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

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

Abstract

Aim: 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.

Methods and results: 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.

Conclusion: 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.

Figures

Figure 1
Figure 1
Recruitment of cases in the SAFEHEART study.

References

    1. Goldstein JL, Hobbs HH, Brown MS. In: The metabolic and molecular basis of inherited disease. Scriver CR, Beaudet AL, Sly WS, Valle D, editor. II. McGraw-Hill, New York; 2001. Familial Hypercholesterolemia; pp. 2863–2913.
    1. Alonso R, Defesche J, Tejedor D, Castillo S, Stef M, Mata N, Gomez-Enterria P, Martinez-Faedo C, Forga L, Mata P. Genetic diagnosis of familial hypercholesterolemia using a DNA-array based platform. Clin Biochem. 2009;42:899–903. doi: 10.1016/j.clinbiochem.2009.01.017.
    1. WHO Human Genetic Program. Familial Hypercholesterolemia. WHO/HGN/FH/CONS/98.7 Paris; 1997. Report of a WHO consultation.
    1. Slack J. Risks of ischaemic heart-disease in familial hyperlipoproteinaemic states. Lancet. 1969;2:1380–2.
    1. Scientific Steering Committee on behalf of the Simon Broome Register Group. The risk of fatal coronary heart disease in familial hypercholesterolaemia. BMJ. 1991;303:893–6.
    1. Pimstone SN, Sun XM, du Souich C, Frohlich JJ, Hayden MR, Soutar AK. Phenotypic variation in heterozygous familial Hypercholesterolemia: a comparison of Chinese patients with the same or similar mutations in the LDL receptor gene in China or Canada. Arterioscler ThrombVasc Biol. 1998;18:309–15.
    1. Alonso R, Mata N, Castillo S, Fuentes F, Saenz P, Muñiz O, Galiana J, Figueras R, Diaz JL, Gomez-Enterría P, Mauri M, Piedecausa M, Irigoyen L, Aguado R, Mata P. Cardiovascular disease in familial hypercholesterolaemia: Influence of low-density lipoprotein receptor mutation type and classic risk factors. Atherosclerosis. 2008;200:315–21. doi: 10.1016/j.atherosclerosis.2007.12.024.
    1. Jansen AC, van Wissen S, Defesche J, Kastelein JJ. Phenotypic variability in familial hypercholesterolaemia: an update. Curr Opin Lipidol. 2002;13:165–71. doi: 10.1097/00041433-200204000-00008.
    1. Scientific Steering Committee on behalf of the Simon Broome Register Group. Mortality in treated heterozygous familial hypercholesterolaemia: implications for clinical management. Atherosclerosis. 1999;142:105–12.
    1. Neil A, Cooper J, Betteridge J, Capps N, McDowell I, Durrington P, Seed M, Humphries SE. Reductions in all-cause, cancer, and coronary mortality in statin-treated patients with heterozygous familial hypercholesterolaemia: a prospective registry study. Eur Heart J. 2008;29:2625–33. doi: 10.1093/eurheartj/ehn422.
    1. Versmissen J, Oosterveer DM, Yazdanpanah M, Defesche JC, Basart DC, Liem AH, Heeringa J, Witteman JC, Lansberg PJ, Kastelein JJ, Sijbrands EJ. Efficacy of statins in familial hypercholesterolaemia: a long term cohort study. BMJ. 2008;337:a2423. doi: 10.1136/bmj.a2423.
    1. Piljman AH, Huijgen R, Verhagen SN, Imholz BP, Liem AH, Kastelein JJ, Abbink EJ, Stalenhoef AF, Visseren FL. Evaluation of cholesterol lowering treatment of patients with Familial hypercholesterolemia: A large cross-sectional study in the Netherlands. Atherosclerosis. 2010;209:189–94. doi: 10.1016/j.atherosclerosis.2009.09.014.
    1. Böthig S. WHO MONICA Project. WHO MONICA Project: objectives and design. Int J Epidemiol. 1989;18(suppl 1):29–37.
    1. Vilagut G, Valderas JM, Ferrer M, Garin O, López-García E, Alonso J. Interpretation of SF-36 and SF-12 questionnaires in Spain: physical and mental components. Med Clin (Barc) 2008;130:726–35. doi: 10.1157/13121076.
    1. Rütten A, Ziemainz H, Schena F, Stahl T, Stiggelbout M, Auweele YV, Welshman J, Ziemainz H. Using different physical activity measurements in eight European countries. Results of the European Physical Activity Surveillance System (EUPASS) time series survey. Public Health Nutr. 2003;6:371–6.
    1. Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem. 1972;18:499–502.
    1. Leren TP. Cascade genetic screening for familial hypercholesterolemia. Clin Genet. 2004;66:483–7. doi: 10.1111/j.1399-0004.2004.00320.x.
    1. Wierzbicki AS, Humphries SE, Minhas R. Familial hypercholesterolaemia: summary of NICE guidance. BMJ. 2008;337:a1095. doi: 10.1136/bmj.a1095.
    1. Oliva J, López-Bastidas J, Gutierrez S, Mata P, Alonso R. Cost-efectiveness analysis of a genetic screening program in the close relatives of Spanish patients with familial hypercholesterolemia. Rev Esp Cardiol. 2009;62:57–65.
    1. Spanish National Health Survey. Spanish Ministry of Health, Social Policy and Equality. 2006.
    1. Civeira F. Guidelines for the diagnosis and management of heterozygous familial hypercholesterolemia. Atherosclerosis. 2004;173:55–68. doi: 10.1016/j.atherosclerosis.2003.11.010.
    1. Graham I, Atar D, Borch-Johnsen K, Boysen G, Burell G, Cifkova R, Dallongeville J, De Backer G, Ebrahim S, Gjelsvik B, Herrmann-Lingen C, Hoes A, Humphries S, Knapton M, Perk J, Priori SG, Pyorala K, Reiner Z, Ruilope L, Sans-Menendez S, Scholte op Reimer W, Weissberg P, Wood D, Yarnell J, Zamorano JL, Walma E, Fitzgerald T, Cooney MT, Dudina A. European Society of Cardiology (ESC) Committee for Practice Guidelines (CPG) European guidelines on cardiovascular disease prevention in clinical practice: executive summary. Fourth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice. Eur Heart J. 2007;28:2375–414.
    1. Kastelein JJ, Akdim F, Stroes ES, Zwinderman AH, Bots ML, Stalenhoef AF, Visseren FL, Sijbrands EJ, Trip MD, Stein EA, Gaudet D, Duivenvoorden R, Veltri EP, Marais AD, de Groot E. ENHANCE Investigators. Simvastatin with or without ezetimibe in familial hypercholesterolemia. N Engl J Med. 2008;358:1431–43. doi: 10.1056/NEJMoa0800742.
    1. Sampalis JS, Bissonnette S, Habib R, Boukas S. Ezetrol Add-On Investigators. Reduction in estimated risk for coronary artery disease after use of ezetimibe with a statin. Ann Pharmacother. 2007;41:1345–51. doi: 10.1345/aph.1K140.

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