The dedicated “Lp(a) clinic”: A concept whose time has arrived?

  • Sotirios Tsimikas
    Corresponding author. Sulpizio Cardiovascular Center, University of California San Diego, 9500 Gilman Drive, BSB 1080, La Jolla, CA, 92093-0682, USA.
    Vascular Medicine Program, Sulpizio Cardiovascular Center, Division of Cardiology, Department of Medicine, University of California San Diego, La Jolla, CA, USA

    Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands
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  • Erik S.G. Stroes
    Vascular Medicine Program, Sulpizio Cardiovascular Center, Division of Cardiology, Department of Medicine, University of California San Diego, La Jolla, CA, USA

    Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands
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      • Lp(a) is a causal risk factor for cardiovascular disease (CVD) and calcific aortic valve disease.
      • Novel Lp(a) lowering approaches have re-invigorated clinical interest in Lp(a).
      • Elevated Lp(a) (>50 mg/dL) is estimated to be present in >1.4 billion people.
      • Patients with elevated Lp(a) are significantly under-diagnosed.
      • A rationale of an outpatient “Lp(a) clinic” is presented.


      The emergence of pathophysiological, epidemiologic, and genetic data strongly supports the causality for lipoprotein(a) [Lp(a)] in cardiovascular disease (CVD) and calcific aortic valve disease (CAVD). In parallel, novel Lp(a) lowering approaches have been developed that have re-invigorated clinical interest in Lp(a). Because Lp(a) is the most prevalent monogenetic lipid disorder globally, with prevalence of Lp(a) > 50 mg/dL estimated at >1.4 billion people, the rationale for diagnosing and managing Lp(a)-mediated risk is now stronger than ever. Patients with elevated Lp(a) are significantly under-diagnosed and the diagnosis is frequently made ad hoc rather than systematically. Elevated Lp(a) levels are associated with atherothrombotic risk and patients present with varied clinical phenotypes, ranging from stroke in pediatric age groups, to ST-segment elevation myocardial infarction in young males, to CAVD in elderly individuals. A new clinical care paradigm of a dedicated “Lp(a) Clinic” would serve to evaluate and manage such patients who have elevated Lp(a) as the pathophysiological etiology. Such a clinic would include multidisciplinary expertise in lipid metabolism, clinical cardiology, vascular medicine, valvular disease, thrombosis, and pediatric aspects of clinical care. This viewpoint argues for the rationale of an Lp(a) outpatient clinic where patients with elevated Lp(a) and their affected relatives can be referred, evaluated, managed and followed, to ultimately reduce Lp(a)-mediated CVD and CAVD risk.


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        • Gibbons R.J.
        Get with the guidelines: a new chapter?.
        Circulation. 2010; 121: 194-196
        • Tsimikas S.
        A test in context: lipoprotein(a): diagnosis, prognosis, controversies, and emerging therapies.
        J. Am. Coll. Cardiol. 2017; 69: 692-711
        • Erqou S.
        • Kaptoge S.
        • Perry P.L.
        • et al.
        Emerging Risk Factors Collaboration. Lipoprotein(a) concentration and the risk of coronary heart disease, stroke, and nonvascular mortality.
        J. Am. Med. Assoc. 2009; 302: 412-423
        • Kamstrup P.R.
        • Benn M.
        • Tybjaerg-Hansen A.
        • et al.
        Extreme lipoprotein(a) levels and risk of myocardial infarction in the general population: the Copenhagen City Heart Study.
        Circulation. 2008; 117: 176-184
        • Willeit P.
        • Ridker P.M.
        • Nestel P.J.
        • 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: 1311-1320
        • O'Donoghue M.L.
        • Fazio S.
        • Giugliano R.P.
        • et al.
        Lipoprotein(a), PCSK9 inhibition, and cardiovascular risk.
        Circulation. 2019; 139: 1483-1492
        • Bittner V.A.
        • Szarek M.
        • Aylward P.E.
        • et al.
        Effect of alirocumab on lipoprotein(a) and cardiovascular risk after acute coronary syndrome.
        J. Am. Coll. Cardiol. 2020; 75: 133-144
        • Jaeger B.R.
        • Richter Y.
        • Nagel D.
        • et al.
