Risk for Silent Stroke Twice as High With Afib
Published: Nov 4, 2014 | Updated: Nov 4, 2014
Atrial fibrillation was associated with a more than twofold increased risk for silent cerebral infarctions (SCIs), according to researchers.
Having atrial fibrillation (Afib) was associated with SCIs in patients with no history of symptomatic stroke (odds ratio 2.62, 95% CI 1.81-3.80), and this association was independent of Afib type (paroxysmal versus persistent), reported researcher Jeremy N. Ruskin, MD, of Massachusetts General Hospital in Boston, and colleagues.
Their meta-analysis, published online in Annals of Internal Medicine, included data on patients with and without Afib and with no history of clinical stroke.
They found that association was similar when the analysis was restricted to the highest quality studies, which met at least 70% of the maximum possible quality score (OR 3.06, 95% CI 2.24-4.19).
The patients were enrolled in five studies that used MRI and four that used computed tomography (CT) to screen for lesions consistent with SCI. All nine studies reported adjusted risk estimates.
Individual studies have consistently shown an increased risk for SCI in patients with Afib, but significant between-study variation in the definition of SCI, along with differences in imaging modalities and other variables have led to confusion about the magnitude of this risk, Ruskin told MedPage Today.
"MRI is by far the most sensitive imaging we have to look for silent cerebral infarctions, but even within the MRI studies there were variations," he said.
'The Elusiveness of the Mechanisms'
Afib affects more than 2.7 million people in the U.S. and is the most common arrhythmia in the elderly, with a projected prevalence of 5.6 to 12.1 million by 2050, the researchers wrote.
Patients with Afib have a four- to five-fold increased risk for clinically evident stroke, and they are also at risk for larger brain infarctions and worse outcomes following stroke, compared with the general population.
A recent meta-analysis showed Afib to be associated with a 40% increase in the risk for cognitive impairment (relative risk, 1.40, 95% CI 1.19 to 1.64). The association was independent of symptomatic stroke history and other comorbid conditions, such as advanced age, hypertension, heart failure, and diabetes.
"These findings highlight the elusiveness of the mechanisms underlying this association and suggest pathways other than symptomatic stroke and shared risk factors listed previously as the underlying cause of this association," Ruskin and colleagues wrote. "One such mechanism may be silent cerebral infarctions."
The researchers noted that understanding the true prevalence of SCI in patients with Afib is critical because SCI may be a mediating factor in the link between Afib and cognitive impairment, and also because SCI may prove to be a predictor of clinical symptomatic stroke and death.
Study Details
The systematic review and meta-analysis by Ruskin's group focused on 11 studies with a total of 5,317 people (five using MRI, four using CT, and two using autopsy) that reported on the association between Afib and SCI. However, the researchers found the two autopsy studies to be heterogeneous and low quality and excluded them from the meta-analysis of the risk estimates.
When CT and MRI studies were combined, 4,407 patients (505 with Afib and 3,902 without Afib) were included in the analysis; 230 atrial fibrillation patients (45.54%) and 610 patients without Afib (15.63%) had SCIs.
The authors reported that the overall prevalence of SCI lesions on MRI and CT among patients with Afib was 40% and 22%, respectively.
They also found that the pooled OR for the association between paroxysmal Afib and SCIs (OR 3.83, 95% CI 2.17-6.75, P=0.18 for heterogeneity) was similar to the pooled OR for the association between persistent Afib and SCIs (OR 3.87, 95% 2.20-6.80, P=0.32 for heterogeneity).
The 2.62-fold increase in SCI risk among Afib patients in the pooled analysis was smaller than the association reported in several recent trials.
An MRI study published in July of 2013 (not included in this meta-analysis) found a 7.2-fold higher risk of silent stroke in Afib patients, compared with patients without Afib, after controlling for age, stroke risk score, and anticoagulant treatment. Cognitive performance among patients with persistent or paroxysmal Afib was also significantly worse than among patients with sinus rhythm.
Another study published in 2013, which was included, also showed a more significant association between Afib and SCI in patients with diabetes mellitus, leading Ruskin and colleagues to conclude that diabetes may accentuate the vascular effect of Afib on the brain.
Impact of Anticoagulation
Other than rhythm-control strategies, anticoagulation is the main treatment to prevent thromboembolic complications that may lead to SCI and symptomatic stroke in Afib patients.
"The threshold for anticoagulation therapy in patients with atrial fibrillation has been decreasing fairly consistently," Ruskin said.
Although the benefit of anticoagulant therapy for the prevention of symptomatic stroke in Afib patients is well documented, the effect of the therapy on SCI incidence is not known, he added.
Two studies included in the meta-analysis did not show a reduction in the incidence of SCIs associated with anticoagulation.
Ruskin said a challenge has been that only more recent MRI studies include information about anticoagulation status. Because this imaging technique is far more sensitive than previous techniques, they tend to show a higher prevalence of SCI.
"From a biological perspective, anticoagulation should be protective against silent cerebral infarctions, but we don't have enough information at the moment to say this," he said.
The researchers noted that studies are needed to determine if anticoagulation is associated with lower SCI incidence and whether a change in SCI incidence will translate into a reduction in symptomatic stroke, dementia, and death.
More Research Needed
Data on the location of SCIs within the brain were limited, so the analysis did not include information on risk by SCI lesion site.
"Although the determinants of SCI versus symptomatic stroke are not well-defined, smaller lesions in deep white matter are more likely to remain silent, and larger cortical lesions are more likely to become symptomatic," they wrote, adding that the location of an infarction provides insight into the underlying mechanism of its formation.
They noted that cortical and subcortical wedge-shaped infarctions indicate a thromboembolic mechanism, whereas small infarctions in deep subcortical white matter indicate intrinsic small vessel disease, and junctional or watershed infarctions indicate hypoperfusion that may be caused by proximal arterial stenoses or cardiogenic shock.
And unlike embolic infarctions, non-embolic infarctions due to intrinsic small vessel disease usually occur in the subcortical white matter and can be confused with leukoaraiosis or chronic white matter hyperintensities that occur secondary to nonacute ischemic mechanisms.
Other study limitations included the significant heterogeneity in the two autopsy studies and the lack of good-quality longitudinal studies. The prevalence of MRI-defined SCIs also varied depending on the MRI diagnostic criteria. The researchers noted that while studies defining SCIs as lesions of any size -- with low signal intensity on T1-weighted images and high signal intensity on T2-weighted images -- may overestimate SCI prevalence, those that only consider lesions of greater than 3 mm with signal intensity similar to cerebrospinal fluid may underestimate SCIs.
"We clearly need a lot more uniformity with regard to imaging modalities and definitions within those modalities of what is likely to constitute a silent cerebral infarction," Ruskin said.
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