Preserved endothelial function in patients with severe hypertriglyceridemia and low functional lipoprotein lipase activity.
OBJECTIVE
We sought to determine whether hypertriglyceridemia 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 hypercholesterolemia and normalized by L-arginine, suggesting dysfunction of the L-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 plasma 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 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
Acetylcholine (7.5 and 15 microg/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 L-arginine (10 mg/min) and nitroprusside (3 and 10 microg/min) were also similar in hypertriglyceridemic patients and control subjects (p = 0.93 and p = 0.27 for acetylcholine with L-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 (alpha = 0.05) to detect a difference >30% in this ratio.


CONCLUSIONS
Severe hypertriglyceridemia associated with LPL dysfunction is not associated with the degree of endothelial dysfunction seen in moderate hypercholesterolemia when responses to acetylcholine are impaired by >40%.
Chowienczyk
P J
PJ
Department of Clinical Pharmacology, United Medical and Dental School of Guy's and St. Thomas' Hospital, London, England, United Kingdom.
Watts
G F
GF
Wierzbicki
A S
AS
Cockcroft
J R
JR
Brett
S E
SE
Ritter
J M
JM
D000109:Acetylcholine / Q000494:pharmacology; D000328:Adult; D000959:Antihypertensive Agents / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D005542:Forearm / Q000098:blood supply; D006801:Humans; D015228:Hypertriglyceridemia / Q000503:physiopathology*; D008071:Lipoprotein Lipase / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009599:Nitroprusside / Q000494:pharmacology; D012039:Regional Blood Flow / Q000187:drug effects
D000959:Antihypertensive Agents; D009599:Nitroprusside; D008071:Lipoprotein Lipase; D000109:Acetylcholine