15 Hyperlipidemia Steinberg Flashcards
Obesity in Childhood: Imposed risk in adulthood?
High adiposity status from childhood to adulthood had increased risk of: T2DM, HTN, Elevated LDL, Reduced HDL, Elevated TG, Increased cIMT
What happens to subjects overweight or obese during childhood, but were nonobese as adults?
They had outcomes risks similar to those who had a normal BMI consistently from childhood to adulthood
What is the Atherosclerotic process in children?
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.
What happens in increasing age in regards to fatty streaks?
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
What are the results of a mother with high cholesterol?
Fetuses and young infants autopsies: aortic atherosclerosis increased more rapidly in hypercholesterolemic compared to normocholesterolemic mothers (despite normal lipid levels in the children)
What is Carotid Intima Media Thickness detected by?
Ultrasonography. Increases likelihood of a CV event
What is Arterial Stiffness measured by?
Aortic pulse wave velocity between 2 major arteries, one of which is located in the upper body and the other in the lower body
What does Flow-Mediated Dilation measure?
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
What predictive factors is cIMT (carotid Intima Media Thickness) associated with?
Associated with predictive factors for metabolic syndrome in children 2-hr oGTT, waist circumference, Systolic BP
What is Familial Hypercholesterolemia (FH)?
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
What are some effects of LH?
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
What are some medications that can cause Drug-Induced Dyslipidemia?
Atypical antipsychotics (Clozapine > Olanzapine > Risperidone»_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
How does Nephrotic Syndroem cause Dyslipidemia?
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
What are acceptable lipid values (< 75th percentile)?
TC < 170, LDL < 110, HDL > 45, TG < 75 (0-9 yo), TG < 90 (10-19 yo)
What are considered elevated lipid values (> 95th percentile)?
TC > 200, LDL > 130, HDL < 40. TG > 100 (0-9 yo), TG > 130 (10-19 yo)
What are the opinions of cholesterol screening, targeted or universal?
Should have universal screening, even if children don’t meet guidelines, they still have high (if not higher) percentage of increased LDL
What is the diet for pediatric lifestyle modifications in infants?
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
What is the diet for pediatric lifestyle modifications in 12-24 mo?
Begin nutritional therapy with reduced-fat milk at 1 year; total fat 30% of daily kcal. Cholesterol < 300mg/d
What is the diet for pediatric lifestyle modifications in 2-10 yo?
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
What is the diet for pediatric lifestyle modifications in 11-21 yo?
Same as 2-10 yo; dietary fiber goal: 14g/1,000 kcal
What are the first-line agents for hypercholesterolemia?
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
What are the recommended cut points to initiate therapy for 8+ yo with no other risk factors for CVD?
LDL persistently > 190 despite diet therapy
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?
LDL persistently > 160 despite diet therapy
What are the recommended cut points to initiate therapy for 8+ yo with DM?
Pharmacologic treatment should be considered when LDL > 130
What are the pediatric FDA indications for statin therapy?
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
What is statin therapy like in FH?
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
What is the pediatric dose of Simvastatin?
Initial dose 10mg daily; max 40mg daily; 40-80mg/day
What is the pediatric dose of Atorvastatin?
Initial dose 10mg daily; max 20mg daily; 10-80 mg/day
When should statin doses be adjusted?
> 4 week intervals to attain the target LDL goals
What did the Pravastatin study show?
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
What is statin initiation like?
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
What are some drug interactions to advise about with Statins?
Cyclosporine, fibric acid derivatives, niacin, erythromycin, azole antifungals, nefazadone, and many protease inhibitors
What should be done after 4 weeks of statin initiation?
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
What are the target levels for LDL?
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
What happens with statin therapy if LDL levels are not achieved?
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
