Abstract

Stroke is the second most common cause of death worldwide. The rates of stroke are increasing in less affluent countries predominantly because of a high prevalence of modifiable risk factors. The Lipid Association of India (LAI) has provided a risk stratification algorithm for patients with ischaemic stroke and recommended low density lipoprotein cholesterol (LDL-C) goals for those in very high risk group and extreme risk group (category A) of <50 mg/dl (1.3 mmol/l) while the LDL-C goal for extreme risk group (category B) is ≤30 mg/dl (0.8 mmol/l). High intensity statins are the first-line lipid lowering therapy. Nonstatin therapy like ezetimibe and proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors may be added as an adjunct to statins in patients who do not achieve LDL-C goals with statins alone. In acute ischaemic stroke, high intensity statin therapy improves neurological and functional outcomes regardless of thrombolytic therapy. Although conflicting data exist regarding increased risk of intracerebral haemorrhage (ICH) with statin use, the overall benefit risk ratio favors long-term statin therapy necessitating detailed discussion with the patient. Patients who have statins withdrawn while being on prior statin therapy at the time of acute ischaemic stroke have worse functional outcomes and increased mortality. LAI recommends that statins be continued in such patients. In patients presenting with ICH, statins should not be started in the acute phase but should be continued in patients who are already taking statins. ICH patients, once stable, need risk stratification for atherosclerotic cardiovascular disease (ASCVD).

Keywords: Stroke, statin, ischaemic stroke, carotid stenosis, intracerebral haemorrhage, low density lipoprotein cholesterol.

Graphical Abstract

[1]
Mehta V, Iyengar SS, Yusuf J, Mukhopadhyay S, Sattur GB, Puri R. Fighting the atherosclerotic cardiovascular disease epidemic: Declaring war on lipids by Lipid Association of India. J Assoc Physicians India 2020; 68(11[Special]): 6-7.
[PMID: 33350609]
[2]
GBD 2016 stroke collaborators. Global, regional, and national burden of stroke, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol 2019; 18(5): 439-58.
[http://dx.doi.org/10.1016/S1474-4422(19)30034-1] [PMID: 30871944]
[3]
WHO. The top 10 causes of death. 2019. Available from: https://www.who.int/news-room/fact-sheets/detail/the-top-10-causes-of-death
[4]
Feigin VL, Lawes CMM, Bennett DA, Barker-Collo SL, Parag V. Worldwide stroke incidence and early case fatality reported in 56 population-based studies: a systematic review. Lancet Neurol 2009; 8(4): 355-69.
[http://dx.doi.org/10.1016/S1474-4422(09)70025-0] [PMID: 19233729]
[5]
Strong K, Mathers C, Bonita R. Preventing stroke: saving lives around the world. Lancet Neurol 2007; 6(2): 182-7.
[http://dx.doi.org/10.1016/S1474-4422(07)70031-5] [PMID: 17239805]
[6]
Kamalakannan S, Gudlavalleti ASV, Gudlavalleti VSM, Goenka S, Kuper H. Incidence & prevalence of stroke in India: A systematic review. Indian J Med Res 2017; 146(2): 175-85.
[http://dx.doi.org/10.4103/ijmr.IJMR_516_15] [PMID: 29265018]
[7]
O’Donnell MJ, Xavier D, Liu L, et al. Risk factors for ischaemic and intracerebral haemorrhagic stroke in 22 countries (the INTERSTROKE study): a case-control study. Lancet 2010; 376(9735): 112-23.
[http://dx.doi.org/10.1016/S0140-6736(10)60834-3] [PMID: 20561675]
[8]
Yusuf S, Hawken S, Ounpuu S, et al. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet 2004; 364(9438): 937-52.
[http://dx.doi.org/10.1016/S0140-6736(04)17018-9] [PMID: 15364185]
[9]
Goldstein LB, Amarenco P, Bogousslavsky J, et al. Statins for secondary stroke prevention in patients without known coronary heart disease: the jury is still out. Cerebrovasc Dis 2004; 18(1): 1-2.
