Pediatric Dyslipidemia: Angela Gooden MSN, RN, CPNP- AC/PC, Texas Children s Hospital, Pediatric Cardiology

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1 Pediatric Dyslipidemia: Angela Gooden MSN, RN, CPNPAC/PC, Texas Children s Hospital, Pediatric Cardiology Objectives Define pediatric dyslipidemia Describe the association between pediatric dyslipidemia and atherosclerosis Review screening guidelines to identify children with lipid disorders Review primary and secondary causes of dyslipidemia Review preventative measures to prevent or reduce early atherosclerosis and cardiovascular disease Review pharmacologic management strategies for children with dyslipidemia Know when to refer to a lipid specialist Dyslipidemia Dyslipidemia is a disorder of lipoprotein metabolism resulting in an abnormal amount of lipids in the blood There are primary and secondary causes of dyslipidemia Cholesterol Metabolism Bile salts in the GI tract dissolve the fats we eat and form chylomicrons Chylomicrons are absorbed by the small intestine, into the lymphatic system, and enter the bloodstream through the thoracic duct Lipoprotein lipase, found in the walls of blood vessels and on the cell membranes of fat and muscle, process the chylomicrons Triglycerides are removed, chylomicron remnants remain Cholesterol Metabolism The liver absorbs chylomicron remnants and processes them into VLDL particles and empty HDL particles

2 Empty HDL particles take cholesterol and lipids from tissues and are digested harmlessly VLDL is converted into LDL and is used in the production of fatty plaques à atherosclerosis Atherosclerosis This is the pathologic process that causes plaque to build up in arteries Plaque is made of fat, cholesterol, calcium, and other substances found in blood Atherosclerosis can affect any artery in the body Cardiovascular disease events CV events occur when there is arterial obstruction or rupture Coronary artery disease, myocardial infarction Carotid artery disease, stroke Renal artery disease, chronic kidney disease Peripheral artery disease, extremity numbness, pain, infection These events are rare in the pediatric population So, what s the big deal? Dyslipidemia begins in childhood and adolescence & is an established risk factor for the onset and severity of atherosclerosis Correcting dyslipidemia early can reduce the risk of premature CVD, especially in high risk individuals with severe dyslipidemia Landmark Studies linking childhood risk factors & Adult CVD Bogalusa Heart Study Framingham Heart Study

3 Muscatine Study Special Turku Coronary Risk Factor Intervention Project Child & Adolescent Trial for Cardiovascular Health CATCH Cardiovascular Risk in Young Finns Study Pathobiological Determinants of Atherosclerosis in Youth PDAY Pathological Determinants of Atherosclerosis in Youth (PDAY) Autopsy studies of y.o. Examination of CVD risk factors Lipid profiles Obesity Smoking Vascular evidence of hypertension Evaluation of fatty streaks & fibrous plaques in aorta, coronary arteries TC HDLC = nonhdlc Risk scores showed high correlation between nonhdlc & atherosclerosis In adults, non HDLC was a better independent predictor of CVD than LDLC Bogalusa Heart Study Risk factor status for > 3000 children aged 514 y.o. followed for 12 years Autopsy studies done on children who died of accidental causes Atherosclerotic lesions examined Fatty streaks and fibrous plaques increase with age, nearly 70% in young adulthood Cholesterol levels (NonHDLC, LDLC, TC and HDLC) predict degree of arterial plaque Obesity in childhood with HTN, hypercholesterolemia à tracks to adulthood

4 Overweight children 2.5 x more likely to have high cholesterol than those with BMI <85% The purpose of lipid screening Selective screening based on family history alone will miss 3060% of children with dyslipidemia Universal screening can identify children & adolescents at high risk for premature CVD due to: Inherited or acquired lipid disorders Moderate or high risk factors Screening guidelines helps us implement primordial and primary prevention measures Those that prevent development of risk factors Those that improve outcomes in children with multiple risk factors Lipid & Lipoprotein guidelines Old guidelines, National Cholesterol Education Program (NCEP), 1992 Focused on children with elevated LDLC New guidelines, National Heart, Lung, & Blood Institute (NHLBI), 2011 Universal screening Guidelines for selective and universal screening Includes patterns of dyslipidemia associated with obesity which are different that those seen in 1992 The pros and cons Moderate to severe TG elevation Normal to mild elevation in LDLC Reduced HDLC What you need to know before screening Total cholesterol (TC) levels are age, gender, and sexual maturityspecific

