Do cardiovascular risk factors modify the cardiotoxicity of lymphoma treatments?

描述（由申请人提供）：本提案的总体目标是更好地了解既存心血管风险因素如何与心脏毒性治疗相互作用，以提高淋巴瘤幸存者发生重大心脏事件的风险。心血管疾病是癌症幸存者过早死亡的主要原因。心血管风险主要来自癌症治疗，高血压、血脂异常和糖尿病也会导致这种风险。目前的建议集中在侵袭性淋巴瘤幸存者中主要心血管事件的发展。我们的目的是研究预先存在的心血管危险因素和心脏毒性治疗对主要心血管事件的相互作用。有初步证据表明儿童癌症幸存者之间存在这些相互作用，但从未在成人癌症中进行过系统研究。目的1关注心血管危险因素如何与蒽环类药物相互作用，蒽环类药物可损害心脏及其心血管系统，增加心力衰竭、心肌梗死和中风的风险。目标2关注心血管危险因素如何与辐射相互作用， 颈部的辐射会增加中风的风险，胸部的辐射会导致心力衰竭和心肌梗死。侵袭性淋巴瘤是研究这些相互作用的理想范例，因为有大量的幸存者接受了关键的心脏毒性治疗，后来经历了显著的心血管发病率和死亡率。此外，许多人被诊断得足够晚，心血管风险因素很常见。为了研究心血管危险因素是否会增加癌症治疗对心力衰竭、心肌梗死和中风风险的心脏毒性作用，我们将使用丹麦人口登记处，这是一个丰富的详细纵向数据来源。心血管风险因素、治疗和心脏结局的数据均前瞻性采集。我们对淋巴瘤幸存者心血管风险的大部分理解来自随机临床试验，这些试验通常包括最健康的癌症患者。我们的数据中发现，纳入具有全方位心血管危险因素的患者势在必行。如果高血压、血脂异常和糖尿病在蒽环类药物或放射治疗的存在下对心血管损伤的贡献超过了相加作用，则具有预先存在的风险因素的淋巴瘤幸存者在治疗完成后可能需要积极的风险降低策略。这项研究的发现将为未来的研究提供信息，以开发心肌梗死，中风和心力衰竭的风险预测模型。淋巴瘤幸存者的危险分层将使临床医生能够识别高风险幸存者，以进行更密集的心血管预防工作。

DESCRIPTION (provided by applicant): The overarching goal of this proposal is to better understand how pre-existing cardiovascular risk factors interact with cardiotoxic therapies to heighten the risk of developing major cardiac events among lymphoma survivors. Cardiovascular disease is a leading cause of premature mortality among cancer survivors. Cardiovascular risk arises predominantly from cancer treatments, and hypertension, dyslipidemia, and diabetes contribute to this risk. The current proposal focuses on the development of major cardiovascular events among survivors of aggressive lymphoma. We aim to investigate the interaction of pre-existing cardiovascular risk factors and cardiotoxic therapie on major cardiovascular events. There is preliminary evidence for these interactions among survivors of childhood cancer, but they have never been systematically investigated in adult cancers. Aim 1 focuses on how cardiovascular risk factors interact with anthracyclines, which can damage the heart and its cardiovascular system to increase risk for heart failure, myocardial infarction, and stroke. Aim 2 focuses on how cardiovascular risk factors interact with radiation to the neck, which can contribute to the risk of stroke, and with radiation to the chest, which can contribute to heart failure and myocardial infarction. Aggressive lymphoma is an ideal paradigm for investigating these interactions, because there is a large population of survivors who were treated with key cardiotoxic therapies and who later experience significant cardiovascular morbidity and mortality. Further, many are diagnosed late enough that cardiovascular risk factors are common. To investigate whether cardiovascular risk factors heighten the cardiotoxic effects of cancer therapies on the risk of heart failure, myocardial infarction, and stroke, we wil use the Danish population registry, a rich source of detailed longitudinal data. Data on cardiovascular risk factors, therapies, and cardiac outcomes are all captured prospectively. Much of our understanding of cardiovascular risk among lymphoma survivors comes from randomized clinical trials, which typically include the healthiest cancer patients. It is imperativ to include patients with a full range of cardiovascular risk factors, which are found in our data. f hypertension, dyslipidemia, and diabetes contribute more than additively to cardiovascular damage in the presence of anthracyclines or radiation therapy, lymphoma survivors who had both pre-existing risk factors may require aggressive risk reduction strategies after treatment completion. Findings from this study will inform a future study to develop risk prediction models for myocardial infarction, stroke, and heart failure. Risk stratification of lymphoma survivors wil enable clinicians to identify high-risk survivors for more intensive cardiovascular preventive efforts.