BACKGROUND: Traditional beta-quantification of plasma lipoproteins by ultracentrifugation separates triglyceride-rich lipoproteins (TGRL) from higher density lipoproteins. The cholesterol in the TGRL fraction is referred to as measured very low-density lipoprotein cholesterol (VLDL-C) recognizing that other TGRL may be present. The measured VLDL-C to total plasma triglyceride (VLDL-C/TG) has long been considered an index of average TGRL composition with abnormally high VLDL-C/TG ratios (>or=0.30 with TG>150mg/dL) indicative of atherogenic remnant accumulation (type III hyperlipidemia). However, virtually no reports are available which examine potential associations between CAD and VLDL-C/TG at the lower end of the spectrum. METHODS AND RESULTS: We performed ultracentrifugation in 1170 cases with premature-onset, familial CAD and 1759 population-based controls and examined the VLDL-C/TG ratio as an index of TGRL composition. As expected, we found very high CAD risk associated with severe type III hyperlipidemia (OR 10.5, p=0.02). Unexpectedly, however, we found a robust, graded, and independent association between CAD risk and lower than average VLDL-C/TG ratios (p<0.0001 as ordered categories or as a continuous variable). Among those in the lowest VLDL-C/TG category (a ratio <0.12), CAD risk was clearly increased (OR 4.5, 95% CI 2.9-6.9) and remained significantly elevated in various subgroups including those with triglycerides below 200mg/dl, in males and females separately, as well as among those with no traditional CAD risk factors (OR 5.8, 95% CI 1.5-22). Significant compositional differences by case status were confirmed in a subset whose samples were re-spun with measurement of lipids and apolipoprotein B (apo B) in each subfraction. CONCLUSIONS: We found a strong, graded, independent, and robust association between CAD and lower VLDL-C/TG ratios. We consider this a novel, hypothesis-generating observation which will hopefully generate additional future studies to provide confirmation and further insight into potential mechanisms.
BACKGROUND: Traditional beta-quantification of plasma lipoproteins by ultracentrifugation separates triglyceride-rich lipoproteins (TGRL) from higher density lipoproteins. The cholesterol in the TGRL fraction is referred to as measured very low-density lipoprotein cholesterol (VLDL-C) recognizing that other TGRL may be present. The measured VLDL-C to total plasma triglyceride (VLDL-C/TG) has long been considered an index of average TGRL composition with abnormally high VLDL-C/TG ratios (>or=0.30 with TG>150mg/dL) indicative of atherogenic remnant accumulation (type III hyperlipidemia). However, virtually no reports are available which examine potential associations between CAD and VLDL-C/TG at the lower end of the spectrum. METHODS AND RESULTS: We performed ultracentrifugation in 1170 cases with premature-onset, familial CAD and 1759 population-based controls and examined the VLDL-C/TG ratio as an index of TGRL composition. As expected, we found very high CAD risk associated with severe type III hyperlipidemia (OR 10.5, p=0.02). Unexpectedly, however, we found a robust, graded, and independent association between CAD risk and lower than average VLDL-C/TG ratios (p<0.0001 as ordered categories or as a continuous variable). Among those in the lowest VLDL-C/TG category (a ratio <0.12), CAD risk was clearly increased (OR 4.5, 95% CI 2.9-6.9) and remained significantly elevated in various subgroups including those with triglycerides below 200mg/dl, in males and females separately, as well as among those with no traditional CAD risk factors (OR 5.8, 95% CI 1.5-22). Significant compositional differences by case status were confirmed in a subset whose samples were re-spun with measurement of lipids and apolipoprotein B (apo B) in each subfraction. CONCLUSIONS: We found a strong, graded, independent, and robust association between CAD and lower VLDL-C/TG ratios. We consider this a novel, hypothesis-generating observation which will hopefully generate additional future studies to provide confirmation and further insight into potential mechanisms.
Authors: K Hirano; S Yamashita; N Nakajima; T Arai; T Maruyama; Y Yoshida; M Ishigami; N Sakai; K Kameda-Takemura; Y Matsuzawa Journal: Arterioscler Thromb Vasc Biol Date: 1997-06 Impact factor: 8.311
Authors: O D Williams; S Stinnett; L E Chambless; K E Boyle; P S Bachorik; J J Albers; K Lippel Journal: Circulation Date: 1986-01 Impact factor: 29.690
Authors: Susanna E Borggreve; Hans L Hillege; Geesje M Dallinga-Thie; Paul E de Jong; Bruce H R Wolffenbuttel; Diederik E Grobbee; Arie van Tol; Robin P F Dullaart Journal: Eur Heart J Date: 2007-04-04 Impact factor: 29.983
Authors: André J Tremblay; Hugo Morrissette; Jean-Marc Gagné; Jean Bergeron; Claude Gagné; Patrick Couture Journal: Clin Biochem Date: 2004-09 Impact factor: 3.281
Authors: Annelise M Poss; J Alan Maschek; James E Cox; Benedikt J Hauner; Paul N Hopkins; Steven C Hunt; William L Holland; Scott A Summers; Mary C Playdon Journal: J Clin Invest Date: 2020-03-02 Impact factor: 14.808
Authors: Britt E Heidemann; Charlotte Koopal; Alexis Baass; Joep C Defesche; Linda Zuurbier; Monique T Mulder; Jeanine E Roeters van Lennep; Niels P Riksen; Christopher Boot; A David Marais; Frank L J Visseren Journal: Clin Genet Date: 2022-08-22 Impact factor: 4.296