[Show abstract][Hide abstract] ABSTRACT: Mannose-binding lectin (MBL) and ficolins activate the complement cascade, which is involved in atherogenesis. Based on a pilot study, we hypothesized that functional polymorphisms in the MBL gene (MBL2) leading to dysfunctional protein are related to development of myocardial infarction (MI). The aim of the present study was to study polymorphisms in MBL2 and ficolin genes in relation to the risk of MI.
Using the population-based HUNT Study in Norway, 57,133 persons were followed up for a first-time MI from 1995-1997 until the end of 2008. The 370 youngest MI patients were matched by age (range 29-62 years) and gender to 370 controls. A younger population was selected because disease in this group might be less dependent on non-genetic risk factors. The study size was based on power calculation. Polymorphisms in MBL2 and in the genes of ficolin-1, ficolin-2 and ficolin-3 were genotyped by pyrosequencing and related to the risk of MI, estimated as odds ratios (OR). Functional haplotypes were analyzed and stringent alpha levels of significance were set by permutation testing. Variant MBL2 haplotypes causing MBL deficiency were associated with a two-fold higher risk of MI (OR 2.04, 95%CI 1.29-3.24). Adjustments for conventional cardiovascular risk factors did not substantially influence the association. The ficolins were not associated with MI risk.
In a young to middle aged and relatively healthy Caucasian population, MBL2 variants related to functional MBL deficiency were associated with a doubling of the risk for MI, independent of conventional risk factors. This supports that MBL deficiency may lead to increased atherosclerosis or development of vulnerable plaques.
[Show abstract][Hide abstract] ABSTRACT: 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.
Prospective population-based cohort study.
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.
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.
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.
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.
[Show abstract][Hide abstract] ABSTRACT: Neopterin has emerged as a novel predictor of coronary events. The study aim was to compare the predictive value of neopterin and C-reactive protein (CRP) on long-term risk for fatal ischemic heart disease (IHD) in persons with newly diagnosed diabetes compared to persons without diabetes.
In 1984-1986 a large population study, HUNT 1, was conducted in Norway. During the study, 205 patients were diagnosed with formerly unknown diabetes. A matched control group without diabetes was selected from the HUNT 1 population. Fatal IHD was registered until 2004. Blood samples were drawn at baseline and serum was analysed for neopterin and CRP. Cox regression analysis with correction for age, gender, hypertension, body mass index, established cardiovascular disease and total cholesterol was used to estimate hazard ratios (HR) for fatal IHD. In the diabetes group, neopterin and CRP were independent predictors of fatal IHD, HR 2.59 (1.11-6.01) and 2.45 (1.05-5.69), respectively. Neither CRP nor neopterin were significant predictors of fatal IHD in the control group.
In subjects with diabetes, both neopterin and CRP were independent predictors of fatal IHD, suggesting that these two markers reflect different aspects of the pathogenesis underlying fatal coronary events.