Mayo Clinic Proceedings Home

Lipoprotein(a), Cardiovascular Disease, and Contemporary Management

  • Terry A. Jacobson
    Correspondence
    Correspondence: Address to Terry A. Jacobson, MD, Office of Health Promotion and Disease Prevention, Department of Medicine, Emory University, Faculty Office Building, 49 Jesse Hill Jr Dr SE, Atlanta, GA 30303.
    Affiliations
    Office of Health Promotion and Disease Prevention, Department of Medicine, Emory University School of Medicine, Atlanta, GA
    Search for articles by this author

      Abstract

      Elevated lipoprotein(a) (Lp[a]) is a causal genetic risk factor for cardiovascular disease. To determine if current evidence supports both screening and treatment for elevated Lp(a) in high-risk patients, an English-language search of PubMed and MEDLINE was conducted. In population studies, there is a continuous association between Lp(a) concentrations and cardiovascular risk, with synergistic effects when low-density lipoprotein (LDL) is also elevated. Candidates for Lp(a) screening include patients with a personal or family history of premature cardiovascular disease, familial hypercholesterolemia, recurrent cardiovascular events, or inadequate LDL cholesterol (LDL-C) responses to statins. Given the comparative strength of clinical evidence, reducing LDL-C to the lowest attainable value with a high-potency statin should be the primary focus of lipid-modifying therapies. If the Lp(a) level is 30 mg/dL or higher in a patient who has the aforementioned characteristics plus residual LDL-C elevations (≥70-100 mg/dL) despite maximum-potency statins or combination statin therapy, the clinician may consider adding niacin (up to 2 g/d). If, after these interventions, the patient has progressive coronary heart disease (CHD) or LDL-C levels of 160-200 mg/dL or higher, LDL apheresis should be contemplated. Although Lp(a) is a major causal risk factor for CHD, no currently available controlled studies have suggested that lowering it through either pharmacotherapy or LDL apheresis specifically and significantly reduces coronary risk. Further research is needed to (1) optimize management in order to reduce CHD risk associated with elevated Lp(a) and (2) determine what other intermediate- or high-risk groups might benefit from Lp(a) screening.

      Abbreviations and Acronyms:

      AIM-HIGH ( Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides: Impact on Global Health Outcomes ), apo ( apolipoprotein), CCHS ( Copenhagen City Heart Study), CHD ( coronary heart disease), CV ( cardiovascular), CVD ( CV disease), FH ( familial hypercholesterolemia), HDL-C ( high-density lipoprotein cholesterol), HPS2-THRIVE ( Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events), HRT ( hormone replacement therapy), KIV-2 ( kringle IV type 2), LDL ( low-density lipoprotein), LDL-C ( LDL cholesterol), Lp(a) ( lipoprotein(a)), Lp(a)-C ( Lp(a) cholesterol), Lp(a)-P ( Lp(a) particle), PN ( pentanucleotide), RCT ( randomized controlled trial), SNP ( single-nucleotide polymorphism)

