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Secondary Dyslipidemia In Obese Children - Is There Evidence For Pharmacological Treatment?

Keywords:
Heart Defects, Congenital; Dyslipidemias; Oxidative Stress; Metabolic Syndrome; Indicators of Morbidity and Mortality

Obesity is a condition that has progressively increased throughout the world, also affecting children and adolescents, leading to high costs for health systems. Pediatric obesity is associated with dyslipidemia, oxidative stress, insulin resistance, and endothelial dysfunction, cardiovascular risk factors and components of the metabolic syndrome,11 Chandrasekhar T, Suchitra MM, Pallavi M, Srinivasa Rao PV,Pallavi M, Sachan A. Risk factors for cardiovascular disease in obese children. Indian Pediatr. 2017;54(9):752-5. and leads to adverse consequences such as early mortality and physical morbidity in adulthood in the short and long term.

Obesity-related dyslipidemia consists of increased triglycerides and free fatty acids, and decreased HDL-c (high-density cholesterol), normal or slightly increased LDL-c (low-density cholesterol), and increased VLDL-c (cholesterol of very low density). Plasma apolipoprotein B (apo B) concentrations are also frequently increased, in part due to increased hepatic production of apo B-containing lipoproteins.22 Franssen R, Monajemi H, Stroes ES, Kastelein JJ. Obesity and dyslipidemia. Med Clin North Am. 2011,95(5):893-902.,33 Wang H, Peng DQ. New insights into the mechanism of low high-density lipoprotein cholesterol in obesity. Lipids Health Dis. 2011 Oct 12;10:176

In most cases, dyslipidemia is a consequence of bad lifestyle habits, such as a diet rich in saturated or trans fats, and sedentarism. To plan monitoring and treatment, a cardiovascular risk stratification should be done since childhood, and not only the child, but especially the entire family living with him/her, should be educated. Longitudinal studies have shown that interventions in children are effective in the prevention of cardiovascular disease in adults.

The treatment of obesity-related dyslipidemia should be directed to weight loss through increased physical exercise and better eating habits, with a reduction in total calorie intake and reduced intake of essential fatty acids. Lifestyle changes synergistically improve insulin resistance and dyslipidemia.44 Klop B, Cabezas MC. Chylomicrons: a key biomarker and risk fator for cardiovascular disease and for the understanding of obesity. Curr Cardiovasc Risk Rep. 2012.6(1):27-34. The child and the adolescent should be ideally followed by a nutritionist or nutrologist, because of the risk of growth and development impairment.

Interaction among genes, obesity and lipid levels, but also with the type of fat taken in the diet, was recently described.55 Yin RX, Wu DF, Misao L, Aung LH, Cao XL, Yan TT, et al. Several genetic polymorphisms Interact with overweight/obesity to influence serum lipid levels. Cardiovasc Diabetol. 2012 Oct 8;11:123.,66 Sanchez-Moreno C, Ordovas JM, Smith CE, Craza JC, Lee YC, Garaulet M APOAS gene variation interacts with dietary fat intake to modulate obesity and circulating triglycerids in a Mediterranean population. J Nutr.2012;141(5):380-5. Studies suggest the potential utility of a nutrigenomic approach to dietary interventions to prevent or treat obesity and its associated dyslipidemia.55 Yin RX, Wu DF, Misao L, Aung LH, Cao XL, Yan TT, et al. Several genetic polymorphisms Interact with overweight/obesity to influence serum lipid levels. Cardiovasc Diabetol. 2012 Oct 8;11:123.,66 Sanchez-Moreno C, Ordovas JM, Smith CE, Craza JC, Lee YC, Garaulet M APOAS gene variation interacts with dietary fat intake to modulate obesity and circulating triglycerids in a Mediterranean population. J Nutr.2012;141(5):380-5.

