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Very low lipoprotein(a) and increased mortality risk after myocardial infarction

      Highlights

      • Both high and very low concentrations of Lp(a) are associated with an increased risk of total mortality and recurrent cardiovascular events after myocardial infarction type I.
      • The excess of mortality associated with Lp(a) is partially attributable to more prevalent heart failure.

      Abstract

      Background

      Inconclusive data exist on risk associated with Lp(a) in patients after myocardial infarction (MI). Aims of the present study were to evaluate the association of Lp(a) level with total mortality and recurrent cardiovascular events.

      Design and methods

      Single center prospective registry of consecutive patients hospitalized for acute myocardial infarction between June 2017 and June 2020 at a large tertiary cardiac center with available blood samples drawn <24h of admission.

      Results

      Data from 851 consecutive patients hospitalized for MI were evaluated. During the median follow-up of 19 months (interquartile range 10–27), 58 (6.8%) patients died. Nonlinear modelling revealed a U-shaped association between Lp(a) and total mortality risk. Compared to patients with Lp(a) ranging between 10-30 nmol/L and after multivariate adjustment, total mortality risk was increased both in patients with Lp(a)<7 nmol/L (hazard ratio (HR) 4.08, 95% confidence interval (CI) 1.72–9.68) and Lp(a) ≥125 nmol/L (HR 2.92, 95% CI 1.16–7.37), respectively. Similarly, the risk of combined endpoint of acute coronary syndrome recurrence or cardiovascular mortality was increased both in patients with low (sub-HR 2.60, 95% CI 1.33–5.08) and high (sub-HR 2.10, 95% CI 1.00–4.39) Lp(a). Adjustment for heart failure signs at the time of hospitalization weakened the association with total mortality and recurrent cardiovascular events.

      Conclusions

      In the present analysis, both high and low concentrations of Lp(a) were associated with an increased risk of total mortality and recurrent cardiovascular events after MI. The excess of mortality associated with Lp(a) was partially attributable to more prevalent heart failure.

      Graphical abstract

      Keywords

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      References

        • Erqou S
        • Kaptoge S
        • Perry PL
        • Di Angelantonio E
        • Thompson A
        • White IR
        • et al.
        Lipoprotein(a) concentration and the risk of coronary heart disease, stroke, and nonvascular mortality.
        Jama. 2009; 302: 412-423
        • Kamstrup PR
        • Tybjærg-Hansen A
        • Nordestgaard BG.
        Extreme lipoprotein(a) levels and improved cardiovascular risk prediction.
        J Am Coll Cardiol. 2013; 61: 1146-1156
        • Clarke R
        • Peden JF
        • Hopewell JC
        • Kyriakou T
        • Goel A
        • Heath SC
        • et al.
        Genetic variants associated with Lp(a) lipoprotein level and coronary disease.
        N Engl J Med. 2009; 361: 2518-2528
        • Mach F
        • Baigent C
        • Catapano AL
        • Koskinas KC
        • Casula M
        • Badimon L
        • et al.
        2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk: the task force for the management of dyslipidaemias of the European society of cardiology (ESC) and European atherosclerosis society (EAS).
        European Heart J. 2019; 41: 111-188
      1. Arnett DK, Blumenthal RS, Albert MA, Buroker AB, Goldberger ZD, Hahn EJ, et al. 2019 ACC/AHA guideline on the primary prevention of cardiovascular disease. A report of the American college of cardiology/American Heart Association Task Force on Clinical Practice Guidelines. 2019;74:e177-e232.

