoogle Scholar
  • 4 Ponto KA, Scharrer I, Binder H. et al. Hypertension and multiple cardiovascular risk factors increase the risk for retinal vein occlusions: results from the Gutenberg Retinal Vein Occlusion Study. J Hypertens 2019; 37 (07) 1372-1383
    CrossrefPubMedGoogle Scholar
  • 5 Wu CY, Riangwiwat T, Limpruttidham N. et al. Association of retinal vein occlusion with cardiovascular risk factors: a systematic review and meta-analysis. Retina 2019; 39 (09) 1635-1645
    CrossrefPubMedGoogle Scholar
  • 6 Ageno W, Cattaneo R, Manfredi E. et al. Parnaparin versus aspirin in the treatment of retinal vein occlusion. A randomized, double blind, controlled study. Thromb Res 2010; 125 (02) 137-141
    CrossrefPubMedGoogle Scholar
  • 7 Tsimikas S. A test in context: lipoprotein(a): diagnosis, prognosis, controversies, and emerging therapies. J Am Coll Cardiol 2017; 69 (06) 692-711
    CrossrefPubMedGoogle Scholar
  • 8 Reyes-Soffer G, Ginsberg HN, Ramakrishnan R. The metabolism of lipoprotein (a): an ever-evolving story. J Lipid Res 2017; 58 (09) 1756-1764
    CrossrefPubMedGoogle Scholar
  • 9 Nordestgaard BG, Langsted A. Lipoprotein (a) as a cause of cardiovascular disease: insights from epidemiology, genetics, and biology. J Lipid Res 2016; 57 (11) 1953-1975
    CrossrefPubMedGoogle Scholar
  • 10 Paciullo F, Momi S, Gresele P. PCSK9 in haemostasis and thrombosis: possible pleiotropic effects of PCSK9 inhibitors in cardiovascular prevention. Thromb Haemost 2019; 119 (03) 359-367
    Article in Thieme ConnectPubMedGoogle Scholar
  • 11 Stulnig TM, Morozzi C, Reindl-Schwaighofer R, Stefanutti C. Looking at Lp(a) and related cardiovascular risk: from scientific evidence and clinical practice. Curr Atheroscler Rep 2019; 21 (10) 37
    CrossrefPubMedGoogle Scholar
  • 12 Willeit P, Ridker PM, Nestel PJ. et al. Baseline and on-statin treatment lipoprotein(a) levels for prediction of cardiovascular events: individual patient-data meta-analysis of statin outcome trials. Lancet 2018; 392 (10155): 1311-1320
    CrossrefPubMedGoogle Scholar
  • 13 Sharrett AR, Ballantyne CM, Coady SA. et al; Atherosclerosis Risk in Communities Study Group. Coronary heart disease prediction from lipoprotein cholesterol levels, triglycerides, lipoprotein(a), apolipoproteins A-I and B, and HDL density subfractions: the Atherosclerosis Risk in Communities (ARIC) Study. Circulation 2001; 104 (10) 1108-1113
    CrossrefPubMedGoogle Scholar
  • 14 Kouvari M, Panagiotakos DB, Chrysohoou C. et al. Lipoprotein (a) and 10-year cardiovascular disease incidence in apparently healthy individuals: a sex-based sensitivity analysis from ATTICA cohort study. Angiology 2019; 70 (09) 819-829
    CrossrefPubMedGoogle Scholar
  • 15 Kronenberg F, Kronenberg MF, Kiechl S. et al. Role of lipoprotein(a) and apolipoprotein(a) phenotype in atherogenesis: prospective results from the Bruneck study. Circulation 1999; 100 (11) 1154-1160
    CrossrefPubMedGoogle Scholar
  • 16 Ariyo AA, Thach C, Tracy R. Cardiovascular Health Study Investigators. Lp(a) lipoprotein, vascular disease, and mortality in the elderly. N Engl J Med 2003; 349 (22) 2108-2115
    CrossrefPubMedGoogle Scholar
  • 17 Keil JE, Loadholt CB, Weinrich MC, Sandifer SH, Boyle Jr E. Incidence of coronary heart disease in blacks in Charleston, South Carolina. Am Heart J 1984; 108 (3 Pt 2): 779-786
    CrossrefPubMedGoogle Scholar
