Enfermedad cardiovascular y calidad de vida en la hipercolesterolemia familiar

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Medicina Preventiva y Salud Pública y Microbiología. Fecha de lectura: 23/06/201

Clinical characteristics and evaluation of LDL-cholesterol treatment of the Spanish Familial Hypercholesterolemia Longitudinal Cohort Study (SAFEHEART)

<p>Abstract</p> <p>Aim</p> <p>Familial hypercholesterolemia (FH) patients are at high risk for premature coronary heart disease (CHD). Despite the use of statins, most patients do not achieve an optimal LDL-cholesterol goal. The aims of this study are to describe baseline characteristics and to evaluate Lipid Lowering Therapy (LLT) in FH patients recruited in SAFEHEART.</p> <p>Methods and Results</p> <p>A cross-sectional analysis of cases recruited in the Spanish FH cohort at inclusion was performed. Demographic, lifestyle, medical and therapeutic data were collected by specific surveys. Blood samples for lipid profile and DNA were obtained. Genetic test for FH was performed through DNA-microarray. Data from 1852 subjects (47.5% males) over 19 years old were analyzed: 1262 (68.1%, mean age 45.6 years) had genetic diagnosis of FH and 590 (31.9%, mean age 41.3 years) were non-FH. Cardiovascular disease was present in 14% of FH and in 3.2% of non-FH subjects (P < 0.001), and was significantly higher in patients carrying a null mutation compared with those carrying a defective mutation (14.87% vs. 10.6%, respectively, P < 0.05). Prevalence of current smokers was 28.4% in FH subjects. Most FH cases were receiving LLT (84%). Although 51.5% were receiving treatment expected to reduce LDL-c levels at least 50%, only 13.6% were on maximum statin dose combined with ezetimibe. Mean LDL-c level in treated FH cases was 186.5 mg/dl (SD: 65.6) and only 3.4% of patients reached and LDL-c under 100 mg/dl. The best predictor for LDL-c goal attainment was the use of combined therapy with statin and ezetimibe.</p> <p>Conclusion</p> <p>Although most of this high risk population is receiving LLT, prevalence of cardiovascular disease and LDL-c levels are still high and far from the optimum LDL-c therapeutic goal. However, LDL-c levels could be reduced by using more intensive LLT such as combined therapy with maximum statin dose and ezetimibe.</p

Adults with familial hypercholesterolaemia have healthier dietary and lifestyle habits compared with their non-affected relatives: the SAFEHEART study

[Objective] Healthy lifestyle habits are the cornerstone in the management offamilial hypercholesterolaemia (FH). Nevertheless, dietary studies on FH-affectedpopulations are scarce. The present study analyses dietary habits, adherence to aMediterranean diet pattern and physical activity in an adult population with FHand compares them with their non-affected relatives.[Design] Cross-sectional study.[Setting] Data came from SAFEHEART, a nationwide study in Spain.[Participants] Individuals (n 3714) aged ≥18 years with a genetic diagnosis of FH (n2736) and their non-affected relatives (n 978). Food consumption was evaluated using a validated FFQ.[Results] Total energy intake was lower in FH patients v. non-affected relatives (P<0·005). Percentage of energy from fats was also lower in the FH population (35 % in men, 36 % in women) v. those non-affected (38 % in both sexes, P<0·005), due to the lower consumption of saturated fats (12·1 % in FH patients, 13·2 % in non-affected, P<0·005). Consumption of sugars was lower in FH patients v. non-affected relatives (P<0·05). Consumption of vegetables, fish and skimmed milk was higher in the FH population (P<0·005). Patients with FH showed greater adherence to a Mediterranean diet pattern v. non-affected relatives (P<0·005). Active smoking was lower and moderate physical activity was higher in people with FH, especially women (P<0·005).[Conclusions] Adult patients with FH report healthier lifestyles than their non-affected family members. They eat a healthier diet, perform more physical activity and smoke less. However, this patient group’s consumption of saturated fats and sugars still exceeds guidelines.This work was supported by Fundación Hipercolesterolemia Familiar; the Instituto de Salud Carlos III (ISCIII; grant numbers G03/181 and FIS PI12/01289); and Centro Nacional de Investigación Cardiovascular (CNIC; grant number 08-2008)

Genetic diagnosis of familial hypercholesterolemia using a DNA-array based platform

The aim of this study was to validate the Lipochip genetic diagnostic platform by assessing effectiveness, sensitivity, specificity and costs for the identification of patients with familial hypercholesterolemia (FH) in Spain. This platform includes the use of a DNA micro array, the detection of large gene rearrangements and the complete resequencing of the low-density lipoprotein receptor gene. DNA samples of patients with clinically diagnosed FH were analyzed for mutations by application of the Lipochip platform. Results obtained were confirmed by DNA sequencing and MLPA analysis by two other, independent laboratories. Of 808 patients tested, Lipochip detected a mutation in 66% of the cases and of these 78% were detected by the micro array. A specificity of 99.5% at a sensitivity of 99.8% was reached. A positive test result could be reported within 22 days after start of analysis. The total average screening costs of $350 per case were significantly lower compared to other existing screening programs. Lipochip provides a reliable, fast and cheap alternative for the genetic testing of patients with clinically diagnosed F