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CLINICAL STUDIES

Endothelium-dependent relaxation by acetylcholine is impaired in hypertriglyceridemic humans with normal levels of plasma LDL cholesterol

^a Alfred and Baker Medical Unit, Baker Medical Research Institute and The Alfred Hospital, Commercial Road, Prahran, Victoria, Australia 3181

Manuscript received September 8, 1997; revised manuscript received September 18, 1998, accepted October 30, 1998.

Reprint requests and correspondence: Jaye P.F. Chin-Dusting, Alfred and Baker Medical Unit, Baker Medical Research Institute, Commercial Road, Prahran, Victoria, Australia 3181
jaye.chin{at}baker.edu.au

OBJECTIVES

Patients with high triglyceride (of which very low density lipoproteins [VLDL] are the main carriers), but with normal low density lipoprotein (LDL) cholesterol levels, were examined for in vivo endothelium function status.

BACKGROUND

Very low density lipoproteins inhibit endothelium-dependent, but not -independent, vasorelaxation in vitro.

METHODS

Three groups were studied: 1) healthy volunteers (n = 10; triglyceride 1.24 ± 0.14 mmol/liter, LDL cholesterol 2.99 ± 0.24 mmol/liter); 2) hypertriglyceridemic (n = 11; triglyceride 6.97 ± 1.19 mmol/liter,* LDL cholesterol 2.17 ± 0.2 mmol/liter, *p < 0.05); and 3) hypercholesterolemic (n = 10; triglyceride 2.25 ± 0.29 mmol/liter,* LDL cholesterol 5.61 ± 0.54 mmol/liter*; *p < 0.05) patients. Vasoactive responses to acetylcholine, sodium nitroprusside, noradrenaline, N^G-monomethyl-L-arginine and postischemic hyperemia were determined using forearm venous occlusion plethysmography.

RESULTS

Responses to acetylcholine (37 µg/min) were significantly dampened both in hypercholesterolemic (% increase in forearm blood flow: 268.2 ± 62) and hypertriglyceridemic patients (232.6 ± 45.2) when compared with controls (547.8 ± 108.9; ANOVA p < 0.05). Responses to sodium nitroprusside (at 1.6 µg/min: controls vs. hypercholesterolemics vs. hypertriglyceridemic: 168.7 ± 25.1 vs. 140.6 ± 38.9 vs. 178.5 ± 54.5% increase), noradrenaline, N^G-monomethyl-L-arginine and postischemic hyperemic responses were not different among the groups examined.

CONCLUSIONS

Acetylcholine responses are impaired in patients with pathophysiologic levels of plasma triglycerides but normal plasma levels of LDL cholesterol. The impairment observed was comparable to that obtained in hypercholesterolemic patients. We conclude that impaired responses to acetylcholine normally associated with hypercholesterolemia also occur in hypertriglyceridemia. These findings identify a potential mechanism by which high plasma triglyceride levels may be atherogenic independent of LDL cholesterol levels.

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