🫀 Mirza's Cardiology Notes

Hyperlipidemia

5 min read

Approach to Hyperlipidemia

  1. Rule out secondary causes
  2. Assess risk: Ask 3 Questions
    1. Do you have ASCVD? 2. ASCVD is defined as any CAD/angina, TIA, PAD, aortic aneurysm (all of atherosclerotic origin), or any artery revascularization. 3. 📝 CAC is not included as an ASCVD category
  3. Discuss lifestyle & options
  4. Initiate treatment & monitor
flowchart TD
    A[Is ASCVD present?] --> |Yes| B("Secondary Prevention\nGoal LDL < 55 (very high risk) or < 70")
    A --> |No| C(Primary Prevention)
    C --> D[Is LDL ≥ 190 mg/dL?]
    D --> |Yes| E([Familial Hyperlipidemia\nGoal LDL < 55/70])
    D --> |No| F[Is DM Present?]
    F --> |Yes| G([T1DM or T2DM\nGoal LDL < 55/70/100])
    F --> |No| H([No DM\nGoal LDL < 55/70/100])

flowchart TD
    A[Primary Prevention\n no DM] --> B["AHA/ACC ASCVD Risk\nEstimator Plus\n(40-75 yo)"]
    B --> |"High (≥ 20%)"| C([High-intensity Statin])
    B --> |"Intermediate (7.5-<20%)"| E(["Evaluate 'Risk-Enhancers'\nIf +: moderate statin"])
    E --> H["If uncertain, check CAC"]
    B --> |"Borderline (5-<7.5%)"| F(["Evaluate 'Risk-Enhancers'\nIf +: moderate statin (IIb)"])
    B --> |"Low (≤5%)"| G([Lifestyle Mod])

Very High Risk ASCVD

  • Very High Risk ASCVD is if patient has had ≥ 2 ASCVD events or (1 Event + ≥ 2 Conditions)
    • Events
      • Recent ACS (<12 mo)
      • MI (other than above)
      • Ischemic stroke
      • PAD (Claudication w/ ABI <0.85, or revascularization or amputation)
    • Conditions
      • Figure source: 1

‘Risk Enhancers’

  • Diabetes “Risk Enhancers” → if present, LDL goal < 70; if not present, then LDL goal < 100
    • Duration:
      • T2DM for 10 years
      • T1DM for 20 years
    • Ur Albumin ≥30 mcg/mg Creat
    • eGFR <60 ml/min/1.73 m2
    • Diabetic retinopathy
    • Diabetic neuropathy
    • ABI <0.9
  • Primary Prevention ‘Risk Enhancers’
    • History and Co-morbidities (Think Inflammation)
      • Fam Hx premature ASCVD
      • Ethnicity (eg, South Asian ancestry)
      • CKD
      • Metabolic Syndrome
      • Conditions specific to women (eg, Pre-eclampsia, premature menopause)
      • Inflammatory diseases (esp Rh Arthritis, psoriasis, HIV)
    • Lipids/Biomarkers
      • LDL-C ≥ 160
      • Persistently elevated TG ≥175
    • Other
      • hsCRP ≥ 2.0
      • ABI < 0.9
      • Lp(a) >50 mg/dL or 125 nmol/L
      • ApoB > 130 mg/dL
        • especially if TG > 200

Secondary Causes of HLD Commonly Encountered

Secondary CauseElevated LDL-CElevated TG
DietSaturated fat or keto, weight gain, anorexiaWeight gain, very low-fat diet, high refined carbs, excess alcohol
DrugsDiuretics, Amiodarone, retinoic acid (even topical), glucocorticoids, cyclosporineBeta-blockers (except carvedilol), thiazides, anabolic steroids, retinoic acid, oral estrogens, glucocorticoids, protease inhibitors, sirolimus, raloxifene, tamoxifen
DiseasesBiliary obstruction, Nephrotic syndromeNephrotic syndrome, chronic renal failure, lipodystrophies
Disorders of metabolismLow T4, obesity, pregnancyDM (poorly controlled), Low T4, obesity, pregnancy

LDL Goals

Figure source: 2

Lifestyle Modifications

  • Daily physical activity
  • Weight management
  • Diet: reduced intake of saturated fats (to <7% of total calories), trans fatty acids (to <1% of total calories), and cholesterol (to <200 mg/d)
  • Moderate- or high-intensity statin

Pharmacotherapy

  • Statins
  • Ezetimibe
  • PCSK9 Inhibitors
  • Bempedoic Acid
  • Inclisiran
  • Omega-3
  • Fibrates
  • Others
    • Bile Acid Sequestrants (colestipol and colesevelam)
      • Limited use due to low efficacy, significant drug interactions, pill burden
    • Evinacumab
      • mAb that inhibits ANGPTL3 to promote VLDL processing and clearance upstream from LDL formation.
      • Monthly IV infusion administered by healthcare professional.
      • Only approved for HoFH although has shown benefit for other causes of hyperlipidemia
      • Robust LDL-C lowering - ~50%
    • Lomitapide
      • Inhibits synthesis of chylomicrons and VLDL, resulting in ↓ LDL-C
      • Daily tablet only approved for HoFH.
      • Robust LDL-C lowering - ~40-50%.
      • Hepatotoxicity concern - requires REMS program. Significant drug interactions

High Intensity Statins

  • Rosuvastatin 20-40 & Atorvastatin 40-80 mg
  • Maximally tolerated statin still the foundation
  • ↓ LDL-C ~50%
  • Can get creative to identify “maximally tolerated” to manage intolerance
    • Symmetric myalgias in large proximal muscle groups may indicate true statin intolerance; RARE
      • SAMSON trial - 90% of muscle symptoms attributed to “nocebo effect”
    • Rule out/correct other causes of muscle symptoms: hypothyroidism, vitamin D deficiency, exercise
    • Hydrophilic statins potentially less muscle symptoms (rosuvastatin, pravastatin)
    • Up to 90% of initially intolerant do fine with re-challenge
      • Allow 2-4 week wash out

Variability in individual response to statins

Statin-Intolerance

  1. Try 2-3 different daily Statins and allow a 1 mo washout between each of them
  2. Try less than daily statin (e.g. 1x/week, every other day, etc.)
    1. Kopecky likes to do rosuvastatin 1x/week → ↑ LDL receptors will improve the efficacy of Ezetimibe, PCKS9i
  3. Start Ezetimibe
  4. Add PCSK9 Inhibitors if high-risk
  5. Add Bempedoic Acid if not high-risk

Primary Prevention

Secondary Prevention

Footnotes

  1. Lloyd-Jones, D. M., Morris, P. B., Ballantyne, C. M., Birtcher, K. K., Covington, A. M., DePalma, S. M., Minissian, M. B., Orringer, C. E., Smith, S. C., Waring, A. A., & Wilkins, J. T. (2022). 2022 ACC Expert Consensus Decision Pathway on the Role of Nonstatin Therapies for LDL-Cholesterol Lowering in the Management of Atherosclerotic Cardiovascular Disease Risk. Journal of the American College of Cardiology, 80(14), 1366–1418. https://doi.org/10.1016/j.jacc.2022.07.006 ↩

  2. LDL Cholesterol Management Simplified in (Adults) - Lower for Longer is Better: Guidance from the National Lipid Association. Jackson, Elizabeth J. et al. ↩

Graph View

Backlinks