Performance of novel low-density lipoprotein-cholesterol calculation methods in predicting clinical and subclinical atherosclerotic cardiovascular disease risk: The Multi-Ethnic Study of Atherosclerosis

Background and aims: This study examined the performance of two novel low-density lipoprotein-cholesterol (LDL-C) calculations, LDL_Martin and LDL_Sampson, on predicting atherosclerotic cardiovascular diseases (ASCVD) risk compared to traditional LDL_Friedewald according to the 2018 American Heart Association/American College of Cardiology (AHA/ACC) primary prevention guidelines. Methods: A total of 6701 randomly recruited Multi-Ethnic Study of Atherosclerosis (MESA) participants free of ASCVD at baseline were followed for ASCVD during a median of 13.9 years and for subclinical ASCVD-coronary artery calcium (CAC) during a median of 12.5 years. Prevalence of borderline high triglyceride (≥1.7 mmol/L) was 15.2% and was at 13.5% for high triglyceride (≥2.3 mmol/L). Results: Applying the criteria of LDL-C<1.8 mmol/L in 40–75 year olds without diabetes mellitus to be exempt from risk discussion, LDL_Martin and LDL_Sampson classified less individuals in this category than LDL_Friedewald (p < 0.001), both had 20 individuals with ASCVD, versus 22 by LDL_Friedewald. Positive CAC in the discussion-exempt group were over 38% higher (p < 0.001) when classified by LDL_Friedewald than by LDL_Martin or LDL_Sampson. Individuals with LDL-C≥4.9 mmol/L are recommended to high-intensity statin therapy by the AHA/ACC guidelines. The LDL_Friedewald≥4.9 mmol/L group had 20 ASCVD events, versus 21 in LDL_Martin and 22 in LDL_Sampson group. Conclusions: In a multi-ethnic USA population, LDL_Martin and LDL_Sampson did not over- or under-estimate ASCVD risk compared to LDL_Friedewald in primary prevention according to AHA/ACC guidelines, while LDL_Friedewald under-estimated subclinical ASCVD risk in the low-risk population. These findings support the replacement of LDL_Friedewald by LDL_Martin or LDL_Sampson for lipid screen in the general population.