title: The relationship between smoking intensity and subclinical cardiovascular injury: The Multi-Ethnic Study of Atherosclerosis (MESA).
abstract: Modern tobacco regulatory science requires an understanding of which biomarkers of cardiovascular injury are most sensitive to cigarette smoking exposure.
  
  
  
  We studied self-reported current smokers from the Multi-Ethnic Study of Atherosclerosis. Smoking intensity was defined by number of cigarettes/day and urinary cotinine levels. Subclinical cardiovascular injury was assessed using markers of inflammation [high-sensitivity C-reactive protein (hsCRP), interleukin 6 & 2 (IL-2 & IL-6), tumor necrosis factor alpha (TNF-α)], thrombosis (fibrinogen, D-dimer, homocysteine), myocardial injury (troponin T; TnT), endothelial damage (albumin: creatinine ratio), and vascular function [aortic & carotid distensibility, flow-mediated dilation (FMD)]. Biomarkers were modeled as absolute and percent change using multivariable-adjusted linear regression models adjusted for cardiovascular risk factors and smoking duration.
  
  
  
  Among 843 current smokers, mean age was 58 (9) years, 53% were men, 39% were African American, mean number of cigarettes per day was 13 (10), and median smoking duration was 39 (15) years. Cigarette count was significantly associated with higher hsCRP, IL-6 and fibrinogen (β coefficients: 0.013, 0.011, 0.60 respectively), while ln-transformed cotinine was associated with the same biomarkers (β coefficients: 0.12, 0.04, 5.3 respectively) and inversely associated with aortic distensibility (β coefficient: -0.13). There was a limited association between smoking intensity and homocysteine, D-dimer, and albumin:creatinine ratio in partially adjusted models only, while there was no association with IL-2, TNF-α, carotid distensibility, FMD, or TnT in any model. In percent change analyses, relationships were strongest with hsCRP.
  
  
  
  Smoking intensity was associated with early biomarkers of CVD, particularly, markers of systemic inflammation. Of these, hsCRP may be the most sensitive.
authors.affiliation: Department of Medicine, University of Kansas School of Medicine, Wichita, KS, USA; Johns Hopkins Ciccarone Center for Prevention of Heart Disease, Baltimore, MD, USA.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Al Rifai
authors.affiliation: Johns Hopkins Ciccarone Center for Prevention of Heart Disease, Baltimore, MD, USA; Diabetes and Obesity Center, University of Louisville School of Medicine, Louisville, KY, USA; Division of Cardiology, University of Louisville School of Medicine, Louisville, KY, USA.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: DeFilippis
authors.affiliation: Johns Hopkins Ciccarone Center for Prevention of Heart Disease, Baltimore, MD, USA.
authors.forename: John W
authors.initials: JW
authors.lastname: McEvoy
authors.affiliation: University of Mississippi Medical Center, Division of Cardiology, Jackson, MS, USA.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Hall
authors.affiliation: Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
authors.forename: Ana Navas
authors.initials: AN
authors.lastname: Acien
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
authors.forename: Miranda R
authors.initials: MR
authors.lastname: Jones
authors.affiliation: Diabetes and Obesity Center, University of Louisville School of Medicine, Louisville, KY, USA; Division of Cardiology, University of Louisville School of Medicine, Louisville, KY, USA.
authors.forename: Rachel
authors.initials: R
authors.lastname: Keith
authors.affiliation: UC Berkeley School of Public Health, Berkley, CA, USA.
authors.forename: Hoda S
authors.initials: HS
authors.lastname: Magid
authors.affiliation: Maya Angelou Center for Health Equity, Wake Forest University, Winston-Salem, NC, USA.
authors.forename: Carlos J
authors.initials: CJ
authors.lastname: Rodriguez
authors.affiliation: Columbia University Medical Center, Division of Pulmonary, Allergy and Critical Care Medicine, New York, NY, USA.
authors.forename: Graham R
authors.initials: GR
authors.lastname: Barr
authors.affiliation: Boston University, School of Medicine, Vascular Testing and Echocardiography, Boston, MA, USA.
authors.forename: Emelia J
authors.initials: EJ
authors.lastname: Benjamin
authors.affiliation: American Heart Association, Chief Science Office, Dallas, TX, USA.
authors.forename: Rose Marie
authors.initials: RM
authors.lastname: Robertson
authors.affiliation: Diabetes and Obesity Center, University of Louisville School of Medicine, Louisville, KY, USA; Division of Cardiology, University of Louisville School of Medicine, Louisville, KY, USA.
authors.forename: Aruni
authors.initials: A
authors.lastname: Bhatnagar
authors.affiliation: Johns Hopkins Ciccarone Center for Prevention of Heart Disease, Baltimore, MD, USA. Electronic address: mblaha1@jhmi.edu.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Blaha
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood / Q000652:urine; D001777:Blood Coagulation; D002097:C-Reactive Protein / Q000032:analysis; D002318:Cardiovascular Diseases / Q000175:diagnosis / Q000208:ethnology / Q000209:etiology* / Q000503:physiopathology; D016009:Chi-Square Distribution; D003367:Cotinine / Q000652:urine; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000097:blood; D042241:Early Diagnosis; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products; D005340:Fibrinogen; D006710:Homocysteine / Q000097:blood; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D018570:Risk Assessment; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects* / Q000208:ethnology / Q000652:urine; D020107:Troponin T / Q000097:blood; D014481:United States / Q000453:epidemiology; D059289:Vascular Stiffness; D014664:Vasodilation
chemical_list: D015415:Biomarkers; D016207:Cytokines; D005338:Fibrin Fibrinogen Degradation Products; D018836:Inflammation Mediators; D020107:Troponin T; C036309:fibrin fragment D; D006710:Homocysteine; D005340:Fibrinogen; D002097:C-Reactive Protein; D003367:Cotinine
keywords: Cigarette smoking; Endothelial damage; Inflammation; Myocardial injury; Smoking intensity; Thrombosis; Tobacco regulatory science; Vascular dysfunction