Background: The effects of lipid levels on clinical outcomes after ischemic stroke are controversial. Whether admission lipid levels and prior statin use are associated with early intracerebral hemorrhage (ICH) and long-term functional outcome after recombinant tissue plasminogen activator (rt-PA) therapy for stroke patients was investigated. Methods: Ischemic stroke patients who received intravenous rt-PA from a multicenter registry were studied. Lipid levels on admission, including total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, and triglyceride levels, as well as prior statin use, were assessed. The primary outcome was favorable outcome at 3 months corresponding to a modified Rankin Scale score ≤1. The secondary outcome was any or symptomatic ICH within the initial 36 h. Results: Of 489 enrolled patients (171 women, 70.8 ± 11.6 years old), 60 used statins prior to stroke, 93 developed ICH (19.0%), and 188 (38.4%) had a favorable 3-month outcome. Of the lipid levels, only the HDL-C level was an independent predictor of favorable outcome after multivariate adjustment for baseline characteristics (OR 1.95, 95% CI 1.10–3.47 per 1 mmol/l; p = 0.023) and after further adjustment for pretreatment radiological findings (OR 2.03, 95% CI 1.07–3.84; p = 0.029). For the 187 stroke patients without cardioembolism, the HDL-C level was more strongly associated with favorable outcome (OR 4.94, 95% CI 1.91–12.76 per 1 mmol/l; p = 0.001). There were no significant associations between ICH and any lipid levels. Prior statin use was not associated with outcomes. Conclusions: The admission HDL-C level was associated with favorable outcome 3 months after intravenous rt-PA therapy in stroke patients without cardioembolism.

1.
Kurth T, Everett BM, Buring JE, Kase CS, Ridker PM, Gaziano JM: Lipid levels and the risk of ischemic stroke in women. Neurology 2007;68:556–562.
2.
Tirschwell DL, Smith NL, Heckbert SR, Lemaitre RN, Longstreth WT Jr, Psaty BM: Association of cholesterol with stroke risk varies in stroke subtypes and patient subgroups. Neurology 2004;63:1868–1875.
3.
Amarenco P, Labreuche J, Touboul PJ: High-density lipoprotein-cholesterol and risk of stroke and carotid atherosclerosis: a systematic review. Atherosclerosis 2008;196:489–496.
4.
Amarenco P, Goldstein LB, Callahan A 3rd, Sillesen H, Hennerici MG, O’Neill BJ, Rudolph AE, Simunovic L, Zivin JA, Welch KMA; on behalf of the SPARCL Investigators: Baseline blood pressure, low- and high-density lipoproteins, and triglycerides and the risk of vascular events in the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial. Atherosclerosis 2009;204:515–520.
5.
The Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) Investigators: High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med 2006;355:549–559.
6.
Leppälä JM, Virtamo J, Fogelholm R, Albanes D, Heinonen OP: Different risk factors for different stroke subtypes: association of blood pressure, cholesterol, and antioxidants. Stroke 1999;30:2535–2540.
7.
Sturgeon JD, Folsom AR, Longstreth WT Jr, Shahar E, Rosamond WD, Cushman M: Risk factors for intracerebral hemorrhage in a pooled prospective study. Stroke 2007;38:2718–2725.
8.
Li W, Liu M, Wu B, Liu H, Wang LC, Tan S: Serum lipid levels and 3-month prognosis in Chinese patients with acute stroke. Adv Ther 2008;25:329–341.
9.
Cuadrado-Godia E, Jiménez-Conde J, Ois A, Rodríguez-Campello A, García-Ramallo E, Roquer J: Sex differences in the prognostic value of the lipid profile after the first ischemic stroke. J Neurol 2009;256:989–995.
10.
Vauthey C, de Freitas GR, van Melle G, Devuyst G, Bogousslavsky J: Better outcome after stroke with higher serum cholesterol levels. Neurology 2000;54:1944–1949.
11.
Dyker AG, Weir CJ, Lees KR: Influence of cholesterol on survival after stroke: retrospective study. BMJ 1997;314:1584–1588.
12.
Olsen TS, Christensen RHB, Kammersgaard LP, Andersen KK: Higher total serum cholesterol levels are associated with less severe strokes and lower all-cause mortality: ten-year follow-up of ischemic strokes in the Copenhagen Stroke Study. Stroke 2007;38:2646–2651.
13.
Newman GC, Bang H, Hussain SI, Toole JF: Association of diabetes, homocysteine, and HDL with cognition and disability after stroke. Neurology 2007;69:2054–2062.
14.
Bang OY, Saver JL, Liebeskind DS, Starkman S, Villablanca P, Salamon N, Buck B, Ali L, Restrepo L, Vinuela F, Duckwiler G, Jahan R, Razinia T, Ovbiagele B: Cholesterol level and symptomatic hemorrhagic transformation after ischemic stroke thrombolysis. Neurology 2007;68:737–742.