        Longitudinal cohort study on the effectiveness of lipid apheresis treatment to reduce high lipoprotein(a) levels and prevent major adverse coronary events.
        Nat. Clin. Pract. Cardiovasc. Med. 2009; 6: 229-239
        • Leebmann J.
        • Roeseler E.
        • Julius U.
        • et al.
        Lipoprotein apheresis in patients with maximally tolerated lipid-lowering therapy, lipoprotein(a)-hyperlipoproteinemia, and progressive cardiovascular disease: prospective observational multicenter study.
        Circulation. 2013; 128: 2567-2576
        • Roeseler E.
        • Julius U.
        • Heigl F.
        • et al.
        Lipoprotein apheresis for lipoprotein(a)-associated cardiovascular disease: prospective 5 Years of follow-up and apolipoprotein(a) characterization.
        Arterioscler. Thromb. Vasc. Biol. 2016; 36: 2019-2027
        • Moriarty P.M.
        • Gray J.V.
        • Gorby L.K.
        Lipoprotein apheresis for lipoprotein(a) and cardiovascular disease.
        J. Clin. Lipidol. 2019; 13: 894-900
        • Hohenstein B.
        • Julius U.
        • Lansberg P.
        • et al.
        Rationale and design of MultiSELECt: a European multicenter study on the effect of lipoprotein(a) elimination by lipoprotein apheresis on cardiovascular outcomes.
        Atherosclerosis Suppl. 2017; 30: 180-186
        • Tsimikas S.
        • Viney N.J.
        • Hughes S.G.
        • et al.
        Antisense therapy targeting apolipoprotein(a): a randomised, double-blind, placebo-controlled phase 1 study.
        Lancet. 2015; 386: 1472-1483
        • Viney N.J.
        • van Capelleveen J.C.
        • Geary R.S.
        • et al.
        Antisense oligonucleotides targeting apolipoprotein(a) in people with raised lipoprotein(a): two randomised, double-blind, placebo-controlled, dose-ranging trials.
        Lancet. 2016; 388: 2239-2253
        • Tsimikas S.
        • Karwatowska-Prokopczuk E.
        • Gouni-Berthold I.
        • et al.
        Lipoprotein(a) reduction in persons with cardiovascular disease.
        N. Engl. J. Med. 2020; 382: 244-255
        • Tsimikas S.
        • Fazio S.
        • Ferdinand K.C.
        • et al.
        NHLBI Working Group recommendations to reduce lipoprotein(a)-mediated risk of cardiovascular disease and aortic stenosis.
        J. Am. Coll. Cardiol. 2018; 71: 177-192
        • Ellis K.L.
        • Perez de Isla L.
        • Alonso R.
        • et al.
        Value of measuring lipoprotein(a) during cascade testing for familial hypercholesterolemia.
        J. Am. Coll. Cardiol. 2019; 73: 1029-1039
        • Tsimikas S.
        • Gordts P.
        • Nora C.
        • et al.
        Statin therapy increases lipoprotein(a) levels.
        Eur. Heart J. 2019;
        • Viney N.J.
        • Yeang C.
        • Yang X.
        • et al.
        Relationship between "LDL-C", estimated true LDL-C, apolipoprotein B-100, and PCSK9 levels following lipoprotein(a) lowering with an antisense oligonucleotide.
        J. Clin. Lipidol. 2018; 12: 702-710
        • Kostner G.M.
        • Avogaro P.
        • Cazzolato G.
        • et al.
        Lipoprotein Lp(a) and the risk for myocardial infarction.
        Atherosclerosis. 1981; 38: 51-61
        • Varvel S.
        • McConnell J.P.
        • Tsimikas S.
        Prevalence of elevated Lp(a) mass levels and patient thresholds in 532 359 Patients in the United States.
        Arterioscler. Thromb. Vasc. Biol. 2016; 36: 2239-2245
        • Mach F.
        • Baigent C.
        • Catapano A.L.
        • et al.
        ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk.
        Eur. Heart J. 2020; 41 (2019): 111-188
        • Afshar M.
        • Pilote L.
        • Dufresne L.
        • et al.
        Lipoprotein(a) interactions with low-density lipoprotein cholesterol and other cardiovascular risk factors in premature acute coronary syndrome (ACS).
        J. .Am. Heart Asso. 2016; 5e003012
        • Chieng D.
        • Pang J.
        • Ellis K.L.
        • et al.
        Elevated lipoprotein(a) and low-density lipoprotein cholesterol as predictors of the severity and complexity of angiographic lesions in patients with premature coronary artery disease.
        J. Clin. Lipidol. 2018; 12: 1019-1026
        • Weiss M.C.
        • Berger J.S.
        • Gianos E.
        • et al.
        Lipoprotein(a) screening in patients with controlled traditional risk factors undergoing percutaneous coronary intervention.
        J. Clin. Lipidol. 2017; 11: 1177-1180
        • Wilkinson M.J.
        • Ma G.S.
        • Yeang C.
        • et al.
        The prevalence of lipoprotein(a) measurement and degree of elevation among 2710 patients with calcific aortic valve stenosis in an academic echocardiography laboratory setting.
        Angiology. 2017; 68: 795-798
        • Ridker P.M.
        • Hennekens C.H.
        • Stampfer M.J.
        A prospective study of lipoprotein(a) and the risk of myocardial infarction.
        J. Am. Med. Assoc. 1993; 270: 2195-2199
        • Rifai N.
        • Ma J.
        • Sacks F.M.
        • et al.
        Apolipoprotein(a) size and lipoprotein(a) concentration and future risk of angina pectoris with evidence of severe coronary atherosclerosis in men: the Physicians' Health Study.
        Clin. Chem. 2004; 50: 1364-1371
        • Goldstein J.L.
        • Brown M.S.
        The LDL receptor locus and the genetics of familial hypercholesterolemia.
        Annu. Rev. Genet. 1979; 13: 259-289
        • Yeang C.
        • Witztum J.L.
        • Tsimikas S.
        'LDL-C' = LDL-C + Lp(a)-C: implications of achieved ultra-low LDL-C levels in the proprotein convertase subtilisin/kexin type 9 era of potent LDL-C lowering.
        Curr. Opin. Lipidol. 2015; 26: 169-178
        • Giugliano R.P.
        • Pedersen T.R.
        • Park J.G.
        • et al.
        Clinical efficacy and safety of achieving very low LDL-cholesterol concentrations with the PCSK9 inhibitor evolocumab: a prespecified secondary analysis of the FOURIER trial.
        Lancet. 2017; 390: 1962-1971
        • Stefanutti C.
        • Julius U.
        • Watts G.F.
        • et al.
        Toward an international consensus-Integrating lipoprotein apheresis and new lipid-lowering drugs.
        J. Clin. Lipidol. 2017; 11: 858-871 e853
        • Grundy S.M.
        • Stone N.J.
        • Bailey A.L.
        • et al.
        AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: executive summary: a report of the American College of cardiology/American heart association Task Force on clinical practice guidelines.
        J. Am. Coll. Cardiol. 2018; 73 (2019): 3168-3209
        • Anderson T.J.
        • Gregoire J.
        • Pearson G.J.
        • et al.
        Canadian Cardiovascular Society guidelines for the management of dyslipidemia for the prevention of cardiovascular disease in the adult.
        Can. J. Cardiol. 2016; 32 (2016): 1263-1282
        • Cegla J.
        • Neely R.D.G.
        • France M.
        • et al.
        HEART UK consensus statement on Lipoprotein(a): a call to action.
        Atherosclerosis. 2019; 291: 62-70
        • Catapano A.L.
        • Graham I.
        • De Backer G.
        • et al.
        ESC/EAS guidelines for the management of dyslipidaemias.
        Eur. Heart J. 2016; 37 (2016): 2999-3058
        • Lee S.R.
        • Prasad A.
        • Choi Y.S.
        • et al.
        LPA gene, ethnicity, and cardiovascular events.
        Circulation. 2017; 135: 251-263
        • Cai D.P.
        • He Y.M.
        • Yang X.J.
        • et al.
        Lipoprotein (a) is a risk factor for coronary artery disease in Chinese Han ethnic population modified by some traditional risk factors: a cross-sectional study of 3462 cases and 6125 controls.
        Clin. Chim. Acta. 2015; 451: 278-286
        • Kwon S.W.
        • Lee B.K.
        • Hong B.K.
        • et al.
        Prognostic significance of elevated lipoprotein(a) in coronary artery revascularization patients.
