title: Reflection magnitude as a predictor of mortality: the Multi-Ethnic Study of Atherosclerosis.
abstract: Arterial wave reflections have been associated with mortality in an ethnically homogenous Asian population. It is unknown whether this association is present in a multiethnic population or whether it is independent of subclinical atherosclerosis. We hypothesized that reflection magnitude (defined as the ratio of the amplitude of the backward wave [Pb] to that of the forward wave [Pf]) is associated with all-cause mortality in a large multiethnic adult community-based sample. We studied 5984 participants enrolled in the Multi-Ethnic Study of Atherosclerosis who had analyzable arterial tonometry waveforms. During 9.8±1.7 years of follow-up, 617 deaths occurred, of which 134 (22%) were adjudicated cardiovascular deaths. In Cox proportional hazards models, each 10% increase in reflection magnitude was associated with a 31% increased risk for all-cause mortality (hazard ratio [HR]=1.31; 95% confidence interval [CI]=1.11-1.55; P=0.001). This relationship persisted after adjustment for various confounders and for markers of subclinical atherosclerosis (HR=1.23; 95% CI=1.01-1.51; P=0.04), including the coronary calcium score, ankle-brachial index, common carotid intima-media thickness, and ascending thoracic aortic Agatston score. Pb was independently associated with all-cause mortality in a similarly adjusted model (HR per 10 mm Hg increase in P(b)=2.18; 95% CI=1.21-3.92; P=0.009). Reflection magnitude (HR=1.71; 95% CI=1.06-2.77; P=0.03) and P(b) (HR=5.02; 95% CI=1.29-19.42; P=0.02) were mainly associated with cardiovascular mortality. In conclusion, reflection magnitude is independently associated with all-cause mortality in a multiethnic population initially free of clinically evident cardiovascular disease. This relationship persists after adjustment for a comprehensive set of markers of subclinical atherosclerosis.
authors.affiliation: From the Division of Cardiovascular Medicine, Hospital of the University of Pennsylvania, Perelman School of Medicine and Philadelphia VA Medical Center, Philadelphia (P.Z., J.A.C.); Division of Epidemiology and Community Health, School of Public Health (D.R.J., P.H.) and Division of Cardiology, School of Medicine (D.A.D.), University of Minnesota. Minneapolis; Biofluid, Tissue, and Solid Mechanics for Medical Applications, IBiTech, iMinds Future Health Department, Ghent University, Ghent, Belgium (P.S.); Department of Biostatistics, School of Public Health, University of Washington, Seattle (L.B., R.A.K.); Division of Cardiovascular Medicine, The Ohio State University Heart and Vascular Center, Columbus (S.M.L.); Division of Nephrology/Hypertension, Perelman School of Medicine, University of Pennsylvania, Philadelphia (R.R.T.); Los Angeles Biomedical Research Institute, Torrance, CA (M.B.); and Division of Cardiology, Johns Hopkins Hospital, Baltimore, MD (J.A.L.). pzamani@upenn.edu.
authors.forename: Payman
authors.initials: P
authors.lastname: Zamani
authors.affiliation: From the Division of Cardiovascular Medicine, Hospital of the University of Pennsylvania, Perelman School of Medicine and Philadelphia VA Medical Center, Philadelphia (P.Z., J.A.C.); Division of Epidemiology and Community Health, School of Public Health (D.R.J., P.H.) and Division of Cardiology, School of Medicine (D.A.D.), University of Minnesota. Minneapolis; Biofluid, Tissue, and Solid Mechanics for Medical Applications, IBiTech, iMinds Future Health Department, Ghent University, Ghent, Belgium (P.S.); Department of Biostatistics, School of Public Health, University of Washington, Seattle (L.B., R.A.K.); Division of Cardiovascular Medicine, The Ohio State University Heart and Vascular Center, Columbus (S.M.L.); Division of Nephrology/Hypertension, Perelman School of Medicine, University of Pennsylvania, Philadelphia (R.R.T.); Los Angeles Biomedical Research Institute, Torrance, CA (M.B.); and Division of Cardiology, Johns Hopkins Hospital, Baltimore, MD (J.A.L.).