15.
Restrepo L, Bang OY, Ovbiagele B, Ali L, Kim D, Liebeskind DS, Starlman S, Vinuela F, Duckwiler GR, Jahan R, Saver JL: Impact of hyperlipidemia and statins on ischemic stroke outcomes after intra-arterial fibrinolysis and percutaneous mechanical embolectomy. Cerebrovasc Dis 2009;28:384–390.
16.
Toyoda K, Koga M, Naganuma M, Shiokawa Y, Nakagawara J, Furui E, Kimura K, Yamagami H, Okada Y, Hasegawa Y, Kario K, Okuda S, Nishiyama K, Minematsu K; for the Stroke Acute Management with Urgent Risk-factor Assessment and Improvement (SAMURAI) Study Investigators: Routine use of intravenous low-dose recombinant tissue plasminogen activator in Japanese patients: general outcomes and prognostic factors from the SAMURAI register. Stroke 2009;40:3591–3595.
17.
Nezu T, Koga M, Kimura K, Shiokawa Y, Nakagawara J, Furui E, Yamagami H, Okada Y, Hasegawa Y, Kario K, Okuda S, Nishiyama K, Naganuma M, Minematsu K, Toyoda K: Pretreatment ASPECTS on DWI predicts 3-month outcome following rt-PA: SAMURAI rt-PA Registry. Neurology 2010;75:555–561.
18.
Naganuma M, Koga M, Shiokawa Y, Nakagawara J, Furui E, Kimura K, Yamagami H, Okada Y, Hasegawa Y, Kario K, Okuda S, Nishiyama K, Minematsu K, Toyoda K: Reduced estimated glomerular filtration rate is associated with stroke outcome after intravenous rt-PA: the Stroke Acute Management with Urgent Risk-factor Assessment and Improvement (SAMURAI) rt-PA Registry. Cerebrovasc Dis 2011;31:123–129.
19.
Koga M, Kimura K, Shibazaki K, Shiokawa Y, Nakagawara J, Furui E, Yamagami H, Okada Y, Hasegawa Y, Kario K, Okuda S, Naganuma M, Nezu T, Maeda K, Minematsu K, Toyoda K: CHADS2 score is associated with 3-month clinical outcomes after intravenous rt-PA therapy in stroke patients with atrial fibrillation: SAMURAI rt-PA Registry. J Neurol Sci 2011;306:49–53.
20.
Shinohara Y, Yamaguchi T: Outline of the Japanese Guidelines for the Management of Stroke 2004 and subsequent revision. Int J Stroke 2008;3:55–62.
21.
Teramoto T, Sasaki J, Ueshima H, Egusa G, Kinoshita M, Shimamoto K, Daida H, Biro S, Hirobe K, Funahashi T, Yokote K, Yokode M: Executive summary of Japan Atherosclerosis Society (JAS) guideline for diagnosis and prevention of atherosclerotic cardiovascular diseases for Japanese. J Atheroscler Thromb 2007;14:45–50.
22.
Barber PA, Hill MD, Eliasziw M, Demchuk AM, Pexman JHW, Hudon ME, Tomanek A, Frayne R, Buchan AM; for the ASPECTS Study Group: Imaging of the brain in acute ischaemic stroke: comparison of computed tomography and magnetic resonance diffusion-weighted imaging. J Neurol Neurosurg Psychiatry 2005;76:1528–1533.
23.
Nakashima T, Toyoda K, Koga M, Matsuoka H, Nagatsuka K, Naritomi H, Minematsu K: Arterial occlusion sites on magnetic resonance angiography influence the efficacy of intravenous low-dose (0.6 mg/kg) alteplase therapy for ischaemic stroke. Int J Stroke 2009;4:425–431.
24.
Adams HP Jr, Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL, Marsh EE 3rd: Classification of subtype of acute ischemic stroke: definitions for use in a multicenter clinical trial: TOAST: Trial of Org 10172 in Acute Stroke Treatment. Stroke 1993;24:35–41.
25.
Wahlgren N, Ahmed N, Dávalos A, Ford GA, Grond M, Hacke W, Hennerici MG, Kaste M, Kuelkens S, Larrue V, Lees KR, Roine RO, Soinne L, Toni D, Vanhooren G; for the SITS-MOST investigators: Thrombolysis with alteplase for acute ischaemic stroke in the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST): an observational study. Lancet 2007;369:275–282.
26.
Sanossian N, Saver JL, Navab M, Ovbiagele B: High-density lipoprotein cholesterol: an emerging target for stroke treatment. Stroke 2007;38:1104–1109.
27.
Lapergue B, Moreno JA, Dang BQ, Coutard M, Delbosc S, Raphaeli G, Auge N, Klein I, Mazighi M, Michel JB, Amarenco P, Meilhac O: Protective effect of high-density lipoprotein-based therapy in a model of embolic stroke. Stroke 2010;41:1536–1542.
