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

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, NG-monomethyl-l-arginine and postischemic hyperemi 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; ANOV 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, NG-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 plasm triglycerides but normal plasm 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 hypercholesterolemi also occur in hypertriglyceridemia. These findings identify potential mechanism by which high plasm triglyceride levels may be atherogenic independent of LDL cholesterol levels.