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

Nelva Mata,Francisco Fuentes,Pedro Mata,Jose L Díaz,Teresa Padró,Jose I Vidal,José M Ordovas,José López-Miranda,Mar Piedecausa,Luis Irigoyen,Rodrigo Alonso,Juan F Sanchez,Francisco Perez-Jiménez,Lina Badimón,Eliseo Guallar,A Barba,Ovidio Muñiz

doi:10.1186/1476-511x-10-94

Abstract

AimFamilial 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.Methods and ResultsA 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.ConclusionAlthough 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.

Highlights

Heterozygous familial hypercholesterolemia (FH) is the most common genetic disorder associated with the development of premature coronary heart disease (CHD) with an autosomal dominant mode of inheritance, and a prevalence of one case in 400 to 500 in the general population [1]
120 different functional mutations in low-density lipoprotein receptor (LDL-r) and Apo B genes have been identified in this cohort and 25 mutations represent 65.0% of the cases recruited
The present study shows that most of FH cases are on Lipid Lowering Therapy (LLT), cardiovascular risk is still high, in part due to the high low-density lipoprotein cholesterol (LDL-c) levels

Summary

Introduction

Heterozygous familial hypercholesterolemia (FH) is the most common genetic disorder associated with the development of premature CHD with an autosomal dominant mode of inheritance, and a prevalence of one case in 400 to 500 in the general population [1]. The disorder is caused by mutations in the gene that encodes the low-density lipoprotein receptor (LDL-r), leading to an increase in plasma low-density lipoprotein cholesterol (LDL-c) levels. Since 1990’s, coronary mortality and total mortality in FH patients have markedly decreased in part due to the use of statins [9,10,11]. Despite the use of statins, most of these patients do not achieve an optimal therapeutic LDL-c level [12] and still have a high risk for the development of premature CHD

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