AUTHOR=Wolska Anna , Sampson Maureen , Zubirán Rafael , Meeusen Jeff W. , Donato Leslie J. , Jaffe Allan S. , Remaley Alan T. 

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

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=11

YEAR=2024

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2024.1452869

DOI=10.3389/fcvm.2024.1452869

ISSN=2297-055X

ABSTRACT=<sec><title>Background</title><p>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 (<italic>e</italic>LDL-TG) based on the standard lipid panel and to compare it to estimated LDL-C as an ASCVD risk biomarker.</p></sec><sec><title>Methods</title><p>Using least-square regression analysis, the following <italic>e</italic>LDL-TG equation was developed: <inline-formula><mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="IM1"><mml:mi>e</mml:mi><mml:mrow><mml:mi mathvariant="normal">LDL</mml:mi></mml:mrow><mml:mstyle displaystyle="false" scriptlevel="0"><mml:mtext>-</mml:mtext></mml:mstyle><mml:mrow><mml:mi mathvariant="normal">TG</mml:mi></mml:mrow><mml:mo>=</mml:mo><mml:mrow><mml:mfrac><mml:mrow><mml:mrow><mml:mi mathvariant="normal">TG</mml:mi></mml:mrow></mml:mrow><mml:mrow><mml:mn>38.5</mml:mn></mml:mrow></mml:mfrac></mml:mrow><mml:mo>+</mml:mo><mml:mrow><mml:mfrac><mml:mrow><mml:mrow><mml:mi mathvariant="normal">NonHDL</mml:mi></mml:mrow><mml:mstyle displaystyle="false" scriptlevel="0"><mml:mtext>-</mml:mtext></mml:mstyle><mml:mrow><mml:mi mathvariant="normal">C</mml:mi></mml:mrow></mml:mrow><mml:mrow><mml:mn>5.75</mml:mn></mml:mrow></mml:mfrac></mml:mrow><mml:mo>+</mml:mo><mml:mrow><mml:mfrac><mml:mrow><mml:mn>9</mml:mn><mml:mrow><mml:mn>.75</mml:mn><mml:mspace width="0.25em" /><mml:mi mathvariant="normal">TG</mml:mi></mml:mrow></mml:mrow><mml:mrow><mml:mrow><mml:mi mathvariant="normal">NonHDL</mml:mi></mml:mrow><mml:mstyle displaystyle="false" scriptlevel="0"><mml:mtext>-</mml:mtext></mml:mstyle><mml:mrow><mml:mi mathvariant="normal">C</mml:mi></mml:mrow></mml:mrow></mml:mfrac></mml:mrow><mml:mo>+</mml:mo><mml:mrow><mml:mfrac><mml:mn>244</mml:mn><mml:mrow><mml:mrow><mml:mi mathvariant="normal">HDL</mml:mi></mml:mrow><mml:mstyle displaystyle="false" scriptlevel="0"><mml:mtext>-</mml:mtext></mml:mstyle><mml:mrow><mml:mi mathvariant="normal">C</mml:mi></mml:mrow></mml:mrow></mml:mfrac></mml:mrow><mml:mo>−</mml:mo><mml:mn>2.95</mml:mn></mml:math></inline-formula>. LDL-TG was measured by the <italic>β</italic>-quantification (BQ) reference method (<italic>N</italic> = 40,202). LDL-C was calculated by the Sampson-NIH equation. The association of LDL-C and <italic>e</italic>LDL-TG with ASCVD risk markers was performed in the National Heart and Nutrition Examination Survey (NHANES) (<italic>N</italic> = 37,053) and with ASCVD events in a primary prevention cohort from the UK Biobank (UKB) (<italic>N</italic> = 429,367) and the Atherosclerosis Risk in Communities (ARIC) study (<italic>N</italic> = 14,632).</p></sec><sec><title>Results</title><p><italic>e</italic>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 <italic>e</italic>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 <italic>e</italic>LDL-TG had a similar risk as the high LDL-C/high <italic>e</italic>LDL-TG group. Furthermore, these same two groups with the highest <italic>e</italic>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 <italic>e</italic>LDL-TG groups. Using <italic>e</italic>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 <italic>e</italic>LDL-TG as a risk-enhancer test leads to reclassification of 50% more high-risk individuals than current lipid-enhancer test rules.</p></sec><sec><title>Conclusions</title><p>Like LDL-C, LDL-TG can also be calculated from the results of the standard lipid panel. Compared to estimated LDL-C, <italic>e</italic>LDL-TG was a better risk marker for primary prevention and hence could improve initial ASCVD risk stratification.</p></sec>