title: Relations of Arterial Stiffness and Brachial Flow-Mediated Dilation With New-Onset Atrial Fibrillation: The Framingham Heart Study.
abstract: The relations of measures of arterial stiffness, pulsatile hemodynamic load, and endothelial dysfunction to atrial fibrillation (AF) remain poorly understood. To better understand the pathophysiology of AF, we examined associations between noninvasive measures of vascular function and new-onset AF. The study sample included participants aged ≥45 years from the Framingham Heart Study offspring and third-generation cohorts. Using Cox proportional hazards regression models, we examined relations between incident AF and tonometry measures of arterial stiffness (carotid-femoral pulse wave velocity), wave reflection (augmentation index), pressure pulsatility (central pulse pressure), endothelial function (flow-mediated dilation), resting brachial arterial diameter, and hyperemic flow. AF developed in 407/5797 participants in the tonometry sample and 270/3921 participants in the endothelial function sample during follow-up (median 7.1 years, maximum 10 years). Higher augmentation index (hazard ratio, 1.16; 95% confidence interval, 1.02-1.32; P=0.02), baseline brachial artery diameter (hazard ratio, 1.20; 95% confidence interval, 1.01-1.43; P=0.04), and lower flow-mediated dilation (hazard ratio, 0.79; 95% confidence interval, 0.63-0.99; P=0.04) were associated with increased risk of incident AF. Central pulse pressure, when adjusted for age, sex, and hypertension (hazard ratio, 1.14; 95% confidence interval, 1.02-1.28; P=0.02) was associated with incident AF. Higher pulsatile load assessed by central pulse pressure and greater apparent wave reflection measured by augmentation index were associated with increased risk of incident AF. Vascular endothelial dysfunction may precede development of AF. These measures may be additional risk factors or markers of subclinical cardiovascular disease associated with increased risk of incident AF.
authors.affiliation: From the Department of Medicine, University of Massachusetts Medical School, Worcester (A.Y.S.); Data Coordinating Center (N.W.), Department of Biostatistics (X.Y., M.G.L.), Department of Epidemiology (R.S.V.), and Department of Epidemiology (E.J.B.), Boston University School of Public Health, MA; National Heart Lung and Blood Institute's and Boston University's Framingham Heart Study, MA (X.Y., M.G.L., R.S.V., E.J.B.); Section of Cardiovascular Medicine, Preventive Medicine and Epidemiology, Department of Medicine (R.S.V.) and Cardiology Division, Department of Medicine (N.M.H., J.W.M.), Boston University School of Medicine, MA; Cardiology Division, Department of Medicine, Massachusetts General Hospital and Harvard Medical School (P.T.E., S.A.L.); The Broad Institute of Harvard and MIT, Cambridge, MA (P.T.E., S.A.L.); Cardiovascular Engineering, Inc, Norwood, MA (G.F.M.); Evans Memorial Medicine Department, Cardiology Section, and Preventive Medicine Section, School of Medicine, Boston University, MA (E.J.B.); and Cardiology Division, Department of Medicine, University of Massachusetts Medical School, Worcester (D.D.M.). Amir.Shaikh@umassmemorial.org.
authors.forename: Amir Y
authors.initials: AY
authors.lastname: Shaikh
authors.affiliation: From the Department of Medicine, University of Massachusetts Medical School, Worcester (A.Y.S.); Data Coordinating Center (N.W.), Department of Biostatistics (X.Y., M.G.L.), Department of Epidemiology (R.S.V.), and Department of Epidemiology (E.J.B.), Boston University School of Public Health, MA; National Heart Lung and Blood Institute's and Boston University's Framingham Heart Study, MA (X.Y., M.G.L., R.S.V., E.J.B.); Section of Cardiovascular Medicine, Preventive Medicine and Epidemiology, Department of Medicine (R.S.V.) and Cardiology Division, Department of Medicine (N.M.H., J.W.M.), Boston University School of Medicine, MA; Cardiology Division, Department of Medicine, Massachusetts General Hospital and Harvard Medical School (P.T.E., S.A.L.); The Broad Institute of Harvard and MIT, Cambridge, MA (P.T.E., S.A.L.); Cardiovascular Engineering, Inc, Norwood, MA (G.F.M.); Evans Memorial Medicine Department, Cardiology Section, and Preventive Medicine Section, School of Medicine, Boston University, MA (E.J.B.); and Cardiology Division, Department of Medicine, University of Massachusetts Medical School, Worcester (D.D.M.).
authors.forename: Na
authors.initials: N
authors.lastname: Wang
authors.affiliation: From the Department of Medicine, University of Massachusetts Medical School, Worcester (A.Y.S.); Data Coordinating Center (N.W.), Department of Biostatistics (X.Y., M.G.L.), Department of Epidemiology (R.S.V.), and Department of Epidemiology (E.J.B.), Boston University School of Public Health, MA; National Heart Lung and Blood Institute's and Boston University's Framingham Heart Study, MA (X.Y., M.G.L., R.S.V., E.J.B.); Section of Cardiovascular Medicine, Preventive Medicine and Epidemiology, Department of Medicine (R.S.V.) and Cardiology Division, Department of Medicine (N.M.H., J.W.M.), Boston University School of Medicine, MA; Cardiology Division, Department of Medicine, Massachusetts General Hospital and Harvard Medical School (P.T.E., S.A.L.); The Broad Institute of Harvard and MIT, Cambridge, MA (P.T.E., S.A.L.); Cardiovascular Engineering, Inc, Norwood, MA (G.F.M.); Evans Memorial Medicine Department, Cardiology Section, and Preventive Medicine Section, School of Medicine, Boston University, MA (E.J.B.); and Cardiology Division, Department of Medicine, University of Massachusetts Medical School, Worcester (D.D.M.).
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Yin
authors.affiliation: From the Department of Medicine, University of Massachusetts Medical School, Worcester (A.Y.S.); Data Coordinating Center (N.W.), Department of Biostatistics (X.Y., M.G.L.), Department of Epidemiology (R.S.V.), and Department of Epidemiology (E.J.B.), Boston University School of Public Health, MA; National Heart Lung and Blood Institute's and Boston University's Framingham Heart Study, MA (X.Y., M.G.L., R.S.V., E.J.B.); Section of Cardiovascular Medicine, Preventive Medicine and Epidemiology, Department of Medicine (R.S.V.) and Cardiology Division, Department of Medicine (N.M.H., J.W.M.), Boston University School of Medicine, MA; Cardiology Division, Department of Medicine, Massachusetts General Hospital and Harvard Medical School (P.T.E., S.A.L.); The Broad Institute of Harvard and MIT, Cambridge, MA (P.T.E., S.A.L.); Cardiovascular Engineering, Inc, Norwood, MA (G.F.M.); Evans Memorial Medicine Department, Cardiology Section, and Preventive Medicine Section, School of Medicine, Boston University, MA (E.J.B.); and Cardiology Division, Department of Medicine, University of Massachusetts Medical School, Worcester (D.D.M.).
authors.forename: Martin G
authors.initials: MG
authors.lastname: Larson
authors.affiliation: From the Department of Medicine, University of Massachusetts Medical School, Worcester (A.Y.S.); Data Coordinating Center (N.W.), Department of Biostatistics (X.Y., M.G.L.), Department of Epidemiology (R.S.V.), and Department of Epidemiology (E.J.B.), Boston University School of Public Health, MA; National Heart Lung and Blood Institute's and Boston University's Framingham Heart Study, MA (X.Y., M.G.L., R.S.V., E.J.B.); Section of Cardiovascular Medicine, Preventive Medicine and Epidemiology, Department of Medicine (R.S.V.) and Cardiology Division, Department of Medicine (N.M.H., J.W.M.), Boston University School of Medicine, MA; Cardiology Division, Department of Medicine, Massachusetts General Hospital and Harvard Medical School (P.T.E., S.A.L.); The Broad Institute of Harvard and MIT, Cambridge, MA (P.T.E., S.A.L.); Cardiovascular Engineering, Inc, Norwood, MA (G.F.M.); Evans Memorial Medicine Department, Cardiology Section, and Preventive Medicine Section, School of Medicine, Boston University, MA (E.J.B.); and Cardiology Division, Department of Medicine, University of Massachusetts Medical School, Worcester (D.D.M.).
authors.forename: Ramachandran S
authors.initials: RS
authors.lastname: Vasan
authors.affiliation: From the Department of Medicine, University of Massachusetts Medical School, Worcester (A.Y.S.); Data Coordinating Center (N.W.), Department of Biostatistics (X.Y., M.G.L.), Department of Epidemiology (R.S.V.), and Department of Epidemiology (E.J.B.), Boston University School of Public Health, MA; National Heart Lung and Blood Institute's and Boston University's Framingham Heart Study, MA (X.Y., M.G.L., R.S.V., E.J.B.); Section of Cardiovascular Medicine, Preventive Medicine and Epidemiology, Department of Medicine (R.S.V.) and Cardiology Division, Department of Medicine (N.M.H., J.W.M.), Boston University School of Medicine, MA; Cardiology Division, Department of Medicine, Massachusetts General Hospital and Harvard Medical School (P.T.E., S.A.L.); The Broad Institute of Harvard and MIT, Cambridge, MA (P.T.E., S.A.L.); Cardiovascular Engineering, Inc, Norwood, MA (G.F.M.); Evans Memorial Medicine Department, Cardiology Section, and Preventive Medicine Section, School of Medicine, Boston University, MA (E.J.B.); and Cardiology Division, Department of Medicine, University of Massachusetts Medical School, Worcester (D.D.M.).
