{"title":"基于Friedewald公式计算的过量甘油三酯可能是生产大量极低密度脂蛋白的替代标记物,这是PROUD48研究的事后分析。","authors":"Tsutomu Hirano, Yasutaka Takeda, Ichiro Sakuma, Shinya Hiramitsu, Mizuho Okada, Shinichiro Ueda, Masaru Sakurai","doi":"10.5551/jat.65870","DOIUrl":null,"url":null,"abstract":"<p><strong>Aim: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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 changes in VLDL subfractions using lipid-lowering agents.</p><p><strong>Conclusions: </strong>The behavior of Ex-TG appears consistent with previous kinetic studies showing that omega-3FAs primarily suppress VLDL1 production, whereas fibrates promote TG removal, suggesting that Ex-TG serves as a surrogate marker for VLDL1 overproduction.</p>","PeriodicalId":15128,"journal":{"name":"Journal of atherosclerosis and thrombosis","volume":" ","pages":""},"PeriodicalIF":2.8000,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"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.\",\"authors\":\"Tsutomu Hirano, Yasutaka Takeda, Ichiro Sakuma, Shinya Hiramitsu, Mizuho Okada, Shinichiro Ueda, Masaru Sakurai\",\"doi\":\"10.5551/jat.65870\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Aim: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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 changes in VLDL subfractions using lipid-lowering agents.</p><p><strong>Conclusions: </strong>The behavior of Ex-TG appears consistent with previous kinetic studies showing that omega-3FAs primarily suppress VLDL1 production, whereas fibrates promote TG removal, suggesting that Ex-TG serves as a surrogate marker for VLDL1 overproduction.</p>\",\"PeriodicalId\":15128,\"journal\":{\"name\":\"Journal of atherosclerosis and thrombosis\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":2.8000,\"publicationDate\":\"2025-09-18\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of atherosclerosis and thrombosis\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.5551/jat.65870\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"PERIPHERAL VASCULAR DISEASE\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of atherosclerosis and thrombosis","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.5551/jat.65870","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PERIPHERAL VASCULAR DISEASE","Score":null,"Total":0}
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.
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 changes in VLDL subfractions using lipid-lowering agents.
Conclusions: The behavior of Ex-TG appears consistent with previous kinetic studies showing that omega-3FAs primarily suppress VLDL1 production, whereas fibrates promote TG removal, suggesting that Ex-TG serves as a surrogate marker for VLDL1 overproduction.