Novel Lipoproteins, Cardiometabolic Risk, and Statin Therapy

应聘者：萨米亚·莫拉，医学博士，医学硕士，哈佛医学院布里格姆妇女医院预防和心血管内科助理教授。她接受过心血管医学的培训和认证，并拥有约翰霍普金斯大学彭博公共卫生学院的流行病学硕士学位。她的长期职业目标是成为心血管疾病(CVD)预防和流行病学领域的领导者。为了实现这一目标，她制定了以导师为基础的研究职业发展计划，提供培训以实现3个短期目标：1)在脂类和脂蛋白风险因素、心脏代谢紊乱和妇女健康方面获得了解和能力；2)获得设计、管理和解释大型前瞻性研究和临床试验所需的经验和技能；3)发展专业和职业生涯建设领导技能。目前的预防指南建议测量标准血脂以评估心血管疾病的风险，并将重点放在降低低密度脂蛋白胆固醇作为治疗的主要目标上。这些指南不建议对新的脂蛋白进行常规测量，因为尚不清楚它们是否在标准的脂类测量之外提供了心血管风险信息。这项研究建议的中心目标是确定在心血管疾病和2型糖尿病的一级预防中，新的脂蛋白是否比标准脂类更好地衡量心脏代谢风险。我们建议进行一项新的脂蛋白(免疫测定测定的载脂蛋白和核磁共振测定的脂蛋白)与心血管疾病和2型糖尿病发病的关系的全面研究，对象为表面上健康的个体和有代谢综合征的人，分别使用和不使用他汀类药物治疗。特殊目的1测试新的脂蛋白在预测心血管疾病和2型糖尿病发病中的关联性。特殊目的2测试新的脂蛋白是否增加了与心血管疾病和2型糖尿病风险相关的代谢综合征的定义。具体目标3研究了他汀类药物治疗引起的新型脂蛋白的变化，以及它们与代谢综合征患者心血管疾病风险降低的关系。相关性(见说明)：尽管心血管疾病和2型糖尿病带来了广泛的负担，但根据目前依赖于标准血脂测试的指南，大约1.4亿无症状的美国成年人被归类为低风险。在这大量无症状的成年人中，对更好的风险评估和成本效益治疗的需求尚未得到满足。新的脂蛋白可能会促进心血管疾病和代谢性疾病的风险检测和治疗。

DESCRIPTION (provided by applicant): The candidate, Samia Mora, MD, MHS, is an Assistant Professor of Medicine in the Divisions of Preventive and Cardiovascular Medicine at the Brigham and Women's Hospital, Harvard Medical School. She is trained and certified in Cardiovascular Medicine and has an MHS in Epidemiology from the Johns Hopkins Bloomberg School of Public Health. Her long-term career goal is to become a leader in the field of cardiovascular disease (CVD) prevention and epidemiology. To realize this goal, she has developed a mentor-based research career development plan which provides training to achieve 3 short-term goals: 1) to gain understanding and competence in lipid and lipoprotein risk factors, cardiometabolic disorders, and women's health, 2) to gain experience and skills necessary to design, manage, and interpret large prospective studies and clinical trials, and 3) to develop professional and career-building leadership skills. Current prevention guidelines recommend measurement of standard lipids to assess CVD risk and focus on LDL cholesterol lowering as the primary target of therapy. These guidelines do not recommend the routine measurement of novel lipoproteins since it is unclear whether they contribute CVD risk information beyond standard lipid measurements. The central goal of this research proposal is to ascertain whether novel lipoproteins are better measures of cardiometabolic risk than standard lipids for the primary prevention of CVD and type 2 diabetes. We propose to conduct a comprehensive study of novel lipoproteins (immunoassay-measured apolipoproteins and nuclear magnetic resonance-measured lipoproteins) in relation to incident CVD and type 2 diabetes in apparently healthy individuals and those with the metabolic syndrome, with and without statin therapy. Specific Aim 1 tests the association of novel lipoproteins in predicting incident CVD and type 2 diabetes. Specific Aim 2 tests whether novel lipoproteins add to the definition of the metabolic syndrome in relation to risk of CVD and type 2 diabetes. Specific Aim 3 examines changes in novel lipoproteins that result from statin therapy and their association with CVD risk reduction in individuals with and without the metabolic syndrome. RELEVANCE (See instructions): Despite the extensive burden of CVD and type 2 diabetes, approximately 140 million asymptomatic US adults are classified as low risk by current guidelines that rely on standard lipid tests. There is an unmet need for better risk assessment and cost-effective therapies in this large number of asymptomatic adults. Novel lipoproteins may advance risk detection and therapies for CVD and metabolic diseases.