Akoudad Saloua, Ikram Mohammad Arfan, Koudstaal Peter J, Hofman Albert, Niessen Wiro J, Greenberg Steven M, van der Lugt Aad, Vernooij Meike W
Department of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
Cerebrovasc Dis. 2014;37(5):382-8. doi: 10.1159/000362590. Epub 2014 Jun 26.
Despite their different appearance on imaging, hemorrhagic and ischemic vascular lesions frequently co-occur in the brain and are hypothesized to progress concurrently. Although silent hemorrhagic and ischemic vascular brain lesions are highly prevalent in the general population, the concomitant progression of these lesions has only been studied to a limited extent in this population. We therefore aimed to investigate whether pre-existing and incident cerebral microbleeds (CMBs) are related to the progression of ischemic lesions in the general population.
In the prospective population-based Rotterdam Scan Study, 803 individuals aged ≥60 years underwent magnetic resonance imaging at baseline and after an average interval of 3.4 years. The presence of microbleeds and lacunes was visually rated by trained research physicians, and white matter lesions (WMLs) were automatically segmented at both time points. Logistic regression was used to investigate the association of microbleeds with incident lacunes, and linear regression was used to investigate the relation between microbleeds and progression of WML volume. All analyses were adjusted for age, sex and the time interval between baseline and follow-up scanning. The analyses were repeated after additional adjustments for cardiovascular risk factors: blood pressures; total and high-density lipoprotein cholesterol; smoking; diabetes mellitus; lipid lowering, antihypertensive and antiplatelet medications, and apolipoprotein E ε4. The analyses involving WMLs were also adjusted for intracranial volume.
We found that pre-existing microbleeds in any location of the brain were related to a higher incidence of lacunes (odds ratio [OR] adjusted for age, sex and scan interval: 4.67; 95% confidence interval [CI]: 1.84-11.85). Pre-existing microbleeds were not related to progression of WML volume (mean difference in WML volume increase: -0.03; 95% CI: -0.15 to 0.09). Additional adjustments for cardiovascular risk factors did not change the results considerably. Incident microbleeds in any location of the brain were associated with a higher incidence of lacunes (OR: 9.18; 95% CI: 3.61-23.35), whereas only incident microbleeds located in cortico-subcortical regions were related to progression of WML volume (mean difference in WML volume increase: 0.41; 95% CI: 0.21-0.62). Again, adjustments for cardiovascular risk factors did not change the results significantly.
Our findings suggest that in the general population, CMBs serve as a predictor of ischemic brain lesions and may represent an imaging marker of active vasculopathy. These results support the hypothesis of a common underlying pathway in the development of ischemic and hemorrhagic brain lesions.
尽管出血性和缺血性血管病变在影像学上表现不同，但它们在大脑中经常同时出现，并且据推测会同时进展。虽然无症状性出血性和缺血性脑血管病变在普通人群中非常普遍，但在该人群中，这些病变的伴随进展仅在有限程度上得到研究。因此，我们旨在调查既往存在的和新发的脑微出血（CMB）是否与普通人群中缺血性病变的进展有关。
在基于人群的前瞻性鹿特丹扫描研究中，803名年龄≥60岁的个体在基线时以及平均间隔3.4年后接受了磁共振成像检查。训练有素的研究医师通过视觉评估微出血和腔隙的存在情况，并且在两个时间点对白质病变（WML）进行自动分割。使用逻辑回归来研究微出血与新发腔隙的关联，使用线性回归来研究微出血与WML体积进展之间的关系。所有分析均针对年龄、性别以及基线和随访扫描之间的时间间隔进行了调整。在对心血管危险因素进行额外调整后重复分析：血压；总胆固醇和高密度脂蛋白胆固醇；吸烟；糖尿病；降脂、抗高血压和抗血小板药物，以及载脂蛋白Eε4。涉及WML的分析还针对颅内体积进行了调整。
我们发现，大脑任何部位既往存在的微出血与腔隙的更高发生率相关（调整年龄、性别和扫描间隔后的优势比[OR]：4.67；95%置信区间[CI]：1.84 - 11.85）。既往存在的微出血与WML体积的进展无关（WML体积增加的平均差异：-0.03；95%CI：-0.15至0.09）。对心血管危险因素进行额外调整并没有显著改变结果。大脑任何部位新发的微出血与腔隙的更高发生率相关（OR：9.18；95%CI：3.61 - 23.35），而仅位于皮质 - 皮质下区域的新发微出血与WML体积的进展有关（WML体积增加的平均差异：0.41；95%CI：0.21 - 0.62）。同样，对心血管危险因素进行调整并没有显著改变结果。
我们的研究结果表明，在普通人群中，CMB可作为缺血性脑病变的预测指标，并且可能代表活跃血管病变的一种影像学标志物。这些结果支持了缺血性和出血性脑病变发展存在共同潜在途径的假说。
