Nonaspirin Nonsteroidal Anti-Inflammatory Drugs and Risk of Hemorrhagic Stroke: A Systematic Review and Meta-Analysis of Observational Studies
Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used as over-the-counter and prescription analgesics. Because of inhibition of cyclo-oxygenases-1 and -2, they are linked to substantial risk of gastrointestinal hemorrhage. In this meta-analysis of observational studies, Ungprasert et al sought to elucidate the association between exposure to NSAIDs and hemorrhagic stroke. Ten case–control and 3 cohort studies met the criteria set by the authors and were included in the final analysis. A slight but statistically insignificant increase in the odds of hemorrhage risk was observed for NSAIDs as a single group. The type of study from which the data was derived (case–control versus cohort) did not affect this observation. Analysis of data individually for ibuprofen, meloxicam, indomethacin, naproxen, and diclofenac showed a small trend toward increased hemorrhagic stroke risk (relative risk of 1.09), although this was statistically significant only for diclofenac and meloxicam (relative risk of 1.27 for both). This trend toward increased hemorrhage risk is attributed mainly to the effect of NSAIDs on vascular tone and renal sodium and water reabsorption, leading to an increase in blood pressure. The limitations of this meta-analysis reflect limitations inherent to the studies included: recall bias, incomplete ascertainment of length of exposure to NSAIDs, and adjudication of concurrent use of other medications found to increase the intracranial hemorrhage risk in population-wide studies, such as selective serotonin reuptake inhibitors. In summary, although there seems to be an association between NSAID exposure and hemorrhagic stroke, it is weak. See p 356.
Progression of White Matter Disease and Cortical Thinning Are Not Related in Older Community-Dwelling Subjects
Higher white matter hyperintensity (WMH) volume has been linked to reduced cortical thickness in cross-sectional studies which, by nature, did not allow causal inferences to be made. Dickie et al examined the above association longitudinally, investigating the relationship between WMH and regional cortical volume in a group of community-dwelling adults from ≈73 to ≈76 years of age. Several associations were tested between all combinations of baseline and follow-up WMH and cortical volume, as well as change in WMH volume and cortical thickness over 3 years. The authors accounted for multiple testing. No association was found between global cortical thickness and global WMH volume or change thereof over 3 years. On the contrary, strong cross-sectional associations were found between global WMH volume and reduced cortical thickness in certain areas, centered around and within the Sylvian fissure. However, longitudinal analyses were all negative: neither did baseline WMH volume predict change in cortical thickness, nor did baseline cortical thickness predict change in WMH volume. Finally, change in WMH volume and change in cortical thickness were not significantly associated with each other. In essence, the findings of this study suggest that although WMH volume and regional cortical thinning might share some common underlying causes (hence the strong cross-sectional associations) and they progress with age, they progress independent of each other. The major limitations of this otherwise well executed study is the population homogeneity, relatively short duration of follow up of only 3 years, and underrepresentation of cognitively impaired individuals (only 16 of 351 analyzed subjects had a Mini-Mental Status Exam score of ≤26), limiting the generalizability of the findings to the general population. See p 410.
Perihematomal Edema Is Greater in the Presence of a Spot Sign but Does Not Predict Intracerebral Hematoma Expansion
The relationship among perihematomal edema, hematoma expansion, and clinical outcome in intracerebral hemorrhage (ICH) is complex and not completely understood. Using data from the Predicting Hematoma Growth and Outcome in Intracerebral Hemorrhage Using Contrast Bolus CT (PREDICT) study, the authors examined the relationship among baseline perihematomal edema, the computed tomographic angiogram spot sign (considered a surrogate marker of active bleeding), and subsequent hematoma expansion, hypothesizing that smaller volume of baseline perihematomal edema indicates earlier imaging time relative to ICH onset time and, therefore, higher likelihood of active bleeding and subsequent hematoma expansion.
The authors found a robust association (correlation coefficient of 0.877) between absolute perihematomal edema volume and ICH volume, even adjusting for covariates. Although absolute perihematomal edema was associated with hematoma expansion, this association was lost after adjusting for ICH volume, which was found to be the sole more robust predictor of subsequent hematoma expansion. In essence, baseline perihematomal edema is a surrogate marker of ICH volume without inherent prognostic value.
Additionally, there was no correlation between either absolute or relative baseline perihematomal edema volume and onset-to-computed tomographic time; therefore, this study’s results do not support the notion that the perihematomal edema volume at the baseline computed tomography could be a surrogate marker of the time from symptom onset.
Finally, the presence of spot sign did not have predictive value in this analysis: perihematomal edema volume, frequency of hematoma expansion, and frequency of poor clinical outcomes were comparable in spot sign–positive and spot sign–negative patients with the common denominator, and the most potent independent predictor being the ICH volume. See p 350.
- © 2016 American Heart Association, Inc.
- Nonaspirin Nonsteroidal Anti-Inflammatory Drugs and Risk of Hemorrhagic Stroke: A Systematic Review and Meta-Analysis of Observational Studies
- Progression of White Matter Disease and Cortical Thinning Are Not Related in Older Community-Dwelling Subjects
- Perihematomal Edema Is Greater in the Presence of a Spot Sign but Does Not Predict Intracerebral Hematoma Expansion
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