      References

        • Bennet A.
        • Di Angelantonio E.
        • Erqou S.
        • et al.
        Lipoprotein(a) levels and risk of future coronary heart disease: large-scale prospective data.
        Arch Intern Med. 2008; 168 ([published corrections appear in Arch Intern Med. 2008;168(10):1089 and Arch Intern Med. 2008;168(10):1096]): 598-608
        • Kamstrup P.R.
        • Tybjaerg-Hansen A.
        • Steffensen R.
        • Nordestgaard B.G.
        Genetically elevated lipoprotein(a) and increased risk of myocardial infarction.
        JAMA. 2009; 301: 2331-2339
        • Suk Danik J.
        • Rifai N.
        • Buring J.E.
        • Ridker P.M.
        Lipoprotein(a), measured with an assay independent of apolipoprotein(a) isoform size, and risk of future cardiovascular events among initially healthy women.
        JAMA. 2006; 296: 1363-1370
        • 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
        • Berg K.
        A new serum type system in man–the Lp system.
        Acta Pathol Microbiol Scand. 1963; 59: 369-382
        • Krempler F.
        • Kostner G.M.
        • Bolzano K.
        • Sandhofer F.
        Turnover of lipoprotein (a) in man.
        J Clin Invest. 1980; 65: 1483-1490
        • Scanu A.M.
        Lp(a) lipoprotein—coping with heterogeneity.
        N Engl J Med. 2003; 349: 2089-2090
        • Siekmeier R.
        • Scharnagl H.
        • Kostner G.M.
        • Grammer T.
        • Stojakovic T.
        • März W.
        Variation of Lp(a) plasma concentrations in health and disease.
        Open Clin Chem J. 2010; 3: 72-79
        • Frank S.
        • Hrzenjak A.
        • Blaschitz A.
        • Dohr G.
        • Kostner G.M.
        Role of various tissues in apo(a) fragmentation and excretion of fragments by the kidney.
        Eur J Clin Invest. 2001; 31: 504-512
        • Tsimikas S.
        • Brilakis E.S.
        • Miller E.R.
        • et al.
        Oxidized phospholipids, Lp(a) lipoprotein, and coronary artery disease.
        N Engl J Med. 2005; 353: 46-57
        • Marcovina S.M.
        • Albers J.J.
        • Wijsman E.
        • Zhang Z.
        • Chapman N.H.
        • Kennedy H.
        Differences in Lp[a] concentrations and apo[a] polymorphs between black and white Americans.
        J Lipid Res. 1996; 37: 2569-2585
        • Sandholzer C.
        • Hallman D.M.
        • Saha N.
        • et al.
        Effects of the apolipoprotein(a) size polymorphism on the lipoprotein(a) concentration in 7 ethnic groups.
        Hum Genet. 1991; 86: 607-614
        • Luke M.M.
        • Kane J.P.
        • Liu D.M.
        • et al.
        A polymorphism in the protease-like domain of apolipoprotein(a) is associated with severe coronary artery disease.
        Arterioscler Thromb Vasc Biol. 2007; 27: 2030-2036
        • Edelstein C.
        • Italia J.A.
        • Scanu A.M.
        Polymorphonuclear cells isolated from human peripheral blood cleave lipoprotein(a) and apolipoprotein(a) at multiple interkringle sites via the enzyme elastase: generation of mini-Lp(a) particles and apo(a) fragments.
        J Biol Chem. 1997; 272: 11079-11087
        • Røsby O.
        • Berg K.
        LPA gene: interaction between the apolipoprotein(a) size ('kringle IV' repeat) polymorphism and a pentanucleotide repeat polymorphism influences Lp(a) lipoprotein level.
        J Intern Med. 2000; 247: 139-152
        • Clarke R.
        • Peden J.F.
        • Hopewell J.C.
        • et al.
        • PROCARDIS Consortium
        Genetic variants associated with Lp(a) lipoprotein level and coronary disease.
        N Engl J Med. 2009; 361: 2518-2528
        • Clarke R.
        • Xu P.
        • Bennett D.
        • et al.
        • International Study of Infarct Survival (ISIS) Collaborators
        Lymphotoxin-alpha gene and risk of myocardial infarction in 6,928 cases and 2,712 controls in the ISIS case-control study.
        PLoS Genet. 2006; 2: e107
        • Lamon-Fava S.
        • Marcovina S.M.
        • Albers J.J.
        • et al.
        Lipoprotein(a) levels, apo(a) isoform size, and coronary heart disease risk in the Framingham Offspring Study.
        J Lipid Res. 2011; 52: 1181-1187
        • Hopewell J.C.
        • Clarke R.
        • Parish S.
        • et al.
        • Heart Protection Study Collaborative Group
        Lipoprotein(a) genetic variants associated with coronary and peripheral vascular disease but not with stroke risk in the Heart Protection Study.
        Circ Cardiovasc Genet. 2011; 4: 68-73
        • Deo R.C.
        • Wilson J.G.
        • Xing C.
        • et al.
        Single-nucleotide polymorphisms in LPA explain most of the ancestry-specific variation in Lp(a) levels in African Americans.
        PLoS One. 2011; 6: e14581
        • Helgadottir A.
