LONDON, Nov 26: Cholesterol, long classified simply as “good” or “bad,” is now understood to be far more complex, with scientists identifying multiple types of lipoproteins that influence cardiovascular risk in different ways.

Traditionally, low-density lipoproteins (LDLs) were considered harmful, contributing to arterial plaque formation, while high-density lipoproteins (HDLs) were deemed protective. Public-health guidance has focused on reducing LDL through diet and medications such as statins and increasing HDL through exercise and healthy eating.

Recent research, however, shows that standard cholesterol measures fail to capture the riskiest forms of LDL. Lipoprotein(a), or Lp(a), a modified LDL particle carrying apolipoprotein(a), is linked to a significantly higher risk of premature heart disease. Remnant particles, the leftovers of larger lipoproteins like chylomicrons, carry several times more cholesterol per particle than standard LDLs and may be up to four times more likely to trigger heart disease.

Scientists are also re-evaluating HDL. Once universally considered protective, very high levels of HDL have been associated with increased mortality and a range of health conditions, including diabetes, non-alcoholic fatty liver disease, chronic kidney disease, Alzheimer’s, age-related macular degeneration, and some cancers. Dysfunctional HDL particles, possibly carrying abnormal proteins, may contribute to these risks.

Cholesterol remains an essential molecule in the body, critical for cell membranes, nerve insulation, and hormone production. Problems arise when lipoprotein systems fail, causing cholesterol to accumulate in arterial walls, forming plaques that can rupture and trigger heart attacks or strokes.

Medical experts are now focusing on measuring the number of potentially harmful lipoprotein particles rather than just cholesterol content. Apolipoprotein-B (ApoB), present on each LDL-like particle, is emerging as a better predictor of cardiovascular risk. The European Society of Cardiology has endorsed ApoB testing, though it is not yet widely used in routine checkups. Studies indicate that 20-30% of people may have high ApoB despite normal LDL levels, leaving them falsely reassured by standard tests.

Researchers are also examining the complex roles of HDL proteins, which can fight inflammation, reduce blood clots, and support immune responses. Some 280 proteins have been identified on HDL particles, but identifying the ones linked to dysfunction remains challenging.

The evolving understanding of cholesterol highlights a diverse “lipoprotein ecosystem” where some particles are more harmful than others. Experts say this emerging science could transform how heart disease risk is assessed and treated, and may pave the way for new therapies targeting high-risk lipoproteins such as Lp(a).

“This is a rapidly developing field,” researchers said. “Untangling the lipoprotein ecosystem is challenging, but promises to improve cardiovascular health assessment and intervention.”