Familial combined hyperlipidemia – the most common genetic dyslipidemia in population and in patients with premature atherothrombotic cardiovascular disease

Česká verzia

Authors: Helena Vaverková; David Karásek
Authors place of work: III. interní klinika – nefrologická, revmatologická a endokrinologická LF UP a FN Olomouc
Published in the journal: Vnitř Lék 2018; 64(1): 25-29
Category: Reviews

Summary

Familial combined hyperlipidemia (FCH) is the most frequent genetic dyslipidemia (DLP) with high risk of early atherosclerosis manifestation. It is characterized by elevated both triglycerides ≥ 1.5 mmol/l and apolipoprotein B ≥ 1.2 g/l (hyper-TG/hyper-ApoB fenotype), with at least two affected family members. Despite the fact that plasmatic levels of total cholesterol and LDL-C are usually lower than in familial hypercholesterolemia and full expression of DLP in FCH occurs in adulthood, risk of premature manifestation of atherosclerosis is similar in both these familial DLP. It is probably due to the presence of other atherogenic lipid and non-lipid risk factors, such as increased levels of triglyceride rich lipoprotein remnants, presence of small dense LDL, reduction of HDL-C, presence of insulin resistance with impaired glucose homeostasis, hepatic steatosis, arterial hypertension, hyperuricemia and presence of increased markers of systemic inflammation. The term “familial” usually implicates a monogenic trait. However, FCH is almost always nonmendelian. According to recent knowledge FCH is mostly polygenic with variable presence of large effect mutations, accumulation of several small-effect polymorphisms and some environmental influences. Therefore, FCH is rather a syndrome with common clinical presentation but multigenic causes. The term „familial combined hyperlipidemia“ is embedded in clinical practice and so it is not necessary to abandon it, as it nearly urges to examination of first degree relatives. This might help to identify a great number of risk subjects who deserve appropriate management.

Key words:
apolipoprotein B – familial combined hyperlipidemia – genetics – insulin resistance – premature atherosclerosis – triglycerides

Zdroje

1. Goldstein JL, Schrott HG, Hazzard WR et al. Hyperlipidemia in coronary heart disease. II. Genetic analysis of lipid levels in 176 families and delineation of a new inherited disorder, combined hyperlipidemia. J Clin Invest 1973; 52(7): 1544–1568. Dostupné z DOI: <http://dx.doi.org/10.1172/JCI107332>.

2. Hazzard WR, Goldstein JL, Schrott MG et al. Hyperlipidemia in coronary heart disease.

3. Evaluation of lipoprotein phenotypes of 156 genetically defined survivors of myocardial infarction. J Clin Invest 1973; 52(7): 1569–1577. Dostupné z DOI: <http://dx.doi.org/10.1172/JCI107333>.

3. Wiesbauer F, Blessberger H, Azar D et al. Familial-combined hyperlipidaemia in very young myocardial infarction survivors (< or=40 years of age). Eur Heart J 2009; 30(9): 1073–1079. Dostupné z DOI: <http://dx.doi.org/10.1093/eurheartj/ehp051>.

4. Vaverková H, Weinbergová O, Horčička V et al. Rodinná kombinovaná hyperlipidemie. II. Riziko ischemické choroby srdeční. Vnitř Lék 1986; 32(9): 887–893.

5. Vaverková H, Ficker L, Vlachová I et al. Familiární dyslipidémie v rodinách po předčasné ischemické cévní mozkové příhodě. Čs Neurol Neurochir 1992; 55/88(4): 129–134.

6. Vaverková H, Weinbergová O, Horčička V et al. Rodinná kombinovaná hyperlipidemie. I. Rozmanitost lipoproteinového obrazu. Vnitř Lék 1986; 32(9): 878–886.

7. Brouwers MC, van Greevenbroek MM, Stehouwer CD et al. The genetics of familial combined hyperlipidaemia. Nat Rev Endocrinol 2012; 8(6): 352–362. Dostupné z DOI: <http://dx.doi.org/10.1038/nrendo.2012.15>.