        • Gretarsdottir S.
        • Thorleifsson G.
        • et al.
        Apolipoprotein(a) genetic sequence variants associated with systemic atherosclerosis and coronary atherosclerotic burden but not with venous thromboembolism.
        J Am Coll Cardiol. 2012; 60: 722-729
        • 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
        • 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.
        JAMA. 2009; 302: 412-423
        • Kamstrup P.R.
        • Benn M.
        • Tybjærg-Hansen A.
        • Nordestgaard B.G.
        Extreme lipoprotein(a) levels and risk of myocardial infarction in the general population: the Copenhagen City Heart Study.
        Circulation. 2008; 117: 176-184
        • Ariyo A.A.
        • Thach C.
        • Tracy R.
        • Cardiovascular Health Study Investigators
        Lp(a) lipoprotein, vascular disease, and mortality in the elderly.
        N Engl J Med. 2003; 349: 2108-2115
        • von Eckardstein A.
        • Schulte H.
        • Cullen P.
        • Assmann G.
        Lipoprotein(a) further increases the risk of coronary events in men with high global cardiovascular risk.
        J Am Coll Cardiol. 2001; 37: 434-439
        • Danesh J.
        • Collins R.
        • Peto R.
        Lipoprotein(a) and coronary heart disease: meta-analysis of prospective studies.
        Circulation. 2000; 102: 1082-1085
        • Paultre F.
        • Pearson T.A.
        • Wei H.F.
        • et al.
        High levels of Lp(a) with a small apo(a) isoform are associated with coronary artery disease in African American and white men.
        Arterioscler Thromb Vasc Biol. 2000; 20: 2619-2624
        • Tyroler H.A.
        • Heiss G.
        • Schonfeld G.
        • Cooper G.
        • Heyden S.
        • Hames C.G.
        Apolipoprotein A-I, A-II and C- II in black and white residents of Evans County.
        Circulation. 1980; 62: 249-254
        • Morrison J.A.
        • deGroot I.
        • Kelly K.A.
        • et al.
        Black-white differences in plasma lipoproteins in Cincinnati schoolchildren (one-to-one pair matched by total plasma cholesterol, sex, and age).
        Metabolism. 1979; 28: 241-245
        • Srinivasan S.R.
        • Frerichs R.R.
        • Webber L.S.
        • Berenson G.S.
        Serum lipoprotein profile in children from a biracial community: the Bogalusa Heart Study.
        Circulation. 1976; 54: 309-318
        • Wild S.H.
        • Fortmann S.P.
        • Marcovina S.M.
        A prospective case-control study of lipoprotein(a) levels and apo(a) size and risk of coronary heart disease in Stanford Five-City Project participants.
        Arterioscler Thromb Vasc Biol. 1997; 17 ([published correction appears in Arterioscler Throm Vasc Biol. 1997;17(5):1010]): 239-245
        • Shai I.
        • Rimm E.B.
        • Hankinson S.E.
        • et al.
        Lipoprotein(a) and coronary heart disease among women: beyond a cholesterol carrier?.
        Eur Heart J. 2005; 26: 1633-1639
        • Coronary Drug Project Research Group
        Clofibrate and niacin in coronary heart disease.
        JAMA. 1975; 231: 360-381
        • 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
        • Jauhiainen M.
        • Koskinen P.
        • Ehnholm C.
        • et al.
        Lipoprotein (a) and coronary heart disease risk: a nested case-control study of the Helsinki Heart Study participants.
        Atherosclerosis. 1991; 89: 59-67
        • Maher V.M.
        • Brown B.G.
        • Marcovina S.M.
        • Hillger L.A.
        • Zhao X.Q.
        • Albers J.J.
        Effects of lowering elevated LDL cholesterol on the cardiovascular risk of lipoprotein(a).
        JAMA. 1995; 274: 1771-1774
        • Brown G.
        • Albers J.J.
        • Fisher L.D.
        • et al.
        Regression of coronary artery disease as a result of intensive lipid-lowering therapy in men with high levels of apolipoprotein B.
        N Engl J Med. 1990; 323: 1289-1298
        • Brown B.G.
        • Zhao X.Q.
        • Chait A.
        • et al.
        Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease.
        N Engl J Med. 2001; 345: 1583-1592
        • Investigators A.I.M.-H.I.G.H.
        • Boden W.E.
        • Probstfield J.L.
        • Anderson T.
        • et al.
        Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy.
        N Engl J Med. 2011; 365 ([published correction appears in N Engl J Med. 2012;367(2):189]): 2255-2267
      1. MRC/Cancer Research UK/BHF Clinical Trial Service Unit & Epidemiological Studies Unit, Nuffield Department of Clinical Medicine, Medical Sciences Division, Oxford University. HPS2-THRIVE: Preliminary results. January 2013. University of Oxford CTSU website. http://www.ctsu.ox.ac.uk/hps2-thrive/index.htm. Updated May 2, 2013. Accessed September 15, 2013.

