Remnant cholesterol is mainly composed of cholesterol content of very low-density lipoprotein (VLDL) and intermediate-density lipoprotein (IDL). Simply put, all cholesterol that is not HDL or LDL is remnant cholesterol and can be directly taken by macrophages and converts them to foam cells thus initiating and enhancing the atherosclerotic process.¹ Remnant cholesterol is simple to calculate by using the equation “total cholesterol minus LDL-cholesterol minus HDL-cholesterol” in a non-fasting state. A standard lipid profile is all that is required to measure remnant cholesterol. The LDL cholesterol has been traditionally known as the “bad” cholesterol, but remnant cholesterol is a very atherogenic cholesterol and high levels correlate with risk of major cardiovascular events.

For instance, in a person with total cholesterol 200 mg/dL, LDL cholesterol 147 mg/dL and HDL cholesterol 40 mg/dL, the remnant cholesterol would be 13 mg/dL. Remnant cholesterol value ≥30 is of great concern.

The risk of ischemic cardiovascular event in a person without a history of ischemic heart disease or diabetes or use of statin can be predicted better with the addition of remnant cholesterol to standard risk prediction models, according to a recent study published in the Journal of the American College of Cardiology.¹

For this study, researchers examined data from 41,928 individuals enrolled in the Copenhagen General Population Study. None of these participants had either ischemic cardiovascular disease or diabetes and they were also not taking statins at study entry. Their aim was to explore if addition of remnant cholesterol would enhance prediction of future risk of ischemic heart disease, myocardial infarction and coronary revascularization. The follow-up period was for 12 years (median). The national Danish Causes of Death Registry and national Danish Patient Registry were used to obtain data about diagnosis of MI, IHD and all hospitalizations. The covariates for adjustment were age, sex, smoking status, LDL cholesterol and systolic blood pressure. Researchers estimated the net reclassification index (NRI) from below to above 5%, 7.5%, and/or 10% 10-year occurrence of myocardial infarction and ischemic heart disease, which was defined as a composite of death from myocardial infarction, ischemic heart disease and coronary revascularization.

Results showed that addition of remnant cholesterol ≥95th percentile (≥1.6 mmol/L, 61 mg/dL) to models based on the traditional risk factors for ASCVD led to correct reclassification of 23% of those who later had an MI and 21% of those with ischemic heart disease from below to above 5% for 10-year occurrence. Addition of remnant cholesterol levels greater than the 75th percentile (≥1.0 mmol/L, 37 mg/dL) correctly reclassified 10% of those who had an MI and 8% for ischemic heart disease. There were no incorrectly reclassified cardiac events. When reclassifications were combined from below to above 5%, 7.5% and 10% risk of events, 42% of individuals with myocardial infarction and 41% with ischemic heart disease were reclassified appropriately yielding a NRI of 20% and 11%, respectively.

In this study, addition of elevated remnant cholesterol levels to standard risk prediction models correctly reclassified up to 40% of participants suggesting that incorporation of raised remnant cholesterol levels together with LDL cholesterol in risk stratification algorithms would significantly improve risk prediction of MI and IHD in persons without a history of ischemic cardiovascular disease and diabetes and statin use. Hence, clinicians should be aware of the significance of remnant cholesterol levels in detecting individuals at high risk of ischemic cardiovascular events and in whom statin therapy would be beneficial.

Reference

1. Varbo A, Freiberg JJ, Nordestgaard BG. Remnant cholesterol and myocardial infarction in normal weight, overweight, and obese individuals from the Copenhagen General Population Study. Clin Chem. 2018 Jan;64(1):219-230. doi: 10.1373/clinchem.2017.279463
2. Doi T, et al. Elevated remnant cholesterol reclassifies risk of ischemic heart disease and myocardial infarction. J Am Coll Cardiol. 2022 Jun 21;79(24):2383-2397. doi: 10.1016/j.jacc.2022.03.384.