Discordance Analysis of VLDL-C and ApoB in UK Biobank and Framingham Study: A Prospective Observational Study.

Autor:	Bilgic S; Department of Medicine, Mike and Valeria Rosenbloom Centre for Cardiovascular Prevention, McGill University Health Centre, Montreal, Quebec, Canada (S.B., K.M.P., J.C., L.D., G.T., A.D.S.)., Pencina KM; Department of Medicine, Mike and Valeria Rosenbloom Centre for Cardiovascular Prevention, McGill University Health Centre, Montreal, Quebec, Canada (S.B., K.M.P., J.C., L.D., G.T., A.D.S.).; Brigham and Women's Hospital, Harvard Medical School, Boston, MA (K.M.P.)., Pencina MJ; Duke University School of Medicine, Biostatistics and Bioinformatics, Duke Clinical Research Institute, Durham, NC (M.J.P.)., Cole J; Department of Medicine, Mike and Valeria Rosenbloom Centre for Cardiovascular Prevention, McGill University Health Centre, Montreal, Quebec, Canada (S.B., K.M.P., J.C., L.D., G.T., A.D.S.)., Dufresne L; Department of Medicine, Mike and Valeria Rosenbloom Centre for Cardiovascular Prevention, McGill University Health Centre, Montreal, Quebec, Canada (S.B., K.M.P., J.C., L.D., G.T., A.D.S.)., Thanassoulis G; Department of Medicine, Mike and Valeria Rosenbloom Centre for Cardiovascular Prevention, McGill University Health Centre, Montreal, Quebec, Canada (S.B., K.M.P., J.C., L.D., G.T., A.D.S.)., Sniderman AD; Department of Medicine, Mike and Valeria Rosenbloom Centre for Cardiovascular Prevention, McGill University Health Centre, Montreal, Quebec, Canada (S.B., K.M.P., J.C., L.D., G.T., A.D.S.).
Jazyk:	angličtina
Zdroj:	Arteriosclerosis, thrombosis, and vascular biology [Arterioscler Thromb Vasc Biol] 2024 Oct; Vol. 44 (10), pp. 2244-2251. Date of Electronic Publication: 2024 Aug 15.
DOI:	10.1161/ATVBAHA.124.321165
Abstrakt:	Background: Recent observational and Mendelian randomization analyses have reported significant effects of VLDL-C (very-low density lipoprotein cholesterol) on risk that is independent of ApoB (apolipoprotein B). We aim to determine the independent association of VLDL-C and ApoB with the risk of new onset cardiovascular events in the UK Biobank and Framingham Heart Study cohorts. Methods: We included 294 289 UK Biobank participants with a median age of 56 years, 42% men, and 2865 Framingham Heart Study participants (median age, 53 years; 47% men). The residual resulting from regressing VLDL-C on ApoB expresses the portion of VLDL-C not explained by ApoB, while the residual from regressing ApoB on VLDL-C expresses the portion of ApoB not explained by VLDL-C. Cox proportional hazards models for atherosclerotic cardiovascular disease incidence were created for residual VLDL-C and residual ApoB. Models were analyzed with and without high-density lipoprotein cholesterol (HDL-C). Furthermore, we investigated the independent effects of VLDL-C after accounting for ApoB and HDL-C and of HDL-C after accounting for ApoB and VLDL-C. Results: In the UK Biobank, ApoB was highly correlated with VLDL-C (r=0.70; P <0.001) but weakly negatively correlated with HDL-C (r=-0.11; P <0.001). The ApoB residual and the VLDL-C residual were significantly associated with new-onset atherosclerotic cardiovascular disease (hazard ratio [HR], 1.08 and 1.05, respectively; P <0.001). After adjusting for HDL-C, the ApoB residual remained similar in magnitude (HR, 1.10; P <0.001), whereas the effect size of the VLDL-C residual was reduced (HR, 1.02; P =0.029). The independent effect of HDL-C (after accounting for ApoB and VLDL-C) remained robust (HR, 0.86; P <0.0001), while the independent effect of VLDL-C (after accounting for ApoB and HDL-C) was modest (HR, 1.02; P =0.029). All results were consistent in the Framingham cohort. Conclusions: When adjusted for HDL-C, the association of VLDL-C with cardiovascular risk was no longer clinically meaningful. Our residual discordance analysis suggests that adjustment for HDL-C cannot be ignored. Competing Interests: M.J. Pencina reports funding from the nonprofit Doggone Foundation, consulting fees from Cleerly, Inc, and advisory board fees from Eli Lilly and Janssen. K.M. Pencina reports funding from the nonprofit Doggone Foundation. G. Thanassoulis has participated in advisory boards or speaker bureaus for Amgen, Regeneron/Sanofi, HLS Therapeutics, Ionis, Servier, and Novartis and has received grant funding from Servier and Ionis. The other authors report no conflicts.
Databáze:	MEDLINE
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