HDL-C
High-density lipoprotein cholesterol — involved in reverse cholesterol transport from arteries back to the liver.
Optimal Range
> 50 mg/dL (men) · > 60 mg/dL (women)
Risk-Stratified Targets
| Population / Context | Target |
|---|---|
| Low (increased risk) | < 40 mg/dL (men) · < 50 mg/dL (women) |
| Desirable | 40–60 mg/dL (men) · 50–70 mg/dL (women) |
| Optimal | > 50 mg/dL (men) · > 60 mg/dL (women) |
| Potentially paradoxicalMay indicate HDL dysfunction; warrants investigation | > 90 mg/dL |
Why It Matters
HDL helps remove cholesterol from arterial walls. However, extremely high HDL (>90 mg/dL) may paradoxically indicate dysfunction and does not always confer additional cardiovascular protection.
Understanding HDL-C
HDL cholesterol has long been called 'good cholesterol' for its role in reverse cholesterol transport — the process of picking up excess cholesterol from arterial walls and returning it to the liver for disposal. Epidemiologically, higher HDL-C levels correlate with lower cardiovascular risk across dozens of large population studies.
However, our understanding of HDL has evolved considerably. Drugs that raise HDL-C (such as niacin and CETP inhibitors) have consistently failed to reduce cardiovascular events in clinical trials, challenging the notion that simply raising the number is beneficial. Current thinking emphasizes HDL function over HDL quantity — specifically, how efficiently your HDL particles perform cholesterol efflux. This functional capacity is not captured by standard HDL-C measurement.
Paradoxically, very high HDL-C levels (above 90 mg/dL) have been associated with increased cardiovascular and all-cause mortality in some studies. This may reflect dysfunctional HDL particles that are elevated in number but impaired in their protective function. For clinical purposes, HDL-C is best interpreted in context with other lipid markers — the triglyceride-to-HDL ratio, for example, is a useful surrogate marker for insulin resistance and small dense LDL.
Key Research
Extreme high high-density lipoprotein cholesterol is paradoxically associated with high mortality in men and women
Madsen CM et al. · Eur Heart J (2017)
Key finding: U-shaped relationship between HDL-C and mortality, with increased risk at both very low and very high levels.
Cholesterol Efflux Capacity, High-Density Lipoprotein Function, and Atherosclerosis
Khera AV et al. · N Engl J Med (2011)
Key finding: HDL cholesterol efflux capacity was inversely associated with coronary disease independent of HDL-C levels, supporting function over quantity.