Original Article| Volume 12, ISSUE 3, P597-603.e1, May 2018

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Elevated lipoprotein(a) levels are associated with coronary artery calcium scores in asymptomatic individuals with a family history of premature atherosclerotic cardiovascular disease

Published:February 17, 2018DOI:


      Elevated lipoprotein(a) (Lp(a)) levels are associated with increased risk for atherosclerotic cardiovascular disease (ASCVD). Individuals with a family history of premature ASCVD are at increased cardiovascular risk with concomitantly a higher burden of (subclinical) atherosclerosis. However, whether Lp(a) contributes to the increased atherosclerotic burden in these individuals remains to be established.


      In this study, we evaluated the association between Lp(a) levels and coronary atherosclerotic burden, assessed by coronary arterty calcium (CAC) scores, in asymptomatic individuals with a family history of premature ASCVD.


      Lp(a) levels and other ASCVD risk factors were assessed in 432 individuals with premature ASCVD and in 937 healthy asymptomatic family members. CAC scores were only measured in asymptomatic family members.


      In this cohort, 16% had elevated Lp(a) levels, defined as ≥ 50 mg/dL. Among healthy family members, elevated Lp(a) levels were associated with both absolute CAC scores of ≥ 100 (odds ratio [OR] 1.79 [95% confidence interval {CI} 1.13–2.83]) as well as with age- and gender-corrected CAC scores ≥ 80th percentile (OR 1.69 [95% CI 1.14–2.50]). This coincides with a higher prevalence of cardiovascular events (OR 1.48 [95% CI 1.11–2.01]) in the whole cohort.


      Elevated Lp(a) levels were associated with higher CAC scores, both absolute as well as age- and gender-corrected percentiles, in individuals with a family history of premature ASCVD. These data imply that Lp(a) accelerates progression of atherosclerosis in these individuals, thereby contributing to their increased ASCVD risk.


