Environmental Toxicants, Race, and Cardiovascular Disease Risk in Children

描述(申请人提供)：心血管疾病(CVD)仍然是美国主要的死亡原因，每年导致1000万美国人残疾。然而，在美国，非裔美国人(AA)的心血管疾病风险比欧洲裔美国人(EA)更高。除了心血管疾病风险的R/E差异外，还有大量数据表明，相对于 尽管如此，AAS的贫困率更高，他们的血液和骨骼中的环境毒物，包括铅(铅)的暴露也相应增加。此外，研究表明，铅与血压、左心室肥厚和心血管疾病死亡率呈正相关。目前的提案涉及的问题是，心血管疾病的R/E差异是否部分是环境中铅暴露的相应差异的结果。此外，该建议还考虑了这些影响是否会因心理社会背景中的R/E差异而被放大，包括社会控制动机、背景压力和种族歧视。具体地说，我们的建议侧重于铅暴露的R/E差异是否可能通过心血管对急性心理应激反应的潜在变化而产生不同的心血管风险，这是一种心理社会环境影响心血管风险的机制。在最近的研究中(Gump等人，2011年)，血铅的增加与心脏自主神经调节的改变有关，这反映了交感和副交感神经活动的“共同抑制”，这通常与更大的血管阻力有关，我们已经在儿童早期血铅升高的儿童中观察到了这种心血管模式(Gump等人，2005年)。这种对应激的血管反应也被证明与较大的左心室质量有关，这是心血管发病率的重要预测指标。有趣的是，许多研究已经注意到，相对于EA典型的心脏反应，AA以血管模式对心理应激做出反应，并且在相似的血压水平下比EA更有可能发展为左室肥厚，并且有更快的脉搏波速度反映的更大的动脉僵硬。综上所述，有证据表明：1)AAs(相对于EAs)有更高的血铅水平，2)Aa(相对于EAs)通常以更多的血管模式以及更大的动脉僵硬来应对压力，以及 3)铅含量增加与血管对急性应激的反应增强有关。这些积累的证据有力地支持了这一假说，即铅暴露的R/E差异可能解释了心血管对急性应激反应的R/E差异以及左心室质量和动脉僵硬的R/E差异。

DESCRIPTION (provided by applicant): Cardiovascular disease (CVD) remains the leading cause of death in the United States and disables 10 million Americans each year. However, CVD risk in the US is higher for African Americans (AAs) relative to European Americans (EAs). In addition to R/E differences in CVD risk, there is extensive data demonstrating that, relative to EAs, AAs have higher rates of poverty and a corresponding increase in exposure to environmental toxicants, including lead (Pb), both in their blood and in their bones. Moreover, studies suggest a positive association between Pb and blood pressure, left ventricular hypertrophy, and CVD mortality. The current proposal addresses the question of whether R/E differences in CVD are partially a consequence of corresponding differences in exposure to Pb from the environment. Furthermore, this proposal considers whether these effects might be amplified by R/E differences in psychosocial background, including social control motives, background stress, and racial discrimination. Specifically, our proposal focuses on whether R/E differences in Pb exposure might produce differing rates of CVD risk through underlying alterations in cardiovascular responses to acute psychological stress, a mechanism whereby the psychosocial environment can affect CVD risk. In recent research (Gump, et al., 2011), increasing blood Pb was associated with alterations in cardiac autonomic regulation reflecting "co-inhibition" of both sympathetic and parasympathetic activity that is typically associated with greater vascular resistance, a cardiovascular pattern we had already observed in children with heightened early childhood blood Pb (Gump, et al., 2005). This vascular response to stress has also been shown to be associated with greater left ventricular mass, a significant predictor of cardiovascular morbidity. Interestingly, a number of studies have noted that AAs respond to psychological stress with a vascular pattern relative to EAs typical cardiac response and are more likely than EAs to develop left ventricular hypertrophy at similar levels of blood pressure, and have greater arterial stiffness as reflected by faster pulse wave velocity. In sum, there is evidence that: 1) AAs (relative to EAs) have higher levels of blood Pb, 2) AAs (relative to EAs) typically respond to stress with a more vascular pattern, as well as greater arterial stiffness and left ventricular mass, and 3) increasing Pb is associated with a heightened vascular response to acute stress. This accumulated evidence provides strong support for testing the hypothesis that R/E differences in Pb exposure might account for R/E differences in cardiovascular patterns of response to acute stress and R/E differences in left ventricular mass and arterial stiffness.