CLINICAL STUDY
Mild-to-moderate hypertriglyceridemia in young men is associated with endothelial dysfunction and increased plasma concentrations of asymmetric dimethylarginine
Pia Lundman, MDa  ,
Maria J. Eriksson, MD, PhD ,
Markus Stühlinger, MD||,
John P. Cooke, MD, PhD||,
Anders Hamsten, MD, PhDa and
Per Tornvall, MD, PhDa
a Department of Cardiology, Karolinska Institutet, Stockholm, Sweden
Department of Clinical Physiology, Karolinska Institutet, Stockholm, Sweden
Atherosclerosis Research Unit, King Gustaf V Research Institute, Karolinska Institutet, Stockholm, Sweden
Department of Medicine, Danderyd Hospital, Stockholm, Sweden
|| Falk Cardiovascular Research Center, Stanford University School of Medicine, Stanford, California, USA
Manuscript received November 7, 2000;
revised manuscript received March 9, 2001,
accepted March 26, 2001.
Reprint requests and correspondence: Dr. Pia Lundman, Atherosclerosis Research Unit, King Gustaf V Research Institute, Karolinska Hospital, SE-171 76 Stockholm, Sweden
Pia.Lundman{at}medks.ki.se
OBJECTIVES
The aim of this study was to investigate endothelial function and common carotid intima-media thickness (IMT) in healthy young men with mild-to-moderate hypertriglyceridemia. Plasma asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase inhibitor, was measured to further elucidate the mechanisms involved.
BACKGROUND
Hypertriglyceridemia is a risk factor for coronary heart disease although the mechanisms behind the increased risk remain to be defined. Acute elevation of plasma triglycerides induced by an intravenous fat load is associated with impaired endothelial function. The results of studies examining acute effects induced by a high-fat meal or effects of chronic hypertriglyceridemia on endothelial function are more inconsistent.
METHODS
Flow-mediated vasodilation and nitroglycerin-induced vasodilation of the brachial artery and common carotid IMT were measured noninvasively by ultrasound technique in 15 hypertriglyceridemic (HTG) subjects and 15 matched controls, mean age 34 years. Plasma concentrations of ADMA were measured by high-performance liquid chromatography.
RESULTS
Flow-mediated vasodilation was decreased in the HTG group (p < 0.0001), whereas nitroglycerin-induced vasodilation and carotid IMT did not differ significantly. Asymmetric dimethylarginine concentrations were higher in the HTG group (p < 0.05).
CONCLUSIONS
Hypertriglyceridemia in young men is associated with endothelial dysfunction and increased plasma concentration of ADMA but not with increased IMT of the common carotid artery. The corollary is that chronic hypertriglyceridemia results in endothelial dysfunction, possibly due to increased ADMA concentration, and that endothelial dysfunction might precede increased IMT among the early manifestations of atherosclerosis.
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Abbreviations and Acronyms
| | ADMA | = asymmetric dimethylarginine | | BMI | = body mass index | | CHD | = coronary heart disease | | FFA | = free fatty acids | | FMD | = flow-mediated vasodilation | | HDL | = high-density lipoprotein | | HTG | = hypertriglyceridemic | | IMT | = intima-media thickness | | LDL | = low-density lipoprotein | | LPL | = lipoprotein lipase | | NTG | = nitroglycerin | | VLDL | = very low-density lipoprotein |
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