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Thrombin, Inflammation, and Cardiovascular Disease: Inflammation Markers and CVD Risk

PAI-1 levels are associated with insulin, suggesting that the role of PAI-1 may be particularly important in people with the metabolic syndrome or type 2 diabetes. The regulation of PAI-1 levels—at least in blood—is in part mediated by regulators of glycemic control and inflammation: insulin and proinsulin can stimulate endothelial cells and hepatocytes to produce PAI-1,’ and PAI-1 is believed to be a weak acute-phase reactant. In addition, adipocytes can directly synthesize and secrete PAI-1, helping to explain the known association of PAI-1 levels with body mass index. this

All of these factors associated with PAI-1 levels are also correlated with each other; this high degree of covariance makes it difficult to establish independent associations. To help make these connections, we performed a factor analysis as part of the data analysis of the Cardiovascular Health Study. Factor analysis is a statistical approach that computes a set of hypothetical uncorrelated “factors” from a set of covariate variables. This method has been used to analyze the components of the metabolic syndrome; in several studies, it has consistently yielded four factors: BP, body mass, insulin/glucose, and lipids. We entered these variables, as well as variables related to inflammation and hemostasis; this analysis yielded the established four factors, plus three new factors, which we termed inflammation, vitamin K-dependent coagulation factors, and procoagulant activity.4 PAI-1 was associated with the insulin/glucose factor and the body mass factor, and not with the others, supporting the notion that PAI-1 reflects both insulin level and adiposity, but only weakly, if at all, inflammation or ongoing coagulant activity.
Research done over the last 10 years has played an important role in identifying inflammation as a key process in atherosclerosis and CVD.