Valvular Heart Disease Stages Among Older Adults And The Proteomic Markers of Aortic Stenosis: The Atherosclerosis Risk in Communities Study
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Shelbaya, Khaled
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Shelbaya, Khaled. 2022. Valvular Heart Disease Stages Among Older Adults And The Proteomic Markers of Aortic Stenosis: The Atherosclerosis Risk in Communities Study. Master's thesis, Harvard Medical School.Abstract
Valvular heart disease (VHD) includes stenosis and regurgitation of the mitral and aorticvalves (AV). The prevalence of moderate to severe VHD is ~2.5% in the general population,
with aortic stenosis (AS) the most common moderate to severe valvular heart disease in the
United States. The prevalence of less than severe VHD is more common. (1,2) VHD prevalence
increases with advancing age, and the burden of VHD is expected to increase, as the US
population ages.(3) The American College of Cardiology /American Heart Association
(ACC/AHA) introduced the framework of VHD Stages to emphasize its progressive nature and
potential opportunities for prevention.(4) However, little is known regarding the communitybased
prevalence, prognostic relevance, and progression of ACC/AHA VHD Stages, particularly
those capturing non-severe VHD (i.e., Stage A and B). Furthermore, despite the progressive
nature of VHD, biomarkers to identify persons at risk and interventions to prevent VHD
progression are limited. The available biomarkers for its most common lesion (i.e., AS) –
troponin and NT-proBNP – are related to sequelae of AS on the left ventricle as opposed to
underlying mechanisms driving disease progression.(4)
In this work, we estimated the prevalence of VHD stages, their prognostic relevance for
incident cardiovascular diseases, and their progression over 6 years in late-life. In order to enable
preventive tools, we use high-throughput proteomics to discover potential biomarkers and
molecular pathways related to the progression of AS.
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