PRESERVED ENDOTHELIAL FUNCTION IN PATIENTS WITH SEVERE HYPERTRIGLYCERIDEMIA AND LOW FUNCTIONAL LIPOPROTEIN-LIPASE ACTIVITY

Objectives. We sought to determine whether hypertriglyceridemia in pat ients with lipoprotein lipase (LPL) dysfunction is associated with end othelial dysfunction in resistance vessels of the forearm vasculature. Background. Vasodilator responses to acetylcholine, acting through st imulation of nitric oxide (NO) release from the endothelium, are impai red in hypercholesterolemia and normalized by L-arginine, suggesting d ysfunction of the L-arginine/NO pathway. Similar abnormalities have be en reported in conditions associated ,vith hypertriglyceridemia, such as non-insulin-dependent diabetes. The relation between endothelial fu nction and plasma triglyceride concentrations has, however, not previo usly been studied in vivo. Methods. We examined forearm blood flow res ponses to brachial artery infusions of acetylcholine (alone and with L -arginine) and nitroprusside (an NO donor) in 17 patients with severe hypertriglyceridemia (mean [+/-SD] plasma triglyceride concentration 1 ,914 +/- 1,288 mg/dl) but normal low density lipoprotein cholesterol ( 89 +/- 31 mg/dl) and in 34 normolipidemic control subjects. Severe LPL dysfunction was demonstrated in 10 of 17 patients. Results. Acetylcho line (7.5 and 15 mu g/min) produced similar forearm blood flow respons es in hypertriglyceridemic patients (mean [+/-SEM] 7.7 +/- 0.9 and 10. 5 +/- 1.2 ml/min per 100 ml) and in control subjects (7.5 +/- 0.6 and 11.0 +/- 0.8 ml/min per 100 mi, p = 0.78 by analysis of variance). Res ponses to acetylcholine co infused with L-arginine (10 mg/min) and nit roprusside (3 and 10 mu g/min) were also similar in hypertriglyceridem ic patients and control subjects (p = 0.93 and p = 0.27 for acetylchol ine with L-arginine and nitroprusside, respectively). The ratio respon se to acetylcholine/response to nitroprusside differed between hypertr iglyceridemic patients and control subjects by only 1%, The study had >90% power (alpha = 0.05) to detect a difference >30% in this ratio. C onclusions. Severe hypertriglyceridemia associated with LPL dysfunctio n is not associated,vith the degree of endothelial dysfunction seen in moderate hypercholesterolemia when responses to acetylcholine are imp aired by >40%.