Further studies should be conducted on the behavior of coronary artery disease markers, and of serum levels of total cholesterol, low-density lipoprotein, apolipoprotein B, and high-density lipoprotein in children and adolescents compared to adults,22 Franssen R, Monajemi H, Stroes ES, Kastelein JJ. Obesity and dyslipidemia. Med Clin North Am. 2011,95(5):893-902. both in the pre- and post-treatment of obesity-related dyslipidemia, and in the short and long term, considering the cardiovascular risks, and the adverse effects resulting from pharmacological treatment, especially of statins.33 Wang H, Peng DQ. New insights into the mechanism of low high-density lipoprotein cholesterol in obesity. Lipids Health Dis. 2011 Oct 12;10:176,77 Ferguson MA, Alderson NL, Trost SG, Essig DA, Burke JR, et al. Effects of four diferente single exercice session on lipids, lipoproteins, and liporprotein lipase. J Appl Physiol. 1998;85(3):1169-74.

8 Zhou YH, Ma XQ, Wu C, Lu J, Zhang SS,Gui J, et al. Effect of anti-obesity drug on cardiovascular risk factors: a systematic review and meta-analysis of randomized controlled trials. PLos One. 2012;7(6):e39062.

9 Catapano AL, Reiner Z, Backer G, Graham I, Taskinen MR Wiklund O, et al. ESC/EAS Guidelines for the management of dyslipidaemias: The Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). Atherosclerosis. 2011; 217(1):1-44

10 Berglun L, Brunzess JD, Goldberg IJ, Sacks F, Murad MH, Stalenhoef AF, et al. Evaluation and treatment of hypertriglyceridemia: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2012;97(9):2969-89.
-1111 Watts GF, Karpe F. Triglycerides and atherogenic dyslipidaemia: extending treatment beyond statins in the high-risk cardiovascular patient. Heart. 2011;97(5):350-5.

Lipid-lowering therapy should be started after at least six months of intensive lifestyle modification. The drugs used are statins, cholesterol absorption inhibitors (ezetimibe), bile acid sequestrants, phytosterol supplements, omega-3s, and fibrates.

Statins are the drugs of choice among all pharmacological agents to reduce LDL-c, non-HDL-c and/or apoB. However, statins do not lower triglycerides well, and do not completely correct the characteristic dyslipidemia observed in obesity, keeping a residual risk after therapy initiation.1111 Watts GF, Karpe F. Triglycerides and atherogenic dyslipidaemia: extending treatment beyond statins in the high-risk cardiovascular patient. Heart. 2011;97(5):350-5. Recently, strategies for therapies combined with statins and other drugs to achieve even lower cholesterol levels have been reviewed.1111 Watts GF, Karpe F. Triglycerides and atherogenic dyslipidaemia: extending treatment beyond statins in the high-risk cardiovascular patient. Heart. 2011;97(5):350-5.

12 Watts GF, Karpe F. Why, when and how should hypertriglyceridemia be treated in the high-risk cardiovascular patient? Expert Rev Cardiovasc Ther. 2011;9(8):987-97.

13 Dujovne CA, Williams CA, Williams CD, Ito MK, What combination therapy with a statin, ef any, would you recommend? Curr Atheroscler Rep. 2011;13(1):12-22.

14 Rubenfire M, Brook RD, Rosenson RS. Treating mixed hyerlipidemia and the atherogenic lipid phenotype for prevention of cardiovascular events. Am J Med. 2010;123(10:892-8.
-1515 Toth PP. Drug treatment of hyperlipidaemia: a guide to the rational use of lipid-loweing drugs. Drugs. 2010;70(11):1363-79.

Children and adolescents with dyslipidemias who do not adequately respond to changes in lifestyle and habitual doses of lipid-lowering medications should be referred to specialist centers.

The work presented in this issue on secondary dyslipidemia in obese children demonstrates the scarcity of randomized clinical trials in the literature on the use of statins for the treatment of children and adolescents with obesity-related dyslipidemia.

Undoubtedly, this is a topic that should be investigated in depth and in details, with well-defined studies, to prove the efficacy of the several treatments already consecrated for the adult population in the pediatric and adolescent age.

  • Short Editorial regarding the article: Secondary Dyslipidemia In Obese Children - Is There Evidence For Pharmacological Treatment?

