How LDL Cholesterol Drives Heart Attacks: Step-by-Step Pathophysiology

From LDL to Myocardial Infarction

1. LDL Infiltration & Modification

Apolipoprotein B-100 particles enter arterial intima → become oxidized (oxLDL) → trigger endothelial activation.

2. Foam Cell Formation & Fatty Streak

Monocytes differentiate to macrophages → engulf oxLDL via scavenger receptors → become lipid-laden foam cells → form fatty streaks (reversible).

3. Atherosclerotic Plaque Progression

Smooth muscle migration, collagen deposition, calcification → fibrous cap over lipid-rich necrotic core. Narrows lumen → ischemia on exertion (stable angina).

4. Plaque Rupture & Thrombosis

Thin-cap fibroatheromas vulnerable. Rupture exposes tissue factor → platelet adhesion/aggregation → thrombin burst → occlusive thrombus.

5. Myocardial Infarction

Abrupt coronary occlusion → supply-demand mismatch → cardiomyocyte necrosis (STEMI/NSTEMI). Time = muscle.

6. Modifiable Amplifiers

• Hypertension (shear stress)
• Smoking (endothelial dysfunction, oxLDL)
• Diabetes (glycation, inflammation)
• Obesity/insulin resistance
• Low HDL, high triglycerides

LDL-Lowering Strategies

• High-intensity statin (atorvastatin 40–80 mg, rosuvastatin 20–40 mg).
• Ezetimibe add-on.
• PCSK9 inhibitors (evolocumab, alirocumab) for very high risk.
• Lifestyle: Mediterranean diet, soluble fiber, plant sterols, aerobic exercise 150 min/week, weight control, smoking cessation.

Guideline targets: LDL <70 mg/dL (very high risk), <55 mg/dL (extreme risk). Lifelong adherence reduces recurrent events.