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Coronary artery calcification and cardiovascular risk factors: impact of the analytic approach

  • Muredach P Reilly
    Correspondence
    Corresponding author. Tel.: +1-215-573-1214; fax: +1-215-573-9004.
    Affiliations
    Cardiovascular Division, Department of Medicine, Centers for Experimental Therapeutics, and Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, 909 BRB 2/3, 421 Curie Blvd., Philadelphia, PA 19004-6160, USA
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  • Megan L Wolfe
    Affiliations
    Cardiovascular Division, Department of Medicine, Centers for Experimental Therapeutics, and Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, 909 BRB 2/3, 421 Curie Blvd., Philadelphia, PA 19004-6160, USA
    Search for articles by this author
  • A.Russell Localio
    Affiliations
    Cardiovascular Division, Department of Medicine, Centers for Experimental Therapeutics, and Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, 909 BRB 2/3, 421 Curie Blvd., Philadelphia, PA 19004-6160, USA
    Search for articles by this author
  • Daniel J Rader
    Affiliations
    Cardiovascular Division, Department of Medicine, Centers for Experimental Therapeutics, and Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, 909 BRB 2/3, 421 Curie Blvd., Philadelphia, PA 19004-6160, USA
    Search for articles by this author

      Abstract

      Coronary artery calcification (CAC) may help identify novel risk factors for coronary atherosclerosis. However, analysis of CAC is challenging because of the distribution of CAC in the population. This has resulted in difficulty in interpreting and comparing results across studies. We applied several analytic approaches to CAC data in order to determine the impact of analytic methods on the association with established cardiovascular risk factors in 914 asymptomatic subjects in the Study of Inherited Risk Factors for Coronary Atherosclerosis. Multivariable analyses included: (1) linear regression of different transformations of CAC scores; (2) tobit regression of the log of (CAC+1); (3) logistic regression using CAC zero as a cut-point; and (4) ordinal logistic regression using CAC categories. Linear regression of the log CAC scores and logistic regression of CAC zero cut-point failed to detect associations with some risk factors. In contrast, linear and tobit regression of the log (CAC+1) and ordinal regression of CAC categories identified more associations and provided consistent results. Commonly applied methods of CAC analysis may fail to detect associations with cardiovascular risk factors. We present analytic approaches that are likely to provide consistent results and recommend the use of at least two distinct multivariable methods.

