Resolution of childhood non-HDL-c hyperlipidemia by adulthood associated with lower risk of CVD events
In an analysis of 6 prospective cohorts, individuals who resolved childhood non-HDL-c hyperlipidemia by adulthood had a similar risk of CVD events as individuals who never had hyperlipidemia.
This summary is based on the publication of Wu F, Jacobs D, Daniel S, et al. - Non–High-Density Lipoprotein Cholesterol Levels From Childhood to Adulthood and Cardiovascular Disease Events. JAMA. 2024 Jun 4;331(21):1834-1844. doi: 10.1001/jama.2024.4819.
Introduction and methods
Background
Non-HDL-c hyperlipidemia, which is causal risk factor for ASCVD, is common in children [1,2]. There is a lack of direct evidence linking childhood non-HDL-c levels and changes in these levels from childhood to adulthood with long-term risk of cardiovascular events.
Aim of the study
The aim of this study was to determine whether the association between childhood non-HDL-c and CVD events is independent of adult non-HDL-c or changes in non-HDL-c levels from childhood to adulthood. Moreover, this study evaluated whether resolution of childhood non-HDL-c hyperlipidemia by adulthood is associated with attenuated risk of CVD events in adulthood.
Methods
The authors used pooled individual participant data of 6 cohorts from the International Childhood Cardiovascular Cohort (i3C) Consortium (5 cohorts were from the US and 1 cohort was from Finland) that recruited participants from 1970 to 1996, with a final follow-up in 2019. In this analysis, data of 5121 participants (60% women) were included who had non-HDL-c measurements available at childhood (age 3 to 19 years) and adulthood (age 20 to 40 years). At each visit, non-HDL-c levels were standardized as age- and sex-specific z scores. For each participant, the mean of all z scores across childhood and adulthood measurements were used to obtain a single value for analysis.
Participants were stratified into 4 groups based on the change in non-HDL-c level between childhood and adulthood: persistent hyperlipidemia (i.e. hyperlipidemia both in childhood and adulthood; n=252); incident hyperlipidemia (i.e. nonhyperlipidemia in childhood and hyperlipidemia in adulthood; n=158); resolution (i.e. hyperlipidemia in childhood and nonhyperlipidemia in adulthood; n=937); and persistent levels within the guideline-recommended range (i.e. nonhyperlipidemia in both childhood and adulthood; n=3774). Hyperlipidemia was defined as non-HDL-c ≥145 mg/dL (3.75 mmol/L) in childhood and ≥190 mg/dL (4.91 mmol/L) in adulthood. Mean follow-up duration was 8.9 years after age 40 years.
Outcomes
The main outcomes were fatal and nonfatal CVD events. Nonfatal CVD events included the first occurrence of adjudicated MI, stroke, transient ischemic attack, ischemic HF, angina, peripheral artery disease, carotid intervention, abdominal aortic aneurysm, and coronary revascularization.
Main results
Childhood and adulthood non-HDL-c ⴭ scores and change in scores
- A total of 147 fatal or nonfatal CVD events occurred during the follow-up period.
- There was a modest correlation between childhood and adult non-HDL-c ⴭ scores (r=0.587; P<0.001)
- Childhood non-HDL-c was associated with the risk of CVD events (HR per 1-unit increase in ⴭ score: 1.42; 95%CI: 1.18-1.70), but this association was reduced when correcting for adulthood non-HDL-c (HR per 1-unit increase in ⴭ score: 1.12; 95%CI: 0.89-1.41).
- Adulthood non-HDL-c was associated with the risk of CVD events (HR per 1-unit increase in ⴭ score: 1.50; 95%CI: 1.26-1.78), and this association remained significant when adjusting for childhood levels (HR per 1-unit increase in ⴭ score: 1.41; 95%CI: 1.14-1.74).
- When both childhood ⴭ score and the change in ⴭ score from childhood to adulthood were included in the same model, both childhood ⴭ score and the change in ⴭ score were independent predictors of CVD events (HR per 1-unit increase in ⴭ score: 1.58; 95%CI: 1.30-1.92 for childhood ⴭ score; and HR per 1-unit increase in ⴭ score: 1.41; 95%CI: 1.14-1.74 for change in ⴭ score).
Change in non-HDL-c status
- Compared with individuals who persistently were within guideline range, participants with incident hyperlipidemia and persistent hyperlipidemia had a higher risk 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 resolved childhood non-HDL-c hyperlipidemia by adulthood had a similar risk of CVD events as individuals who persistently were within guideline range (HR: 1.13; 95%CI: 0.50-2.56).
Conclusion
In this analysis using data from 6 prospective cohort studies among 5121 children, childhood non-HDL-c was associated with CVD events later in life, but this association was largely attenuated by adjusting for adulthood non-HDL-c levels. Furthermore, individuals who resolved childhood non-HDL-c hyperlipidemia by adulthood had a similar risk of CVD events compared with individuals who never had hyperlipidemia. Persistent non-HDL-c hyperlipidemia from childhood to adulthood was associated with an increased risk of CVD events compared with individuals who were persistently within guideline range.
The authors conclude that “these findings suggest that primordial and primary interventions to prevent and reduce elevated childhood non–HDL-c levels may help prevent premature CVD”.
References
- Perak AM, Ning H, Kit BK, et al. Trends in levels of lipids and apolipoprotein B in US youths aged 6 to 19 years, 1999-2016.JAMA. 2019;321(19):1895-1905. doi:10.1001/jama.2019.4984
- Pirillo A, Casula M, Olmastroni E, et al. Global epidemiology of dyslipidaemias. Nat Rev Cardiol. 2021;18(10):689-700. doi:10.1038/s41569-021-00541-4