Atopic dermatitis in childhood and risk of early cardiovascular disease
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PROJECT SUMMARY/ABSTRACT Cardiovascular disease, the leading cause of death worldwide, often begins in childhood. Cardiovascular risk factors including hypertension, dyslipidemia, insulin resistance, and obesity can be detected before adolescence and are highly predictive of later life cardiovascular morbidity and mortality. Similarly, in adolescence and early adulthood, subclinical evidence of atherosclerotic disease based on non-invasive imaging and measures of endothelial function are important predictors of long-term risk. Children with specific underlying conditions, including chronic inflammatory disease, have been identified by the American Heart Association as having an increased risk for accelerated atherosclerosis and early cardiovascular disease, and specific screening and therapeutic targets have been proposed for these children. There has been a recent paradigm shift towards understanding atopic dermatitis as a systemic inflammatory condition and severe atopic dermatitis in adults has been associated with cardiovascular outcomes, but very little is known about the possible association between atopic dermatitis and cardiovascular risk among children. It is important to address this research gap because atopic dermatitis is the most common chronic inflammatory disease of children, affecting up to 25% of the population. The overall objective of this proposal to evaluate whether atopic dermatitis is associated with cardiovascular risk factors and subclinical atherosclerosis in children and young adults. We propose a secondary analysis of the Avon Longitudinal Study of Parents and Children (ALSPAC), a population-based birth cohort of 14,000 individuals designed to study health and development with over 20 years of follow-up. This cohort is unique in that it contains repeated assessments of atopic dermatitis severity and detailed measures of cardiovascular risk. Specifically, we will (1) examine the extent to which atopic dermatitis is associated with contemporaneous hypertension, insulin resistance, dyslipidemia, and obesity at twelve time points between birth and age 17, and (2) determine if subgroups of individuals with a more active and severe pattern of atopic dermatitis throughout childhood and adolescence have evidence of subclinical atherosclerosis as measured by carotid intima-media thickness, distensibility coefficients, and pulse wave velocity at ages 17 and 24. The proposed research will lead to a better understanding of how atopic dermatitis disease activity and severity over time affect cardiovascular risk in early life. This research which will provide a proof of principle to justify a prospective cohort study designed to better characterize temporal changes in cardiovascular risk and identify potential mechanisms among subgroups of patients with atopic dermatitis, and provide preliminary data to plan future comparative clinical trials of the impact of atopic dermatitis treatment on early cardiovascular risk, timely now with many new targeted anti-inflammatory biologic treatments approved and/or in testing.
