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Carotid Atherosclerosis and Cerebral Microbleeds: The Framingham Heart Study
José R Romero1, Sarah R Preis2, Alexa Beiser3
1Department of Neurology, School of Public Health at Boston University, Boston, MA joromero@bmc.org.
Insights
Carotid atherosclerosis, a marker of cerebrovascular disease, is linked to an increased risk of cerebral microbleeds (CMB), particularly in deep brain regions. Intensive vascular risk factor treatment may reduce this risk.
Area of Science:
- Neurology
- Vascular Medicine
- Radiology
Background:
- Carotid atherosclerosis is linked to ischemic cerebrovascular disease.
- Its association with cerebral microbleeds (CMB), a marker of small vessel disease, is not well understood.
- Vascular risk factors contribute to both conditions.
Purpose of the Study:
- To investigate the association between carotid atherosclerosis and the prevalence and location of CMB.
- To explore whether carotid atherosclerosis predicts deep CMB.
Main Methods:
- 1243 participants from the Framingham Offspring Study underwent carotid ultrasound and brain MRI.
- Carotid stenosis, intima-media thickness (IMT), and IMT progression were assessed.
- Logistic regression models related carotid measures to CMB prevalence and location.
Main Results:
- Carotid stenosis ≥25% was associated with an increased odds of CMB overall (OR 2.20) and in deep/mixed locations (OR 3.60).
- Baseline carotid IMT was not associated with CMB.
- Progression of common carotid artery IMT in hypertensive patients on treatment was associated with a lower risk of deep/mixed CMB (OR 0.41 per SD).
Conclusions:
- Cumulative vascular risk factor exposure may elevate CMB risk, especially in deep brain regions.
- The observed inverse association between IMT progression and CMB might reflect benefits of intensive risk factor management.
- Findings may inform preventive and therapeutic strategies for subclinical cerebral hemorrhage.
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.
Methods And 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.