title: Sex dependent risk factors for mortality after myocardial infarction: individual patient data meta-analysis.
abstract: BACKGROUND
  Although a number of risk factors are known to predict mortality within the first years after myocardial infarction, little is known about interactions between risk factors, whereas these could contribute to accurate differentiation of patients with higher and lower risk for mortality. This study explored the effect of interactions of risk factors on all-cause mortality in patients with myocardial infarction based on individual patient data meta-analysis.
  
  
  METHODS
  Prospective data for 10,512 patients hospitalized for myocardial infarction were derived from 16 observational studies (MINDMAPS). Baseline measures included a broad set of risk factors for mortality such as age, sex, heart failure, diabetes, depression, and smoking. All two-way and three-way interactions of these risk factors were included in Lasso regression analyses to predict time-to-event related all-cause mortality. The effect of selected interactions was investigated with multilevel Cox regression models.
  
  
  RESULTS
  Lasso regression selected five two-way interactions, of which four included sex. The addition of these interactions to multilevel Cox models suggested differential risk patterns for males and females. Younger women (age<50) had a higher risk for all-cause mortality than men in the same age group (HR 0.7 vs. 0.4), while men had a higher risk than women if they had depression (HR 1.4 vs. 1.1) or a low left ventricular ejection fraction (HR 1.7 vs. 1.3). Predictive accuracy of the Cox model was better for men than for women (area under the curves: 0.770 vs. 0.754).
  
  
  CONCLUSIONS
  Interactions of well-known risk factors for all-cause mortality after myocardial infarction suggested important sex differences. This study gives rise to a further exploration of prediction models to improve risk assessment for men and women after myocardial infarction.
authors.affiliation: Interdisciplinary Center Psychopathology and Emotion Regulation (ICPE), Department of Psychiatry, University of Groningen, University Medical Center Groningen, Hanzeplein 1, PO box 30.001, 9700 RB, Groningen, The Netherlands. h.van.loo@umcg.nl.
authors.forename: Hanna M
authors.initials: HM
authors.lastname: van Loo
authors.affiliation: Department of Mathematics and Computer Science, Eindhoven University of Technology, Den Dolech 2, 5612 AZ, Eindhoven, The Netherlands. e.r.v.d.heuvel@tue.nl.
authors.forename: Edwin R
authors.initials: ER
authors.lastname: van den Heuvel
authors.affiliation: Interdisciplinary Center Psychopathology and Emotion Regulation (ICPE), Department of Psychiatry, University of Groningen, University Medical Center Groningen, Hanzeplein 1, PO box 30.001, 9700 RB, Groningen, The Netherlands. r.a.schoevers@umcg.nl.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Schoevers
authors.affiliation: Division of Cardiology, Department of Medical Sciences, Città della Salute e della Scienza, University of Turin, C.so A.M. Dogliotti, 14, 10126, Turin, Italy. matteo.anselmino@unito.it.
authors.forename: Matteo
authors.initials: M
authors.lastname: Anselmino
authors.affiliation: Department of Psychiatry, Washington University School of Medicine, 4320 Forest Park Avenue, St. Louis, Missouri, 63108, USA. carneyr@bmc.wustl.edu.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Carney
authors.affiliation: CoRPS-Center of Research on Psychology in Somatic diseases, Tilburg University, Warandelaan 2, 5000 LE, Tilburg, The Netherlands. j.denollet@uvt.nl.
authors.forename: Johan
authors.initials: J
authors.lastname: Denollet
authors.affiliation: Division of Population Health Sciences (Psychology), Royal College of Surgeons in Ireland, 123 St Stephen's Green, Dublin 2, Ireland. fdoyle4@rcsi.ie.
authors.forename: Frank
authors.initials: F
authors.lastname: Doyle
authors.affiliation: Department of Psychiatry, Washington University School of Medicine, 4320 Forest Park Avenue, St. Louis, Missouri, 63108, USA. freedlak@bmc.wustl.edu.
authors.forename: Kenneth E
authors.initials: KE
authors.lastname: Freedland
authors.affiliation: Faculty of Health, York University and University Health Network, 368 Norman Bethune, 4700 Keele Street, Toronto, M3J 1P3, Canada. sgrace@yorku.ca.
authors.forename: Sherry L
authors.initials: SL
authors.lastname: Grace
authors.affiliation: Psychiatry and Behavioral Sciences Research Center, Addiction Institute, Mazandaran University of Medical Sciences, Psychosomatic department, Imam hospital, Sari, Iran. hosseinish20@gmail.com.
authors.forename: Seyed H
authors.initials: SH
authors.lastname: Hosseini
authors.affiliation: John Hopkins School of Medicine, John Hopkins Bloomberg School of Public Health, John Hoplins Bayview Medical Center, 4940 Eastern Avenue, Baltimore, Maryland, 21224, USA. kapil.parakh@gmail.com.
authors.forename: Kapil
authors.initials: K
authors.lastname: Parakh
authors.affiliation: Division of General Internal Medicine, McGill University, McGill University Health Centre, 687 Pine Avenue West, V Building, V2.17, Montreal, H3A 1A1, Canada. louise.pilote@mcgill.ca.
authors.forename: Louise
authors.initials: L
authors.lastname: Pilote
authors.affiliation: Department of Psychology, University of Bologna, Viale Berti Pichat 5, 40127, Bologna, Italy. crafanelli@libero.it.
authors.forename: Chiara
authors.initials: C
authors.lastname: Rafanelli
authors.affiliation: Interdisciplinary Center Psychopathology and Emotion Regulation (ICPE), Department of Psychiatry, University of Groningen, University Medical Center Groningen, Hanzeplein 1, PO box 30.001, 9700 RB, Groningen, The Netherlands. a.m.roest@umcg.nl.
authors.forename: Annelieke M
authors.initials: AM
authors.lastname: Roest
authors.affiliation: School of Human Welfare Studies, Kwansei Gakuin University, 1-1-155, Uegahara, Nishinomiya, Hyogo, 662-8501, Japan. sato3hiroshi@gmail.com.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sato
authors.affiliation: Department of Cardiology, Queen Elizabeth Hospital, Edgbaston, Birmingham, B15 2TH, West Midlands, UK. rick.steeds@uhb.nhs.uk.
authors.forename: Richard P
authors.initials: RP
authors.lastname: Steeds
authors.affiliation: Department of Health Care Policy, Harvard Medical School, 180 Longwood Avenue, Boston, Massachusetts, 02115, USA. kessler@hcp.med.harvard.edu.
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Kessler
authors.affiliation: Interdisciplinary Center Psychopathology and Emotion Regulation (ICPE), Department of Psychiatry, University of Groningen, University Medical Center Groningen, Hanzeplein 1, PO box 30.001, 9700 RB, Groningen, The Netherlands. peter.de.jonge@umcg.nl.
authors.forename: Peter
authors.initials: P
authors.lastname: de Jonge
mesh_terms: D000368:Aged; D003920:Diabetes Mellitus; D005260:Female; D014943:Global Health; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000150:complications / Q000401:mortality*; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012044:Regression Analysis; D012307:Risk Factors; D012737:Sex Factors; D012907:Smoking