        Int. J. Cardiol. 2013; 167: 1990-1994
        • Virani S.S.
        • Brautbar A.
        • Davis B.C.
        • et al.
        Associations between lipoprotein(a) levels and cardiovascular outcomes in black and white subjects: the atherosclerosis risk in communities (ARIC) study.
        Circulation. 2012; 125: 241-249
        • Madsen C.M.
        • Kamstrup P.R.
        • Langsted A.
        • et al.
        Lp(a) (Lipoprotein[a])-Lowering by 50 mg/dL (105 nmol/L) may Be needed to reduce cardiovascular disease 20% in secondary prevention: a population-based study.
        Arterioscler. Thromb. Vasc. Biol. 2020; 40 (Atvbaha119312951): 255-266
        • Wilson D.P.
        • Jacobson T.A.
        • Jones P.H.
        • et al.
        Use of lipoprotein(a) in clinical practice: a biomarker whose time has come. A scientific statement from the National Lipid Association.
        J. Clin. Lipidol. 2019; 13: 374-392
        • Tsimikas S.
        • Fazio S.
        • Viney N.J.
        • et al.
        Relationship of lipoprotein(a) molar concentrations and mass according to lipoprotein(a) thresholds and apolipoprotein(a) isoform size.
        J. Clin. Lipidol. 2018; 12: 1313-1323
        • Willeit P.
        • Kiechl S.
        • Kronenberg F.
        • et al.
        Discrimination and net reclassification of cardiovascular risk with lipoprotein(a): prospective 15-year outcomes in the Bruneck Study.
        J. Am. Coll. Cardiol. 2014; 64: 851-860
        • Verbeek R.
        • Sandhu M.S.
        • Hovingh G.K.
        • et al.
        Lipoprotein(a) improves cardiovascular risk prediction based on established risk algorithms.
        J. Am. Coll. Cardiol. 2017; 69: 1513-1515
        • Hoogeveen R.M.
        • Opstal T.S.J.
        • Kaiser Y.
        • et al.
        PCSK9 antibody alirocumab attenuates arterial wall inflammation without changes in circulating inflammatory markers.
        JACC Cardiovasc. Imag. 2019; 12: 2571-2573
        • van Wijk D.F.
        • Sjouke B.
        • Figueroa A.
        • et al.
        Nonpharmacological lipoprotein apheresis reduces arterial inflammation in familial hypercholesterolemia.
        J. Am. Coll. Cardiol. 2014; 64: 1418-1426
        • Stiekema L.C.A.
        • Stroes E.S.G.
        • Verweij S.L.
        • et al.
        Persistent arterial wall inflammation in patients with elevated lipoprotein(a) despite strong low-density lipoprotein cholesterol reduction by proprotein convertase subtilisin/kexin type 9 antibody treatment.
        Eur. Heart J. 2019; 40: 2775-2781
        • Superko H.R.
        • Zhao X.Q.
        • Hodis H.N.
        • et al.
        Niacin and heart disease prevention: engraving its tombstone is a mistake.
        J. Clin. Lipidol. 2017; 11: 1309-1317
        • Canner P.L.
        • Berge K.G.
        • Wenger N.K.
        • et al.
        Fifteen year mortality in Coronary Drug Project patients: long-term benefit with niacin.
        J. Am. Coll. Cardiol. 1986; 8: 1245-1255
        • Chasman D.I.
        • Shiffman D.
        • Zee R.Y.
        • et al.
        Polymorphism in the apolipoprotein(a) gene, plasma lipoprotein(a), cardiovascular disease, and low-dose aspirin therapy.
        Atherosclerosis. 2009; 203: 371-376
        • Patrono C.
        • Baigent C.
        Role of aspirin in primary prevention of cardiovascular disease.
        Nat. Rev. Cardiol. 2019; 16: 675-686
        • Ma G.S.
        • Wilkinson M.J.
        • Reeves R.R.
        • et al.
        Lipoprotein(a) in patients undergoing transcatheter aortic valve replacement.
        Angiology. 2019; 70: 332-336
        • Kang D.H.
        • Park S.J.
        • Lee S.A.
        • et al.
        Early surgery or conservative care for asymptomatic aortic stenosis.
        N. Engl. J. Med. 2020; : 382