Abstract
Low-density lipoprotein cholesterol (LDL-C) is typically estimated by the Friedewald equation to guide atherosclerotic cardiovascular disease (ASCVD) management despite its flaws. Martin-Hopkins and Sampson-NIH equations were shown to outperform Friedewald's in various populations. Our aim was to derive a novel equation for accurate LDL-C estimation in Saudi Arabians and to compare it to Friedewald, Martin-Hopkins and Sampson-NIH equations. This is a cross-sectional study on 2245 subjects who were allocated to 2 cohorts; a derivation (1) and a validation cohort (2). Cohort 1 was analyzed in a multiple regression model to derive an equation (equation(D)) for estimating LDL-C. The agreement between the measured (LDL-C(DM)) and calculated levels was tested by Bland-Altman analysis, and the biases by absolute error values. Validation of the derived equation was carried out across LDL-C and triglyceride (TG)-stratified groups. The mean LDL-C(DM) was 3.10 ± 1.07 and 3.09 ± 1.06 mmol/L in cohorts 1 and 2, respectively. The derived equation is: LDL-C(D) = 0.224 + (TC × 0.919) - (HDL-C × 0.904) - (TG × 0.236) - (age × 0.001) - 0.024. In cohort 2, the mean LDL-C (mmol/L) was estimated as 3.09 ± 1.06 by equation(D), 2.85 ± 1.12 by Friedewald, 2.95 ± 1.09 by Martin-Hopkins, and 2.93 ± 1.11 by Sampson-NIH equations; statistically significant differences between direct and calculated LDL-C was observed with the later three equations (P < 0.001). Bland-Altman analysis showed the lowest bias (0.001 mmol/L) with equation(D) as compared to 0.24, 0.15, and 0.17 mmol/L with Friedewald, Martin-Hopkins, and Sampson-NIH equations, respectively. The absolute errors in all guideline-stratified LDL-C categories was the lowest with equation(D), which also showed the best classifier of LDL-C according to guidelines. Moreover, equation(D) predicted LDL-C levels with the lowest error with TG levels up to 5.63 mmol/L. Equation(D) topped the other equations in estimating LDL-C in Saudi Arabians as it could permit better estimation when LDL-C is < 2.4 mmol/L, in familial hyperlipidemia, and in hypertriglyceridemia, which improves cardiovascular outcomes in high-risk patients. We recommend further research to validate equation(D) in a larger dataset and in other populations.