HDL Cholesterol (HDL-C)

•Meta-analysis— Causality undermined by MR studies

What it measures

HDL particles transport cholesterol from peripheral tissues back to the liver (reverse cholesterol transport). HDL-C reports the cholesterol mass these particles carry.

The shifting interpretation

For decades, raising HDL was a target. Two lines of evidence reshaped this:

1. CETP inhibitors (anacetrapib, evacetrapib) raised HDL dramatically — most failed to reduce cardiovascular events.
2. Mendelian randomisation (Voight 2012): genetic variants that isolate HDL changes did not alter MI risk, contrary to LDL.

Current view: HDL is a marker of overall metabolic and lifestyle state, not an independent therapeutic target.

When low HDL still matters

• It tracks insulin resistance and metabolic syndrome.
• Very low HDL often coincides with high apoB and triglycerides — the underlying cardiometabolic disorder is what to treat.

Very high HDL

Cohort data (CANHEART, others) suggest a U-shape: HDL above ~100 mg/dL associates with slightly higher mortality. Don’t chase ever-higher HDL.

Related entries

Triglycerides, TG/HDL ratio, ApoB, Cardiovascular disease.