Reducing elevated non-HDL-C levels in childhood could prevent premature cardiovascular disease

Reducing elevated non-HDL-C levels in childhood could prevent premature cardiovascular disease | Image Credit: © yodiyim - © yodiyim - stock.adobe.com.

A study recently published in JAMA Network found that children who resolved dyslipidemic non-high-density lipoprotein cholesterol (non-HDL-C) by adulthood have similar risk of cardiovascular disease (CVD) events with those who never had dyslipidemia. This suggests interventions to prevent and reduce elevated non-HDL-C levels could prevent premature CVD.

To determine associations of non-HDL-C status among childhood and adulthood with CVD events, investigators pooled individual data of 6 prospective cohorts of children in the United States and Finland. Mean age at baseline was 10.7 years, and recruitment took place from 1970 to 1996, with a final follow-up in 2019.

After all exclusion/inclusion criteria, 5121 participants were included in the primary analysis. Standardized questionnaires and laboratory protocols were used to collect childhood (aged 3 to 19 years) and adulthood (aged 20 years or older) information for:

- Total cholesterol and HDL-C levels from fasting samples

- Age

- Sex

- Smoking habits

- Lipid-lowering medications

- Type 2 diabetes

- Blood pressure

- Body mass index

Non-HDL-C measurements taken between ages 20 and 40 years were used to define adulthood non-HDL-C exposures. The childhood non-HDL-C levels at each visit were standardized as age- and sex-specific z scores because of age-related developmental changes. The mean z scores across childhood measurements for each participant was calculated for a single mean z score for analysis. Single mean z scores were also calculated for adults using the same method.

There were 147 fatal or nonfatal CVD events that occurred among 5121 participants over a mean length of follow-up of 8.9 years after age 40. From childhood to adulthood, 937 (18%) had resolution of dyslipidemia, 252 (5%) had persistent dyslipidemia, 158 (3%) had incident dyslipidemia, and 3774 (74%) had non-HDL-C levels “that were persistently within the guideline-recommended range,” the investigators wrote.

Childhood and adult non-HDL-C z scores were moderately correlated (r = 0.587 [P < .001]). Both childhood and adult non-HDL-C z scores were associated with increased risk of fatal or nonfatal CVD events when analyzed separately (HRs, 1.42 [95% CI, 1.18-1.70] and 1.50 [95% CI, 1.26-1.78] for a 1-unit increase in z score, respectively).

When both childhood and adult z scores were included in the same model, the childhood non-HDL-C z score was reduced ((HR, 1.12 [95% CI, 0.89-1.41]), while the adult z score remained significant (HR, 1.41 [95% CI, 1.14-1.74]).

When both z score and change in non-HDL-C z scores between childhood and adulthood were included in the same model, “childhood non–HDL-C z score remained a significant predictor of the outcome (HR, 1.58 [95% CI, 1.30-1.92]) and the incremental change in the z score was an additional independent predictor (HR, 1.41, [95% CI, 1.14-1.74]),” noted the study authors.

Participants who had incident dyslipidemia had a significantly increased risk of fatal or nonfatal CVD events compared to those with persistently normal non-HDL-C in childhood and adulthood (HR, 2.17 [95% CI, 1.00-4.69]). Those with persistent non-HDL-C dyslipidemia from childhood to adulthood had double that risk (HR, 5.17 [95% CI, 2.80-9.56]).

Overall, results revealed that those with persistent non-HDL-C dyslipidemia from childhood to adulthood had an increased risk of CVD events. Those who had non-HDL-C dyslipidemia resolved by adulthood shared a similar risk as individuals with normal HDL-C in childhood and adulthood, leading the study investigators to conclude, “These findings suggest that primordial and primary interventions to prevent and reduce elevated childhood non–HDL-C levels may help prevent premature CVD.”

Reference:

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