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）是美国人死亡的主要原因，南亚人（祖籍在印度次大陆的人，即印度、巴基斯坦、孟加拉国、尼泊尔、不丹和斯里兰卡）患冠心病和代谢综合征的负担更大。代谢异常似乎对遗传易感个体的CAD发展有协同作用。尽管南亚移民是美国增长第二快的亚洲移民，但人们对他们患冠心病的风险却知之甚少。由于传统的风险因素可能不能完全解释冠心病风险的增加，因此假设南亚人的高冠心病发病率是由于独特的遗传易感性和生活方式因素的结合。早期发现亚临床冠心病可以预防冠心病事件，并大大降低南亚移民冠心病的死亡率和发病率。这项可行性研究的主要目的是(a)利用颈总动脉内膜-中膜厚度（IMT）作为动脉粥样硬化的替代指标，评估南亚移民中亚临床CAD的患病率；(b)评估招募程序、试验可重复性，并确定仪器的准确性。此外，我们将确定南亚移民中功能失调的HDL和Apo a - i多态性，并利用颈动脉IMT作为动脉粥样硬化的替代标记物，探讨其与亚临床CAD的相关性。我们计划招募150名居住在佐治亚州亚特兰大和奥古斯塔两个主要城市的南亚移民，进行颈动脉多普勒超声检查，并评估CAD的几个危险因素，如总胆固醇、低密度脂蛋白、高密度脂蛋白、载脂蛋白A-I （Apo A-I）、同型半胱氨酸和C反应蛋白水平。我们将专门评估功能失调HDL（促炎性HDL）的水平和载脂蛋白A-I多态性的存在。本研究的广泛、长期目标是探索冠心病的一些未知原因，这些原因可能解释南亚移民患冠心病的风险增加。这项可行性研究的结果将有助于确定患者招募、方案实施、质量控制和数据管理方面的潜在问题，这将有助于开展更大规模的研究（R01）。此外，确定南亚移民中HDL功能障碍的存在将回答与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是有用的。这项研究的结果将有助于开展长期的前瞻性研究，以评估载脂蛋白a - 1基因多态性与冠心病风险的关系。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CAD风险，基因与环境的相互作用起着重要作用。使用颈动脉IMT测量作为动脉粥样硬化的替代标记物来早期检测亚临床CAD将有助于对高危人群进行分层，他们可以从预防策略中获益以减少冠状动脉事件。这项研究还将确定南亚移民中高CAD的一些未知原因。功能失调的HDL和载脂蛋白a -1多态性在CAD中起着重要作用，从本研究中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，基因多态性的识别可能导致筛查测试，这将使有患CAD风险的人能够及早发现，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.