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
