title: Role of Coronary Artery Calcium Score of Zero and Other Negative Risk Markers for Cardiovascular Disease: The Multi-Ethnic Study of Atherosclerosis (MESA).
abstract: BACKGROUND
  Limited attention has been paid to negative cardiovascular disease (CVD) risk markers despite their potential to improve medical decision making. We compared 13 negative risk markers using diagnostic likelihood ratios (DLRs), which model the change in risk for an individual after the result of an additional test.
  
  
  RESULTS
  We examined 6814 participants from the Multi-Ethnic Study of Atherosclerosis. Coronary artery calcium score of 0, carotid intima-media thickness <25th percentile, absence of carotid plaque, brachial flow-mediated dilation >5% change, ankle-brachial index >0.9 and <1.3, high-sensitivity C-reactive protein <2 mg/L, homocysteine <10 µmol/L, N-terminal pro-brain natriuretic peptide <100 pg/mL, no microalbuminuria, no family history of coronary heart disease (any/premature), absence of metabolic syndrome, and healthy lifestyle were compared for all and hard coronary heart disease and all CVD events over the 10-year follow-up. Models were adjusted for traditional CVD risk factors. Among all negative risk markers, coronary artery calcium score of 0 was the strongest, with an adjusted mean DLR of 0.41 (SD, 0.12) for all coronary heart disease and 0.54 (SD, 0.12) for CVD, followed by carotid intima-media thickness <25th percentile (DLR, 0.65 [SD, 0.04] and 0.75 [SD, 0.04], respectively). High-sensitivity C-reactive protein <2 mg/L and normal ankle-brachial index had DLRs >0.80. Among clinical features, absence of any family history of coronary heart disease was the strongest (DLRs, 0.76 [SD, 0.07] and 0.81 [SD, 0.06], respectively). Net reclassification improvement analyses yielded similar findings, with coronary artery calcium score of 0 resulting in the largest, most accurate downward risk reclassification.
  
  
  CONCLUSIONS
  Negative results of atherosclerosis-imaging tests, particularly coronary artery calcium score of 0, resulted in the greatest downward shift in estimated CVD risk. These results may help guide discussions on the identification of individuals less likely to receive net benefit from lifelong preventive pharmacotherapy.
authors.affiliation: From Ciccarone Center for the Prevention of Heart Disease, Johns Hopkins Medical Institutions, Baltimore, MD (M.J.B., M.C.-A., J.W.M., Z.D., R.S.B., K.N.); Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, MD (M.C.-A.); Departments of Medicine and Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL (P.G.); Brigham and Women's Hospital, Boston, MA (R.B.); Los Angeles Biomedical Research Institute at Harbor-UCLA, Torrance, CA (M.J.B.); Knight Cardiovascular Institute, Oregon Health and Science University, Portland (C.T.S.); Department of Public Health Sciences, Wake Forest University, Winston-Salem, NC (G.L.B.); University of Washington, Seattle (R.A.K.); Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (M.J.B., M.S.); Center for Healthcare Advancement and Outcomes, and Miami Cardiac and Vascular Institute, Baptist Heath South Florida, Miami (K.N.). mblaha1@jhmi.edu.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Blaha
authors.affiliation: From Ciccarone Center for the Prevention of Heart Disease, Johns Hopkins Medical Institutions, Baltimore, MD (M.J.B., M.C.-A., J.W.M., Z.D., R.S.B., K.N.); Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, MD (M.C.-A.); Departments of Medicine and Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL (P.G.); Brigham and Women's Hospital, Boston, MA (R.B.); Los Angeles Biomedical Research Institute at Harbor-UCLA, Torrance, CA (M.J.B.); Knight Cardiovascular Institute, Oregon Health and Science University, Portland (C.T.S.); Department of Public Health Sciences, Wake Forest University, Winston-Salem, NC (G.L.B.); University of Washington, Seattle (R.A.K.); Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (M.J.B., M.S.); Center for Healthcare Advancement and Outcomes, and Miami Cardiac and Vascular Institute, Baptist Heath South Florida, Miami (K.N.).
authors.forename: Miguel
authors.initials: M
authors.lastname: Cainzos-Achirica
authors.affiliation: From Ciccarone Center for the Prevention of Heart Disease, Johns Hopkins Medical Institutions, Baltimore, MD (M.J.B., M.C.-A., J.W.M., Z.D., R.S.B., K.N.); Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, MD (M.C.-A.); Departments of Medicine and Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL (P.G.); Brigham and Women's Hospital, Boston, MA (R.B.); Los Angeles Biomedical Research Institute at Harbor-UCLA, Torrance, CA (M.J.B.); Knight Cardiovascular Institute, Oregon Health and Science University, Portland (C.T.S.); Department of Public Health Sciences, Wake Forest University, Winston-Salem, NC (G.L.B.); University of Washington, Seattle (R.A.K.); Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (M.J.B., M.S.); Center for Healthcare Advancement and Outcomes, and Miami Cardiac and Vascular Institute, Baptist Heath South Florida, Miami (K.N.).
