title: Value of the Definition of Severe Familial Hypercholesterolemia for Stratification of Heterozygous Patients.
abstract: Familial hypercholesterolemia (FH) is characterized by high low-density lipoprotein (LDL) cholesterol with co-dominant transmission and high risk of cardiovascular disease (CVD), although with high variability among subjects. Currently, CVD stratification tools for heterozygous FH (HeFH) are not available. A definition of severe HeFH has been recently proposed by the International Atherosclerosis Society (IAS), but it has not been validated. Our study aims to see clinical characteristics and prevalence of CVD in subjects defined as severe HeFH by IAS criteria. Probable or definite HeFH introduced in the Dyslipidemia Registry of Spanish Arteriosclerosis Society were analyzed by the IAS criteria. Univariate and multivariate analysis was used to assess the association of CVD with the IAS criteria. About 1,732 HeFH cases were analyzed. Severe HeFH had higher prevalence of familial history of CVD, personal history of tendon xanthomas, LDL cholesterol, and CVD than nonsevere HeFH. A total of 656 (77.1%) and 441 (50.1%) of men and women, respectively, fulfilled the IAS criteria of severe HeFH. In the univariate analysis, subjects defined as severe HeFH showed odds ratio 3.016 (95% CI 3.136 to 4.257, p <0.001) for CVD. However, when traditional risk factors were included in the multivariate analysis, only the presence of cholesterol >400 mg/dl had a statistically significant association with CVD odds ratio 8.76 (95% CI 3.90 to 19.69, p <0.001). In conclusion, the IAS definition of severe HeFH is not significantly associated with CVD when adjusted for classic risk factors. Risk stratification in HeFH is an important issue, but the proposed criteria do not seem to solve this problem.
authors.affiliation: Unidad Clínica e Investigación en Lípidos y Arteriosclerosis, Hospital Universitario Miguel Servet, IIS Aragón, Universidad de Zaragoza, Zaragoza, Spain. Electronic address: sperezc@iisaragon.es.
authors.forename: Sofia
authors.initials: S
authors.lastname: Pérez-Calahorra
authors.affiliation: Endocrinology Department, Hospital Universitario Insular de Gran Canaria, Instituto Universitario de Investigaciones Biomédicas y Sanitarias, Las Palmas de Gran Canaria, Spain.
authors.forename: Rosa María
authors.initials: RM
authors.lastname: Sánchez-Hernández
authors.affiliation: Unitat de Medicina Vascular i Metabolism, Hospital Universitari Sant Joan, Institut d'Investigación Sanitaria Pere Virgili (IISPV), Reus, Tarragona, Spain.
authors.forename: Núria
authors.initials: N
authors.lastname: Plana
authors.affiliation: Unidad Clínica e Investigación en Lípidos y Arteriosclerosis, Hospital Universitario Miguel Servet, IIS Aragón, Universidad de Zaragoza, Zaragoza, Spain.
authors.forename: Victoria
authors.initials: V
authors.lastname: Marco-Benedi
authors.affiliation: Lipid and Vascular Risk Unit, Department of Endocrinology and Nutrition, Hospital del Mar, Universitat Autónoma de Barcelona, Barcelona, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Pedro-Botet
authors.affiliation: Hospital Donostia, Unidad de Lípidos, San Sebastián, Spain.
authors.forename: Fátima
authors.initials: F
authors.lastname: Almagro
authors.affiliation: Hospital San Pedro, Unidad de Lípidos, Logroño, La Rioja, Spain.
authors.forename: Angel
authors.initials: A
authors.lastname: Brea
authors.affiliation: Servicio de Endocrinología y Nutrición, Hospital Clínico Universitario, Universitat de Valencia, Valencia, Spain.
authors.forename: Juan Francisco
authors.initials: JF
authors.lastname: Ascaso
authors.affiliation: Atherosclerosis Unit, Hospital Carlos III, Madrid, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Lahoz
authors.affiliation: Unidad Clínica e Investigación en Lípidos y Arteriosclerosis, Hospital Universitario Miguel Servet, IIS Aragón, Universidad de Zaragoza, Zaragoza, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Civeira
mesh_terms: D000328:Adult; D002318:Cardiovascular Diseases / Q000453:epidemiology*; D008078:Cholesterol, LDL / Q000097:blood; D005260:Female; D006579:Heterozygote; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000145:classification / Q000453:epidemiology* / Q000235:genetics; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009135:Muscular Diseases / Q000453:epidemiology*; D015995:Prevalence; D018570:Risk Assessment; D012720:Severity of Illness Index; D013710:Tendons; D014973:Xanthomatosis / Q000453:epidemiology*
chemical_list: D008078:Cholesterol, LDL