Protease Inhibitor Related Dyslipidemia

描述（由申请人提供）：本申报资料是6年前资助的一个项目的延续，该项目旨在确定HIV感染者心血管疾病相关因素的RFA。我们最初的项目描述了以3年为间隔的CVD异常替代标志物（颈动脉内膜中层厚度和冠状动脉钙评分）的预测因子。检查抗逆转录病毒治疗方案、HIV疾病活动性标志物、C-反应蛋白和血脂谱（包括常规血脂谱、富含甘油三酯的残余脂蛋白、Lp（a）、同型半胱氨酸、空腹血糖、游离脂肪酸和胰岛素水平）、BMI、人体测量法测定的身体组成、BIA和DXA以及传统危险因素（吸烟、饮食、血压、年龄、性别、家族史）。从我们的原始拨款以及其他人的分析表明，传统的心血管危险因素是最常见的预测异常替代标志物在这个患者人群中，Pis或其他抗逆转录病毒药物诱导的血脂异常的影响和HIV及其相关炎症的作用，这种风险增加仍不清楚。迄今为止，尚无HIV替代标志物研究对HIV感染患者进行了为期6年的随访，这可能是检测血脂异常或HIV对个体疾病进展影响的最佳方法。很明显，HIV感染本身诱导低HDL-胆固醇水平，我们有初步的数据表明，HIV感染者具有致动脉粥样硬化的HDL亚群特征。高密度脂蛋白亚群对心血管疾病风险的预测价值可能比单独的高密度脂蛋白胆固醇更高。我们现在知道，它是选定的抗逆转录病毒药物，而不是代理的类别，与更严重的血脂异常的HIV感染人群，并建议检查这些代理（洛匹那韦/利托那韦，d4 t，依法韦仑）以及传统的和新兴的危险因素对HDL亚谱和CVD的替代标志物的影响。慢性炎症标志物被认为是CVD的独立预测因子;它们还预测HIV感染的进展，并可能反映感染个体中HIV疾病的累积负担。我们建议扩大我们的慢性炎症研究，增加CRP亚型和sPLA 2的CRP测定，以检查这些与致动脉粥样硬化的血脂谱和异常的替代标记物在我们的队列。我们建议在R 01的延续中延长我们的替代标志物研究的持续时间，以研究6年内HIV感染人群中c-IMT和冠状动脉钙评分的进展，并记录HIV感染队列中HDL亚群和炎症标志物在新的资助期内的变化。HDL亚群的纵向测定，同时测定cIMT和冠状动脉钙评分在6年的HIV感染队列是新的这个项目。

DESCRIPTION (provided by applicant): This submission is the renewal of a project that was funded 6 years ago in response to an RFA that sought to determine the factors associated with cardiovascular disease in HI V-infected individuals. Our original project described predictors of abnormal surrogate markers of CVD (carotid intimal medial thickness and coronary calcium score) done at a 3 year interval. Antiretroviral regimens, markers of HIV disease activity, C- reactive protein and lipid profiles (including conventional lipid profiles, triglyceride-rich remnant lipoproteins, Lp(a), homocysteine, fasting blood glucose, free fatty acids and insulin levels), BMI, body composition by anthropometery , BIA and DXA as well as traditional risk factors (smoking, diet, blood pressure, age, gender, family history) were examined. Analyses from our original grant as well as others have suggested that traditional cardiovascular risk factors are the most common predictors for abnormal surrogate markers in this patient population; the impact of the dyslipidemia induced by Pis or other antiretroviral agents and the role of HIV and its associated inflammation on this increased risk remain unclear. To date no HIV surrogate marker studies have followed HIV-infected patients for the 6 year period that may be optimal detect the impact of the dyslipidemia or HIV on progression of disease in individuals. It remains clear that HIV infection itself induces low HDL-cholesterol levels and we have preliminary data that suggest that HIV infected individuals have an atherogenic HDL subpopulation profile. It appears that HDL-subpopulations may have a greater predictive value for risk of CVD than HDL-C alone. We now know that it is selected antiretroviral agents, not classes of agents, that are associated with more severe dyslipidemia in HIV-infected populations and propose to examine the impact of these agents (lopinavir/ritonavir, d4t, efavirenz) as well as traditional and emerging risk factors on HDL subprofiles and on surrogate markers of CVD. Markers of chronic inflammation are considered to be independent predictors of CVD; they also predict progression in HIV-infection and may reflect the cumulative burden of HIV disease in an infected individual. We propose to expand our studies of chronic inflammation adding CRP isoforms and sPLA2 to the determination of CRP to examine the association of these with atherogenic lipid profiles and with abnormal surrogate makers in our cohort. We propose to extend the duration of our surrogate marker studies in this continuation of our R01, to study the progression of c-IMT and coronary calcium score in an HIV infected population over 6 years and to document the changes in HDL subpopulations and inflammatory markers over the new grant period in our HIV infected cohort. The longitudinal determination of HDL subpopulations, the simultaneous determination of both cIMT and coronary calcium scores at 6 years in an HIV infected cohort are novel to this project.