An equation for estimating low-density lipoprotein-triglyceride content and its use for cardiovascular disease risk stratification.

Background: The triglyceride (TG) content of low-density lipoprotein (LDL-TG) has been shown to be more predictive of atherosclerotic cardiovascular disease (ASCVD) events than the cholesterol content of LDL (LDL-C). The goal of our study was to develop an equation for estimating LDL-TG (LDL-TG) based on the standard lipid panel and to compare it to estimated LDL-C as an ASCVD risk biomarker.

Methods: Using least-square regression analysis, the following LDL-TG equation was developed: . LDL-TG was measured by the -quantification (BQ) reference method ( = 40,202). LDL-C was calculated by the Sampson-NIH equation. The association of LDL-C and LDL-TG with ASCVD risk markers was performed in the National Heart and Nutrition Examination Survey (NHANES) ( = 37,053) and with ASCVD events in a primary prevention cohort from the UK Biobank (UKB) ( = 429,367) and the Atherosclerosis Risk in Communities (ARIC) study ( = 14,632).

Results: LDL-TG showed better ASCVD risk stratification of UKB participants than LDL-C (Wilcoxon Chi-Square: 2,099.6 vs. 418.7, respectively). Receiving-operating characteristics analysis revealed that LDL-TG had a stronger association with ASCVD events than LDL-C (AUC: 0.596 vs. 0.542, respectively) and other conventional lipid markers. Similar findings were found in ARIC. Discordance analysis in UKB showed that the group with low LDL-C/high LDL-TG had a similar risk as the high LDL-C/high LDL-TG group. Furthermore, these same two groups with the highest LDL-TG levels and the highest ASCVD event rate also had higher mean levels of systolic blood pressure, Body Mass Index, hemoglobin A1C, and C-reactive protein than the two lower LDL-TG groups. Using LDL-TG > 44.6 mg/dl (80th percentile) as a cut-point leads to a hazard ratio of 1.32 (95% CI, 1.29-1.36) for ASCVD events, which remained significant after adjustment for LDL-C and apoB. Furthemore, using LDL-TG as a risk-enhancer test leads to reclassification of 50% more high-risk individuals than current lipid-enhancer test rules.

Conclusions: Like LDL-C, LDL-TG can also be calculated from the results of the standard lipid panel. Compared to estimated LDL-C, LDL-TG was a better risk marker for primary prevention and hence could improve initial ASCVD risk stratification.