Statin Treatment Not Linked to Intracerebral Hemorrhage After Ischemic Stroke
Treatment with statins following acute ischemic stroke is not associated with intracerebral hemorrhage (ICH), researchers reported in the September 12 online issue of Archives of Neurology.
Recent research has suggested that statin use increases ICH risk, noted Daniel G. Hackam, MD, PhD, Assistant Professor of Clinical Pharmacology at the University of Western Ontario in London, Canada, and colleagues. They investigated the issue further by retrospectively analyzing data on 17,872 persons age 65 or older who were admitted to hospitals with ICH between 1994 and 2008. Of the participants, 8,936 started statin therapy following stroke and 8,936 were propensity-matched controls who did not receive statin therapy. The participants were followed for a median of 4.2 years, with the main outcome measure of a hospitalization or emergency department visit for intracerebral hemorrhage.
The researchers identified 213 episodes of ICH during follow-up. ICH occurred slightly more frequently in controls (3.71 events per 1,000 patient years) than in patients treated with statins (2.94 events per 1,000 patient years). There was no association between statins and ICH (hazard ratio, 0.87) in the primary analysis, although statins had a borderline protective association with ICH. However, hypertension, previous ICH, chronic liver disease, and previous anticoagulants or antiplatelet therapy were associated with ICH, while female sex and use of potassium-sparing diuretics protected against it. Neither the subgroup analysis nor a dose-response analysis found any association between statins and ICH.
These results were not affected by healthy user bias or differences in quality of care, according to the researchers. “In tests of specificity, statin therapy was not associated with bone mineral density testing, vitamin D or B12 screening, gastrointestinal endoscopy, or elective knee arthroplasty,” they wrote.
“The clinical decision to administer a statin following ICH remains a challenging one, with available evidence tilting in the direction of withholding such therapy, especially when there is a history of lobar brain hemorrhage,” stated Philip B. Gorelick, MD, MPH, Head of the Department of Neurology and Rehabilitation and the Director of Stroke Research at the University of Illinois College of Medicine at Chicago, in an accompanying editorial. Until more evidence accrues, he noted, clinicians should consider such risk factors as history of hemorrhage, antithrombotic therapy, and cerebral microbleeds when deciding whether to use statin therapy in stroke patients. Dr. Gorelick also recommended controlling blood pressure and other modifiable risks during such therapy.
Hackam DG, Austin PC, Huang A, et al. Statins and intracerebral hemorrhage: a retrospective cohort study. Arch Neurol. 2011 Sep 12; [Epub ahead of print].
Gorelick PB. Statin use and intracerebral hemorrhage: evidence for safety in recurrent stroke prevention? Arch Neurol. 2011 Sep 12; [Epub ahead of print].
Vitamin B12 Deficiency May Be Associated With Low Brain Volumes and Cognitive Problems
A low level of vitamin B12 may be a risk factor for cognitive impairment due to brain atrophy and white matter hyperintensity volume, researchers concluded in the September 27 issue of Neurology.
Christine C. Tangney, PhD, Associate Professor of Clinical Nutrition at Rush University Medical Center in Chicago, and colleagues compared markers of vitamin B12 status, cognitive performance, and brain scans in a cohort of 121 participants ages 65 and older. First, the participants’ blood samples were analyzed for vitamin B12 and markers of B12 deficiency (methylmalonic acid, cystathionine, 2-methylcitric acid, and homocysteine). Next, a team of neurologists tested the participants’ episodic memory, visuospatial ability/perceptual organization, perceptual speed, semantic memory, and working memory, and the patients’ B12 markers were compared with their neuropsychologic results. An average of 4.6 years later, MRI measures were obtained for the participants and compared with the other data.
Although vitamin B12 itself was not associated with global cognitive scores, each of the B12 deficiency markers was associated with these scores in models that were adjusted for age, sex, education, race, and serum creatinine concentrations. Each increase of 1 µmol/L in homocysteine concentration was associated with a decrease of 0.03 standardized units on the global cognitive score, for example.
The markers also had various associations with individual cognitive domains. Higher concentrations of methylmalonic acid, cystathionine, and 2-methylcitric acid were associated with reduced episodic memory scores; higher concentrations of cystathionine and 2-methylcitric acid were associated with reduced semantic memory scores; and higher concentrations of methylmalonic acid were associated with reduced perceptual speed. These associations remained in analyses that adjusted for BMI, smoking status, lifetime alcohol intake, hypertension, dementia, and APOE4.
Although vitamin B12 itself was not associated with MRI measures in any of the study’s adjusted models, each of the B12 deficiency markers was significantly associated with decreased total brain volume. Furthermore, each µmol/L increase in homocysteine concentration was associated with a 0.103 increase in white matter hyperintensity volume. In contrast to previous research, however, the researchers did not observe associations between vitamin B12 markers and cerebral infarcts.