Objective: Most infections occur in pre-school children but the severity of the inflammatory response to common pathogens varies considerably. We examined the relationship between early childhood infections of sufficient severity to warrant hospitalisation, and markers of subclinical atherosclerosis in adulthood.
Methods: We investigated whether infection-related hospitalisation (IRH) in early childhood (0-5 years) was associated with adverse non-invasive phenotypes of atherosclerosis (carotid artery distensibility and intima-media thickness (IMT), and brachial artery flow-mediated dilation (FMD)) in adulthood in participants from the Cardiovascular Risk in Young Finns study. Analyses were adjusted for age, sex, and socioeconomic status and cardiovascular risk factors in childhood and adulthood. 1043 participants had lifetime IRH data with a mean age at adult follow-up of 33 years.
Results: Brachial FMD levels were significantly lower among individuals with early child IRH (mean ± SEM 8.15 ± 0.37 vs. 9.10 ± 0.16%, p = 0.03). These individuals had a 1.84% (95% CI 0.64-3.04, p = 0.002) greater decrease in FMD over a 6-year interval between two adult follow-ups at mean ages 27 and 33 years. Childhood IRH was associated with increased asymmetrical dimethylarginine (ADMA) in adulthood (0.62 ± 0.01 vs. 0.59 ± 0.01 μmol/l, p = 0.04), adjusted for age, sex, adult body mass index, and serum creatinine. Early childhood IRH was associated with lower carotid distensibility levels (1.95 ± 0.06 vs. 2.09 ± 0.02%/10 mmHg, p = 0.02), but not with carotid intima-media thickness (0.601 ± 0.006 vs. 0.596 ± 0.003 mm). All findings remained unchanged after adjustments for age, sex and conventional cardiovascular risk factors in childhood or adulthood.
Conclusion: Infection-related hospitalisation in the pre-school period was associated with adverse adult atherosclerotic phenotypes and increased ADMA. Infection may contribute to causal pathways leading to the development of endothelial dysfunction and early atherosclerosis.
Keywords: Asymmetric dimethylarginine; Atherosclerosis; Child; Infection.
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