Influence of HDL cholesterol on preclinical carotid atherosclerosis in familial hypercholesterolemia.
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.


RESULTS
Risk factors and carotid IMT were assessed in 196 asymptomatic subjects aged > or =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 < or =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.
Junyent
Mireia
M
Servei d'Endocrinologia i Nutrició, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Hospital Clínic, Barcelona, Spain.
Cofán
Montserrat
M
Núñez
Isabel
I
Gilabert
Rosa
R
Zambón
Daniel
D
Ros
Emilio
E
D000328:Adult; D000367:Age Factors; D000368:Aged; D001057:Apolipoproteins E / Q000235:genetics; D002339:Carotid Arteries / Q000473:pathology*; D002340:Carotid Artery Diseases / Q000209:etiology*; D008076:Cholesterol, HDL / Q000097:blood*; D008078:Cholesterol, LDL / Q000097:blood; D003327:Coronary Disease / Q000209:etiology; D005260:Female; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000150:complications*; D006965:Hyperplasia; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D012307:Risk Factors; D012737:Sex Factors; D013599:Systole; D017539:Tunica Intima / Q000473:pathology*
D001057:Apolipoproteins E; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL