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Calculated Excess-Triglyceride Based on the Friedewald Formula is a Possible Surrogate Marker for the Production of Large Very-Low Density Lipoprotein, A Post-Hoc Analysis of the PROUD48 Study

Hirano T, Takeda Y, Sakuma I, Hiramitsu S, Okada M, Ueda S, Sakurai M

Journal of atherosclerosis and thrombosis, 2026

56 participants

Abstract

AIM: Overproduction of large very low-density lipoprotein1 (VLDL1) is a central abnormality in metabolic dyslipidemia. Excess-triglycerides (Ex-TG), based on the Friedewald equation, is considered to be a marker for TG-rich VLDL, but it remains uncertain whether Ex-TG reflects large VLDL particles.

METHODS: We conducted a retrospective sub-analysis of the PROUD48 study, which compared the effects of pemafibrate and omega-3 fatty acids (FAs) on apolipoprotein B48, with data available on VLDL subfractions. Hyperlipidemic patients on statins were treated with pemafibrate (n = 56) or omega-3FAs (n = 56) for 16 weeks. VLDL subfractions: large (L), middle (M), and small (S) were separated using high-performance liquid chromatography. Ex-TG was calculated as plasma TG minus 5 x calculated VLDL-cholesterol (C).Calculated VLDL=total-C minus directly measured LDL-C minus HDL-C.

RESULTS: Pemafibrate and omega-3FAs reduced plasma TG levels by 42% and 27%, respectively; however, a marked reduction in Ex-TG was observed only with omega-3 FAs. Ex-TG was positively correlated with L-VLDL-TG, %L-VLDL-TG, (L-M+S)-VLDL-TG, and L-VLDL-TG/C, while it showed no positive correlation with smaller VLDLs and apoB48. TG exhibited stronger correlations with L-VLDL-related parameters than Ex-TG, but was also positively associated with smaller VLDLs and apoB48. These correlation patterns remained consistent even when examining the relationship between changes in Ex-TG, TG, or apoB48 and corresponding…

How strong is the evidence?

Evidence Hub reads this as a secondary / pooled analysis, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 56 participants or records.

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