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Persistent Non-HDL-C Dyslipidemia Starting in Childhood Tied to Higher CVD Risk

— But this was not the case for those with dyslipidemic levels that resolved by adulthood

MedpageToday
A photo of the results of a lipid profile.

Patients with persistent non-high-density lipoprotein (HDL) cholesterol dyslipidemia from childhood to adulthood had an increased risk of cardiovascular disease (CVD) events, but those who had resolved this by adulthood had a similar risk to those who were never dyslipidemic, according to data from six prospective cohort studies.

Compared with patients who had persistently normal non-HDL cholesterol levels in childhood and adulthood, those who had incident non-HDL cholesterol dyslipidemia and those with persistent dyslipidemia had significantly increased risks of fatal or nonfatal CVD events (HR 2.17, 95% CI 1.00-4.69 and HR 5.17, 95% CI 2.80-9.56, respectively), reported Costan Magnussen, PhD, of the Baker Heart and Diabetes Institute in Melbourne, Australia, and colleagues.

However, those who had dyslipidemic non-HDL cholesterol levels in childhood and subsequent levels that were within the guideline-recommended range in adulthood did not have a significantly increased risk (HR 1.13, 95% CI 0.50-2.56), they noted .

"These findings suggest that primordial and primary interventions to prevent and reduce elevated childhood non-HDL cholesterol levels may help prevent premature CVD," Magnussen and team concluded.

"Childhood dyslipidemia is common and increases the risk of premature atherosclerotic cardiovascular disease (ASCVD), but it is unknown whether resolving childhood dyslipidemia by adulthood would lead to a reduced risk of ASCVD events," Magnussen and co-author Feitong Wu, PhD, also of the Baker Heart and Diabetes Institute, wrote in emailed remarks to app.

Data from the study "suggest there is a window of opportunity prior to or during young adulthood when effective interventions may reverse the detrimental effect of childhood dyslipidemia regarding CVD later in life," they added.

"Moreover, the findings suggest that childhood non-HDL cholesterol levels are associated with adult CVD events due to its strong tracking from childhood into adulthood," they noted. "Also, both childhood and adulthood non-HDL cholesterol levels are independently associated with adult CVD events, pointing to a life-course approach to the prevention of early-onset CVD, in which monitoring non-HDL cholesterol levels from childhood could help early identification of individuals at high lipid-related risk of developing future CVD events, and the risk could be offset by improving non-HDL cholesterol levels through to adulthood."

When analyzed separately, both childhood (ages 3 to 19) and adult (ages 20 to 40) non-HDL cholesterol z scores were associated with increased risk of fatal or nonfatal CVD events (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).

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

However, when both childhood non-HDL cholesterol z score and change in non-HDL cholesterol z scores between childhood and adulthood were included in the same model, childhood z score was still 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).

Study recruitment took place from 1970 to 1996 in the U.S. and Finland, with a final follow-up in 2019. Median age at first childhood visit for non-HDL cholesterol measurement was 10.7 years, 60% were female, and most were white.

Among the 5,121 participants in the study, 18% had resolution of dyslipidemia, 5% had persistent dyslipidemia, 3% had incident dyslipidemia, and 74% had non-HDL cholesterol levels that were persistently within the recommended range.

Over a mean follow-up of 8.9 years after age 40, a total of 147 fatal or nonfatal CVD events occurred.

The study was "not specifically powered to detect subgroup differences by age, sex, or race and ethnicity," which was a limitation, the authors noted.

Furthermore, they said they were unable to determine an "optimal adult age when elevated childhood dyslipidemia should be resolved," and they did not have full information on the use of lipid-lowering medications. In addition, most of the cohorts studied did not have data on possible childhood confounders, such as socioeconomic factors.

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    Jennifer Henderson joined app as an enterprise and investigative writer in Jan. 2021. She has covered the healthcare industry in NYC, life sciences and the business of law, among other areas.

Disclosures

The study was supported by a grant from the NIH. Magnussen is supported by a National Health and Medical Research Council Investigator grant.

Co-authors reported receiving grants from the NIH; personal fees from Astellas Pharma and Targus Medical; and personal fees from Amgen, AstraZeneca, Boehringer Ingelheim, Novo Nordisk, and Sanofi.

Primary Source

JAMA

Wu F, et al "Non-high-density lipoprotein cholesterol levels from childhood to adulthood and cardiovascular disease events" JAMA 2024; DOI: 10.1001/jama.2024.4819.