8. van Greevenbroek MM, Stalenhoef AF, de Graaf J et al. Familial combined hyperlipidemia: from molecular insights to tailored therapy. Curr Opin Lipidol 2014; 25(3): 176–182. Dostupné z DOI: <http:// dx.doi.org/10.1097/MOL.0000000000000068>.

9. Gaddi A, Galetti C, Pauciullo P et al. Familial combined hyperlipoproteinemia: experts panel position on diagnostic criteria for clinical practice. Committee of experts of the Atherosclerosis and Dysmetabolic Disorders Study Group. Nutr Metab Cardiovasc Dis 1999; 9(6): 304–311.

10. Veerkamp MJ, de Graaf J, Bredie SJ et al. Diagnosis of familial combined hyperlipidemia based on lipid phenotype expression in 32 families: results of a 5-year follow-up study. Arterioscler Thromb Vasc Biol 2002; 22(2): 274–282.

11. Veerkamp MJ, de Graaf J, Hendriks JC et al. Nomogram to diagnose familial combined hyperlipidemia on the basis of results of a 5-year follow-up study. Circulation 2004; 109(24): 2980–2985. Dostupné z DOI: <http://dx.doi.org/10.1161/01.CIR.0000130646.93255.86>.

12. Sniderman AD, Ribalta J, Castro Cabezes M. How should FCHL be defined and how should we think about its metabolic bases. Nutr Metab Cardiovasc Dis 2001; 11(4): 259–273. Erratum in Nutr Metab Cardiovasc Dis 2001; 11(6): 412.

13. Civeira F, Jarauta E, Cenarro A et al. Frequency of low-density lipoprotein receptor gene mutations in patients with a clinical diagnosis of familial combined hyperlipidemia in a clinical setting. J Am Coll Cardiol 2008; 52(19): 1546–1553. Dostupné z DOI: <http://dx.doi.org/10.1016/j.jacc.2008.06.050>.

14. Abifadel M, Bernier L, Dubuc G et al. A PCSK9 variant and familial combined hyperlipidaemia. J Med Genet 2008; 45(12): 780–786. Dostupné z DOI: <http://dx.doi.org/10.1136/jmg.2008.059980>.

15. Brahm AJ, Hegele RA. Combined hyperlipidemia: familial but not (usually) monogenic. Curr Opin Lipidol 2016; 27(2): 131–140. Dostupné z DOI: <http://dx.doi.org/10.1097/MOL.0000000000000270>.

16. Sharma K, Baliga RR. Genetics of Dyslipidemia and Ischemic Heart Disease. Curr Cardiol Rep 2017; 19(5): 46. Dostupné z DOI: <http:// dx.doi.org/10.1007/s11886–017–0855–9>.

17. Pajucanta P, Lilja HE, Sinsheimer JS et al. Familial combined hyperlipidemia is associated with upstream transcription factor 1 (USF1). Nat Genet 2004; 36(4): 371–376. Dostupné z DOI: <http://dx.doi.org/10.1038/ng1320>.

18. Vaverková H, Novotný D, Karásek D et al. Familiární kombinovaná hyperlipidemie: asociace s dalšími rizikovými faktory aterosklerózy. Šobrova přednáška : IX. kongres o ateroskleróze, Špindlerův Mlýn, 1.- 3.12.2005. DMEV 2005; 8(Suppl 3): 5–11.

19. Halenka M, Vaverková H, Hutyra M et al. Detection of early atherosclerosis using the ultrasound parameter of the intima-media thickness of the common carotid artery in families with familial combined hyperlipidemia. Intern Angiol 2004; 23(3): 230–237.

20. Keulen ET, Kruijshoop M, Schaper NC et al. Increased intima-media thickness in familial combined hyperlipidemia associated with apolipoprotein B. Arterioscler Thromb Vasc Biol 2002; 22(2): 283–288.

21. Ylitalo K, Syvänne M, Salonen R et al. Carotid artery intima-media thickness in Finnish families with familial combined hyperlipidemia. Atherosclerosis 2002; 162(1): 171–178.

22. Karásek D, Vaverková H, Halenka M ez al. Brachial endothelial function in subjects with familial combined hyperlipidemia and its relationships to carotid artery intima-media thickness. Int Angiol 2006; 25(4): 418–426.

