Updated management of Hyperlipidemia in children.pptx

For updated management of dyslipidemia in children

1. Presentation on Hyperlipidemia in Children Presented by: Dr Ratan Krishna Shaha Phase B Resident BSMMU

2. Introduction: Coronary artery disease and stroke are the most common causes of morbidity and mortality in developed countries. In the past, atherosclerosis has been viewed as a problem of adults and has not been a focus in the pediatric age range. This is because the clinical manifestations of atherosclerosis are often not observed until middle age. However, there is increasing evidence that the process of atherosclerosis begins in childhood and is progressive throughout life.

3. Risk factors for coronary artery disease Non modifiable -Age -Sex -Family history Modifiable -Dyslipidemia -Hypertension -Diabetes Mellitus -Cigarette smoking -Obesity/metabolic syndrome -Coagulation factors

4. Mechanism of atherosclerosis formation Atherosclerosis results from deposition of lipid and cholesterol in the intima of the arterial wall. The earliest abnormality is thought to be the fatty streak which is an accumulation of lipid-filled macrophages within the intima. These lesions progress to raised plaques. Plaques formed as a result of continued lipid accumulation and proliferation of macrophages and smooth muscle cells. In this lesion, smooth muscle–type cells form a fibrous cap over a deposition of necrotic debris, cholesterol crystals, and, ultimately calcification within the arterial wall.

5. Mechanism of atherosclerosis formation These raised lesions that result in a myocardial infarction because of either their increasing size and obstruction of the arterial lumen or their rupture, which results in the release of thrombogenic substances from the necrotic core. Fibrous plaques tend to develop at anatomic sites where fatty streaks are formed in children. Common site of these lesions to occur at branching sites of the coronary arteries. Turbulent blood flow is important for formation of plaque. Plaques develop in the coronary arteries prior to their appearance in the cerebral arteries.

6. Lipids and Lipoproteins Lipids are organic compounds that are not soluble in water but are soluble in organic solvents. Plasma lipids are transported by lipoproteins. This combination of lipids (including cholesterol triglycerides and phospholipids) and protein (called apolipoproteins) allows the lipid component to become soluble in water and blood. Lipids are important components of cell membranes and also serve as building blocks for some hormones.

7. The principal apolipoproteins are A-1, A-II, B-100, and C-II. Apolipoproteins have several functions. -They bind with specific receptor sites in cells. -They also are cofactors for enzymes involved in lipid metabolism such as lecithin cholesterol acyltransferase and lipoprotein lipase. -They function as structural protein for the biosynthesis and secretion of plasma lipoproteins. For example, Apo A-1 has been proposed as an important structural protein for the biosynthesis of HDL.

8. Chylomicrons Chylomicrons are triglyceride-rich particles produced by the intestine. They are the largest lipoprotein. Their primary function is to transport cholesterol and triglycerides from the diet to sites for metabolism or storage. Chylomicrons are usually not present during fasting and normally are rapidly cleared after a meal. The clearance occurs as a result of lipoprotein lipase, which creates remnants of chylomicrons. These remnants are thought to be atherogenic and are cleared by the liver.

9. VLDL & HDL VLDL particles are also relatively large particles. VLDL is produced by the liver. VLDL transports triglycerides and cholesterol, which is endogenously synthesized, to the periphery. HDLs can be produced in several ways. They can be produced by the liver and the gastrointestinal tract. HDL particles are also produced by catabolism of chylomicrons and VLDL particles. HDL particles are also thought to be heterogeneous. HDL2 is the subfraction that is thought to be most protective against atherosclerosis.

10. LDL LDL is the major carrier of cholesterol to peripheral tissues. LDL is made up of 45% cholesterol. LDL particles are found in atherosclerotic plaque and are associated with increased risk of cardiovascular disease. In particular, small dense LDL particles are considered especially atherogenic. LDL particles are recognized by specific receptors on the cell wall. When LDL particles bind to the receptor on the cell wall, they are then internalized into the cell. It has been estimated that approximately 75% of LDL particles are removed by binding with receptors, whereas the remaining particles are removed by macrophages.