authors.forename: Philip
authors.initials: P
authors.lastname: Greenland
authors.affiliation: From Ciccarone Center for the Prevention of Heart Disease, Johns Hopkins Medical Institutions, Baltimore, MD (M.J.B., M.C.-A., J.W.M., Z.D., R.S.B., K.N.); Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, MD (M.C.-A.); Departments of Medicine and Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL (P.G.); Brigham and Women's Hospital, Boston, MA (R.B.); Los Angeles Biomedical Research Institute at Harbor-UCLA, Torrance, CA (M.J.B.); Knight Cardiovascular Institute, Oregon Health and Science University, Portland (C.T.S.); Department of Public Health Sciences, Wake Forest University, Winston-Salem, NC (G.L.B.); University of Washington, Seattle (R.A.K.); Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (M.J.B., M.S.); Center for Healthcare Advancement and Outcomes, and Miami Cardiac and Vascular Institute, Baptist Heath South Florida, Miami (K.N.).
authors.forename: John W
authors.initials: JW
authors.lastname: McEvoy
authors.affiliation: From Ciccarone Center for the Prevention of Heart Disease, Johns Hopkins Medical Institutions, Baltimore, MD (M.J.B., M.C.-A., J.W.M., Z.D., R.S.B., K.N.); Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, MD (M.C.-A.); Departments of Medicine and Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL (P.G.); Brigham and Women's Hospital, Boston, MA (R.B.); Los Angeles Biomedical Research Institute at Harbor-UCLA, Torrance, CA (M.J.B.); Knight Cardiovascular Institute, Oregon Health and Science University, Portland (C.T.S.); Department of Public Health Sciences, Wake Forest University, Winston-Salem, NC (G.L.B.); University of Washington, Seattle (R.A.K.); Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (M.J.B., M.S.); Center for Healthcare Advancement and Outcomes, and Miami Cardiac and Vascular Institute, Baptist Heath South Florida, Miami (K.N.).
authors.forename: Ron
authors.initials: R
authors.lastname: Blankstein
authors.affiliation: From Ciccarone Center for the Prevention of Heart Disease, Johns Hopkins Medical Institutions, Baltimore, MD (M.J.B., M.C.-A., J.W.M., Z.D., R.S.B., K.N.); Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, MD (M.C.-A.); Departments of Medicine and Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL (P.G.); Brigham and Women's Hospital, Boston, MA (R.B.); Los Angeles Biomedical Research Institute at Harbor-UCLA, Torrance, CA (M.J.B.); Knight Cardiovascular Institute, Oregon Health and Science University, Portland (C.T.S.); Department of Public Health Sciences, Wake Forest University, Winston-Salem, NC (G.L.B.); University of Washington, Seattle (R.A.K.); Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (M.J.B., M.S.); Center for Healthcare Advancement and Outcomes, and Miami Cardiac and Vascular Institute, Baptist Heath South Florida, Miami (K.N.).
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Budoff
authors.affiliation: From Ciccarone Center for the Prevention of Heart Disease, Johns Hopkins Medical Institutions, Baltimore, MD (M.J.B., M.C.-A., J.W.M., Z.D., R.S.B., K.N.); Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, MD (M.C.-A.); Departments of Medicine and Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL (P.G.); Brigham and Women's Hospital, Boston, MA (R.B.); Los Angeles Biomedical Research Institute at Harbor-UCLA, Torrance, CA (M.J.B.); Knight Cardiovascular Institute, Oregon Health and Science University, Portland (C.T.S.); Department of Public Health Sciences, Wake Forest University, Winston-Salem, NC (G.L.B.); University of Washington, Seattle (R.A.K.); Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (M.J.B., M.S.); Center for Healthcare Advancement and Outcomes, and Miami Cardiac and Vascular Institute, Baptist Heath South Florida, Miami (K.N.).
authors.forename: Zeina
authors.initials: Z
authors.lastname: Dardari
authors.affiliation: From Ciccarone Center for the Prevention of Heart Disease, Johns Hopkins Medical Institutions, Baltimore, MD (M.J.B., M.C.-A., J.W.M., Z.D., R.S.B., K.N.); Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, MD (M.C.-A.); Departments of Medicine and Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL (P.G.); Brigham and Women's Hospital, Boston, MA (R.B.); Los Angeles Biomedical Research Institute at Harbor-UCLA, Torrance, CA (M.J.B.); Knight Cardiovascular Institute, Oregon Health and Science University, Portland (C.T.S.); Department of Public Health Sciences, Wake Forest University, Winston-Salem, NC (G.L.B.); University of Washington, Seattle (R.A.K.); Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (M.J.B., M.S.); Center for Healthcare Advancement and Outcomes, and Miami Cardiac and Vascular Institute, Baptist Heath South Florida, Miami (K.N.).
