on March 23, 2006
Published online before print March 23, 2006, doi: 10.1161/01.ATV.0000218507.95149.42
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Submitted on November 11, 2005
Accepted on March 9, 2006
Influence of HDL Cholesterol on Preclinical Carotid Atherosclerosis in Familial Hypercholesterolemia
Mireia Junyent ;
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.
* To whom correspondence should be addressed. 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.
Key words: atherosclerosis • carotid intima-media thickness • cardiovascular risk factors • cholesterol • familial hypercholesterolemia • lipoprotein
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