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        • Kostner K.M.
        • Kostner G.M.
        Lipoprotein (a): a historical appraisal.
        J Lipid Res. 2017; 58: 1-14
        • 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
        • Danesh J.
        • Collins R.
        • Peto R.
        Lipoprotein(a) and coronary heart disease. Meta-analysis of prospective studies.
        Circulation. 2000; 102: 1082-1085
        • Kamstrup P.R.
        • Tybjaerg-Hansen A.
        • Steffensen R.
        • et al.
        Genetically elevated lipoprotein(a) and increased risk of myocardial infarction.
        JAMA. 2009; 301: 2331-2339
        • Clarke R.
        • Peden J.F.
        • Hopewell J.C.
        • et al.
        Genetic variants associated with Lp(a) lipoprotein level and coronary disease.
        N Engl J Med. 2009; 361: 2518-2528
        • 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 Assoc. 2016; 5
        • Lloyd-Jones D.M.
        • Nam B.H.
        • D'Agostino Sr., R.B.
        • et al.
        Parental cardiovascular disease as a risk factor for cardiovascular disease in middle-aged adults: a prospective study of parents and offspring.
        JAMA. 2004; 291: 2204-2211
        • Parikh N.I.
        • Hwang S.J.
        • Larson M.G.
        • et al.
        Parental occurrence of premature cardiovascular disease predicts increased coronary artery and abdominal aortic calcification in the Framingham Offspring and Third Generation cohorts.
        Circulation. 2007; 116: 1473-1481
        • Agatston A.S.
        • Janowitz W.R.
        • Hildner F.J.
        • et al.
        Quantification of coronary artery calcium using ultrafast computed tomography.
        J Am Coll Cardiol. 1990; 15: 827-832
        • Kondos G.T.
        • Hoff J.A.
        • Sevrukov A.
        • et al.
        Electron-beam tomography coronary artery calcium and cardiac events: a 37-month follow-up of 5635 initially asymptomatic low- to intermediate-risk adults.
        Circulation. 2003; 107: 2571-2576
        • Greif M.
        • Arnoldt T.
        • von Ziegler F.
        • et al.
        Lipoprotein (a) is independently correlated with coronary artery calcification.
        Eur J Intern Med. 2013; 24: 75-79
        • Qasim A.N.
        • Martin S.S.
        • Mehta N.N.
        • et al.
        Lipoprotein(a) is strongly associated with coronary artery calcification in type-2 diabetic women.
        Int J Cardiol. 2011; 150: 17-21
        • Guerra R.
        • Yu Z.
        • Marcovina S.
        • et al.
        Lipoprotein(a) and apolipoprotein(a) isoforms: no association with coronary artery calcification in the Dallas Heart Study.
        Circulation. 2005; 111: 1471-1479
        • Lee T.C.
        • O'Malley P.G.
        • Feuerstein I.
        • et al.
        The prevalence and severity of coronary artery calcification on coronary artery computed tomography in black and white subjects.
        J Am Coll Cardiol. 2003; 41: 39-44
        • Raggi P.
        • Cooil B.
        • Hadi A.
        • et al.
        Predictors of aortic and coronary artery calcium on a screening electron beam tomographic scan.
        Am J Cardiol. 2003; 91: 744-746
        • Demacker P.N.
        • Bolat E.
        • Toenhake-Dijkstra H.I.
        • et al.
        Factors influencing isoprotein dependency of polyclonal apolipoprotein(a) assays.
        Clin Chem. 2004; 50: 2161-2163
        • Catapano A.L.
        • Graham I.
        • De Backer G.
        • et al.
        • Authors/Task Force, M
        2016 ESC/EAS Guidelines for the Management of Dyslipidaemias: The Task Force for the Management of Dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS) Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR).
        Atherosclerosis. 2016; 253: 281-344
        • Cantin B.
        • Lamarche B.
        • Despres J.P.
        • et al.
        Does correction of the friedewald formula using lipoprotein(a) change our estimation of ischemic heart disease risk? The Quebec Cardiovascular Study.
        Atherosclerosis. 2002; 163: 261-267
        • Arad Y.
        • Goodman K.J.
        • Roth M.
        • et al.
        Coronary calcification, coronary disease risk factors, C-reactive protein, and atherosclerotic cardiovascular disease events - The St. Francis Heart Study.
        J Am Coll Cardiol. 2005; 46: 158-165
        • Brundage B.H.
        Don't throw the baby out with the bath water.
        J Am Coll Cardiol. 2009; 54 (author reply 574–575): 574
        • Raggi P.
        • Callister T.Q.
        • Cooil B.
        • et al.
        Identification of patients at increased risk of first unheralded acute myocardial infarction by electron-beam computed tomography.
        Circulation. 2000; 101: 850-855
        • Mulders T.A.
        • Sivapalaratnam S.
        • Stroes E.S.
        • et al.
        Asymptomatic individuals with a positive family history for premature coronary artery disease and elevated coronary calcium scores benefit from statin treatment: a post hoc analysis from the St. Francis Heart Study.
        JACC Cardiovasc Imaging. 2012; 5: 252-260
        • Verbeek R.
        • Boekholdt S.M.
        • Stoekenbroek R.M.
        • et al.
        Population and assay thresholds for the predictive value of lipoprotein (a) for coronary artery disease: the EPIC-Norfolk Prospective Population Study.
        J Lipid Res. 2016; 57: 697-705
        • Nordestgaard B.G.
        • Chapman M.J.
        • Ray K.
        • et al.
        Lipoprotein(a) as a cardiovascular risk factor: Current status.
        Eur Heart J. 2010; 31: 2844-2853
        • Cho J.H.
        • Lee da Y.
        • Lee E.S.
        • et al.
        Increased risk of coronary artery calcification progression in subjects with high baseline Lp(a) levels: The Kangbuk Samsung Health Study.
        Int J Cardiol. 2016; 222: 233-237
        • Kullo I.J.
        • Bailey K.R.
        • Bielak L.F.
        • et al.
        Lack of association between lipoprotein(a) and coronary artery calcification in the Genetic Epidemiology Network of Arteriopathy (GENOA) study.
        Mayo Clin Proc. 2004; 79: 1258-1263
        • Reblin T.
        • Meyer N.
        • Labeur C.
        • et al.
        Extraction of lipoprotein(a), apo B, and apo E from fresh human arterial wall and atherosclerotic plaques.
        Atherosclerosis. 1995; 113: 179-188
        • Keesler G.A.
        • Li Y.
        • Skiba P.J.
        • et al.
        Macrophage foam cell lipoprotein(a)/apoprotein(a) receptor. Cell-surface localization, dependence of induction on new protein synthesis, and ligand specificity.
        Arterioscler Thromb. 1994; 14: 1337-1345
        • Stary H.C.
        • Chandler A.B.
        • Glagov S.
        • et al.
        A definition of initial, fatty streak, and intermediate lesions of atherosclerosis. A report from the Committee on Vascular Lesions of the Council on Arteriosclerosis, American Heart Association.
        Circulation. 1994; 89: 2462-2478
        • Bergmark C.
        • Dewan A.
        • Orsoni A.
        • et al.
        A novel function of lipoprotein [a] as a preferential carrier of oxidized phospholipids in human plasma.
        J Lipid Res. 2008; 49: 2230-2239
        • van der Valk F.M.
        • Bekkering S.
        • Kroon J.
        • et al.
        Oxidized Phospholipids on Lipoprotein(a) Elicit Arterial Wall Inflammation and an Inflammatory Monocyte Response in Humans.
        Circulation. 2016; 134: 611-624
        • Tsimikas S.
        • Witztum J.L.
        The role of oxidized phospholipids in mediating lipoprotein(a) atherogenicity.
        Curr Opin Lipidol. 2008; 19: 369-377