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      References

        • Grover S.A
        • Coupal L
        • Hu X.P
        Identifying adults at increased risk of coronary disease. How well do the current cholesterol guidelines work?.
        J. Am. Med. Assoc. 1995; 274: 801-806
        • Rumberger J.A
        • Simons D.B
        • Fitzpatrick L.A
        • Sheedy P.F
        • Schwartz R.S
        Coronary artery calcium area by electron-beam computed tomography and coronary atherosclerotic plaque area. A histopathologic correlative study.
        Circulation. 1995; 92: 2157-2162
        • Rumberger J.A
        • Sheedy P.F
        • Breen J.F
        • Schwartz R.S
        Electron beam computed tomographic coronary calcium score cutpoints and severity of associated angiographic lumen stenosis.
        J. Am. Coll. Cardiol. 1997; 29: 1542-1548
        • Keelan P.C
        • Bielak L.F
        • Ashai K
        • Jamjoum L.S
        • Denktas A.E
        • Rumberger J.A
        • et al.
        Long-term prognostic value of coronary calcification detected by electron-beam computed tomography in patients undergoing coronary angiography.
        Circulation. 2001; 104: 412-417
        • Arad Y
        • Spadaro L.A
        • Goodman K
        • Newstein D
        • Guerci A.D
        Prediction of coronary events with electron beam computed tomography.
        J. Am. Coll. Cardiol. 2000; 36: 1253-1260
        • Wong N.D
        • Budoff M.J
        • Pio J
        • Detrano R.C
        Coronary calcium and cardiovascular event risk: evaluation by age- and sex-specific quartiles.
        Am. Heart J. 2002; 143: 456-459
        • Colhoun H.M
        • Francis D.P
        • Rubens M.B
        • Underwood S.R
        • Fuller J.H
        The association of heart-rate variability with cardiovascular risk factors and coronary artery calcification: a study in type 1 diabetic patients and the general population.
        Diabetes Care. 2001; 24: 1108-1114
        • Wagenknecht L.E
        • Bowden D.W
        • Carr J.J
        • Langefeld C.D
        • Freedman B.I
        • Rich S.S
        Familial aggregation of coronary artery calcium in families with type 2 diabetes.
        Diabetes. 2001; 50: 861-866
        • Raggi P
        • Boulay A
        • Chasan-Taber S
        • Amin N
        • Dillon M
        • Burke S.K
        • 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
        • Valdes A.M
        • Wolfe M.L
        • Tate H.C
        • Gefter W
        • Rut A
        • Rader D.J
        Association of traditional risk factors with coronary calcification in persons with a family history of premature coronary heart disease: the study of the inherited risk of coronary atherosclerosis.
        J. Investig. Med. 2001; 49: 353-361
        • Budoff M.J
        • Yang T.P
        • Shavelle R.M
        • Lamont D.H
        • Brundage B.H
        Ethnic differences in coronary atherosclerosis.
        J. Am. Coll. Cardiol. 2002; 39: 408-412
        • Lange L.A
        • Lange E.M
        • Bielak L.F
        • Langefeld C.D
        • Kardia S.L
        • Royston P
        • et al.
        Autosomal genome-wide scan for coronary artery calcification loci in sibships at high risk for hypertension.
        Arterioscler. Thromb. Vasc. Biol. 2002; 22: 418-423
        • Yang T
        • Doherty T.M
        • Wong N.D
        • Detrano R.C
        Alcohol consumption, coronary calcium, and coronary heart disease events.
        Am. J. Cardiol. 1999; 84: 802-806
        • Arad Y
        • Newstein D
        • Cadet F
        • Roth M
        • Guerci A.D
        Association of multiple risk factors and insulin resistance with increased prevalence of asymptomatic coronary artery disease by an electron-beam computed tomographic study.
        Arterioscler. Thromb. Vasc. Biol. 2001; 21: 2051-2058
        • Kardia S.L
        • Haviland M.B
        • Ferrell R.E
        • Sing C.F
        The relationship between risk factor levels and presence of coronary artery calcification is dependent on apolipoprotein E genotype.
        Arterioscler. Thromb. Vasc. Biol. 1999; 19: 427-435
        • O’Malley P.G
        • Jones D.L
        • Feuerstein I.M
        • Taylor A.J
        Lack of correlation between psychological factors and subclinical coronary artery disease.
        N. Engl. J. Med. 2000; 343: 1298-1304
        • Bielak L.F
        • Klee G.G
        • Sheedy II, P.F
        • Turner S.T
        • Schwartz R.S
        • Peyser P.A
        Association of fibrinogen with quantity of coronary artery calcification measured by electron beam computed tomography.
        Arterioscler. Thromb. Vasc. Biol. 2000; 20: 2167-2171
        • Ellsworth D.L
        • Bielak L.F
        • Turner S.T
        • Sheedy II, P.F
        • Boerwinkle E
        • Peyser P.A
        Gender- and age-dependent relationships between the E-selectin S128R polymorphism and coronary artery calcification.
        J. Mol. Med. 2001; 79: 390-398
        • Newman A.B
        • Naydeck B.L
        • Sutton-Tyrrell K
        • Feldman A
        • Edmundowicz D
        • Kuller L.H
        Coronary artery calcification in older adults to age 99: prevalence and risk factors.
        Circulation. 2001; 104: 2679-2684
        • Hunt M.E
        • O’Malley P.G
        • Vernalis M.N
        • Feuerstein I.M
        • Taylor A.J
        C-reactive protein is not associated with the presence or extent of calcified subclinical atherosclerosis.
        Am. Heart J. 2001; 141: 206-210
        • Bild D.E
        • Folsom A.R
        • Lowe L.P
        • Sidney S
        • Kiefe C
        • Westfall A.O
        • et al.
        Prevalence and correlates of coronary calcification in black and white young adults: the Coronary Artery Risk Development in Young Adults (CARDIA) Study.
        Arterioscler. Thromb. Vasc. Biol. 2001; 21: 852-857
        • Mahoney L.T
        • Burns T.L
        • Stanford W
        • Thompson B.H
        • Witt J.D
        • Rost C.A
        • et al.
        Usefulness of the Framingham risk score and body mass index to predict early coronary artery calcium in young adults (Muscatine Study).
        Am. J. Cardiol. 2001; 88: 509-515
        • Turner S.T
        • Bielak L.F
        • Narayana A.K
        • Sheedy II, P.F
        • Schwartz G.L
        • Peyser P.A
        Ambulatory blood pressure and coronary artery calcification in middle-aged and younger adults.
        Am. J. Hypertens. 2002; 15: 518-524
        • Hoff J.A
        • Daviglus M.L
        • Chomka E.V
        • Krainik A.J
        • Sevrukov A
        • Kondos G.T
        Conventional coronary artery disease risk factors and coronary artery calcium detected by electron beam tomography in 30,908 healthy individuals.
        Ann. Epidemiol. 2003; 13: 163-169
        • Newman A.B
        • Naydeck B.L
        • Whittle J
        • Sutton-Tyrrell K
        • Edmundowicz D
        • Kuller L.H
        Racial differences in coronary artery calcification in older adults.
        Arterioscler. Thromb. Vasc. Biol. 2002; 22: 424-430
        • Wolfe M.L
        • Iqbal N
        • Gefter W
        • Mohler E.R
        • Rader D.J
        • Reilly M.P
        Coronary artery calcification at electron beam computed tomography is increased in asymptomatic type 2 diabetics independent of traditional risk factors.
        J. Cardiovasc. Risk. 2002; 9: 369-676
        • Jamjoum L.S
        • Bielak L.F
        • Turner S.T
        • Sheedy I.P
        • Boerwinkle E
        • Raghunathan T.E
        • et al.
        Relationship of blood pressure measures with coronary artery calcification.
        Med. Sci. Monit. 2002; 8: CR775-CR781
        • Maher J.E
        • Raz J.A
        • Bielak L.F
        • Sheedy II, P.F
        • Schwartz R.S
        • Peyser P.A
        Potential of quantity of coronary artery calcification to identify new risk factors for asymptomatic atherosclerosis.
        Am. J. Epidemiol. 1996; 144: 943-953
        • Mahoney L.T
        • Burns T.L
        • Stanford W
        • Thompson B.H
        • Witt J.D
        • Rost C.A
        • et al.
        Coronary risk factors measured in childhood and young adult life are associated with coronary artery calcification in young adults: the Muscatine Study.
        J. Am. Coll. Cardiol. 1996; 27: 277-284
        • Valdes A.M
        • Wolfe M.L
        • O’Brien E.J
        • Spurr N.K
        • Gefter W
        • Rut A
        • et al.
        Val64Ile polymorphism in the C-C chemokine receptor 2 is associated with reduced coronary artery calcification.
        Arterioscler. Thromb. Vasc. Biol. 2002; 22: 1924-1928
      1. Long J. Regression models for categorical and limited dependent variables. Sage; 1997. p. 196–210.