authors.forename: David R
authors.initials: DR
authors.lastname: Jacobs
authors.affiliation: From the Division of Cardiovascular Medicine, Hospital of the University of Pennsylvania, Perelman School of Medicine and Philadelphia VA Medical Center, Philadelphia (P.Z., J.A.C.); Division of Epidemiology and Community Health, School of Public Health (D.R.J., P.H.) and Division of Cardiology, School of Medicine (D.A.D.), University of Minnesota. Minneapolis; Biofluid, Tissue, and Solid Mechanics for Medical Applications, IBiTech, iMinds Future Health Department, Ghent University, Ghent, Belgium (P.S.); Department of Biostatistics, School of Public Health, University of Washington, Seattle (L.B., R.A.K.); Division of Cardiovascular Medicine, The Ohio State University Heart and Vascular Center, Columbus (S.M.L.); Division of Nephrology/Hypertension, Perelman School of Medicine, University of Pennsylvania, Philadelphia (R.R.T.); Los Angeles Biomedical Research Institute, Torrance, CA (M.B.); and Division of Cardiology, Johns Hopkins Hospital, Baltimore, MD (J.A.L.).
authors.forename: Patrick
authors.initials: P
authors.lastname: Segers
authors.affiliation: From the Division of Cardiovascular Medicine, Hospital of the University of Pennsylvania, Perelman School of Medicine and Philadelphia VA Medical Center, Philadelphia (P.Z., J.A.C.); Division of Epidemiology and Community Health, School of Public Health (D.R.J., P.H.) and Division of Cardiology, School of Medicine (D.A.D.), University of Minnesota. Minneapolis; Biofluid, Tissue, and Solid Mechanics for Medical Applications, IBiTech, iMinds Future Health Department, Ghent University, Ghent, Belgium (P.S.); Department of Biostatistics, School of Public Health, University of Washington, Seattle (L.B., R.A.K.); Division of Cardiovascular Medicine, The Ohio State University Heart and Vascular Center, Columbus (S.M.L.); Division of Nephrology/Hypertension, Perelman School of Medicine, University of Pennsylvania, Philadelphia (R.R.T.); Los Angeles Biomedical Research Institute, Torrance, CA (M.B.); and Division of Cardiology, Johns Hopkins Hospital, Baltimore, MD (J.A.L.).
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Duprez
authors.affiliation: From the Division of Cardiovascular Medicine, Hospital of the University of Pennsylvania, Perelman School of Medicine and Philadelphia VA Medical Center, Philadelphia (P.Z., J.A.C.); Division of Epidemiology and Community Health, School of Public Health (D.R.J., P.H.) and Division of Cardiology, School of Medicine (D.A.D.), University of Minnesota. Minneapolis; Biofluid, Tissue, and Solid Mechanics for Medical Applications, IBiTech, iMinds Future Health Department, Ghent University, Ghent, Belgium (P.S.); Department of Biostatistics, School of Public Health, University of Washington, Seattle (L.B., R.A.K.); Division of Cardiovascular Medicine, The Ohio State University Heart and Vascular Center, Columbus (S.M.L.); Division of Nephrology/Hypertension, Perelman School of Medicine, University of Pennsylvania, Philadelphia (R.R.T.); Los Angeles Biomedical Research Institute, Torrance, CA (M.B.); and Division of Cardiology, Johns Hopkins Hospital, Baltimore, MD (J.A.L.).
authors.forename: Lyndia
authors.initials: L
authors.lastname: Brumback
authors.affiliation: From the Division of Cardiovascular Medicine, Hospital of the University of Pennsylvania, Perelman School of Medicine and Philadelphia VA Medical Center, Philadelphia (P.Z., J.A.C.); Division of Epidemiology and Community Health, School of Public Health (D.R.J., P.H.) and Division of Cardiology, School of Medicine (D.A.D.), University of Minnesota. Minneapolis; Biofluid, Tissue, and Solid Mechanics for Medical Applications, IBiTech, iMinds Future Health Department, Ghent University, Ghent, Belgium (P.S.); Department of Biostatistics, School of Public Health, University of Washington, Seattle (L.B., R.A.K.); Division of Cardiovascular Medicine, The Ohio State University Heart and Vascular Center, Columbus (S.M.L.); Division of Nephrology/Hypertension, Perelman School of Medicine, University of Pennsylvania, Philadelphia (R.R.T.); Los Angeles Biomedical Research Institute, Torrance, CA (M.B.); and Division of Cardiology, Johns Hopkins Hospital, Baltimore, MD (J.A.L.).