5 Screening at 911 years of age, will precede the onset of puberty for most, but you have to take ethnic differences in onset of puberty into account NonHDLC, a nonfasting test, has emerged as a better assessment of persistent dyslipidemia The presence of moderate and high risk factors will dictate the timing of screening Why NonHDLC? It is the cholesterol present in lipoprotein particles that are atherogenic In the PDAY study, every 30 mg/dl increase in nonhdlc was associated with a visible incremental increase in the extent and severity of atherosclerosis It provides a better assessment of persistent dyslipidemia It is accurate in nonfasting individuals! Determining risk Moderate level risk factors Hypertension not requiring drug therapy BMI 95 th and < 97th percentile Moderate risk conditions Kawasaki disease coronary aneurysm regression Chronic inflammatory disease, e.g. lupus, JRA HIV Nephrotic syndrome High level risk factors Hypertension requiring drug therapy Significant smoke exposure BMI 97 th percentile High risk conditions

6 Diabetes, type 1 and 2 Chronic or endstage renal disease Heart transplant recipient Kawasaki disease with aneurysms Acceptable Values, 911 years Below the 75 th percentile (except for HDLC) TC <170 mg/dl LDLC <110 mg/dl NonHDLC <120 mg/dl TG <75 mg/dl (Birth9 y) OR <90 mg/dl (10 19 y) HDLC >45 mg/dl, above the 20 th percentile Borderline Values, 911 years Between the 75 th and 95 th percentile (except HDLC) HDL between the 10 th and 25 th percentile TC: 170 to 199 mg/dl LDLC: 110 to 129 mg/dl NonHDLC: 120 to 144 mg/dl TG 7599 mg/dl (Birth9 y) OR mg/dl (10 19 y) HDLC: 40 to 45 mg/dl, value between 10 th and 25 th percentile Abnormal Values, 911 years Greater than the 95 th percentile (except HDLC) TC >200 mg/dl

7 LDLC >130 mg/dl NonHDLC >145 mg/dl TG > 100 mg/dl (Birth9 y) OR > 130 mg/dl (10 19 y) HDLC <40 mg/dl, value below the 10 th percentile If FLP, obtain another > 2 weeks & < 3 months, average the two If nonhdlc, follow with FLP, then another > 2 weeks & < 3 months, average the two Abnormal lipid profile Differentiate primary and secondary causes Implement diet & lifestyle modifications Evaluate for other risk factors and refer for specialty care as needed Primary & secondary causes of dyslipidemia Familial hypercholesterolemia Homozygous Near total loss of LDL receptor function Severely elevated TC & LDLC Incidence: 1 per 1,000,000 (worldwide) Rapid atherosclerosis development with CVD events beginning early in life Skin lesions, called xanthomas, often seen Heterozygous Elevation of TC & LDLC, but less severe Incidence: 1 per 500 (US) 20 fold risk for CVD if untreated Coronary events begin in the 34 th decade of life

8 Several hundred defects cause elevated LDLC Most common cause Absence of receptor expression Abnormalities in receptor function 2 nd most common cause Defects in the formation of the major protein on LDL resulting in impaired protein binding Secondary dyslipidemia Exogenous: Alcohol, corticosteroids, chemotherapy Endocrine: hypothyroid, hypo pituitary, DM, PCOS Renal: chronic disease, HUS, nephrotic syndrome Infectious: HIV, acute bacterial/viral syndrome, hepatitis Hepatic: obstructive liver disease, cholestasis, cirrhosis, Alagille syndrome Inflammatory: Lupus, JRA Storage: glycogen, Gaucher s, Juvenile TaySach s disease Others: KD, anorexia, solid organ transplant, childhood cancer survivors, Klinefelter s Dietary recommendations Balanced diet of fruits, vegetables, fish, whole grains, and lowfat dairy products Total fat intake no more than 30% daily Limited intake of saturated fats (< 10% of daily total), cholesterol (<300 mg d/l daily), & trans fatty acids (< 1% daily) Reduced fat (fat free, 2%) milk at 12 months of age Decreased intake of fruit juice (no more than 4 oz), sugarsweetened drinks & foods, salt