28.
Paternò R, Ruocco A, Postiglione A, Hubsch A, Andresen I, Lang MG: Reconstituted high-density lipoprotein exhibits neuroprotection in two rat models of stroke. Cerebrovasc Dis 2004;17:204–211.
29.
Wilder LB, Bachorik PS, Finney CA, Moy TF, Becker DM: The effect of fasting status on the determination of low-density and high-density lipoprotein cholesterol. Am J Med 1995;99:374–377.
30.
Martí-Fàbregas J, Gomis M, Arboix A, Aleu A, Pagonabarraga J, Belvís R, Cocho D, Roquer J, Rodríguez A, García MD, Molina-Porcel L, Díaz-Manera J, Martí-Vilalta JL: Favorable outcome of ischemic stroke in patients pretreated with statins. Stroke 2004;35:1117–1123.
31.
Reeves MJ, Gargano JW, Luo Z, Mullard AJ, Jacobs BS, Majid A; for the Paul Coverdell National Acute Stroke Registry Michigan Prototype Investigators: Effect of pretreatment with statins on ischemic stroke outcomes. Stroke 2008;39:1779–1785.
32.
Yoon SS, Dambrosia J, Chalela J, Ezzeddine M, Warach S, Haymore J, Davis L, Baird AE: Rising statin use and effect on ischemic stroke outcome. BMC Med 2004;2:4.
33.
Arboix A, García-Eroles L, Oliveres M, Targa C, Balcells M, Massons J: Pretreatment with statins improves early outcome in patients with first-ever ischaemic stroke: a pleiotropic effect of statins or a beneficial effect of hypercholesterolemia? BMC Neurol 2010;10:47.
34.
Álvarez-Sabín J, Huertas R, Quintana M, Rubiera M, Delgado P, Ribó M, Molina CA, Montaner J: Prior statin use may be associated with improved stroke outcome after tissue plasminogen activator. Stroke 2007;38:1076–1078.
35.
Miedema I, Uyttenboogaart M, Koopman K, De Keyser J, Luijckx GJ: Statin use and functional outcome after tissue plasminogen activator treatment in acute ischaemic stroke. Cerebrovasc Dis 2010;29:263–267.
36.
Meier N, Nedeltchev K, Brekenfeld C, Galimanis A, Fischer U, Findling O, Remonda L, Schroth G, Mattle HP, Arnold M: Prior statin use, intracranial hemorrhage, and outcome after intra-arterial thrombolysis for acute ischemic stroke. Stroke 2009;40:1729–1737.
37.
Kuwashiro T, Sugimori H, Kamouchi M, Ago T, Kitazono T, Iida M: Lower levels of high-density lipoprotein cholesterol on admission and a recurrence of ischemic stroke: a 12-month follow-up of the Fukuoka Stroke Registry. J Stroke Cerebrovasc Dis 2011, E-pub ahead of print.
38.
Matsumoto S, Nomura E, Ohtsuki T, Kohriyama T, and J-STARS Investigators: Statin trial for secondary prevention of ischemic stroke: J-STARS. Jpn J Stroke 2005;27:474–479.
39.
Sato S, Uehara T, Toyoda K, Yasui N, Hata T, Ueda T, Okada Y, Toyota A, Hasegawa Y, Naritomi H, Minematsu K, and the Stroke Unit Multicenter Observational (SUMO) Study Group: Impact of the approval of intravenous recombinant tissue plasminogen activator therapy on the processes of acute stroke management in Japan: the SUMO study. Stroke 2009;40:30–34.
40.
Chapman MJ: Are the effects of statins on HDL-cholesterol clinically relevant? Eur Heart J 2004;6(suppl C):C58.
41.
Chyu KY, Peter A, Shah PK: Progress in HDL-based therapies for atherosclerosis. Curr Atheroscler Rep 2011;13:405–412.
42.
LaRosa JC, Grundy SM, Waters DD, Shear C, Barter P, Fruchart JC, Gotto AM, Greten H, Kastelein JJP, Shepherd J, Wenger NK, for the Treating to New Targets (TNT) Investigators: Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med 2005;352:1425–1435.
43.
Stein EA, Stroes ESG, Steiner G, Buckley BM, Capponi AM, Burgess T, Niesor EJ, Kallend D, Kastelein JJP: Safety and tolerability of dalcetrapib. Am J Cardiol 2009;104:82–91.
44.
Cannon CP, Shah S, Dansky HM, Davidson MD, Brinton EA, Gotto AM Jr, Stepanavage M, Liu SX, Gibbons P, Ashraf TB, Zafarino J, Mitchel Y, Barter P; for the DEFINE Investigators: Safety of anacetrapib in patients with or at high risk for coronary heart disease. N Engl J Med 2010;363:2406–2415.
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