Clinical and molecular characteristics of homozygous familial hypercholesterolemia patients: Insights from SAFEHEART registry.

BACKGROUND: Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disorder associated with very high levels of cholesterol, accelerated atherosclerosis and very premature death, often secondary to occlusion of the coronary ostia by supravalvular atheroma in untreated individuals. OBJECTIVE: To describe molecular and clinical characteristics of HoFH enrolled at SAFEHEART registry and to evaluate the role of the type of mutation in clinical expression. METHODS: SAFEHEART is a registry of molecularly defined familial hypercholesterolemia patients. A standardized phone call is made every year for the follow-up. Patients with confirmed HoFH were selected. Molecular and clinical characteristics were analyzed. RESULTS: Thirty-four HoFH patients (27 true HoFH, 4 compound heterozygous familial hypercholesterolemia, and 3 autosomal recessive hypercholesterolemia) have been enrolled in the period 2004-2015. Twenty different mutations in LDLR gene have been detected. Sixteen patients carry defective mutations (DMs), and 15 carry null mutations (NMs). Only patients with NMs met low-density lipoprotein cholesterol (LDL-C) criteria for clinical diagnosis. Patients with NMs had higher untreated LDL-C levels (P < .0001), more aortic valve stenosis (P < .05), and lower age at first cardiovascular event (P < .05) compared to patients with DMs. In the follow-up, 1 liver transplant patient died and 3 cases underwent revascularization procedures. Eight cases started LDL apheresis and 1 case had a liver transplant. CONCLUSIONS: HoFH phenotypic expression is highly variable. These patients have high atherosclerotic coronary artery disease risk including aortic valve stenosis and do not achieve the LDL-C treatment goals with standard therapy.

Educational gradient in HIV diagnosis delay, mortality, antiretroviral treatment initiation and response in a country with universal health care.

BACKGROUND: The aim of this study was to analyse associations between educational level and delayed HIV diagnosis (DD), late initiation of combined antiretroviral therapy (cART), overall and in subjects with timely HIV diagnosis, virological and immunological responses to cART, and mortality from HIV diagnosis and cART initiation. METHODS: This was a multicentre cohort study of HIV-positive treatment-naive subjects in Spain between 2004-2009. Logistic and Cox regression analyses were used. RESULTS: Of 4,549 subjects, 44.5% had low education level (LOW), 34.4% medium education level (MED) and 21.1% high education level (HIG). In men, DD was more common in MED (OR 1.3 [95% CI 1.0, 1.7]) or LOW [OR 1.8 (95% CI 1.4, 2.3)] compared to HIG. In women, the opposite was observed; women with HIG were 40% more likely to have DD than those with LOW (OR 1.4 [95% CI 0.8, 2.5]). In individuals with timely HIV diagnoses, percentages of late cART initiators were similar (LOW 9.5%, MED 11.4% and HIG 7.0%; P=0.114). Immunological (LOW 68%, MED 76% and HIG 84%) and virological (LOW 76%, MED 83% and HIG 86%) responses to cART increased significantly with educational level; these increases remained significant in multivariate analyses. Mortality for LOW subjects was higher than for HIG, from HIV diagnosis (hazard ratio [HR] 2.3 [95% CI 1.1, 4.9]) and from cART initiation (HR 1.8 [95% CI 0.8, 3.9]). CONCLUSIONS: We found important differences by educational level in diagnosis delay, virological and immunological responses to cART and mortality in a country with universal health care. Women with high educational level are at higher risk of having delayed HIV diagnoses. Educational level should be taken into account when designing HIV testing and clinical management strategies.