Coronary artery calcium progresses rapidly and discriminates incident cardiovascular events in chronic kidney disease regardless of diabetes: The Multi-Ethnic Study of Atherosclerosis (MESA)


      • Clinicians are skeptical about prognostic role of coronary artery calcium (CAC) in chronic kidney disease (CKD) due to confounding by altered milieu of calcium/phosphorus metabolism.
      • This study demonstrates the role of CAC in predicting and discriminating cardiovascular disease outcomes in CKD.
      • Findings are particularly relevant in CKD without diabetes mellitus, in whom lipid lowering therapies are typically underutilized.


      Background and aims

      Chronic kidney disease (CKD) is associated with high prevalence of cardiovascular disease (CVD) events. We sought to assess the prognostic utility of coronary artery calcium (CAC) scores in discriminating incident CVD events among subpopulations of CKD, particularly those without diabetes mellitus (DM).


      Using the Multi-Ethnic Study of Atherosclerosis, we identified 4 groups based on present/absent CKD/diabetes (CKD-/DM-, n = 5308; CKD-/DM+, n = 586, CKD+/DM-, n = 620; CKD+/DM+, n = 266). Baseline and follow-up CAC (Agatston units) measurements, and association between CAC and incident CVD events in median follow-up of 13 years were evaluated using proportional hazards regression adjusting for demographics, clinical, biomarker variables.


      Prevalence of CKD and DM in the cohort was 13% and 12.5% respectively. Annual progression in adjusted median CAC score was 24.8%, 27.9%, 26.7%, 36.8% and unadjusted cumulative incident CVD rates were 12.6%, 22.3%, 23.1%, 39.8% for CKD-/DM-, CKD-/DM+, CKD+/DM-, CKD+/DM+, respectively. After full adjustment (CKD-/DM-referent), hazard ratios (HR, 95% CI) for incident CVD events were 1.25 (1.01–1.53) CKD-/DM+, 1.10 (0.90–1.33) CKD+/DM- and 2.18 (1.73–2.76) CKD+/DM+. Using CKD-/DM-/baseline CAC = 0 referent, adjusted HRs (95% CI) for incident CVD in CKD+/DM- were 1.30 (0.81–2.07), 2.05 (1.4–2.99), and 4.15 (2.94–5.86) for baseline CAC = 0, 1–100, and >300 Agatston units respectively while for CKD+/DM+, adjusted HRs were 3.15 (2.04–4.86), 3.56 (2.26–5.62), 7.90 (5.35–11.67), respectively.


      CAC provides incremental prognostic information to predict incident CVD events in CKD regardless of DM. Moreover, baseline CAC categories discriminate incident CVD among CKD without DM, which may have implications in individualizing approach to primary prevention in this high-risk population.

      Graphical abstract


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        • Centers for Disease Control and Prevention
        Chronic Kidney Disease in the United States, 2019.
        US Department of Health and Human Services, Centers for Disease Control and Prevention, Atlanta, GA2019
        • Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group
        KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease.
        Kidney Int. Suppl. 2013; 3: 1-150
        • Matsushita K.
        • van der Velde M.
        • Astor B.C.
        • et al.
        Association of estimated glomerular filtration rate and albuminuria with all-cause and cardiovascular mortality in general population cohorts: a collaborative meta-analysis.
        Lancet. 2010; 375: 2073-2081
        • Go A.S.
        • Chertow G.M.
        • Fan D.
        • McCulloch C.E.
        • Hsu C.Y.
        Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization.
        N. Engl. J. Med. 2004; 351: 1296-1305
        • Saran R.
        • Robinson B.
        • Abbott K.C.
        • et al.
        US renal data system 2016 annual data report: epidemiology of kidney disease in the United States.
        Am. J. Kidney Dis. 2017; 69: A7-A8
        • Baigent C.
        • Landray M.J.
        • Reith C.
        • et al.
        The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial.
        Lancet. 2011; 377: 2181-2192
        • 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: a report of the American college of cardiology/American heart association task force on clinical practice guidelines.
        J. Am. Coll. Cardiol. 2018; 73 (2019): e285-e350
        • Wanner C.
        • Tonelli M.
        • Kidney Disease
        Improving global outcomes lipid guideline development work group members. KDIGO clinical practice guideline for lipid management in CKD: summary of recommendation statements and clinical approach to the patient.
        Kidney Int. 2014; 85: 1303-1309
        • Matsushita K.
        • Ballew S.H.
        • Coresh J.
        Cardiovascular risk prediction in people with chronic kidney disease.
        Curr. Opin. Nephrol. Hypertens. 2016; 25: 518-523
        • Budoff M.J.
        • Young R.
        • Burke G.
        • et al.
        Ten-year association of coronary artery calcium with atherosclerotic cardiovascular disease (ASCVD) events: the multi-ethnic study of atherosclerosis (MESA).
        Eur. Heart J. 2018; 39: 2401-2408
        • Detrano R.
        • Guerci A.D.
        • Carr J.J.
        • et al.
        Coronary calcium as a predictor of coronary events in four racial or ethnic groups.
        N. Engl. J. Med. 2008; 358: 1336-1345
        • Lamprea-Montealegre J.A.
        • McClelland R.L.
        • Astor B.C.
        • et al.
        Chronic kidney disease, plasma lipoproteins, and coronary artery calcium incidence: the Multi-Ethnic Study of Atherosclerosis.
        Arterioscler. Thromb. Vasc. Biol. 2013; 33: 652-658
        • Kestenbaum B.R.
        • Adeney K.L.
        • de Boer I.H.
        • Ix J.H.
        • Shlipak M.G.
        • Siscovick D.S.
        Incidence and progression of coronary calcification in chronic kidney disease: the Multi-Ethnic Study of Atherosclerosis.
        Kidney Int. 2009; 76: 991-998
        • Bundy J.D.
        • Chen J.
        • Yang W.
        • et al.
        Risk factors for progression of coronary artery calcification in patients with chronic kidney disease: the CRIC study.
        Atherosclerosis. 2018; 271: 53-60
        • Vervloet M.
        • Cozzolino M.
        Vascular calcification in chronic kidney disease: different bricks in the wall?.
        Kidney Int. 2017; 91: 808-817
        • Bashir A.
        • Moody W.E.
        • Edwards N.C.
        • Ferro C.J.
        • Townend J.N.
        • Steeds R.P.
        Coronary artery calcium assessment in CKD: utility in cardiovascular disease risk assessment and treatment?.
        Am. J. Kidney Dis. 2015; 65: 937-948
        • Hakeem A.
        • Bhatti S.
        • Chang S.M.
        Screening and risk stratification of coronary artery disease in end-stage renal disease.
        JACC Cardiovasc Imaging. 2014; 7: 715-728
        • Tangri N.
        • Komenda P.V.
        • Rigatto C.
        Chronic kidney disease and heart disease: after 179 years, do we yet understand the link?.
        Kidney Int. 2015; 88: 11-13
        • Raggi P.
        • Boulay A.
        • Chasan-Taber S.
        • et al.
        Cardiac calcification in adult hemodialysis patients. A link between end-stage renal disease and cardiovascular disease?.
        J. Am. Coll. Cardiol. 2002; 39: 695-701
        • Sharples E.J.
        • Pereira D.
        • Summers S.
        • et al.
        Coronary artery calcification measured with electron-beam computerized tomography correlates poorly with coronary artery angiography in dialysis patients.
        Am. J. Kidney Dis. 2004; 43: 313-319
        • Chen J.
        • Budoff M.J.
        • Reilly M.P.
        • et al.
        Coronary artery calcification and risk of cardiovascular disease and death among patients with chronic kidney disease.
        JAMA Cardiol. 2017; 2: 635-643
        • Murphy D.
        • McCulloch C.E.
        • Lin F.
        • et al.
        Trends in prevalence of chronic kidney disease in the United States.
        Ann. Intern. Med. 2016; 165: 473-481
        • Matsushita K.
        • Sang Y.
        • Ballew S.H.
        • et al.
        Subclinical atherosclerosis measures for cardiovascular prediction in CKD.
        J. Am. Soc. Nephrol. 2015; 26: 439-447
        • Ix J.H.
        • Katz R.
        • Kestenbaum B.
        • et al.
        Association of mild to moderate kidney dysfunction and coronary calcification.
        J. Am. Soc. Nephrol. 2008; 19: 579-585
        • Inker L.A.
        • Schmid C.H.
        • Tighiouart H.
        • et al.
        Estimating glomerular filtration rate from serum creatinine and cystatin C.
        N. Engl. J. Med. 2012; 367: 20-29
        • Bertoni A.G.
        • Goff Jr., D.C.
        • D'Agostino Jr., R.B.
        • et al.
        Diabetic cardiomyopathy and subclinical cardiovascular disease: the Multi-Ethnic Study of Atherosclerosis (MESA).
        Diabetes Care. 2006; 29: 588-594
        • Carr J.J.
        • Nelson J.C.
        • Wong N.D.
        • et al.
        Calcified coronary artery plaque measurement with cardiac CT in population-based studies: standardized protocol of Multi-Ethnic Study of Atherosclerosis (MESA) and Coronary Artery Risk Development in Young Adults (CARDIA) study.
        Radiology. 2005; 234: 35-43
        • Yeboah J.
        • McClelland R.L.
        • Polonsky T.S.
        • et al.
        Comparison of novel risk markers for improvement in cardiovascular risk assessment in intermediate-risk individuals.
        J. Am. Med. Assoc. 2012; 308: 788-795
        • Kovell L.
        Lipid management guidelines for adults with chronic kidney disease.
        Date: May 31, 2016