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 #
5R01NS017950-32
Application #
8488487
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
2013-07-01
Budget End
2014-06-30
Support Year
32
Fiscal Year
2013
Total Cost
$827,250
Indirect Cost
$316,235
Name
Boston University
Department
Neurology
Type
Schools of Medicine
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02118
Adams, Shayna; Conner, Sarah; Himali, Jayandra J et al. (2018) Vascular risk factor burden and new-onset depression in the community. Prev Med 111:348-350
Satizabal, Claudia L; Samieri, C├ęcilia; Davis-Plourde, Kendra L et al. (2018) APOE and the Association of Fatty Acids With the Risk of Stroke, Coronary Heart Disease, and Mortality. Stroke 49:2822-2829
McGrath, Emer R; Seshadri, Sudha (2018) Author response: Blood pressure from mid- to late life and risk of incident dementia. Neurology 91:149
Seiler, Stephan; Fletcher, Evan; Hassan-Ali, Kinsy et al. (2018) Cerebral tract integrity relates to white matter hyperintensities, cortex volume, and cognition. Neurobiol Aging 72:14-22
Nishtala, Arvind; Piers, Ryan J; Himali, Jayandra J et al. (2018) Atrial fibrillation and cognitive decline in the Framingham Heart Study. Heart Rhythm 15:166-172
Jian, Xueqiu; Satizabal, Claudia L; Smith, Albert V et al. (2018) Exome Chip Analysis Identifies Low-Frequency and Rare Variants in MRPL38 for White Matter Hyperintensities on Brain Magnetic Resonance Imaging. Stroke 49:1812-1819
Weinstein, Galit; Zelber-Sagi, Shira; Preis, Sarah R et al. (2018) Association of Nonalcoholic Fatty Liver Disease With Lower Brain Volume in Healthy Middle-aged Adults in the Framingham Study. JAMA Neurol 75:97-104
Bangen, Katherine J; Preis, Sarah R; Delano-Wood, Lisa et al. (2018) Baseline White Matter Hyperintensities and Hippocampal Volume are Associated With Conversion From Normal Cognition to Mild Cognitive Impairment in the Framingham Offspring Study. Alzheimer Dis Assoc Disord 32:50-56
Tynkkynen, Juho; Chouraki, Vincent; van der Lee, Sven J et al. (2018) Association of branched-chain amino acids and other circulating metabolites with risk of incident dementia and Alzheimer's disease: A prospective study in eight cohorts. Alzheimers Dement 14:723-733
Davies, Gail; Lam, Max; Harris, Sarah E et al. (2018) Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function. Nat Commun 9:2098

Showing the most recent 10 out of 501 publications