A new analysis from the Rotterdam Scan Study shows that cerebral microbleeds on magnetic resonance imaging (MRI) are more prevalent in elderly subjects who use platelet-aggregation inhibitors than in nonusers.
In particular, strictly lobar microbleeds — which may indicate the presence of cerebral amyloid angiopathy and possibly bleeding-prone microvessels — were more frequent among those who used aspirin vs users of carbasalate calcium, the researchers report. The association between anticoagulant use and microbleeds was not significant.
The researchers, with senior author Monique M. B. Breteler, MD, PhD, from Erasmus MC University Medical Center, in Rotterdam, the Netherlands, caution that the cross-sectional design of their study prevents determining whether these microbleeds increase the risk for symptomatic hemorrhage and point out that the benefits of antithrombotic therapy in patients with a history of myocardial infarction and cerebrovascular disease have been shown to outweigh the risks.
"Nevertheless, it may be that in selected persons (eg, those with signs of cerebral amyloid angiopathy), this risk/benefit ratio may differ for certain drugs (eg, aspirin), thus influencing treatment decisions," they conclude.
Their report, with first author Meike W. Vernooij, MD, also from Erasmus MC University Medical Center, is published online April 13 and will appear in the June issue of the Archives of Neurology.
New Markers of Small Vessel Disease
Cerebral microbleeds consist of deposits of hemosiderin in macrophages and can be seen on T2-weighted gradient recalled echo (GRE) MRI as small areas of hypointensity, the authors write. In the past decade, "these microbleeds have become acknowledged as new markers of small vessel disease in the brain."
Microbleeds are thought to occur in the setting of either cerebral amyloid angiopathy or arteriosclerotic microangiopathy, they note. Their location in the brain is thought to reflect their underlying origin: microbleeds in the deep or infratentorial locations, for example, are thought to relate to hypertensive or arteriosclerotic microangiopathy, while those in the strictly lobar brain sites result from cerebral amyloid angiopathy, a bleeding-prone state, they write.
Previous work has linked the use of platelet-aggregation inhibitors and anticoagulants to increased risk for symptomatic hemorrhage in patients with cerebral amyloid angiopathy, raising the question of whether asymptomatic microbleeds might also be accelerated by use of these drugs.
"We hypothesized that microbleeds, especially those with strictly lobar locations, occur more often in persons using antithrombotic drugs," they write.
To investigate this relationship, Dr. Breteler and colleagues used data from the Rotterdam Scan Study, a large, population-based cross-sectional imaging study of community-dwelling elderly in the Netherlands. A total of 1062 subjects who were 60 years of age or older and free of dementia underwent MRI imaging between August 15, 2005 and November 22, 2006. Complete information on their use of antithrombotic drugs was obtained from automated pharmacy records.
Of the 1062 subjects, 363 (34.2%) had used any antithrombotic agent. Of these, 245 (23.1%) took platelet-aggregation inhibitors, including 67 who used aspirin and 141 taking carbasalate calcium.
Compared with nonusers, those taking platelet-aggregation inhibitors had a significantly increased prevalence of cerebral microbleeds. The relationship between microbleeds and anticoagulant use was not significant.
Table 1. Risk for Cerebral Microbleeds Among Users of Antiplatelet and Anticoagulant Therapy vs Nonusers
Group Adjusted Odds Ratio 95% CI
Antiplatelet therapy 1.71 1.21 – 2.41
Anticoagulant therapy 1.49 0.82 – 2.71
When they looked by type of antiplatelet medication, strictly lobar microbleeds were more prevalent among users of aspirin than among those taking carbasalate calcium.
Table 2. Prevalence of Strictly Lobar Microbleeds by Treatment vs Nonusers
Group Adjusted Odds Ratio 95% CI
Aspirin 2.70 1.45 – 5.04
Carbasalate calcium 1.16 0.66 – 2.02
The difference in risk for microbleeds was even more pronounced when they compared those who were using similar doses of each drug, they note.
These findings justify further longitudinal research into this association, the authors conclude. "Of particular clinical interest would be a study of whether the presence of microbleeds increases the risk of symptomatic intracerebral hemorrhage in persons using antithrombotic medication."
