目标:尽管越来越多的证据表明载脂蛋白B(apoB)是动脉粥样硬化性心血管疾病(ASCVD)风险的最准确标记,它在临床实践中的采用一直很低。这项研究试图确定低密度脂蛋白胆固醇(LDL-C)非高密度脂蛋白胆固醇(HDL-C),和甘油三酯足以进行常规心血管护理。
方法:对293876名英国生物库成年人(年龄:40-73岁,42%的男性),没有心血管疾病,纳入新发ASCVD的中位随访时间为11年.apoB在预定LDL-C水平的分布,非HDL-C,用图形检查甘油三酯,和10年ASCVD事件发生率比较高与低apoB.apoB在LDL-C上的回归后,构建apoB的残差,非HDL-C,和对数变换的甘油三酯,并在针对标准风险因素调整后的新发ASCVD的比例风险回归模型中用作预测因子,包括HDL-C。
结果:ApoB与LDL-C和非HDL-C高度相关(Pearson\'sr=.96,P<.001),但与对数甘油三酯(r=.42,P<.001)的相关性较小。然而,在预定的LDL-C水平下捕获所有观测值的95%所需的apoB范围,非HDL-C,或者甘油三酯很宽,当LDL-C130mg/dL时,跨度为85.8-108.8md/dL,88.3-112.4mg/dL当非HDL-C160mg/dL时,当甘油三酯为115mg/dL时,为67.8-147.4md/dL。在这些水平(±10mg/dL),apoB高于平均值+1SD的10年ASCVD率与低于平均值-1标准差为7.3vs.LDL-C为4.0,6.4vs.4.6对于非HDL-C,和7.0vs.甘油三酯为4.6(所有P<.001)。随着19982例新发ASCVD事件的随访,在调整后的模型中,在考虑LDL-C和HDL-C后,残留的apoB仍然具有统计学意义(风险比1.06,95%置信区间1.0-1.07),在考虑非HDL-C和HDL-C后(风险比1.04,95%置信区间1.03-1.06),并在考虑甘油三酯和HDL-C后(风险比1.13,95%置信区间1.12-1.15)。没有LDL-C的残差,非HDL-C,当模型中包含apoB时,甘油三酯的对数或对数保持显著。
结论:apoB在LDL-C个体水平上的高变异性,非HDL-C,和甘油三酯加上10年ASCVD率的有意义的差异和apoB中包含的用于预测新发ASCVD事件的显著残留信息表明LDL-C,非HDL-C,在临床护理中,甘油三酯并不是apoB的足够代理。
OBJECTIVE: Despite growing evidence that apolipoprotein B (
apoB) is the most accurate marker of atherosclerotic cardiovascular disease (ASCVD) risk, its adoption in clinical practice has been low. This investigation sought to determine whether low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (HDL-C), and triglycerides are sufficient for routine cardiovascular care.
METHODS: A sample of 293 876 UK Biobank adults (age: 40-73 years, 42% men), free of cardiovascular disease, with a median follow-up for new-onset ASCVD of 11 years was included. Distribution of apoB at pre-specified levels of LDL-C, non-HDL-C, and triglycerides was examined graphically, and 10-year ASCVD event rates were compared for high vs. low
apoB. Residuals of
apoB were constructed after regressing
apoB on LDL-C, non-HDL-C, and log-transformed triglycerides and used as predictors in a proportional hazards regression model for new-onset ASCVD adjusted for standard risk factors, including HDL-C.
RESULTS: ApoB was highly correlated with LDL-C and non-HDL-C (Pearson\'s r = .96, P < .001 for both) but less so with log triglycerides (r = .42, P < .001). However, apoB ranges necessary to capture 95% of all observations at pre-specified levels of LDL-C, non-HDL-C, or triglycerides were wide, spanning 85.8-108.8 md/dL when LDL-C 130 mg/dL, 88.3-112.4 mg/dL when non-HDL-C 160 mg/dL, and 67.8-147.4 md/dL when triglycerides 115 mg/dL. At these levels (±10 mg/dL), 10-year ASCVD rates for
apoB above mean + 1 SD vs. below mean - 1 SD were 7.3 vs. 4.0 for LDL-C, 6.4 vs. 4.6 for non-HDL-C, and 7.0 vs. 4.6 for triglycerides (all P < .001). With 19 982 new-onset ASCVD events on follow-up, in the adjusted model, residual apoB remained statistically significant after accounting for LDL-C and HDL-C (hazard ratio 1.06, 95% confidence interval 1.0-1.07), after accounting for non-HDL-C and HDL-C (hazard ratio 1.04, 95% confidence interval 1.03-1.06), and after accounting for triglycerides and HDL-C (hazard ratio 1.13, 95% confidence interval 1.12-1.15). None of the residuals of LDL-C, non-HDL-C, or of log triglycerides remained significant when apoB was included in the model.
CONCLUSIONS: High variability of apoB at individual levels of LDL-C, non-HDL-C, and triglycerides coupled with meaningful differences in 10-year ASCVD rates and significant residual information contained in apoB for prediction of new-onset ASCVD events demonstrate that LDL-C, non-HDL-C, and triglycerides are not adequate proxies for apoB in clinical care.