title: Sex-specific associations of established and emerging cardiac biomarkers with all-cause mortality in older adults: the ActiFE study.
abstract: BACKGROUND
  N-terminal pro B-type natriuretic peptide (NT-proBNP) has strong prognostic value for all-cause mortality in the general population. High-sensitivity assays now allow detection of cardiac troponins even in asymptomatic populations. We examined the association between NT-proBNP, high-sensitivity cardiac troponin T (hs-cTnT), and hs-cTnI and all-cause mortality in older adults.
  
  
  METHODS
  We conducted a longitudinal cohort study [Activity and Function in the Elderly in Ulm (ActiFE Ulm)] including 1506 community-dwelling adults ≥65 years old with NT-proBNP, hs-cTnT, and hs-cTnI measured at baseline. We evaluated the associations between log-transformed biomarker concentrations and 4-year total mortality, accounting for possible confounders, with Cox proportional hazards models.
  
  
  RESULTS
  We observed 125 deaths among 1422 participants (median follow-up 4 years). We detected effect modification by sex for all biomarkers (all P values <0.05) expressed as hazard ratio (HR) for death per 1-unit increment of ln(biomarker concentration) in women (n = 618, 37 deaths) compared with men (n = 804, 88 deaths): HR 2.97 (95% CI 2.04-4.33) vs 1.73 (1.40-2.13) for NT-proBNP; 3.67 (2.31-5.81) vs 2.15 (1.61-2.87) for hs-cTnT; and 3.32 (2.13-5.18) vs 1.92 (1.55-2.38) for hs-cTnI. Among 777 participants with undetectable hs-cTnT (<5 ng/L), hs-cTnI remained associated with all-cause mortality in age- and sex-adjusted analysis.
  
  
  CONCLUSIONS
  NT-proBNP, hs-cTnT, and hs-cTnI were independently associated with all-cause mortality in older adults. The strength of these associations varied between men and women, emphasizing the need for additional sex-specific research among older people.
authors.affiliation: Department of Internal Medicine II-Cardiology, University of Ulm Medical Center, Ulm, Germany; Department of Epidemiology, Boston University School of Public Health, Boston, MA;
authors.forename: Dhayana
authors.initials: D
authors.lastname: Dallmeier
authors.affiliation: Agaplesion Bethesda Clinic Ulm, Geriatric Center Ulm/Alb-Donau, Ulm, Germany; Institute of Molecular Medicine and Stem Cell Research.
authors.forename: Michael
authors.initials: M
authors.lastname: Denkinger
authors.affiliation: Institute of Epidemiology and Medical Biometry, and Institute of the History, Philosophy, and Ethics of Medicine, Ulm University, Ulm, Germany;
authors.forename: Richard
authors.initials: R
authors.lastname: Peter
authors.affiliation: Clinic for Geriatric Rehabilitation, Robert-Bosch Hospital, Stuttgart, Germany;
authors.forename: Kilian
authors.initials: K
authors.lastname: Rapp
authors.affiliation: Mayo Clinic College of Medicine, Division of Cardiovascular Diseases, Rochester, MN.
authors.forename: Allan S
authors.initials: AS
authors.lastname: Jaffe
authors.affiliation: Department of Internal Medicine II-Cardiology, University of Ulm Medical Center, Ulm, Germany; wolfgang.koenig@uniklinik-ulm.de.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Koenig
authors.affiliation: Institute of Epidemiology and Medical Biometry, and.
authors.forename: Dietrich
authors.initials: D
authors.lastname: Rothenbacher
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D003643:Death; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D016016:Proportional Hazards Models; D012307:Risk Factors; D012737:Sex Factors; D019210:Troponin I / Q000097:blood*; D020107:Troponin T / Q000097:blood*
chemical_list: D010446:Peptide Fragments; D019210:Troponin I; D020107:Troponin T; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain