Our purpose was to study the determinants of coronary and carotid subclinical atherosclerosis, aortic stiffness and their relation with inflammatory biomarkers in familial hypercholesterolemia (FH) subjects. Furthermore, we evaluated the agreement degree of imaging and inflammatory markers' severity used for coronary heart disease (CHD) prediction. Coronary calcium scores (CCS), carotid intima media thickness (IMT), carotid-femoral pulse wave velocity (PWV), C reactive protein (CRP) and white blood cells count (WBC) were determined in 89 FH patients (39+/-14 years, mean LDL-C=279 mg/dl) and in 31 normal subjects (NL). The following values were considered as imaging and biomarkers' severity: CCS>75th% for age and sex, IMT>900 microm, PWV>12 m/s, and CRP>3mg/l. Coronary artery calcification (CAC) prevalence and severity, IMT, PWV and WBC values were higher in FH than in NL (all parameters, p<0.05). After multivariate analysis, the following variables were considered independent determinants of (1) IMT: systolic blood pressure, 10-year CHD risk by Framingham risk scores (FRS) and apolipoprotein B (r(2)=0.33); (2) PWV: age (r(2)=0.35); (3) CAC as a continuous variable: male gender and LDL-cholesterol year score (LYS) (r(2)=0.32); (4) presence of CAC as dichotomous variable: FRS (p=0.0027) and LYS (p=0.0228). With the exception of a moderate agreement degree between IMT and PWV severity (kappa=0.5) all other markers had only a slight agreement level (kappa<0.1). In conclusion, clinical parameters poorly explained IMT, CAC and PWV variability in FH subjects. Furthermore, imaging markers and inflammatory biomarkers presented a poor agreement degree of their severity for CHD prediction.