THE RELATIONSHIPS BETWEEN INSULIN AND PLASMINOGEN-ACTIVATOR INHIBITOR-1 LEVELS - ASSESSMENT IN GROUPS OF SUBJECTS WITH DYSLIPIDEMIA AND HYPERTENSION

Elevated plasminogen activator inhibitor-1 (PAI-1) levels have been de scribed in some populations to associate with hyperinsulinaemia in the metabolic syndrome which predisposes to coronary heart disease (CHD). This association, if consistently present, could provide more evidenc e for a synergistic role for insulin resistance and altered fibrinolys is in the pathogenesis of CHD. To test the hypothesis further therefor e. we explored the relationships between the fasting levels of insulin and PAI-I and lipids in groups of non-diabetic Arab subjects classifi ed as: A: normolipidaemic (II = 148); B: hyperlipidaemic: (n = 99), su bdivided into - C: normotensive (n = 71) and D: hypertensive (n = 28); and E: patients with CHD (n = 12). In Group A, fasting insulin (FI) w as 7.2+/-(SD) 3.4 mU/l, PAI-1 30.6+/-9.7 ng/ml, both levels significan tly lower (P < 0.05) than in Group B as a whole (FI 9.7+/-5.2, PAI-1 3 6.9+/-10.6), or as normotensive Group C (FI 9.4+/-5.4, PAI-1 36.7+/-10 .3) or hypertensive Group D (FI 10.9+/-4.8, PAI-1 37.2+/-11.5). These values were highest in the hyperlipidaemic hypertensive Group D. There were no significant differences relative to the hyperlipidaemic pheno type of predominant hypercholesterolaemia, hypertriglyceridaemia or mi xed hyperlipidaemia. PAI-1 (34.7+/-13.8) and Fl (7.0+/-2.4) levels in Group E with CHD were similar to those of Group A but lower than Value s seen in Groups B, C and D, Consistent positive correlations (r = 0.3 2-0.41, P < 0.01) were demonstrable in all the groups between PAI-1 an d triglycerides levels. There were also significant correlations betwe en insulin and PAI-1 (r = 0.20, P < 0.1) in all the subjects (grouped as a whole, n = 259) and in normolipidaemic Group A (r = 0.29, P < 0.0 1) but not in any of the hyperlipidaemic groups or in patients with CH D. This study therefore suggests that levels of insulin and PAI-1 are increased in hyperlipidaemic subjects, particularly when also hyperten sive. The further observation of significant correlations between insu lin and PAI-1 levels only in normolipidaemic subjects and not those wh o were hyperlipidaemic or with CHD is at variance with observations in Caucasians in whom strong positive correlations between insulin and P AI-1 had suggested that elevated PAI-I levels should constitute one mo re component of the metabolic syndrome which strongly predisposes to C HD. Whether this is a racial variation or an artifact of the insulin/P AI-1 assay methodology is unclear and deserves further study. (C) 1998 Elsevier Science B.V. All rights reserved.