Please cite this article in press as: Junyent M, et al., Carotid atherosclerosis in familial combined hyperlipidemia associated with the APOB/APOA-I ratio, Atherosclerosis (2007), doi:10.1016/j.atherosclerosis.2007.07.008 ARTICLE IN PRESS ATH-10033; No. of Pages 7 Atherosclerosis xxx (2007) xxx–xxx Carotid atherosclerosis in familial combined hyperlipidemia associated with the APOB/APOA-I ratio Mireia Junyent a,c,∗ , Daniel Zamb ´ on a,c , Rosa Gilabert b , Montserrat Cof´ an a,c , Isabel N ´ u˜ nez b,c , Emilio Ros a,c a Unitat de L´ ıpids, Servei d’Endocrinologia i Nutrici´ o, Institut d’Investigacions Biom` ediques August Pi i Sunyer, Hospital Cl´ ınic, Barcelona, Spain b Secci´ o d’Ecografia, Centre de Diagn` ostic per l’Imatge, Institut d’Investigacions Biom` ediques August Pi i Sunyer, Hospital Cl´ ınic, Barcelona, Spain c Ciber Fisiopatolog´ ıa Obesidad y Nutrici ´ on (CB06/03), Instituto de Salud Carlos III, Spain Received 2 April 2007; received in revised form 29 June 2007; accepted 11 July 2007 Abstract Objectives: The effects of risk factors on carotid atherosclerosis in familial combined hyperlipidemia (FCHL) remain unclear. We assessed carotid intima-media thickness (IMT) and plaque in relation to classical risk factors and apolipoprotein A-I (apoA-I) and B (apoB) levels in patients with FCHL. Methods and results: We included 131 unrelated FCHL patients (27 with prior cardiovascular disease (CVD)) diagnosed by standard criteria and 190 age- and sex-matched control subjects. Cardiovascular risk factors were assessed and IMT in the far wall of all carotid segments and plaque burden were determined in FCHL patients and controls. All carotid measurements were increased in FCHL patients compared to controls (P < 0.001), irrespective of CVD status. For asymptomatic FCHL, the adjusted difference in mean common carotid IMT was 0.08 mm, corresponding to ≈16 years of physiological IMT increase. By multivariate analysis in a model with all risk factors, inclusive of the metabolic syndrome, independent associations of IMT were age, the apoB/apoA-I ratio, systolic blood pressure, fasting glucose, family history of CVD and total/HDL cholesterol ratio (r 2 = 0.475, P < 0.001). The strongest determinant of IMT was the apoB/apoA-I ratio (β = 0.422, P < 0.001). Conclusions: Patients with FCHL have increased carotid IMT that is strongly related to the apoB/apoA-I ratio, a measure of overall lipid abnormalities. The findings support the atherogenicity of the lipid phenotype in FCHL beyond associated risk factors. They also have implications for diagnosis and management of CVD risk in this condition. © 2007 Published by Elsevier Ireland Ltd. Keywords: Familial combined hyperlipidemia; Sonography; Carotid IMT; Carotid plaque; Metabolic syndrome; Apolipoprotein B/apolipoprotein A-I ratio Familial combined hyperlipidemia (FCHL, OMIM- 144250) is the most common genetic lipid disorder, affecting up to 5% of the general population [1]. When surveying patients or families ascertained for premature coronary artery disease (CAD), FCHL is identified as the most common familial dyslipidemia, with reported frequencies from 11% to 17% [1–3]. Substantial increases in both prevalent CAD ∗ Corresponding author at: Unitat de L´ ıpids, Hospital Cl´ ınic, Villarroel 170, 08036 Barcelona, Spain. Tel.: +34 93 2279383; fax: +34 93 4537829. E-mail address: mjunyent@clinic.ub.es (M. Junyent). [4] and incident cardiovascular disease (CVD) mortality [5] have been reported among FCHL families. The disorder is associated with variable lipid and lipoprotein phenotypes, both in affected individuals and family members. Key com- ponents of FCHL imparting an increased cardiovascular risk are hypertriglyceridemia and associated metabolic abnor- malities: low levels of HDL cholesterol, accumulation of triglyceride-rich lipoproteins, small and dense LDL sub- classes, and elevated apolipoprotein B (apoB) levels [6]. In addition, a large proportion of patients with FCHL disclose features of the metabolic syndrome (MetS), and the presence 0021-9150/$ – see front matter © 2007 Published by Elsevier Ireland Ltd. doi:10.1016/j.atherosclerosis.2007.07.008