title: Cigarette smoking and cardiovascular events: role of inflammation and subclinical atherosclerosis from the MultiEthnic Study of Atherosclerosis.
abstract: OBJECTIVE
  To examine the contemporary effect of smoking in a multiethnic sample, and to explore the respective contributions of inflammation and subclinical atherosclerosis to the cardiovascular consequences of smoking.
  
  
  RESULTS
  We studied 6814 participants free of cardiovascular disease and coronary heart disease (CHD) from the Multiethnic Study of Atherosclerosis. Smoking status and cumulative exposure were determined by self-report and confirmed by urinary cotinine. Multivariable Cox regression was used to estimate the association between smoking parameters and all-cause cardiovascular disease, all-cause CHD, and hard CHD events. We further adjusted for high-sensitivity C-reactive protein and coronary artery calcium (CAC) in hierarchical Cox models. We identified 3218 never smokers, 2607 former smokers, and 971 current smokers. Median follow-up was 10.2 years. Compared with never smokers, adjusted hazard ratios in current smokers were 1.7 (95% confidence interval, 1.3-2.2) for all-cause cardiovascular disease, 1.6 (1.1-2.1) for all-cause CHD, and 1.7 (1.2-2.4) for hard CHD. Similarly, among current smokers, hazard ratios were higher in the 4th versus 1st quartile of pack-years (eg, all-cause CHD hazard ratio=2.7 [1.1-6.6]). Both CAC>100 and high-sensitivity C-reactive protein ≥3 mg/L identified higher relative risk among current smokers (eg, all-cause CHD hazard ratio of 3.0 [1.5-6.0, compared with CAC=0] and 2.6 [1.4-4.8, compared with high-sensitivity C-reactive protein <2 mg/L], respectively). However, CAC was a stronger mediator of events and adversely modified the effect of smoking on events (eg, P-interaction=0.02 for hard CHD). Compared with never smokers, former smokers (median cessation interval=22 years) had similar adjusted hazard for events.
  
  
  CONCLUSIONS
  In this multiethnic cohort, current smoking and cumulative exposure remain important modifiable determinants of cardiovascular disease. Both high-sensitivity C-reactive protein ≥3 mg/L and, particularly, CAC>100 identified high-risk smokers who may benefit from more intensive smoking-cessation efforts.
authors.affiliation: From the Ciccarone Center for the Prevention of Heart Disease (J.W.M., M.J. Blaha, A.P.D., R.S.B., K.N.) and Division of Cardiology (J.A.C.L.), Johns Hopkins University, Baltimore, MD; Division of Cardiology, Rudd Heart and Lung Center, University of Louisville, KY (A.P.D.); Radiology and Imaging Sciences, National Institutes of Health, Bethesda, MD (D.A.B.); Division of Cardiology, Wake Forest University Health Center, Winston-Salem, NC (W.G.H.); Division of Cardiology, Cedars Sinai Medical Center, Heart Institute, Los Angeles, CA (J.K.M.); Division of Cardiology, Emory University School of Medicine, Atlanta, GA (L.J.S.); Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL (D.M.L.-J.); Division of General Medicine, Division of Pulmonary, Allergy and Critical Care, Department of Medicine and Department of Epidemiology, Columbia University Medical Center, New York, NY (R.G.B.); Los Angeles Biomedical Research Institute at Harbor-UCLA, Torrance, CA (M.J. Budoff); Center for Wellness and Prevention, and Miami Cardiovascular Institute (MCVI), Baptist Health South Florida, Miami (K.N.); and Department of Medicine, Herbert Wertheim College of Medicine, and Department of Epidemiology, Robert Stempel College of Public Health, Florida International University, Miami (K.N.).
authors.forename: John W
authors.initials: JW
authors.lastname: McEvoy
authors.affiliation: From the Ciccarone Center for the Prevention of Heart Disease (J.W.M., M.J. Blaha, A.P.D., R.S.B., K.N.) and Division of Cardiology (J.A.C.L.), Johns Hopkins University, Baltimore, MD; Division of Cardiology, Rudd Heart and Lung Center, University of Louisville, KY (A.P.D.); Radiology and Imaging Sciences, National Institutes of Health, Bethesda, MD (D.A.B.); Division of Cardiology, Wake Forest University Health Center, Winston-Salem, NC (W.G.H.); Division of Cardiology, Cedars Sinai Medical Center, Heart Institute, Los Angeles, CA (J.K.M.); Division of Cardiology, Emory University School of Medicine, Atlanta, GA (L.J.S.); Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL (D.M.L.-J.); Division of General Medicine, Division of Pulmonary, Allergy and Critical Care, Department of Medicine and Department of Epidemiology, Columbia University Medical Center, New York, NY (R.G.B.); Los Angeles Biomedical Research Institute at Harbor-UCLA, Torrance, CA (M.J. Budoff); Center for Wellness and Prevention, and Miami Cardiovascular Institute (MCVI), Baptist Health South Florida, Miami (K.N.); and Department of Medicine, Herbert Wertheim College of Medicine, and Department of Epidemiology, Robert Stempel College of Public Health, Florida International University, Miami (K.N.).
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Blaha
authors.affiliation: From the Ciccarone Center for the Prevention of Heart Disease (J.W.M., M.J. Blaha, A.P.D., R.S.B., K.N.) and Division of Cardiology (J.A.C.L.), Johns Hopkins University, Baltimore, MD; Division of Cardiology, Rudd Heart and Lung Center, University of Louisville, KY (A.P.D.); Radiology and Imaging Sciences, National Institutes of Health, Bethesda, MD (D.A.B.); Division of Cardiology, Wake Forest University Health Center, Winston-Salem, NC (W.G.H.); Division of Cardiology, Cedars Sinai Medical Center, Heart Institute, Los Angeles, CA (J.K.M.); Division of Cardiology, Emory University School of Medicine, Atlanta, GA (L.J.S.); Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL (D.M.L.-J.); Division of General Medicine, Division of Pulmonary, Allergy and Critical Care, Department of Medicine and Department of Epidemiology, Columbia University Medical Center, New York, NY (R.G.B.); Los Angeles Biomedical Research Institute at Harbor-UCLA, Torrance, CA (M.J. Budoff); Center for Wellness and Prevention, and Miami Cardiovascular Institute (MCVI), Baptist Health South Florida, Miami (K.N.); and Department of Medicine, Herbert Wertheim College of Medicine, and Department of Epidemiology, Robert Stempel College of Public Health, Florida International University, Miami (K.N.).
authors.forename: Andrew P
authors.initials: AP
authors.lastname: DeFilippis
authors.affiliation: From the Ciccarone Center for the Prevention of Heart Disease (J.W.M., M.J. Blaha, A.P.D., R.S.B., K.N.) and Division of Cardiology (J.A.C.L.), Johns Hopkins University, Baltimore, MD; Division of Cardiology, Rudd Heart and Lung Center, University of Louisville, KY (A.P.D.); Radiology and Imaging Sciences, National Institutes of Health, Bethesda, MD (D.A.B.); Division of Cardiology, Wake Forest University Health Center, Winston-Salem, NC (W.G.H.); Division of Cardiology, Cedars Sinai Medical Center, Heart Institute, Los Angeles, CA (J.K.M.); Division of Cardiology, Emory University School of Medicine, Atlanta, GA (L.J.S.); Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL (D.M.L.-J.); Division of General Medicine, Division of Pulmonary, Allergy and Critical Care, Department of Medicine and Department of Epidemiology, Columbia University Medical Center, New York, NY (R.G.B.); Los Angeles Biomedical Research Institute at Harbor-UCLA, Torrance, CA (M.J. Budoff); Center for Wellness and Prevention, and Miami Cardiovascular Institute (MCVI), Baptist Health South Florida, Miami (K.N.); and Department of Medicine, Herbert Wertheim College of Medicine, and Department of Epidemiology, Robert Stempel College of Public Health, Florida International University, Miami (K.N.).
authors.forename: Joao A C
authors.initials: JA
authors.lastname: Lima
authors.affiliation: From the Ciccarone Center for the Prevention of Heart Disease (J.W.M., M.J. Blaha, A.P.D., R.S.B., K.N.) and Division of Cardiology (J.A.C.L.), Johns Hopkins University, Baltimore, MD; Division of Cardiology, Rudd Heart and Lung Center, University of Louisville, KY (A.P.D.); Radiology and Imaging Sciences, National Institutes of Health, Bethesda, MD (D.A.B.); Division of Cardiology, Wake Forest University Health Center, Winston-Salem, NC (W.G.H.); Division of Cardiology, Cedars Sinai Medical Center, Heart Institute, Los Angeles, CA (J.K.M.); Division of Cardiology, Emory University School of Medicine, Atlanta, GA (L.J.S.); Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL (D.M.L.-J.); Division of General Medicine, Division of Pulmonary, Allergy and Critical Care, Department of Medicine and Department of Epidemiology, Columbia University Medical Center, New York, NY (R.G.B.); Los Angeles Biomedical Research Institute at Harbor-UCLA, Torrance, CA (M.J. Budoff); Center for Wellness and Prevention, and Miami Cardiovascular Institute (MCVI), Baptist Health South Florida, Miami (K.N.); and Department of Medicine, Herbert Wertheim College of Medicine, and Department of Epidemiology, Robert Stempel College of Public Health, Florida International University, Miami (K.N.).
