Final‑week Rapid Revision — Molecular Cad (ss / Dm Cardiology)

Final‑Week Rapid Revision Tables

1. Inflammatory Pathways in Coronary Artery Disease

Pathway / Molecule	Source	Key Effect in CAD	Drug / Trial Link	Exam Pearl
IL‑1β	Activated macrophages (NLRP3)	Upstream driver of vascular inflammation	Canakinumab – CANTOS	LDL unchanged but events reduced
IL‑6	Downstream of IL‑1β	Hepatic CRP synthesis, plaque instability	Ziltivekimab (ongoing)	Best marker of residual inflammatory risk
CRP	Liver	Risk marker, not causal	JUPITER (selection marker)	Not a therapeutic target
TNF‑α	Macrophages, T‑cells	Endothelial dysfunction	No CV outcome benefit	Trap option
IFN‑γ	Th1 cells	Inhibits collagen → cap thinning	—	Plaque rupture biology

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2. Landmark Trials — Mechanism‑Linked

Trial	Intervention	Primary Mechanism	Key Result	SS Take‑Home
CANTOS	Canakinumab	IL‑1β inhibition	↓ MACE without LDL change	Proved inflammation hypothesis
FOURIER	Evolocumab	PCSK9 mAb	LDL ~30 mg/dL, ↓ events	Very‑low LDL is safe
ODYSSEY OUTCOMES	Alirocumab	PCSK9 mAb	↓ MACE post‑ACS	ACS population difference
IMPROVE‑IT	Ezetimibe + statin	Cholesterol absorption	Incremental benefit	LDL causality
REDUCE‑IT	Icosapent ethyl	Plaque stabilization	↓ CV death	Not TG alone
EVAPORATE	EPA	↓ low‑attenuation plaque	Plaque regression	Imaging evidence
LoDoCo2	Colchicine	NLRP3 inhibition	↓ stable CAD events	Inflammation control
COLCOT	Colchicine	NLRP3 inhibition	↓ post‑MI events	Early post‑MI

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3. Genetic & RNA Targets (Very High Yield)

Target	Mutation / Drug	Effect	Exam Anchor
PCSK9	LOF mutation / Evolocumab / Inclisiran	↑ LDL‑R recycling	Strong Mendelian causality
LPA	Pelacarsen	↓ Lp(a)	Atherothrombosis focus
ANGPTL3	Evinacumab	LDL ↓ independent of LDL‑R	HoFH clue
CHIP	DNMT3A / TET2	↑ Myeloid inflammation	MI despite low LDL
miR‑92a	Endothelial miRNA	↓ KLF2 → atherogenesis	Shear stress link

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4. Plaque Biology & Rupture

Component	Role	Clinical Relevance
Thin fibrous cap	Low collagen	Rupture‑prone
Necrotic core	Lipid + dead macrophages	Non‑obstructive MI
MMP‑9	Cap degradation	ACS trigger
MerTK	Efferocytosis	Defective → necrotic core
M1 macrophages	Pro‑inflammatory	Plaque instability

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5. Residual Risk — Exam Favorite

Residual Risk Type	Marker	Best Strategy
Residual cholesterol risk	LDL‑C	PCSK9 / Ezetimibe
Residual inflammatory risk	IL‑6 / CRP	Colchicine / IL‑1β targeting
Residual thrombotic risk	Platelet reactivity	Intensified antiplatelets

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6. Ultra‑High‑Yield One‑Liners

• LDL causality proven genetically (PCSK9, LDL‑R)
• HDL raising ≠ outcome benefit
• Most MIs arise from non‑obstructive plaques
• Inflammation reduction improves outcomes only when upstream (IL‑1β)
• TG lowering alone failed (PROMINENT)

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Use this page for last 48‑hour SS revision.

Your Final-Week 1-Page Rapid Revision Tables are now available in the canvas.

This sheet is intentionally compressed, exam-oriented, and elimination-focused, designed for last 24–48 hour SS / DM cardiology revision.

How to use this optimally

• Read once end-to-end (15–20 minutes)
• Second pass: focus only on
  • IL-1β → IL-6 → CRP axis
  • PCSK9 vs Lp(a) vs ANGPTL3
  • CANTOS vs FOURIER vs REDUCE-IT vs PROMINENT
• Final pass: memorize the one-liners (most SS questions collapse to these)

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