title: Additive prognostic value of plasma N-terminal pro-brain natriuretic peptide and coronary artery calcification for cardiovascular events and mortality in asymptomatic patients with type 2 diabetes.
abstract: BACKGROUND
  In patients with type 2 diabetes, cardiovascular disease (CVD) is the major cause of morbidity and mortality. We evaluated the combination of NT-proBNP and coronary artery calcium score (CAC) for prediction of combined fatal and non-fatal CVD and mortality in patients with type 2 diabetes and microalbuminuria (>30 mg/24-h), but without known coronary artery disease. Moreover, we assessed the predictive value of a predefined categorisation of patients into a high- and low-risk group at baseline.
  
  
  METHODS
  Prospective study including 200 patients. All received intensive multifactorial treatment. Patients with baseline NT-proBNP > 45.2 ng/L and/or CAC ≥ 400 were stratified as high-risk patients (n = 133). Occurrence of fatal- and nonfatal CVD (n = 40) and mortality (n = 26), was traced after 6.1 years (median).
  
  
  RESULTS
  High-risk patients had a higher risk of the composite CVD endpoint (adjusted hazard ratio [HR] 10.6 (95 % confidence interval [CI] 2.4-46.3); p = 0.002) and mortality (adjusted HR 5.3 (95 % CI 1.2-24.0); p = 0.032) compared to low-risk patients. In adjusted continuous analysis, both higher NT-proBNP and CAC were strong predictors of the composite CVD endpoint and mortality (p ≤ 0.0001). In fully adjusted models mutually including NT-proBNP and CAC, both risk factors remained associated with risk of CVD and mortality (p ≤ 0.022). There was no interaction between NT-proBNP and CAC for the examined endpoints (p ≥ 0.31).
  
  
  CONCLUSIONS
  In patients with type 2 diabetes and microalbuminuria but without known coronary artery disease, NT-proBNP and CAC were strongly associated with fatal and nonfatal CVD, as well as with mortality. Their additive prognostic capability holds promise for identification of patients at high risk.
authors.affiliation: Steno Diabetes Center, Niels Steensens Vej 1, Gentofte, 2820, Denmark. bjos@steno.dk.
authors.forename: Bernt Johan
authors.initials: BJ
authors.lastname: von Scholten
authors.affiliation: Steno Diabetes Center, Niels Steensens Vej 1, Gentofte, 2820, Denmark. hrhl@dadlnet.dk.
authors.forename: Henrik
authors.initials: H
authors.lastname: Reinhard
authors.affiliation: Steno Diabetes Center, Niels Steensens Vej 1, Gentofte, 2820, Denmark. twih@steno.dk.
authors.forename: Tine Willum
authors.initials: TW
authors.lastname: Hansen
authors.affiliation: Steno Diabetes Center, Niels Steensens Vej 1, Gentofte, 2820, Denmark. mkfl@steno.dk.
authors.forename: Morten
authors.initials: M
authors.lastname: Lindhardt
authors.affiliation: Center for Functional and Diagnostic Imaging and Research, Hvidovre Hospital, University of Copenhagen, Compenhagen, Denmark. claus.leth.petersen@hvh.regionh.dk.
authors.forename: Claus Leth
authors.initials: CL
authors.lastname: Petersen
authors.affiliation: Frederiksberg Hospital, Frederiksberg, Denmark. Niels.Wiinberg@regionh.dk.
authors.forename: Niels
authors.initials: N
authors.lastname: Wiinberg
authors.affiliation: Gentofte Hospital, Gentofte, Denmark. prh@dadlnet.dk.
authors.forename: Peter Riis
authors.initials: PR
authors.lastname: Hansen
authors.affiliation: Rigshospitalet, Copenhagen, Denmark. hhparving@dadlnet.dk.|University of Copenhagen, Copenhagen, Denmark. hhparving@dadlnet.dk.
authors.forename: Hans-Henrik
authors.initials: HH
authors.lastname: Parving
authors.affiliation: The Heart Center, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. pjc@dadlnet.dk.
authors.forename: Peter Karl
authors.initials: PK
authors.lastname: Jacobsen
authors.affiliation: Steno Diabetes Center, Niels Steensens Vej 1, Gentofte, 2820, Denmark. pro@steno.dk.|University of Copenhagen, Copenhagen, Denmark. pro@steno.dk.|Aarhus University, Aarhus, Denmark. pro@steno.dk.
authors.forename: Peter
authors.initials: P
authors.lastname: Rossing
mesh_terms: D000368:Aged; D000419:Albuminuria; D058070:Asymptomatic Diseases; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood / Q000000981:diagnostic imaging / Q000401:mortality*; D015331:Cohort Studies; D003324:Coronary Artery Disease / Q000000981:diagnostic imaging*; D003924:Diabetes Mellitus, Type 2; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D061330:Multidetector Computed Tomography; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D061205:Vascular Calcification / Q000000981:diagnostic imaging*
chemical_list: D015415:Biomarkers; D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain