Approach to Lipid Disorders
Familial Hypercholesterolemia
Lack of either LDL-R, ApoB, or increase in PCSK9
Leads to high Cholesterol (VLDL, LDL, CM)
Symptoms
Tendon Xanthoma, Xanthelasma, Corneal Arcus
Treatment
Statin (inhibit HMG-Coa which produces cholesterol), Ezetimibe (Cholesterol absorption inhibitor), bile acid sequestrant (blocks bile acid reabsorption), PCSK9 inhibitor (inhibit production of PCSK)
Regulation of LDL receptors
In response to low levels of free cholesterol, liver increases LDL receptors to increase uptake of LDL particles
Diet changes: Decrease diet cholesterol to increase LDLr expression
Evolocumab (Monoclonal antibody), Inclisiran (RNA interference to prevent translation of PCSk9)
Lack of LDL Receptors
LDL Apheresis (plasmapheresis)
Targeting ANGPTL3
LDL-C lowers when there is no LDL receptors
Hypertriglyceridemia
Genetic Factors
LPL mutations, ApoC2 mutations, ApoE2, Dysbetalipoproteinemia (ApoE)
All lead to increase in VLDL, CM (lack of metabolism to further small molecules)
Clinical Factors
Hyperglycemia, Retinoids/Corticosteroids
Lifestyle Facotrs (alsochol excess, Obesity, sedentary Lifestyle)
Excess Substrate for hepatic triglyceride synthesis
Treatment
Increase ASCVD risk with high TG
Approach
Glycemic control, lifestyle often enough, high dose statins, Fibrates, Niacin
Insulin can increase LPL synthesis and metabolism
Fibrates
Indicated in severe hypertriglyceridemia
Leads to increase in Creatine (avoid in CKD)
Generaly safe in combination with fibrates
Other therapies
Increase LPL
Antisense to APOC3, Direct activation of LPL, APOA5 enhancer