Wang Jing, Kartiosuo Noora, Raitakari Olli, Viikari Jorma, Juonala Markus, Bazzano Lydia, Sinaiko Alan R, Steinberger Julia, Daniels Stephen R, Venn Alison, Magnussen Costan, Woo Jessica G, Ramakrishnan Rema, Urbina Elaine M, Kähönen Mika, Jacobs David R, Dwyer Terence
Murdoch Children's Research Institute, The Royal Children's Hospital, Parkville, Victoria, Australia.
Department of Paediatrics, The University of Melbourne, Parkville, Victoria, Australia.
Eur J Prev Cardiol. 2025 Mar 5. doi: 10.1093/eurjpc/zwaf117.
The role of adult HDL-C in atherosclerotic cardiovascular disease (ASCVD) faces challenges from Mendelian randomisations and drug trials. However, the association between childhood HDL-C and its changes and adult ASCVD remains undefined. This study aimed to determine this association.
Participants: Children in the International Childhood Cardiovascular Cohort (i3C) Consortium with childhood HDL-C and adult ASCVD follow-up. Age- and sex-standardized HDL-C z-scores were calculated for childhood (3-19 years), early childhood (3-11 years), and adolescence (12-19 years); Low HDL-C defined as <1.03mmol/L; Participants classified as consistently normal, low-to-normal, normal-to-low, and consistently low based on HDL-C status at early childhood and adolescence. ASCVD events: Identified using self-reports adjudicated by medical records or death registries. Analysis: Cox proportional hazards models quantified the associations between childhood HDL-C and adult ASCVD.
The study included 38,589 participants (49.7% males, mean age in 2016: 46.4 years) with 779 ASCVD and 784 imputed ASCVD events. After adjusting for sex, cohort, age and HDL-C measurement year, higher HDL-C z-scores in childhood, early childhood and adolescence were associated with lower adult ASCVD risk (HRs: 0.81-0.82), with the lowest risk at HDL-C >1.50mmol/L. Normal-to-low (HR 1.38, 95%CI 1.04-1.82) and consistently low (HR 1.94, 95%CI 1.45-2.63) childhood HDL-C increased adult ASCVD risk compared to consistently normal HDL-C. Adjusting for BMI and triglycerides weakened these associations.
Childhood and adolescent HDL-C were prospectively and inversely associated with adult ASCVD, suggesting that low HDL-C could be a risk maker of adult ASCVD. Future replications, mechanistic studies and Mendelian randomisations on childhood HDL-C may clarify its causal effects on adult ASCVD.
成人高密度脂蛋白胆固醇（HDL-C）在动脉粥样硬化性心血管疾病（ASCVD）中的作用面临孟德尔随机化研究和药物试验的挑战。然而，儿童期HDL-C及其变化与成人ASCVD之间的关联仍不明确。本研究旨在确定这种关联。
参与者：国际儿童心血管队列（i3C）联盟中具有儿童期HDL-C和成人ASCVD随访数据的儿童。计算儿童期（3 - 19岁）、幼儿期（3 - 11岁）和青春期（12 - 19岁）年龄和性别标准化的HDL-C z评分；低HDL-C定义为<1.03mmol/L；根据幼儿期和青春期的HDL-C状态，参与者分为持续正常、低到正常、正常到低和持续低四类。ASCVD事件：通过病历或死亡登记处判定的自我报告来确定。分析：Cox比例风险模型量化儿童期HDL-C与成人ASCVD之间的关联。
该研究纳入了38589名参与者（49.7%为男性，2016年平均年龄：46.4岁），有779例ASCVD事件和784例推定的ASCVD事件。在调整性别、队列、年龄和HDL-C测量年份后，儿童期、幼儿期和青春期较高的HDL-C z评分与较低的成人ASCVD风险相关（风险比：0.81 - 0.82），HDL-C>1.50mmol/L时风险最低。与持续正常的HDL-C相比，儿童期正常到低（风险比1.38，95%置信区间1.04 - 1.82）和持续低（风险比1.94，95%置信区间1.45 - 2.63）的HDL-C增加了成人ASCVD风险。调整体重指数和甘油三酯后，这些关联减弱。
儿童期和青春期的HDL-C与成人ASCVD呈前瞻性负相关，表明低HDL-C可能是成人ASCVD的一个风险指标。未来对儿童期HDL-C进行重复研究、机制研究和孟德尔随机化研究可能会阐明其对成人ASCVD的因果效应。
