Lipid Basics - Cholesterol Crew Intro
-
Lipoproteins: Vehicles for lipid transport.
- Chylomicrons (CM): Carry dietary triglycerides (TGs); Key apolipoproteins: ApoB48, ApoCII (LPL activator), ApoE (remnant uptake).
- VLDL: Carry endogenous TGs; ApoB100, ApoCII, ApoE.
- IDL: VLDL remnant; ApoB100, ApoE.
- LDL ("Bad"): Delivers cholesterol to cells; ApoB100 (receptor binding).
- HDL ("Good"): Reverse cholesterol transport; ApoA1 (LCAT activator).
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Lipid Pathways:
⭐ Apolipoprotein B-100 is the primary apolipoprotein of LDL particles and is essential for their binding to the LDL receptor.
Dyslipidemia Types - Rogue Lipid Lineup
Fredrickson Classification
| Type | ↑Lipoprotein | Plasma (Stored) | Notes |
|---|---|---|---|
| I | CM | Creamy top | LPL/ApoCII def; pancreatitis, eruptive xanth. |
| IIa | LDL | Clear | LDLR def; tendinous xanth., CAD |
| IIb | LDL, VLDL | Clear/Turbid | ↑ApoB; CAD |
| III | IDL (Broad β) | Turbid | ApoE2/E2; palmar/tuboeruptive xanth., CAD |
| IV | VLDL | Turbid | ↑VLDL prod/↓clear; pancreatitis, DM |
| V | CM, VLDL | Creamy top, turbid | Mixed; pancreatitis, eruptive xanth. |
Primary Hyperlipidemias:
- Familial Hypercholesterolemia (FH): LDLR defect → ↑LDL. Tendinous xanth.
- Familial Combined Hyperlipidemia (FCHL): ↑LDL &/or ↑VLDL (↑ApoB). Common.
- Dysbetalipoproteinemia (Type III): ApoE2/E2 → ↑IDL. Palmar/tuboeruptive xanth.
- LPL Deficiency (Type I): LPL/ApoCII defect → ↑CM. Eruptive xanth., pancreatitis.
⭐ Type III HLP shows broad beta band on lipoprotein electrophoresis.
Screening & Goals - Lipid Detective Work
- Screening: Universal for adults >20 yrs (Fasting Lipid Profile - FLP every 4-6 yrs). Selective for high-risk (earlier/frequent).
- Lipid Profile: TC, TG, HDL-C.
- LDL-C (Friedewald): $LDL‑C = TC - HDL‑C - (TG/5)$ (mg/dL).
- Non-HDL-C: $TC - HDL‑C$ (TC minus HDL-C).
- ASCVD Risk Assessment: Tools like Framingham or Pooled Cohort Equations (PCE).
- Key Goals (Indian Context):
- Very High Risk (e.g., CAD, Diabetes Mellitus + Target Organ Damage): LDL-C <70 mg/dL.
- LDL-C >190 mg/dL: Severe hypercholesterolemia (consider Familial Hypercholesterolemia - FH).
- TG >500 mg/dL: ↑ Pancreatitis risk.
⭐ Friedewald formula for LDL-C is inaccurate if TG >400 mg/dL, chylomicronemia (Type I HLP), or dysbetalipoproteinemia (Type III HLP).
Treatment Toolkit - Plaque Attack Plan
- Lifestyle Modification First!
- Diet: Low saturated/trans fat, high fiber.
- Exercise: Regular physical activity.
- Weight loss: If overweight/obese.
- Smoking cessation.
Pharmacotherapy: Key Drug Classes
| Drug Class | MOA | Primary Effect | Key S/E |
|---|---|---|---|
| Statins | HMG-CoA Reductase Inhibitors | ↓LDL-C | Myopathy, hepatotoxicity (📌 HMG: Hepatotoxicity, Myalgia, Glucose) |
| Ezetimibe | Inhibits cholesterol absorption | ↓LDL-C | Generally well-tolerated |
| Fibrates | PPAR-α agonists | ↓TG, ↑HDL | Myopathy (esp. with statins), gallstones |
| PCSK9 Inhibitors | Monoclonal antibodies vs PCSK9 | ↓↓LDL-C | Injection site reactions |
| Bile Acid Sequest. | Binds bile acids in intestine | ↓LDL-C | GI upset, drug interactions |
| Nicotinic Acid | Inhibits lipolysis, ↓VLDL prod. | ↓LDL, ↓TG, ↑HDL | Flushing, PUD, gout (Limited use) |
Stepwise Pharmacological Management:
⭐ Gemfibrozil should generally be avoided with statins due to increased risk of myopathy; fenofibrate is a safer option if combination is necessary.
Secondary Causes - The Usual Suspects
| Condition | Characteristic Lipid Pattern |
|---|---|
| Diabetes Mellitus | ↑TG, ↓HDL, small dense LDL |
| Hypothyroidism | ↑LDL, ↑TG |
| Nephrotic Syndrome | ↑TC, ↑LDL, ↑TG |
| Cholestatic Liver Disease | ↑TC, ↑Unconj. Bilirubin, Lipoprotein-X |
| Drugs | Variable (Steroids, Thiazides, β-blockers) |
| Alcohol | ↑TG, ↑HDL |
| Obesity | ↑TG, ↓HDL |
| Pregnancy | Physiologic ↑TC, ↑TG, ↑LDL |
High‑Yield Points - ⚡ Biggest Takeaways
- Familial Hypercholesterolemia (FH): Autosomal dominant, ↑LDL, tendon xanthomas, premature CAD.
- Statins: HMG-CoA reductase inhibitors, first-line for ↑LDL-C; monitor LFTs, risk of myopathy.
- Fibrates: Activate PPAR-α, best for ↑Triglycerides; risk of myopathy (with statins), gallstones.
- Ezetimibe: Inhibits cholesterol absorption at brush border; adjunct to statins.
- PCSK9 Inhibitors: Potent LDL-C lowering; for statin-intolerant or severe FH.
- Metabolic Syndrome: Includes central obesity, ↑Triglycerides, ↓HDL-C, hypertension, hyperglycemia.
- Lipid Profile Targets: LDL <100 mg/dL (general), <70 mg/dL (high-risk); TG <150 mg/dL.
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