[http://dx.doi.org/10.1159/000078600] [PMID: 15159613]
[10]
Wang Y, Zhao X, Liu L, et al. Prevalence and outcomes of symptomatic intracranial large artery stenoses and occlusions in China: the Chinese Intracranial Atherosclerosis (CICAS) Study. Stroke 2014; 45(3): 663-9.
[http://dx.doi.org/10.1161/STROKEAHA.113.003508] [PMID: 24481975]
[11]
Sun Y, Hou XH, Wang DD, et al. Apolipoprotein B/AI ratio as an independent risk factor for intracranial atherosclerotic stenosis. Aging (Albany NY) 2019; 11(17): 6851-62.
[http://dx.doi.org/10.18632/aging.102216] [PMID: 31479420]
[12]
Baigent C, Blackwell L, Emberson J, et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet 2010; 376(9753): 1670-81.
[http://dx.doi.org/10.1016/S0140-6736(10)61350-5] [PMID: 21067804]
[13]
Brugts JJ, Yetgin T, Hoeks SE, et al. The benefits of statins in people without established cardiovascular disease but with cardiovascular risk factors: meta-analysis of randomised controlled trials. BMJ 2009; 338: b2376.
[http://dx.doi.org/10.1136/bmj.b2376] [PMID: 19567909]
[14]
Iyengar SS, Puri R, Narasingan SN, et al. Lipid association of India expert consensus statement on management of dyslipidemia in Indians 2016: part 1. J Assoc Physicians India 2016; 64(3)(Suppl.): 7-52.
[PMID: 28762263]
[15]
Amarenco P, Bogousslavsky J, Callahan A III, et al. High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med 2006; 355(6): 549-59.
[http://dx.doi.org/10.1056/NEJMoa061894] [PMID: 16899775]
[16]
Huisa BN, Stemer AB, Zivin JA. Atorvastatin in stroke: a review of SPARCL and subgroup analysis. Vasc Health Risk Manag 2010; 6: 229-36.
[PMID: 20407630]
[17]
Goldstein LB, Amarenco P, Szarek M, et al. Hemorrhagic stroke in the stroke prevention by aggressive reduction in cholesterol levels study. Neurology 2008; 70(24 Pt 2): 2364-70.
[http://dx.doi.org/10.1212/01.wnl.0000296277.63350.77] [PMID: 18077795]
[18]
Amarenco P, Goldstein LB, Szarek M, et al. Effects of intense low-density lipoprotein cholesterol reduction in patients with stroke or transient ischemic attack: the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial. Stroke 2007; 38(12): 3198-204.
[http://dx.doi.org/10.1161/STROKEAHA.107.493106] [PMID: 17962589]
[19]
Sillesen H, Amarenco P, Hennerici MG, et al. Atorvastatin reduces the risk of cardiovascular events in patients with carotid atherosclerosis: a secondary analysis of the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial. Stroke 2008; 39(12): 3297-302.
[http://dx.doi.org/10.1161/STROKEAHA.108.516450] [PMID: 18845807]
[20]
Sandercock P, Gubitz G, Foley P, Counsell C. Antiplatelet therapy for acute ischaemic stroke. Cochrane Database Syst Rev 2003; (2): CD000029.
[PMID: 12804384]
[21]
Szarek M, Amarenco P, Callahan A, et al. Atorvastatin reduces first and subsequent vascular events across vascular territories: The SPARCL trial. J Am Coll Cardiol 2020; 75(17): 2110-8.
[http://dx.doi.org/10.1016/j.jacc.2020.03.015] [PMID: 32194196]
[22]
Amarenco P, Kim JS, Labreuche J, et al. A comparison of two LDL cholesterol targets after ischemic stroke. N Engl J Med 2020; 382(1): 9-19.
