Atherogenic dyslipidemia typical for metabolic syndrome

Czech version

Authors: Vladimír Bláha; Jakub Víšek; Martina Lášticová
Authors‘ workplace: III. interní gerontometabolická klinika Lékařské fakulty UK a Fakultní nemocnice Hradec Králové
Published in: Vnitř Lék 2020; 66(1): 15-20
Category: Main Topic

Overview

Atherogenic dyslipidemias plays an important role in determining the cardiovascular risk. In these patients, insulin resistance is responsible for overproduction and secretion of atherogenic very low density lipoprotein. In addition, insulin resistance promotes the production of small dense low-density lipoprotein (LDL) and reduces high-density lipoprotein (HDL) production. Cardiovascular disease remains a leading cause of morbidity and mortality in these patients. The most European guidelines for the management of dyslipidemias recommend the goal values of LDL-c for moderate cardiovascular risk < 2.6 mmol/l (patients < 50 years with diabetes duration < 10 years, without other risk factors), for high-risk < 1.8 mmol/l and > 50% lowering (patients with diabetes mellitus type 2 without target organ damage, with diabetes duration > 10 years or another additional risk factor), and for very-high-risk < 1.4 mmol/l a > 50% lowering (diabetes with target organ damage, or at least three major risk factors). Moreover in the patients with recurrent atherothrombotic event within two years from the first event with maximal tolerated statin and ezetimibe is the goal LDL-c < 1.0 mmol/l. The secondary goal mainly in hypertriglyceridemia is non-HDL-C, the goal is 0,8 mmol/l higher than recommended goal LDL-C in defined risk category. The monitoring of apoB is also recommended, the goals in the very-high-risk patients are < 0.65 g/l, in high-risk < 0.8 g/l and in moderate-risk < 1.0 g/l. Triglycerides > 1.7 mmol/l and HDL-C < 1.0 mmol/l in man and < 1.2 mmol/l in woman are the risk modulators, but not the therapeutic goals. Both these parameters are included in the goals of non-HDL-C or apolipoprotein B. Statins are the first line of LDL-lowering therapy in atherogenic dyslipidemia and combined therapy with ezetimibe and statins could be useful in very high cardiovascular risk subjects. Furthermore, the effect of a fibrate as an add-on treatment to a statin could improve the lipid profile in individuals with high TG and low HDL cholesterol. Regarding new therapies, recent data from phase III trials show that proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors considerably decrease LDL cholesterol. Thus, they may be useful in patients with concomitant risk diseases or conditions, recurrent cardiovascular events, and elevated LDL cholesterol after second drug administration in addition to maximal statin dose or statin intolerance. Other hypolipidemic therapies with the potential of favorable influencing of atherogenic dyslipidemia are being developed.

Keywords:

Atherosclerosis – LDL-cholesterol – diabetes mellitus – cardiovascular disease – metabolic syndrom – Hypercholesterolemia – cardiovascular risk

Sources

1. Xiao C, Dash S, Morgantini C, Hegele RA, Lewis GF. Pharmacological targeting of the atherogenic dyslipidemia complex: the next frontier in CVD prevention beyond lowering LDL cholesterol. Diabetes 2016; 65: 1767–1778.

2. Dunn FL. Management of dyslipidemia in people with type 2 diabetes mellitus. Rev Endocr Metab Disord 2010; 11: 41–51.

3. Hayward RA, Reaven PD, Wiitala WL, et al. Follow-up of glycemic control and cardiovascular outcomes in type 2 diabetes. N Engl J Med 2015; 372: 2197–2206.

4. Stahel P, Xiao C, Hegele RA, Lewis GF. The Atherogenic Dyslipidemia Complex and Novel Approaches to Cardiovascular Disease Prevention in Diabetes. Canadian Journal of Cardiology 34 (2018) 595–604.

5. Adeli K, Sacco J, Farr S, Xiao C, Lewis GF. Dyslipidemia of obesity and diabetes. In: Biochemistry of Lipids, Lipoproteins and Membranes. 6th ed. Amsterdam, the Netherlands: Elsevier, 2015: 549–573.

6. Dash S, Xiao C, Morgantini C, Lewis GF. New insights into the regulation of chylomicron production. Annu Rev Nutr 2015; 35: 265–294.

7. Krauss RM. All low-density lipoprotein particles are not created equal. Arterioscler Thromb Vasc Biol 2014; 34: 959–961.

8. Lewis GF, Rader DJ. New insights into the regulation of HDL metabolism and reverse cholesterol transport. Circ Res 2005; 96: 1221–1232.

9. Krauss RM. Lipids and lipoproteins in patients with type 2 diabetes. Diabetes Care 2004; 27: 1496–504.

10. Ferreira-Pêgo C, Babio N, Bes-Rastrollo M et al. PREDIMED Investigators. Frequent Consumption of Sugar- and Artifi cially Sweetened Beverages and Natural and Bottled Fruit Juices Is Associated with an Increased Risk of Metabolic Syndrome in a Mediterranean Population at High Cardiovascular Disease Risk. J Nutr. 2016; 146(8): 1528–1536.

