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Background: It is well accepted that heavy physical exertion can trigger the onset of myocardial infarction, but the mechanism is uncertain. As platelet and endothelial function play an important role in thrombotic events, platelet and prostacyclin responses to maximal treadmill exercise were studied.Methods/results: The study subjects were 40 healthy men, mean (SEM) age 29 (5) years. Platelet aggregation was measured on a four channel aggregometer. Plasma 6-keto-prostaglandin F1alpha was analysed using an enzyme immunoassay technique. Upright posture and exercise produced an increase in platelet aggregability, as indicated by a fall in the threshold concentration of adrenaline (epinephrine) from 7.6 (1.5) microM at rest to 4.3 (1.0) microM after exercise (p = 0.002). The collagen lag time became significantly shorter with exercise (from 79.1 (3.1) seconds at rest to 71.9 (2.6) seconds after exercise, p = 0.003). Exercise was also associated with a 55% increase in plasma 6-keto-prostaglandin F1alpha (from 38.1 (75%CI 29.0 to 46.5) pg/ml at rest to 59.2 (47.3 to 66.8) pg/ml after exercise, p<0.001).Conclusions: In healthy male subjects, upright posture and maximal exercise increased platelet aggregability but this increase was counteracted by an increase in prostacyclin production. In patients with endothelial dysfunction, a reduced prostacyclin response to exercise may promote a transient prothrombotic imbalance that may trigger cardiovascular disease onset. [ABSTRACT FROM AUTHOR]

Background: Lipoxins represent a group of lipoxygenase derived eicosanoids which, in contrast to leukotrienes, are potent anti-inflammatory mediators. The aim of our study was to determine lipoxin A4 (LXA4) and leukotriene C4 (LTC4) levels in nasal lavages after intranasal challenge with aspirin in aspirin intolerant (AIA) in comparison to aspirin tolerant (ATA) asthmatics and after allergen challenge in patients suffering from allergic rhinitis. Methods: Twelve AIA, 8 ATA and 20 allergic patients were challenged with placebo, 16 mg of lysine-aspirin (Lys-ASA) or allergen (grasses). Nasal lavages were collected and eicosanoids’ levels were determined using ELISA. Results: Clinically positive Lys-ASA challenge in AIA resulted in influx of leukocytes (eosinophils and basophils) to nasal secretions and increase of LTC4 to 106.82 pg/ml ( P < 0.05 vs baseline (26.58 pg/ml)) on first hour after the challenge. We did not observe any differences in LTC4 level before and after ASA challenge in ATA. In AIA group the mean level of LXA4 was 43 ± 21.5 pg/ml after placebo and decreased in 2 h after Lys-ASA challenge (29 ± 17 pg/ml, P = 0.015). We found an increase in LXA4 in ATA after ASA provocation as compared to placebo (33 ± 16 pg/ml vs 52 ± 31 pg/ml, P = 0.046). In atopic patients baseline level of LXA4 was 33.49 ± 16.95 pg/ml with no difference after the clinically positive allergen challenge (36.22 ± 13.26 pg/ml, P = 0.23). Conclusions: Results of our study confirm that AIA have diminished LXs’ biosynthesis capacities in vivo after ASA challenge. Taking into consideration anti-inflammatory properties of lipoxins this phenomenon may be partially responsible for the development of chronic inflammation in AIA patients. [ABSTRACT FROM AUTHOR]

Endothelial dysfunction may precede development of type 2 diabetes. We tested the hypothesis that elevated levels of hemostatic markers of endothelial dysfunction, plasminogen activator inhibitor-1 (PAI-1) antigen, and von Willebrand factor (vWF) antigen predicted incident diabetes independent of other diabetes risk factors. We followed 2,924 Framingham Offspring subjects (54% women, mean age 54 years) without diabetes at baseline (defined by treatment, fasting plasma glucose > or =7 or 2-h postchallenge glucose > or =11.1 mmol/l) over 7 years for new cases of diabetes (treatment or fasting plasma glucose > or =7.0 mmol/l). We used a series of regression models to estimate relative risks for diabetes per interquartile range (IQR) increase in PAI-1 (IQR 16.8 ng/ml) and vWF (IQR 66.8% of control) conditioned on baseline characteristics. Over follow-up, there were 153 new cases of diabetes. Age- and sex-adjusted relative risks of diabetes were 1.55 per IQR for PAI-1 (95% CI 1.41-1.70) and 1.49 for vWF (1.21-1.85). These effects remained after further adjustment for diabetes risk factors (including physical activity; HDL cholesterol, triglyceride, and blood pressure levels; smoking; parental history of diabetes; use of alcohol, nonsteroidal anti-inflammatory drugs, exogenous estrogen, or hypertension therapy; and impaired glucose tolerance), waist circumference, homeostasis model assessment of insulin resistance, and inflammation (assessed by levels of C-reactive protein): the adjusted relative risks were 1.18 per IQR for PAI-1 (1.01-1.37) and 1.39 for vWF (1.09-1.77). We conclude that in this community-based sample, plasma markers of endothelial dysfunction increased risk of incident diabetes independent of other diabetes risk factors including obesity, insulin resistance, and inflammation. [ABSTRACT FROM AUTHOR]

Context: Increased risk for cardiovascular disease in persons with glucose intolerance (impaired glucose tolerance and type 2 diabetes mellitus) is not fully explained by concomitant elevations in traditional atherosclerosis risk factors. Hyperinsulinemia associated with glucose intolerance may increase risk directly, or its effect could be mediated through impaired hemostatic function.Objective: To evaluate associations between fasting insulin levels and hemostatic factors in subjects with normal and impaired glucose homeostasis.Design: Cross-sectional analysis conducted between January 1991 and June 1995.Setting: The population-based Framingham Offspring Study.Subjects: A total of 1331 men and 1631 women aged 26 to 82 years, without diagnosed diabetes or cardiovascular disease and classified as having normal glucose tolerance (80.2%) or glucose intolerance (impaired glucose tolerance and impaired fasting glucose combined, 15.2%; previously undiagnosed diabetes, 4.7%) using an oral glucose tolerance test.Main Outcome Measures: Trends across quintiles of fasting insulin in levels of plasminogen activator inhibitor 1 (PAI-1) antigen, tissue-type plasminogen activator (tPA) antigen, von Willebrand factor (vWF) antigen, factor VII antigen, fibrinogen, and plasma viscosity. We stratified analyses by sex and glucose tolerance status and adjusted hemostatic factor levels for obesity, lipid levels, and traditional cardiovascular disease risk factors.Results: Mean levels of all hemostatic factors (except for fibrinogen in men) increased across fasting insulin quintiles among subjects with normal glucose tolerance (P<.001 for trend). Levels of PAI-1 and tPA antigens, but not other hemostatic factors, were higher comparing subjects with glucose intolerance with those with normal glucose tolerance (P<.001). Among subjects with glucose intolerance, levels of PAI-1 and tPA antigen in men and women (P<.01 for trend) and vWF antigen in men (P<.05 for trend) increased significantly across insulin quintiles, but levels of factor VII antigen, fibrinogen, and plasma viscosity did not increase.Conclusions: Elevated levels of fasting insulin are associated with impaired fibrinolysis and hypercoagulability in subjects with normal glucose tolerance. Hyperinsulinemia is associated primarily with impaired fibrinolysis in subjects with glucose intolerance. Excess risk for cardiovascular disease associated with hyperinsulinemia and glucose intolerance may be mediated in part by enhanced potential for acute thrombosis. [ABSTRACT FROM AUTHOR]