Racial and Cardiovascular Risk Factor Anomalies in CKD

描述（由申请人提供）：在接受维持性透析治疗的慢性肾病 (CKD) 患者中，非洲裔美国患者的比例明显高于非西班牙裔白人患者，而高胆固醇血症、高血压和肥胖等心血管疾病的传统危险因素似乎与不良结果呈反常的负相关关系。非裔美国人中终末期肾病 (ESRD) 的患病率异常高，可能是其较高的 CKD 发病率和/或较快的 CKD 进展、较低的死亡率和较低的肾移植可能性之间复杂相互作用的结果。 ESRD 中异常的心血管危险因素可能是与营养不良和炎症相关的短期竞争风险的结果，看似不利的传统心血管危险因素与更好的营养状态相关，这可能对非裔美国人产生不同的影响，从而为他们在 ESRD 中更好的生存提供了一种解释。非透析依赖型 CKD 阶段的死亡率是否存在类似的矛盾差异尚不清楚；它们的存在、程度、发生的 CKD 阶段及其作用机制都需要足够详细地阐明，以便设计适当的诊断和干预策略，以降低心血管风险并减轻结局中的种族差异。本着 PA-09-196 的精神，我们将利用从国家 VA 研究数据库获得的数据，该数据库是唯一一个大型管理数据库，包含美国各地大量个体（超过 400 万人，其中包括超过 50 万人患有 CKD）的详细社会人口统计和临床信息。我们将通过纵向检查一组估计肾小球滤过率正常的患者，研究 CKD 事件和死亡率对种族构成和心血管危险因素概况变化的人群动态影响。我们将使用复杂的流行病学方法探讨各种社会人口特征、合并症、生化测量和药物使用对死亡率和进行性 CKD 的影响，包括联合建模，以评估危险因素参数纵向变化对死亡率和边际结构模型的影响，以便调整基线和时间依赖性混杂因素。这个为期三年的项目将产生大量信息，以更可靠地检验上述与各种肾功能水平患者的结果中的种族和心血管差异相关的假设，这可能对公共卫生产生重大影响。

DESCRIPTION (provided by applicant): Among individuals with chronic kidney disease (CKD) receiving maintenance dialysis therapy the proportion of African American patients is significantly higher compared to their non-Hispanic white counterparts, and traditional risk factors of cardiovascular disease such as hypercholesterolemia, hypertension and obesity show seemingly anomalous, inverse associations with adverse outcomes. The exceptionally high prevalence of end- stage renal disease (ESRD) among African Americans is likely a result of the complex interaction of their higher rates of CKD incidence and/or faster CKD progression, lower mortality, and lower likelihood of kidney transplantation. The anomalous cardiovascular risk factor profile in ESRD could be the result of short-term competing risks related to malnutrition and inflammation, with the seemingly unfavorable traditional cardiovascular risk factors associating with a better nutritional state, which could differentially affect African Americans an hence provide one explanation for their better survival in ESRD. Whether similar paradoxical differences in mortality rates in non-dialysis dependent CKD stages exist is not clear; their presence, extent, the CKD stage of its occurrence and their mechanisms of action all need to be clarified in sufficient detail to allow for the design of proper diagnostic and interventional strategies towards cardiovascular risk reduction and towards alleviating racial disparities in outcomes. In the spirit of PA-09-196 we will utilize data obtained from the national VA research database which is the only large administrative database with detailed socio-demographic and clinical information on very large numbers of individuals (over 4 million individuals including ove 0.5 million with CKD) across all parts of the US. We will examine the population-wide dynamic effects of incident CKD and mortality on racial composition and on changes in cardiovascular risk factor profiles by examining longitudinally a cohort of patients with normal estimated glomerular filtration rate. We will explore the effects of various socio-demographic characteristics, co-morbidities, biochemical measurements and medication use on mortality and progressive CKD using complex epidemiologic methods including joint modeling to assess the effect of longitudinal changes in risk factor parameters on mortality and marginal structural models in order to adjust for both baseline and time-dependent confounders. This three-year project will generate a wealth of information to more reliably examine the above hypotheses related to racial and cardiovascular discrepancies in the outcomes of patients with all levels of kidney function that could have significant public health implications.