Elevated remnant cholesterol improves MI and IHD risk prediction
Elevated remnant cholesterol reclassifies risk of ischemic heart disease and myocardial infarction
Introduction and methods
Remnant cholesterol consists of the cholesterol content of triglyceride-rich VLDL, IDL and chylomicron remnants. Observational studies and Mendelian randomization studies have demonstrated robust associations of elevated remnant cholesterol levels with an increased risk of ischemic heart disease (IHD), including myocardial infarction (MI) [1-7]. In most guidelines, total cholesterol and HDL-c levels are included for predicting the 10-year risk of ischemic and atherosclerotic heart disease, but remnant cholesterol levels are not.
Aim of the study
The aim of this study was to determine whether adding remnant cholesterol to a risk model with conventional risk factors leads to better identification of individuals who later experience MI or IHD.
The researchers used data from 41,928 white Danish individuals who were enrolled in the Copenhagen General Population Study. The median follow-up time was 12 years (IQR: 10.7-13.5). At baseline, participants did not have IHD or diabetes and were not taking a statin. Nonfasting remnant cholesterol levels were calculated by subtracting LDL-c and HDL-c levels from total cholesterol levels. The researchers used a risk model with and without remnant cholesterol levels as a risk factor to predict the 10-year risk of MI and IHD. Conventional risk factors were age, sex, smoking, LDL-c levels and systolic blood pressure. Participants were divided into predefined 10-year risk categories: <5% and ≥5%, <7.5% and ≥7.5%, and <10% and ≥10%.
Based on predefined cut points for elevated remnant cholesterol levels, the researchers calculated the net reclassification improvement (NRI) for MI and IHD for each of the 10-year risk categories. IHD was defined as death from IHD, MI or coronary revascularization.
- For participants with remnant cholesterol levels ≥95th percentile (≥1.6 mmol/L, 61 mg/dL), 23% (P<0.001) of patients with MI and 21% (P<0.001) of patients with IHD were correctly reclassified estimating above or below 5% risk in 10 years when remnant cholesterol was added to a risk model with conventional risk factors; this resulted in an NRI of 10% (95%-CI: 1-20) for MI and 5% (95%-CI: 3-13) for IHD.
- For participants with remnant cholesterol levels ≥75th percentile (≥1.0 mmol/L, 37 mg/dL), 10% (P<0.001) of patients with MI and 8% (P<0.001) of patients with IHD were correctly reclassified from below to above 5% for 10-year risk when remnant cholesterol was added to a risk model with conventional risk factors; this resulted in an NRI of 4% (95%-CI: 1-6) for MI and 2% (95%-CI: -3-4) for IHD.
- For all 10-year risk categories combined (below to above 5%, 7.5% and 10-year risk), 42% (P<0.001) of patients with MI and 41% (P<0.001) of patients with IHD were correctly reclassified when remnant cholesterol was added to a risk model with conventional risk factors for remnant cholesterol levels ≥95th percentile; this resulted in an NRI of 20% (95%-CI: 9-31) for MI and 11% (95%-CI: 2-21) for IHD.
The results of this large-scale Danish population study suggest that adding remnant cholesterol to a risk model with conventional risk factors leads to a considerable improvement in MI and IHD risk prediction in individuals with elevated remnant cholesterol.