Lactoferrin is a novel predictor of fatal ischemic heart disease in diabetes mellitus type 2: long-term follow-up of the HUNT 1 study.
OBJECTIVE
The pathogenesis of diabetes and atherosclerosis is linked through inflammation. Neutrophils contribute to atherosclerotic plaque development, and are dysfunctional in diabetes. The aim of this study was to compare the predictive values of two neutrophil degranulation products, myeloperoxidase and lactoferrin, on long-term risk for fatal ischemic heart disease in persons with newly diagnosed diabetes and controls.


METHODS
Prospective population-based cohort study.


METHODS
In 1984-1986, a large population study, HUNT 1, was conducted in Norway. Previously unknown diabetes was diagnosed in 205 persons. A matched control group without diabetes was selected from the HUNT 1.


METHODS
Fatal ischemic heart disease was registered until 2004. Baseline serum was analysed for myeloperoxidase and lactoferrin. Cox regression analysis with adjustments for age, gender, hypertension, body mass index, established cardiovascular disease and total cholesterol was used to estimate hazard ratios for fatal ischemic heart disease.


RESULTS
In the diabetes group (200 subjects), the two highest tertiles of lactoferrin predicted fatal ischemic heart disease, hazard ratio 2.54 (95% CI, 1.00-6.45) and 4.06 (1.72-9.60). Myeloperoxidase did not predict death from ischemic heart disease in subjects with diabetes. In the controls (198 subjects), none of the biomarkers predicted fatal ischemic heart disease.


CONCLUSIONS
Increased baseline concentration of lactoferrin strongly predicted the long-term risk for fatal ischemic heart disease in patients with newly diagnosed diabetes. Based on the literature, we hypothesize that the increased concentrations may reflect neutrophil priming caused by hyperglycemia.
Vengen
Inga Thorsen
IT
Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology, and Department of Cardiology, Trondheim University Hospital, Trondheim, Norway.
Dale
Ane Cecilie
AC
Wiseth
Rune
R
Midthjell
Kristian
K
Videm
Vibeke
V
D000368:Aged; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000175:diagnosis*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007249:Inflammation; D007781:Lactoferrin / Q000097:blood* / Q000378:metabolism; D008297:Male; D017202:Myocardial Ischemia / Q000378:metabolism* / Q000401:mortality*; D009504:Neutrophils / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D016016:Proportional Hazards Models; D012307:Risk Factors; D013997:Time Factors
D009195:Peroxidase; D007781:Lactoferrin