on July 14, 2005
Published online before print July 14, 2005, doi: 10.1161/01.ATV.0000177811.14176.2b
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Submitted on March 18, 2005
Accepted on June 30, 2005
Tendon Xanthomas in Familial Hypercholesterolemia Are Associated With Cardiovascular Risk Independently of the Low-Density Lipoprotein Receptor Gene Mutation
Fernando Civeira *;
From Unidad de Lípidos and Laboratorio de Investigación Molecular (F.C., E.M.-I., A.C., M.A., P.M.F.), Hospital Universitario Miguel Servet, Instituto Aragonés de Ciencias de la Salud, Zaragoza, Spain; Departamento de Bioquímica (S.C., M.P.), Biología Molecular y Celular, Universidad de Zaragoza, Spain; Fundación Jiménez Díaz (R.A., P.M.), Madrid, Spain; Unidad de Lípidos, Servicio de Endocrinología y Nutrición (E.R.), Institut d’Investigacions Biomediques August Pi Sunyer, Hospital Clínico, Barcelona, Spain.
* To whom correspondence should be addressed. E-mail: civeira{at}unizar.es.
Objective--To investigate the significance of tendon xanthomas (TX) in heterozygous subjects with familial hypercholesterolemia (hFH).
Methods and Results--951 men and women with genetic diagnosis of hFH were studied, of whom 278 (29.2%) presented TX. TX frequency increased with age from 6.9% in subjects 20 to 30 years to 38.3% at 51 to 60 years, with a decrease in those older than 60 years. Total and low-density lipoprotein (LDL) cholesterol were higher in TX+ than in TX- subjects (439.0±78.5 mg/dL and 363.1±76.5 mg/dL versus 400.6±73.4 and 323.3±71.0, respectively; P=0.001). High-density lipoprotein (HDL) cholesterol was lower in TX+ than in TX- subjects (50.4±15.0 mg/dL versus 53.1±14.8 mg/dL; P=0.005). Lp(a), apolipoprotein E genotype, and type of LDL receptor gene mutation showed no differences between groups. 102 TX+ reported premature cardiovascular disease (CVD) (36.7%) versus 93 TX- (13.8%) (P=0.001). The relative odds for premature CVD were higher in women (4.49 versus 2.26), and increased in hFH younger than 51 years to 3.60 (95% CI, 1.703 to 7.608) in men and to 17.1 (95% CI, 2.697 to 108.920) in women. In the multivariate analysis, age, male sex, LDL cholesterol, and hypertension showed significant positive association with TX, whereas body mass index showed negative association with TX.
Conclusions--TX are associated with cardiovascular risk factors and higher CVD, indicating that their detection indicates the need for more aggressive lipid-lowering intervention.
Key words: cardiovascular disease • familial hypercholesterolemia • xanthomas
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