Impact of biomarkers for endothelial dysfunction and procoagulant state on 10‐year cardiovascular risk in Type 2 diabetes1

• Published in: Diabetic medicine Vol. 28; no. 10; pp. 1201 - 1205
• Main Authors: Natarajan, A., Marshall, S. M., Kesteven, P. J., McComb, J. M., Rutter, M. K.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.10.2011
• Subjects: acute cerebral infarction; acute myocardial infarction; epidemiology; risk factors; Type 2 diabetes
• ISSN: 0742-3071; 1464-5491
• DOI: 10.1111/j.1464-5491.2011.03311.x

Diabet. Med. 28, 1201–1205 (2011) Aims  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.