        • Fu V
        Estimating generalized ordered logit models.
        Stata Tech. Bull. 1998; 44: 27-30
        • Etzioni R.D
        • Fienberg S.E
        • Gilula Z
        • Haberman S.J
        Statistical models for the analysis of ordered categorical data in public health and medical research.
        Stat. Methods Med. Res. 1994; 3: 179-204
        • Rumberger J.A
        • Brundage B.H
        • Rader D.J
        • Kondos G
        Electron beam computed tomographic coronary calcium scanning: a review and guidelines for use in asymptomatic persons.
        Mayo Clin. Proc. 1999; 74: 243-252
      2. Davison A, Hinkley D. Bootstrap methods and their applications. Cambridge: Cambridge University Press; 1997.

        • Lindsey J.K
        • Jones B
        Choosing among generalized linear models applied to medical data.
        Stat. Med. 1998; 17: 59-68
        • Flegal K.M
        • Carroll M.D
        • Ogden C.L
        • Johnson C.L
        Prevalence and trends in obesity among US adults, 1999–2000.
        J. Am. Med. Assoc. 2002; 288: 1723-1727
        • Hoff J.A
        • Chomka E.V
        • Krainik A.J
        • Daviglus M
        • Rich S
        • Kondos G.T
        Age and gender distributions of coronary artery calcium detected by electron beam tomography in 35,246 adults.
        Am. J. Cardiol. 2001; 87: 1335-1339
        • Peyser P.A
        • Bielak L.F
        • Chu J.S
        • Turner S.T
        • Ellsworth D.L
        • Boerwinkle E
        • et al.
        Heritability of coronary artery calcium quantity measured by electron beam computed tomography in asymptomatic adults.
        Circulation. 2002; 106: 304-308
        • Ferraro K.F
        • Su Y.P
        • Gretebeck R.J
        • Black D.R
        • Badylak S.F
        Body mass index and disability in adulthood: a 20-year panel study.
        Am. J. Public Health. 2002; 92: 834-840
      3. Amemiya T. Advanced econometrics. Cambridge, MA: Harvard University Press; 1985. p. 360–411.