authors.forename: Naomi M
authors.initials: NM
authors.lastname: Hamburg
authors.affiliation: From the Department of Medicine, University of Massachusetts Medical School, Worcester (A.Y.S.); Data Coordinating Center (N.W.), Department of Biostatistics (X.Y., M.G.L.), Department of Epidemiology (R.S.V.), and Department of Epidemiology (E.J.B.), Boston University School of Public Health, MA; National Heart Lung and Blood Institute's and Boston University's Framingham Heart Study, MA (X.Y., M.G.L., R.S.V., E.J.B.); Section of Cardiovascular Medicine, Preventive Medicine and Epidemiology, Department of Medicine (R.S.V.) and Cardiology Division, Department of Medicine (N.M.H., J.W.M.), Boston University School of Medicine, MA; Cardiology Division, Department of Medicine, Massachusetts General Hospital and Harvard Medical School (P.T.E., S.A.L.); The Broad Institute of Harvard and MIT, Cambridge, MA (P.T.E., S.A.L.); Cardiovascular Engineering, Inc, Norwood, MA (G.F.M.); Evans Memorial Medicine Department, Cardiology Section, and Preventive Medicine Section, School of Medicine, Boston University, MA (E.J.B.); and Cardiology Division, Department of Medicine, University of Massachusetts Medical School, Worcester (D.D.M.).
authors.forename: Jared W
authors.initials: JW
authors.lastname: Magnani
authors.affiliation: From the Department of Medicine, University of Massachusetts Medical School, Worcester (A.Y.S.); Data Coordinating Center (N.W.), Department of Biostatistics (X.Y., M.G.L.), Department of Epidemiology (R.S.V.), and Department of Epidemiology (E.J.B.), Boston University School of Public Health, MA; National Heart Lung and Blood Institute's and Boston University's Framingham Heart Study, MA (X.Y., M.G.L., R.S.V., E.J.B.); Section of Cardiovascular Medicine, Preventive Medicine and Epidemiology, Department of Medicine (R.S.V.) and Cardiology Division, Department of Medicine (N.M.H., J.W.M.), Boston University School of Medicine, MA; Cardiology Division, Department of Medicine, Massachusetts General Hospital and Harvard Medical School (P.T.E., S.A.L.); The Broad Institute of Harvard and MIT, Cambridge, MA (P.T.E., S.A.L.); Cardiovascular Engineering, Inc, Norwood, MA (G.F.M.); Evans Memorial Medicine Department, Cardiology Section, and Preventive Medicine Section, School of Medicine, Boston University, MA (E.J.B.); and Cardiology Division, Department of Medicine, University of Massachusetts Medical School, Worcester (D.D.M.).
authors.forename: Patrick T
authors.initials: PT
authors.lastname: Ellinor
authors.affiliation: From the Department of Medicine, University of Massachusetts Medical School, Worcester (A.Y.S.); Data Coordinating Center (N.W.), Department of Biostatistics (X.Y., M.G.L.), Department of Epidemiology (R.S.V.), and Department of Epidemiology (E.J.B.), Boston University School of Public Health, MA; National Heart Lung and Blood Institute's and Boston University's Framingham Heart Study, MA (X.Y., M.G.L., R.S.V., E.J.B.); Section of Cardiovascular Medicine, Preventive Medicine and Epidemiology, Department of Medicine (R.S.V.) and Cardiology Division, Department of Medicine (N.M.H., J.W.M.), Boston University School of Medicine, MA; Cardiology Division, Department of Medicine, Massachusetts General Hospital and Harvard Medical School (P.T.E., S.A.L.); The Broad Institute of Harvard and MIT, Cambridge, MA (P.T.E., S.A.L.); Cardiovascular Engineering, Inc, Norwood, MA (G.F.M.); Evans Memorial Medicine Department, Cardiology Section, and Preventive Medicine Section, School of Medicine, Boston University, MA (E.J.B.); and Cardiology Division, Department of Medicine, University of Massachusetts Medical School, Worcester (D.D.M.).
