title: Microvascular Function Contributes to the Relation Between Aortic Stiffness and Cardiovascular Events: The Framingham Heart Study.
abstract: BACKGROUND
  Arterial dysfunction contributes to cardiovascular disease (CVD) progression and clinical events. Inter-relations of aortic stiffness and vasodilator function with incident CVD remain incompletely studied.
  
  
  RESULTS
  We used proportional hazards models to relate individual measures of vascular function to incident CVD in 4547 participants (mean age, 51±11 years; 54% women) in 2 generations of Framingham Heart Study participants. During follow-up (0.02-13.83 years), 232 participants (5%) experienced new-onset CVD events. In multivariable models adjusted for cardiovascular risk factors, both higher carotid-femoral pulse wave velocity (hazard ratio [HR], 1.32; 95% confidence interval [CI], 1.07-1.63; P=0.01) and lower hyperemic mean flow velocity (HR, 0.84; 95% CI, 0.71-0.99; P=0.04) were associated significantly with incident CVD, whereas primary pressure wave amplitude (HR, 1.12; 95% CI, 0.99-1.27; P=0.06), baseline brachial diameter (HR, 1.09; 95% CI, 0.90-1.31; P=0.39), and flow-mediated vasodilation (HR, 0.85; 95% CI, 0.69-1.04; P=0.12) were not. In mediation analyses, 8% to 13% of the relation between aortic stiffness and CVD events was mediated by hyperemic mean flow velocity.
  
  
  CONCLUSIONS
  Our results suggest that associations between aortic stiffness and CVD events are mediated by pathways that include microvascular damage and remodeling.
authors.affiliation: From the Cardiovascular Engineering, Inc., Norwood, MA (L.L.C., G.F.M.); Cardiovascular Research Center, Lifespan Cardiovascular Institute, W. Alpert Medical School of Brown University, Providence, RI (L.L.C.); Data Coordinating Center (J.N.P.), Department of Epidemiology (E.J.B., R.S.V.), and Department of Biostatistics (M.G.L.), Boston University School of Public Health, MA; Boston University and the National Heart, Lung, and Blood Institute's Framingham Study, MA (E.J.B., M.G.L., R.S.V.); and Cardiology and Preventive Medicine Sections, Department of Medicine (E.J.B., R.S.V.), Evans Department of Medicine (E.J.B., R.S.V., N.M.H.), and Whitaker Cardiovascular Institute (E.J.B., R.S.V., N.M.H.), Boston University School of Medicine, MA.
authors.forename: Leroy L
authors.initials: LL
authors.lastname: Cooper
authors.affiliation: From the Cardiovascular Engineering, Inc., Norwood, MA (L.L.C., G.F.M.); Cardiovascular Research Center, Lifespan Cardiovascular Institute, W. Alpert Medical School of Brown University, Providence, RI (L.L.C.); Data Coordinating Center (J.N.P.), Department of Epidemiology (E.J.B., R.S.V.), and Department of Biostatistics (M.G.L.), Boston University School of Public Health, MA; Boston University and the National Heart, Lung, and Blood Institute's Framingham Study, MA (E.J.B., M.G.L., R.S.V.); and Cardiology and Preventive Medicine Sections, Department of Medicine (E.J.B., R.S.V.), Evans Department of Medicine (E.J.B., R.S.V., N.M.H.), and Whitaker Cardiovascular Institute (E.J.B., R.S.V., N.M.H.), Boston University School of Medicine, MA.
authors.forename: Joseph N
authors.initials: JN
authors.lastname: Palmisano
authors.affiliation: From the Cardiovascular Engineering, Inc., Norwood, MA (L.L.C., G.F.M.); Cardiovascular Research Center, Lifespan Cardiovascular Institute, W. Alpert Medical School of Brown University, Providence, RI (L.L.C.); Data Coordinating Center (J.N.P.), Department of Epidemiology (E.J.B., R.S.V.), and Department of Biostatistics (M.G.L.), Boston University School of Public Health, MA; Boston University and the National Heart, Lung, and Blood Institute's Framingham Study, MA (E.J.B., M.G.L., R.S.V.); and Cardiology and Preventive Medicine Sections, Department of Medicine (E.J.B., R.S.V.), Evans Department of Medicine (E.J.B., R.S.V., N.M.H.), and Whitaker Cardiovascular Institute (E.J.B., R.S.V., N.M.H.), Boston University School of Medicine, MA.