23. Karásek D, Vaverková H, Halenka M et al. Soluble cell adhesion molecules s-VCAM-1 in subjects with familial combined hyperlipidemia. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2005; 149(1): 101–108.

24. Keulen ET, Kruijshoop M, Schaper NC et al. Increased intima-media thickness in familial combined hyperlipidemia associated with apolipoprotein B. Arterioscler Thromb Vasc Biol 2002; 22(2): 283–288.

25. Ylitalo K, Syvänne M, Salonen R et al. Carotid artery intima-media thickness in Finnish families with familial combined hyperlipidemia. Atherosclerosis 2002; 162(1): 171–178.

26. Jackuliaková D, Vaverková H, Karásek D. Relationship between familial combined hyperlipidemia and insulin resistance. Vnitř Lék 2008; 54(11): 1045–1053.

27. Gaddi A, Cicero AF, Odoo FO et al. Atherosclerosis and Metabolic Diseases Study Group. Practical guidelines for familial combined hyperlipidemia diagnosis: an up-date. Vasc Health Risk Manag 2007; 3(6): 877–886.

28. Catapano AL, Graham I, De Backer G et al. [Authors/Task Force Members; Additional Contributor]. 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias. Eur Heart J 2016; 37(39): 2999–3058. Dostupné z DOI: <http://dx.doi.org/10.1093/eurheartj/ehw272>.

29. Sacks FM, Carey VJ, Fruchart JC. Combination of lipid therapy in type 2 diabetes. NEJM 2010; 363(7): 692–694.

30. Hiramitsu S, Miyagishima K, Ishii J et al. The effect of ezetimibe on lipid and glucose metabolism after a fat and glucose load. J Cardiol 2012; 60(5): 395–400. Dostupné z DOI: <http://dx.doi.org/10.1016/j. jjcc.2012.07.010>.

31. Winkler K, Jacob S, Müller-Schewe T et al. Ezetimibe alone and in combination lowers the concentration of small, dense low-density lipoproteins in type 2 diabetes mellitus. Atherosclerosis 2012; 220(1): 189–193. Dostupné z DOI: <http://dx.doi.org/10.1016/j. atherosclerosis.2011.10.043>.

32. Takase H, Dohi Y, Okado T et al. Effects of ezetimibe on visceral fat in the metabolic syndrome: a randomised controlled study. Eur J Clin Invest 2012; 42(12): 1287–1294. Dostupné z DOI: <http://dx.doi. org/10.1111/eci.12000>.

33. Ushio M, Nishio Y, Sekine O et al. Ezetimibe prevents hepatic steatosis induced by a high-fat but not a high-fructose diet. Am J Physiol Endocrinol Metab 2013; 305(2): E293-E304. Dostupné z DOI: <http:// dx.doi.org/10.1152/ajpendo.00442.2012>.

34. Simon TG, Corey KE, Chung RT et al. Cardiovascular Risk Reduction in Patients with Nonalcoholic Fatty Liver Disease: The Potential Role of Ezetimibe. Dig Dis Sci 2016; 61(12): 3425–3435. Dostupné z DOI: <http://dx.doi.org/10.1007/s10620–016–4330-z>.

35. Pearson TA, Ballantyne CM, Veltri E et al. Pooled analyses of effects on C-reactive protein and LDL-cholesterol in placebo-controlled trials of ezetimibe monotherapy or ezetimibe addend to baseline statin therapy. Am J Cardiol 2009; 103(3): 369–374. Dostupné z DOI: <http://dx.doi.org/10.1016/j.amjcard.2008.09.090>.

36. Vaverkova H, Farnier M, Averna M et al. Lipid-altering efficacy of ezetimibe/simvastatin 10/20 mg compared to rosuvastatin 10 mg in high-risk patients with and without type 2 diabetes mellitus inadequately controlled despite prior statin monotherapy. Cardiovasc Ther 2012; 30(2): 61–74. Dostupné z DOI: <http://dx.doi.org/10.111 1/j.1755–5922.2010.00181.x>.

37. Cannon CP, Blazing MA, Giugliano RP et al. [IMPROVE-IT Investigators]. Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes. N Engl J Med 2015; 372(25): 2387–2397. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa1410489>.