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Cardiology

HDL Cholesterol: Function Over Quantity

HDL (high-density lipoprotein) is called 'good' cholesterol, but the relationship is complex. Quality matters more than quantity—HDL function determines protection, not just the number.

Reference: > 60 mg/dL (protective), 40-60 mg/dL (normal), < 40 mg/dL (low - risk factor) mg/dL

Key Takeaway

HDL is your body's garbage truck for cholesterol—collecting excess from tissues and returning it to the liver. But having many trucks doesn't help if they're not working. Low HDL indicates risk, but raising HDL with medications doesn't reduce events—function matters more than quantityRader DJ, et al. 2019.

What is HDL Cholesterol?

High-density lipoprotein (HDL) is the smallest, densest lipoprotein particle. Unlike LDL which delivers cholesterol to tissues, HDL scavenges excess cholesterol from artery walls and transports it back to the liver for elimination—this process is called reverse cholesterol transportToth PP, et al. 2020.

Think of HDL as a cleanup crew. When plaques start forming in arteries, HDL particles extract cholesterol from the developing plaque and carry it away. More effective cleanup crews (better HDL function) protect against plaque accumulation.

Why HDL is Complicated

  • Low HDL: Clearly associated with increased cardiovascular riskRosenson RS, et al. 2022
  • High HDL: Not always protective—genetic variants can cause high HDL without benefitVoight BF, et al. 2012
  • Drug trials: Raising HDL pharmacologically doesn't reduce eventsBarter PJ, et al. 2021
  • Function matters: HDL quality (cholesterol efflux capacity) predicts risk better than HDL-CRader DJ, et al. 2019
  • High (> 60 mg/dL): Considered protective, associated with lower riskAHA, 2020
  • Normal (40-60 mg/dL): Typical range for most adults
  • Low (＜ 40 mg/dL men, ＜ 50 mg/dL women): Independent risk factor for heart diseaseRosenson RS, et al. 2022
  • Very low (＜ 30 mg/dL): Strong risk marker, often indicates metabolic dysfunction

The Low HDL Pattern

Low HDL rarely occurs in isolation—it's usually part of a metabolic patternRosenson RS, et al. 2022:

High HDL Isn't Always Good

Some people have genetically very high HDL (＞ 80-100 mg/dL) but still develop heart disease. Their HDL is plentiful but dysfunctional—like having many garbage trucks that don't actually pick up trashVoight BF, et al. 2012. SCARB1 mutations cause this pattern. This is why HDL function matters more than the number.

Factors That Affect HDL

Lower HDL:

  • Insulin resistance and metabolic syndromeRosenson RS, et al. 2022
  • High triglycerides (inverse relationship)
  • Sedentary lifestyle
  • Smoking
  • Obesity (especially abdominal)
  • Certain medications (beta-blockers, anabolic steroids, progestins)
  • Genetic factors (ApoA1 mutations)Khera AV, et al. 2017

Raise HDL:

  • Regular exercise (especially aerobic + resistance)
  • Weight loss
  • Smoking cessation
  • Moderate alcohol intake (but risks may outweigh benefits)
  • Healthy fats (olive oil, nuts, avocados)
  • Estrogen (premenopausal women have higher HDL)

The Cholesterol Ratios

HDL is often used in ratios to assess riskNLA, 2021:

  • Total Cholesterol:HDL: Target ＜ 4.0, optimal ＜ 3.5
  • LDL:HDL: Target ＜ 2.5, optimal ＜ 2.0
  • Triglyceride:HDL: Target ＜ 2.0 (strong marker of insulin resistance)

Related Testing

  • ApoA1: Main protein component of HDL
  • Triglycerides: Calculate TG:HDL ratio
  • hs-CRP: Inflammation can make HDL dysfunctional

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HDL Cholesterol: Function Over Quantity | Biomarker Guide