title: Forced Expiratory Volume in the First Second and Aldosterone as Mediators of Smoking Effect on Stroke in African Americans: The Jackson Heart Study.
abstract: BACKGROUND
  Cigarette smoking is a risk factor for stroke, but the mechanisms by which smoking contributes to stroke are not well understood. This study aimed to evaluate the roles of lung function (represented by forced expiratory volume in the first second (FEV1)) and aldosterone as potential mediators of the association of smoking with stroke.
  
  
  RESULTS
  The data were derived from 5010 Jackson Heart Study participants who had mean follow-up of 97.9 months. Using the Cox proportional hazards model, we estimated the hazard ratios of smoking for total stroke with and without adjustment for FEV1 and/or aldosterone at baseline after controlling for the confounders. The hazard ratio for current smoking (versus never smoking) was 2.70 (95% CI 1.71 to 4.25) for total stroke after adjustment for the confounders. Additional adjustment for FEV1 and aldosterone reduced the hazard ratio to 2.32 (95% CI 1.42 to 3.79), suggesting that 22.4% of the excess risk of current smoking for total stroke is mediated by these factors. FEV1 and aldosterone account for 13.1% and 12.1%, respectively, of the excess risk. The hazard ratio for FEV1 increased (0.61 versus 0.65) after including systemic inflammatory marker C-reactive protein, and the hazard ratios for aldosterone were comparable for the models that included all confounders and smoking status with or without different blood pressure measurements.
  
  
  CONCLUSIONS
  Our findings suggest that the difference in stroke risk between current and never smokers may develop partially through pathways involving lung function and aldosterone and that the mediation effect through aldosterone is independent of blood pressure.
authors.affiliation: Center of Biostatistics and Bioinformatics, University of Mississippi Medical Center, Jackson, MS (W.W., M.E.G.).
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Mathematics and Statistics, Mississippi State University, Mississippi State, MS (G.S.).
authors.forename: Gui
authors.initials: G
authors.lastname: Shen
authors.affiliation: Department of Epidemiology and Biostatistics, Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, AZ (E.S.).
authors.forename: Eyal
authors.initials: E
authors.lastname: Shahar
authors.affiliation: Department of Epidemiology and Biostatistics, Indiana University School of Public Health, Bloomington, IN (A.B., S.H.).
authors.forename: Aurelian
authors.initials: A
authors.lastname: Bidulescu
authors.affiliation: Department of Neurology, Massachusetts General Hospital, Boston, MA (T.K.).
authors.forename: W Taylor
authors.initials: WT
authors.lastname: Kimberly
authors.affiliation: Division of Neurocritical Care & Emergency Neurology, School of Medicine, Yale University, New Haven, CT (K.N.S.).
authors.forename: Kevin N
authors.initials: KN
authors.lastname: Sheth
authors.affiliation: Jackson State University, Jackson, MS (B.W.C.).
authors.forename: Brenda W
authors.initials: BW
authors.lastname: Campbell
authors.affiliation: Department of Epidemiology and Biostatistics, Indiana University School of Public Health, Bloomington, IN (A.B., S.H.).
authors.forename: Steven
authors.initials: S
authors.lastname: Horbal
authors.affiliation: Jackson Heart Study, Department of Medicine, University of Mississippi Medical Center, Jackson, MS (A.C.).
authors.forename: Adolfo
authors.initials: A
authors.lastname: Correa
authors.affiliation: Center of Biostatistics and Bioinformatics, University of Mississippi Medical Center, Jackson, MS (W.W., M.E.G.).
authors.forename: Michael E
authors.initials: ME
authors.lastname: Griswold
mesh_terms: D000328:Adult; D001741:Black or African American; D000368:Aged; D000450:Aldosterone / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D016014:Linear Models; D008168:Lung / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D008922:Mississippi / Q000453:epidemiology; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects* / Q000097:blood / Q000208:ethnology*; D020521:Stroke / Q000097:blood / Q000175:diagnosis / Q000208:ethnology* / Q000209:etiology* / Q000503:physiopathology; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D000450:Aldosterone
keywords: aldosterone; lung function; mediation effects; smoking; stroke
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