Flow-mediated vasoactivity and circulating adhesion molecules in hypertriglyceridemia: Association with small, dense LDL cholesterol particles

doi:10.1067/mhj.2000.108508

American Heart Journal

Volume 140, Issue 3, September 2000, Pages 521-526

https://doi.org/10.1067/mhj.2000.108508 Get rights and content

Abstract

Background Endothelial dysfunction is considered one of the earliest events in the process of atherosclerosis, and an impaired vasodilatory response has been reported in patients with dyslipidemias. However, the independent association between hypertriglyceridemia and endothelial dysfunction is controversial, and the relation between endothelium-dependent vasodilation and circulating cell adhesion molecules as markers of endothelial dysfunction has not been fully determined. Methods Brachial artery flow mediated vasodilation (FMV) and the soluble forms of vascular cell adhesion molecule-1 (sVCAM-1) and intercellular adhesion molecule-1 (sICAM-1) were determined after overnight fasting in 16 men with hypertriglyceridemia (age 33 ± 6 years) and in 16 age-matched healthy men with normal triglycerides and cholesterol. Subjects who smoked and those with known cardiovascular disease, diabetes, hypertension, recent or active infections, or any other disease that could affect leukocyte activation were excluded from the study. Results Compared with normal subjects, subjects with hypertriglyceridemia showed a higher level of sVCAM-1 and sICAM-1 (both P <.001), a reduced FMV (P <.01), and a smaller LDL particle size (P <.05). FMV had a significant inverse correlation with sVCAM-1 (r = –0.61, P <.001) and sICAM-1 (r = –0.38, P <.03). LDL particle size had a strong, direct association with FMV (r = 0.75, P <.001) and an inverse association with adhesion molecules. By multiple regression analysis, triglycerides (P <.001) and small LDL particle size (P <.002) predicted a reduced FMV. Conclusions Serum level of cell adhesion molecules is increased and FMV is impaired in young healthy men with hypertriglyceridemia compared with age-matched men with normal lipid levels. Small, dense LDL particles may play a role in determining endothelial dysfunction in these subjects. (Am Heart J 2000;140:521-6.)

Section snippets

Subjects

Between December 1998 and April 1999, we measured FMV of the brachial artery and circulating cell adhesion molecules, serum lipids, and LDL particle size in 32 healthy male volunteers (age range 25 to 45 years) selected among the staff of Perugia General Hospital. We excluded subjects with any of the following conditions: known cardiovascular disease, cigarette smoking, diabetes, hypertension, recent or active infections, and any other disease that could affect leukocyte activation. Sixteen

Results

Clinical characteristics of the study subjects are reported in Table I.

. Clinical characteristics of study subjects

Empty Cell	Hypertriglyceridemic (n = 16)	Normal (n = 16)	P value
Age (y)	33 ± 6	32 ± 5	0.46
Body mass index (kg × m^-2)	26.2 ± 1.4	26.1 ± 1.2	0.69
Triglycerides (mg/dL)	304 ± 80	139 ± 24	<.001
Total cholesterol (mg/dL)	250 ± 26	209 ± 12	<.002
HDL cholesterol (mg/dL)	38.3 ± 3	43.6 ± 4	<.001
LDL cholesterol (mg/dL)	151 ± 32	137 ± 12	0.12
LDL size (nm)	25.3 ± 1.1	26.5 ± 1.0	<.006
Blood pressure (mm Hg)
Systolic	123 ± 8	118 ± 9	0.13

Discussion

The main finding of this study is that young healthy men with hypertriglyceridemia and no other cardiovascular risk factors or disease exhibited a reduced FMV of the brachial artery and higher levels of circulating cell adhesion molecules than age-matched normolipemic controls. Second, we found a significant inverse correlation between brachial artery FMV and serum cell adhesion molecule concentration. Third, LDL particle size had a strong negative correlation with FMV and a direct association

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^☆: Reprint requests: Graziana Lupattelli, MD, Internal Medicine, Angiology and Atherosclerosis, University of Perugia, Policlinico Monteluce, via Brunamonti 51, 06122 Perugia, Italy. E-mail: [email protected]

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Secondary Prevention and RehabilitationFlow-mediated vasoactivity and circulating adhesion molecules in hypertriglyceridemia: Association with small, dense LDL cholesterol particles☆

Abstract

Section snippets

Subjects

Results

Discussion

J Am Coll Cardiol

J Am Coll Cardiol

Lancet

Am J Cardiol

Am J Cardiol

J Am Coll Cardiol

J Lipid Res

J Am Coll Cardiol

Immunol Today

J Am Coll Cardiol

Am J Med

The pathogenesis of coronary artery disease

N Engl J Med

Atherosclerosis: an inflammatory disease

N Engl J Med

Postischemic vasodilation in human forearm is dependent on endothelium-derived nitric oxide

Am J Physiol

Soluble cell adhesion molecules in hypertriglyceridemia and potential significance on monocyte adhesion

Arterioscler Thromb Vasc Biol

Levels of soluble cell adhesion molecules in patients with dyslipidemia

Circulation

Circulating adhesion molecules VCAM-1, ICAM-1, and E-selectin in carotid atherosclerosis and incident coronary heart disease cases. The Atherosclerosis Risk In Communities (ARIC) study

Circulation

Endothelium-mediated coronary blood flow modulation in humans: effects of age, atherosclerosis, hypercholesterolemia, and hypertension

J Clin Invest

Secondary Prevention and Rehabilitation
Flow-mediated vasoactivity and circulating adhesion molecules in hypertriglyceridemia: Association with small, dense LDL cholesterol particles☆