9 Soluble Fiber: Daily intake = age + 5g/day for young children or 14 g/1000 kcal for adolescents Should come from foods (fruits, veggies, whole grains, nuts, legumes) and not supplements Plant stanols & sterols* Spreads, margarine, OJ, cereal bars, yogurt drinks Decreased TC and LDL levels Randomized clinical trial showed 20g/day intake reduced LDL concentration by 8% Physical activity recommendations At least 60 min of physical activity daily Moderate: walking briskly, jogging Vigorous (3x/week): running, tennis, soccer Limit sedentary activities to < 2 hours daily Video games Computer time TV watching Physical activity benefits Lower systolic/diastolic BP Lower body fat and BMI Improved fitness measures Increased amount of lipoprotein lipase activity in skeletal muscle instead of fat à fatty acids & TG are used for energy Lower TC, TG, and LDLC Higher HDLC Decreased insulin resistance

10 Pharmacologic agents Statins Inhibits an enzyme used in endogenous synthesis of cholesterol Lowers intracellular cholesterol level Upregulates LDL receptors leading to increased clearance of circulating LDL Lowers cholesterol 2050% below baseline Adverse effects: Increased hepatic transaminase levels, elevations of creatine kinase, teratogenesis Pravastatin, Atorvastatin, Simvastatin Fibrates Therapy for elevated TGs Fibric acid derivatives that inhibit synthesis and increase clearance of VLDL apoprotein Bà lower VLDL production Inhibit peripheral lipolysis and decrease hepatic extraction of free fatty acidsà reduced hepatic TG production Use cautiously with supervision of a pediatric lipid specialist Niacin (Nicotinic Acid) Decreases hepatic production of VLDL Can lower LDL & triglyceride levels & increase HDL Adverse effects limit use in pedi population: flushing, liver failure, myopathy, glucose intolerance, hyperuricemia Pharmacologic agents Bile AcidBinding Resins

11 Binds intestinal cholesterol in bile acids blocking reuptake Can lower cholesterol 1020% below baseline No systemic effects Adverse effects: GI discomfort; difficult to take (large pill) CholesterolAbsorption Inhibitors Acts mainly on intestinal absorption, but is absorbed and has systemic effects Reduce LDL by 20% Used in conjunction with statins Palatable, small tablet form Adverse effects: GI discomfort Baseline monitoring Before starting Creatinine Kinase, Hepatic panel At 4 weeks Measure a fasting lipid profile (FLP), ALT, and AST ALT or AST 3 times the upper limit of normal is worrisome If normal, recheck at 8 weeks and 3 months If abnormal, stop the medication and repeat levels in 2 weeks Maintenance monitoring Growth, sexual maturation (contraceptive counseling), development Surveillance for myopathy symptoms, risk factors FLP, AST, and ALT

12 Every 34 months during 1 st year Every 6 months in the 2 nd year and beyond When clinically indicated When to refer to a lipid specialist Family history of early and/or multiple CVrelated events Family history of abnormal lipid profile LDLC 250 mg/dl, TG 500 mg/dl Unsuccessful lifestyle modification (36 months) Comorbid conditions requiring more aggressive treatment Diabetes Renal disease Congenital heart disease Collagen vascular diseases Childhood cancer survivors Medication therapy needed < 10 years of age Take home messages Selective screening alone is insufficient in detecting dyslipidemia in children All children should be screened at 911 and 1720 years of age Implementing primordial and primary prevention measures are key in reducing the risk of early CVD We must continue to evaluate for risk factors and moderate and high risk conditions Diet and lifestyle modifications are an important part of every treatment plan

Learning Objectives. Cholesterol and Lipids in Kids: It s a Matter of the Heart. Is Atherosclerosis a Pediatric Disease?

Learning Objectives. Cholesterol and Lipids in Kids: It s a Matter of the Heart. Is Atherosclerosis a Pediatric Disease? Scott J. Soifer, MD Professor and Vice Chair Department of Pediatrics University of California, San Francisco UCSF Benioff Children s Hospital Cholesterol and Lipids in Kids: It s a Matter of the Heart