Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia (F.W., A.J.V., T.D., C.G.M.).
Baker Heart and Diabetes Institute, Melbourne, Australia (F.W., C.G.M.).
Circulation. 2024 Jan 16;149(3):217-226. doi: 10.1161/CIRCULATIONAHA.123.064296. Epub 2023 Nov 28.
Although low-density lipoprotein cholesterol (LDL-C) remains the primary cholesterol target in clinical practice in children and adults, non-high-density lipoprotein cholesterol (non-HDL-C) has been suggested as a more accurate measure of atherosclerotic cardiovascular disease (ASCVD) risk. We examined the associations of childhood non-HDL-C and LDL-C levels with adult ASCVD events and determined whether non-HDL-C has better utility than LDL-C in predicting adult ASCVD events.
This prospective cohort study included 21 126 participants from the i3C Consortium (International Childhood Cardiovascular Cohorts). Proportional hazards regressions were used to estimate the risk for incident fatal and fatal/nonfatal ASCVD events associated with childhood non-HDL-C and LDL-C levels (age- and sex-specific scores; concordant/discordant categories defined by guideline-recommended cutoffs), adjusted for sex, Black race, cohort, age at and calendar year of child measurement, body mass index, and systolic blood pressure. Predictive utility was determined by the C index.
After an average follow-up of 35 years, 153 fatal ASCVD events occurred in 21 126 participants (mean age at childhood visits, 11.9 years), and 352 fatal/nonfatal ASCVD events occurred in a subset of 11 296 participants who could be evaluated for this outcome. Childhood non-HDL-C and LDL-C levels were each associated with higher risk of fatal and fatal/nonfatal ASCVD events (hazard ratio ranged from 1.27 [95% CI, 1.14-1.41] to 1.35 [95% CI, 1.13-1.60] per unit increase in the risk factor score). Non-HDL-C had better discriminative utility than LDL-C (difference in C index, 0.0054 [95% CI, 0.0006-0.0102] and 0.0038 [95% CI, 0.0008-0.0068] for fatal and fatal/nonfatal events, respectively). The discordant group with elevated non-HDL-C and normal LDL-C had a higher risk of ASCVD events compared with the concordant group with normal non-HDL-C and LDL-C (fatal events: hazard ratio, 1.90 [95% CI, 0.98-3.70]; fatal/nonfatal events: hazard ratio, 1.94 [95% CI, 1.23-3.06]).
Childhood non-HDL-C and LDL-C levels are associated with ASCVD events in midlife. Non-HDL-C is better than LDL-C in predicting adult ASCVD events, particularly among individuals who had normal LDL-C but elevated non-HDL-C. These findings suggest that both non-HDL-C and LDL-C are useful in identifying children at higher risk of ASCVD events, but non-HDL-C may provide added prognostic information when it is discordantly higher than the corresponding LDL-C and has the practical advantage of being determined without a fasting sample.
虽然在儿童和成人的临床实践中，低密度脂蛋白胆固醇（LDL-C）仍然是胆固醇的主要目标，但非高密度脂蛋白胆固醇（non-HDL-C）已被认为是动脉粥样硬化性心血管疾病（ASCVD）风险的更准确衡量指标。我们研究了儿童时期的 non-HDL-C 和 LDL-C 水平与成人 ASCVD 事件之间的关联，并确定了 non-HDL-C 是否比 LDL-C 在预测成人 ASCVD 事件方面具有更好的效用。
这项前瞻性队列研究包括来自 i3C 联盟（国际儿童心血管队列）的 21126 名参与者。使用比例风险回归来估计与儿童期 non-HDL-C 和 LDL-C 水平相关的致命和致命/非致命 ASCVD 事件的风险（年龄和性别特异性评分；通过指南推荐的临界值定义一致/不一致类别），并根据性别、黑种人、队列、儿童测量时的年龄和日历年份、体重指数和收缩压进行调整。预测效用通过 C 指数确定。
在平均 35 年的随访后，21126 名参与者中发生了 153 例致命 ASCVD 事件（儿童就诊时的平均年龄为 11.9 岁），在能够评估该结局的 11296 名参与者的亚组中发生了 352 例致命/非致命 ASCVD 事件。儿童时期的 non-HDL-C 和 LDL-C 水平均与更高的致命和致命/非致命 ASCVD 事件风险相关（风险比范围为每单位风险因素评分增加 1.27[95%CI，1.14-1.41]至 1.35[95%CI，1.13-1.60]）。Non-HDL-C 比 LDL-C 具有更好的区分能力（致命事件的差异 C 指数为 0.0054[95%CI，0.0006-0.0102]和 0.0038[95%CI，0.0008-0.0068]；致命/非致命事件分别）。与正常 non-HDL-C 和 LDL-C 相比，non-HDL-C 升高且 LDL-C 正常的不一致组发生 ASCVD 事件的风险更高（致命事件：风险比，1.90[95%CI，0.98-3.70]；致命/非致命事件：风险比，1.94[95%CI，1.23-3.06]）。
儿童时期的 non-HDL-C 和 LDL-C 水平与中年的 ASCVD 事件相关。非-HDL-C 比 LDL-C 更能预测成人 ASCVD 事件，尤其是在 LDL-C 正常但 non-HDL-C 升高的个体中。这些发现表明，非-HDL-C 和 LDL-C 均可用于识别 ASCVD 事件风险较高的儿童，但当 non-HDL-C 与相应的 LDL-C 不一致且升高时，非-HDL-C 可能提供额外的预后信息，并且具有实用优势，因为它可以在不进行禁食样本的情况下确定。
