Abstract: Autosomal dominant hypercholesterolaemia (ADH) are a heterogeneous group of monogenic lipid disorders. The plasma level of lipoprotein(a) (Lp(a)) is a heritable trait associated with increased coronary heart disease (CHD) risk. OBJECTIVE: To evaluate the frequency of elevated Lp(a) as a cause of ADH and the characteristics of subjects with high Lp(a) (hyperLp(a)). MATERIAL AND METHODS: 200 healthy subjects and 933 unrelated Spanish subjects with a clinical diagnosis of ADH who were screened for low-density lipoprotein receptor (LDLR) and apolipoprotein B (APOB) gene mutations. Standard cardiovascular risk factors and blood lipid levels, including Lp(a), were evaluated. HyperLp(a) was defined as Lp(a) levels >or=95th centile of control values. RESULTS: Lp(a) was higher in 263 subjects without LDLR or APOB mutations (nonLDLR/nonAPOB group) than in 670 subjects with mutations (FH group): 40.0 mg/dl (interquartile range (IR) 15.0-89.0) versus 31.0 mg/dl (IR 11.0-73.7) respectively, p = 0.002. HyperLp(a) was present in 23% of ADH subjects (odds ratio (OR) 5.6 (95% CI, 2.9 to 10.7) versus controls) and 29% of nonLDLR/nonAPOB subjects (OR 7.7; 3.9 to 15.4). After adjusting for Lp(a), LDL cholesterol levels were <95th centile in 28 (10.6%) nonLDLR/nonAPOB subjects and in 9 (1.3%) FH subjects. Lp(a) levels were nonsignificantly higher in ADH subjects with early-onset CHD than in those without (43.5 mg/dl, (IR, 12.0-82.0) versus 31.7 mg/dl (11.8-76.5), respectively). CONCLUSIONS: HyperLp(a) is responsible for ADH in approximately 6% of nonLDLR/nonAPOB subjects. HyperLp(a) would not appear to be a risk factor for early-onset CHD in ADH, independently of whether genetic defects have or have not been demonstrated.
Abstract: OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD) frequently coexists with obesity, diabetes, and dyslipidemia. We examined whether NAFLD was associated with atherosclerosis, as measured by ultrasound in the carotid arteries. METHODS AND RESULTS: Carotid atherosclerosis and cardiovascular risk factors were assessed in 40 patients with an ultrasound diagnosis of primary NAFLD and 40 matched population controls. The metabolic syndrome and all its individual traits, including elevated C-reactive protein, were significantly (P<0.005) more frequent in NAFLD patients than in control subjects. Patients with NAFLD showed more carotid atherosclerosis than controls, with mean intima-media thickness (IMT) of 0.70+/-0.20 mm and 0.54+/-0.13 mm (P<0.0001) and plaque prevalence of 50% and 25% (P=0.021), respectively. By multivariate analysis, older age (odds ratio [OR], 2.5 per 10 years; 95% CI, 1.4 to 4.4; P=0.002), the presence of NAFLD (OR, 8.4; 95% CI, 2.49 to 29.4; P=0.001), and elevated serum ferritin (OR, 3.1; 95% CI, 1.2 to 7.9; P=0.016) were independent predictors of an increased IMT. CONCLUSIONS: Patients with NAFLD show a cluster of risk factors of the metabolic syndrome and advanced carotid atherosclerosis. NAFLD appears to be a feature of the metabolic syndrome, and its detection on abdominal ultrasound should alert to the existence of an increased cardiovascular risk.
