title: Excess Cardiovascular Risk in Women Relative to Men Referred for Coronary Angiography Is Associated With Severely Impaired Coronary Flow Reserve, Not Obstructive Disease.
abstract: Cardiovascular disease (CVD) fatality rates are higher for women than for men, yet obstructive coronary artery disease (CAD) is less prevalent in women. Coronary flow reserve (CFR), an integrated measure of large- and small-vessel CAD and myocardial ischemia, identifies patients at risk for CVD death, but is not routinely measured in clinical practice. We sought to investigate the impact of sex, CFR, and angiographic CAD severity on adverse cardiovascular events.
  
  
  
  Consecutive patients (n=329, 43% women) referred for invasive coronary angiography after stress testing with myocardial perfusion positron emission tomography and with left ventricular ejection fraction >40% were followed (median, 3.0 years) for a composite end point of major adverse cardiovascular events, including cardiovascular death and hospitalization for nonfatal myocardial infarction or heart failure. The extent and severity of angiographic CAD were estimated by using the CAD prognostic index, and CFR was quantified by using positron emission tomography.
  
  
  
  Although women in comparison with men had lower pretest clinical scores, rates of prior myocardial infarction, and burden of angiographic CAD (P<0.001), they demonstrated greater risk of CVD events, even after adjustment for traditional risk factors, imaging findings, and early revascularization (adjusted hazard ratio, 2.05; 95% confidence interval, 1.05-4.02; P=0.03). Impaired CFR was similarly present among women and men, but in patients with low CFR (<1.6, n=163), women showed a higher frequency of nonobstructive CAD, whereas men showed a higher frequency of severely obstructive CAD (P=0.002). After also adjusting for CFR, the effect of sex on outcomes was no longer significant. When stratified by sex and CFR, only women with severely impaired CFR demonstrated significantly increased adjusted risk of CVD events (P<0.0001, P for interaction=0.04).
  
  
  