11. Acceptable, Borderline-High, and High Plasma Lipid, Lipoprotein, and Apolipoprotein Concentrations for Children and Adolescents Category Low mg/dl Acceptable mg/dl Borderline high mg/dl High mg/dl TC - <170 170-190 ≥190 LDL cholesterol - <110 110-129 ≥130 Non HDL cholesterol - <120 120-144 ≥145 Apolipoprotein B - <90 90-109 ≥110 TG 0-9 yr - <75 75-99 ≥100 TG 10-19 yr - <90 90-129 ≥130 HDL cholesterol <40 <45 40-45 - Apolipoprotein A1 <115 <120 115-120 -

12. Causes of secondary dyslipidemia: Exogenous- alcohol, drug- β blocker, OCP, chemotherapeutic agent. Endocrine/metabolic- hypothyroidism, T1DM, T2DM, Pregnancy, Lipodystrophy. Renal- chronic renal failure, HUS, NS Infectious- Acute viral/bacterial infection, HIV, Hepatitis. Hepatic- Obstructive liver dis, Biliary cirrhosis, Alagille syndrome. Inflammatory dis- SLE, JIA Storage- Glycogen storage syndrome, Gaucher disease, Others- Kawasaki disease, Anorexia nervosa, Klinefelter syndrome, Progeria, Idiopathic hypercalciuria.

13. Assessment of Atherosclerosis non invasively with: Coronary calcium on electron beam CT imaging. Carotid intimal medial thickness assessed with ultrasound. Endothelial dysfunction (reduced arterial dilation) with brachial ultrasound imaging. Increased left ventricular mass with echocardiography.

14. Risk factors of hyperlipidemia Positive family history: MI, angina, coronary artery bypass graft/stent/angioplasty, sudden cardiac death in parent, grandparent, aunt, or uncle at 55 y for males, 65 y for females. High level risk factor- -HTN that require drug therapy -Current cigarette smoking -BMI ≥97 th percentile -Presence of high risk condition like- T1DM/T2DM, CKD/ESRF, Post renal transfer, Post orthotropic heart transplant, Kawasaki disease with current aneurysm.

15. Risk factors of hyperlipidemia Moderate level risk factor: - HTN that does not require drug therapy - BMI ≥95 th centile <97 th centile - HDL < 40mg/dl - Presence of moderate risk condition like Kawasaki disease with regressed coronary aneurism, chronic inflammatory disease(SLE, JIA), Nephrotic syndrome, HIV infection.

16. Evidence based recommendation for lipid assessment Birth to 2yrs age- no routine screening 2yrs to 8yrs age- no routine screening (measure FLP twice average 2wks apart but not beyond 3months) only if -Parent, grandparent, aunt/uncle, or sibling with MI, angina, stroke, CABG/stent/angioplasty at 55 y in males, 65 y in females. - Parent with TC ≥240 mg/dL or known dyslipidemia - Child has diabetes, hypertension, BMI ≥95th percentile or smokes cigarettes. - Child has a moderate- or high-risk medical condition

17. Evidence based recommendation for lipid assessment 9 to 11yrs age- universal lipid screening -If non-HDL ≥ 145 mg/dL ± HDL < 40 mg/dL : Obtain FLP twice & average results OR -If LDL cholesterol ≥ 130 mg/dL ± non-HDL cholesterol ≥ 145 mg/dL ± HDL cholesterol < 40 mg/dL ± triglycerides ≥ 100 mg/dL if < 10 y, ≥130 mg/dL if ≥ 10 y. 12 to 16 yrs – no routine screening -Measure if new knowledge of: Parent, grandparent with MI, angina, stroke, CABG/stent/angioplasty, sudden death at < 55 yr in male, <65 yr in female or parent with TC ≥ 240 mg/dL or known dyslipidemia. -Patient has diabetes, hypertension, BMI ≥ 85th percentile or smokes cigarettes or Patient has a moderate or high-risk medical condition.

18. Evidence based recommendation for lipid assessment 17 to 19 yrs age- universal lipid screening once in this period -If non-HDL ≥ 145 mg/dL ± HDL < 40 mg/dL : Obtain FLP twice & average results OR -If LDL cholesterol ≥ 130 mg/dL ± non-HDL cholesterol ≥ 145 mg/dL ± HDL cholesterol < 40 mg/dL ± triglycerides ≥ 130 mg/dL. 20 to 21 yrs – universal lipid screening once in this period - If non-HDL ≥ 190 mg/dL ± HDL < 40 mg/dL : Obtain FLP twice & average results OR - If LDL cholesterol ≥ 160 mg/dL ± non-HDL cholesterol ≥ 190 mg/dL ± HDL cholesterol < 40 mg/dL ± triglycerides ≥ 150 mg/dL Obtain FLP twice & average results.

