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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25:1960.)
© 2005 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Tendon Xanthomas in Familial Hypercholesterolemia Are Associated With Cardiovascular Risk Independently of the Low-Density Lipoprotein Receptor Gene Mutation

Fernando Civeira; Sergio Castillo; Rodrigo Alonso; Erardo Meriño-Ibarra; Ana Cenarro; Marta Artied; Paula Martín-Fuentes; Emilio Ros; Miguel Pocoví; Pedro Mata for the Spanish Familial Hypercholesterolemia Group

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.

Correspondence to Fernando Civeira, MD, Laboratorio de Investigación Molecular, Hospital Universitario Miguel Servet, Isabel La Católica 1-3, Zaragoza 50009, Spain. 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.

In 951 subjects with hFH, significance of TX was studied. 278 (29.2%) presented TX (TX⁺) and 102 TX⁺ reported premature CVD (36.7%) versus 93 TX^– (13.8%) (P=0.001). Age, male sex, LDL cholesterol, and hypertension showed positive association and body mass index showed negative association with TX.

Key Words: cardiovascular disease • familial hypercholesterolemia • xanthomas

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