title: NT-proBNP linking low-moderately impaired renal function and cardiovascular mortality in diabetic patients: the population-based Casale Monferrato Study.
abstract: BACKGROUND
  Few data are available to assess whether a low-moderate reduction in estimated glomerular filtration rates (eGFR) has a role per se on cardiovascular (CV) mortality or other biomarkers such as NT-proBNP allow to explain such association.
  
  
  RESULTS
  In a prospective study including 1,645 type 2 diabetic subjects of the population-based Casale Monferrato Study, who had no clinical evidence of heart failure and eGFR >45 ml/min/1.73 m2, we examined 6 years CV mortality. Multivariate Cox proportional hazards modeling were used to estimate the effect of NT-proBNP on the association between eGFR and mortality, independently of baseline CV risk factors, albumin excretion rate (AER) and C-reactive protein (CRP). During follow-up, 327 people died (149 of CV diseases) out of 8334.5 person-years. Compared to eGFR≥90 ml/min/1.73 m2, values of 60-89 and 45-59 ml/min/1.73 m2 conferred a fully adjusted hazard ratios (HRs) of CV mortality of 1.74 (1.08-2.82) and 1.95 (1.03-3.68), respectively. After further adjustment for NT-proBNP, however, HRs were no longer significant (HRs 1.42, 0.83-2.42 and 1.22, 0.59-2.51). In this model, HR for logNT-proBNP was 1.84 (1.52-2.22). Adding NT-proBNP to the model improved the C-statistic of CV mortality from 0.79 (0.76-0.83) to 0.84 (0.81-0.87), yielded an IDI of 0.03 (p = 0.02), and a NRI of 0.44 (p = 0.016).
  
  
  CONCLUSIONS
  In diabetic people a modest reduction in renal function increased 6-year CV mortality independently of albuminuria. This association, however, was mainly explained by the effect of NT-proBNP, that remained the strongest prognostic marker for a worse CV outcome, even after adjustment for other CV risk factors and pre-existing CVD.
authors.affiliation: Department of Medical Sciences, University of Turin, Turin, Italy.
authors.forename: Graziella
authors.initials: G
authors.lastname: Bruno
authors.affiliation: Department of Medical Sciences, University of Turin, Turin, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Barutta
authors.affiliation: Department of Medical Sciences, University of Turin, Turin, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Landi
authors.affiliation: Department of Medical Sciences, University of Turin, Turin, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Cavallo Perin
authors.affiliation: Department of Medical Sciences, University of Turin, Turin, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Gruden
mesh_terms: D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000150:complications / Q000401:mortality; D005260:Female; D005919:Glomerular Filtration Rate; D006333:Heart Failure / Q000097:blood* / Q000150:complications / Q000401:mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D009026:Mortality; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D011379:Prognosis; D016016:Proportional Hazards Models; D051437:Renal Insufficiency / Q000097:blood* / Q000209:etiology / Q000401:mortality
chemical_list: D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain