This HDL-C test measures cholesterol cargo, not HDL function, i.e. how well HDL particles remove cholesterol from cells, carry it toward the liver, and provide anti-inflammatory or antioxidant effects.
Metabolic pattern: insulin resistance, high triglycerides, excess adiposity, type 2 diabetes, and low physical activity commonly lower HDL-C, especially when triglycerides are elevated.
Lifestyle and inflammation: cigarette smoking, acute or chronic inflammation, severe illness, malnutrition or malabsorption, liver disease, kidney disease, and hyperthyroidism can reduce HDL-C or impair HDL function.
Medications and genetics: androgens, progestins, anabolic steroids, some beta blockers, thiazide diuretics, and rare disorders such as apoA-I deficiency or Tangier disease can cause very low values.
Genetics and alcohol: familial high HDL, CETP-related variants, and higher alcohol intake can raise HDL-C; very high HDL-C does not necessarily mean better HDL function.
Hormonal and inflammatory: hypothyroidism, menopause-related changes, chronic inflammation, infection, and some liver or biliary disorders can be associated with high or dysfunctional HDL.
Less common: endurance training, medications, or markedly elevated HDL-C above about 100 mg/dL should be interpreted with apoB, triglycerides, liver enzymes, thyroid status, and family history.
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