title: Impact of biomarkers for endothelial dysfunction and procoagulant state on 10-year cardiovascular risk in Type 2 diabetes.
abstract: OBJECTIVE
  To estimate the coronary heart disease and cardiovascular disease risk associated with novel biomarkers in Type 2 diabetes mellitus.
  
  
  METHODS
  We measured baseline peripheral blood concentrations of soluble E-selectin, factor XIIa, thrombin-antithrombin III complex and plasminogen activator inhibitor-1 in 86 patients with Type 2 diabetes free of known coronary heart disease. We used Cox proportional hazard models to estimate multivariable-adjusted hazard ratios associated with biomarker levels for 10-year coronary heart disease risk (n = 33 events) or total cardiovascular disease risk (n = 45 events).
  
  
  RESULTS
  At baseline, mean (sd) age was 62 years (7 years); 62 were men; and 43 had microalbuminuria. Soluble E-selectin demonstrated cross-sectional relationships with glucose and factor XIIa was related to plasminogen activator inhibitor-1 and triglycerides (all P < 0.05). Baseline log soluble E-selectin was significantly related to incident coronary heart disease and cardiovascular disease. Hazard ratios (95% CIs) associated with a 1-unit increase in log soluble E-selectin in age- and sex-adjusted models were: coronary heart disease : 4.6 (95% CI 1.9-11.3), P = 0.001; cardiovascular disease: 3.6 (95% CI 1.7-7.4, P = 0.001); and in multivariable-adjusted models were: coronary heart disease: 2.9 (95% CI 1.2-7.1, P = 0.02); cardiovascular disease: 2.3 (95% CI 1.1-4.8), P = 0.02. Factor XIIa was significantly related to incident cardiovascular disease. The hazard ratios associated with a 1-unit increase in factor XIIa in age- and sex-adjusted models was 1.5 (95% CI 1.1-1.9, P = 0.003) and in a multivariable-adjusted model was 1.3 (95% CI 1.0-1.6, P = 0.047). Plasminogen activator inhibitor-1 and thrombin-antithrombin III complex were not related to cardiovascular disease events.
  
  
  CONCLUSIONS
  In our study, soluble E-selectin and factor XIIa were significantly related to 10-year incident macrovascular events in patients with Type 2 diabetes. These preliminary findings call for replication in larger studies.
authors.affiliation: Department of Cardiology, Essex Cardiothoracic Centre, Basildon, UK.
authors.forename: A
authors.initials: A
authors.lastname: Natarajan
authors.forename: S M
authors.initials: SM
authors.lastname: Marshall
authors.forename: P J
authors.initials: PJ
authors.lastname: Kesteven
authors.forename: J M
authors.initials: JM
authors.lastname: McComb
authors.forename: M K
authors.initials: MK
authors.lastname: Rutter
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D003327:Coronary Disease / Q000097:blood* / Q000503:physiopathology; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000503:physiopathology; D003925:Diabetic Angiopathies / Q000097:blood* / Q000378:metabolism / Q000503:physiopathology; D019040:E-Selectin / Q000097:blood*; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000503:physiopathology; D015956:Factor XIIa / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D019040:E-Selectin; D015956:Factor XIIa