authors.forename: Steven A
authors.initials: SA
authors.lastname: Lubitz
authors.affiliation: From the Department of Medicine, University of Massachusetts Medical School, Worcester (A.Y.S.); Data Coordinating Center (N.W.), Department of Biostatistics (X.Y., M.G.L.), Department of Epidemiology (R.S.V.), and Department of Epidemiology (E.J.B.), Boston University School of Public Health, MA; National Heart Lung and Blood Institute's and Boston University's Framingham Heart Study, MA (X.Y., M.G.L., R.S.V., E.J.B.); Section of Cardiovascular Medicine, Preventive Medicine and Epidemiology, Department of Medicine (R.S.V.) and Cardiology Division, Department of Medicine (N.M.H., J.W.M.), Boston University School of Medicine, MA; Cardiology Division, Department of Medicine, Massachusetts General Hospital and Harvard Medical School (P.T.E., S.A.L.); The Broad Institute of Harvard and MIT, Cambridge, MA (P.T.E., S.A.L.); Cardiovascular Engineering, Inc, Norwood, MA (G.F.M.); Evans Memorial Medicine Department, Cardiology Section, and Preventive Medicine Section, School of Medicine, Boston University, MA (E.J.B.); and Cardiology Division, Department of Medicine, University of Massachusetts Medical School, Worcester (D.D.M.).
authors.forename: Gary F
authors.initials: GF
authors.lastname: Mitchell
authors.affiliation: From the Department of Medicine, University of Massachusetts Medical School, Worcester (A.Y.S.); Data Coordinating Center (N.W.), Department of Biostatistics (X.Y., M.G.L.), Department of Epidemiology (R.S.V.), and Department of Epidemiology (E.J.B.), Boston University School of Public Health, MA; National Heart Lung and Blood Institute's and Boston University's Framingham Heart Study, MA (X.Y., M.G.L., R.S.V., E.J.B.); Section of Cardiovascular Medicine, Preventive Medicine and Epidemiology, Department of Medicine (R.S.V.) and Cardiology Division, Department of Medicine (N.M.H., J.W.M.), Boston University School of Medicine, MA; Cardiology Division, Department of Medicine, Massachusetts General Hospital and Harvard Medical School (P.T.E., S.A.L.); The Broad Institute of Harvard and MIT, Cambridge, MA (P.T.E., S.A.L.); Cardiovascular Engineering, Inc, Norwood, MA (G.F.M.); Evans Memorial Medicine Department, Cardiology Section, and Preventive Medicine Section, School of Medicine, Boston University, MA (E.J.B.); and Cardiology Division, Department of Medicine, University of Massachusetts Medical School, Worcester (D.D.M.).
authors.forename: Emelia J
authors.initials: EJ
authors.lastname: Benjamin
authors.affiliation: From the Department of Medicine, University of Massachusetts Medical School, Worcester (A.Y.S.); Data Coordinating Center (N.W.), Department of Biostatistics (X.Y., M.G.L.), Department of Epidemiology (R.S.V.), and Department of Epidemiology (E.J.B.), Boston University School of Public Health, MA; National Heart Lung and Blood Institute's and Boston University's Framingham Heart Study, MA (X.Y., M.G.L., R.S.V., E.J.B.); Section of Cardiovascular Medicine, Preventive Medicine and Epidemiology, Department of Medicine (R.S.V.) and Cardiology Division, Department of Medicine (N.M.H., J.W.M.), Boston University School of Medicine, MA; Cardiology Division, Department of Medicine, Massachusetts General Hospital and Harvard Medical School (P.T.E., S.A.L.); The Broad Institute of Harvard and MIT, Cambridge, MA (P.T.E., S.A.L.); Cardiovascular Engineering, Inc, Norwood, MA (G.F.M.); Evans Memorial Medicine Department, Cardiology Section, and Preventive Medicine Section, School of Medicine, Boston University, MA (E.J.B.); and Cardiology Division, Department of Medicine, University of Massachusetts Medical School, Worcester (D.D.M.).
authors.forename: David D
authors.initials: DD
authors.lastname: McManus
mesh_terms: D000367:Age Factors; D000368:Aged; D001281:Atrial Fibrillation / Q000453:epidemiology* / Q000503:physiopathology*; D001783:Blood Flow Velocity; D015331:Cohort Studies; D018450:Disease Progression; D004730:Endothelium, Vascular / Q000503:physiopathology; D005260:Female; D006801:Humans; D008297:Male; D008365:Manometry; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D063177:Pulse Wave Analysis / Q000009:adverse effects* / Q000379:methods; D012189:Retrospective Studies; D018570:Risk Assessment; D012720:Severity of Illness Index; D012737:Sex Factors; D014481:United States; D059289:Vascular Stiffness / Q000502:physiology*
keywords: arrhythmia; augmentation index; flow-mediated dilation; pulse wave velocity; tonometry