Novel Lipoproteins, Cardiometabolic Risk, and Statin Therapy

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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.