authors.forename: David A
authors.initials: DA
authors.lastname: Bluemke
authors.affiliation: From the Ciccarone Center for the Prevention of Heart Disease (J.W.M., M.J. Blaha, A.P.D., R.S.B., K.N.) and Division of Cardiology (J.A.C.L.), Johns Hopkins University, Baltimore, MD; Division of Cardiology, Rudd Heart and Lung Center, University of Louisville, KY (A.P.D.); Radiology and Imaging Sciences, National Institutes of Health, Bethesda, MD (D.A.B.); Division of Cardiology, Wake Forest University Health Center, Winston-Salem, NC (W.G.H.); Division of Cardiology, Cedars Sinai Medical Center, Heart Institute, Los Angeles, CA (J.K.M.); Division of Cardiology, Emory University School of Medicine, Atlanta, GA (L.J.S.); Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL (D.M.L.-J.); Division of General Medicine, Division of Pulmonary, Allergy and Critical Care, Department of Medicine and Department of Epidemiology, Columbia University Medical Center, New York, NY (R.G.B.); Los Angeles Biomedical Research Institute at Harbor-UCLA, Torrance, CA (M.J. Budoff); Center for Wellness and Prevention, and Miami Cardiovascular Institute (MCVI), Baptist Health South Florida, Miami (K.N.); and Department of Medicine, Herbert Wertheim College of Medicine, and Department of Epidemiology, Robert Stempel College of Public Health, Florida International University, Miami (K.N.).
authors.forename: W Gregory
authors.initials: WG
authors.lastname: Hundley
authors.affiliation: From the Ciccarone Center for the Prevention of Heart Disease (J.W.M., M.J. Blaha, A.P.D., R.S.B., K.N.) and Division of Cardiology (J.A.C.L.), Johns Hopkins University, Baltimore, MD; Division of Cardiology, Rudd Heart and Lung Center, University of Louisville, KY (A.P.D.); Radiology and Imaging Sciences, National Institutes of Health, Bethesda, MD (D.A.B.); Division of Cardiology, Wake Forest University Health Center, Winston-Salem, NC (W.G.H.); Division of Cardiology, Cedars Sinai Medical Center, Heart Institute, Los Angeles, CA (J.K.M.); Division of Cardiology, Emory University School of Medicine, Atlanta, GA (L.J.S.); Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL (D.M.L.-J.); Division of General Medicine, Division of Pulmonary, Allergy and Critical Care, Department of Medicine and Department of Epidemiology, Columbia University Medical Center, New York, NY (R.G.B.); Los Angeles Biomedical Research Institute at Harbor-UCLA, Torrance, CA (M.J. Budoff); Center for Wellness and Prevention, and Miami Cardiovascular Institute (MCVI), Baptist Health South Florida, Miami (K.N.); and Department of Medicine, Herbert Wertheim College of Medicine, and Department of Epidemiology, Robert Stempel College of Public Health, Florida International University, Miami (K.N.).
authors.forename: James K
authors.initials: JK
authors.lastname: Min
authors.affiliation: From the Ciccarone Center for the Prevention of Heart Disease (J.W.M., M.J. Blaha, A.P.D., R.S.B., K.N.) and Division of Cardiology (J.A.C.L.), Johns Hopkins University, Baltimore, MD; Division of Cardiology, Rudd Heart and Lung Center, University of Louisville, KY (A.P.D.); Radiology and Imaging Sciences, National Institutes of Health, Bethesda, MD (D.A.B.); Division of Cardiology, Wake Forest University Health Center, Winston-Salem, NC (W.G.H.); Division of Cardiology, Cedars Sinai Medical Center, Heart Institute, Los Angeles, CA (J.K.M.); Division of Cardiology, Emory University School of Medicine, Atlanta, GA (L.J.S.); Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL (D.M.L.-J.); Division of General Medicine, Division of Pulmonary, Allergy and Critical Care, Department of Medicine and Department of Epidemiology, Columbia University Medical Center, New York, NY (R.G.B.); Los Angeles Biomedical Research Institute at Harbor-UCLA, Torrance, CA (M.J. Budoff); Center for Wellness and Prevention, and Miami Cardiovascular Institute (MCVI), Baptist Health South Florida, Miami (K.N.); and Department of Medicine, Herbert Wertheim College of Medicine, and Department of Epidemiology, Robert Stempel College of Public Health, Florida International University, Miami (K.N.).
