Hostname: page-component-78c5997874-g7gxr Total loading time: 0 Render date: 2024-11-17T14:43:12.215Z Has data issue: false hasContentIssue false
  • English
  • Français

Statins May Increase Intracerebral Hemorrhage Volume

Published online by Cambridge University Press:  23 September 2016

Geneviève Ricard ,
Marie-Pierre Garant ,
Nathalie Carrier ,
Nancy Leblanc  and
Jean-Martin Boulanger
Geneviève Ricard
Affiliation:
Centre Hospitalier, Universitaire de Sherbrooke CHUS Department of Neurology, University of Sherbrooke, Sherbrooke, Quebec, Canada
Marie-Pierre Garant
Affiliation:
Étienne-Le Bel Clinical Research Center, Universitaire de Sherbrooke CHUS Centre Hospitalier, Universitaire de Sherbrooke CHUS
Nathalie Carrier
Affiliation:
Étienne-Le Bel Clinical Research Center, Universitaire de Sherbrooke CHUS Centre Hospitalier, Universitaire de Sherbrooke CHUS
Nancy Leblanc
Affiliation:
Hôpital Charles Lemoyne, University of Sherbrooke, Sherbrooke, Quebec, Canada
Jean-Martin Boulanger*
Affiliation:
Department of Neurology, University of Sherbrooke, Sherbrooke, Quebec, Canada Hôpital Charles Lemoyne, University of Sherbrooke, Sherbrooke, Quebec, Canada
*
Neuro Rive-Sud Clinic, 4896 Boulevard Taschereau #250, Greenfield Park, Quebec, J4V 2J2, Canada
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.
Background:

Some studies have suggested an association between hypocholesterolemia and intracerebral hemorrhage (ICH). In the SPARCL trial, statin use increased ICH risk. We tested the hypothesis that use of statins affects the volume of spontaneous ICH and contributes to the progression of ICH volume between baseline and follow-up CT scans.

Methods:

Consecutive cases of spontaneous ICH were reviewed. Secondary causes were excluded. We measured ICH volume on the baseline and follow-up CT scans using the AxBxC/2 method. Multivariate analysis and logistic regression modeling were used. The primary outcome was the ICH volume on the baseline CT scan. Secondary outcomes included volume variation between the baseline and the first follow up CT scans and death.

Results:

Of 303 subjects, 71 were taking a statin at the time of the ICH (23%). Statin users were significantly more likely to be younger, to have co-morbidities and take anticoagulant or anti-platelet medication. They also had a higher baseline ICH volume than non-statin users (median 31.2 [10,82.1] ml vs 16 [4,43.8] ml; p=0.006). Adjusting for possible confounders, statins remained associated with an increased ICH volume (p=0.007). There was a significant mean ICH volume progression between the first and second CT scans in statin users (+10.8 vs +0.9 ml; p=0.03; 95% CI: [-1,+22.6] [-2.5,+4.3]). No difference in mortality was seen between the two groups.

Conclusion:

Treatment with HMG-CoA reductase inhibitors may be a risk factor for increased ICH volume in spontaneous brain hemorrhages and could contribute to hemorrhage's volume progression.

Résumé

RésuméContexte:

Selon certaines études, il existerait une association entre l'hypocholestérolémie et l'hémorragie intracérébrale (HIC). Dans l'essai clinique SPARCL, l'utilisation d'une statine augmentait le risque d'HIC. Nous avons vérifié l'hypothèse selon laquelle l'utilisation de statines influence le volume de l'HIC spontanée et contribue à la progression du volume de l'HIC à la tomodensitométrie cérébrale initiale et de suivi.

Méthodes:

Des cas consécutifs d'HIC spontanée ont été révisés. Les causes secondaires ont été exclues. Nous avons mesuré le volume de l'HIC à la tomodensitométrie initiale et à celle de suivi au moyen de la formule AxBxC/2. L'analyse multivariée et la régression logistique ont été utilisées pour l'analyse des données. L'issue primaire était le volume de l'HIC à la tomodensitométrie initiale. Les issues secondaires étaient la variation du volume entre la tomodensitométrie initiale et la première effectuée au cours du suivi et le décès.

