What is remnant cholesterol?

Remnant cholesterol refers to the cholesterol content within triglyceride-rich lipoproteins (TRLs) in the bloodstream after the removal of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol. And therefore commonly measured: Total cholesterol - LDL - HDL.

It encompasses very-low-density lipoproteins (VLDL) and intermediate-density lipoproteins (IDL), as well as chylomicron remnants.

Many publications suggest that remnant particles are atherogenic (leading to plaque formation in your arteries), can cross the endothelial barrier and get trapped in the intima of the arterial wall. (1)

Varbo et al. suggested a significant genetic association between remnant cholesterol and ischemic heart disease: “A nonfasting remnant cholesterol increase of 1 mmol/l (39 mg/dl) is associated with a 2.8-fold causal risk for ischemic heart disease, independent of reduced HDL cholesterol.“ (2)

In a prospective study of the Danish general population Langsted et al. found reducing remnant cholesterol levels by 32 mg/dl (or 0.83 mmol/l) could decrease recurrent major adverse cardiovascular events (MACE) by 20%. (3)

Furthermore, the study by Duran et al. found that remnant cholesterol was strongly associated with future myocardial infarction and peripheral artery disease events. (4)

A Chinese study involving 409 patients indicated that remnant cholesterol is an independent predictor of coronary heart disease. (5)

Remnant cholesterol vs LDL

Many publications indicate that remnant cholesterol may be a much more significant "predictor" of future cardiac events than any other commonly used marker, including the still popular total cholesterol and especially LDL.

In a study involving 17,532 participants elevated remnant cholesterol levels were associated with atherosclerotic cardiovascular disease (ASCVD) independent of traditional risk factors, LDL-C, and apoB levels. (6)

Different study concluded: “Increased concentrations of both calculated and measured remnant cholesterol were associated with increased all-cause mortality in patients with ischemic heart disease, which was not the case for increased concentrations of measured LDL cholesterol.” (7)

In a study on patients with stable coronary artery disease (CAD) who had on-statin LDL-C levels over 70 mg/dL Fujihara et al. found that higher remnant lipoprotein levels were a residual risk factor for future cardiovascular events. (8)

Similarly, Liyao Fu et al. concluded remnant cholesterol levels are associated with major adverse cardiovascular events in patients with type 2 diabetes, regardless of LDL-C levels. (9)

Spanish researchers found that regardless of whether LDL cholesterol levels were above or below 100 mg/dL, individuals with fasting remnant cholesterol (VLDL-C levels exceeding 30 mg/dL or 0.77 mmol/L) were identified as having a higher risk of significant cardiovascular events. (10)

There is little consistency in the health world, but most scientists agree that inflammation plays a primary role in atherosclerosis. For example, according to a 2023 review by researchers Evgenii Gusev and Alexey Sarapultsev, the inflammatory processes in atherosclerosis, from especially its initiation to the formation of atheroma, is closely related and shares many common mechanisms with low-grade inflammation, as well as with productive inflammation of the classical type. (11) This is relevant to the following:

“Furthermore, genetically increased remnant cholesterol was also associated with low-grade inflammation, whereas genetically increased LDL cholesterol was not (6)” (12)

Researchers concluded: “Even after reducing LDL cholesterol below recommended concentrations, there is still a substantial residual risk of cardiovascular disease. There might therefore be a need to look beyond LDL cholesterol reduction to reduce this residual risk, possibly by lowering nonfasting remnant cholesterol concentrations.”

Remnant cholesterol usually correlates with another good marker of heart health, TG/HDL ratio, see "TG/HDL | Calculator."

Bottom line

Association between remnant cholesterol and cardiac events surpasses that of traditional lipid profiles. Based on the above-mentioned studies and the fact that traditional lipid tests (TC, LDL, etc.) often do not correlate with remnant cholesterol, it can be concluded that health-conscious people as well as patients should be informed about it more often by professionals, which can protect against the misdiagnosis that the problem is there although in fact it is not, or that it is not there because traditional lipid tests are in the "normal range" although in fact it is.