  Women referred for coronary angiography had a significantly lower burden of obstructive CAD in comparison with men but were not protected from CVD events. Excess cardiovascular risk in women was independently associated with impaired CFR, representing a hidden biological risk, and a phenotype less amenable to revascularization. Impaired CFR, particularly absent severely obstructive CAD, may represent a novel target for CVD risk reduction.
authors.affiliation: From Noninvasive Cardiovascular Imaging Program, Division of Cardiovascular Medicine, Department of Medicine, Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (V.R.T., N.R.S., C.R.F., J.H., R.B., S.D., M.F.D.C.); Emory Clinical Cardiovascular Research Institute, Emory University School of Medicine, Atlanta, GA (L.J.S.); Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital, Boston, MA (N.R.C.); and Divisions of Nuclear Medicine, Cardiothoracic Imaging, and Cardiovascular Medicine, Departments of Medicine and Radiology, University of Michigan, Ann Arbor (V.L.M.). vtaqueti@partners.org.
authors.forename: Viviany R
authors.initials: VR
authors.lastname: Taqueti
authors.affiliation: From Noninvasive Cardiovascular Imaging Program, Division of Cardiovascular Medicine, Department of Medicine, Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (V.R.T., N.R.S., C.R.F., J.H., R.B., S.D., M.F.D.C.); Emory Clinical Cardiovascular Research Institute, Emory University School of Medicine, Atlanta, GA (L.J.S.); Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital, Boston, MA (N.R.C.); and Divisions of Nuclear Medicine, Cardiothoracic Imaging, and Cardiovascular Medicine, Departments of Medicine and Radiology, University of Michigan, Ann Arbor (V.L.M.).
authors.forename: Leslee J
authors.initials: LJ
authors.lastname: Shaw
authors.affiliation: From Noninvasive Cardiovascular Imaging Program, Division of Cardiovascular Medicine, Department of Medicine, Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (V.R.T., N.R.S., C.R.F., J.H., R.B., S.D., M.F.D.C.); Emory Clinical Cardiovascular Research Institute, Emory University School of Medicine, Atlanta, GA (L.J.S.); Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital, Boston, MA (N.R.C.); and Divisions of Nuclear Medicine, Cardiothoracic Imaging, and Cardiovascular Medicine, Departments of Medicine and Radiology, University of Michigan, Ann Arbor (V.L.M.).
authors.forename: Nancy R
authors.initials: NR
authors.lastname: Cook
authors.affiliation: From Noninvasive Cardiovascular Imaging Program, Division of Cardiovascular Medicine, Department of Medicine, Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (V.R.T., N.R.S., C.R.F., J.H., R.B., S.D., M.F.D.C.); Emory Clinical Cardiovascular Research Institute, Emory University School of Medicine, Atlanta, GA (L.J.S.); Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital, Boston, MA (N.R.C.); and Divisions of Nuclear Medicine, Cardiothoracic Imaging, and Cardiovascular Medicine, Departments of Medicine and Radiology, University of Michigan, Ann Arbor (V.L.M.).
authors.forename: Venkatesh L
authors.initials: VL
authors.lastname: Murthy
authors.affiliation: From Noninvasive Cardiovascular Imaging Program, Division of Cardiovascular Medicine, Department of Medicine, Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (V.R.T., N.R.S., C.R.F., J.H., R.B., S.D., M.F.D.C.); Emory Clinical Cardiovascular Research Institute, Emory University School of Medicine, Atlanta, GA (L.J.S.); Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital, Boston, MA (N.R.C.); and Divisions of Nuclear Medicine, Cardiothoracic Imaging, and Cardiovascular Medicine, Departments of Medicine and Radiology, University of Michigan, Ann Arbor (V.L.M.).
authors.forename: Nishant R
authors.initials: NR
authors.lastname: Shah
authors.affiliation: From Noninvasive Cardiovascular Imaging Program, Division of Cardiovascular Medicine, Department of Medicine, Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (V.R.T., N.R.S., C.R.F., J.H., R.B., S.D., M.F.D.C.); Emory Clinical Cardiovascular Research Institute, Emory University School of Medicine, Atlanta, GA (L.J.S.); Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital, Boston, MA (N.R.C.); and Divisions of Nuclear Medicine, Cardiothoracic Imaging, and Cardiovascular Medicine, Departments of Medicine and Radiology, University of Michigan, Ann Arbor (V.L.M.).
authors.forename: Courtney R
authors.initials: CR
authors.lastname: Foster
authors.affiliation: From Noninvasive Cardiovascular Imaging Program, Division of Cardiovascular Medicine, Department of Medicine, Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (V.R.T., N.R.S., C.R.F., J.H., R.B., S.D., M.F.D.C.); Emory Clinical Cardiovascular Research Institute, Emory University School of Medicine, Atlanta, GA (L.J.S.); Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital, Boston, MA (N.R.C.); and Divisions of Nuclear Medicine, Cardiothoracic Imaging, and Cardiovascular Medicine, Departments of Medicine and Radiology, University of Michigan, Ann Arbor (V.L.M.).
authors.forename: Jon
authors.initials: J
authors.lastname: Hainer
authors.affiliation: From Noninvasive Cardiovascular Imaging Program, Division of Cardiovascular Medicine, Department of Medicine, Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (V.R.T., N.R.S., C.R.F., J.H., R.B., S.D., M.F.D.C.); Emory Clinical Cardiovascular Research Institute, Emory University School of Medicine, Atlanta, GA (L.J.S.); Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital, Boston, MA (N.R.C.); and Divisions of Nuclear Medicine, Cardiothoracic Imaging, and Cardiovascular Medicine, Departments of Medicine and Radiology, University of Michigan, Ann Arbor (V.L.M.).
authors.forename: Ron
authors.initials: R
authors.lastname: Blankstein
authors.affiliation: From Noninvasive Cardiovascular Imaging Program, Division of Cardiovascular Medicine, Department of Medicine, Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (V.R.T., N.R.S., C.R.F., J.H., R.B., S.D., M.F.D.C.); Emory Clinical Cardiovascular Research Institute, Emory University School of Medicine, Atlanta, GA (L.J.S.); Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital, Boston, MA (N.R.C.); and Divisions of Nuclear Medicine, Cardiothoracic Imaging, and Cardiovascular Medicine, Departments of Medicine and Radiology, University of Michigan, Ann Arbor (V.L.M.).
authors.forename: Sharmila
authors.initials: S
authors.lastname: Dorbala
authors.affiliation: From Noninvasive Cardiovascular Imaging Program, Division of Cardiovascular Medicine, Department of Medicine, Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (V.R.T., N.R.S., C.R.F., J.H., R.B., S.D., M.F.D.C.); Emory Clinical Cardiovascular Research Institute, Emory University School of Medicine, Atlanta, GA (L.J.S.); Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital, Boston, MA (N.R.C.); and Divisions of Nuclear Medicine, Cardiothoracic Imaging, and Cardiovascular Medicine, Departments of Medicine and Radiology, University of Michigan, Ann Arbor (V.L.M.).
authors.forename: Marcelo F
authors.initials: MF
authors.lastname: Di Carli
mesh_terms: D000368:Aged; D017023:Coronary Angiography / Q000379:methods*; D003324:Coronary Artery Disease / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000379:methods*; D012307:Risk Factors
keywords: coronary angiography; coronary flow reserve; myocardial ischemia; positron-emission tomography; women