Harumitsu Suzuki1, Kendra Davis-Plourde2,3, Alexa Beiser3,4, Ayako Kunimura2,5, Katsuyuki Miura6, Charles DeCarli7, Pauline Maillard7, Gary F Mitchell8, Ramachandran S Vasan2,9,10,11, Sudha Seshadri2,4,12, Akira Fujiyoshi1. 1. Department of Hygiene, Wakayama Medical University, Japan (H.S., A.F.). 2. The Framingham Heart Study, MA (K.D.-P., A.B., R.S.V., S.S.). 3. Department of Biostatistics, Boston University School of Public Health, MA (K.D.-P., A.B.). 4. Department of Neurology (A.B., S.S.), Boston University School of Medicine, MA. 5. Kobe Rosai Hospital, Japan (A.K.). 6. NCD Epidemiology Research Center and Department of Public Health, Shiga University of Medical Science, Japan (K.M.). 7. Department of Neurology and Center for Neuroscience, University of California Davis (C.D., P.M.). 8. Cardiovascular Engineering Inc, Norwood, MA (G.F.M.). 9. Section of Cardiovascular Medicine (R.S.V.), Boston University School of Medicine, MA. 10. Sections of Preventive Medicine and Epidemiology (R.S.V.), Boston University School of Medicine, MA. 11. Department of Epidemiology, Boston University School of Public Health, MA (R.S.V.). 12. Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, University of Texas Health Sciences Center, San Antonio (S.S.).
Abstract
BACKGROUND: Using magnetic resonance diffusion tensor imaging, we previously showed a cross-sectional association between carotid-femoral pulse wave velocity, a measure of aortic stiffness, and subtle white matter injury in clinically asymptomatic middle-age adults. While coronary artery calcium (CAC) is a robust measure of atherosclerosis, and a predictor of stroke and dementia, whether it predicts diffusion tensor imaging-based subtle white matter injury in the brain remains unknown. METHODS: In FHS (Framingham Heart Study), an observational study, third-generation participants were assessed for CAC (2002-2005) and brain magnetic resonance imaging (2009-2014). Outcomes were diffusion tensor imaging-based measures; free water, fractional anisotropy, and peak width of mean diffusivity. After excluding the participants with neurological conditions and missing covariates, we categorized participants into 3 groups according to CAC score (0, 0 < to 100, and >100) and calculated a linear trend across the CAC groups. In secondary analyses treating CAC score as continuous, we computed slope of the outcomes per 20 to 80th percentiles higher log-transformed CAC score using linear regression. RESULTS: In a total of 1052 individuals analyzed (mean age 45.4 years, 45.4% women), 71.6%, 22.4%, and 6.0% had CAC score of 0, 0 < to 100, and >100, respectively. We observed a significant linear trend of fractional anisotropy, but not other measures, across the CAC groups after multivariable adjustment. In the secondary analyses, CAC was associated with lower fractional anisotropy in men but not in women. CONCLUSIONS: CAC may be a promising tool to predict prevalent subtle white matter injury of the brain in asymptomatic middle-aged men.
BACKGROUND: Using magnetic resonance diffusion tensor imaging, we previously showed a cross-sectional association between carotid-femoral pulse wave velocity, a measure of aortic stiffness, and subtle white matter injury in clinically asymptomatic middle-age adults. While coronary artery calcium (CAC) is a robust measure of atherosclerosis, and a predictor of stroke and dementia, whether it predicts diffusion tensor imaging-based subtle white matter injury in the brain remains unknown. METHODS: In FHS (Framingham Heart Study), an observational study, third-generation participants were assessed for CAC (2002-2005) and brain magnetic resonance imaging (2009-2014). Outcomes were diffusion tensor imaging-based measures; free water, fractional anisotropy, and peak width of mean diffusivity. After excluding the participants with neurological conditions and missing covariates, we categorized participants into 3 groups according to CAC score (0, 0 < to 100, and >100) and calculated a linear trend across the CAC groups. In secondary analyses treating CAC score as continuous, we computed slope of the outcomes per 20 to 80th percentiles higher log-transformed CAC score using linear regression. RESULTS: In a total of 1052 individuals analyzed (mean age 45.4 years, 45.4% women), 71.6%, 22.4%, and 6.0% had CAC score of 0, 0 < to 100, and >100, respectively. We observed a significant linear trend of fractional anisotropy, but not other measures, across the CAC groups after multivariable adjustment. In the secondary analyses, CAC was associated with lower fractional anisotropy in men but not in women. CONCLUSIONS: CAC may be a promising tool to predict prevalent subtle white matter injury of the brain in asymptomatic middle-aged men.
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