  • 18 Rajecki M, Pajunen P, Jousilahti P, Rasi V, Vahtera E, Salomaa V. Hemostatic factors as predictors of stroke and cardiovascular diseases: the FINRISK '92 Hemostasis Study. Blood Coagul Fibrinolysis 2005; 16 (02) 119-124
    CrossrefPubMedGoogle Scholar
  • 19 Lakka HM, Lakka TA, Tuomilehto J, Sivenius J, Salonen JT. Hyperinsulinemia and the risk of cardiovascular death and acute coronary and cerebrovascular events in men: the Kuopio Ischaemic Heart Disease Risk Factor Study. Arch Intern Med 2000; 160 (08) 1160-1168
    CrossrefPubMedGoogle Scholar
  • 20 Dentali F, Gessi V, Marcucci R, Gianni M, Grandi AM, Franchini M. Lipoprotein(a) as a risk factor for venous thromboembolism: a systematic review and meta-analysis of the literature. Semin Thromb Hemost 2017; 43 (06) 614-620
    Article in Thieme ConnectPubMedGoogle Scholar
  • 21 Kunutsor SK, Mäkikallio TH, Kauhanen J, Voutilainen A, Laukkanen JA. Lipoprotein(a) is not associated with venous thromboembolism risk. Scand Cardiovasc J 2019; 53 (03) 125-132
    CrossrefPubMedGoogle Scholar
  • 22 Kuhli-Hattenbach C, Miesbach W, Lüchtenberg M, Kohnen T, Hattenbach LO. Elevated lipoprotein (a) levels are an independent risk factor for retinal vein occlusion. Acta Ophthalmol 2017; 95 (02) 140-145
    CrossrefPubMedGoogle Scholar
  • 23 Bandello F, Viganò D'Angelo S, Parlavecchia M. et al. Hypercoagulability and high lipoprotein(a) levels in patients with central retinal vein occlusion. Thromb Haemost 1994; 72 (01) 39-43
    Article in Thieme ConnectPubMedGoogle Scholar
  • 24 Murata M, Saito T, Takahashi S, Ichinose A. Plasma lipoprotein(a) levels are high in patients with central retinal artery occlusion. Thromb Res 1998; 91 (04) 169-175
    CrossrefPubMedGoogle Scholar
  • 25 Sofi F, Marcucci R, Fedi S. et al. High lipoprotein (a) levels are associated with an increased risk of retinal vein occlusion. Atherosclerosis 2010; 210 (01) 278-281
    CrossrefPubMedGoogle Scholar
  • 26 Stojakovic T, Scharnagl H, März W, Winkelmann BR, Boehm BO, Schmut O. Low density lipoprotein triglycerides and lipoprotein(a) are risk factors for retinal vascular occlusion. Clin Chim Acta 2007; 382 (1-2): 77-81
    CrossrefPubMedGoogle Scholar
  • 27 Wong TY, Larsen EK, Klein R. et al. Cardiovascular risk factors for retinal vein occlusion and arteriolar emboli: the Atherosclerosis Risk in Communities & Cardiovascular Health studies. Ophthalmology 2005; 112 (04) 540-547
    CrossrefPubMedGoogle Scholar
  • 28 Kuhli-Hattenbach C, Hellstern P, Miesbach W, Kohnen T, Hattenbach LO. Prevalence of elevated lipoprotein (a) levels in patients < 60 years of age with retinal vein occlusion. Klin Monatsbl Augenheilkd 2018; 235 (01) 81-86
    Article in Thieme ConnectPubMedGoogle Scholar
  • 29 Ribeaudeau-Saindelle F, Glacet-Bernard A, Lelong F, Coscas G, Soubrane G. Retinal vein occlusion and lipoprotein (a). J Fr Ophtalmol 1998; 21 (04) 245-250
    PubMedGoogle Scholar
  • 30 Müller HM, Diekstall FF, Schmidt E, März W, Canzler H, Demeler U. Lipoprotein (a): a risk factor for retinal vascular occlusion. Ger J Ophthalmol 1992; 1 (05) 338-341
    PubMedGoogle Scholar
  • 31 Glueck CJ, Bell H, Vadlamani L. et al. Heritable thrombophilia and hypofibrinolysis. Possible causes of retinal vein occlusion. Arch Ophthalmol 1999; 117 (01) 43-49
    CrossrefPubMedGoogle Scholar
  • 32 Glueck CJ, Hutchins RK, Jurantee J, Khan Z, Wang P. Thrombophilia and retinal vascular occlusion. Clin Ophthalmol 2012; 6: 1377-1384