        • Nordestgaard B.G.
        • Chapman M.J.
        • Ray K.
        • et al.
        European Atherosclerosis Society Consensus Panel. Lipoprotein(a) as a cardiovascular risk factor: current status.
        Eur Heart J. 2010; 31: 2844-2853
        • National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III)
        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. 2002; 106: 3143-3421
        • Marcovina S.M.
        • Koschinsky M.L.
        • Albers J.J.
        • 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
        • Ballantyne C.M.
        • Davidson M.H.
        • McKenney J.
        • Keller L.H.
        • Bajorunas D.R.
        • Karas R.H.
        Comparison of the safety and efficacy of a combination tablet of niacin extended release and simvastatin vs simvastatin monotherapy in patients with increased non-HDL cholesterol (from the SEACOAST I study).
        Am J Cardiol. 2008; 101: 1428-1436
        • Chen F.
        • Maccubbin D.
        • Yan L.
        • et al.
        Lipid-altering efficacy and safety profile of co-administered extended release niacin/laropiprant and simvastatin versus atorvastatin in patients with mixed hyperlipidemia.
        Int J Cardiol. 2013; 167: 225-231
        • Ballantyne C.M.
        • Davidson M.H.
        • McKenney J.M.
        • Keller L.H.
        • Bajorunas D.R.
        • Karas R.H.
        Comparison of the efficacy and safety of a combination tablet of niacin extended-release and simvastatin with simvastatin 80 mg monotherapy: the SEACOAST II (high-dose) study.
        J Clin Lipidol. 2008; 2: 79-90
        • Insull Jr., W.
        • Basile J.N.
        • Vo A.N.
        • Jiang P.
        • Thakkar R.
        • Padley R.J.
        Efficacy and safety of combination therapy with niacin extended-release and simvastatin versus atorvastatin in patients with dyslipidemia: the SUPREME Study.
        J Clin Lipidol. 2009; 3: 109-118
        • Maccubbin D.
        • Bays H.E.
        • Olsson A.G.
        • et al.
        Lipid-modifying efficacy and tolerability of extended-release niacin/laropiprant in patients with primary hypercholesterolaemia or mixed dyslipidaemia.
        Int J Clin Pract. 2008; 62: 1959-1970
        • Karas R.H.
        • Kashyap M.L.
        • Knopp R.H.
        • Keller L.H.
        • Bajorunas D.R.
        • Davidson M.H.
        Long-term safety and efficacy of a combination of niacin extended release and simvastatin in patients with dyslipidemia: the OCEANS study.
        Am J Cardiovasc Drugs. 2008; 8: 69-81
        • Capuzzi D.M.
        • Morgan J.M.
        • Weiss R.J.
        • Chitra R.R.
        • Hutchinson H.G.
        • Cressman M.D.
        Beneficial effects of rosuvastatin alone and in combination with extended-release niacin in patients with a combined hyperlipidemia and low high-density lipoprotein cholesterol levels.
        Am J Cardiol. 2003; 91: 1304-1310
        • Kashyap M.L.
        • McGovern M.E.
        • Berra K.
        • et al.
        Long-term safety and efficacy of a once-daily niacin/lovastatin formulation for patients with dyslipidemia.
        Am J Cardiol. 2002; 89: 672-678
        • Guyton J.R.
        • Blazing M.A.
        • Hagar J.
        • et al.
        • Niaspan-Gemfibrozil Study Group
        Extended-release niacin vs gemfibrozil for the treatment of low levels of high-density lipoprotein cholesterol.
        Arch Intern Med. 2000; 160: 1177-1184
        • Goldberg A.
        • Alagona Jr., P.
        • Capuzzi D.M.
        • et al.
        Multiple-dose efficacy and safety of an extended-release form of niacin in the management of hyperlipidemia.
        Am J Cardiol. 2000; 85: 1100-1105
        • Morgan J.M.
        • Capuzzi D.M.
        • Guyton J.R.
        A new extended-release niacin (Niaspan): efficacy, tolerability, and safety in hypercholesterolemic patients.
        Am J Cardiol. 1998; 82: 29U-34U
        • Morgan J.M.
        • Capuzzi D.M.
        • Guyton J.R.
        • et al.
        Treatment effect of Niaspan, a controlled-release niacin, in patients with hypercholesterolemia: a placebo-controlled trial.
        J Cardiovasc Pharmacol Ther. 1996; 1: 195-202
        • Capuzzi D.M.
        • Guyton J.R.
        • Morgan J.M.
        • et al.
        Efficacy and safety of an extended-release niacin (Niaspan): a long-term study.
        Am J Cardiol. 1998; 82: 74U-81U
        • Seed M.
        • O'Connor B.
        • Perombelon N.
        • O'Donnell M.
        • Reaveley D.
        • Knight B.L.
        The effect of nicotinic acid and acipimox on lipoprotein(a) concentration and turnover.
        Atherosclerosis. 1993; 101: 61-68
        • Carlson L.A.
        • Hamsten A.
        • Asplund A.
        Pronounced lowering of serum levels of lipoprotein Lp(a) in hyperlipidaemic subjects treated with nicotinic acid.
        J Intern Med. 1989; 226: 271-276
        • Goldberg A.C.
        Clinical trial experience with extended-release niacin (Niaspan): dose-escalation study.
        Am J Cardiol. 1998; 82: 35U-38U
        • McKenney J.M.
        • Jones P.H.
        • Bays H.E.
        • et al.
        Comparative effects on lipid levels of combination therapy with a statin and extended-release niacin or ezetimibe versus a statin alone (the COMPELL study).
        Atherosclerosis. 2007; 192: 432-437
        • Ganji S.H.
        • Kamanna V.S.
        • Kashyap M.L.
        Niacin and cholesterol: role in cardiovascular disease (review).
        J Nutr Biochem. 2003; 14: 298-305
        • Orth-Gomér K.
        • Mittleman M.A.
        • Schenck-Gustafsson K.
        • et al.
        Lipoprotein(a) as a determinant of coronary heart disease in young women.
        Circulation. 1997; 95: 329-334
      2. US Preventive Services Task Force. Menopausal Hormone Therapy for the Primary Prevention of Chronic Conditions: Clinical Summary of US Preventive Services Task Force Recommendation. AHRQ Publication No. 12-05168-EF-4. http://www.uspreventiveservicestaskforce.org/uspstf12/menohrt/menohrtsum.htm. Published October 2012. Accessed September 15, 2013.