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Sibley
authors.affiliation: From Ciccarone Center for the Prevention of Heart Disease, Johns Hopkins Medical Institutions, Baltimore, MD (M.J.B., M.C.-A., J.W.M., Z.D., R.S.B., K.N.); Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, MD (M.C.-A.); Departments of Medicine and Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL (P.G.); Brigham and Women's Hospital, Boston, MA (R.B.); Los Angeles Biomedical Research Institute at Harbor-UCLA, Torrance, CA (M.J.B.); Knight Cardiovascular Institute, Oregon Health and Science University, Portland (C.T.S.); Department of Public Health Sciences, Wake Forest University, Winston-Salem, NC (G.L.B.); University of Washington, Seattle (R.A.K.); Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (M.J.B., M.S.); Center for Healthcare Advancement and Outcomes, and Miami Cardiac and Vascular Institute, Baptist Heath South Florida, Miami (K.N.).
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Burke
authors.affiliation: From Ciccarone Center for the Prevention of Heart Disease, Johns Hopkins Medical Institutions, Baltimore, MD (M.J.B., M.C.-A., J.W.M., Z.D., R.S.B., K.N.); Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, MD (M.C.-A.); Departments of Medicine and Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL (P.G.); Brigham and Women's Hospital, Boston, MA (R.B.); Los Angeles Biomedical Research Institute at Harbor-UCLA, Torrance, CA (M.J.B.); Knight Cardiovascular Institute, Oregon Health and Science University, Portland (C.T.S.); Department of Public Health Sciences, Wake Forest University, Winston-Salem, NC (G.L.B.); University of Washington, Seattle (R.A.K.); Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (M.J.B., M.S.); Center for Healthcare Advancement and Outcomes, and Miami Cardiac and Vascular Institute, Baptist Heath South Florida, Miami (K.N.).
authors.forename: Richard A
authors.initials: RA
authors.lastname: Kronmal
authors.affiliation: From Ciccarone Center for the Prevention of Heart Disease, Johns Hopkins Medical Institutions, Baltimore, MD (M.J.B., M.C.-A., J.W.M., Z.D., R.S.B., K.N.); Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, MD (M.C.-A.); Departments of Medicine and Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL (P.G.); Brigham and Women's Hospital, Boston, MA (R.B.); Los Angeles Biomedical Research Institute at Harbor-UCLA, Torrance, CA (M.J.B.); Knight Cardiovascular Institute, Oregon Health and Science University, Portland (C.T.S.); Department of Public Health Sciences, Wake Forest University, Winston-Salem, NC (G.L.B.); University of Washington, Seattle (R.A.K.); Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (M.J.B., M.S.); Center for Healthcare Advancement and Outcomes, and Miami Cardiac and Vascular Institute, Baptist Heath South Florida, Miami (K.N.).
authors.forename: Moyses
authors.initials: M
authors.lastname: Szklo
authors.affiliation: From Ciccarone Center for the Prevention of Heart Disease, Johns Hopkins Medical Institutions, Baltimore, MD (M.J.B., M.C.-A., J.W.M., Z.D., R.S.B., K.N.); Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, MD (M.C.-A.); Departments of Medicine and Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL (P.G.); Brigham and Women's Hospital, Boston, MA (R.B.); Los Angeles Biomedical Research Institute at Harbor-UCLA, Torrance, CA (M.J.B.); Knight Cardiovascular Institute, Oregon Health and Science University, Portland (C.T.S.); Department of Public Health Sciences, Wake Forest University, Winston-Salem, NC (G.L.B.); University of Washington, Seattle (R.A.K.); Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (M.J.B., M.S.); Center for Healthcare Advancement and Outcomes, and Miami Cardiac and Vascular Institute, Baptist Heath South Florida, Miami (K.N.).
authors.forename: Roger S
authors.initials: RS
authors.lastname: Blumenthal
authors.affiliation: From Ciccarone Center for the Prevention of Heart Disease, Johns Hopkins Medical Institutions, Baltimore, MD (M.J.B., M.C.-A., J.W.M., Z.D., R.S.B., K.N.); Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, MD (M.C.-A.); Departments of Medicine and Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL (P.G.); Brigham and Women's Hospital, Boston, MA (R.B.); Los Angeles Biomedical Research Institute at Harbor-UCLA, Torrance, CA (M.J.B.); Knight Cardiovascular Institute, Oregon Health and Science University, Portland (C.T.S.); Department of Public Health Sciences, Wake Forest University, Winston-Salem, NC (G.L.B.); University of Washington, Seattle (R.A.K.); Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (M.J.B., M.S.); Center for Healthcare Advancement and Outcomes, and Miami Cardiac and Vascular Institute, Baptist Heath South Florida, Miami (K.N.).
authors.forename: Khurram
authors.initials: K
authors.lastname: Nasir
mesh_terms: D000368:Aged; D050197:Atherosclerosis / Q000097:blood* / Q000175:diagnosis / Q000208:ethnology*; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D002118:Calcium / Q000097:blood*; D002318:Cardiovascular Diseases / Q000097:blood / Q000175:diagnosis / Q000208:ethnology; D015331:Cohort Studies; D003331:Coronary Vessels / Q000378:metabolism* / Q000473:pathology; D005006:Ethnicity / Q000208:ethnology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D002097:C-Reactive Protein; D002118:Calcium
keywords: biomarkers; calcium; cardiac imaging techniques; cardiovascular diseases; risk assessment