What does this research mean for the field?

An equation estimating low-density lipoprotein-triglyceride (eLDL-TG) from a standard lipid panel provides better atherosclerotic cardiovascular disease risk stratification for primary prevention than estimated LDL-C. Novelty: ClaimNovelty.METHODOLOGICAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

October 25, 2024Open Access

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

Structured PICO

Does estimated LDL-TG improve ASCVD risk stratification compared to estimated LDL-C in primary prevention populations?

Population

Primary prevention cohorts including participants from the UK Biobank (N=429,367, analyzed N=271,760 without lipid-lowering meds), Atherosclerosis Risk in Communities (ARIC) study (N=14,632), National Health and Nutrition Examination Survey (NHANES) (N=37,053), and a dataset for equation development (N=40,202).

Intervention

Estimated LDL-TG (eLDL-TG) calculated using a novel equation based on standard lipid panel results (TG, NonHDL-C, HDL-C).

Comparator

Estimated LDL-C (calculated by the Sampson-NIH equation) and other conventional lipid markers.

Outcome

Atherosclerotic cardiovascular disease (ASCVD) events (fatal and non-fatal myocardial infarction and stroke).hard clinical

Estimated LDL-TG calculated from a standard lipid panel is a superior ASCVD risk marker compared to estimated LDL-C for primary prevention and can improve initial risk stratification.

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 ( e 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 e LDL-TG equation was developed: eLDL-TG=TG38.5+NonHDL-C5.75+9.75TGNonHDL-C+244HDL-C−2.95 . LDL-TG was measured by the β -quantification (BQ) reference method ( N = 40,202). LDL-C was calculated by the Sampson-NIH equation. The association of LDL-C and e LDL-TG with ASCVD risk markers was performed in the National Heart and Nutrition Examination Survey (NHANES) ( N = 37,053) and with ASCVD events in a primary prevention cohort from the UK Biobank (UKB) ( N = 429,367) and the Atherosclerosis Risk in Communities (ARIC) study ( N = 14,632). Results e 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 e 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 e LDL-TG had a similar risk as the high LDL-C/high e LDL-TG group. Furthermore, these same two groups with the highest e 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 e LDL-TG groups. Using e 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 e 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, e LDL-TG was a better risk marker for primary prevention and hence could improve initial ASCVD risk stratification.

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