IM2.1-5 | Atherosclerosis and IHD Foundations — Summary & Reflection

KEY TAKEAWAYS

Epidemiology: IHD is India's leading cause of death; Indians develop IHD ~10 years earlier than Western populations. INTERHEART identified 9 modifiable risk factors accounting for >90% of population-attributable MI risk.

Risk factors: Non-modifiable — age, male sex, family history of premature CAD, South Asian ethnicity. Major modifiable — smoking, dyslipidaemia, hypertension, diabetes, abdominal obesity, physical inactivity, psychosocial stress.

Lipid cycle: Exogenous path: dietary chylomicrons (ApoB-48) → LPL hydrolysis → remnants cleared by liver. Endogenous path: hepatic VLDL → IDL → LDL (ApoB-100) cleared by LDLR. Reverse transport: HDL (ApoA-I) extracts cholesterol from tissues via ABCA1 → liver. LDL is the primary atherogenic lipoprotein; atherogenic dyslipidaemia = elevated TG + low HDL + small dense LDL. Lp(a) is not reduced by statins.

Pathogenesis: Endothelial dysfunction (step 1) → monocyte adhesion/foam cell formation/fatty streak (step 2) → VSMC migration/fibrous cap/intermediate plaque (step 3) → thin-cap fibroatheroma → plaque rupture → acute thrombus (step 4). Glagov remodelling means plaques may be large without causing stenosis until late.

ACS spectrum:
- STEMI: complete occlusion, ST elevation ≥2 mm (precordial) or ≥1 mm (limb leads) in ≥2 contiguous leads or new LBBB, troponin positive; transmural necrosis → emergency reperfusion
- NSTEMI: partial occlusion, ST depression/T-inversion or normal ECG, troponin positive; subendocardial necrosis → risk-stratified early invasive strategy
- Unstable angina: partial/transient occlusion, ischaemic symptoms at rest or crescendo pattern, troponin negative
- Chronic coronary syndrome: stable fixed stenosis, exertional symptoms, CCS class I–IV

REFLECT

Reflect on the two patients in the opening hook — Ramesh (asymptomatic, high LDL, family history) and Suresh (STEMI in the ED). Both share the same biological starting point: an atherosclerotic process progressing silently over decades. Think about the point in the natural history at which each intervention — lifestyle modification, statin therapy, blood pressure control, smoking cessation — would have had the maximum impact for Suresh. Which risk factor in Suresh's profile (smoker, diabetic) was likely the most important accelerant of his plaque progression — and why, mechanistically, does smoking have such a potent atherogenic effect? For Ramesh, what would you tell him about his elevated LDL and low HDL in a 10-minute consultation — and how would you frame the concept of 'silent' plaque vulnerability in a way that motivates him to take a statin without alarming him unnecessarily?