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Current Pharmaceutical Design

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ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

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Meta-Analysis

Lipoprotein (a) Levels and Abdominal Aortic Aneurysm. A Systematic Review and Meta-analysis

Author(s): Stamatios Lampsas, Evangelos Oikonomou*, Panteleimon Pantelidis, Panagiotis Theofilis, Konstantinos Grammatopoulos, Anastasios Marathonitis, Michael A Vavuranakis, Gerasimos Siasos, Dimitris Tousoulis and Manolis Vavuranakis

Volume 28, Issue 43, 2022

Published on: 09 December, 2022

Page: [3492 - 3499] Pages: 8

DOI: 10.2174/1381612829666221124110920

Price: $65

Abstract

Background: Several studies have linked high Lipoprotein (a) (Lp(a)) concentrations to cardiovascular events, including the formation of Abdominal Aortic Aneurysms (AAA). We review and meta-analyze existing evidence on the association of Lp(a) levels with AAA.

Methods: Studies evaluating the link of Lp(a) with AAA, up to December 27th 2021, were identified by a systematic search of PubMed, SCOPUS, and Web of Science databases. The results were qualitatively and quantitatively synthesized according to PRISMA guidelines. Results are presented as standardized mean differences (SMD) with 95% confidence intervals (CI).

Results: A total of 5,078 subjects (1,637 patients with AAA vs. 3,441 controls) from 11 studies were included in the meta-analysis, with a mean age of 69.9 years and a male sex prevalence of 85.8%. Based on the qualitative synthesis, high Lp(a) concentrations are linked to abdominal aortic wall degradation and extracellular matrix disarrangement. Moreover, despite the considerable variability among races, high Lp(a) levels are related to increased AAA risk, independently of race differences. Accordingly, patients with AAA displayed significantly higher Lp(a) levels compared to controls (SMD: 0.86, 95% CI: 0.55-1.17, p < 0.001). The outcome was not affected in a sensitivity analysis excluding three outlying studies (SMD: 0.40, 95% CI: 0.22-0.58, p < 0.001).

Conclusion: This meta-analysis indicates the association between high Lp(a) levels and the presence of AAA, although existing literature presents high heterogeneity. Further studies are needed to standardize Lp(a) measurements and to conclude whether Lp(a) can be used as a sensitive biomarker of early presymptomatic AAA diagnosis.

