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Predictive value of lipoprotein(a) for assessing the prevalence and severity of lower-extremity peripheral artery disease among patients with acute coronary syndrome

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Abstract

Lipoprotein(a) [Lp(a)] is a reliable lipid marker for atherosclerosis. However, the clinical relevance of Lp(a) to lower-extremity peripheral artery disease (LE-PAD) and coronary artery disease (CAD) in the same patient has not been investigated. Patients who received primary percutaneous coronary intervention for the acute coronary syndrome (ACS) were enrolled. Patients who received hemodialysis, required multidisciplinary treatments, or had incomplete medical history were excluded. A total of 175 patients were divided into two groups according to whether they had LE-PAD (n = 21) or did not (n = 154), and three multivariable logistic regression models were used to assess if Lp(a) level is associated with LE-PAD prevalence. In addition, serum Lp(a) levels were compared among three groups according to the severity of LE-PAD (none, unilateral, or bilateral) and CAD. Serum Lp(a) levels were significantly higher in patients with LE-PAD than in those without (31.0 mg/dL vs. 13.5 mg/dL, p = 0.002). After adjusting for confounding factors, higher Lp(a) levels were independently associated with the prevalence of LE-PAD in all three models (p < 0.001 for all). With respect to LE-PAD severity, serum Lp(a) levels were significantly higher in the bilateral LE-PAD groups than in the group with no LE-PAD (p = 0.005 for all), whereas Lp(a) was not associated with CAD severity. Though Lp(a) levels are associated with the prevalence and severity of LE-PAD, are not associated with the severity of CAD among patients with ACS.

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References

  1. Kamstrup PR, Tybjaerg-Hansen A, Steffensen R, Nordestgaard BG (2009) Genetically elevated lipoprotein(a) and increased risk of myocardial infarction. JAMA 301:2331–2339

    Article  CAS  Google Scholar 

  2. Kamstrup PR, Benn M, Tybjaerg-Hansen A, Nordestgaard BG (2008) Extreme lipoprotein(a) levels and risk of myocardial infarction in the general population. The Copenhagen city heart study. Circulation 117:176–184

    Article  CAS  Google Scholar 

  3. Clarke R, Peden JF, Hopewell JC, Kyriakou T, Goel A, Heath SC, Parish S, Barlera S, Franzosi MG, Rust S, Bennett D, Silveira A, Malarstig A, Green FR, Lathrop M, Gigante B, Leander K, de Faire U, Seedorf U, Hamsten A, Collins R, Watkins H, Farrall M (2009) Genetic variants associated with Lp(a) lipoprotein level and coronary disease. N Engl J Med 361:2518–2528

    Article  CAS  Google Scholar 

  4. Song P, Seok JM, Kim WS, Lee YT, Kim DK, Kim GM (2011) Increased lipoprotein(a) is associated with polyvascular disease in patients undergoing coronary artery bypass graft. Atherosclerosis 219:285–290

    Article  CAS  Google Scholar 

  5. Gudbjartsson DF, Thorgeirsson G, Sulem P, Helgadottir A, Gylfason A, Saemundsdottir J, Bjornsson E, Norddahl GL, Jonasdottir A, Jonasdottir A, Eggertsson HP, Gretarsdottir S, Thorleifsson G, Indridason OS, Palsson R, Jonasson F, Jonsdottir I, Eyjolfsson GI, Sigurdardottir O, Olafsson I, Danielsen R, Matthiasson SE, Kristmundsdottir S, Halldorsson BV, Hreidarsson AB, Valdimarsson EM, Gudnason T, Benediktsson R, Steinthorsdottir V, Thorsteinsdottir U, Holm H, Stefansson K (2019) Lipoprotein(a) concentration and risks of cardiovascular disease and diabetes. J Am Coll Cardiol 74:2982–2994

    Article  CAS  Google Scholar 

  6. Ooi EM, Ellis KL, Barrett PHR, Watts GF, Hung J, Beilby JP, Thompson PL, Stobie P, McQuillan BM (2018) Lipoprotein(a) and apolipoprotein(a) isoform size: associations with angiographic extent and severity of coronary artery disease, and carotid artery plaque. Atherosclerosis 275:232–238

