Improving treatment of cardiovascular risk factors in childhood cancer survivors

摘要 被诊断患有癌症的儿童和青少年现在平均有80%的5年存活率。然而， 过早的心血管疾病已成为晚年死亡的主要非癌症原因。 儿童癌症幸存者。我们现有的工作表明，传统的心血管危险因素，如高血压， 血脂异常、胰岛素抵抗/糖尿病仍然非常重要，因为它们(以协同方式)增加了患上 重大心血管事件，如缺血性心脏病和心力衰竭。然而，现有的研究一直是 受限于简历风险因素状态的错误分类(即，通过自我报告或药物使用来定义 单独)，包括诊断不足的问题(即，存在这些风险因素的人 不知情)和疾病控制的不确定性(即潜在的治疗不足)。这项提议将利用 世界上最大、特征最好的儿童癌症幸存者队列，儿童癌症幸存者研究 (CCSS；n=24,466)，NCI资助的资源。我们将使用CCSS派生的经过验证的风险预测算法 根据过去的癌症治疗暴露情况选择有严重心脏病高危风险的幸存者(n=800)。 在这800名幸存者中，我们建议确定被低估的诊断和治疗的程度 通过亲自(家庭)测量高血压、血脂异常和糖尿病，并辅之以医疗 记录审查。我们预测，大约60%的幸存者(n~480)将被低估诊断或治疗 这三个简历风险因素中的一个。诊断不足或治疗不足的幸存者将被 有资格参加为期一年的随机对照试验，在该试验中，我们将测量 医学研究所(IOM)推荐强调心血管风险的个性化生存护理计划(SCP)， 辅以远程提供的临床医生主导的自我管理咨询干预，以改善 控制这三个心血管危险因素(即降低未得到充分治疗的高血压、血脂异常和 糖尿病)。被随机分配到对照组的幸存者可以延迟接受干预。最后，我们的 一项提案旨在更好地了解幸存者及其主要医疗保健提供者之间的障碍 导致个人简历风险因素待遇不足。从这项研究中获得的知识将改进评估 以及在这一高危人群中重要的心血管危险因素的治疗。拟议的干预措施，如果成功， 将是可传播的和低成本的，并将有可能改善这些地区的健康和降低死亡率 更年轻的成年人，他们一生中的大部分时间都是癌症幸存者，严重心血管疾病的风险增加。

ABSTRACT Children and adolescents diagnosed with cancer now have on average >80% 5-year survival. However, premature cardiovascular (CV) disease has become the leading non-cancer cause of late mortality among childhood cancer survivors. Our existing work has shown that traditional CV risk factors such as hypertension, dyslipidemia, insulin resistance/diabetes remain very important, by increasing (in synergistic fashion) the risk of major CV events such as ischemic heart disease and heart failure. However, the existing research has been limited by misclassification of CV risk factor status (i.e., when defined by self-report or medication usage alone), including issues with both underdiagnosis (i.e., people with these risk factors present but who are unaware) and uncertainty of disease control (i.e., potential undertreatment). This proposal will utilize the largest, best characterized childhood cancer survivor cohort in the world, the Childhood Cancer Survivor Study (CCSS; n=24,466), a NCI-funded resource. We will use CCSS-derived validated risk prediction algorithms to select survivors at high risk of serious heart disease (n=800) based on past cancer treatment exposures. Among these 800 survivors, we propose to determine the magnitude of underdiagnosis and undertreatment of hypertension, dyslipidemia, and diabetes via in-person (home-based) measurements supplemented by medical record review. We predict that around 60% of survivors (n~480) will be underdiagnosed or undertreated with respect to one of these three CV risk factors. Survivors who are underdiagnosed or undertreated will then be eligible to participate in a 1-year long randomized controlled trial, where we will measure the efficacy of an Institute of Medicine (IOM) recommended personalized survivorship care plan (SCP) emphasizing CV risk, supplemented by a remotely delivered clinician-led self-management counseling intervention, to improve control of these three CV risk factors (i.e., reduce rates of undertreated hypertension, dyslipidemia, and diabetes). Survivors randomized to the control arm can receive the intervention on a delayed basis. Finally, our proposal seeks to better understand barriers among survivors and their primary healthcare providers that contribute to CV risk factor undertreatment. Knowledge derived from this study will improve the assessment and treatment of important CV risk factors in this high risk population. The proposed intervention, if successful, will be disseminable and low cost, and will have the potential to improve health and reduce mortality in these younger adults who live the majority of their lives as cancer survivors at increased risk of serious CV disease.