Atherosclerosis

• HTN/inflammation ➔ endothelial dysfunction

• Monocyte & lymphocyte invade compromised vessel

• Platelets adhere to damaged ➔ inflammatory cytokines & platelet derived growth factor (PDGF)

• PDGF ➔ migration and proliferation of smooth muscle cells ➔ fibroblasts differentiate into myofibroblasts

• Macrophages, SMCs ingest cholesterol (oxidized LDL) ➔ lipid filled macrophages (foam cells) ➔ fatty streaks (atherosclerotic lesions)

• Extracellular matrix with collagen ➔ fibrous plaque (atheroma)

• Macrophages secrete matrix metalloproteinases ➔ break down fibrous cap

• Intima calcified

• Stress ➔ fibrous cap rupture ➔ exposure of thrombogenic material

• Thrombus ➔ occlusion of vessel

SSX

• Premature atherosclerosis likely has genetic source

  • CAD, aortic stenosis, PAD in young and seemingly healthy pt

• Xanthoma: nodular lipid deposits in skin/tendon

  • Histology: Foam cells and multinucleated histiocytes (Touton giant cells)

• Xanthelasma: yellow plaques on medial upper eyelid

• Severe hypertriglyceridemia

  • Pancreatitis (pain radiating to back)

  • Lipemia retinalis (white vessels on fundo exam)

DX

Screening

• Get lipid profile on new, young pts if they weren't screened as a child

  • Make sure familial lipid disorder isn't present

• Get lipid profile if > 20yo without ASCVD but have family hx

• Start lipid screening at 35yo in low risk

Starting Statin

• Start statin if any manifestation of atherosclerotic cardiovascular disease

  • Stroke, MI/angina/HF, PAD, aortic atherosclerosis, thoracic or abdominal aortic aneurysm

• Start statin if 40 - 75yo and diabetic (regardless of ASCVD risk)

  • Aim for LDL of 70

• Start statin immediately if LDL ≥190

  • Initiate statin, aggressive lifestyle modifications, genetic screening

• If LDL < 190:

  • 20 - 39yo with↑ CVD risk (HTN, smoking, ↑ BMI / ↓ SPA, family hx of CHD)

    • Informal CVD risk estimate to determine statin initiation

  • 40 - 75yo

    • Formal ASCVD risk assessment (10 year and lifetime risk) - 10 year risk > 7.5% ➔ start statin

Who wouldn't get a statin?

• 40-75yo with LDL < 70 and ASCVD risk < 7.5%

  • Can confirm that this ridiculously healthy pt with no RF doesn't need statin by coronary artery calcium (CAC) score of 0

  • CAC score 1-99 ➔ statin

• Pregnant or breastfeeding

• Liver disease

• Taking amiodarone or protease inhibitors (HIV)

• Addicted to grapefruit juice (like more than a cup a day) or crossfit