        • Hulley S.
        • Grady D.
        • Bush T.
        • et al.
        • Heart and Estrogen/progestin Replacement Study (HERS) Research Group
        Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women.
        JAMA. 1998; 280: 605-613
        • Furberg C.D.
        • Vittinghoff E.
        • Davidson M.
        • et al.
        Subgroup interactions in the Heart and Estrogen/Progestin Replacement Study: lessons learned.
        Circulation. 2002; 105: 917-922
        • Anderson G.L.
        • Limacher M.
        • Assaf A.R.
        • et al.
        • Women's Health Initiative Steering Committee
        Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women's Health Initiative randomized controlled trial.
        JAMA. 2004; 291: 1701-1712
        • Nelson H.D.
        • Humphrey L.L.
        • Nygren P.
        • Teutsch S.M.
        • Allan J.D.
        Postmenopausal hormone replacement therapy: scientific review.
        JAMA. 2002; 288: 872-881
        • Shlipak M.G.
        • Simon J.A.
        • Vittinghoff E.
        • et al.
        Estrogen and progestin, lipoprotein(a), and the risk of recurrent coronary heart disease events after menopause.
        JAMA. 2000; 283: 1845-1852
        • Thompson G.R.
        • HEART-UK LDL Apheresis Working Group
        Recommendations for the use of LDL apheresis.
        Atherosclerosis. 2008; 198: 247-255
        • Daida H.
        • Lee Y.J.
        • Yokoi H.
        • et al.
        • Low-Density Lipoprotein Apheresis Angioplasty Restenosis Trial (L-ART) Group
        Prevention of restenosis after percutaneous transluminal coronary angioplasty by reducing lipoprotein (a) levels with low-density lipoprotein apheresis.
        Am J Cardiol. 1994; 73: 1037-1040
        • Daida H.
        • Yamaguchi H.
        Clinical application and effectiveness of low-density lipoprotein apheresis in the treatment of coronary artery disease.
        Ther Apher. 1997; 1: 253-254
        • Nicholls S.J.
        • Tang W.H.
        • Scoffone H.
        • et al.
        Lipoprotein(a) levels and long-term cardiovascular risk in the contemporary era of statin therapy.
        J Lipid Res. 2010; 51: 3055-3061
      3. Albers JJ, Slee A, O'Brien K, et al. Relationship of apolipoproteins A-1 and B, and lipoprotein (a) to cardiovascular outcomes in the AIM-HIGH trial [published online ahead of print August 7, 2013]. J Am Coll Cardiol. https://doi.org/10.1016/j.jacc.2013.06.051.

