15 Hyperlipidemia Steinberg

Question 1

Obesity in Childhood: Imposed risk in adulthood?

Answer 1

High adiposity status from childhood to adulthood had increased risk of: T2DM, HTN, Elevated LDL, Reduced HDL, Elevated TG, Increased cIMT

Question 2

What happens to subjects overweight or obese during childhood, but were nonobese as adults?

Answer 2

They had outcomes risks similar to those who had a normal BMI consistently from childhood to adulthood

Question 3

What is the Atherosclerotic process in children?

Answer 3

Atherosclerotic cardiovascular disease begins in children and is progressive –> Incentive for early treatment. Early: fatty streak, which is an accumulation of lipid-filled macrophages within the intima of the artery.

Question 4

What happens in increasing age in regards to fatty streaks?

Answer 4

Lipids may continue to accumulate –> macrophages and smooth muscle cells proliferate and migrate into the intima and media to form a fibrous plaque lesion. Advanced and complicated fibrous plaques are vulnerable to rupture –> thrombus. Vascularization of the plaque, which can lead to hemorrhage and swelling within the plaque and occlusion of the arterial lumen. Subsequent MI or stroke

Question 5

What are the results of a mother with high cholesterol?

Answer 5

Fetuses and young infants autopsies: aortic atherosclerosis increased more rapidly in hypercholesterolemic compared to normocholesterolemic mothers (despite normal lipid levels in the children)

Question 6

What is Carotid Intima Media Thickness detected by?

Answer 6

Ultrasonography. Increases likelihood of a CV event

Question 7

What is Arterial Stiffness measured by?

Answer 7

Aortic pulse wave velocity between 2 major arteries, one of which is located in the upper body and the other in the lower body

Question 8

What does Flow-Mediated Dilation measure?

Answer 8

Measures the endothelial function via response to an adverse stimulus (e.g. ischemia induced by an inflated BP cuff) by brachial artery ultrasonography. Lower response in children with T1DM, family h/o premature CAD, and Kawasaki disease with aneurysms

Question 9

What predictive factors is cIMT (carotid Intima Media Thickness) associated with?

Answer 9

Associated with predictive factors for metabolic syndrome in children 2-hr oGTT, waist circumference, Systolic BP

Question 10

What is Familial Hypercholesterolemia (FH)?

Answer 10

FH is a monogenic, autosomal disorder caused by defects int he gene that encodes for the apo B/E (LDL) receptor –> Reduced LDL clearance from the circulation, increased plasma LDL-C. 4 classes of alleles for mutations at the LDL receptor locus influences phenotypic behavior. Homozygotes more adversely affected than heterozygotes

Question 11

What are some effects of LH?

Answer 11

Some of the excess LDL-C is deposited in the arteries as atheroma and in the tendons and skin as xanthomata and xanthelasma. The prevalence of Xanthomata increases with age, occurring in 75% of FH heterozygotes. Homozygotes with FH also have a high incidence of aortic stenosis (about 50%) d/t atherosclerotic involvement of the aortic root; the incidence is lower in heterozygotes

Question 12

What are some medications that can cause Drug-Induced Dyslipidemia?

Answer 12

Atypical antipsychotics (Clozapine > Olanzapine > Risperidone&raquo_space; Haloperidol; Aripiprazole and Ziprasidone are low). HAART tx for HIV infection. Anti-rejection agents (Cyclosporine > Tacrolimus). Corticosteroids. Carbamazepine, Phenobarbital. Valproic acid (decreases HDL). Diuretics, B-blockers. Oral contraceptives. Isotretinoin

Question 13

How does Nephrotic Syndroem cause Dyslipidemia?

Answer 13

Lose a lot of proteins, so liver actually tries to increase protein concentration by making lipoprotein as well as others to help with osmotic pressure

Question 14

What are acceptable lipid values (< 75th percentile)?

Answer 14

TC < 170, LDL < 110, HDL > 45, TG < 75 (0-9 yo), TG < 90 (10-19 yo)

Question 15

What are considered elevated lipid values (> 95th percentile)?

Answer 15

TC > 200, LDL > 130, HDL < 40. TG > 100 (0-9 yo), TG > 130 (10-19 yo)

Question 16

What are the opinions of cholesterol screening, targeted or universal?

Answer 16

Should have universal screening, even if children don’t meet guidelines, they still have high (if not higher) percentage of increased LDL

Question 17

What is the diet for pediatric lifestyle modifications in infants?

Answer 17

Should be exclusively breastfed (no supplemental Grade B formula or other foods) until age 6 months, continue to 12 months; Limit other drinks to 100% fruit juice < 4 oz/d; no sweetened beverages; encourage water

Question 18

What is the diet for pediatric lifestyle modifications in 12-24 mo?

Answer 18

Begin nutritional therapy with reduced-fat milk at 1 year; total fat 30% of daily kcal. Cholesterol < 300mg/d

Question 19

What is the diet for pediatric lifestyle modifications in 2-10 yo?

Answer 19

Same as 12-24 mo, but lower total fat to 25-30% of daily kcal; encourage high dietary fiber intake from food (age plus 5g/day). Limit sodium intake. Support DASH-style eating plan

Question 20

What is the diet for pediatric lifestyle modifications in 11-21 yo?

Answer 20

Same as 2-10 yo; dietary fiber goal: 14g/1,000 kcal

Question 21

What are the first-line agents for hypercholesterolemia?

Answer 21

Statins (Atorvastatin, Simvastatin, Rosuvastatin, Lovastatin, and Fluvastatin approved for 10 yo). Pravastatin is the only one that can be used as young as 8 yo

Question 22

What are the recommended cut points to initiate therapy for 8+ yo with no other risk factors for CVD?

Answer 22

LDL persistently > 190 despite diet therapy

Question 23

What are the recommended cut points to initiate therapy for 8+ yo with other risk factors present, including obesity, HTN, or cigarette smoking, or (+) family h/o premature CVD?

Answer 23

LDL persistently > 160 despite diet therapy

Question 24

What are the recommended cut points to initiate therapy for 8+ yo with DM?

Answer 24

Pharmacologic treatment should be considered when LDL > 130

Question 25

What are the pediatric FDA indications for statin therapy?

Answer 25

Adjunct to diet to reduce TC, LDL, and Apo B levels in boys and post-menarchal girls, 10-17 years of age with heterozygous FH if after an adequate trial of diet therapy the following findings are present: LDL > 190 or LDL > 160 w/ positive family history of premature CVD or > 2 CVD risk factors

Question 26

What is statin therapy like in FH?

Answer 26

Reduce TC, LDL in patients with homozygous FH as an adjunct to other lipid-lower treatments (e.g. LDL apheresis) or if such treatments are unavailable

Question 27

What is the pediatric dose of Simvastatin?

Answer 27

Initial dose 10mg daily; max 40mg daily; 40-80mg/day

Question 28

What is the pediatric dose of Atorvastatin?

Answer 28

Initial dose 10mg daily; max 20mg daily; 10-80 mg/day

Question 29

When should statin doses be adjusted?

Answer 29

> 4 week intervals to attain the target LDL goals

Question 30

What did the Pravastatin study show?

Answer 30

A significant decline in both TC and LDL. No differences in growth, muscle or liver enzymes, endocrine function parameters, tanner staging scores, onset of menses, or testicular volume between Pravastatin and Placebo groups

Question 31

What is statin initiation like?

Answer 31

Start with the lowest dose given QD, usually at bedtime. Measure baseline CK, ALT, and AST. Instruct the patient/parent to report all potential ADRs, especially myopathy immediately

Question 32

What are some drug interactions to advise about with Statins?

Answer 32

Cyclosporine, fibric acid derivatives, niacin, erythromycin, azole antifungals, nefazadone, and many protease inhibitors

Question 33

What should be done after 4 weeks of statin initiation?

Answer 33

Measure fasting lipoprotein profile, CK, ALT, and AST; threshold for worrisome CK, ALT, or AST is 10 times above the upper limit of reported normal; consider impact of physical activity

Question 34

What are the target levels for LDL?

Answer 34

Minimal 130 mg/dL; ideal, 110 mg/dL; if target LDL levels achieved + no toxicity/lab abnormalities, continue and recheck in 8-24 weeks. IF toxicity Sxs or abnormal labs persist, temporarily d/c drug and repeat blood work in 2 weeks. When abnormalities normalized, the drug may be restarted with close monitoring

Question 35

What happens with statin therapy if LDL levels are not achieved?

Answer 35

Double the dose, and repeat the blood work in 4 weeks. Continue stepped titration up to the maximum recommended dose until target LDL levels are achieved or there is evidence of toxicity