Hyperlipidemia Flashcards
Primary Dyslipidemia
Familial hypoalphalipoproteinemia ApoAl Mutations LCAT deficiency ABCA1 deficiency
Secondary Dyslipidemia
Anabolic Steroids Retinoids
Primary Causes of Hyperlipidemia
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
Familial Hypercholesterolemia
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
Familial Defective Apolipoprotein B100
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
Elevated Plasma Lipoprotein (a)
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
Familial COMBINED Hyperlipoproteinemia
• 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
Familial Dysbetalipoproteinemia
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.
Lipoprotein Lipase Deficiency
• Homozygous: TG> 1,000mg/dL • Heterozygous: TG 250-750mg/dL • Lipoprotein lipase (LPL) gene deficiency • Severely increased triglycerides
Apolipoprotein C-II Deficiency
• Autosomal recessive • Rare • Apo C-II deficiency causing decreased lipoprotein lipase activation. • Elevated triglycerides
Familial hypertriglyceridemia
• Autosomal Dominant • Triglycerides 200-500mg/dL • HDL <35mg/dL • Liver overproduces VLDL and increased catabolism of HDL. • Elevated triglycerides and decreased HDL
Secondary Causes of Elevated LDL
Hypothyroidism, Nephrotic syndrome, cholestasis, acute intermittent poryphyria, anorexia, hepatoma, drugs: thiazide, cyclosporin, carbamazepine
Secondary Causes of Reduced LDL
Severe Liver Disease, malabsorption, malnutrition, gaucher’s disease, chronic infections, disease, hyperthyroidism, Drugs: niacin
Secondary Causes of Elevated HDL
Alcohol, exercise, exposure to chlorine, drugs: estrogen
Secondary Causes of Reduced HDL
smoking, DM2, obesity, malnutrition, gaucher’s, cholesteryl ester storage disease, drugs: steroids, BB
IDL Elevation
multiple myeloma, monoclonal gammopathy, AI disease, hypothyroidism
Cholymicrons elevated
AI Disease DM type 2
Lp(a) Elevated
chronic kidney disease, nephrotic syndrome Inflammation, menopause, orchidectomy, hypothyroidism, acromegaly, Drugs: GH, Isotretinoin
Secondary Causes of VLDL Elevation
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
Fats
• 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
Obesity/Insulin Resistance
• Obesity → Insulin Resistance → Increases in liver synthesized fatty acids, and decreased lipolysis • Decreased HDL and increased Triglycerides • Variable effect on LDL
Hypothyroidism
Due to decrease in LDL receptor synthesis and function
Nephrotic syndrome
Complex, but increased production of LDL and VLDL
Diabetes
– increased insulin – Increases HMG CoA Reductase
Liver Failure
decreased cholesterol and triglycerides
Cholestasis
decreased bile secretion – increase in total cholesterol
Estrogen
Elevated triglycerides and HDL (can be pronounced)
Thiazides
Elevated LDL and triglycerides
Beta Blockers
Increased triglycerides and decreased HDL
Clozapine & Olanzapine
Weight gain / Obesity / Diabetes → Elevated triglycerides
Protease Inhibitors
Lipodystrophy → Elevated triglycerides
Evaluation of Hyperlipidemia
Hx: family, social, medical (ASCVD, nephrotic syndrome, diabetes, pancreatitis) Physical: xanthoma, hepatosplenomegaly LAbs: Lipid panel, creat, urine pt, liver enxymes, TSH, fasting glucose
Xanthoma
fatty rash: eyes, joints (esp elbow/knee)
AHA/ACOC recommendations on cardiac risk
assess risk factors for those >21 every 4-6 yrs blood testing: fasting lipid panel, ALT, A1c, CK, consider more eval
Goal of Treatment and Approaches
•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
Therapeutic Lifestyle Changes
•Decrease saturated fatty acids, trans fatty acids •Decrease added sugar intake •Increase exercise •Increase plant sterols and soluble fiber intake •Reduce body weight
Key Guidelines (10)
- 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
