Non–HDL-C Levels From Childhood to Adulthood and CVD Events (2024)

• ¹Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia

• ²Baker Department of Cardiometabolic Health, Faculty of Medicine, Dentistry, and Health Sciences, University of Melbourne, Melbourne, Victoria, Australia

• ³Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis

• ⁴Department of Pediatrics, University of Colorado School of Medicine, Children’s Hospital Colorado, Aurora

• ⁵Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland

• ⁶Department of Clinical Physiology, Tampere University Hospital, Tampere, Finland

• ⁷Division of Biostatistics and Epidemiology, Cincinnati Children’s Hospital Medical Center, and Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio

• ⁸University of Minnesota Medical School, Minneapolis

• ⁹Department of Medicine, University of Turku, Turku, Finland

• ¹⁰Division of Medicine, Turku University Hospital, Turku, Finland

• ¹¹Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana

• ¹²Department of Pediatrics, University of Minnesota School of Medicine, Minneapolis

• ¹³The Heart Institute, Cincinnati Children’s Hospital Medical Center, and Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio

• ¹⁴Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia

• ¹⁵Centre for Population Health Research, University of Turku and Turku University Hospital, Turku, Finland

• ¹⁶Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland

• ¹⁷Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland

• ¹⁸InFLAMES Research Flagship, University of Turku, Turku, Finland

• ¹⁹Nuffield Department of Women’s and Reproductive Health, University of Oxford, Oxford, United Kingdom

• ²⁰Murdoch Children’s Research Institute, Melbourne, Victoria, Australia

Key Points

Question Do children who resolve dyslipidemic non–high-density lipoprotein cholesterol (non–HDL-C) levels by adulthood have attenuated risk of developing cardiovascular disease (CVD) events?

Findings Among 5121 children pooled from 6 prospective cohort studies in the US and Finland (mean follow-up, 8.9 years after age 40 years), individuals who had dyslipidemic non–HDL-C in childhood that resolved during adulthood did not have a significantly increased risk of fatal or nonfatal CVD events (hazard ratio, 1.13) than those whose non–HDL-C levels were persistently within the guideline-recommended range in childhood and adulthood.

Meaning Children in whom dyslipidemic non–HDL-C resolves by adulthood have similar risk of CVD to those who never had dyslipidemia.

Importance Elevated non–high-density lipoprotein cholesterol (non–HDL-C; a recommended measure of lipid-related cardiovascular risk) is common in children and increases risk of adult cardiovascular disease (CVD). Whether resolution of elevated childhood non–HDL-C levels by adulthood is associated with reduced risk of clinical CVD events is unknown.

Objective To examine the associations of non–HDL-C status between childhood and adulthood with incident CVD events.

Design, Setting, and Participants Individual participant data from 6 prospective cohorts of children (mean age at baseline, 10.7 years) in the US and Finland. Recruitment took place between 1970 and 1996, with a final follow-up in 2019.

Exposures Child (age 3-19 years) and adult (age 20-40 years) non–HDL-C age- and sex-specific z scores and categories according to clinical guideline–recommended cutoffs for dyslipidemia.

Main Outcomes and Measures Incident fatal and nonfatal CVD events adjudicated by medical records.

Results Over a mean length of follow-up of 8.9 years after age 40 years, 147 CVD events occurred among 5121 participants (60% women; 15% Black). Both childhood and adult non–HDL-C levels were associated with increased risk of CVD events (hazard ratio [HR], 1.42 [95% CI, 1.18-1.70] and HR, 1.50 [95% CI, 1.26-1.78] for a 1-unit increase in z score, respectively), but the association for childhood non–HDL-C was reduced when adjusted for adult levels (HR, 1.12 [95% CI, 0.89-1.41]). A complementary analysis showed that both childhood non–HDL-C levels and the change between childhood and adulthood were independently associated with the outcome, suggesting that from a preventive perspective, both childhood non–HDL-C levels and the change into adulthood are informative. Compared with those whose non-HDL-C levels remained within the guideline-recommended range in childhood and adulthood, participants who had incident non–HDL-C dyslipidemia from childhood to adulthood and those with persistent dyslipidemia had increased risks of CVD events (HR, 2.17 [95% CI, 1.00-4.69] and HR, 5.17 [95% CI, 2.80-9.56], respectively). Individuals who had dyslipidemic non–HDL-C in childhood but whose non-HDL-C levels were within the guideline-recommended range in adulthood did not have a significantly increased risk (HR, 1.13 [95% CI, 0.50-2.56]).

Conclusions and Relevance Individuals with persistent non–HDL-C dyslipidemia from childhood to adulthood had an increased risk of CVD events, but those in whom dyslipidemic non–HDL-C levels resolve by adulthood have similar risk to individuals who were never dyslipidemic. These findings suggest that interventions to prevent and reduce elevated childhood non–HDL-C levels may help prevent premature CVD.

Dyslipidemia Cardiovascular Risk Factors Cardiology Pediatrics

Citation

Wu F, Jacobs DR, Daniels SR, et al. Non–High-Density Lipoprotein Cholesterol Levels From Childhood to Adulthood and Cardiovascular Disease Events. JAMA. Published online April 12, 2024. doi:10.1001/jama.2024.4819

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