Stroke is the 3rd leading cause of death in the United States and is the major disabling neurological disease of adults, particularly the elderly. Risk factors predisposing to stroke have been identified through prospective epidemiologic studies including the Framingham Heart Study. Control of stroke risk factors has guided preventive efforts and has led to significant reduction in death and disability from stroke;however, much work remains to be done. Since 1981, the Precursors of Stroke Incidence and Prognosis study has enabled us to identify risk factors for stroke, report on secular trends, lifetime risk and manifestations of stroke and of specific stroke subtypes using consistent clinical and imaging criteria. Twelve hundred nineteen completed strokes have been documented to date. We plan to maintain surveillance and identify incident and recurrent strokes in this 3 generation community- based epidemiologic study and to personally evaluate subjects at the time of stroke in the local hospital, and at 3, 6, 12 and 24 months. We will systematically assess neurological, imaging (MRI &MRAs), functional, cognitive and mood outcomes in these subjects and provide estimates of lifetime risk, secular trends in stroke risk factors, incidence and recurrence, case fatality, disability, and institutionalization. In this renewal we propose to utilize an extensive panel of biomarkers, measured prior to stroke and to relate genoptypic data from a 550K Genome Wide Association study to stroke incidence and outcomes. These exciting and innovative additions are available as a result of funding from other NIH sources to the Framingham Heart Study and hold promise to add new insights to the identification of stroke susceptibility. In addition, a wealth of previously collected subclinical vascular disease measures are available including: echocardiography, carotid ultrasound, MRI and CT scans of the heart and aorta;vascular function studies - arterial stiffness, ankle-brachial index and brachial artery reactivity;and baseline and repeated quantitative brain MR scans, including silent strokes on >2,400 Offspring subjects. These indicators of subclinical cardiac and vascular disease may greatly enhance our ability to identify susceptible stroke-prone individuals. It is anticipated that adding this wide array of biomarker, GWA and subclinical disease data to conventional and newer risk factor measures will facilitate better stroke prediction by an improved Stroke Risk Profile.

Public Health Relevance

The public health burden of stroke is substantial in our aging population. The goal of this renewal application is to continue to prospectively identify health and genetic factors that contribute to placing a person at high risk of stroke. Understanding these interactions will advance our ability to formulate strategies to prevent stroke and minimize disability resulting from stroke.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS017950-31
Application #
8300940
Study Section
Special Emphasis Panel (ZRG1-HOP-V (02))
Program Officer
Moy, Claudia S
Project Start
1981-12-01
Project End
2014-06-30
Budget Start
2012-07-01
Budget End
2013-06-30
Support Year
31
Fiscal Year
2012
Total Cost
$847,393
Indirect Cost
$390,443
Name
Boston University
Department
Neurology
Type
Schools of Medicine
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02118
Weinstein, Galit; Beiser, Alexa S; Preis, Sarah R et al. (2016) Plasma clusterin levels and risk of dementia, Alzheimer's disease, and stroke. Alzheimers Dement (Amst) 3:103-9
Rahman, Faisal; Wang, Na; Yin, Xiaoyan et al. (2016) Atrial flutter: Clinical risk factors and adverse outcomes in the Framingham Heart Study. Heart Rhythm 13:233-40
de Vries, Paul S; Chasman, Daniel I; Sabater-Lleal, Maria et al. (2016) A meta-analysis of 120 246 individuals identifies 18 new loci for fibrinogen concentration. Hum Mol Genet 25:358-70
Karakis, Ioannis; Pase, Matthew P; Beiser, Alexa et al. (2016) Association of Serum Vitamin D with the Risk of Incident Dementia and Subclinical Indices of Brain Aging: The Framingham Heart Study. J Alzheimers Dis 51:451-61
Choi, Seung Hoan; Ruggiero, Daniela; Sorice, Rossella et al. (2016) Six Novel Loci Associated with Circulating VEGF Levels Identified by a Meta-analysis of Genome-Wide Association Studies. PLoS Genet 12:e1005874
Williams, Stephen R; Hsu, Fang-Chi; Keene, Keith L et al. (2016) Shared genetic susceptibility of vascular-related biomarkers with ischemic and recurrent stroke. Neurology 86:351-9
Yu, Bing; Pulit, Sara L; Hwang, Shih-Jen et al. (2016) Rare Exome Sequence Variants in CLCN6 Reduce Blood Pressure Levels and Hypertension Risk. Circ Cardiovasc Genet 9:64-70
Qiu, Wei Qiao; Himali, Jayandra J; Wolf, Philip A et al. (2016) Effects of white matter integrity and brain volumes on late life depression in the Framingham Heart Study. Int J Geriatr Psychiatry :
Nayor, Matthew; Enserro, Danielle M; Beiser, Alexa S et al. (2016) Association of Exhaled Carbon Monoxide With Stroke Incidence and Subclinical Vascular Brain Injury: Framingham Heart Study. Stroke 47:383-9
Pase, Matthew P; Beiser, Alexa; Himali, Jayandra J et al. (2016) Aortic Stiffness and the Risk of Incident Mild Cognitive Impairment and Dementia. Stroke 47:2256-61

Showing the most recent 10 out of 367 publications