The candidate's previous activity has been devoted to patient-oriented research. In recent years, he has focused on the use of echocardiography to identify new cardioembolic sources for ischemic stroke, especially patent foramen ovale and aortic arch plaques, and has`been awarded two R01 grants from NINDS for such efforts. The candidate's overall career goal is to continue his research in the field of cardioembolic stroke, contributing to the explanation of the mechanisms of some cryptogenic strokes and therefore to a rational preventive and therapeutic approach. The candidate is also committed to mentoring young investigators, as documented by his long-standing and successful training of cardiology, fellows. Columbia University is an ideal environment to foster the candidate's career growth because of the strong, infrastructure for clinical research, the presence of world renowned cardiologists and neurologists for consultation and collaboration, and the firm institutional commitment to patient-oriented research. Crucial to the candidate's career development will be the transition from the relatively small case-control studies performed so far to the proposed large prospective study of subclinical echocardiocraphic abnormalities and stroke risk. A population-based prospective cohort study is proposed to determine the independent contribution of left ventricular hypertrophy (LVH) and geometric pattern, decreased LV ejection fraction, segmental wall motion abnormalities and left atrial enlargement to the risk of ischemic stroke and vascular events in a tri-ethnic population, and the existence of a dose-response relationship. The progression of these abnormalities over time will also be assessed. Secondary aims will be to evaluate the modification of risk by traditional stroke risk factors, and the assessment of the risk associated with less frequent abnormalities (patent foramen ovale, mitral annular calcification, mitral valve prolapse). Finally, the prevalence of a patent foramen ovale in each race-ethnic group will be evaluated. A cohort of 2500 white, black and Hispanic adults over age 55 will be enrolled from the ongoing Northern Manhattan Stroke Study (NOMASS), assuring cost-effective recruitment, data collection and follow-up. Two-dimensional echocardiography with contrast injection will be performed. A new three-dimensional technique will also be used to assess LVH. Annual telephone follow-up will be performed to ascertain stroke, myocardial infarction and death. In-person follow-up will be done in subjects with suspected outcome and in a random 10% of the cohort. Kaplan Meier curves and Cox-proportional hazard models will be used to calculate adjusted event rates and assess the dependence of exposures of interest on stroke and vascular events adjusting for demographics and stroke risk factors. In a subgroup of 900 subjects, echocardiography will be repeated 3 years after the first test to study the progession of echocardioaraphic abnormalities. This study will be the first prospective cohort study to evaluate the role of multiple echocardiographic risk factors for ischemic stroke in a community of whites, blacks and Hispanics living in the same area.
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