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    HDL-C
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    HDL-C

    HDL cholesterol: reverse cholesterol transport, risk thresholds for men and women, why very high HDL is not always protective.

    HDL cholesterol (HDL-C) is the cholesterol carried in high-density lipoproteins, the smallest and densest lipoprotein particles. HDL takes part in reverse cholesterol transport: it collects excess cholesterol from cells, including macrophages in artery walls, and returns it to the liver for excretion in bile. Low HDL-C is a well-established marker of increased cardiovascular risk. However, raising HDL-C with medicines has not been shown to prevent heart attacks, and extremely high values are not always protective.

    Lipid profileReverse cholesterol transportCardiovascular risk
    Men — increased risk< 1.0 mmol/L (40 mg/dL)
    Women — increased risk< 1.2 mmol/L (45–50 mg/dL)
    Typical healthy range1.0–2.0 mmol/L
    Very high> 2.3–2.5 mmol/L — no added benefit
    Lipoprotein classes from largest to smallest: chylomicrons, VLDL, IDL, LDL and HDL, with their size, main lipid cargo and role in atherosclerosis Blood lipoproteins (not to scale) Chylo-VLDLIDLLDLHDL 75–1200 nm30–80 nm25–35 nm18–25 nm5–12 nm dietary TGliver TGTG + cholesterolmostly cholesterolcholesterol, protein remnants atherogenicatherogenicatherogenicmain atherogenicreverse transport apoB-100 on VLDL, IDL, LDL apoA-I on HDL ← larger, lighter, more triglyceride smaller, denser, more protein →
    Figure 1. HDL is the smallest lipoprotein. Unlike the apoB-containing particles, it carries apolipoprotein A-I and transports cholesterol back to the liver.

    What lowers HDL-C

    • Insulin resistance and type 2 diabetes, abdominal obesity, metabolic syndrome — often together with high triglycerides
    • Smoking, physical inactivity, a very high-carbohydrate diet
    • Medicines: anabolic steroids, some progestins, beta-blockers (modestly)
    • Inflammation, chronic kidney disease, rare genetic disorders (Tangier disease, apoA-I or LCAT deficiency)

    What raises HDL-C

    Regular aerobic exercise, weight loss and stopping smoking raise HDL-C modestly. Moderate alcohol intake also raises it, but this is not a reason to drink. Oestrogens raise HDL-C, which partly explains higher values in women.

    Is higher always better?

    Population studies show a U-shaped relation: risk is higher with low HDL-C, but also not reduced, and possibly increased, at very high levels (above about 2.3–2.5 mmol/L). Genetic studies and trials of HDL-raising drugs (niacin, CETP inhibitors) did not reduce cardiovascular events. For this reason HDL-C is used to estimate risk, but not as a treatment target. Its function, the ability to remove cholesterol, matters more than the measured amount.

    Derived indices

    HDL-C is used to calculate non-HDL cholesterol (TC − HDL-C, an estimate of all atherogenic particles), the atherogenic coefficient (TC − HDL-C) / HDL-C, and the atherogenic index of plasma log(TG/HDL-C).

    What to do

    Low HDL-C is a signal to address the whole metabolic picture: weight, physical activity, blood glucose, triglycerides and smoking. Your doctor will include HDL-C when estimating your overall cardiovascular risk.

    References

    1. Mach F, Baigent C, Catapano AL, et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J. 2020;41(1):111–188. doi:10.1093/eurheartj/ehz455
    2. Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol. Circulation. 2019;139(25):e1082–e1143. doi:10.1161/CIR.0000000000000625

    This article is for general information and does not replace a consultation with a doctor. Laboratory results must be interpreted by a physician together with symptoms and other tests.

    Published on 1 July 2019