    Article  CAS  Google Scholar 

  7. Sun D, Zhou BY, Zhao X, Li S, Zhu CG, Guo YL, Gao Y, Wu NQ, Liu G, Dong Q, Li JJ (2018) Lipoprotein(a) level associates with coronary artery disease rather than carotid lesions in patients with familial hypercholesterolemia. J Clin Lab Anal 32:e22442

    Article  Google Scholar 

  8. Adler AI, Stevens RJ, Neil A, Stratton IM, Boulton AJ, Holman RR (2002) UKPDS 59: hyperglycemia and other potentially modifiable risk factors for peripheral vascular disease in type 2 diabetes. Diabetes Care 25:894–899

    Article  Google Scholar 

  9. Mohammedi K, Woodward M, Hirakawa Y, Zoungas S, Williams B, Lisheng L, Rodgers A, Mancia G, Neal B, Harrap S, Marre M, Chalmers J (2016) Microvascular and macrovascular disease and risk for major peripheral arterial disease in patients with type 2 diabetes. Diabetes Care 39:1796–1803

    Article  CAS  Google Scholar 

  10. Althouse AD, Abbott JD, Forker AD, Bertolet M, Barinas-Mitchell E, Thurston RC, Mulukutla S, Aboyans V, Brooks MM (2014) Risk factors for incident peripheral arterial disease in type 2 diabetes: results from the bypass angioplasty revascularization investigation in type 2 diabetes (BARI 2D) Trial. Diabetes Care 37:1346–1352

    Article  CAS  Google Scholar 

  11. Meijer WT, Grobbee DE, Hunink MG, Hofman A, Hoes AW (2000) Determinants of peripheral arterial disease in the elderly: the Rotterdam study. Arch Intern Med 160:2934–2938

    Article  CAS  Google Scholar 

  12. Gerhard-Herman MD, Gornik HL, Barrett C, Barshes NR, Corriere MA, Drachman DE, Fleisher LA, Fowkes FG, Hamburg NM, Kinlay S, Lookstein R, Misra S, Mureebe L, Olin JW, Patel RA, Regensteiner JG, Schanzer A, Shishehbor MH, Stewart KJ, Treat-Jacobson D, Walsh ME (2017) 2016 AHA/ACC guideline on the management of patients with lower extremity peripheral artery disease: a report of the American college of cardiology/american heart association task force on clinical practice guidelines. Circulation 135:e726–e779

    Google Scholar 

  13. Aboyans V, Ricco JB, Bartelink MEL, Bjorck M, Brodmann M, Cohnert T, Collet JP, Czerny M, De Carlo M, Debus S, Espinola-Klein C, Kahan T, Kownator S, Mazzolai L, Naylor AR, Roffi M, Rother J, Sprynger M, Tendera M, Tepe G, Venermo M, Vlachopoulos C, Desormais I (2018) 2017 ESC guidelines on the diagnosis and treatment of peripheral arterial diseases, in collaboration with the European society for vascular surgery (ESVS): document covering atherosclerotic disease of extracranial carotid and vertebral, mesenteric, renal, upper and lower extremity arteries Endorsed by: the European stroke organization (ESO) the task force for the diagnosis and treatment of peripheral arterial diseases of the european society of cardiology (ESC) and of the European society for vascular surgery (ESVS). Eur Heart J 39:763–816

    Article  Google Scholar 

  14. Takahara M, Iida O, Kohsaka S, Soga Y, Fujihara M, Shinke T, Amano T, Ikari Y (2019) Diabetes mellitus and other cardiovascular risk factors in lower-extremity peripheral artery disease versus coronary artery disease: an analysis of 1,121,359 cases from the nationwide databases. Cardiovasc Diabetol 18:155

    Article  Google Scholar 

  15. Steg PG, Bhatt DL, Wilson PW, D’Agostino R Sr, Ohman EM, Röther J, Liau CS, Hirsch AT, Mas JL, Ikeda Y, Pencina MJ, Goto S (2007) One-year cardiovascular event rates in outpatients with atherothrombosis. JAMA 297:1197–1206

    Article  CAS  Google Scholar 

  16. Bonaca MP, Gutierrez JA, Cannon C, Giugliano R, Blazing M, Park JG, White J, Tershakovec A, Braunwald E (2018) Polyvascular disease, type 2 diabetes, and long-term vascular risk: a secondary analysis of the IMPROVE-IT trial. Lancet Diabetes Endocrinol 6:934–943