authors.forename: Leslee J
authors.initials: LJ
authors.lastname: Shaw
authors.affiliation: From the Ciccarone Center for the Prevention of Heart Disease (J.W.M., M.J. Blaha, A.P.D., R.S.B., K.N.) and Division of Cardiology (J.A.C.L.), Johns Hopkins University, Baltimore, MD; Division of Cardiology, Rudd Heart and Lung Center, University of Louisville, KY (A.P.D.); Radiology and Imaging Sciences, National Institutes of Health, Bethesda, MD (D.A.B.); Division of Cardiology, Wake Forest University Health Center, Winston-Salem, NC (W.G.H.); Division of Cardiology, Cedars Sinai Medical Center, Heart Institute, Los Angeles, CA (J.K.M.); Division of Cardiology, Emory University School of Medicine, Atlanta, GA (L.J.S.); Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL (D.M.L.-J.); Division of General Medicine, Division of Pulmonary, Allergy and Critical Care, Department of Medicine and Department of Epidemiology, Columbia University Medical Center, New York, NY (R.G.B.); Los Angeles Biomedical Research Institute at Harbor-UCLA, Torrance, CA (M.J. Budoff); Center for Wellness and Prevention, and Miami Cardiovascular Institute (MCVI), Baptist Health South Florida, Miami (K.N.); and Department of Medicine, Herbert Wertheim College of Medicine, and Department of Epidemiology, Robert Stempel College of Public Health, Florida International University, Miami (K.N.).
authors.forename: Donald M
authors.initials: DM
authors.lastname: Lloyd-Jones
authors.affiliation: From the Ciccarone Center for the Prevention of Heart Disease (J.W.M., M.J. Blaha, A.P.D., R.S.B., K.N.) and Division of Cardiology (J.A.C.L.), Johns Hopkins University, Baltimore, MD; Division of Cardiology, Rudd Heart and Lung Center, University of Louisville, KY (A.P.D.); Radiology and Imaging Sciences, National Institutes of Health, Bethesda, MD (D.A.B.); Division of Cardiology, Wake Forest University Health Center, Winston-Salem, NC (W.G.H.); Division of Cardiology, Cedars Sinai Medical Center, Heart Institute, Los Angeles, CA (J.K.M.); Division of Cardiology, Emory University School of Medicine, Atlanta, GA (L.J.S.); Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL (D.M.L.-J.); Division of General Medicine, Division of Pulmonary, Allergy and Critical Care, Department of Medicine and Department of Epidemiology, Columbia University Medical Center, New York, NY (R.G.B.); Los Angeles Biomedical Research Institute at Harbor-UCLA, Torrance, CA (M.J. Budoff); Center for Wellness and Prevention, and Miami Cardiovascular Institute (MCVI), Baptist Health South Florida, Miami (K.N.); and Department of Medicine, Herbert Wertheim College of Medicine, and Department of Epidemiology, Robert Stempel College of Public Health, Florida International University, Miami (K.N.).
authors.forename: R Graham
authors.initials: RG
authors.lastname: Barr
authors.affiliation: From the Ciccarone Center for the Prevention of Heart Disease (J.W.M., M.J. Blaha, A.P.D., R.S.B., K.N.) and Division of Cardiology (J.A.C.L.), Johns Hopkins University, Baltimore, MD; Division of Cardiology, Rudd Heart and Lung Center, University of Louisville, KY (A.P.D.); Radiology and Imaging Sciences, National Institutes of Health, Bethesda, MD (D.A.B.); Division of Cardiology, Wake Forest University Health Center, Winston-Salem, NC (W.G.H.); Division of Cardiology, Cedars Sinai Medical Center, Heart Institute, Los Angeles, CA (J.K.M.); Division of Cardiology, Emory University School of Medicine, Atlanta, GA (L.J.S.); Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL (D.M.L.-J.); Division of General Medicine, Division of Pulmonary, Allergy and Critical Care, Department of Medicine and Department of Epidemiology, Columbia University Medical Center, New York, NY (R.G.B.); Los Angeles Biomedical Research Institute at Harbor-UCLA, Torrance, CA (M.J. Budoff); Center for Wellness and Prevention, and Miami Cardiovascular Institute (MCVI), Baptist Health South Florida, Miami (K.N.); and Department of Medicine, Herbert Wertheim College of Medicine, and Department of Epidemiology, Robert Stempel College of Public Health, Florida International University, Miami (K.N.).
