15 Year Old Female with Familial Hypercholesterolemia Case

15 Year Old Female with Familial Hypercholesterolemia Case Category: Pediatric Case History of present illness: 15 year old female with hypercholesterolemia, low HDL, elevated Lp. PLA 2 and family history of early onset for CVD.

Patient Information Age Gender 12 Female Postmenarche Height (in) Weight (lbs) BMI 65 123 20. 47 Waist Circumference (CM) (in) Exercise 29 Light Smoking Allergies Alcohol No Zithromax No BP Systolic (mm/Hg) BP Diastolic (mm/Hg) 102 62 Pulse Rate (beats/min) Fasting Status 70 F

Patient History High Cholesterol Surgical History none Family History MGF Died age 58, heart MGM Age 82, HTN PGM Heart disease, diabetes, cholesterol Father Age 50, cholesterol Mother Age 43, no health issues Brother No health issues

Current Medications Current Medication Prior to this Visit Fish oil 4000 mg Daily Metamucil 1 tbsp Daily

Labs Worth Noting Lab Test Normal Range Patient Value LDL Particle (LDL-P) (nmol/L) <1300 1687 LDL-C (mg/d. L) <100 205 HIGH HDL-C (mg/d. L) >50 36 Triglycerides (mg/d. L) <150 36 Total Cholesterol (mg/d. L) <200 248 Small LDL-P (nmol/L) <850 770 Lp. PLA 2 (ng/m. L) <200 237. 8 HIGH Vitamin D 25 -OH (ng/m. L) >30 16 VERY LOW

Questions to Consider • Question 1: Exercise and diet? • Question 2: Menarche? If not yet menstruating may want to wait to treat dyslipidemia as hormonal shifts may change lipid profile • Question 3: Have all family members been screened for Familial Hypercholesterolemia? • Question 4: Labs prior to use of omega 3 fish oil which can raise LDL –C? In her case >220 prior to any supplements.

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NMR Discussion • This pediatric patient has a pattern very characteristic of Familial Hypercholesterolemia with high LDL–C and high LDL-P but large LDL particle size. If Apo B was done this would be high too. Generally the pattern on NMR shows large buoyant LDL or Pattern A. A key clinical pearl is to recognize regardless of particle size that risk is carried in the LDL Particle concentration. Familial Hypercholesterolemia is a key example of this.

Other Labs Lab Test Normal Range Patient Value ALT (U/L) Up to 33 13 AST (U/L) Up to 32 21 Glucose (mg/dl) 70 -99 82 Hb. AIC (%) <5. 6 5. 4 TSH (u. IU/m. L) 0. 27 -4. 20 2. 22 CRP (mg/L) <1. 0 0. 8

Initial Treatment & Management • Continue fish oil and soluble fiber • Start Vitamin D 3 4000 -5000 IU/day • Discussed use of statin due to LDL-C>200 and diagnosis of Familial Hypercholesterolemia. Needs to be used cautiously in a girl of childbearing potential. Her family was resistant to use a statin in a young girl but wishes to treat her risk with alternative agent. • Start Niaspan 500 mg/day with Ibuprofen as needed for flushing

Discussion Problem Issues Treatment Options Familial Hypercholesterolemia Atherosclerosis leading to heart attack and stroke; Meets diagnosis criteria for Friedrickson type 2 based on history of LDL-C; This is a common autosomal dominant disorder in which LDL clearance is impaired; Differential diagnosis also includes Familial Defective Apo B 100. Treatment includes a statin which is appropriate for use in children. Taking fish oil to decrease LDL-P by 10% (goal is <1300) and address increased inflammation from high Lpp. LA 2; May benefit from Niaspan 500 mg/day to raise HDL, lower triglycerides, lower LDL-C, and lower LDL-P; Statin also indicated in children with FH after lifestyle failed. Family uncomfortable with statin in her age group so alternative treatments discussed. Elevated Lp. PLA 2 Elevations suggest active plaque; Involved in vascular inflammation process leading to formation of vulnerable rupture prone plaque; Risk of stroke and CVD. Taking fish oil.

