GENDER DIFFERENCES IN THE RELATIONSHIPS BETWEEN PLASMA PLASMINOGEN-ACTIVATOR INHIBITOR-1 ACTIVITY AND FACTORS LINKED TO THE INSULIN-RESISTANCE SYNDROME IN ESSENTIAL-HYPERTENSION

Impaired fibrinolysis due to elevated levels of plasma plasminogen act ivator inhibitor type 1 (PAI-1) is a risk factor for thromboembolic di sease. Hypertension, obesity, derangements in lipid and glucose homeos tasis, and elevated levels of PAI-1 are features of the insulin resist ance syndrome. The interrelationships between PAI-1 and the metabolic disturbances seen in this condition are unsettled. We investigated the associations between PAI-1 activity and components of the insulin res istance syndrome in 53 men and 31 women with untreated hypertension. I n men, PAI-1 activity correlated significantly with plasma glucose (r= .41, P=.002), insulin sensitivity (r=-.35, P=.01), and insulin-induced suppression of nonesterified fatty acid (NEFA) (r=-.43, P=.007). Plas ma glucose and NEFA suppression were independently associated with PAI -1 activity in a multivariate analysis. In women, PAI-1 activity corre lated with body mass index (r=.62, P=.0005), waist-to-hip ratio (r=.75 , P=.0001), plasma glucose (r=.50, P=.007), insulin (r=.49, P=.009), p roinsulin (r=.57, P=.002), C-peptide (r=.60, P=.0009), insulin sensiti vity (r=-.74, P=.0001), NEFA suppression (r=-.64, P=.003), and triglyc erides (r=.58, P=.001). In multivariate analyses, insulin sensitivity and NEFA suppression were independently associated with PAI-1 if waist -to-hip ratio was not included in the model. After introduction of wai st-to-hip ratio into the model, waist-to-hip ratio was the only indepe ndent predictor of PAI-1 activity. We conclude that in women, waist-to -hip ratio, body mass index, and insulin-induced NEFA suppression are determinants for PAI-1 activity. In men, insulin-induced NEFA suppress ion and plasma glucose are independently associated with PAI-1 activit y.