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Remnant Cholesterol Improves CVD Risk Prediction

The accuracy of cardiovascular risk prediction is crucial for primary prevention. On July 13, a new paper was published online in the Journal of the American College of Cardiology, which suggests that adding remnant cholesterol to guideline prediction models should improve the identification of individuals who would benefit the most from statin treatment for the primary prevention of heart disease. Remnant cholesterol includes the cholesterol content of the triglyceride-rich very-low-density lipoproteins, intermediate-density lipoproteins, and chylomicron remnants. Despite the limited availability of remnant cholesterol measurements in routine practice, it can be calculated from a standard lipid profile in the nonfasting state as total cholesterol minus LDL-cholesterol minus HDL-cholesterol.

The researchers analyzed data from the Copenhagen General Population Study, which recruited individuals from the White Danish general population from 2003-2015 and followed them until 2018. Information on lifestyle, health, and medication, including statin therapy, was obtained through a questionnaire, and participants underwent physical examinations and had nonfasting blood samples drawn for biochemical measurements. For the current study, they included 41,928 individuals aged 40-100 years enrolled before 2009 without a history of ischemic cardiovascular disease, diabetes, and statin use at baseline. The median follow-up time was 12 years. Information on diagnoses of MI and ischemic heart disease was collected from the national Danish Causes of Death Registry and all hospital admissions and diagnoses entered in the national Danish Patient Registry.

During the first 10 years of follow-up there were 1063 MIs and 1460 ischemic heart disease events (death of ischemic heart disease, nonfatal MI, and coronary revascularization). For individuals with remnant cholesterol levels ≥95th percentile (≥1.6 mmol/L, 61 mg/dL), 23% (P < 0.001) of myocardial infarction and 21% (P < 0.001) of ischemic heart disease were reclassified correctly from below to above 5% for 10-year occurrence when remnant cholesterol levels were added to models based on conventional risk factors, whereas no events were reclassified incorrectly. Consequently, the addition of remnant cholesterol levels yielded NRI of 10% (95% CI: 1%-20%) for myocardial infarction and 5% (95% CI: −3% to 13%) for ischemic heart disease. Correspondingly, when reclassifications were combined from below to above 5%, 7.5%, and 10% risk of events, 42% (P < 0.001) of individuals with myocardial infarction and 41% (P < 0.001) with ischemic heart disease were reclassified appropriately, leading to NRI of respectively 20% (95% CI: 9%-31%) and 11% (95% CI: 2%-21%).

Reference: https://www.jacc.org/doi/abs/10.1016/j.jacc.2022.03.384

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