    Article  Google Scholar 

  17. Cotter G, Cannon CP, McCabe CH, Michowitz Y, Kaluski E, Charlesworth A, Milo O, Bentley J, Blatt A, Krakover R, Zimlichman R, Reisin L, Marmor A, Lewis B, Vered Z, Caspi A, Braunwald E (2003) Prior peripheral arterial disease and cerebrovascular disease are independent predictors of adverse outcome in patients with acute coronary syndromes: are we doing enough? Results from the orbofiban in patients with unstable coronary syndromes-thrombolysis in myocardial infarction (OPUS-TIMI) 16 study. Am Heart J 145:622–627

    Article  CAS  Google Scholar 

  18. Froehlich JB, Mukherjee D, Avezum A, Budaj A, Kline-Rogers EM, López-Sendón J, Allegrone J, Eagle KA, Mehta RH, Goldberg RJ (2006) Association of peripheral artery disease with treatment and outcomes in acute coronary syndromes: the global registry of acute coronary events (GRACE). Am Heart J 151:1123–1128

    Article  Google Scholar 

  19. Kronenberg F, Utermann G, Dieplinger H (1996) Lipoprotein(a) in renal disease. Am J Kidney Dis 27:1–25

    Article  CAS  Google Scholar 

  20. Sianos G, Morel MA, Kappetein AP, Morice MC, Colombo A, Dawkins K, van den Brand M, Van Dyck N, Russell ME, Mohr FW, Serruys PW (2005) The SYNTAX score: an angiographic tool grading the complexity of coronary artery disease. EuroIntervention 1:219–227

    Google Scholar 

  21. Serruys PW, Onuma Y, Garg S, Vranckx P, De Bruyne B, Morice MC, Colombo A, Macaya C, Richardt G, Fajadet J, Hamm C, Schuijer M, Rademaker T, Wittebols K, Stoll HP (2010) 5-year clinical outcomes of the ARTS II (arterial revascularization therapies study II) of the sirolimus-eluting stent in the treatment of patients with multivessel de novo coronary artery lesions. J Am Coll Cardiol 55:1093–1101

    Article  Google Scholar 

  22. Magro M, Nauta S, Simsek C, Onuma Y, Garg S, van der Heide E, van der Giessen WJ, Boersma E, van Domburg RT, van Geuns RJ, Serruys PW (2011) Value of the SYNTAX score in patients treated by primary percutaneous coronary intervention for acute ST-elevation myocardial infarction: the MI SYNTAXscore study. Am Heart J 161:771–781

    Article  Google Scholar 

  23. Matsumoto Y, Daida H, Watanabe Y, Sunayama S, Mokuno H, Yokoi H, Yamaguchi H (1998) High level of lipoprotein(a) is a strong predictor for progression of coronary artery disease. J Atheroscler Thromb 5:47–53

    Article  CAS  Google Scholar 

  24. National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) (2002) 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 106:3143–3421

    Article  Google Scholar 

  25. Erqou S, Kaptoge S, Perry PL, Di Angelantonio E, Thompson A, White IR, Marcovina SM, Collins R, Thompson SG, Danesh J (2009) Lipoprotein(a) concentration and the risk of coronary heart disease, stroke, and nonvascular mortality. JAMA 302:412–423

    Article  CAS  Google Scholar 

  26. Kanda Y (2013) Investigation of the freely available easy-to-use software “EZR” for medical statistics. Bone Marrow Transplant 48:452–458

    Article  CAS  Google Scholar 

  27. Danesh J, Collins R, Peto R (2000) Lipoprotein(a) and coronary heart disease. Meta-analysis of prospective studies. Circulation 102:1082–1085

    Article  CAS  Google Scholar 

  28. Niccoli G, Cin D, Scalone G, Panebianco M, Abbolito S, Cosentino N, Jacoangeli F, Refaat H, Gallo G, Salerno G, Volpe M, Crea F, De Biase L (2016) Lipoprotein (a) is related to coronary atherosclerotic burden and a vulnerable plaque phenotype in angiographically obstructive coronary artery disease. Atherosclerosis 246:214–220

    Article  CAS  Google Scholar 

  29. Cheng SW, Ting AC, Wong J (1997) Lipoprotein (a) and its relationship to risk factors and severity of atherosclerotic peripheral vascular disease. Eur J Vasc Endovasc Surg 14:17–23