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Budoff
authors.affiliation: From the Ciccarone Center for the Prevention of Heart Disease (J.W.M., M.J. Blaha, A.P.D., R.S.B., K.N.) and Division of Cardiology (J.A.C.L.), Johns Hopkins University, Baltimore, MD; Division of Cardiology, Rudd Heart and Lung Center, University of Louisville, KY (A.P.D.); Radiology and Imaging Sciences, National Institutes of Health, Bethesda, MD (D.A.B.); Division of Cardiology, Wake Forest University Health Center, Winston-Salem, NC (W.G.H.); Division of Cardiology, Cedars Sinai Medical Center, Heart Institute, Los Angeles, CA (J.K.M.); Division of Cardiology, Emory University School of Medicine, Atlanta, GA (L.J.S.); Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL (D.M.L.-J.); Division of General Medicine, Division of Pulmonary, Allergy and Critical Care, Department of Medicine and Department of Epidemiology, Columbia University Medical Center, New York, NY (R.G.B.); Los Angeles Biomedical Research Institute at Harbor-UCLA, Torrance, CA (M.J. Budoff); Center for Wellness and Prevention, and Miami Cardiovascular Institute (MCVI), Baptist Health South Florida, Miami (K.N.); and Department of Medicine, Herbert Wertheim College of Medicine, and Department of Epidemiology, Robert Stempel College of Public Health, Florida International University, Miami (K.N.).
authors.forename: Roger S
authors.initials: RS
authors.lastname: Blumenthal
authors.affiliation: From the Ciccarone Center for the Prevention of Heart Disease (J.W.M., M.J. Blaha, A.P.D., R.S.B., K.N.) and Division of Cardiology (J.A.C.L.), Johns Hopkins University, Baltimore, MD; Division of Cardiology, Rudd Heart and Lung Center, University of Louisville, KY (A.P.D.); Radiology and Imaging Sciences, National Institutes of Health, Bethesda, MD (D.A.B.); Division of Cardiology, Wake Forest University Health Center, Winston-Salem, NC (W.G.H.); Division of Cardiology, Cedars Sinai Medical Center, Heart Institute, Los Angeles, CA (J.K.M.); Division of Cardiology, Emory University School of Medicine, Atlanta, GA (L.J.S.); Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL (D.M.L.-J.); Division of General Medicine, Division of Pulmonary, Allergy and Critical Care, Department of Medicine and Department of Epidemiology, Columbia University Medical Center, New York, NY (R.G.B.); Los Angeles Biomedical Research Institute at Harbor-UCLA, Torrance, CA (M.J. Budoff); Center for Wellness and Prevention, and Miami Cardiovascular Institute (MCVI), Baptist Health South Florida, Miami (K.N.); and Department of Medicine, Herbert Wertheim College of Medicine, and Department of Epidemiology, Robert Stempel College of Public Health, Florida International University, Miami (K.N.). khurramn@baptisthealth.net.
authors.forename: Khurram
authors.initials: K
authors.lastname: Nasir
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D058070:Asymptomatic Diseases; D050197:Atherosclerosis / Q000097:blood / Q000175:diagnosis / Q000208:ethnology* / Q000401:mortality; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D002561:Cerebrovascular Disorders / Q000175:diagnosis / Q000208:ethnology* / Q000401:mortality / Q000517:prevention & control / Q000628:therapy; D016009:Chi-Square Distribution; D003327:Coronary Disease / Q000175:diagnosis / Q000208:ethnology* / Q000401:mortality / Q000517:prevention & control / Q000628:therapy; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000175:diagnosis / Q000208:ethnology* / Q000401:mortality; D018836:Inflammation Mediators / Q000097:blood; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D040242:Risk Reduction Behavior; D012907:Smoking / Q000009:adverse effects* / Q000208:ethnology* / Q000401:mortality; D000074606:Smoking Prevention; D013997:Time Factors; D014481:United States / Q000453:epidemiology; D061205:Vascular Calcification / Q000208:ethnology
chemical_list: D015415:Biomarkers; D018836:Inflammation Mediators; D002097:C-Reactive Protein
keywords: coronary artery disease; inflammation; smoking