title: Bloodstream Amyloid-beta (1-40) Peptide, Cognition, and Outcomes in Heart Failure.
abstract: OBJECTIVE
  In the brain, amyloid-beta generation participates in the pathophysiology of cognitive disorders; in the bloodstream, the role of amyloid-beta is uncertain but may be linked to sterile inflammation and senescence. We explored the relationship between blood levels of amyloid-beta 1-40 peptide (Aβ40), cognition, and mortality (all-cause, cardiovascular, and heart failure [HF]-related) in ambulatory patients with HF.
  
  
  METHODS
  Bloodstream Aβ40 was measured in 939 consecutive patients with HF. Cognition was evaluated with the Pfeiffer questionnaire (adjusted for educational level) at baseline and during follow-up. Multivariate Cox regression analyses and measurements of performance (discrimination, calibration, and reclassification) were used, with competing risk for specific causes of death.
  
  
  RESULTS
  Over 5.1 ± 2.9 years, 471 patients died (all-cause): 250 from cardiovascular causes and 131 HF-related. The median Aβ40 concentration was 519.1 pg/mL [Q1-Q3: 361.8-749.9 pg/mL]. The Aβ40 concentration correlated with age, body mass index, renal dysfunction, and New York Heart Association functional class (all P < .001). There were no differences in Aβ40 in patients with and without cognitive impairment at baseline (P = .97) or during follow-up (P = .20). In multivariable analysis, including relevant clinical predictors and N-terminal pro-B-type natriuretic peptide, Aβ40 remained significantly associated with all-cause death (HR, 1.22; 95%CI, 1.10-1.35; P < .001) and cardiovascular death (HR, 1.18; 95%CI, 1.03-1.36; P = .02), but not with HF-related death (HR, 1.13; 95%CI, 0.93-1.37; P = .22). Circulating Aβ40 improved calibration and patient reclassification.
  
  
  CONCLUSIONS
  Blood levels of Aβ40 are not associated with cognitive decline in HF. Circulating Aβ40 was predictive of mortality and may indicate systemic aging.
authors.affiliation: Unidad de Insuficiencia Cardiaca, Servicio de Cardiología, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain; Departamento de Medicina, Universidad Autónoma de Medicina, Barcelona, Spain; CIBERCV (CB16/11/00403), Instituto de Salud Carlos III, Madrid, Spain. Electronic address: abayesgenis@gmail.com.
authors.forename: Antoni
authors.initials: A
authors.lastname: Bayes-Genis
authors.affiliation: Servicio de Bioquímica, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain.
authors.forename: Jaume
authors.initials: J
authors.lastname: Barallat
authors.affiliation: Unidad de Insuficiencia Cardiaca, Servicio de Cardiología, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain; Departamento de Medicina, Universidad Autónoma de Medicina, Barcelona, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: de Antonio
authors.affiliation: Unidad de Insuficiencia Cardiaca, Servicio de Cardiología, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain; CIBERCV (CB16/11/00403), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Mar
authors.initials: M
authors.lastname: Domingo
authors.affiliation: Unidad de Insuficiencia Cardiaca, Servicio de Cardiología, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain; CIBERCV (CB16/11/00403), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Elisabet
authors.initials: E
authors.lastname: Zamora
authors.affiliation: CIBER de Epidemiología y Salud Pública, Barcelona, Spain; Grupo de estudio en Genética y Epidemiología Cardiovascular, Grupo de estudio REGICOR, IMIM (Instituto de Investigación Médica del Hospital del Mar), Barcelona, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Vila
authors.affiliation: CIBER de Epidemiología y Salud Pública, Barcelona, Spain; Grupo de estudio en Genética y Epidemiología Cardiovascular, Grupo de estudio REGICOR, IMIM (Instituto de Investigación Médica del Hospital del Mar), Barcelona, Spain.
authors.forename: Isaac
authors.initials: I
authors.lastname: Subirana
authors.affiliation: Unidad de Insuficiencia Cardiaca, Servicio de Cardiología, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain; CIBERCV (CB16/11/00403), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Paloma
authors.initials: P
authors.lastname: Gastelurrutia
authors.affiliation: Departamento de Medicina, Universidad Autónoma de Medicina, Barcelona, Spain.
authors.forename: M Cruz
authors.initials: MC
authors.lastname: Pastor
authors.affiliation: Cardiology Division, Massachusetts General Hospital, Harvard Clinical Research Institute, Boston, Massachusetts, United States.
authors.forename: James L
authors.initials: JL
authors.lastname: Januzzi
authors.affiliation: Unidad de Insuficiencia Cardiaca, Servicio de Cardiología, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain; Departamento de Medicina, Universidad Autónoma de Medicina, Barcelona, Spain; CIBERCV (CB16/11/00403), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Josep
authors.initials: J
authors.lastname: Lupón
mesh_terms: D000368:Aged; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D003072:Cognition Disorders / Q000097:blood* / Q000401:mortality; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000097:blood* / Q000401:mortality / Q000523:psychology; D006801:Humans; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism*; D011379:Prognosis
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain
keywords: Amiloide-beta; Amyloid-beta; Biomarcadores; Biomarkers; Cognición; Cognition; Heart failure; Insuficiencia cardiaca; Prognosis; Pronóstico