« Previous Next »
[1]
Purushothaman KR, Purushothaman M, Levy AP, et al. Increased expression of oxidation-specific epitopes and apoptosis are associated with haptoglobin genotype: Possible implications for plaque progression in human atherosclerosis. J Am Coll Cardiol 2012; 60(2): 112-9.
[http://dx.doi.org/10.1016/j.jacc.2012.04.011] [PMID: 22766337]
[2]
Teles J, Teles N, Sousa H. Screening of the abdominal aortic aneurysm: Cost-effectiveness and health benefits. Port J Card Thorac Vasc Surg 2021; 28(2): 39-48.
[PMID: 35302328]
[3]
Rehberger Likozar A, Zavrtanik M, Šebeštjen M. Lipoprotein (a) in atherosclerosis: From pathophysiology to clinical relevance and treatment options. Ann Med 2020; 52(5): 162-77.
[http://dx.doi.org/10.1080/07853890.2020.1775287] [PMID: 32453609]
[4]
Lim TS, Yun JS, Cha SA, et al. Elevated lipoprotein(a) levels predict cardiovascular disease in type 2 diabetes mellitus: A 10-year prospective cohort study. Korean J Intern Med 2016; 31(6): 1110-9.
[http://dx.doi.org/10.3904/kjim.2016.030] [PMID: 27756118]
[5]
Kubota Y, Folsom AR, Ballantyne CM, Tang W. Lipoprotein (a) and abdominal aortic aneurysm risk: The atherosclerosis risk in communities study. Atherosclerosis 2018; 268: 63-7.
[http://dx.doi.org/10.1016/j.atherosclerosis.2017.10.017] [PMID: 29182987]
[6]
Sofi F, Marcucci R, Giusti B, et al. High levels of homocysteine, lipoprotein (a) and plasminogen activator inhibitor-1 are present in patients with abdominal aortic aneurysm. Thromb Haemost 2005; 94(5): 1094-8.
[PMID: 16363254]
[7]
O’Donoghue ML, Fazio S, Giugliano RP, et al. Lipoprotein (a), PCSK9 inhibition, and cardiovascular risk. Circulation 2019; 139(12): 1483-92.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.118.037184] [PMID: 30586750]
[8]
Schwartz GG, Steg PG, Szarek M, et al. Peripheral artery disease and venous thromboembolic events after acute coronary syndrome. Circulation 2020; 141(20): 1608-17.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.120.046524] [PMID: 32223446]
[9]
Scipione CA, Sayegh SE, Romagnuolo R, et al. Mechanistic insights into Lp(a)-induced IL-8 expression: a role for oxidized phospholipid modification of apo(a). J Lipid Res 2015; 56(12): 2273-85.
[http://dx.doi.org/10.1194/jlr.M060210] [PMID: 26474593]
[10]
Gawinecka J, Schnrath F, von Eckardstein A. Acute aortic dissection: pathogenesis, risk factors and diagnosis. Swiss Med Wkly 2017; 147: w14489.
[http://dx.doi.org/10.4414/smw.2017.14489] [PMID: 28871571]
[11]
Yang Y, Hong Y, Yang W, Zheng Z. Association of lipoprotein (a) with aortic dissection. Clin Cardiol 2022; 45(9): 908-12.
[http://dx.doi.org/10.1002/clc.23834] [PMID: 35925003]
[12]
Altobelli E, Rapacchietta L, Profeta V, Fagnano R. Risk factors for abdominal aortic aneurysm in population-based studies: A systematic review and meta-analysis. Int J Environ Res Public Health 2018; 15(12): 2805.
[http://dx.doi.org/10.3390/ijerph15122805] [PMID: 30544688]
[13]
Ugovšek S, Šebeštjen M. Lipoprotein (a)—The crossroads of atherosclerosis, atherothrombosis and inflammation. Biomolecules 2021; 12(1): 26.
[http://dx.doi.org/10.3390/biom12010026] [PMID: 35053174]
[14]
Trollope AF, Golledge J. Angiopoietins, abdominal aortic aneurysm and atherosclerosis. Atherosclerosis 2011; 214(2): 237-43.
[http://dx.doi.org/10.1016/j.atherosclerosis.2010.08.051] [PMID: 20832800]
[15]
Deb A, Caplice NM. Lipoprotein (a): New insights into mechanisms of atherogenesis and thrombosis. Clin Cardiol 2004; 27(5): 258-64.
[http://dx.doi.org/10.1002/clc.4960270503] [PMID: 15188938]
[16]
Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. BMJ 2021; 372(71): n71.
[http://dx.doi.org/10.1136/bmj.n71] [PMID: 33782057]
[17]
Wells GA, Shea B, O’Connell D. The Newcastle-Ottawa Scale (NOS) for Assessing the Quality of Nonrandomised Studies in Meta-Analyses. 2000 Available from: https://www.ohri.ca/programs/clinical_epidemiology/oxford.asp
[18]
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(1): 135.
[http://dx.doi.org/10.1186/1471-2288-14-135] [PMID: 25524443]
[19]
Golledge J, Rowbotham S, Velu R, et al. Association of serum Lipoprotein (a) with the requirement for a peripheral artery operation and the incidence of major adverse cardiovascular events in people with peripheral artery disease. J Am Heart Assoc 2020; 9(6): e015355.
[http://dx.doi.org/10.1161/JAHA.119.015355] [PMID: 32172653]
[20]
Petersen E, Wågberg F, Ängquist KA. Does lipoprotein (a) inhibit elastolysis in abdominal aortic aneurysms? Eur J Vasc Endovasc Surg 2003; 26(4): 423-8.
[http://dx.doi.org/10.1016/S1078-5884(03)00178-3] [PMID: 14512007]
[21]
Norrgård O, Angquist KA, Dahlen G. High concentrations of Lp(a) lipoprotein in serum are common among patients with abdominal aortic aneurysms. Int Angiol 1988; 7(1): 46-9.
[PMID: 2968425]
[22]
Schillinger M, Domanovits H, Ignatescu M, et al. Lipoprotein (a) in patients with aortic aneurysmal disease. J Vasc Surg 2002; 36(1): 25-30.
[http://dx.doi.org/10.1067/mva.2002.124371] [PMID: 12096252]
[23]
Larsson SC, Gill D, Mason AM, et al. Lipoprotein (a) in Alzheimer, Atherosclerotic, Cerebrovascular, Thrombotic, and Valvular Disease. Circulation 2020; 141(22): 1826-8.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.120.045826] [PMID: 32479194]
[24]
Papagrigorakis E, Iliopoulos D, Asimacopoulos PJ, et al. Lipoprotein (a) in plasma, arterial wall, and thrombus from patients with aortic aneurysm. Clin Genet 1997; 52(5): 262-71.
[http://dx.doi.org/10.1111/j.1399-0004.1997.tb04343.x] [PMID: 9520116]
[25]
Chou EL, Pettinger M, Haring B, et al. Lipoprotein (a) levels and risk of abdominal aortic aneurysm in the women’s health initiative. J Vasc Surg 2021; 73(4): 1245-1252.e3.
[http://dx.doi.org/10.1016/j.jvs.2020.07.106] [PMID: 32882349]
[26]
Galora S, Saracini C, Palombella AM, et al. Low-density lipoprotein receptor-related protein 5 gene polymorphisms and genetic susceptibility to abdominal aortic aneurysm. J Vasc Surg 2013; 58(4): 1062-1068.e1.
[http://dx.doi.org/10.1016/j.jvs.2012.11.092] [PMID: 23490293]
[27]
Jones GT, van Rij AM, Cole J, et al. Plasma lipoprotein (a) indicates risk for 4 distinct forms of vascular disease. Clin Chem 2007; 53(4): 679-85.
[http://dx.doi.org/10.1373/clinchem.2006.079947] [PMID: 17303687]
[28]
Franks PJ, Edwards RJ, Greenhalgh RM, Powell JT. Risk factors for abdominal aortic aneurysms in smokers. Eur J Vasc Endovasc Surg 1996; 11(4): 487-92.
[http://dx.doi.org/10.1016/S1078-5884(96)80186-9] [PMID: 8846187]
[29]
Simoni G, Gianotti A, Ardia A, Baiardi A, Galleano R, Civalleri D. Screening study of abdominal aortic aneurysm in a general population: lipid parameters. Cardiovasc Surg 1996; 4(4): 445-8.
[http://dx.doi.org/10.1016/0967-2109(95)00140-9] [PMID: 8866078]
[30]
Vega de Céniga M, Esteban M, Quintana JM, et al. Search for serum biomarkers associated with abdominal aortic aneurysm growth-a pilot study. Eur J Vasc Endovasc Surg 2009; 37(3): 297-9.
[http://dx.doi.org/10.1016/j.ejvs.2008.11.014] [PMID: 19111482]
[31]
Watt H, Law MR, Wald NJ, Craig WY, Ledue TB, Haddow JE. Serum triglyceride: A possible risk factor for ruptured abdominal aortic aneurysm. Int J Epidemiol 1998; 27(6): 949-52.
[http://dx.doi.org/10.1093/ije/27.6.949] [PMID: 10024187]
[32]
Lindholt JS, Heegaard NHH, Vammen S, Fasting H, Henneberg EW, Heickendorff L. Smoking, but not lipids, lipoprotein (a) and antibodies against oxidised LDL, is correlated to the expansion of abdominal aortic aneurysms. Eur J Vasc Endovasc Surg 2001; 21(1): 51-6.
[http://dx.doi.org/10.1053/ejvs.2000.1262] [PMID: 11170878]
[33]
Craig WY, Kloza EM, Haddow JE, Hitchcock JL, Eldrup-Jorgensen J. Lipoprotein (a) levels in peripheral atherosclerotic disease. J Vasc Surg 1995; 21(3): 541-2.
[http://dx.doi.org/10.1016/S0741-5214(95)70302-0] [PMID: 7877242]
[34]
Tsimikas S. A test in context: Lipoprotein (a). J Am Coll Cardiol 2017; 69(6): 692-711.
[http://dx.doi.org/10.1016/j.jacc.2016.11.042] [PMID: 28183512]
[35]
Enkhmaa B, Anuurad E, Berglund L. Lipoprotein (a): Impact by ethnicity and environmental and medical conditions. J Lipid Res 2016; 57(7): 1111-25.
[http://dx.doi.org/10.1194/jlr.R051904] [PMID: 26637279]
[36]
Matthews KA, Sowers MF, Derby CA, et al. Ethnic differences in cardiovascular risk factor burden among middle-aged women: Study of women’s health across the nation (SWAN). Am Heart J 2005; 149(6): 1066-73.