The Rotterdam Study is supported by the Erasmus MC University Medical Center and Erasmus University Rotterdam; the Netherlands Organization for Scientific Research; the Netherlands Organization for Health Research and Development; the Research Institute for Diseases in the Elderly; the Ministry of Education, Culture, and Science; the Ministry of Health, Welfare, and Sports; the European Commission; and the Municipality of Rotterdam. The study was further supported by grants from the Netherlands Organization for Scientific Research. The authors have disclosed no relevant financial relationships.
Arch Neurol. Published online April 13, 2009. Abstract
Clinical Context
Cerebral microbleeds are brain lesions containing hemosiderin, visualized on MRI, which indicate the presence of small blood vessel disease known as microangiopathy. On T2-weighted GRE MRI, microbleeds appear as hemosiderin deposits in macrophages.
When microbleeds occur in strictly lobar brain locations, this distribution may indicate the presence of cerebral amyloid angiopathy, a bleeding-prone disease state resulting from accumulations of amyloid in the vessel wall. In cerebral amyloid angiopathy, the use of platelet aggregation inhibitors and anticoagulants has been found to be associated with increased occurrence of symptomatic hemorrhage.
Study Highlights
* The Rotterdam Scan Study is a population-based imaging study in a general elderly community in the Netherlands.
* The goal of the study was to evaluate the association between use of antithrombotic drugs and the presence of cerebral microbleeds, particularly those in strictly lobar locations.
* In this cross-sectional analysis, MRI was used to evaluate the presence and location of microbleeds.
* Automated pharmacy records were used to obtain complete data regarding outpatient use of platelet aggregation inhibitors and anticoagulant drugs before MRI was performed.
* The study sample consisted of 1062 persons from a longitudinal, population-based cohort.
* Inclusion criteria were age 60 years and older, absence of dementia, and MRI scan performed between August 15, 2005, and November 22, 2006.
* The primary endpoint of the study was the presence of cerebral microbleeds on MRI.
* To minimize confounding by indication, analyses were adjusted for cardiovascular risk, and persons with a known history of cerebrovascular disease were excluded.
* Cerebral microbleeds were more prevalent among users vs nonusers of platelet aggregation inhibitors (adjusted odds ratio [OR], 1.71; 95% confidence interval [CI], 1.21 -2.41).
* There was no apparent significant association between anticoagulant drugs and the presence of microbleeds (OR, 1.49; 95% CI, 0.82 - 2.71).
* Aspirin users had a greater prevalence of strictly lobar microbleeds vs nonusers (adjusted OR, 2.70; 95% CI, 1.45 - 5.04) and vs users of carbasalate calcium (adjusted OR, 1.16; 95% CI, 0.66 - 2.02).
* This difference between aspirin and carbasalate calcium was even more pronounced when comparing persons who had used similar dosages of both drugs.
* This difference between aspirin and carbasalate calcium was not observed for deep or infratentorial microbleeds.
* The investigators concluded that use of platelet aggregation inhibitors is related to the presence of cerebral microbleeds and that aspirin and carbasalate calcium use may relate differently to the presence of strictly lobar microbleeds.
* Limitations of this study include cross-sectional vs prospective design; inability to date cerebral microbleeds seen on MRI, so that some of the microbleeds may have occurred before use of antithrombotic drugs; and possible confounding by indication.
Clinical Implications
* In the Rotterdam Scan Study, cerebral microbleeds visualized on MRI were more prevalent among users vs nonusers of platelet aggregation inhibitors. There was no apparent significant association between anticoagulant drugs and the presence of microbleeds.
* Aspirin users had a greater prevalence of strictly lobar microbleeds vs nonusers and vs users of carbasalate calcium. This difference between aspirin and carbasalate calcium was even more pronounced when comparing persons who had used similar dosages of both drugs and was not observed for deep or infratentorial microbleeds.
Source : http://cme.medscape.com/viewarticle/701679?src=cmemp
Subscribe to:
Post Comments (Atom)
No comments:
Post a Comment