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Mechanistic Deep Dive
Atherosclerosis Initiation + Progression
- Endothelial dysfunction â LDL infiltration â oxidized LDL â macrophage foam cells
- Fatty streak â fibrous plaque â vulnerable plaque
- Rupture â ACS
Inflammation in Atherosclerosis
- IL-6, IL-1β, TNF-α, CRP
- CANTOS trial 2017: canakinumab (anti-IL-1β) â MACE
- LoDoCo2 + COLCOT: colchicine
Recent Trials & Updates
SELECT (2023) â Semaglutide
- N = 17,604 obese (BMI ⥠27) + ASCVD without DM
- Semaglutide 2.4 mg weekly vs placebo
- â MACE 20%
- Expanded GLP-1 indication beyond DM
CLEAR Outcomes (2023) â Bempedoic Acid
- N = 13,970 statin-intolerant + â ASCVD risk
- Bempedoic acid vs placebo
- â MACE 13%
- Established for statin-intolerant
PREVENT (2024 AHA)
- New risk calculator
- Includes social determinants
- Separate 10-year + 30-year risks
LoDoCo2 (2020) Long-Term Follow-Up
- Colchicine 0.5 mg/d in CCS
- â MACE
- AHA/ACC 2023 Class IIa
REDUCE-IT Subgroups (2024 updates)
- High TG + ASCVD + on statin â icosapent ethyl benefit
- Mechanism likely beyond TG reduction (anti-inflammatory)
EMPA-KIDNEY (2023)
- Empagliflozin in CKD (with or without DM)
- â progression of kidney disease + CV events
- Non-DM CKD benefit confirmed
High-Yield Specialist Points
Statin Intolerance
- True intolerance: 5-10% (vs nocebo effect 80-90% of complaints)
- SAMS (statin-associated muscle symptoms): myalgia, weakness
- Less common: rhabdomyolysis, hepatotoxicity, diabetes (small increase)
- Manage: dose â, alternate-day, switch agent
- Add ezetimibe, PCSK9i, bempedoic acid
When to Use CAC
- Borderline (5-7.5%) â CAC informs decision
- Intermediate (7.5-19.9%) â CAC + risk enhancers
- High (⥠20%) â already statin warranted
- Family hx of premature CAD without other RF â CAC
Apo B / Non-HDL
- Apo B more accurate than LDL in select populations
- Diabetic, insulin resistance, hypertriglyceridemia
- 2024 guidelines: Apo B optional secondary target
Lipoprotein(a) Pearls
- Genetic, not modifiable by lifestyle
- High Lp(a) ⥠50 mg/dL â independent risk
- Single test in lifetime
- Aggressive other RF control
- Future: pelacarsen, olpasiran, muvalaplin
Diabetes Primary Prevention Pearls
- SGLT2i + GLP-1 RA both reduce CV events in DM + ASCVD
- ADA + ACC alignment 2024
- Earlier intervention paying off
- Tirzepatide weight + glycemic
Pediatric + Young Adult
- Family hx + lipid measurement age 9-11
- FH screening
- Lifestyle + statin (over 8 yo for FH)
Sex Differences
- Women: protective until menopause
- Microvascular more common
- Treatment thresholds similar but consider sex-specific risk enhancers (preeclampsia, early menopause)
Social Determinants of Health (SDOH)
- Income, education, access, food insecurity, housing
- Major CV risk modifiers
- PREVENT calculator integrates
Personalized Prevention
- Polygenic risk scores (emerging)
- Lp(a) testing
- CAC scoring
- Imaging-guided therapy
Pearls
- PCE / SCORE2 / PREVENT for risk assessment
- LDL target: very high < 55, high < 70, intermediate < 100
- Statin start ASCVD ⥠7.5%; high-intensity ⥠20%
- ASA primary prevention 2024: avoid ⥠70 yo (ASPREE)
- CAC for borderline / intermediate decisions
- SELECT (2023): semaglutide for obese + ASCVD â MACE
- CLEAR Outcomes (2023): bempedoic acid for statin-intolerant
- Lp(a) once in lifetime; aggressive other RF control
- Lifestyle: Mediterranean diet + 150 min/wk exercise + æèž + éé
+ æ§é
- Emerging: pelacarsen (Lp(a)), tirzepatide, polygenic risk scores
297.3.3.8 Social Determinants of Health (SDOH)