title: Mediation analysis of the relationship between sex, cardiovascular risk factors and mortality from coronary heart disease: Findings from the population-based VHM&PP cohort.
abstract: BACKGROUND
  In Europe, annually about 77,000 women, but 253,000 men die prematurely from coronary heart disease (CHD) before the age of 65 years. This gap narrows with increasing age and disappears after the eighth life decade. However, little is known regarding the contribution of cardiovascular risk factors to this sex difference.
  
  
  OBJECTIVE
  We investigated to what extent men's higher risk of dying from CHD is explained through a different risk factor profile, as compared to women.
  
  
  METHODS
  Mediation analysis technique was used to assess the specific contributions of blood pressure, cholesterol, glucose, and smoking to the difference between men and women regarding CHD mortality in a large Austrian cohort consisting of 117,264 individuals younger than 50 years (as a proxy for pre-menopausal status) and 54,998 older ones, with 3892 deaths due to CHD during a median follow-up of 14.6 years.
  
  
  RESULTS
  Adjusting for age and year of examination, we observed a male versus female CHD mortality hazard ratio (HR) of 4.7 (95% CI: 3.4-5.9) in individuals younger than 50 years, of which 40.9% (95% CI: 27.1%-54.7%) was explained through risk factor pathways, mainly through blood pressure. In older participants, there was a HR of 1.9 (95% CI: 1.8-2.0) of which 8.2% (95% CI: 4.6%-11.7%) was mediated through the risk factors.
  
  
  CONCLUSIONS
  The extent to which major risk factors contribute to the sex difference regarding CHD mortality decreases with age. The female survival advantage was explained to a substantial part through the pathways of major risk factors only in younger individuals.
authors.affiliation: Department of Medical Statistics, Informatics and Health Economics, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Josef
authors.initials: J
authors.lastname: Fritz
authors.affiliation: Department of Medical Statistics, Informatics and Health Economics, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Edlinger
authors.affiliation: School of Public Health, Physiotherapy and Population Science, University College Dublin, Dublin, Ireland.
authors.forename: Cecily
authors.initials: C
authors.lastname: Kelleher
authors.affiliation: Oslo Centre for Biostatistics and Epidemiology, University of Oslo, Oslo, Norway.
authors.forename: Susanne
authors.initials: S
authors.lastname: Strohmaier
authors.affiliation: Institute of Epidemiology and Medical Biometry, Ulm University, Ulm, Germany; Agency for Preventive and Social Medicine, Bregenz, Austria.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Nagel
authors.affiliation: Agency for Preventive and Social Medicine, Bregenz, Austria.
authors.forename: Hans
authors.initials: H
authors.lastname: Concin
authors.affiliation: Department of Cardiac Surgery, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Elfriede
authors.initials: E
authors.lastname: Ruttmann
authors.affiliation: Women's Health Centre, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Margarethe
authors.initials: M
authors.lastname: Hochleitner
authors.affiliation: Department of Medical Statistics, Informatics and Health Economics, Medical University of Innsbruck, Innsbruck, Austria. Electronic address: hanno.ulmer@i-med.ac.at.
authors.forename: Hanno
authors.initials: H
authors.lastname: Ulmer
mesh_terms: D001317:Austria; D001786:Blood Glucose / Q000032:analysis / Q000378:metabolism; D001795:Blood Pressure Determination; D002318:Cardiovascular Diseases / Q000150:complications* / Q000401:mortality; D002784:Cholesterol / Q000097:blood; D015331:Cohort Studies; D003327:Coronary Disease / Q000150:complications* / Q000401:mortality; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012307:Risk Factors; D012737:Sex Factors
chemical_list: D001786:Blood Glucose; D002784:Cholesterol
keywords: Cardiovascular disease risk factors; Coronary heart disease; Epidemiology; Gender; Mediation analysis; Sex