{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T18:14:12Z","timestamp":1787163252023,"version":"build-2736575974"},"reference-count":48,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>We included 294\u2005289 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      In the UK Biobank, ApoB was highly correlated with VLDL-C (r=0.70;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;0.001) but weakly negatively correlated with HDL-C (r=\u22120.11;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;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;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;0.001). After adjusting for HDL-C, the ApoB residual remained similar in magnitude (HR, 1.10;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;0.001), whereas the effect size of the VLDL-C residual was reduced (HR, 1.02;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.029). The independent effect of HDL-C (after accounting for ApoB and VLDL-C) remained robust (HR, 0.86;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;0.0001), while the independent effect of VLDL-C (after accounting for ApoB and HDL-C) was modest (HR, 1.02;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.029). All results were consistent in the Framingham cohort.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/atvbaha.124.321165","type":"journal-article","created":{"date-parts":[[2024,8,15]],"date-time":"2024-08-15T05:00:58Z","timestamp":1723698058000},"page":"2244-2251","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":14,"title":["Discordance Analysis of VLDL-C and ApoB in UK Biobank and Framingham Study: A Prospective Observational Study"],"prefix":"10.1161","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-8997-8178","authenticated-orcid":true,"given":"Selin","family":"Bilgic","sequence":"first","affiliation":[{"name":"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.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karol M.","family":"Pencina","sequence":"additional","affiliation":[{"name":"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.)."},{"name":"Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA (K.M.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1968-2641","authenticated-orcid":true,"given":"Michael J.","family":"Pencina","sequence":"additional","affiliation":[{"name":"Duke University School of Medicine, Biostatistics and Bioinformatics, Duke Clinical Research Institute, Durham, NC (M.J.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0278-4094","authenticated-orcid":true,"given":"Justine","family":"Cole","sequence":"additional","affiliation":[{"name":"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.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Line","family":"Dufresne","sequence":"additional","affiliation":[{"name":"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.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9930-7189","authenticated-orcid":true,"given":"George","family":"Thanassoulis","sequence":"additional","affiliation":[{"name":"Department of Medicine, Mike and 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