Résultats:

Soixante et onze des 303 sujets prenaient une statine au moment de l'HIC (23%). Les sujets qui prenaient une statine avaient une plus forte probabilité d'être plus jeunes, d'avoir des comorbidités et de prendre des anticoagulants ou des antiplaquettaires. Ils avaient également un volume initial d'HIC plus grand que ceux qui ne prenaient pas de statines (médiane 31,2 [10,82,1] ml versus 16 [4, 43,8] ml ; p = 0,006). Après ajustement pour les variables confondantes possibles, les statines demeuraient associées à un volume plus grand d'HIC (p = 0,007). Il y avait une progression significative du volume de l'HIC entre la première et la seconde tomodensitométrie chez les sujets qui prenaient une statine (+10,8 versus +0,9 ml ; p = 0,03 ; IC à 95% : -1 à +22,6 et -2,5 à +4,3 respectivement). Nous n'avons pas observé de différence de mortalité entre les deux groupes.

Conclusion:

Le traitement par les inhibiteurs de l'HMG-CoA réductase pourrait constituer un facteur de risque d'un plus grand volume d'HIC dans les hémorragies cérébrales spontanées et pourrait contribuer à la progression du volume de l'hémorragie.

Type
Original Articles
Information
Canadian Journal of Neurological Sciences , Volume 37 , Issue 6 , November 2010 , pp. 791 - 796
Copyright
Copyright © The Canadian Journal of Neurological 2010

