Changes in Coronary Noncalcified Volume in Relation to Changes in Cocaine Use

描述（由申请人提供）：虽然可卡因对临床心血管事件的影响已经被确定和研究，但可卡因使用对亚临床冠状动脉疾病（CAD）的影响尚未被彻底研究。在过去的12年里，我们在巴尔的摩跟踪调查了大约1000名非裔美国人（AA）可卡因使用者，以调查艾滋病毒感染者和非艾滋病毒感染者使用可卡因的心血管并发症。我们发现：(1)长期使用可卡因与冠状动脉非钙化斑块的存在有关；(2)长期使用可卡因与内皮功能障碍标志物有关；(3)他汀类药物可以逆转动脉粥样硬化斑块。尽管非钙化斑块更容易破裂，但它们是早期病变，可以通过他汀类药物逆转。由于新开发的软件可以测量冠状动脉非钙化斑块体积的变化，以及第二代西门子CT扫描仪低辐射剂量模式的可用性，冠状动脉CT血管造影（CTA）现在可以用于量化冠状动脉非钙化斑块体积的变化。由于很大一部分可卡因使用者感染了艾滋病毒和/或丙型肝炎，这可能使他们面临他汀类药物引起的肝毒性风险增加，因此迫切需要对可卡因引起的CAD进行非药物干预。针对这一RFA，我们建议进行一项为期3年的纵向研究，以确定减少可卡因使用是否会导致慢性可卡因使用者冠状动脉非钙化斑块体积的减少。减少可卡因的使用将通过采用行之有效的基于代金券的奖励办法来实现。本研究将招募140名非钙化斑块且Framingham评分较低的AA级慢性可卡因使用者。每个参与者都将参加一项为期12个月的以凭证为基础的奖励计划，以促进可卡因戒断或减少可卡因的使用，并在此期间进行密集跟踪，以收集吸毒数据。研究期间将进行3次冠状动脉CTA造影：基线、6个月随访和12个月随访。我们将把可卡因用量的变化与冠状动脉非钙化斑块的体积变化联系起来。本研究的具体目的如下：(1)评估基于凭证的激励疗法对慢性可卡因使用者冠状动脉非钙化斑块体积的影响；(2)使用冠状动脉CT血管造影检查与可卡因使用水平变化相关的冠状动脉非钙化体积的变化；(3)评估与可卡因使用水平变化相关的内皮功能生物标志物的变化。如果减少可卡因的使用会带来有利的结果，那么这项研究可以转化为精心设计的临床试验来证实和验证我们的发现。拟议的研究将是第一个

DESCRIPTION (provided by applicant): Although the impact of cocaine on clinical cardiovascular events has been identified and studied, the effects of cocaine use on subclinical coronary artery disease (CAD) has not yet been thoroughly investigated. In the past 12 years, we have been following up approximately 1,000 African American (AA) cocaine users in Baltimore to investigate cardiovascular complications of its use in people with and without HIV infection. We have found that (1) long-term cocaine use is associated with the presence of coronary noncalcified plaque, (2) long-term cocaine use is associated with endothelial dysfunction markers, and (3) atherosclerotic plaque can be reversed with statins medication. Although noncalcified plaques tend to be more vulnerable to rupture, they are early lesions and could be reversed with statin medication. Because of newly developed software that measures changes in coronary noncalcified plaque volume and the availability of low radiation dose modality with the second-generation Siemens CT scanner, coronary CT angiography (CTA) can now be used to quantify changes in coronary noncalcified plaque volume. Since a large proportion of cocaine users are infected with HIV and/or hepatitis C, which may put them at increased risk of statin-induced hepatotoxicity, a nonpharmaceutical intervention for cocaine-induced CAD is urgently needed for this population. Responding to this RFA, we propose to conduct a 3-year longitudinal study to determine whether reductions in cocaine use lead to reductions in coronary noncalcified plaque volume in chronic cocaine users. The reductions in cocaine use will be achieved with the use of well-established voucher-based incentives. A total of 140 AA chronic cocaine users with noncalcified plaques and low Framingham scores will be recruited into this investigation. Each participant will participate in a 12-month voucher-based incentives program to promote cocaine abstinence or reduce cocaine use and will be followed intensively during this time for collection of drug use data. Coronary CTA with contrast will be performed 3 times during the study: baseline, 6-month follow-up, and 12-month follow-up. We will correlate the changes in cocaine use with changes in volume of coronary noncalcified plaque. The specific aims of this proposed study are as follows: (1) To evaluate the effects of voucher-based incentives therapy on coronary noncalcified plaque volume in chronic cocaine users, (2) To use coronary CT angiography to examine changes in coronary noncalcified volume associated with changes in the levels of cocaine use, and (3) To evaluate changes in biomarkers of endothelial function associated with changes in the levels of cocaine use. If reductions in cocaine use lead to a favorable outcome, this study could be translated into well-designed clinical trials to confirm and validate our findings. The proposed study will be the first to focus on secondary prevention of CAD with the use of voucher-based interventions in chronic cocaine users.