Preserved Endothelial Function in Patients With Severe Hypertriglyceridemi and Low Functional Lipoprotein Lipase Activity

Objectives. We sought to determine whether hypertriglyceridemi in patients with lipoprotein lipase (LPL) dysfunction is associated with endothelial dysfunction in resistance vessels of the forearm vasculature. Background. Vasodilator responses to acetylcholine, acting through stimulation of nitric oxide (NO) release from the endothelium, are impaired in hypercholesterolemi and normalized by image-arginine, suggesting dysfunction of the image-arginine/NO pathway. Similar abnormalities have been reported in conditions associated with hypertriglyceridemia, such as non–insulin-dependent diabetes. The relation between endothelial function and plasm triglyceride concentrations has, however, not previously been studied in vivo. Methods. We examined forearm blood flow responses to brachial artery infusions of acetylcholine (alone and with image-arginine) and nitroprusside (an NO donor) in 17 patients with severe hypertriglyceridemi (mean [±SD] plasm 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. Acetylcholine (7.5 and 15 μg/min) produced similar forearm blood flow responses 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 ml, p = 0.78 by analysis of variance). Responses to acetylcholine co-infused with image-arginine (10 mg/min) and nitroprusside (3 and 10 μg/min) were also similar in hypertriglyceridemic patients and control subjects (p = 0.93 and p = 0.27 for acetylcholine with image-arginine and nitroprusside, respectively). The ratio response to acetylcholine/response to nitroprusside differed between hypertriglyceridemic patients and control subjects by only 1%. The study had >90% power (alph = 0.05) to detect difference >30% in this ratio. Conclusions. Severe hypertriglyceridemi associated with LPL dysfunction is not associated with the degree of endothelial dysfunction seen in moderate hypercholesterolemi when responses to acetylcholine are impaired by >40%.