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      Interleukin-10 concentration and coronary heart disease (CHD) event risk in the estrogen replacement and atherosclerosis (ERA) study.

      Aged, Biological Markers, blood, C-Reactive Protein, metabolism, Coronary Disease, drug therapy, epidemiology, immunology, Disease Progression, Estrogen Replacement Therapy, Estrogens, administration & dosage, Female, Follow-Up Studies, Humans, Interleukin-10, Interleukin-6, Middle Aged, Postmenopause, drug effects, Predictive Value of Tests, Proportional Hazards Models, Risk Factors, Vasculitis, prevention & control

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          Interleukin-10 (IL-10) is a cytokine with pleiotropic properties. Limited biochemical and clinical evidence suggest a link between IL-10 and coronary heart disease (CHD). However, more data are needed to clarify the relationship between IL-10 and risk for CHD events. The present study was a secondary analysis of the estrogen replacement and atherosclerosis (ERA) trial, a randomized clinical trial that examined the effects of hormone replacement therapy on post-menopausal women with known coronary atherosclerosis. IL-10 concentration, measured at baseline, was treated as both a continuous and categorical variable. Cox proportional hazards models were used to compute hazard ratios as estimates of relative risk for CHD events. There were 71 events over an average 3.2 year follow-up. Incident rates were higher for individuals with IL-10 concentrations equal to or greater than the median level (1.04 pg/mL) compared to those individuals below the median level (30% versus 18.5%, p=0.02). The cumulative incidence of CHD events was significantly greater in individuals with IL-10 concentrations >or=1.04 pg/mL (p=0.01). A one standard deviation increase in baseline IL-10 concentration was associated with a 34% greater risk of a CHD event (HR 1.34 [1.06-1.68], p=0.01). This elevated risk was not altered by interleukin-6, C-reactive protein, or additional cardiovascular risk factors. IL-10 concentration and risk for CHD events was most pronounced in diabetics (HR 2.4 [1.46-3.83], p=0.0005). In the ERA trial, elevated IL-10 concentration was associated with an increased risk for future cardiovascular events in post-menopausal women with established coronary atherosclerosis. Further study of the relationship between IL-10 and the pathogenesis and progression of atherosclerosis and cardiovascular events is warranted.

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