title: Sex Differences in Correlates of Intermediate Phenotypes and Prevalent Cardiovascular Disease in the General Population.
abstract: BACKGROUND
  There are marked sex differences in cardiovascular disease (CVD) manifestation. It is largely unknown how the distribution of CVD risk factors or intermediate phenotypes explain sex-specific differences.
  
  
  RESULTS
  In 5000 individuals of the population-based Gutenberg Health Study, mean age 55 ± 11 years, 51% males, we examined sex-specific associations of classical CVD risk factors with intima-media thickness, ankle-brachial index, flow-mediated dilation, peripheral arterial tonometry, echocardiographic, and electrocardiographic variables. Intermediate cardiovascular phenotypes were related to prevalent CVD [coronary artery disease, heart failure, stroke, myocardial infarction, lower extremity artery disease (LEAD) N = 561]. We observed differential distributions of CVD risk factors with a higher risk factor burden in men. Manifest coronary artery disease, stroke, myocardial infarction, and LEAD were more frequent in men; the proportion of heart failure was higher in women. Intermediate phenotypes showed clear sex differences with more beneficial values in women. Fairly linear changes toward less beneficial values with age were observed in both sexes. In multivariable-adjusted regression analyses, age, systolic blood pressure, and body mass index were consistently associated with intermediate phenotypes in both sexes with different ranking according to random forests, maximum model R(2) 0.43. Risk factor-adjusted associations with prevalent CVD showed some differences by sex. No interactions by menopausal status were observed.
  
  
  CONCLUSIONS
  In a population-based cohort, we observed sex differences in risk factors and a broad range of intermediate phenotypes of non-invasive cardiovascular structure and function. Their relation to prevalent CVD differed markedly. Our results indicate the need of future investigations to understand sex differences in CVD manifestation.
authors.affiliation: Department of General and Interventional Cardiology, University Heart Center Hamburg-Eppendorf , Hamburg , Germany.
authors.forename: Renate B
authors.initials: RB
authors.lastname: Schnabel
authors.affiliation: Center for Thrombosis and Hemostasis, University Medical Center Mainz , Mainz , Germany ; Department of Medicine 2, University Medical Center Mainz , Mainz , Germany ; German Centre for Cardiovascular Research (DZHK), Partner Site RheinMain , Germany.
authors.forename: Philipp S
authors.initials: PS
authors.lastname: Wild
authors.affiliation: Center for Thrombosis and Hemostasis, University Medical Center Mainz , Mainz , Germany ; Department of Medicine 2, University Medical Center Mainz , Mainz , Germany.
authors.forename: Jürgen H
authors.initials: JH
authors.lastname: Prochaska
authors.affiliation: Department of General and Interventional Cardiology, University Heart Center Hamburg-Eppendorf , Hamburg , Germany.
authors.forename: Francisco M
authors.initials: FM
authors.lastname: Ojeda
authors.affiliation: Department of General and Interventional Cardiology, University Heart Center Hamburg-Eppendorf , Hamburg , Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Zeller
authors.affiliation: Department of General and Interventional Cardiology, University Heart Center Hamburg-Eppendorf , Hamburg , Germany.
authors.forename: Nargiz
authors.initials: N
authors.lastname: Rzayeva
authors.affiliation: Department of General and Interventional Cardiology, University Heart Center Hamburg-Eppendorf , Hamburg , Germany.
authors.forename: Ariana
authors.initials: A
authors.lastname: Ebrahim
authors.affiliation: Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center Mainz , Mainz , Germany.
authors.forename: Karl J
authors.initials: KJ
authors.lastname: Lackner
authors.affiliation: Department of Psychosomatic Medicine and Psychotherapy, University Medical Center Mainz , Mainz , Germany.
authors.forename: Manfred E
authors.initials: ME
authors.lastname: Beutel
authors.affiliation: Department of Ophthalmology, University Medical Center Mainz , Mainz , Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Pfeiffer
authors.affiliation: Department of General and Interventional Cardiology, University Heart Center Hamburg-Eppendorf , Hamburg , Germany.
authors.forename: Christoph R
authors.initials: CR
authors.lastname: Sinning
authors.affiliation: Institute of Gender in Medicine (GiM), Center for Cardiovascular Research (CCR), Charité-Universitätsmedizin Berlin , Berlin , Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Oertelt-Prigione
authors.affiliation: Institute of Gender in Medicine (GiM), Center for Cardiovascular Research (CCR), Charité-Universitätsmedizin Berlin , Berlin , Germany ; German Centre for Cardiovascular Research (DZHK), Partner Site Berlin , Germany.
authors.forename: Vera
authors.initials: V
authors.lastname: Regitz-Zagrosek
authors.affiliation: Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), University Medical Center Mainz , Mainz , Germany.
authors.forename: Harald
authors.initials: H
authors.lastname: Binder
authors.affiliation: Department of Medicine 2, University Medical Center Mainz , Mainz , Germany ; German Centre for Cardiovascular Research (DZHK), Partner Site RheinMain , Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Münzel
authors.affiliation: Department of General and Interventional Cardiology, University Heart Center Hamburg-Eppendorf , Hamburg , Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Blankenberg
keywords: cardiac function; cardiovascular epidemiology; non-invasive vascular function; population-based study; sex differences