title: Fibrinogen and AER are major independent predictors of 11-year cardiovascular mortality in type 2 diabetes: the Casale Monferrato Study.
abstract: OBJECTIVE
  Fibrinogen and elevated AER increase cardiovascular mortality, but few data are available in the type 2 diabetic population. We have conducted an 11-year follow-up study of the Casale Monferrato cohort to assess: (1) the long-term predictive role of AER independently of conventional risk factors; (2) the shape of its relationship with cardiovascular mortality; and (3) whether fibrinogen has a predictive effect independent of the increased cardiovascular risk associated with nephropathy.
  
  
  METHODS
  During the follow-up period (1991-2001) a population-based cohort of 1,565 patients was regularly examined, and measurements of HbA1c were centralised. Multivariate Cox proportional hazards modelling was employed to assess the role of fibrinogen and AER as predictors of all-cause and cardiovascular mortality, independently of baseline variables and individual cumulative average values of HbA1c during follow-up.
  
  
  RESULTS
  In 10,890.2 person-years of observations, 685 deaths were identified, giving an all-cause mortality rate of 63.4 per 1,000 person-years (95% CI 58.8-68.3). In Cox regression analyses, the strongest predictor of cardiovascular mortality was macroalbuminuria (relative risk 2.18, 95% CI 1.62-2.94), which was mainly associated with a high risk of short-term mortality. No increased risk was evident until the upper microalbuminuric range of AER values. Plasma fibrinogen was also a major independent predictor, and its role was not modified by AER, or by the exclusion of subjects developing chronic renal failure or diabetic nephropathy during follow-up.
  
  
  CONCLUSIONS
  The results indicate that: (1) AER is the main independent predictor of 11-year cardiovascular mortality; (2) this effect is mainly evident in the upper range of microalbuminuria and in macroalbuminuria; and (3) fibrinogen has an independent effect on cardiovascular mortality, but no synergistic effect with AER, suggesting that both endothelial dysfunction and chronic inflammation are involved in the excess cardiovascular mortality of type 2 diabetic patients.
authors.affiliation: Department of Internal Medicine, University of Turin, corso Dogliotti 14, 10126, Turin, Italy. graziella.bruno@katamail.com
authors.forename: G
authors.initials: G
authors.lastname: Bruno
authors.forename: F
authors.initials: F
authors.lastname: Merletti
authors.forename: A
authors.initials: A
authors.lastname: Biggeri
authors.forename: G
authors.initials: G
authors.lastname: Bargero
authors.forename: S
authors.initials: S
authors.lastname: Ferrero
authors.forename: G
authors.initials: G
authors.lastname: Pagano
authors.forename: P
authors.initials: P
authors.lastname: Cavallo-Perin
mesh_terms: D000368:Aged; D000419:Albuminuria; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000401:mortality*; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000401:mortality*; D003925:Diabetic Angiopathies / Q000401:mortality*; D005340:Fibrinogen / Q000378:metabolism*; D005500:Follow-Up Studies; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008875:Middle Aged; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D012044:Regression Analysis; D012306:Risk; D013997:Time Factors
chemical_list: D015415:Biomarkers; D005340:Fibrinogen