The Impact of Low-Density Lipoprotein Equation Changes on Cholesterol Treatment in Canada

BACKGROUND: In cardiovascular disease prevention, low-density lipoprotein cholesterol (LDL-C) values guide treatment for lowering cholesterol level. After 50 years of clinical laboratories using the Friedewald LDL-C equation, the Canadian Society of Clinical Chemists recently recommended adoption of the new and more accurate Sampson / U.S. National Institutes of Health (NIH) LDL-C equation. Here, we estimate the anticipated population-level impact of this equation change. METHODS: We compared lipid profiles from the Canadian Health Measures Survey (CHMS) year 2019 to those from the National Health and Nutrition Examination Survey (NHANES) years 2017 to 2020. Then, based on 10,828 participants in the latter, we calculated the impact of changing the LDL-C equation from the Friedewald to the Sampson. RESULTS: Sampson- and Friedewald-equation LDL-C values are strongly correlated (r = 0.99, P < 0.001), but differences between them increase with both higher triglyceride and lower LDL-C values. We evaluated the impact of these discordances using LDL-C treatment thresholds from the 2021 Canadian Cardiovascular Society lipid guidelines. Among patients who take cholesterol-lowering medications, the Sampson equation reclassifies 3.3% more patients (95% confidence interval 2.2% to 4.9%), or about 123,000 individuals, as meeting the criteria for treatment intensification. CONCLUSION: Although changing the LDL-C equation used from the Friedewald to the Sampson affects only a small proportion of the population, an estimated 123,000 Canadians who are taking cholesterol-lowering medications may need to intensify treatment to lower their cholesterol level, due to small absolute changes around guideline threshold values of LDL-C.