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Statins and subarachnoid hemorrhage in Medicare patients with unruptured cerebral aneurysms.

ABSTRACT: Statins have been shown to decrease aneurysm progression and rupture in two experimental settings: animals with cerebral aneurysm and humans with abdominal aortic aneurysms.To investigate statin use and outcomes in humans with unruptured cerebral aneurysms through Medicare administrative data.We used a 40% random sample Medicare denominator file and corresponding inpatient, outpatient (2003-2011), and prescription (2006-2011) claims to conduct a retrospective cohort study of patients diagnosed with unruptured cerebral aneurysms, between 2003 and 2011. We used propensity score-adjusted models to investigate the association between statin use and risk of subarachnoid hemorrhage. Secondary analyses repeated the main models stratified on tobacco use status and separately assessed other composite outcomes.We identified 28?931 patients with unruptured cerebral aneurysms (average age 72·0 years, 72·6% female); mean follow-up was 30·0 months; 41·3% used statins. Overall, 593 patients developed subarachnoid hemorrhage, and 703 underwent treatment before subarachnoid hemorrhage. Current or recent statin use was not associated with a difference in subarachnoid hemorrhage risk (odds ratio, 1·03; 95% conflict of interest 0·86-1·23); models stratified on tobacco use status were nearly identical. No association was observed between statin use and the composite outcome of subarachnoid hemorrhage or aneurysm treatment (odds ratio, 0·94; 95% conflict of interest, 0·84-1·06). The risk of subarachnoid hemorrhage or out-of-hospital death was lower among statin users (odds ratio, 0·69; 95% conflict of interest, 0·64-0·74).Statin use by patients with unruptured cerebral aneurysms was not associated with subarachnoid hemorrhage risk. Given the prior animal experimental studies demonstrating a protective effect, further prospective studies are needed to investigate the potential relationship.

SUBMITTER: Bekelis K

PROVIDER: S-EPMC4802155 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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Statins and subarachnoid hemorrhage in Medicare patients with unruptured cerebral aneurysms.

Bekelis Kimon K Smith Jeremy J Zhou Weiping W MacKenzie Todd A TA Roberts David W DW Skinner Jonathan J Morden Nancy E NE

International journal of stroke : official journal of the International Stroke Society 20150629

<h4>Background</h4>Statins have been shown to decrease aneurysm progression and rupture in two experimental settings: animals with cerebral aneurysm and humans with abdominal aortic aneurysms.<h4>Aims</h4>To investigate statin use and outcomes in humans with unruptured cerebral aneurysms through Medicare administrative data.<h4>Methods</h4>We used a 40% random sample Medicare denominator file and corresponding inpatient, outpatient (2003-2011), and prescription (2006-2011) claims to conduct a re ...[more]

PMID: 26120925

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Project description:The diagnosis of cerebral vasospasm after Subarachnoid-Hemorrhage is currently very difficult, additional tools such as blood biomarkers are necessary. We tested the ability of gene expression profiles of blood cells to predict vasospasm. 32 patients suffering subarachnoid-hemorrhage were included in this prospective monocentre study. They were grouped according to have a complicated cerebral vasospasm (Vasospasm) or not (Control) and Paired according to age (+/- 10 years), sex, Fisher grade (+/- 1), location, smoking (at least 3 first parameters). Gene expression profiles of blood cells were determined using 25,000~gene microarray. Blood sample: 2.5 mL harvested in PAXgene® Blood RNA tubes (PreAnalytix) RNA extraction: PAXgene® Blood RNA kit (Qiagen). We used a Universel Reference RNA (Stratagene). RNA amplification and labelling: kit Amino Allyl MessageAmp II (Ambion). We hybridized 4 microarrays per patient using pangenomic microarrays from the "Réseau National des Génopôles" (Illkirch, France). 2 slides were hybridized with reference RNA labelled Cy3 and patient RNA labelled Cy5, and 2 slides were hybridized with reference RNA labelled Cy5 and patient RNA labelled Cy3. Hybridation : Agilent protocol with few modifications : 750 ng of each labelled RNA were hubriddized at 60°C during 17 hours in an Aglient hybridization oven. After washings, Slides were scanned with a GenePix 4000B scanner (Molecular Devices). Image intensity data were extracted with GenePix Pro 6.0 analysis software. Quantification of Cy3 and Cy5 and selection of good spots were performed using the MAIA software (Novikov E and Barillot E. Software package for automatic microarray image analysis (MAIA). The ACUITY software was then used to normalize log ratios Cy3/Cy5 with Lowess non linear normalization, to filter out genes not present in at least 3 slides out of 4, to evaluate the reproducibility of the 4 microarrays of each patient (hierarchical clustering, Self Organizing Maps). Statistical analyses to insure reproducibility was performed using Excel (correlation coefficients, ANOVA). Only slides that passed all reprocubility tests were validated.

Project description:OBJECTIVE The molecular mechanisms behind cerebral aneurysm formation and rupture remain poorly understood. In the past decade, microRNAs (miRNAs) have been shown to be key regulators in a host of biological processes. They are noncoding RNA molecules, approximately 21 nucleotides long, that posttranscriptionally inhibit mRNAs by attenuating protein translation and promoting mRNA degradation. The miRNA and mRNA interactions and expression levels in cerebral aneurysm tissue from human subjects were profiled. METHODS A prospective case-control study was performed on human subjects to characterize the differential expression of mRNA and miRNA in unruptured cerebral aneurysms in comparison with control tissue (healthy superficial temporal arteries [STA]). Ion Torrent was used for deep RNA sequencing. Affymetrix miRNA microarrays were used to analyze miRNA expression, whereas NanoString nCounter technology was used for validation of the identified targets. RESULTS Overall, 7 unruptured cerebral aneurysm and 10 STA specimens were collected. Several differentially expressed genes were identified in aneurysm tissue, with MMP-13 (fold change 7.21) and various collagen genes (COL1A1, COL5A1, COL5A2) being among the most upregulated. In addition, multiple miRNAs were significantly differentially expressed, with miR-21 (fold change 16.97) being the most upregulated, and miR-143-5p (fold change -11.14) being the most downregulated. From these, miR-21, miR-143, and miR-145 had several significantly anticorrelated target genes in the cohort that are associated with smooth muscle cell function, extracellular matrix remodeling, inflammation signaling, and lipid accumulation. All these processes are crucial to the pathophysiology of cerebral aneurysms. CONCLUSIONS This analysis identified differentially expressed genes and miRNAs in unruptured human cerebral aneurysms, suggesting the possibility of a role for miRNAs in aneurysm formation. Further investigation for their importance as therapeutic targets is needed.

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Statins and subarachnoid hemorrhage in Medicare patients with unruptured cerebral aneurysms.

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Statins and subarachnoid hemorrhage in Medicare patients with unruptured cerebral aneurysms.

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