Hyperlipidemia

Question 1

Primary Dyslipidemia

Answer 1

Familial hypoalphalipoproteinemia ApoAl Mutations LCAT deficiency ABCA1 deficiency

Question 2

Secondary Dyslipidemia

Answer 2

Anabolic Steroids Retinoids

Question 3

Primary Causes of Hyperlipidemia

Answer 3

Genetic Conditions • Dyslipidemic patients often have a primary (genetic) underlying cause • Diagnosis of the underlying primary cause may aid in prognostics • (risk of ASCVD, response to treatment, risks in family members) • Very high (>95% of normal) LDL probably has a genetic component • Fortunately clinical treatment is often the same

Question 4

Familial Hypercholesterolemia

Answer 4

rarely homozygous; CHD/aortic stenosis; -LDL 550-900mg/dL -Total 600-1000mg/dL -Fatal MI before age 20 if untreated Heterozygous (1 in 500) -premature heart disease -LDL 250-500 mg/dL -Total 300-600 mg/dL Dx based on numbers and F Hx LDL receptor mutation=increase in LDL and thus total cholesterol

Question 5

Familial Defective Apolipoprotein B100

Answer 5

Autosomal Dominant in 1/750 caucasians Appears similar to familial but is less severe Defective Apo B100 causing POOR BINDING OF LDL TO RECEPTOR Increased LDL and thus total cholesterol

Question 6

Elevated Plasma Lipoprotein (a)

Answer 6

Causes premature coronary heart disease - 1 in 14 MI - 1 in 7 aortic valve disease Increase in LDL binding to apolipoprotein Increased lipoprotein (a) special form of LDL

Question 7

Familial COMBINED Hyperlipoproteinemia

Answer 7

• Autosomal dominant polygenic condition affecting 1-2% of the population. • Triglycerides >175, Total cholesterol >250, & HDL <35 Polygenic causes… • Increase VLDL production • lipoprotein lipase gene defect • Elevated total cholesterol, LDL, & triglycerides • Decreased HDL

Question 8

Familial Dysbetalipoproteinemia

Answer 8

Only a problem when there is another issue… • Diabetes • Hypothyroidism • Alcohol consumption Total cholesterol 300-400mg/dL & Triglycerides 300-400mg/dL • Decreased ApoE2 affinity for LDL receptor • Increased triglycerides, total cholesterol, and LDL.

Question 9

Lipoprotein Lipase Deficiency

Answer 9

• Homozygous: TG> 1,000mg/dL • Heterozygous: TG 250-750mg/dL • Lipoprotein lipase (LPL) gene deficiency • Severely increased triglycerides

Question 10

Apolipoprotein C-II Deficiency

Answer 10

• Autosomal recessive • Rare • Apo C-II deficiency causing decreased lipoprotein lipase activation. • Elevated triglycerides

Question 11

Familial hypertriglyceridemia

Answer 11

• Autosomal Dominant • Triglycerides 200-500mg/dL • HDL <35mg/dL • Liver overproduces VLDL and increased catabolism of HDL. • Elevated triglycerides and decreased HDL

Question 12

Secondary Causes of Elevated LDL

Answer 12

Hypothyroidism, Nephrotic syndrome, cholestasis, acute intermittent poryphyria, anorexia, hepatoma, drugs: thiazide, cyclosporin, carbamazepine

Question 13

Secondary Causes of Reduced LDL

Answer 13

Severe Liver Disease, malabsorption, malnutrition, gaucher’s disease, chronic infections, disease, hyperthyroidism, Drugs: niacin

Question 14

Secondary Causes of Elevated HDL

Answer 14

Alcohol, exercise, exposure to chlorine, drugs: estrogen

Question 15

Secondary Causes of Reduced HDL

Answer 15

smoking, DM2, obesity, malnutrition, gaucher’s, cholesteryl ester storage disease, drugs: steroids, BB

Question 16

IDL Elevation

Answer 16

multiple myeloma, monoclonal gammopathy, AI disease, hypothyroidism

Question 17

Cholymicrons elevated

Answer 17

AI Disease DM type 2

Question 18

Lp(a) Elevated

Answer 18

chronic kidney disease, nephrotic syndrome Inflammation, menopause, orchidectomy, hypothyroidism, acromegaly, Drugs: GH, Isotretinoin

Question 19

Secondary Causes of VLDL Elevation

Answer 19

obesity, stress, DM2, cushings, pregnancy, glycogen storage disease, nephrotic syndrome, acromegaly, hepatits, alcohol, renal failure, sepsis, lipodystrophy, Drugs: estro, BB, bile acid binding resins, retinoic acid

Question 20

Fats

Answer 20

• Saturated fats increase total cholesterol and LDL but may or may not effect coronary heart disease. • Trans fats are harmful in regards to cardiovascular health

Question 21

Obesity/Insulin Resistance

Answer 21

• Obesity → Insulin Resistance → Increases in liver synthesized fatty acids, and decreased lipolysis • Decreased HDL and increased Triglycerides • Variable effect on LDL

Question 22

Hypothyroidism

Answer 22

Due to decrease in LDL receptor synthesis and function

Question 23

Nephrotic syndrome

Answer 23

Complex, but increased production of LDL and VLDL

Question 24

Diabetes

Answer 24

– increased insulin – Increases HMG CoA Reductase

Question 25

Liver Failure

Answer 25

decreased cholesterol and triglycerides

Question 26

Cholestasis

Answer 26

decreased bile secretion – increase in total cholesterol

Question 27

Estrogen

Answer 27

Elevated triglycerides and HDL (can be pronounced)

Question 28

Thiazides

Answer 28

Elevated LDL and triglycerides

Question 29

Beta Blockers

Answer 29

Increased triglycerides and decreased HDL

Question 30

Clozapine & Olanzapine

Answer 30

Weight gain / Obesity / Diabetes → Elevated triglycerides

Question 31

Protease Inhibitors

Answer 31

Lipodystrophy → Elevated triglycerides

Question 32

Evaluation of Hyperlipidemia

Answer 32

Hx: family, social, medical (ASCVD, nephrotic syndrome, diabetes, pancreatitis) Physical: xanthoma, hepatosplenomegaly LAbs: Lipid panel, creat, urine pt, liver enxymes, TSH, fasting glucose

Question 33

Xanthoma

Answer 33

fatty rash: eyes, joints (esp elbow/knee)

Question 34

AHA/ACOC recommendations on cardiac risk

Answer 34

assess risk factors for those >21 every 4-6 yrs blood testing: fasting lipid panel, ALT, A1c, CK, consider more eval

Question 35

Goal of Treatment and Approaches

Answer 35

•Reduce the risk of acute pancreatitis •Prevent coronary heart disease and decrease the risk of heart attack •Prolong life • Therapeutic Lifestyle Changes • Antihyperlipidemic Drug Therapy

Question 36

Therapeutic Lifestyle Changes

Answer 36

•Decrease saturated fatty acids, trans fatty acids •Decrease added sugar intake •Increase exercise •Increase plant sterols and soluble fiber intake •Reduce body weight

Question 37

Key Guidelines (10)

Answer 37

1. heart healthy lifestyle emphasized across all ages 2. Pt w ASCVD: treat with high dose statin 3. In high risk ASCVD pts consider additional therapy to get LDL<70 4. IF LDL>190 recommend high dose statin 5. Diabetics age 40-75 w >70 LDL treat with moderate to high dose statin 6. Before starting statin for primary prevention in 40-75 yr olds have risk/benefit discussion 7. In patients age 40-75 without DM, LDL>70, and ASCVD start moderate statin 8. In patients age 40-75 with out DM but ASCVD risk 7.5-19.9 consider risks and statin 9. In patients 40-75 without DM and with LDL 70-160 and ASCVD (7.5-19.9) but statin desc unclear, get coronary artery calcium 10. Reassess for adherence to statin and lifestyle interventions