[http://dx.doi.org/10.1056/NEJMoa1910355] [PMID: 31738483]
[23]
Bohula EA, Wiviott SD, Giugliano RP, et al. Prevention of stroke with the addition of ezetimibe to statin therapy in patients with acute coronary syndrome in IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial). Circulation 2017; 136(25): 2440-50.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.117.029095] [PMID: 28972004]
[24]
Giugliano RP, Cannon CP, Blazing MA, et al. Benefit of adding ezetimibe to statin therapy on cardiovascular outcomes and safety in patients with versus without diabetes mellitus. Circulation 2018; 137(15): 1571-82.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.117.030950] [PMID: 29263150]
[25]
Giugliano RP, Wiviott SD, Blazing MA, et al. Long-term safety and efficacy of achieving very low levels of low-density lipoprotein cholesterol: a prespecified analysis of the IMPROVE-IT Trial. JAMA Cardiol 2017; 2(5): 547-55.
[http://dx.doi.org/10.1001/jamacardio.2017.0083] [PMID: 28291866]
[26]
Jukema JW, Zijlstra LE, Bhatt DL, et al. Effect of alirocumab on stroke in ODYSSEY OUTCOMES. Circulation 2019; 140(25): 2054-62.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.119.043826] [PMID: 31707788]
[27]
Mach F, Baigent C, Catapano AL, et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J 2020; 41(1): 111-88.
[http://dx.doi.org/10.1093/eurheartj/ehz455] [PMID: 31504418]
[28]
Sabatine MS, Giugliano RP, Keech AC, et al. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med 2017; 376(18): 1713-22.
[http://dx.doi.org/10.1056/NEJMoa1615664] [PMID: 28304224]
[29]
Giugliano RP, Pedersen TR, Saver JL, et al. Stroke prevention with the PCSK9 (Proprotein convertase subtilisin kexin type 9) inhibitor evolocumab added to statin in high-risk patients with stable atherosclerosis. Stroke 2020; 51(5): 1546-54.
[http://dx.doi.org/10.1161/STROKEAHA.119.027759] [PMID: 32312223]
[30]
Tziomalos K, Giampatzis V, Bouziana SD, et al. Comparative effects of more versus less aggressive treatment with statins on the long-term outcome of patients with acute ischemic stroke. Atherosclerosis 2015; 243(1): 65-70.
[http://dx.doi.org/10.1016/j.atherosclerosis.2015.08.043] [PMID: 26355807]
[31]
Puri R, Mehta V, Duell PB, et al. Proposed low-density lipoprotein cholesterol goals for secondary prevention and familial hypercholesterolemia in India with focus on PCSK9 inhibitor monoclonal antibodies: Expert consensus statement from Lipid Association of India. J Clin Lipidol 2020; 14(2): e1-e13.
[http://dx.doi.org/10.1016/j.jacl.2020.01.006] [PMID: 32089456]
[32]
Elkind MS, Sacco RL, MacArthur RB, et al. The Neuroprotection with Statin Therapy for Acute Recovery Trial (NeuSTART): an adaptive design phase I dose-escalation study of high-dose lovastatin in acute ischemic stroke. Int J Stroke 2008; 3(3): 210-8.
[http://dx.doi.org/10.1111/j.1747-4949.2008.00200.x] [PMID: 18705902]
[33]
Hong KS, Lee JS. Statins in acute ischemic stroke: A systematic review. J Stroke 2015; 17(3): 282-301.
[http://dx.doi.org/10.5853/jos.2015.17.3.282] [PMID: 26437994]
[34]
Zhao W, Xiao ZJ, Zhao SP. The benefits and risks of statin therapy in ischemic stroke: A review of the literature. Neurol India 2019; 67(4): 983-92.
[http://dx.doi.org/10.4103/0028-3886.266274] [PMID: 31512619]
[35]
Ní Chróinín D, Asplund K, Åsberg S, et al. Statin therapy and outcome after ischemic stroke: systematic review and meta-analysis of observational studies and randomized trials. Stroke 2013; 44(2): 448-56.
[http://dx.doi.org/10.1161/STROKEAHA.112.668277] [PMID: 23287777]
[36]
Flint AC, Kamel H, Navi BB, et al. Statin use during ischemic stroke hospitalization is strongly associated with improved poststroke survival. Stroke 2012; 43(1): 147-54.