[http://dx.doi.org/10.1016/j.ahj.2004.08.027] [PMID: 15976790]
[37]
Thanassoulis G, Campbell CY, Owens DS, et al. Genetic associations with valvular calcification and aortic stenosis. N Engl J Med 2013; 368(6): 503-12.
[http://dx.doi.org/10.1056/NEJMoa1109034] [PMID: 23388002]
[38]
Kamstrup PR, Nordestgaard BG. Elevated Lipoprotein (a) levels, LPA risk genotypes, and increased risk of heart failure in the general population. JACC Heart Fail 2016; 4(1): 78-87.
[http://dx.doi.org/10.1016/j.jchf.2015.08.006] [PMID: 26656145]
[39]
Arsenault BJ, Boekholdt SM, Dubé MP, et al. Lipoprotein (a) levels, genotype, and incident aortic valve stenosis: A prospective Mendelian randomization study and replication in a case-control cohort. Circ Cardiovasc Genet 2014; 7(3): 304-10.
[http://dx.doi.org/10.1161/CIRCGENETICS.113.000400] [PMID: 24704946]
[40]
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): 1311-20.
[http://dx.doi.org/10.1016/S0140-6736(18)31652-0] [PMID: 30293769]
[41]
Tsimikas S, Duff GW, Berger PB, et al. Pro-inflammatory interleukin-1 genotypes potentiate the risk of coronary artery disease and cardiovascular events mediated by oxidized phospholipids and lipoprotein (a). J Am Coll Cardiol 2014; 63(17): 1724-34.
[http://dx.doi.org/10.1016/j.jacc.2013.12.030] [PMID: 24530664]
[42]
Alexandrou AT, Tsimikas S. Elevated Lp(a) and abdominal aortic aneurysm. Angiology 2017; 68(2): 96-8.
[http://dx.doi.org/10.1177/0003319716650960] [PMID: 27207842]
[43]
Graham MJ, Viney N, Crooke RM, Tsimikas S. Antisense inhibition of apolipoprotein (a) to lower plasma lipoprotein (a) levels in humans. J Lipid Res 2016; 57(3): 340-51.
[http://dx.doi.org/10.1194/jlr.R052258] [PMID: 26538546]
[44]
Khera AV, Everett BM, Caulfield MP, et al. Lipoprotein (a) concentrations, rosuvastatin therapy, and residual vascular risk: an analysis from the JUPITER trial (justification for the Use of statins in prevention: An intervention trial evaluating rosuvastatin). Circulation 2014; 129(6): 635-42.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.113.004406] [PMID: 24243886]
[45]
Fraley AE, Schwartz GG, Olsson AG, et al. Relationship of oxidized phospholipids and biomarkers of oxidized low-density lipoprotein with cardiovascular risk factors, inflammatory biomarkers, and effect of statin therapy in patients with acute coronary syndromes: Results from the MIRACL (myocardial ischemia reduction with aggressive cholesterol lowering) trial. J Am Coll Cardiol 2009; 53(23): 2186-96.
[http://dx.doi.org/10.1016/j.jacc.2009.02.041] [PMID: 19497447]
[46]
van Capelleveen JC, van der Valk FM, Stroes EG. Current therapies for lowering lipoprotein (a). J Lipid Res 2016; 57(9): 1612-8.
[http://dx.doi.org/10.1194/jlr.R053066] [PMID: 26637277]
[47]
Legg JS, Legg LM. Abdominal aortic aneurysms. Radiol Technol 2016; 88(2): 145-63.
[PMID: 27837125]
[48]
Cegla J, France M, Marcovina SM, Neely RDG. Lp(a): When and how to measure it. Ann Clin Biochem 2021; 58(1): 16-21.
[http://dx.doi.org/10.1177/0004563220968473] [PMID: 33040574]
[49]
Scharnagl H, Stojakovic T, Dieplinger B, et al. Comparison of lipoprotein (a) serum concentrations measured by six commercially available immunoassays. Atherosclerosis 2019; 289: 206-13.
[http://dx.doi.org/10.1016/j.atherosclerosis.2019.08.015] [PMID: 31493849]
[50]
Marcovina SM, Navabi N, Allen S, Gonen A, Witztum JL, Tsimikas S. Development and validation of an isoform-independent monoclonal antibody–based ELISA for measurement of lipoprotein(a). J Lipid Res 2022; 63(8): 100239.
[http://dx.doi.org/10.1016/j.jlr.2022.100239] [PMID: 35688187]
[51]
Kronenberg F. Lipoprotein (a) measurement issues: Are we making a mountain out of a molehill? Atherosclerosis 2022; 349: 123-35.
[http://dx.doi.org/10.1016/j.atherosclerosis.2022.04.008] [PMID: 35606072]
[52]
Takeshima N, Sozu T, Tajika A, Ogawa Y, Hayasaka Y, Furukawa TA. Which is more generalizable, powerful and interpretable in meta-analyses, mean difference or standardized mean difference? BMC Med Res Methodol 2014; 14(1): 30.
[http://dx.doi.org/10.1186/1471-2288-14-30] [PMID: 24559167]

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