Discussion Problem Issues Treatment Options Low HDL LDL particles are drivers of atherosclerosis leading to heart attacks and stroke; Residual risk; Family has the same pattern of high LDLP and low HDL. Taking soluble fiber and fish oil. Would benefit from Niaspan 500 mg/day or statin (Rosuvastatin best for HDL raising and indicated for use in pediatrics) Vitamin D Deficiency Increased risk for CVD, fatigue, depression, muscle aching, cancer; Vitamin D 3 4000 -5000 IU

Follow Up • Familial Hyperlipidemia treatment includes a statin which is appropriate for use in children but family declined, she is responding well to Niaspan 500 mg/day. • Elevated Lp. PLA 2 – Improved. • Low HDL – Improved with Niaspan 500 mg/day; HDL increased from 36 to 53; LDL-P decreased from 1687 to 1180; LDL-C decreased to 120 from 205; total cholesterol is now 180 compared to 248; Continue on low dose therapy; May increase to 1000 mg/day in future. • Vitamin D Deficiency – Improved; Levels increased from 16 to 49; Continue supplement.

Clinical Pearls Niacin Therapy • OTC Niacin immediate release is safe and effective if taken 3 times/day but may also be associated with side effects. • OTC Niacin sustained release has potential for liver toxicity and is not advised. • OTC Niacin flush has no effect on cholesterol. • Nicotinic acid is a potent B Vitamin that can raise HDL, lower triglycerides, lower LDL-C, and LDL-P. Clinical trials show it also may regress plaque in arteries. • Take with non-coated aspirin to reduce flushing but in pediatric patients use of Ibuprofen more is more appropriate due to risk of Reye’s syndrome if aspirin used.

Case Summary 1 st Visit Follow Up Goal Medication Fish Oil 4000 mg/day; ; Metamucil cap/daily Niaspan 500 mg/day Vitamin D 3 4000 -5000 IU/day; Fish Oil 4000 mg/day; Metamucil cap/daily Lower LDL-P; Increase Vitamin D LDL Particle (LDL-P) (nmol/L) 1687 1180 <1300 LDL-C (mg/d. L) 205 120 <100 HDL-C (mg/d. L) 36 53 >50 Triglycerides (mg/d. L) 36 33 <150 Total Cholesterol (mg/d. L) 248 180 <200 Small LDL-P (nmol/L) 770 372 <850 Lp. PLA 2 (ng/m. L) 237. 8 CRP 0. 26 <200 Vitamin D 25 -OH (ng/m. L) >16 49 >30

References • • • Aggoun Y, Bonnet D, Sidi D, et al. Arterial mechanical changes in children with familial hypercholesterolemia. Arterioscler Thromb Vasc Biol. Sep 2000; 20(9): 2070 -5. Cortner JA, Coates PM, Liacouras CA, Jarvik GP. Familial combined hyperlipidemia in children: clinical expression, metabolic defects, and management. Curr Probl Pediatr. Oct 1994; 24(9): 295 -305. Daniels SR, Greer FR. Lipid screening and cardiovascular health in childhood. Pediatrics. Jul 2008; 122(1): 198 -208. National Cholesterol Education Program. Report of the Expert Panel on Blood Cholesterol Levels in Children and Adolescents. 1991; US Department of Health and Human Services: NIH Publication No. 91 -2732. Stein EA, Marais AD, Szamosi T, et al. Colesevelam hydrochloride: efficacy and safety in pediatric subjects with heterozygous familial hypercholesterolemia. J Pediatr. Feb 2010; 156(2): 231 -6. e 1 -3. Colletti RB, Neufeld EJ, Roff NK, Mc. Auliffe TL, Baker AL, Newburger JW. Niacin treatment of hypercholesterolemia in children. Pediatrics. Jul 1993; 92(1): 78 -82