        • Lavigne P.M.
        • Karas R.H.
        The current state of niacin in cardiovascular disease prevention: a systematic review and meta-regression.
        J Am Coll Cardiol. 2013; 61: 440-446
        • Lavie C.J.
        • DiNicolantonio J.J.
        • Milani R.V.
        • O'Keefe J.H.
        Niacin therapy lives for another day—maybe? [letter].
        J Am Coll Cardiol. 2013; 61: 2197-2198
        • Ito M.K.
        • McGowan M.P.
        • Moriarty P.M.
        • National Lipid Association Expert Panel on Familial Hypercholesterolemia
        Management of familial hypercholesterolemias in adult patients: recommendations from the National Lipid Association Expert Panel on Familial Hypercholesterolemia.
        J Clin Lipidol. 2011; 5: S38-S45
        • Brown W.V.
        • Ballantyne C.M.
        • Jones P.H.
        • Marcovina S.
        Management of Lp(a).
        J Clin Lipidol. 2010; 4 ([published correction appears in J Clin Lipidol. 2010;4(6):548]): 240-247
      4. Helfand M, Buckley D, Fleming C, et al. Screening for Intermediate Risk Factors for Coronary Heart Disease: Systematic Evidence Synthesis. Evidence Syntheses, No. 73, 2009. AHQR Publication No. 10-05141-EF-1. http://www.ncbi.nlm.nih.gov/books/NBK35208. Accessed September 15, 2013.

