Sub-Clinical Coronary Artery Disease in South Asian Immigrants: Determination of

描述（由申请人提供）：在心血管疾病中，冠状动脉疾病（CAD）是美国的主要死亡原因，南亚人（祖先在印度次大陆的人，即印度、巴基斯坦、孟加拉国、尼泊尔、不丹和斯里兰卡）的CAD和代谢综合征负担不成比例地更大。代谢异常似乎对遗传易感个体CAD的发展有协同作用。虽然南亚移民是美国增长第二快的亚洲移民人口，但关于他们患CAD的风险增加却知之甚少。由于经典的风险因素可能无法完全解释CAD风险的增加，因此假设南亚人的CAD高发病率是由于独特的遗传易感性和生活方式因素的结合。亚临床CAD的早期检测可以预防冠状动脉事件，并大大降低南亚移民CAD的死亡率和发病率。本可行性研究的主要目的是：（a）使用颈总动脉内膜中层厚度（IMT）作为动脉粥样硬化的替代标志物，评估南亚移民中亚临床CAD的患病率;（B）评价招募程序、飞行员再现性，并确定仪器的准确性。此外，我们将确定功能失调的HDL和载脂蛋白A-I多态性在南亚移民，并探讨与亚临床CAD使用颈动脉IMT作为动脉粥样硬化的替代标志物的相关性。我们计划招募150名居住在格鲁吉亚两个主要城市（即亚特兰大和奥古斯塔）的南亚移民，并进行颈动脉多普勒超声检查，并评估CAD的几个风险因素，例如总胆固醇、LDL、HDL、载脂蛋白A-I（Apo A-I）、同型半胱氨酸和C反应蛋白的水平。我们将专门评估该组中功能失调的HDL（促炎性HDL）水平和Apo A-I多态性的存在。这项研究的广泛，长期目标是探索CAD的一些未知原因，这些原因可能解释南亚移民CAD的过度风险增加。本可行性研究的结果将有助于识别患者招募、方案执行、质量控制和数据管理中的潜在问题，这将有助于开展更大规模的研究（R 01）。此外，确定南亚移民中存在功能失调的HDL将回答与HDL水平和功能改变的可能原因相关的几个问题。这些信息不仅有助于对高危人群进行分层，而且从疾病管理的角度来看也很有用。本研究的结果将有助于开展长期前瞻性研究，以评估Apo A-I基因多态性与CAD风险的关联。 公共卫生相关性：南亚移民是美国冠状动脉疾病（CAD）患病率第二高的亚洲移民人口。传统的危险因素可能不能完全解释这种高风险，基因-环境相互作用起重要作用。使用颈动脉IMT测量作为动脉粥样硬化的替代标志物的亚临床CAD的早期检测将有助于分层为高风险组，这些组可以从预防策略中受益以减少冠状动脉事件。该研究还将确定南亚移民中高CAD的一些未知原因。HDL和Apo-A-1基因多态性在CAD中起重要作用，本研究获得的信息不仅有助于对高危人群进行分层，而且从疾病管理的角度来看也是有用的。此外，基因多态性的鉴定可能导致筛查测试，其将允许处于发展CAD的风险中的人足够早地被鉴定，从而可以实施预防/干预策略以预防或改善疾病过程。

DESCRIPTION (provided by applicant): Among cardiovascular diseases, coronary artery disease (CAD) is the leading cause of death in the United States, and South Asians (people whose ancestral origin is in the Indian subcontinent i.e. India, Pakistan, Bangladesh, Nepal, Bhutan, and Sri Lanka) carry a disproportionately larger burden of CAD and metabolic syndrome. Metabolic abnormalities seem to have a synergistic effect on the development of CAD in genetically susceptible individuals. Although South Asian immigrants represent the second fastest growing Asian immigrant population in the United States, little is known regarding their increased risk for CAD. As classical risk factors may not fully explain the increased risk for CAD, the high rate of CAD among South Asians is hypothesized to be due to a combination of unique genetic predisposition and lifestyle factors. Early detection of sub-clinical CAD could prevent coronary events and substantially reduce the level of mortality and morbidity attributable to CAD in South Asian immigrants. The primary objectives of this feasibility study are to (a) assess the prevalence of sub-clinical CAD among South Asian immigrants using common carotid artery intima-media thickness (IMT) as a surrogate marker of atherosclerosis and (b) evaluate recruitment procedures, pilot reproducibility, and determine accuracy of instruments. In addition, we will identify dysfunctional HDL and Apo A-I polymorphisms among South Asian immigrants and explore the correlation with sub-clinical CAD using carotid IMT as a surrogate marker of atherosclerosis. We plan to recruit 150 South Asian immigrants living in two of the main cities in Georgia, i.e. Atlanta and Augusta, and to perform carotid artery Doppler ultrasound, and to assess several risk factors for CAD e.g. the levels of total cholesterol, LDL, HDL, Apo lipoprotein A-I (Apo A-I), homocysteine, and C- reactive proteins. We will specifically assess the level of dysfunctional HDL (pro-inflammatory HDL) and the presence of Apo A-I polymorphisms in this group. The broad, long-term goals of this research are to explore some of the unknown causes of CAD that may explain the increased excess risk of CAD in South Asian immigrants. The results of this feasibility study will assist in identifying potential issues in patient recruitment, protocol conduction, quality control and data management that will be helpful in developing larger studies (R01). In addition, determining the presence of dysfunctional HDL in South Asian immigrants will answer several questions related to the possible causes of altered HDL levels and functions. This information will not only help to stratify a high risk group, but will also be useful from a disease management point of view. The results obtained from this study will be useful to develop long-term prospective studies to assess the association of Apo A-I gene polymorphisms with CAD risk. PUBLIC HEALTH RELEVANCE: South Asian immigrants are the second highest Asian immigrant population in the United State carrying high coronary artery disease (CAD) prevalence. Traditional risk factors may not fully explain this high CAD risk and gene-environment interactions play important role. Early detection of sub- clinical CAD using carotid IMT measurements as a surrogate marker of atherosclerosis will be useful to stratify into high risk group, who can benefit from preventive strategies to reduce coronary events This study will also identify some of the unknown causes of high CAD in South Asian immigrants. Dysfunctional HDL and Apo-A-1 polymorphisms play important role in CAD and information obtained from this study will not only help to stratify high risk group, but will also be useful from a disease management point of view. Furthermore, the identification of gene polymorphisms may lead to screening tests that will allow persons at risk for developing CAD to be identified early enough that prevention/intervention strategies can be implemented to prevent or ameliorate the disease process.