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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:1107.)
© 2006 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Influence of HDL Cholesterol on Preclinical Carotid Atherosclerosis in Familial Hypercholesterolemia

Mireia Junyent; Montserrat Cofán; Isabel Núñez; Rosa Gilabert; Daniel Zambón; Emilio Ros

From Unitat de Lípids, Servei d’Endocrinologia i Nutrició (M.J., M.C., D.Z., E.R.) and Secció d’Ecografia, Centre de Diagnòstic per l’Imatge (I.N., R.G.), Institut d’Investigacions Biomèdiques August Pi i Sunyer, Hospital Clínic, Barcelona, Spain.

Correspondence to Emilio Ros, Unitat de Lípids, Hospital Clínic, Villarroel 170, 08036 Barcelona, Spain. E-mail eros{at}clinic.ub.es

Objective— The effect of risk factors on carotid atherosclerosis in heterozygous familial hypercholesterolemia (FH) is unclear. We evaluated carotid intima-media thickness (IMT) by sonography in relation to classical and emergent risk factors in a large FH cohort.

Methods and Results— Risk factors and carotid IMT were assessed in 196 asymptomatic subjects aged 25 years fulfilling strict diagnostic criteria for clinical FH who were either undertreated or treatment-naive. Conventional risk factors, but not lipoprotein(a), homocysteine, or apolipoprotein E (apoE) genotypes were univariately related to IMT. Age-adjusted and gender-adjusted IMT increased with increasing low-density lipoprotein (LDL) cholesterol and decreased with increasing high-density lipoprotein (HDL) cholesterol. Compared with a total cholesterol/HDL ratio >5.0, a ratio 5.0 was associated with a lower adjusted IMT, with a mean difference of –0. 09 mm (95% confidence interval, –0.13 to –0.04). By multivariate analysis, age, HDL cholesterol (negatively), physical exercise, family history of early-onset coronary heart disease, LDL cholesterol, and leukocyte count, in this order, were independent associations of IMT (r²=0.429, P<0.001).

Conclusions— Traditional risk factors account for a sizeable proportion of variation in carotid IMT in FH. Because the HDL cholesterol level and the total cholesterol/HDL ratio are strong predictors of preclinical carotid atherosclerosis, HDL cholesterol-raising strategies should have an important therapeutic role in FH.

Cardiovascular risk factors and carotid intima-media thickness (IMT) were assessed in 196 asymptomatic adults with familial hypercholesterolemia (FH). Conventional risk factors explained 42.9% of IMT variability. Compared with a total cholesterol/HDL ratio >5.0, a ratio 5.0 was associated with a 0.09-mm thinner IMT. HDL cholesterol has a strong protective role in FH.

Key Words: atherosclerosis • carotid intima-media thickness • cardiovascular risk factors • cholesterol • familial hypercholesterolemia • lipoprotein

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