authors.forename: Richard A
authors.initials: RA
authors.lastname: Kronmal
authors.affiliation: From the Division of Cardiovascular Medicine, Hospital of the University of Pennsylvania, Perelman School of Medicine and Philadelphia VA Medical Center, Philadelphia (P.Z., J.A.C.); Division of Epidemiology and Community Health, School of Public Health (D.R.J., P.H.) and Division of Cardiology, School of Medicine (D.A.D.), University of Minnesota. Minneapolis; Biofluid, Tissue, and Solid Mechanics for Medical Applications, IBiTech, iMinds Future Health Department, Ghent University, Ghent, Belgium (P.S.); Department of Biostatistics, School of Public Health, University of Washington, Seattle (L.B., R.A.K.); Division of Cardiovascular Medicine, The Ohio State University Heart and Vascular Center, Columbus (S.M.L.); Division of Nephrology/Hypertension, Perelman School of Medicine, University of Pennsylvania, Philadelphia (R.R.T.); Los Angeles Biomedical Research Institute, Torrance, CA (M.B.); and Division of Cardiology, Johns Hopkins Hospital, Baltimore, MD (J.A.L.).
authors.forename: Scott M
authors.initials: SM
authors.lastname: Lilly
authors.affiliation: From the Division of Cardiovascular Medicine, Hospital of the University of Pennsylvania, Perelman School of Medicine and Philadelphia VA Medical Center, Philadelphia (P.Z., J.A.C.); Division of Epidemiology and Community Health, School of Public Health (D.R.J., P.H.) and Division of Cardiology, School of Medicine (D.A.D.), University of Minnesota. Minneapolis; Biofluid, Tissue, and Solid Mechanics for Medical Applications, IBiTech, iMinds Future Health Department, Ghent University, Ghent, Belgium (P.S.); Department of Biostatistics, School of Public Health, University of Washington, Seattle (L.B., R.A.K.); Division of Cardiovascular Medicine, The Ohio State University Heart and Vascular Center, Columbus (S.M.L.); Division of Nephrology/Hypertension, Perelman School of Medicine, University of Pennsylvania, Philadelphia (R.R.T.); Los Angeles Biomedical Research Institute, Torrance, CA (M.B.); and Division of Cardiology, Johns Hopkins Hospital, Baltimore, MD (J.A.L.).
authors.forename: Raymond R
authors.initials: RR
authors.lastname: Townsend
authors.affiliation: From the Division of Cardiovascular Medicine, Hospital of the University of Pennsylvania, Perelman School of Medicine and Philadelphia VA Medical Center, Philadelphia (P.Z., J.A.C.); Division of Epidemiology and Community Health, School of Public Health (D.R.J., P.H.) and Division of Cardiology, School of Medicine (D.A.D.), University of Minnesota. Minneapolis; Biofluid, Tissue, and Solid Mechanics for Medical Applications, IBiTech, iMinds Future Health Department, Ghent University, Ghent, Belgium (P.S.); Department of Biostatistics, School of Public Health, University of Washington, Seattle (L.B., R.A.K.); Division of Cardiovascular Medicine, The Ohio State University Heart and Vascular Center, Columbus (S.M.L.); Division of Nephrology/Hypertension, Perelman School of Medicine, University of Pennsylvania, Philadelphia (R.R.T.); Los Angeles Biomedical Research Institute, Torrance, CA (M.B.); and Division of Cardiology, Johns Hopkins Hospital, Baltimore, MD (J.A.L.).
authors.forename: Matthew
authors.initials: M
authors.lastname: Budoff
authors.affiliation: From the Division of Cardiovascular Medicine, Hospital of the University of Pennsylvania, Perelman School of Medicine and Philadelphia VA Medical Center, Philadelphia (P.Z., J.A.C.); Division of Epidemiology and Community Health, School of Public Health (D.R.J., P.H.) and Division of Cardiology, School of Medicine (D.A.D.), University of Minnesota. Minneapolis; Biofluid, Tissue, and Solid Mechanics for Medical Applications, IBiTech, iMinds Future Health Department, Ghent University, Ghent, Belgium (P.S.); Department of Biostatistics, School of Public Health, University of Washington, Seattle (L.B., R.A.K.); Division of Cardiovascular Medicine, The Ohio State University Heart and Vascular Center, Columbus (S.M.L.); Division of Nephrology/Hypertension, Perelman School of Medicine, University of Pennsylvania, Philadelphia (R.R.T.); Los Angeles Biomedical Research Institute, Torrance, CA (M.B.); and Division of Cardiology, Johns Hopkins Hospital, Baltimore, MD (J.A.L.).
authors.forename: Joao A
authors.initials: JA
authors.lastname: Lima
authors.affiliation: From the Division of Cardiovascular Medicine, Hospital of the University of Pennsylvania, Perelman School of Medicine and Philadelphia VA Medical Center, Philadelphia (P.Z., J.A.C.); Division of Epidemiology and Community Health, School of Public Health (D.R.J., P.H.) and Division of Cardiology, School of Medicine (D.A.D.), University of Minnesota. Minneapolis; Biofluid, Tissue, and Solid Mechanics for Medical Applications, IBiTech, iMinds Future Health Department, Ghent University, Ghent, Belgium (P.S.); Department of Biostatistics, School of Public Health, University of Washington, Seattle (L.B., R.A.K.); Division of Cardiovascular Medicine, The Ohio State University Heart and Vascular Center, Columbus (S.M.L.); Division of Nephrology/Hypertension, Perelman School of Medicine, University of Pennsylvania, Philadelphia (R.R.T.); Los Angeles Biomedical Research Institute, Torrance, CA (M.B.); and Division of Cardiology, Johns Hopkins Hospital, Baltimore, MD (J.A.L.).
authors.forename: Peter
authors.initials: P
authors.lastname: Hannan
authors.affiliation: From the Division of Cardiovascular Medicine, Hospital of the University of Pennsylvania, Perelman School of Medicine and Philadelphia VA Medical Center, Philadelphia (P.Z., J.A.C.); Division of Epidemiology and Community Health, School of Public Health (D.R.J., P.H.) and Division of Cardiology, School of Medicine (D.A.D.), University of Minnesota. Minneapolis; Biofluid, Tissue, and Solid Mechanics for Medical Applications, IBiTech, iMinds Future Health Department, Ghent University, Ghent, Belgium (P.S.); Department of Biostatistics, School of Public Health, University of Washington, Seattle (L.B., R.A.K.); Division of Cardiovascular Medicine, The Ohio State University Heart and Vascular Center, Columbus (S.M.L.); Division of Nephrology/Hypertension, Perelman School of Medicine, University of Pennsylvania, Philadelphia (R.R.T.); Los Angeles Biomedical Research Institute, Torrance, CA (M.B.); and Division of Cardiology, Johns Hopkins Hospital, Baltimore, MD (J.A.L.).
authors.forename: Julio A
authors.initials: JA
authors.lastname: Chirinos
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D055109:Ankle Brachial Index; D001213:Asian; D050197:Atherosclerosis / Q000208:ethnology / Q000401:mortality* / Q000503:physiopathology; D044383:Black People; D059168:Carotid Intima-Media Thickness; D005260:Female; D005500:Follow-Up Studies; D006630:Hispanic or Latino; D006801:Humans; D008297:Male; D008365:Manometry / Q000379:methods*; D008875:Middle Aged; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D015996:Survival Rate; D014481:United States; D044465:White People; D001741:Black or African American
keywords: arteries; atherosclerosis; mortality