19. Dietary Management of Elevated LDL Cholesterol, Non-HDL Cholesterol, and Triglyceride Levels Elevated LDL cholesterol - 25%–30% of calories from fat, ≤7% from saturated fat, 10% from monounsaturated fat; <200 mg/d of cholesterol; avoid trans fats as much as possible. - plant stanol esters up to 2 g/d as replacement for usual fat sources can be used after 2 y of age in children with familial hypercholesterolemia - The water-soluble fiber psyllium can be added to a low-fat, low saturated-fat diet as cereal enriched with psyllium at a dose of 6 g/d for children 2–12 y of age and 12 g/d for those ≥ 12 y of age for all children, 1 hr /d of moderate-to-vigorous physical activity and 2 hr /d of sedentary screen time are recommended.

20. Dietary Management of Elevated LDL Cholesterol, Non-HDL Cholesterol, and Triglyceride Levels Elevated TG or non-LDL cholesterol - 25%–30% of calories from fat, ≤7% from saturated fat, 10% from monounsaturated fat; <200 mg/d of cholesterol; avoid trans fats as much as possible. - Decrease sugar intake Replace simple with complex carbohydrates No sugar-sweetened beverages Increase dietary fish to increase omega-3 fatty acids

21. Pharmacological treatment of dyslipidemia Birth to 10 yrs : Pharmacologic treatment is limited to children with severe primary hyperlipidemia (homozygous familial hypercholesterolemia, primary hypertriglyceridemia [triglycerides ≥ 500 mg/dL]), a high-risk condition, or evident cardiovascular disease, all under the care of a lipid specialist. ≥10 to 21 yrs : Detailed family history and RF assessment required before initiation of drug therapy. -LDL cholesterol: If average LDL cholesterol ≥ 250 mg/dL , consult lipid specialist , If average LDL cholesterol ≥130–250 mg/dL, or non-HDL ≥ 145 mg/dL: Refer to dietitian for medical nutrition therapy for 6 m; repeat FLP

22. Pharmacological treatment of dyslipidemia Repeat FLP -LDL cholesterol < 130 mg/dL, continue CHILD-2–LDL, reevaluate in 12 m -LDL cholesterol ≥190 mg/dL consider initiation of statin therapy -LDL cholesterol ≥130–189 mg/dL, negative family history, no other RF or RC, continue CHILD-2–LDL, reevaluate every 6 mo -LDL cholesterol = 160–189 mg/dL + positive family history or ≥1 high-level RF/RC or ≥2 moderate-level RFs/RCs, consider statin therapy -LDL cholesterol ≥ 130–159 mg/dL+ ≥ 2 high-level RFs/RCs or 1 high-level + 2 moderate-level RFs/RCs, consider statin therapy Children on statin therapy should be counseled and carefully monitored.

23. Pharmacological treatment of dyslipidemia ≥10 to 21 yrs : Detailed family history and RF/RC assessment required before initiation of drug therapy. -Triglycerides: If average TG ≥ 250 mg/dL , consult lipid specialist If average TG ≥100 mg/dL in a child aged <10 yr , or TG ≥130 mg/dL in a child aged 10-19 yr , or <500 mg/dL: Refer to dietitian for medical nutrition therapy for 6 m; repeat FLP -TG<100(130)mg/dl continue treatment, monitor every 6-12 m -TG>100(130)mg/dl reconsult dietitian intensified -TG≥200-499mg/dl, non HDL ≥145 mg/dl, consider fish oil ± consult lipid specialist Non HDL cholesterol: children aged ≥10 yr with non HDL cholesterol ≥145 mg/dl after LDL cholesterol goal is achieved may be considered for statin, fibrate or niacin.

24. Medications for Managing Hyperlipidemia

25. Medications for Managing Hyperlipidemia

26. Thank you all Source & futher reading: Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents: Summary Report, Pediatrics.  2011 Dec; 128(Suppl 5): S213–S256. Moss & Adam's Heart Disease in Infants, 10 th Edition extended version. Special thanks to: Asst Prof Dr Tahnia Haque, Dept of endocrine & metabolism, BSMMU Asst Prof Dr Sharmin Mahbuba , Dept of Pediatric endocrine & metabolism , BSMMU.