Lipoprotein(a) levels and risk of cardiovascular disease events in individuals with diabetes mellitus or prediabetes: The Atherosclerosis Risk in Communities study


      • Incident ASCVD rates were higher in adults with diabetes/prediabetes than without.
      • Whites with diabetes/prediabetes and elevated Lp(a) had even greater ASCVD risk.
      • Adding Lp(a) to traditional risk factors improved ASCVD risk prediction.
      • Measuring Lp(a) may benefit ASCVD risk stratification in diabetes/prediabetes.


      Background and aims

      Diabetes increases risk for atherosclerotic cardiovascular disease (ASCVD). Current guidelines do not recommend measuring lipoprotein(a), another ASCVD risk factor, in these individuals. We examined the association of lipoprotein(a) levels with incident ASCVD events in persons with and without diabetes or prediabetes.


      Lipoprotein(a) and other ASCVD risk factors were measured at baseline (1996–1998) in the biracial Atherosclerosis Risk in Communities study; participants without prevalent ASCVD (coronary heart disease or stroke) were monitored ∼15 years for incident ASCVD events.


      Of 9871 eligible participants (mean age 63 years; 5816 women; 2155 African Americans), 1543 had diabetes and 3615 had prediabetes. Cumulative ASCVD incidence rates (event/1000-person years) were higher in participants with diabetes (26%) or prediabetes (13%) than in nondiabetic individuals (10%, p < 0.001). When comparing highest to lowest lipoprotein(a) categories (≥50 mg/dL vs. ≤10 mg/dL), increasing lipoprotein(a) levels were significantly associated with increasing incident ASCVD events in Caucasian participants with prediabetes (hazard ratio [HR] = 1.35; 95% confidence interval [CI] 1.07–1.69); p = 0.03) and diabetes (HR = 1.42; 95% CI 1.10–1.84; p < 0.01), but not those with normal fasting blood glucose. Adding lipoprotein(a) to Pooled Cohort Equation variables improved risk prediction in persons with diabetes (Δ in area under the receiver operating characteristic curve [AUC] 0.0087, net reclassification index [NRI] 0.1761) and prediabetes (ΔAUC 0.0025, NRI 0.0938).


      In this biracial cohort, elevated lipoprotein(a) levels in Caucasian individuals with diabetes or prediabetes were associated with further increased ASCVD risk. Adding lipoprotein(a) to traditional risk factors improved ASCVD risk prediction.


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        • Kamstrup P.R.
        • Tybjaerg-Hansen A.
        • Steffensen R.
        • Nordestgaard B.G.
        Genetically elevated lipoprotein(a) and increased risk of myocardial infarction.
        J. Am. Med. Assoc. 2009; 301: 2331-2339
        • Erqou S.
        • Kaptoge S.
        • Perry P.L.
        • et al.
        Lipoprotein(a) concentration and the risk of coronary heart disease, stroke, and nonvascular mortality.
        J. Am. Med. Assoc. 2009; 302: 412-423
        • 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
        • 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
        • Booth G.L.
        • Kapral M.K.
        • Fung K.
        • Tu J.V.
        Relation between age and cardiovascular disease in men and women with diabetes compared with non-diabetic people: a population-based retrospective cohort study.
        Lancet. 2006; 368: 29-36
        • Stone N.J.
        • Robinson J.G.
        • Lichtenstein A.H.
        • et al.
        2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines.
        J. Am. Coll. Cardiol. 2014; 63: 2889-2934
        • Waldeyer C.
        • Makarova N.
        • Zeller T.
        • et al.
        Lipoprotein(a) and the risk of cardiovascular disease in the European population: results from the BiomarCaRE consortium.
        Eur. Heart J. 2017; 38: 2490-2498
        • 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
        • Investigators ARIC
        The Atherosclerosis Risk in Communities (ARIC) study: design and objectives.
        Am. J. Epidemiol. 1989; 129: 687-702
        • Marcovina S.M.
        • Albers J.J.
        Lipoprotein (a) measurements for clinical application.
        J. Lipid Res. 2016; 57: 526-537
        • Rosamond W.D.
        • Chambless L.E.
        • Folsom A.R.
        • et al.
        Trends in the incidence of myocardial infarction and in mortality due to coronary heart disease, 1987 to 1994.
        N. Engl. J. Med. 1998; 339: 861-867
      1. US Preventive Services Task Force. Aspirin use to prevent cardiovascular disease and colorectal cancer: preventive medication. Accessed 19 March 2018.

        • 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
        • Jacobson T.A.
        • Ito M.K.
        • Maki K.C.
        • et al.
        National Lipid Association recommendations for patient-centered management of dyslipidemia: part 1--full report.
        J. Clin. Lipidol. 2015; 9: 129-169
        • 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
        • 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
        • Ronnemaa T.
        • Laakso M.
        • Pyorala K.
        • Kallio V.
        • Puukka P.
        High fasting plasma insulin is an indicator of coronary heart disease in non-insulin-dependent diabetic patients and nondiabetic subjects.
        Arterioscler. Thromb. 1991; 11: 80-90
        • Selvin E.
        • Lazo M.
        • Chen Y.
        • et al.
        Diabetes mellitus, prediabetes, and incidence of subclinical myocardial damage.
        Circulation. 2014; 130: 1374-1382
        • Emdin C.A.
        • Khera A.V.
        • Natarajan P.
        • et al.
        Phenotypic characterization of genetically lowered human lipoprotein(a) levels.
        J. Am. Coll. Cardiol. 2016; 68: 2761-2772
        • Khera A.V.
        • Everett B.M.
        • Caulfield M.P.
        • et al.
        Lipoprotein(a) concentrations, rosuvastatin therapy, and residual vascular risk: an analysis from the JUPITER trial (justification for the use of statins in prevention: an intervention trial evaluating rosuvastatin).
        Circulation. 2014; 129: 635-642
        • Perrot N.
        • Verbeek R.
        • Sandhu M.
        • et al.
        Ideal cardiovascular health influences cardiovascular disease risk associated with high lipoprotein(a) levels and genotype: the EPIC-Norfolk prospective population study.
        Atherosclerosis. 2017; 256: 47-52
        • 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