EVIDENCE FOR A ROLE OF TUMOR-NECROSIS-FACTOR-ALPHA IN DISTURBANCES OFTRIGLYCERIDE AND GLUCOSE-METABOLISM PREDISPOSING TO CORONARY HEART-DISEASE

Elevated plasma levels of triglyceride-rich lipoproteins, a decreased high-density lipoprotein (HDL) cholesterol concentration, hyperinsulin emia, and impaired fibrinolytic function frequently aggregate in patie nts with premature coronary heart disease (CHD). Experimental studies suggest that the cytokine tumor necrosis factor alpha (TNF alpha) prod uced by adipocytes plays a part in the regulation of triglyceride and glucose metabolism. The present study examined whether TMF alpha is im plicated in these metabolic and fibrinolytic disturbances in young pos tinfarction patients. TNFa levels were determined in two groups of you ng (age <45 years) male postinfarction patients (n = 92 and 60) and in matched, population-based control subjects (n = 63), Plasma TNF alpha was higher in patients than in controls (4.1 +/- 1.6 v 2.5 +/- 0.4 pg /mL, P < .0001). In hyperlipidemic patients, TNF alpha levels correlat ed significantly with the concentrations of very-low-density lipoprote in (VLDL) triglyceride and cholesterol and negatively with HDL cholest erol. Treatment with bezafibrate decreased VLDL triglycerides and incr eased HDL cholesterol, but did not affect TNF alpha levels. The TNF al pha concentration also correlated significantly with fasting glucose a nd proinsulin concentrations, as well as glucose and proinsulin levels after glucose ingestion. In contrast, no relations were found with th e insulin level or degree of insulin resistance. The present results p rovide clinical evidence for a basic role of TNF alpha in hypertriglyc eridemia, glucose intolerance, and the etiology of premature CHD. Copy right (C) 1998 by W.B. Saunders Company.