Filiación institucional

Pablo Corral
Internista, Lipidologo. Universidad Fasta. Facultad de Medicina, Cátedra de Farmacología.
E-mail: drpablocorral@gmail.com

Resumen

La hipercolesterolemia severa (HS) se define cuando el valor del Colesterol-LDL (C-LDL) es mayor a 190 mg/dL. Por otro lado la hipercolesterolemia familiar (HF) es el desorden monogénico autosómico dominante más común, que causa aterosclerosis prematura severa y elevada mortalidad en los individuos afectados sin un tratamiento temprano; está determinada principalmente por la existencia de variantes en genes críticos que intervienen en el metabolismo de las lipoprteínas de baja densidad (LDL). El objetivo del presente trabajo consiste en realizar un análisis detallado clínico, bioquímico y genético al subgrupo con HS en el Municipio de General Pueyrredón Pueyrredón y detectar a los portadores de HF. Se describen estas tres características -clínicas, bioquímicas y genéticas- con el fin de demostrar la relación existente entre el fenotipo con elevación extrema de C-LDL y la presencia de variantes genéticas de esta población.

Bibliografía

1. Santos RD, Gidding SS, Hegele RA, Cuchel MA, Barter PJ, Watts GF, et al. International Atherosclerosis Society Severe Familial Hypercholesterolemia Panel. Defining severe familial hypercholesterolaemia and the implications for clinical management: a consensus statement from the International Atherosclerosis Society Severe Familial Hypercholesterolemia Panel. Lancet Diabetes Endocrinol. 2016;4(10):850–61.
2. Ference BA, Ginsberg HN, Graham I, Ray KK, Packard CJ, Bruckert E, et al. Low-density lipoproteins cause atherosclerotic cardiovascular disease. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel. Eur Heart J. 2017;38(32):2459–72
3. Goldstein JL, Hobbs HH, Brown MS. The metabolic and molecular basis of inherited disease. Scriver CT, Beaudet AL, Sly WS, Valle D, editors. New York: McGraw–Hill; 1995.
4. Bell DA, Watts GF. Progress in the care of familial hypercholesterolaemia: 2016. Med J Aust. 2016;205(5):232–6.
5. Nordestgaard BG, Chapman MJ, Humphries SE, Ginsberg HN, Masana L, Descamps OS, et al. Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease: consensus statement of the European Atherosclerosis Society. Eur Heart J. 2013;34(45):3478–90a.
6. Corral P, Geller AS, Polisecki EY, Lopez GI, Bañares VG, Cacciagiu L, et al. Unusual genetic variants associated with hypercholesterolemia in Argentina. Atherosclerosis. 2018;277:256–61.
7. Arca M. Old challenges and new opportunities in the clinical management of heterozygous familial hypercholesterolemia (HeFH): The promises of PCSK9 inhibitors. 2017;256:134–45.
8. Goldstein JL, Brown MS. A century of cholesterol and coronaries: From plaques to genes to statins. 2015;161(1):161–72.
9. Futema M, Plagnol V, Whittall RA, Neil HAW, Simon Broome Register Group, Humphries SE, et al. Use of targeted exome sequencing as a diagnostic tool for Familial Hypercholesterolaemia. J Med Genet. 2012;49(10):644–9.
10. Programme WHG. Familial hypercholesterolaemia (FH) : report of a second WHO consultation, Geneva, 4 September 1998. World Health Organization; 1999.
11. Khera AV, Won H-H, Peloso GM, Lawson KS, Bartz TM, Deng X, et al. Diagnostic yield and clinical utility of sequencing familial hypercholesterolemia genes in patients with severe hypercholesterolemia. J Am Coll Cardiol. 2016;67(22):2578–89.
12. Corral P, Bañares V, Sáenz B, Zago V, Sarobe A, López G, et al. Phenotype of definite familial hypercholesterolemia with negative genetic study in Argentina. Arch Cardiol Mex. 2020;90(2):130–6.
13. Medeiros AM, Bourbon M. Polygenic contribution for familial hypercholesterolemia (FH). Curr Opin Lipidol. 2021;32(6):392–5.
14. Futema M, Shah S, Cooper JA, Li K, Whittall RA, Sharifi M, et al. Refinement of variant selection for the LDL cholesterol genetic risk score in the diagnosis of the polygenic form of clinical familial hypercholesterolemia and replication in samples from 6 countries. Clin Chem. 2015;61(1):231–8.
15. Sjouke B, Yahya R, Tanck MWT, Defesche JC, de Graaf J, Wiegman A, et al. Plasma lipoprotein(a) levels in patients with homozygous autosomal dominant hypercholesterolemia. J Clin Lipidol. 2017;11(2):507–14.
16. Haralambos K, Whatley SD, Edwards R, Gingell R, Townsend D, Ashfield-Watt P, et al. Clinical experience of scoring criteria for Familial Hypercholesterolaemia (FH) genetic testing in Wales. 2015;240(1):190–6.
17. Richards S, Aziz N, Bale S, Bick D, Das S. ACMG laboratory quality assurance committee. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of medical genetics and Genomics and the association for molecular pathology, Genet. Genet Med. 2015;17:405–e424.
18. Wang JS, Dron MR, Ban JF, Robinson AD. Polygenic versus monogenic causes of hypercholesterolemia ascertained clinically, Arterioscler. Arterioscler Thromb Vasc Biol. 2016;36:2439–e2445.
19. Santos RD, Bourbon M, Alonso R, Cuevas A, Vasques-Cardenas NA, Pereira AC, et al. Clinical and molecular aspects of familial hypercholesterolemia in Ibero-American countries. J Clin Lipidol. 2017;11(1):160-166.
20. Berg G, Mesch V, Boero L, Sayegh F, Prada M, Royer M, et al. Lipid and lipoprotein profile in menopausal transition. Effects of hormones, age and fat distribution. Horm Metab Res. 2004;36(4):215–220.
21. Jacob E, Hegele RA. Monogenic Versus Polygenic Forms of Hypercholesterolemia and Cardiovascular Risk: Are There Any Differences?. Curr Atheroscler Rep. 2022;24(6):419–426.
22. D’Erasmo L, Minicocci I, Di Costanzo A, Pigna G, Commodari D, Ceci F, et al. Clinical Implications of Monogenic Versus Polygenic Hypercholesterolemia: Long-Term Response to Treatment, Coronary Atherosclerosis Burden, and Cardiovascular Events. J Am Heart Assoc. 2021;10(9):e018932.
23. Langsted A, Nordestgaard BG. Lipoprotein(a) as Part of the Diagnosis of Clinical Familial Hypercholesterolemia. Curr Atheroscler Rep. 2022;24(4):289-296.
24. Yeang C, Willeit P, Tsimikas S. The interconnection between lipoprotein(a), lipoprotein(a) cholesterol and true LDL-cholesterol in the diagnosis of familial hypercholesterolemia. Curr Opin Lipidol. 2020;31(6):305–312.
25. Zambon A, Mello E Silva A, Farnier M. The burden of cholesterol accumulation through the lifespan: why pharmacological intervention should start earlier to go further?. Eur Heart J Cardiovasc Pharmacother. 2021;7(5):435–441.
26. Tokgozoglu L, Kayikcioglu M. Familial Hypercholesterolemia: Global Burden and Approaches. Curr Cardiol Rep. 2021;23(10):151.