Atopic dermatitis in childhood and risk of early cardiovascular disease

项目摘要/摘要 心血管疾病是世界范围内主要的死亡原因，通常始于儿童时期。心血管风险 高血压、血脂异常、胰岛素抵抗和肥胖等因素可以在 对青春期心血管疾病的发病率和死亡率有很高的预测性。同样，在 青春期和成年期早期动脉粥样硬化性疾病的亚临床证据 血管内皮细胞功能的成像和测量是预测长期风险的重要指标。患有特殊疾病的儿童 包括慢性炎症性疾病在内的潜在疾病已经被美国心脏协会确认 与动脉粥样硬化加速和早期心血管疾病的风险增加有关 已经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一种全身性炎症 成人的病情和严重的特应性皮炎与心血管结果有关，但非常 对于特应性皮炎与心血管风险之间的可能联系，我们知之甚少。 孩子们。解决这一研究差距很重要，因为特应性皮炎是最常见的慢性皮炎 儿童炎症性疾病，影响高达25%的人口。 这项建议的总体目标是评估特应性皮炎是否与心血管疾病有关 儿童和年轻人的危险因素和亚临床动脉粥样硬化。我们建议对以下问题进行二次分析 雅芳关于父母和孩子的纵向研究(ALSPAC)，一个基于人口的出生队列，有14,000人 旨在研究健康和发展的个人，并进行了20多年的跟踪调查。这一群体是独一无二的 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。 具体地说，我们将(1)检查特应性皮炎与同期发病相关的程度 出生到17岁之间的12个时间点的高血压、胰岛素抵抗、血脂异常和肥胖，以及 (2)确定自始至终具有更活跃和更严重的特应性皮炎模式的个体亚组 根据颈动脉内膜中层测量，儿童和青春期有亚临床动脉粥样硬化的证据。 17岁和24岁时的厚度、膨胀系数和脉搏波速度。 这项拟议的研究将有助于更好地了解特应性皮炎疾病的活动性和严重性 随着时间的推移，会影响早期生活中的心血管风险。这项研究将提供原则证明，以证明 前瞻性队列研究旨在更好地描述心血管风险的时间变化并确定 特应性皮炎患者亚组之间的潜在机制，并为计划提供初步数据 特应性皮炎治疗对早期心血管风险影响的未来对比临床试验 现在，许多新的靶向抗炎生物疗法已经获得批准和/或正在测试中。

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.