References

1. Yano, K, Reed, DM, MacLean, CJ. Serum cholesterol and hemorrhagic stroke in the Honolulu heart program. Stroke. 1989; 20:1460–5.10.1161/01.STR.20.11.14602815179Google Scholar
2. Zhang, X, Patel, A, Horibe, H, et al. Cholesterol, coronary heart disease, and stroke in the Asia Pacific region. Int J Epidemiol. 2003;32:563–72.10.1093/ije/dyg10612913030Google Scholar
3. Iso, H, Jacobs, DR Jr., Wentworth, D, et al. Serum cholesterol levels and six-year mortality from stroke in 350,977 men screened for the multiple risk factor intervention trial. N Engl J Med. 1989;320:904–10.10.1056/NEJM1989040632014052619783Google Scholar
4. Mosheimer, BA, Kaneider, NC, Feistritzer, C, et al. Cd40-ligand-dependent induction of cox-2 gene expression in endothelial cells by activated platelets: Inhibitory effects of atorvastatin. Blood Coagul Fibrinolysis. 2005;16:105–10.15741797Google Scholar
5. Serebruany, VL, Miller, M, Pokov, AN, et al. Effect of statins on platelet par-1 thrombin receptor in patients with the metabolic syndrome (from the par-1 inhibition by statins [Paris] study). Am J Cardiol. 2006;97:1332–6.10.1016/j.amjcard.2005.11.05816635606Google Scholar
6. Kahn, ML, Nakanishi-Matsui, M, Shapiro, MJ, et al. Protease-activated receptors 1 and 4 mediate activation of human platelets by thrombin. J Clin Invest. 1999;103:879–88.10.1172/JCI604210079109Google Scholar
7. Goldstein, LB, Amarenco, P, Szarek, M, et al. Hemorrhagic stroke in the stroke prevention by aggressive reduction in cholesterol levels study. Neurology. 2008;70:2364–70.10.1212/01.wnl.0000296277.63350.7718077795Google Scholar
8. Collins, R, Armitage, J, Parish, S, et al. Effects of cholesterol-lowering with simvastatin on stroke and other major vascular events in 20536 people with cerebrovascular disease or other high-risk conditions. Lancet. 2004;363:757–67.10.1016/S0140-6736(04)15690-015016485Google Scholar
9. Vergouwen, MD, de Haan, RJ, Vermeulen, M, et al. Statin treatment and the occurrence of hemorrhagic stroke in patients with a history of cerebrovascular disease.[see comment]. Stroke. 2008;39:497–502.10.1161/STROKEAHA.107.48879118174491Google Scholar
10. Baigent, C, Keech, A, Kearney, PM, et al. Efficacy and safety of cholesterol-lowering treatment: Prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet. 2005;366:1267–78.10.1016/S0140-6736(05)67394-116214597Google Scholar
11. Kasner, SE, Cucchiara, BL, McGarvey, ML, et al. Modified National Institutes of Health Stroke Scale can be estimated from medical records. Stroke. 2003;34:568–70.10.1161/01.STR.0000052630.11159.2512574577Google Scholar
12. Kothari, RU, Brott, T, Broderick, JP, et al. The ABCs of measuring intracerebral hemorrhage volumes. Stroke. 1996;27:1304–5.10.1161/01.STR.27.8.13048711791Google Scholar
13. Amarenco, P, Bogousslavsky, J, Callahan, A 3rd, et al. High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med. 2006;355:549–59.10.1056/NEJMoa06189416899775Google Scholar
14. Reed, DM. The paradox of high risk of stroke in populations with low risk of coronary heart disease. Am J Epidemiol. 1990;131:579–88.2316492Google Scholar
15. Bang, OY, Saver, JL, Liebeskind, DS, et al. Cholesterol level and symptomatic hemorrhagic transformation after ischemic stroke thrombolysis. Neurology. 2007;68:737–42.10.1212/01.wnl.0000252799.64165.d517182976Google Scholar
16. Kim, BJ, Lee, SH, Ryu, WS, et al. Low level of low-density lipoprotein cholesterol increases hemorrhagic transformation in large artery atherothrombosis but not in cardioembolism. Stroke. 2009;40:1627–32.10.1161/STROKEAHA.108.53964319286585Google Scholar
17. Ramirez-Moreno, JM, Casado-Naranjo, I, Portilla, JC, et al. Serum cholesterol LDL and 90-day mortality in patients with intracerebral hemorrhage. Stroke. 2009;40:1917–20.10.1161/STROKEAHA.108.53669819299638Google Scholar
18. Seyfried, D, Han, Y, Lu, D, et al. Improvement in neurological outcome after administration of atorvastatin following experimental intracerebral hemorrhage in rats. J Neurosurg. 2004;101:104–7.10.3171/jns.2004.101.1.010415255259Google Scholar
19. Naval, NS, Abdelhak, TA, Zeballos, P, et al. Prior statin use reduces mortality in intracerebral hemorrhage. [see comment]. Neurocrit Care. 2008;8:6–12 10.1007/s12028-007-0080-217701108Google Scholar
20. Leker, RR, Khoury, ST, Rafaeli, G, et al. Prior use of statins improves outcome in patients with intracerebral hemorrhage. Prospective data from the national acute stroke Israeli surveys (NASIS). Stroke. 2009;40:2581–4.10.1161/STROKEAHA.108.54625919407227Google Scholar
21. FitzMaurice, E, Wendell, L, Snider, R, et al. Effect of statins on intracerebral hemorrhage outcome and recurrence. Stroke. 2008; 39:2151–4.10.1161/STROKEAHA.107.50886118436876Google Scholar
22. Meier, N, Nedeltchev, K, Brekenfeld, C, et al. Prior statin use, intracranial hemorrhage, and outcome after intra-arterial thrombolysis for acute ischemic stroke. Stroke. 2009;40:1729–37.10.1161/STROKEAHA.108.53247319265056Google Scholar
23. Amarenco, P, Labreuch, J. Lipid management in the prevention of stroke: review and updated meta-analysis of statins for stroke prevention. Lancet Neurol. 2009;8;453–63.10.1016/S1474-4422(09)70058-419375663Google Scholar