        • US Preventive Services Task Force
        Using nontraditional risk factors in coronary heart disease risk assessment: US Preventive Services Task Force recommendation statement.
        Ann Intern Med. 2009; 151: 474-482
        • Anderson T.J.
        • Grégoire J.
        • Hegele R.A.
        • et al.
        2012 Update of the Canadian Cardiovascular Society Guidelines for the Diagnosis and Treatment of Dyslipidemia for the Prevention of Cardiovascular Disease in the Adult.
        Can J Cardiol. 2013; 29: 151-167
        • Kamstrup P.R.
        • Tybjærg-Hansen A.
        • Nordestgaard B.G.
        Extreme lipoprotein(a) levels and improved cardiovascular risk prediction.
        J Am Coll Cardiol. 2013; 61: 1146-1156
        • 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
        • Li Y.
        • Luke M.M.
        • Shiffman D.
        • Devlin J.J.
        Genetic variants in the apolipoprotein(a) gene and coronary heart disease.
        Circ Cardiovasc Genet. 2011; 4: 565-573
        • Shiffman D.
        • Chasman D.I.
        • Ballantyne C.M.
        • Nambi V.
        • Devlin J.J.
        • Boerwinkle E.
        Coronary heart disease risk, aspirin use, and apolipoprotein(a) 4399Met allele in the Atherosclerosis Risk in Communities (ARIC) study.
        Thromb Haemost. 2009; 102: 179-180
        • Ridker P.M.
        • Cook N.R.
        • Lee I.M.
        • et al.
        A randomized trial of low-dose aspirin in the primary prevention of cardiovascular disease in women.
        N Engl J Med. 2005; 352: 1293-1304
        • Marcovina S.M.
        • Koschinsky M.L.
        Lipoprotein (a): structure, measurement and clinical significance.
        in: Rifai N. Warnick G.R. Dominiczak M.H. Handbook of Lipoprotein Testing. 2nd ed. American Association for Clinical Chemistry, Washington, DC2000: 345-385
        • Kulkarni K.R.
        • Garber D.W.
        • Marcovina S.M.
        • Segrest J.P.
        Quantification of cholesterol in all lipoprotein classes by the VAP-II method.
        J Lipid Res. 1994; 35: 159-168
        • Heuck C.C.
        • Schlierf G.
        Beta-lipoprotein cholesterol quantitation with polycations.
        Clin Chem. 1977; 23: 536-540
        • Marcovina S.M.
        • Albers J.J.
        • Gabel B.
        • Koschinsky M.L.
        • Gaur V.P.
        Effect of the number of apolipoprotein(a) kringle 4 domains on immunochemical measurements of lipoprotein(a).
        Clin Chem. 1995; 41: 246-255
        • Marcovina S.M.
        • Albers J.J.
        • Scanu A.M.
        • et al.
        Use of a reference material proposed by the International Federation of Clinical Chemistry and Laboratory Medicine to evaluate analytical methods for the determination of plasma lipoprotein(a).
        Clin Chem. 2000; 46: 1956-1967
        • Nguyen T.T.
        • Ellefson R.D.
        • Hodge D.O.
        • Bailey K.R.
        • Kottke T.E.
        • Abu-Lebdeh H.S.
        Predictive value of electrophoretically detected lipoprotein(a) for coronary heart disease and cerebrovascular disease in a community-based cohort of 9936 men and women.
        Circulation. 1997; 96: 1390-1397
        • Konerman M.
        • Kulkarni K.
        • Toth P.P.
        • Jones S.R.
        Lipoprotein(a) particle concentration and lipoprotein(a) cholesterol assays yield discordant classification of patients into four physiologically discrete groups.
        J Clin Lipidol. 2012; 6: 368-373
        • McConnell J.P.
        • Baudhuin L.M.
        • Berger P.B.
        • et al.
        Lipoprotein(a) cholesterol, but not Lp(a) mass, is an independent predictor of angiographic coronary artery disease and subsequent cardiovascular events in patients referred for coronary angiography.
        Circulation. 2007; 116 (Abstract 3608): 818
        • Akdim F.
        • Visser M.E.
        • Tribble D.L.
        • et al.
        Effect of mipomersen, an apolipoprotein B synthesis inhibitor, on low-density lipoprotein cholesterol in patients with familial hypercholesterolemia.
        Am J Cardiol. 2010; 105: 1413-1419
        • Merki E.
        • Graham M.J.
        • Mullick A.E.
        • et al.
        Antisense oligonucleotide directed to human apolipoprotein B-100 reduces lipoprotein(a) levels and oxidized phospholipids on human apolipoprotein B-100 particles in lipoprotein(a) transgenic mice.
        Circulation. 2008; 118: 743-753
        • Bloomfield D.
        • Carlson G.L.
        • Sapre A.
        • et al.
        Efficacy and safety of the cholesteryl ester transfer protein inhibitor anacetrapib as monotherapy and coadministered with atorvastatin in dyslipidemic patients.
        Am Heart J. 2009; 157: 352-360.e2
        • Gutstein D.E.
        • Krishna R.
        • Johns D.
        • et al.
        Anacetrapib, a novel CETP inhibitor: pursuing a new approach to cardiovascular risk reduction.
        Clin Pharmacol Ther. 2012; 91: 109-122
        • Krauss R.M.
        • Wojnooski K.
        • Orr J.
        • et al.
        Changes in lipoprotein subfraction concentration and composition in healthy individuals treated with the CETP inhibitor anacetrapib.
        J Lipid Res. 2012; 53: 540-547
        • Krishna R.
        • Anderson M.S.
        • Bergman A.J.
        • et al.
        Effect of the cholesteryl ester transfer protein inhibitor, anacetrapib, on lipoproteins in patients with dyslipidaemia and on 24-h ambulatory blood pressure in healthy individuals: two double-blind, randomised placebo-controlled phase I studies.
        Lancet. 2007; 370: 1907-1914
        • Cannon C.P.
        • Shah S.
        • Dansky H.M.
        • et al.
        • DEFINE Investigators
        Safety of anacetrapib in patients with or at high risk for coronary heart disease.
        N Engl J Med. 2010; 363: 2406-2415
        • Cannon C.P.
        • Dansky H.M.
        • Davidson M.
        • et al.
        • DEFINE investigators
        Design of the DEFINE trial: Determining the EFficacy and tolerability of CETP INhibition with AnacEtrapib.
        Am Heart J. 2009; 158: 513-519.e3
        • Stein E.A.
        • Mellis S.
        • Yancopoulos G.D.
        • et al.
        Effect of a monoclonal antibody to PCSK9 on LDL cholesterol.
        N Engl J Med. 2012; 366: 1108-1118

      Linked Article

      • Correction
        Mayo Clinic ProceedingsVol. 89Issue 7
        • In Brief
          In the article “Lipoprotein(a), Cardiovascular Disease, and Contemporary Management,” published in the November 2013 issue of Mayo Clinic Proceedings (2013;88(11):1294-1311), Lp(a) cholesterol and Lp(a)-C should read as Lp(a) throughout the article.
        • Full-Text
        • PDF