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J Am Coll Cardiol, 2001; 38:111-116
© 2001 by the American College of Cardiology Foundation
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CLINICAL STUDY

Mild-to-moderate hypertriglyceridemia in young men is associated with endothelial dysfunction and increased plasma concentrations of asymmetric dimethylarginine

Pia Lundman, MDa{ddagger} §, Maria J. Eriksson, MD, PhD{dagger}, Markus Stühlinger, MD||, John P. Cooke, MD, PhD||, Anders Hamsten, MD, PhDa{ddagger} and Per Tornvall, MD, PhDa{ddagger}

a Department of Cardiology, Karolinska Institutet, Stockholm, Sweden
{dagger} Department of Clinical Physiology, Karolinska Institutet, Stockholm, Sweden
{ddagger} 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.

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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