ABSTRACT
BACKGROUND AND AIMS: Achilles tendon xanthomas (ATX) are a sign of long-term exposure to high blood cholesterol in familial hypercholesterolemia (FH) patients, which have been associated with cardiovascular disease. We evaluated the ATX association with the presence and extent of subclinical coronary atherosclerosis in heterozygous FH patients. METHODS: 102 FH patients diagnosed by US-MEDPED criteria (67% with genetically proven FH), with median LDL-C 279 mg/dL (interquartile range: 240; 313), asymptomatic for cardiovascular disease, underwent computed tomography angiography and coronary artery calcium (CAC) quantification. Subclinical coronary atherosclerosis was quantified by CAC, segment-stenosis (SSS) and segment-involvement (SIS) scores. Adjusted Poisson regression was used to assess the association of ATX with subclinical atherosclerosis burden as continuous variables. RESULTS: Patients with ATX (n = 21, 21%) had higher LDL-C and lipoprotein(a) [Lp(a)] concentrations as well as greater CAC scores, SIS and SSS (p < 0.05). After adjusting for age, sex, smoking, hypertension, previous statin use, HDL-C, LDL-C and Lp(a) concentrations, there was an independent positive association of ATX presence with CAC scores (ß = 1.017, p < 0.001), SSS (ß = 0.809, p < 0.001) and SIS (ß = 0.640, p < 0.001). CONCLUSIONS: ATX are independently associated with the extension of subclinical coronary atherosclerosis quantified by tomographic scores in FH patients.
Subject(s)
Achilles Tendon , Apolipoprotein B-100/genetics , Coronary Artery Disease/etiology , Heterozygote , Hyperlipoproteinemia Type II/genetics , Mutation , Receptors, LDL/genetics , Xanthomatosis/etiology , Achilles Tendon/diagnostic imaging , Adult , Asymptomatic Diseases , Biomarkers/blood , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Computed Tomography Angiography , Coronary Angiography/methods , Coronary Artery Disease/diagnostic imaging , Cross-Sectional Studies , Female , Genetic Predisposition to Disease , Humans , Hyperlipoproteinemia Type II/blood , Hyperlipoproteinemia Type II/complications , Hyperlipoproteinemia Type II/diagnosis , Lipoprotein(a)/blood , Male , Middle Aged , Phenotype , Pilot Projects , Severity of Illness Index , Xanthomatosis/diagnostic imagingABSTRACT
BACKGROUND AND AIMS: Familial hypercholesterolemia (FH) is a common genetic disorder characterized by elevated blood cholesterol, increased prevalence of subclinical atherosclerosis and high risk of premature coronary heart disease. However, this risk is not explained solely by elevated LDL-cholesterol concentrations, and other factors may influence atherosclerosis development. There is evidence that increased adiposity may predispose to atherosclerosis in FH. Epicardial fat has been associated with subclinical coronary atherosclerosis in the general population. This study evaluated the association of epicardial fat (EFV) volume with the presence and extent of subclinical coronary atherosclerosis detected by computed tomography angiography in FH patients. METHODS: Ninety-seven FH subjects (35% male, mean age 45 ± 13 years, LDL-C 281 ± 56 mg/dL, 67% with proven molecular defects) underwent computed tomography angiography and coronary artery calcium (CAC) scoring. EFV was measured in non-contrast images using a semi-automated method. Segment-stenosis score (SSS) and segment-involvement score (SIS) were calculated. Multivariate Poisson regression was utilized to assess an independent association of EFV with coronary atherosclerotic burden. RESULTS: EFV was positively associated with age, body mass index, waist circumference, blood glucose, the presence of the metabolic syndrome components, but not with LDL-C. After adjusting for confounders and abdominal circumference, an independent association (shown as ß coefficients and 95% confidence intervals) of EVF with CAC scores [ß = 0.263 (0.234; 0.292), p=0.000], SIS [ß = 0.304 (0.141; 0.465) p=0.000] and SSS [ß = 0.296 (0.121; 0.471), p=0.001] was found. CONCLUSIONS: In FH, EFV was independently associated with coronary atherosclerotic presence and severity.
