Dyslipidemias and Atherosclerosis

Lipid Profile & Targets - Numbers Game

• Components: Total Cholesterol (TC), LDL-C ("Bad"), HDL-C ("Good"), Triglycerides (TG).
• Desirable Levels (mg/dL):
  • • TC: < 200
  • • LDL-C: < 100 (Optimal)
  • • HDL-C: > 60 (Protective); < 40 (Men) / < 50 (Women) is low
  • • TG: < 150
• Key Formulas:
  • • Friedewald: $LDL-C = TC - HDL-C - (TG/5)$
    • • ⚠️ Valid if TG < 400 mg/dL.
  • • Non-HDL-C: $TC - HDL-C$; Target < 130 mg/dL (or 30 above LDL-C goal).
• LDL-C Targets (mg/dL):
  • • High Risk (DM, ASCVD): < 70 (Consider < 55 for very high/extreme risk).

⭐ Friedewald formula is NOT valid if TG > 400 mg/dL or chylomicrons present.

Dyslipidemia Types - Rogues' Gallery

Primary types (Fredrickson classification) are genetic. Secondary causes (e.g., diabetes, hypothyroidism, drugs) are common.

⭐ Type III Dysbetalipoproteinemia (ApoE2/E2) uniquely presents with palmar xanthomas (xanthoma striatum palmare) and a "broad beta band" on electrophoresis.

Atherosclerosis Unveiled - Plaque Attack

Chronic inflammatory response of arterial wall to endothelial injury. Primarily driven by ↑LDL.

• Pathogenesis Cascade:
  • Endothelial dysfunction → LDL entry & oxidation (oxLDL)
  • Monocyte recruitment → Macrophages engulf oxLDL → Foam Cells
  • Fatty Streaks (earliest lesion)
  • Smooth Muscle Cell (SMC) migration/proliferation → Fibrous Cap
  • Mature Atheromatous Plaque (lipid core, fibrous cap)
  • Complications: Rupture, thrombosis, stenosis, aneurysm.

• Key Players: LDL, macrophages, SMCs, platelets, inflammatory cytokines (e.g., TNF-α, IL-1).
• Vulnerable Plaque: Thin fibrous cap, large lipid core, ↑inflammation.

⭐ Most common sites (decreasing order): Abdominal aorta > Coronary arteries > Popliteal arteries > Internal carotid arteries > Circle of Willis.

• Clinical Impact: Angina, Myocardial Infarction (MI), Stroke, Peripheral Artery Disease (PAD).

Management Strategies - Lipid Warriors

• Lifestyle First:
  • Diet: ↓Saturated/trans fats, ↑fiber.
  • Exercise: ≥150 min/week.
  • Weight: BMI <25 kg/m².
  • No smoking.
• Pharmacotherapy (Statins Cornerstone):
  • Statins (Atorva, Rosuva): ↓LDL significantly. Monitor LFTs, CK.
  • Ezetimibe: ↓Cholesterol absorption. Synergistic with statins.
  • PCSK9 Inhibitors (Evolocumab): Max LDL↓ for very high-risk/intolerance.
  • Fibrates (Fenofibrate): Primarily ↓TGs. Myopathy risk with statins.
  • Niacin: ↑HDL, ↓TGs/LDL. Flushing.
  • Bile Acid Sequestrants (Cholestyramine): ↓LDL. GI issues.
• Targets (Risk-Based):
  • LDL-C: <70 mg/dL (very high risk); <100 mg/dL (high risk).
  • Non-HDL-C, ApoB: Secondary/alternative.

⭐ High-Intensity Statin Therapy aims for ≥50% LDL-C reduction (e.g., Atorvastatin 40-80mg, Rosuvastatin 20-40mg).

High‑Yield Points - ⚡ Biggest Takeaways

• LDL cholesterol (LDL-C) is the primary atherogenic lipoprotein and main therapeutic target.
• Statins are first-line drugs for ↓LDL-C, significantly reducing ASCVD risk.
• Familial Hypercholesterolemia (FH): autosomal dominant, markedly ↑LDL-C, premature ASCVD.
• Atherosclerosis: chronic inflammation, endothelial dysfunction, foam cell accumulation, plaque rupture leads to events.
• HDL cholesterol (HDL-C) is cardioprotective; low levels ↑ cardiovascular risk.
• Very high triglycerides (TGs >500 mg/dL) pose a risk for acute pancreatitis.
• Lipoprotein(a) [Lp(a)] is an independent genetic risk factor for ASCVD development.