11. Becerra -Tomás N, Babio N, Martínez -González MÁ et al. Replacing red meat and processed red meat for white meat, fi sh, legumes or eggs is associated with lower risk of incidence of metabolic syndrome. Clin Nutr. 2016; 35(6): 1442–1449.

12. Kelley GA, Kelley KS. Eff ects of aerobic exercise on lipids and lipoproteins in adults with type 2 diabetes: a meta -analysis of randomizedcontrolled trials. Public Health 2007; 121: 643–655.

13. Gower BA, Goss AM. A lower -carbohydrate, higher-fat diet reduces abdominal and intermuscular fat and increases insulin sensitivity in adults at risk of type 2 diabetes. J Nutr 2015; 145: 177S–83S.

14. Tay J, Luscombe -Marsh ND, Thompson CH et al. A very lowcarbohydrate, low-saturated fat diet for type 2 diabetes management: a randomized trial. Diabetes Care 2014; 37: 2909–2918.

15. Wycherley TP, Thompson CH, Buckley JD et al. Long -term eff ects of weight loss with a very -low carbohydrate, low saturated fat diet on fl ow mediated dilatation in patients with type 2 diabetes: a randomised controlled trial. Atherosclerosis 2016; 252: 28–31.

16. Gaede P, Lund -Andersen H, Parving HH, Pedersen O. Eff ect of a multifactorial intervention on mortality in type 2 diabetes. N Engl J Med 2008; 358: 580–591.

17. The Look AHEAD Research Group. Cardiovascular eff ects of intensive lifestyle intervention in type 2 diabetes. N Engl J Med 2013; 369: 145–154.

18. Mach F, Baigent C, Catapano AL et al. [ESC Scientifi c Document Group]. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modifi cation to reduce cardiovascular risk. Eur Heart J 2019; pii: ehz455.

19. Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20 536 high -risk individuals: a randomised placebo-controlled trial. Lancet 2002;360: 7–22.

20. Booth GL, Kapral MK, Fung K, Tu JV. Relation between age and cardiovascular disease in men and women with diabetes compared with non-diabetic people: a population-based retrospective cohort study. Lancet 2006; 368: 29–36.

21. Anderson TJ, Gregoire J, Pearson GJ et al. 2016 Canadian Cardiovascular Society guidelines for the management of dyslipidemia for the prevention of cardiovascular disease in the adult. Can J Cardiol 2016; 32: 1263–1282.

22. Cannon CP, Blazing MA, Giugliano RP et al. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med 2015; 372: 2387–2397.

23. The Lipid Research Clinics Coronary Primary Prevention Trial Results: I. Reduction in incidence of coronary heart disease. JAMA 1984; 251: 351–364.

24. Jun M, Foote C, Lv J et al. Eff ects of fi brates on cardiovascular outcomes: a systematic review and meta-analysis. Lancet 2010; 375: 1875–1884.

25. Elam MB, Ginsberg HN, Lovato LC et al. Association of fenofi brate therapy with long -term cardiovascular risk in statin-treated patients with type 2 diabetes. JAMA Cardiol 2017; 2: 370–380.

26. Brown BG, Zhao XQ. Nicotinic acid, alone and in combinations, for reduction of cardiovascular risk. Am J Cardiol 2008; 101: S58–62.

27. The HPS2-THRIVE Collaborative Group. Eff ects of extended -release niacin with laropiprant in high-risk patients. N Engl J Med 2014; 371: 203–212.

28. The AIM -HIGH Investigators. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N Engl J Med 2011; 365: 2255–2267.

29. Sabatine MS, Giugliano RP, Keech AC et al. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med 2017; 376: 1713–1722.

30. Leiter LA, Cariou B, Muller -Wieland D et al. Effi cacy and safety of alirocumab in insulin- -treated individuals with type 1 or type 2 diabetes and high cardiovascular risk: the ODYSSEY DM -INSULIN randomized trial. Diabetes Obes Metab. 2017; 19: 1781–1792

31. Ray KK, Leiter LA, Mulle -Wieland D et al. Alirocumab vs usual lipid -lowering care as add -on to statin therapy in individuals with type 2 diabetes and mixed dyslipidaemia: the ODYSSEY DM DYSLIPIDEMIA randomized trial. Diabetes Obes Metab. 2018; 20: 1479–1489.

32. Cicali R, Di Pino A, Ferrari V, Urbano F, Piro S, Rabuazzo AM, Purrello F. New treatment options for lipid-lowering therapy in subjects with type 2 diabetes. Acta Diabetologica (2018); 55: 209–218.

33. Gouni -Berthold I, Alexander V, Digenio A et al. Apolipoprotein C -III inhibition with volanesorsen in patients with hypertriglyceridemia (COMPASS): a randomized, double-blind, placebo-controlled trial. J Clin Lipidol 2017; 11: 794–795.