Atopic dermatitis in childhood and risk of early cardiovascular disease

项目总结/摘要 心血管疾病是全世界死亡的主要原因，通常始于儿童时期。心血管风险 包括高血压、血脂异常、胰岛素抵抗和肥胖在内的因素可以在 青少年期，并高度预测以后的生活心血管疾病的发病率和死亡率。同样在 青少年和成年早期，基于非侵入性的动脉粥样硬化疾病的亚临床证据 内皮功能的成像和测量是长期风险的重要预测因素。患有特定 美国心脏协会已经确定了包括慢性炎症性疾病在内的潜在疾病， 与加速动脉粥样硬化和早期心血管疾病的风险增加有关， 为这些儿童提出了具体的筛查和治疗目标。 最近有一种范式转变，将特应性皮炎理解为全身性炎症 成人中的条件和严重特应性皮炎与心血管结局相关，但 关于特应性皮炎和心血管风险之间的可能联系知之甚少， 孩子重要的是要解决这一研究差距，因为特应性皮炎是最常见的慢性 儿童炎症性疾病，影响高达25%的人口。 本提案的总体目的是评估特应性皮炎是否与心血管疾病相关， 危险因素和亚临床动脉粥样硬化。我们建议对以下内容进行二次分析 雅芳父母和孩子纵向研究（ALSPAC），一项基于人口的14000名出生队列研究， 这些人被设计用于研究健康和发展，并进行了超过20年的随访。这个群体是独一无二的， 它包含对特应性皮炎严重程度的重复评估和心血管疾病的详细测量， 风险 具体而言，我们将（1）检查特应性皮炎与同期发生的 在出生至17岁之间的12个时间点，高血压、胰岛素抵抗、血脂异常和肥胖， (2)确定是否有更活跃和更严重的特应性皮炎模式的个体亚组， 通过颈动脉内膜中层测量，儿童和青少年有亚临床动脉粥样硬化的证据 17岁和24岁时的厚度、扩张系数和脉搏波速度。 拟议的研究将导致更好地了解特应性皮炎疾病的活动和严重程度 随着时间的推移会影响生命早期的心血管风险。这项研究将提供一个原则的证明，以证明一个 前瞻性队列研究，旨在更好地描述心血管风险的时间变化， 特应性皮炎患者亚组之间的潜在机制，并提供初步数据，以计划 未来的比较临床试验的影响，特应性皮炎治疗对早期心血管风险，及时 现在有许多新的靶向抗炎生物治疗被批准和/或在测试中。

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.