Abstract

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 (<i>e</i>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 <i>e</i>LDL-TG equation was developed: <math xmlns="http://www.w3.org/1998/Math/MathML"><mi>e</mi> <mrow><mi>LDL</mi></mrow> <mstyle><mtext>-</mtext></mstyle> <mrow><mi>TG</mi></mrow> <mo>=</mo> <mrow> <mfrac> <mrow><mrow><mi>TG</mi></mrow> </mrow> <mrow><mn>38.5</mn></mrow> </mfrac> </mrow> <mo>+</mo> <mrow> <mfrac> <mrow><mrow><mi>NonHDL</mi></mrow> <mstyle><mtext>-</mtext></mstyle> <mrow><mi>C</mi></mrow> </mrow> <mrow><mn>5.75</mn></mrow> </mfrac> </mrow> <mo>+</mo> <mrow> <mfrac><mrow><mn>9</mn> <mrow><mn>.75</mn> <mspace></mspace> <mi>TG</mi></mrow> </mrow> <mrow><mrow><mi>NonHDL</mi></mrow> <mstyle><mtext>-</mtext></mstyle> <mrow><mi>C</mi></mrow> </mrow> </mfrac> </mrow> <mo>+</mo> <mrow><mfrac><mn>244</mn> <mrow><mrow><mi>HDL</mi></mrow> <mstyle><mtext>-</mtext></mstyle> <mrow><mi>C</mi></mrow> </mrow> </mfrac> </mrow> <mo>-</mo> <mn>2.95</mn></math> . LDL-TG was measured by the <i>β</i>-quantification (BQ) reference method (<i>N</i> = 40,202). LDL-C was calculated by the Sampson-NIH equation. The association of LDL-C and <i>e</i>LDL-TG with ASCVD risk markers was performed in the National Heart and Nutrition Examination Survey (NHANES) (<i>N</i> = 37,053) and with ASCVD events in a primary prevention cohort from the UK Biobank (UKB) (<i>N</i> = 429,367) and the Atherosclerosis Risk in Communities (ARIC) study (<i>N</i> = 14,632). RESULTS: <i>e</i>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 <i>e</i>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 <i>e</i>LDL-TG had a similar risk as the high LDL-C/high <i>e</i>LDL-TG group. Furthermore, these same two groups with the highest <i>e</i>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 <i>e</i>LDL-TG groups. Using <i>e</i>LDL-TG &gt; 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 <i>e</i>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, <i>e</i>LDL-TG was a better risk marker for primary prevention and hence could improve initial ASCVD risk stratification.