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, LDLMartin and LDLSampson, on predicting atherosclerotic cardiovascular diseases (ASCVD) risk compared to traditional LDLFriedewald 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, LDLMartin and LDLSampson classified less individuals in this category than LDLFriedewald (p < 0.001), both had 20 individuals with ASCVD, versus 22 by LDLFriedewald. Positive CAC in the discussion-exempt group were over 38% higher (p < 0.001) when classified by LDLFriedewald than by LDLMartin or LDLSampson. Individuals with LDL-C>4.9 mmol/L are recommended to high-intensity statin therapy by the AHA/ACC guidelines. The LDLFriedewald>4.9 mmol/L group had 20 ASCVD events, versus 21 in LDLMartin and 22 in LDLSampson group. Conclusions: In a multi-ethnic USA population, LDLMartin and LDLSampson did not over- or under-estimate ASCVD risk compared to LDLFriedewald in primary prevention according to AHA/ACC guidelines, while LDLFriedewald under-estimated subclinical ASCVD risk in the low-risk population. These findings support the replacement of LDLFriedewald by LDLMartin or LDLSampson for lipid screen in the general population.