    CrossrefPubMedGoogle Scholar
  • 33 Gumus K, Kadayifcilar S, Eldem B. et al. Is elevated level of soluble endothelial protein C receptor a new risk factor for retinal vein occlusion?. Clin Exp Ophthalmol 2006; 34 (04) 305-311
    CrossrefPubMedGoogle Scholar
  • 34 Lip PL, Blann AD, Jones AF, Lip GY. Abnormalities in haemorheological factors and lipoprotein (a) in retinal vascular occlusion: implications for increased vascular risk. Eye (Lond) 1998; 12 (Pt 2): 245-251
    CrossrefPubMedGoogle Scholar
  • 35 Rosen L. An intuitive approach to understanding the attributable fraction of disease due to a risk factor: the case of smoking. Int J Environ Res Public Health 2013; 10 (07) 2932-2943
    CrossrefPubMedGoogle Scholar
  • 36 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
    CrossrefPubMedGoogle Scholar
  • 37 Kontopantelis E, Reeves D. MetaEasy: a meta-analysis add-in for Microsoft Excel. J Stat Softw 2009; 30: 1-25
    CrossrefPubMedGoogle Scholar
  • 38 Wells GA, Shea B, O'Connell D. et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality if nonrandomized studies in meta-analyses. 2012 . Accessed September 12, 2020 at: http://wwwohrica/programs/clinical_epidemiology/oxfordasp
    PubMedGoogle Scholar
  • 39 Peters JL, Sutton AJ, Jones DR, Abrams KR, Rushton L. Comparison of two methods to detect publication bias in meta-analysis. JAMA 2006; 295 (06) 676-680
    CrossrefPubMedGoogle Scholar
  • 40 Prisco D, Marcucci R. Retinal vein thrombosis: risk factors, pathogenesis and therapeutic approach. Pathophysiol Haemost Thromb 2002; 32 (5-6): 308-311
    CrossrefPubMedGoogle Scholar
  • 41 Langsted A, Nordestgaard BG. Antisense oligonucleotides targeting lipoprotein(a). Curr Atheroscler Rep 2019; 21 (08) 30
    CrossrefPubMedGoogle Scholar
  • 42 Jia X, Liu J, Mehta A, Ballantyne CM, Virani SS. Lipid-lowering biotechnological drugs: from monoclonal antibodies to antisense therapies-a clinical perspective. Cardiovasc Drugs Ther 2020; (e-pub ahead of print) DOI: 10.1007/s10557-020-07082-x.
    CrossrefPubMedGoogle Scholar
  • 43 Tsimikas S, Karwatowska-Prokopczuk E, Gouni-Berthold I. et al; AKCEA-APO(a)-LRx Study Investigators. Lipoprotein(a) reduction in persons with cardiovascular disease. N Engl J Med 2020; 382 (03) 244-255
    CrossrefPubMedGoogle Scholar
  • 44 Blettner M, Sauerbrei W, Schlehofer B, Scheuchenpflug T, Friedenreich C. Traditional reviews, meta-analyses and pooled analyses in epidemiology. Int J Epidemiol 1999; 28 (01) 1-9
    CrossrefPubMedGoogle Scholar
  • 45 Stroup DF, Berlin JA, Morton SC. et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA 2000; 283 (15) 2008-2012
    CrossrefPubMedGoogle Scholar
  • 46 Paez A. Gray literature: an important resource in systematic reviews. J Evid Based Med 2017; 10 (03) 233-240
    CrossrefPubMedGoogle Scholar
  • 47 Cho B-J, Bae SH, Park SM. et al. Comparison of systemic conditions at diagnosis between central retinal vein occlusion and branch retinal vein occlusion. PLoS One 2019; 14 (08) e0220880
    CrossrefPubMedGoogle Scholar
  • 48 Bucciarelli P, Passamonti SM, Gianniello F, Artoni A, Martinelli I. Thrombophilic and cardiovascular risk factors for retinal vein occlusion. Eur J Intern Med 2017; 44: 44-48
    CrossrefPubMedGoogle Scholar
  • 49 Karia N. Retinal vein occlusion: pathophysiology and treatment options. Clin Ophthalmol 2010; 4: 809-816
    CrossrefPubMedGoogle Scholar