Treating Hyperlipidemias Flashcards
What is the difference between a hyperlipidemia and a hyperlipemia?
- hyperlipidemia: elevations in any lipoprotein species
- hyperlipemia: elevation in triglycerides
What are lipoproteins?
high molecular weight complexes of specific proteins and lipids (e.g. VLDL, LDL, HDL) used to transport triglycerides and cholesterol in the blood
Why are hyperlipidemias a clinical problem?
because they can lead to acute pancreatitis or atherosclerosis
Which kind of cholesterol is shown to be beneficial and anti-atherogenic?
HDL
Which lipoproteins tend to contain more triglyceride?
larger, less dense ones
What is the role of chylomicrons?
they are synthesized in the enterocytes and transport dietary lipids into the circulation
What is the role of VLDL?
synthesized in hepatocytes, these transport fatty acids and cholesterol to peripheral tissues
What is the role of HDL?
transfer of cholesterol and apoliporztoeins among different lipoprotein subclasses and the liver
What is the role of LDL?
formed from remnants of depleted VLDL by the action of hepatic lipase, they are catabolized in hepatocytes via receptor-mediated endocytosis
Why is LDL problematic in patients?
because that which isn’t taken up by hepatic LDL receptors migrates into the vascular intima, to be taken up by scavenger receptors, oxidized, and accumulates in foam cells, damaging the intima via foam cell necrosis
Why is HDL good?
it decreases the amount of cholesterol available for tissue deposition by removing it from macrophages and promoting its return to the liver
Primary Hypertriglyceridemia
- a state of high triglycerides
- most commonly in the setting of familial hypertriglyceridemia but occasionally familial lipoprotein lipase deficiency or apoCII deficiency
- fibrates are the drug of choice
- treatment includes dietary change, weight reduction, exercise
Familial Hypercholesterolemia
- presents with high cholesterol and normal triglycerides
- due to a defect in the LDL-receptor
- cholesterol levels are elevated from birth and require treatment
- typically responds well to statins and other lipid lowering drugs
- homozygotes have worse disease than heterozygotes and may have CVD in childhood
Familial Defective ApoB100
- a mutation in ApoB100 leads to a decreased affinity for the LDL-receptor
- present with high cholesterol and normal triglycerides (a primary hypercholesterolemia)
- respond well to statins and niacin
Familial Combined
- a complex lipid profile of elevated cholesterol, LDL, and triglycerides, often with reduced HDL
- relatively common (1% prevalence)
- often presents with obesity, hyperinsulinemia, glucose intolerance, and mild hypertension
- requires treatment; usually statins in combination with fibrates
Dysbetalipoproteinemia
- a mixed hyperlipidemia resulting from an poE defect
- see an increase in chylomicrons and IDL-like particles
- present with elevated total cholesterol, LDL, and triglycerides, often with reduced HDL
- treatment involves decreasing fat and cholesterol intake along with niacin and fibrates
Risk of heart disease correlates with what lipid profiles?
- correlates with increased LDL and increased triglycerides
- inverse correlation with HDL
Describe the protocol for measuring serum lipids.
measure them after a 10-hour fast
What informs the decision of whether to treat elevated cholesterol levels?
risk of CVD, not genetic profile
List five risk factors that modify target LDL.
- smoking
- hypertension
- low HDL
- family history of premature CHD
- older age
What four groups of individuals benefit from stating therapy?
- those with clinical atherosclerotic cardiovascular events
- those with an LDL-C greater than 190
- those between 40-75 years of age with diabetes and LDL-C between 70-189
- those 40-75 years old without atherosclerotic events, with LDL-C between 70-189, and who have an estimated 10 year ASCVD risk of 7.5% or higher
What is the only drug category that provides acceptable ASCVD risk reduction compared to their potential for adverse effects?
statins
Statins
- HMG-CoA analogs that inhibit HMG-CoA reductase
- this reduces hepatic formation of cholesterol and increases LDL receptors in hepatocytes to lower plasma LDL
- added benefit of decreasing plasma triglycerides and increasing HDL
- considered first-line therapy for elevated LDL; significantly reduce mortality from MI and CVD
- best given at night when most cholesterol synthesis occurs
- toxicity: increased creatine kinase activity indicates skeletal muscle toxicity occurring as rhabdo, exacerbated by Gemfibrozil and amiodarone
- measure serum aminotransferase and creatine kinase before treatment
- pleiotropic effects include reversal of endothelial dysfunction, decreased inflammation, decreased coagulation, and improved plaque stability
- contraindicated in pregnancy as cholesterol biosynthesis is important for fetal development
- lovastatin/ simvastatin are given as prodrugs; others in the active from
- most have a 40-75% absorption rate, but fluvastatin is nearly 100%
- absorption enhanced when taken with food
- all have a high first-pass effect and are mostly excreted in the bile
What are the pleiotropic statin effects?
unrelated clinical effects demonstrated only in vitro or in animal models
- reversal of endothelial dysfunction
- decreased infalmmation
- decreased coagulation
- improved plaque stability
