Early Life Infections Linked to Cardio Disease Risk in Adulthood

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Scientists say they have discovered a potential pathway linking early life infections to cardiovascular risk later in adulthood, offering opportunities for targeted intervention. The study “Early life infection and proinflammatory, atherogenic metabolomic and lipidomic profiles in infancy: a population-based cohort study”, led by the Murdoch Children Research Institute (MCRI) and published by eLifefound that elevated inflammation markers and changes in metabolism observed in infection-prone infants resembled those in adults at risk of cardiovascular disease.

“The risk of adult onset cardiovascular and metabolic (cardiometabolic) disease accrues from early life. Infection is ubiquitous in infancy and induces inflammation, a key cardiometabolic risk factor, but the relationship between infection, inflammation, and metabolic profiles in early childhood remains unexplored. We investigated relationships between infection and plasma metabolomic and lipidomic profiles at age six and 12 months, and mediation of these associations by inflammation,” write the investigators.

“Matched infection, metabolomics, and lipidomics data were generated from 555 infants in a pre-birth longitudinal cohort. Infection data from birth to 12 months were parent-reported (total infections at age 1, 3, 6, 9, and 12 months), markers (high-sensitivity C-reactive protein). [hsCRP]; glycoprotein acetyls [GlycA]) were quantified at 12 months. Metabolic profiles were 12-month plasma nuclear magnetic resonance metabolomics (228 metabolites) and liquid chromatography/mass spectrometry lipidomics (776 lipids). Associations were evaluated with multivariable linear regression models. In secondary analyses, corresponding inflammation, and metabolic data from birth (serum) and 6-month (plasma) time points were used.

“At 12 months, more frequent infant infections were associated with adverse metabolomic (elevated inflammation markers, triglycerides and phenylalanine, and lower high-density lipoprotein). [HDL] cholesterol and apolipoprotein A1) and lipidomic profiles (elevated phosphatidylethanolamines and lower trihexosylceramides, dehydrocholesteryl esters, and plasmalogens). Similar, more marked, profiles were observed with higher GlycA, but not hsCRP. GlycA mediated a substantial proportion of the relationship between infection and metabolome/lipidome, with hsCRP generally mediating a lower proportion. Analogous relationships were observed between infection and 6-month inflammation, HDL cholesterol, and apolipoprotein A1.

“Infants with a greater burden of infection in the first year of life had proinflammatory and proatherogenic plasma metabolomic/lipidomic profiles at 12 months of age that in adults are indicative of heightened risk of cardiovascular disease, obesity, and type 2 diabetes.” These findings suggest potentially modifiable pathways linking early life infection and inflammation with subsequent cardiometabolic risk.”

“We found the risk of adult-onset cardiovascular disease could be accruing from early life,” said MCRI researcher Toby Mansell, PhD. “We know babies are prone to infections. This causes inflammation, a key cardiometabolic risk factor, but the relationship between infection, inflammation, and metabolic profiles in early childhood had remained underexplored until this study.”

David Burgner, PhD, professor, noted that infection had been recognized as a potential contributor to cardiovascular disease, one of the leading causes of death in adults globally. He added that the research offered opportunities for early prevention measures such as identifying the types of infection and the children at highest risk, and how these risks might be offset by simple interventions.

“Targeted action could include promoting breastfeeding, ensuring timely vaccinations, and supporting families so that they can keep children at home if they are unwell with an infection,” he said.

Researchers from The Royal Children’s Hospital, the University of Melbourne, Baker Heart and Diabetes Institute, The Florey Institute of Neuroscience and Mental Health, Deakin University, Radboud University Medical Center in the Netherlands, the University of Queensland, Barwon Health, and Monash University also contributed to the study.

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