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.).
Arterioscler Thromb Vasc Biol. 2024 Oct;44(10):2244-2251. doi: 10.1161/ATVBAHA.124.321165. Epub 2024 Aug 15.
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.
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.
In the UK Biobank, ApoB was highly correlated with VLDL-C (r=0.70; <0.001) but weakly negatively correlated with HDL-C (r=-0.11; <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; <0.001). After adjusting for HDL-C, the ApoB residual remained similar in magnitude (HR, 1.10; <0.001), whereas the effect size of the VLDL-C residual was reduced (HR, 1.02; =0.029). The independent effect of HDL-C (after accounting for ApoB and VLDL-C) remained robust (HR, 0.86; <0.0001), while the independent effect of VLDL-C (after accounting for ApoB and HDL-C) was modest (HR, 1.02; =0.029). All results were consistent in the Framingham cohort.
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.
最近的观察性和孟德尔随机化分析报告称，VLDL-C（极低密度脂蛋白胆固醇）对风险的影响独立于 ApoB（载脂蛋白 B）。我们旨在确定 UK Biobank 和 Framingham Heart Study 队列中 VLDL-C 和 ApoB 与新发心血管事件风险的独立相关性。
我们纳入了 294289 名 UK Biobank 参与者，中位年龄 56 岁，42%为男性，2865 名 Framingham Heart Study 参与者（中位年龄 53 岁，47%为男性）。VLDL-C 回归 ApoB 后的残差表示 VLDL-C 中不能由 ApoB 解释的部分，而 ApoB 回归 VLDL-C 后的残差表示 ApoB 中不能由 VLDL-C 解释的部分。对于动脉粥样硬化性心血管疾病发病率的 Cox 比例风险模型，我们为残差 VLDL-C 和残差 ApoB 进行了构建。模型分析包括和不包括高密度脂蛋白胆固醇（HDL-C）。此外，我们在考虑 ApoB 和 HDL-C 后调查了 VLDL-C 的独立影响，以及在考虑 ApoB 和 VLDL-C 后调查了 HDL-C 的独立影响。
在 UK Biobank 中，ApoB 与 VLDL-C 高度相关（r=0.70；<0.001），但与 HDL-C 弱负相关（r=-0.11；<0.001）。ApoB 残差和 VLDL-C 残差与新发动脉粥样硬化性心血管疾病显著相关（危险比[HR]分别为 1.08 和 1.05；<0.001）。在调整 HDL-C 后，ApoB 残差的大小保持相似（HR，1.10；<0.001），而 VLDL-C 残差的效应大小减小（HR，1.02；=0.029）。HDL-C 的独立效应（在考虑 ApoB 和 VLDL-C 后）仍然稳健（HR，0.86；<0.0001），而 VLDL-C 的独立效应（在考虑 ApoB 和 HDL-C 后）则适中（HR，1.02；=0.029）。所有结果在 Framingham 队列中均一致。
当调整 HDL-C 时，VLDL-C 与心血管风险的关联不再具有临床意义。我们的残差不匹配分析表明，不能忽视对 HDL-C 的调整。