        • Schwartz GG
        • Ballantyne CM
        • Barter PJ
        • Kallend D
        • Leiter LA
        • Leitersdorf E
        • et al.
        Association of lipoprotein(a) with risk of recurrent ischemic events following acute coronary syndrome: analysis of the dal-outcomes randomized clinical trial.
        JAMA Cardiol. 2018; 3: 164-168
        • Zewinger S
        • Kleber ME
        • Tragante V
        • McCubrey RO
        • Schmidt AF
        • Direk K
        • et al.
        Relations between lipoprotein(a) concentrations, LPA genetic variants, and the risk of mortality in patients with established coronary heart disease: a molecular and genetic association study.
        Lancet Diabetes Endocrinol. 2017; 5: 534-543
        • Puri R
        • Ballantyne CM
        • Hoogeveen RC
        • Shao M
        • Barter P
        • Libby P
        • et al.
        Lipoprotein(a) and coronary atheroma progression rates during long-term high-intensity statin therapy: Insights from SATURN.
        Atherosclerosis. 2017; 263: 137-144
        • Madsen CM
        • Kamstrup PR
        • Langsted A
        • Varbo A
        • Nordestgaard BG.
        Lipoprotein(a)-lowering by 50 mg/dl (105 nmol/l) may be needed to reduce cardiovascular disease 20% in secondary prevention.
        Arteriosclerosis Thrombosis Vasc Biol. 2020; 40: 255-266
        • Albers JJ
        • Slee A
        • O'Brien KD
        • Robinson JG
        • Kashyap ML
        • Kwiterovich PO
        • et al.
        Relationship of apolipoproteins A-1 and B, and lipoprotein(a) to cardiovascular outcomes: the AIM-HIGH trial (atherothrombosis intervention in metabolic syndrome with low HDL/high triglyceride and impact on global health outcomes).
        J Am Coll Cardiol. 2013; 62: 1575-1579
        • Berg K
        • Dahlén G
        • Christophersen B
        • Cook T
        • Kjekshus J
        • Pedersen T.
        Lp(a) lipoprotein level predicts survival and major coronary events in the scandinavian simvastatin survival study.
        Clin Genet. 1997; 52: 254-261
        • Marcovina SM
        • Koschinsky ML
        • Albers JJ
        • Skarlatos S.
        Report of the national heart, lung, and blood institute workshop on lipoprotein(a) and cardiovascular disease: recent advances and future directions.
        Clin Chem. 2003; 49: 1785-1796
        • Boffa MB
        • Koschinsky ML.
        Lipoprotein(a): truly a direct prothrombotic factor in cardiovascular disease?.
        J Lipid Res. 2016; 57: 745-757
        • Moliterno DJ
        • Lange RA
        • Meidell RS
        • Willard JE
        • Leffert CC
        • Gerard RD
        • et al.
        Relation of plasma lipoprotein(a) to infarct artery patency in survivors of myocardial infarction.
        Circulation. 1993; 88: 935-940
        • Matsuda S
        • Arima M
        • Ohigawa T
        • Tanimoto K
        • Takagi A
        • Kanoh T
        • et al.
        Relation between serum lipoprotein(a) and residual lesion stenosis of coronary artery after myocardial Infarction without reperfusion therapy.
        Jpn Heart J. 2004; 45: 397-407
        • Kim JW
        • Seo HS
        • Suh SY
        • Choi CU
        • Kim EJ
        • Rha SW
        • et al.
        Relationship between lipoprotein(a) and spontaneous recanalization of infarct-related arteries in the early phase of acute myocardial infarction.
        Clin Cardiol. 2008; 31: 211-216
        • Haider AW
        • Andreotti F
        • Thompson GR
        • Kluft C
        • Maseri A
        • Davies GJ.
        Serum lipoprotein(a) level is related to thrombin generation and spontaneous intermittent coronary occlusion in patients with acute myocardial infarction.
        Circulation. 1996; 94: 2072-2076
        • Nordestgaard BG
        • Chapman MJ
        • Ray K
        • Borén J
        • Andreotti F
        • Watts GF
        • et al.
        Lipoprotein(a) as a cardiovascular risk factor: current status.
        European Heart Journal. 2010; 31: 2844-2853
        • Ibanez B
        • James S
        • Agewall S
        • Antunes MJ
        • Bucciarelli-Ducci C
        • Bueno H
        • et al.
        2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: the task force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European society of cardiology (ESC).
        European Heart J. 2017; 39: 119-177
        • Nordestgaard B
        • Langsted A.