    Article  CAS  Google Scholar 

  30. Kim BS, Jung HS, Bang OY, Chung CS, Lee KH, Kim GM (2010) Elevated serum lipoprotein(a) as a potential predictor for combined intracranial and extracranial artery stenosis in patients with ischemic stroke. Atherosclerosis 212:682–688

    Article  CAS  Google Scholar 

  31. Yanaka K, Akahori H, Imanaka T, Miki K, Yoshihara N, Kimura T, Tanaka T, Asakura M, Ishihara M (2021) Relationship between lipoprotein(a) and angiographic severity of femoropopliteal lesions. J Atheroscler Thromb 28:555–561

    Article  CAS  Google Scholar 

  32. Dieter RS, Tomasson J, Gudjonsson T, Brown RL, Vitcenda M, Einerson J, McBride PE (2003) Lower extremity peripheral arterial disease in hospitalized patients with coronary artery disease. Vasc Med 8:233–236

    Article  Google Scholar 

  33. Saleh A, Makhamreh H, Qoussoos T, Alawwa I, Alsmady M, Salah ZA, Shakhatreh A, Alhazaymeh L, Jabber M (2018) Prevalence of previously unrecognized peripheral arterial disease in patients undergoing coronary angiography. Medicine (Baltimore) 97:e11519

    Article  Google Scholar 

  34. Mach F, Baigent C, Catapano AL, Koskinas KC, Casula M, Badimon L, Chapman MJ, De Backer GG, Delgado V, Ference BA, Graham IM, Halliday A, Landmesser U, Mihaylova B, Pedersen TR, Riccardi G, Richter DJ, Sabatine MS, Taskinen MR, Tokgozoglu L, Wiklund O (2020) 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J 41:111–188

    Article  Google Scholar 

  35. Torii S, Mustapha JA, Narula J, Mori H, Saab F, Jinnouchi H, Yahagi K, Sakamoto A, Romero ME, Narula N, Kolodgie FD, Virmani R, Finn AV (2019) Histopathologic characterization of peripheral arteries in subjects with abundant risk factors: correlating imaging with pathology. JACC Cardiovasc Imaging 12:1501–1513

    Article  Google Scholar 

  36. Tsimikas S (2017) A test in context: lipoprotein(a): diagnosis, prognosis, controversies, and emerging therapies. J Am Coll Cardiol 69:692–711

    Article  CAS  Google Scholar 

  37. Virmani R, Kolodgie FD, Burke AP, Farb A, Schwartz SM (2000) Lessons from sudden coronary death: a comprehensive morphological classification scheme for atherosclerotic lesions. Arterioscler Thromb Vasc Biol 20:1262–1275

    Article  CAS  Google Scholar 

  38. Wickström JE, Virtanen J, Aro E, Jalkanen J, Venermo M, Hakovirta H (2019) Bilateral low systolic toe pressure and toe-brachial index are associated with long-term mortality in patients with peripheral artery disease. J Vasc Surg 70:1994–2004

    Article  Google Scholar 

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Acknowledgements

The authors thank Mis. Satomi Sakaguchi, Mr. Tatsuki Tamai, Mr. Mikio Minekawa and Mr. Masahiro Tanaka for data collecting.

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  1. Department of Cardiovascular Medicine, Department of Internal Medicine, Faculty of Medicine, Toho University, 6-11-1 Omori-nishi Ota-ku, Tokyo, 143-8541, Japan

    Ryo Okubo, Rine Nakanishi, Yousuke Oka, Yoshimasa Kojima, Shingo Matsumoto, Hiroto Aikawa, Ryota Noike, Takayuki Yabe, Hideo Amano, Mikihito Toda & Takanori Ikeda

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Correspondence to Ryo Okubo.

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Dr. Ikeda received a research donation from Daiichi Sankyo and received remuneration from Bayer Yakuhin and Ono Pharmaceutical. The remaining authors have no relationships to disclose that are relevant to the contents of this paper.

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Okubo, R., Nakanishi, R., Oka, Y. et al. Predictive value of lipoprotein(a) for assessing the prevalence and severity of lower-extremity peripheral artery disease among patients with acute coronary syndrome. Heart Vessels 38, 177–184 (2023). https://doi.org/10.1007/s00380-022-02163-3

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