title: Carotid Atherosclerosis and Cerebral Microbleeds: The Framingham Heart Study.
abstract: BACKGROUND
  Carotid atherosclerosis is associated with subclinical ischemic cerebrovascular disease, but its role in hemorrhage-prone small vessel disease-represented by cerebral microbleed (CMB)-is unclear, although vascular risk factors underlie both conditions. We hypothesized that persons with carotid atherosclerosis would have higher risk of CMB, particularly in deep regions.
  
  
  RESULTS
  We studied 1243 participants in the Framingham Offspring Study (aged 56.9±8.8 years; 53% women) with carotid ultrasound available on 2 occasions (1995-1998 and 2005-2008) prior to brain magnetic resonance imaging. Using multivariable logistic regression, we related baseline carotid stenosis, baseline intima-media thickness, and site-specific carotid intima-media thickness progression (at internal and common carotid locations) to the prevalence and location (lobar or deep plus mixed) of CMB. In addition, we assessed effect modification by lipid levels and use of statin and antithrombotic medications. Carotid stenosis ≥25% (a marker of cerebrovascular atherosclerosis) was associated with presence of CMB overall (Odds Ratio 2.20, 95% CI 1.10-4.40) and at deep and mixed locations (odds ratio 3.60, 95% CI 1.23-10.5). Baseline carotid intima-media thickness was not associated with CMB. Progression of common carotid artery intima-media thickness among persons on hypertension treatment was associated with lower risk of deep and mixed CMB (odds ratio per SD 0.41, 95% CI 0.18-0.96).
  
  
  CONCLUSIONS
  Cumulative vascular risk factor exposure may increase the risk of CMB, especially in deep regions. The apparent paradoxical association of carotid intima-media thickness progression with lower risk of CMB may reflect benefits of intensive vascular risk factor treatment among persons with higher cardiovascular risk and deserves further investigation. If replicated, the results may have potential implications for assessment of preventive and therapeutic interventions for subclinical cerebral hemorrhage.
authors.affiliation: Department of Neurology, School of Public Health at Boston University, Boston, MA joromero@bmc.org.
authors.forename: José R
authors.initials: JR
authors.lastname: Romero
authors.affiliation: Department of Biostatistics, School of Medicine, School of Public Health at Boston University, Boston, MA NHLBI's Framingham Heart Study, Framingham, MA.
authors.forename: Sarah R
authors.initials: SR
authors.lastname: Preis
authors.affiliation: Department of Neurology, School of Public Health at Boston University, Boston, MA Department of Biostatistics, School of Medicine, School of Public Health at Boston University, Boston, MA NHLBI's Framingham Heart Study, Framingham, MA.
authors.forename: Alexa
authors.initials: A
authors.lastname: Beiser
authors.affiliation: Department of Neurology, University of California- Davis, Sacramento, CA.
authors.forename: Charles
authors.initials: C
authors.lastname: DeCarli
authors.affiliation: Department of Mathematics and Statistics, Boston University, Boston, MA NHLBI's Framingham Heart Study, Framingham, MA.
authors.forename: Ralph B
authors.initials: RB
authors.lastname: D'Agostino
authors.affiliation: Department of Neurology, School of Public Health at Boston University, Boston, MA NHLBI's Framingham Heart Study, Framingham, MA.
authors.forename: Philip A
authors.initials: PA
authors.lastname: Wolf
authors.affiliation: Section of Preventive Medicine, School of Public Health at Boston University, Boston, MA Section of Cardiology, School of Public Health at Boston University, Boston, MA NHLBI's Framingham Heart Study, Framingham, MA.
authors.forename: Ramachandran S
authors.initials: RS
authors.lastname: Vasan
authors.affiliation: Department of Radiology, Tufts University School of Medicine, Boston, MA NHLBI's Framingham Heart Study, Framingham, MA.
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Polak
authors.affiliation: Department of Neurology, School of Public Health at Boston University, Boston, MA NHLBI's Framingham Heart Study, Framingham, MA.
authors.forename: Sudha
authors.initials: S
authors.lastname: Seshadri
mesh_terms: D000368:Aged; D059168:Carotid Intima-Media Thickness; D016893:Carotid Stenosis / Q000175:diagnosis / Q000453:epidemiology*; D002543:Cerebral Hemorrhage / Q000175:diagnosis / Q000453:epidemiology* / Q000503:physiopathology; D059345:Cerebral Small Vessel Diseases / Q000175:diagnosis / Q000453:epidemiology* / Q000503:physiopathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D008055:Lipids / Q000097:blood; D016015:Logistic Models; D008279:Magnetic Resonance Imaging; D008297:Male; D008404:Massachusetts / Q000453:epidemiology; D008833:Microcirculation; D055806:Microvessels / Q000473:pathology / Q000503:physiopathology; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D011379:Prognosis; D018570:Risk Assessment; D012307:Risk Factors; D018616:Ultrasonography, Doppler, Duplex
chemical_list: D008055:Lipids
keywords: brain magnetic resonance imaging; carotid atherosclerosis; carotid intima–media thickness; cerebral microbleeds