30th June 2024, A/Prof Chee L Khoo
We advocate applying protective sunscreens for little babies onwards because most of the sun damage starts from young and often, we fight a losing battle trying to rescue severe sun damaged skin in later life. It wouldn’t be any different in dyslipidaemia in children and adults. When you think about it, it really doesn’t matter what age you are. High lipids will damage the arteries whatever age you are. In many of our patients, especially those with premature cardiovascular disease, much of the damage may have occurred during childhood. What happens to children with dyslipidaemia? Do they grow out of it? Do they sustain the same damage as in adults? When should we start checking lipids? At what age should we be treating childhood dyslipidaemia?
We know that non-optimal childhood levels of lipids (including total cholesterol, high-density lipoprotein cholesterol (HDL-C), non-HDL-C, low-density lipoprotein cholesterol (LDL-C) and triglycerides are associated with presence and extent of early atherosclerotic lesions at autopsy. In addition, childhood apolipoprotein B levels may predict adult subclinical atherosclerosis even more strongly than cholesterol levels (3).
That’s the theory. It would make sense then that we should start screening children for dyslipidaemia as soon as opportunity arises. However, the evidence behind that recommendation is not there (yet). The US Preventative Services Task Force (USPSTF) concluded recently that the current evidence is insufficient to assess the balance of benefits and harms of screening for lipid disorders in children and adolescents 20 years or younger. This statement applies to asymptomatic children and adolescents 20 years or younger without a known diagnosis of a lipid disorder. Children from families with diagnosed premature cardiovascular disease or familial hypercholesterolaemia is different and should be screened early. Atherosclerotic changes are already detected as early as 8 years old in these children (1).
The International Childhood Cardiovascular Cohort (i3C) Consortium is a collaborative effort among 7 longitudinal cohorts across the world that seeks to examine the importance of childhood risk factors as predictors for subsequent clinical cardiovascular disease. The data of more than 40,000 participants aged 3-19 years was obtained from 7 cohorts from 3 continents ((Bogalusa Heart Study, Minnesota Childhood Cardiovascular Cohorts, Muscatine Study, NHLBI Growth and Health and study and Princeton Lipid Research Study), and 1 each from Finland (Cardiovascular Risk in Young Finns Study) and Australia (Childhood Determinants of Adult Health Study).
In a recent analysis of the pooled data from i3C, Wu et al explored whether the association of childhood non–HDL-C with CVD events is independent of adult non–HDL-C levels or independent of the change in non–HDL-C levels from childhood to adulthood and (2) whether resolution of elevated childhood non–HDL-C by adulthood is associated with attenuated risk of developing CVD events in adulthood.
For the purpose of the analysis, fasting non-HDL-C was used instead of LDL-C. Age, sex, smoking habits, lipid lowering medications (age at the first reported use), type 2 diabetes, blood pressure, and body mass index (BMI) and race data were collected.
Comparing childhood with adult levels
The starting follow-up time for events was set at age 40 years (the landmark time) because it is a widely accepted cutoff for young adulthood in clinical guidelines. Non–HDL-C measurements taken between ages 20 and 40 years were used to define adulthood non–HDL-C exposures. Childhood (age 3-19 years) non–HDL-C levels at each visit were standardised as age- and sex-specific z scores. The mean of resulting z scores across childhood measurements for each participant was then calculated to obtain a single childhood mean z score for analysis. A single adult mean z score for adult measurements between ages 20 and 40 years was generated using the same approach.
From the available data, participants were classified into:
- Persistent dyslipidaemia – dyslipidaemia in childhood that persist into adulthood
- Incidental dyslipidaemia – normal in childhood but became dyslipidaemic in adulthood
- Resolution – dyslipidaemia in children but normal in adulthood
- Persistent (normal) – normal in children and normal in adulthood
In children, non-HDL-C is considered elevated and dyslipidaemic if non-HDL-C was ≥ 3.10 mmol/L and ≥ 3.75 mmol/L respectively. In adults, the cut-offs are ≥ 3.88 mmol/L and 4.91 mmol/L respectively. Nonfatal CVD events included the first occurrence of adjudicated myocardial infarction, stroke, transient ischemic attack, ischemic heart failure, angina, peripheral artery disease, carotid intervention, abdominal aortic aneurysm, and coronary revascularisation. Fatal and non-fatal events were included in the analysis.
Of the 42 324 participants in the pooled dataset, after exclusions and those with incomplete or unavailable data, data from 5121 participants were available for the analysis.
Results:
The median age at first childhood visit for non–HDL-C measurements (baseline) was 10.7 years. Over a mean length of follow-up of 8.9 years after age 40 years, 147 fatal or nonfatal CVD events occurred among 5121 participants. From childhood to adulthood, in 18% of the children who had dyslipidaemia, the non-HDL levels became normal. In 5% of the children with dyslipidaemia, the dyslipidaemia persisted. In 3% of the children who had normal non-HDL-C, their non-HDL-C became dyslipidaemic in adulthood (incident dyslipidaemia) and 74% who had normal non–HDL-C levels remain normal.
Association with CVD events
When analysed separately, both childhood and adult non–HDL-C z scores were associated with a 1.42X increased risk of fatal or non-fatal CVD events for a 1-unit increase in z score after adjusting for cohort, sex, Black race, childhood smoking, mean age at and calendar year of childhood measurement, and childhood mean age- and sex-specified z scores for body mass index and systolic blood pressure.
Compared with those who had persistently normal non–HDL-C in childhood and adulthood, participants who had incident dyslipidaemia had a 2.17X increased risk of fatal or nonfatal CVD events and those with persistent non–HDL-C dyslipidaemia from childhood to adulthood had 5.17X the risk.
Individuals who had dyslipidaemia non–HDL-C in childhood but became non-dyslipidaemic as adults had a similar risk (1.13X) as those with both childhood and adulthood non-dyslipidaemia.
In summary, most children who had dyslipidaemia continued to have dyslipidaemia in adulthood. Some children who had dyslipidaemia in childhood normalised their non-HDL-C by the time they become adults. Yet, some children who had normal non-HDL-C developed dyslipidaemia later in adulthood. Compared with those children who had normal non-HDL-C in childhood and adulthood, in children who had dyslipidaemia but normalised in adulthood, their cardiovascular risk is not increased. For the children who had dyslipidaemia either in childhood or shortly after in adulthood, their cardiovascular risk is significantly increased. These findings suggest that from a preventive perspective (1) assessment of non–HDL-C should begin in childhood and (2) efforts to reduce non–HDL-C levels from childhood to adulthood may help prevent premature CVD.
References:
- Guirguis-Blake JM, Evans CV, Coppola EL, Redmond N, Perdue LA. Screening for Lipid Disorders in Children and Adolescents: An Evidence Update for the US Preventive Services Task Force. Evidence Synthesis No. 229. Agency for Healthcare Research and Quality; 2023. AHRQ publication 22-05301-EF-1.
- Wu F, Jacobs DR Jr, Daniels SR, Kähönen M, Woo JG, Sinaiko AR, Viikari JSA, Bazzano LA, Steinberger J, Urbina EM, Venn AJ, Raitakari OT, Dwyer T, Juonala M, Magnussen CG. Non-High-Density Lipoprotein Cholesterol Levels From Childhood to Adulthood and Cardiovascular Disease Events. JAMA. 2024 Jun 4;331(21):1834-1844.
- Gidding SS, Sniderman A. Improving recognition of cardiovascular risk in children. J Pediatr. 2014;164(2):228-230