HDL-C and heart disease
High-density lipoproteins (HDL) are particles that carry cholesterol in the blood stream. Low levels of HDL cholesterol (HDL-C; a marker of HDL levels) in the blood has long been recognized as a risk factor for cardiovascular disease (CVD).[1] As a result, HDL is commonly known as "good cholesterol". However, it's increasingly clear that HDL-C is not inherently good or bad.
Studies testing whether higher HDL lowers the risk heart disease have, by and large, failed to find a benefit. Whether HDL is raised by medication (e.g., CEPT inhibitors, high-dose niacin)[2] or genetic differences,[3] the results are similar — no apparent effect on CVD risk.
One explanation for this apparent paradox is that HDL has no role in heart disease and low HDL is merely a marker of disease and unhealthy habits. This is certainly possible, since HDL is lowered by insulin resistance (the cause of type 2 diabetes)[4] and physical inactivity,[5] among other things.
Alternatively, it's possible that what's actually important is HDL functionality, rather than merely HDL levels. According to this hypothesis, some HDL particles have protective effects (e.g., removing cholesterol from arteries), whereas some HDL particles may actually have harmful effects (e.g., promoting inflammation).[6] As a result, increasing HDL-C levels won't reduce the risk of CVD unless it reliably increases the protective functions of HDL particles. However, there is currently much uncertainty regarding these supposedly protective properties of HDL (e.g., how to measure them and how to target them).