authors.forename: Emelia J
authors.initials: EJ
authors.lastname: Benjamin
authors.affiliation: From the Cardiovascular Engineering, Inc., Norwood, MA (L.L.C., G.F.M.); Cardiovascular Research Center, Lifespan Cardiovascular Institute, W. Alpert Medical School of Brown University, Providence, RI (L.L.C.); Data Coordinating Center (J.N.P.), Department of Epidemiology (E.J.B., R.S.V.), and Department of Biostatistics (M.G.L.), Boston University School of Public Health, MA; Boston University and the National Heart, Lung, and Blood Institute's Framingham Study, MA (E.J.B., M.G.L., R.S.V.); and Cardiology and Preventive Medicine Sections, Department of Medicine (E.J.B., R.S.V.), Evans Department of Medicine (E.J.B., R.S.V., N.M.H.), and Whitaker Cardiovascular Institute (E.J.B., R.S.V., N.M.H.), Boston University School of Medicine, MA.
authors.forename: Martin G
authors.initials: MG
authors.lastname: Larson
authors.affiliation: From the Cardiovascular Engineering, Inc., Norwood, MA (L.L.C., G.F.M.); Cardiovascular Research Center, Lifespan Cardiovascular Institute, W. Alpert Medical School of Brown University, Providence, RI (L.L.C.); Data Coordinating Center (J.N.P.), Department of Epidemiology (E.J.B., R.S.V.), and Department of Biostatistics (M.G.L.), Boston University School of Public Health, MA; Boston University and the National Heart, Lung, and Blood Institute's Framingham Study, MA (E.J.B., M.G.L., R.S.V.); and Cardiology and Preventive Medicine Sections, Department of Medicine (E.J.B., R.S.V.), Evans Department of Medicine (E.J.B., R.S.V., N.M.H.), and Whitaker Cardiovascular Institute (E.J.B., R.S.V., N.M.H.), Boston University School of Medicine, MA.
authors.forename: Ramachandran S
authors.initials: RS
authors.lastname: Vasan
authors.affiliation: From the Cardiovascular Engineering, Inc., Norwood, MA (L.L.C., G.F.M.); Cardiovascular Research Center, Lifespan Cardiovascular Institute, W. Alpert Medical School of Brown University, Providence, RI (L.L.C.); Data Coordinating Center (J.N.P.), Department of Epidemiology (E.J.B., R.S.V.), and Department of Biostatistics (M.G.L.), Boston University School of Public Health, MA; Boston University and the National Heart, Lung, and Blood Institute's Framingham Study, MA (E.J.B., M.G.L., R.S.V.); and Cardiology and Preventive Medicine Sections, Department of Medicine (E.J.B., R.S.V.), Evans Department of Medicine (E.J.B., R.S.V., N.M.H.), and Whitaker Cardiovascular Institute (E.J.B., R.S.V., N.M.H.), Boston University School of Medicine, MA.
authors.forename: Gary F
authors.initials: GF
authors.lastname: Mitchell
authors.affiliation: From the Cardiovascular Engineering, Inc., Norwood, MA (L.L.C., G.F.M.); Cardiovascular Research Center, Lifespan Cardiovascular Institute, W. Alpert Medical School of Brown University, Providence, RI (L.L.C.); Data Coordinating Center (J.N.P.), Department of Epidemiology (E.J.B., R.S.V.), and Department of Biostatistics (M.G.L.), Boston University School of Public Health, MA; Boston University and the National Heart, Lung, and Blood Institute's Framingham Study, MA (E.J.B., M.G.L., R.S.V.); and Cardiology and Preventive Medicine Sections, Department of Medicine (E.J.B., R.S.V.), Evans Department of Medicine (E.J.B., R.S.V., N.M.H.), and Whitaker Cardiovascular Institute (E.J.B., R.S.V., N.M.H.), Boston University School of Medicine, MA. nhamburg@bu.edu.
authors.forename: Naomi M
authors.initials: NM
authors.lastname: Hamburg
mesh_terms: D000328:Adult; D001783:Blood Flow Velocity; D001916:Brachial Artery / Q000000981:diagnostic imaging / Q000503:physiopathology*; D002318:Cardiovascular Diseases / Q000175:diagnosis / Q000453:epidemiology / Q000503:physiopathology*; D002339:Carotid Arteries / Q000000981:diagnostic imaging / Q000503:physiopathology*; D005260:Female; D006801:Humans; D006940:Hyperemia / Q000503:physiopathology; D015994:Incidence; D053208:Kaplan-Meier Estimate; D008297:Male; D008404:Massachusetts / Q000453:epidemiology; D008833:Microcirculation; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D016016:Proportional Hazards Models; D063177:Pulse Wave Analysis; D012039:Regional Blood Flow; D012307:Risk Factors; D013997:Time Factors; D018608:Ultrasonography, Doppler; D059289:Vascular Stiffness; D014664:Vasodilation
keywords: arteries; cardiovascular diseases; endothelium; pulse wave analysis; vascular stiffness