References

  • 1
    Chandrasekhar T, Suchitra MM, Pallavi M, Srinivasa Rao PV,Pallavi M, Sachan A. Risk factors for cardiovascular disease in obese children. Indian Pediatr. 2017;54(9):752-5.
  • 2
    Franssen R, Monajemi H, Stroes ES, Kastelein JJ. Obesity and dyslipidemia. Med Clin North Am. 2011,95(5):893-902.
  • 3
    Wang H, Peng DQ. New insights into the mechanism of low high-density lipoprotein cholesterol in obesity. Lipids Health Dis. 2011 Oct 12;10:176
  • 4
    Klop B, Cabezas MC. Chylomicrons: a key biomarker and risk fator for cardiovascular disease and for the understanding of obesity. Curr Cardiovasc Risk Rep. 2012.6(1):27-34.
  • 5
    Yin RX, Wu DF, Misao L, Aung LH, Cao XL, Yan TT, et al. Several genetic polymorphisms Interact with overweight/obesity to influence serum lipid levels. Cardiovasc Diabetol. 2012 Oct 8;11:123.
  • 6
    Sanchez-Moreno C, Ordovas JM, Smith CE, Craza JC, Lee YC, Garaulet M APOAS gene variation interacts with dietary fat intake to modulate obesity and circulating triglycerids in a Mediterranean population. J Nutr.2012;141(5):380-5.
  • 7
    Ferguson MA, Alderson NL, Trost SG, Essig DA, Burke JR, et al. Effects of four diferente single exercice session on lipids, lipoproteins, and liporprotein lipase. J Appl Physiol. 1998;85(3):1169-74.
  • 8
    Zhou YH, Ma XQ, Wu C, Lu J, Zhang SS,Gui J, et al. Effect of anti-obesity drug on cardiovascular risk factors: a systematic review and meta-analysis of randomized controlled trials. PLos One. 2012;7(6):e39062.
  • 9
    Catapano AL, Reiner Z, Backer G, Graham I, Taskinen MR Wiklund O, et al. ESC/EAS Guidelines for the management of dyslipidaemias: The Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). Atherosclerosis. 2011; 217(1):1-44
  • 10
    Berglun L, Brunzess JD, Goldberg IJ, Sacks F, Murad MH, Stalenhoef AF, et al. Evaluation and treatment of hypertriglyceridemia: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2012;97(9):2969-89.
  • 11
    Watts GF, Karpe F. Triglycerides and atherogenic dyslipidaemia: extending treatment beyond statins in the high-risk cardiovascular patient. Heart. 2011;97(5):350-5.
  • 12
    Watts GF, Karpe F. Why, when and how should hypertriglyceridemia be treated in the high-risk cardiovascular patient? Expert Rev Cardiovasc Ther. 2011;9(8):987-97.
  • 13
    Dujovne CA, Williams CA, Williams CD, Ito MK, What combination therapy with a statin, ef any, would you recommend? Curr Atheroscler Rep. 2011;13(1):12-22.
  • 14
    Rubenfire M, Brook RD, Rosenson RS. Treating mixed hyerlipidemia and the atherogenic lipid phenotype for prevention of cardiovascular events. Am J Med. 2010;123(10:892-8.
  • 15
    Toth PP. Drug treatment of hyperlipidaemia: a guide to the rational use of lipid-loweing drugs. Drugs. 2010;70(11):1363-79.
  • 16
    Radaelli G, Sausen G, Cesa CC, Portal VL, Pellanda LC. Dislipidemia secundária em crianças obesas - Há evidências de tratamento farmacológico. Arq Bras Cardiol. 2018; 111(3):356-361.

Publication Dates

  • Publication in this collection
    Sept 2018
Sociedade Brasileira de Cardiologia - SBC Avenida Marechal Câmara, 160, sala: 330, Centro, CEP: 20020-907, (21) 3478-2700 - Rio de Janeiro - RJ - Brazil, Fax: +55 21 3478-2770 - São Paulo - SP - Brazil
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