        Lipoprotein(a) as a cause of cardiovascular disease: insights from epidemiology, genetics, and biology.
        J Lipid Res. 2016; 57: 1953-1975
        • von Zychlinski A
        • Kleffmann T
        • Williams MJ
        • McCormick SP.
        Proteomics of Lipoprotein(a) identifies a protein complement associated with response to wounding.
        J Proteomics. 2011; 74: 2881-2891
        • Lippi G
        • Guidi G.
        Lipoprotein(a): from ancestral benefit to modern pathogen?.
        QJM. 2000; 93: 75-84
        • Singh M
        • Berger PB
        • Ting HH
        • Rihal CS
        • Wilson SH
        • Lennon RJ
        • et al.
        Influence of coronary thrombus on outcome of percutaneous coronary angioplasty in the current era (the Mayo Clinic experience).
        Am J Cardiol. 2001; 88: 1091-1096
        • White CJ
        • Ramee SR
        • Collins TJ
        • Escobar AE
        • Karsan A
        • Shaw D
        • et al.
        Coronary thrombi increase PTCA risk..
        Circulation. 1996; 93: 253-258
        • Sianos G
        • Papafaklis MI
        • Daemen J
        • Vaina S
        • van Mieghem CA
        • van Domburg RT
        • et al.
        Angiographic stent thrombosis after routine use of drug-eluting stents in ST-segment elevation myocardial infarction: the importance of thrombus burden.
        J Am College Cardiol. 2007; 50: 573-583
        • Fokkema ML
        • Vlaar PJ
        • Svilaas T
        • Vogelzang M
        • Amo D
        • Diercks GFH
        • et al.
        Incidence and clinical consequences of distal embolization on the coronary angiogram after percutaneous coronary intervention for ST-elevation myocardial infarction.
        European Heart J. 2009; 30: 908-915
        • Napodano M
        • Ramondo A
        • Tarantini G
        • Peluso D
        • Compagno S
        • Fraccaro C
        • et al.
        Predictors and time-related impact of distal embolization during primary angioplasty.
        European Heart J. 2009; 30: 305-313
        • Riches K
        • Porter KE.
        Lipoprotein(a): cellular effects and molecular mechanisms.
        Cholesterol. 2012; 2012923289
        • Mao SJT
        • Tucci MA.
        Lipoprotein(a) enhances plasma clot lysis in vitro.
        FEBS Letters. 1990; 267: 131-134
        • Gries A
        • Gries M
        • Wurm H
        • Kenner T
        • Ijsseldijk M
        • Sixma JJ
        • et al.
        Lipoprotein(a) inhibits collagen-induced aggregation of thrombocytes.
        Arteriosclerosis Thrombosis Vasc Biol. 1996; 16: 648-655
        • Barre DE.
        Apoprotein antagonises THE GPIIB/IIIA receptor on collagen and ADP-stimulated human platelets.
        Front Biosci. 2004; 9: 404-410
        • Tsironis LD
        • Mitsios JV
        • Milionis HJ
        • Elisaf M
        • Tselepis AD.
        Effect of lipoprotein(a) on platelet activation induced by platelet-activating factor: role of apolipoprotein(a) and endogenous PAF-acetylhydrolase.
        Cardiovasc Res. 2004; 63: 130-138
        • Andreotti F
        • Becker RC.
        Atherothrombotic disorders.
        Circulation. 2005; 111: 1855-1863
        • Steffen BT
        • Thanassoulis G
        • Duprez D
        • Stein JH
        • Karger AB
        • Tattersall MC
        • et al.
        Race-based differences in lipoprotein(a)-associated risk of carotid atherosclerosis.
        Arteriosclerosis, Thrombosis, and Vascular Biology. 2019; 39: 523-529
        • Paré G
        • Çaku A
        • McQueen M
        • Anand SS
        • Enas E
        • Clarke R
        • et al.
        Lipoprotein(a) levels and the risk of myocardial infarction among 7 ethnic groups.
        Circulation. 2019; 139: 1472-1482
        • Virani SS
        • Brautbar A
        • Davis BC
        • Nambi V
        • Hoogeveen RC
        • Sharrett AR
        • et al.
        Associations between lipoprotein(a) levels and cardiovascular outcomes in black and white subjects.
        Circulation. 2012; 125: 241-249
        • Tsimikas S.
        A Test in context: lipoprotein(a): diagnosis, prognosis, controversies, and emerging therapies.
        J Am College Cardiol. 2017; 69: 692-711
        • Tsimikas S
        • Fazio S
        • Ferdinand KC
        • Ginsberg HN
        • Koschinsky ML
        • Marcovina SM
        • et al.
        NHLBI working group recommendations to reduce lipoprotein(a)-mediated risk of cardiovascular disease and aortic stenosis.
        J Am College Cardiol. 2018; 71: 177-192