The association of childhood HDL cholesterol with atherosclerotic cardiovascular disease events in adults: findings from the International Childhood Cardiovascular Cohort Consortium

The role of adult HDL-C in atherosclerotic cardiovascular disease (ASCVD) faces challenges from Mendelian randomizations 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 <1.03 mmol/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 [hazard ratio (HR): 0.81–0.82], with the lowest risk at HDL-C > 1.50 mmol/L. Normal to low [HR 1.38, 95% confidence intervaI (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 body mass index 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 marker of adult ASCVD. Future replications, mechanistic studies, and Mendelian randomizations on childhood HDL-C may clarify its causal effects on adult ASCVD.

We examined the association between childhood HDL-C measurement and adult atherosclerotic cardiovascular disease (ASCVD) at follow-up in data from the International Childhood Cardiovascular Cohort (i3C) Consortium.

Higher HDL-C levels in childhood were associated with lower risk of a ASCVD event, irrespective of age (early childhood vs. adolescence). The lowest risk was observed at HDL-C concentrations of around and above 1.50 mmol/L (58 mg/dL). A decrease in HDL-C from early childhood to adolescence was associated with an increased risk of adult ASCVD.

When additionally adjusted for body mass index z-score, attenuated associations were noted. Adding triglycerides to models attenuated associations towards null.