[http://dx.doi.org/10.1161/STROKEAHA.111.627729] [PMID: 22020026]
[37]
Bhalla A, Grieve R, Tilling K, Rudd AG, Wolfe CD. Older stroke patients in Europe: stroke care and determinants of outcome. Age Ageing 2004; 33(6): 618-24.
[http://dx.doi.org/10.1093/ageing/afh219] [PMID: 15501838]
[38]
Phipps MS, Zeevi N, Staff I, Fortunato G, Kuchel GA, McCullough LD. Stroke severity and outcomes for octogenarians receiving statins. Arch Gerontol Geriatr 2013; 57(3): 377-82.
[http://dx.doi.org/10.1016/j.archger.2013.05.007] [PMID: 23815970]
[39]
Cappellari M, Bovi P, Moretto G, et al. The THRombolysis and STatins (THRaST) study. Neurology 2013; 80(7): 655-61.
[http://dx.doi.org/10.1212/WNL.0b013e318281cc83] [PMID: 23345634]
[40]
Montaner J, Bustamante A, García-Matas S, et al. STARS Investigators. Combination of thrombolysis and statins in acute stroke is safe: Results of the STARS randomized trial (Stroke Treatment With Acute Reperfusion and Simvastatin). Stroke 2016; 47(11): 2870-3.
[http://dx.doi.org/10.1161/STROKEAHA.116.014600] [PMID: 27758944]
[41]
Tsivgoulis G, Kadlecová P, Kobayashi A, et al. Safety of statin pretreatment in intravenous thrombolysis for acute ischemic stroke. Stroke 2015; 46(9): 2681-4.
[http://dx.doi.org/10.1161/STROKEAHA.115.010244] [PMID: 26173726]
[42]
Tan C, Liu X, Mo L, et al. Statin, cholesterol, and sICH after acute ischemic stroke: systematic review and meta-analysis. Neurol Sci 2019; 40(11): 2267-75.
[http://dx.doi.org/10.1007/s10072-019-03995-0] [PMID: 31267305]
[43]
Cappellari M, Moretto G, Bovi P. Letter by Cappellari et al regarding article, “statin therapy and outcome after ischemic stroke: systematic review and meta-analysis of observational studies and Randomized Trials. Stroke 2013; 44(6): e70.
[http://dx.doi.org/10.1161/STROKEAHA.113.001207] [PMID: 23592766]
[44]
Scheitz JF, Seiffge DJ, Tütüncü S, et al. Dose-related effects of statins on symptomatic intracerebral hemorrhage and outcome after thrombolysis for ischemic stroke. Stroke 2014; 45(2): 509-14.
[http://dx.doi.org/10.1161/STROKEAHA.113.002751] [PMID: 24368561]
[45]
Bang OY, Saver JL, Liebeskind DS, et al. Cholesterol level and symptomatic hemorrhagic transformation after ischemic stroke thrombolysis. Neurology 2007; 68(10): 737-42.
[http://dx.doi.org/10.1212/01.wnl.0000252799.64165.d5] [PMID: 17182976]
[46]
Antonopoulos AS, Margaritis M, Lee R, Channon K, Antoniades C. Statins as anti-inflammatory agents in atherogenesis: molecular mechanisms and lessons from the recent clinical trials. Curr Pharm Des 2012; 18(11): 1519-30.
[http://dx.doi.org/10.2174/138161212799504803] [PMID: 22364136]
[47]
Endres M, Laufs U. Discontinuation of statin treatment in stroke patients. Stroke 2006; 37(10): 2640-3.
[http://dx.doi.org/10.1161/01.STR.0000240690.69406.28] [PMID: 16946153]
[48]
Blanco M, Nombela F, Castellanos M, et al. Statin treatment withdrawal in ischemic stroke: a controlled randomized study. Neurology 2007; 69(9): 904-10.
[http://dx.doi.org/10.1212/01.wnl.0000269789.09277.47] [PMID: 17724294]
[49]
Flint AC, Kamel H, Navi BB, et al. Inpatient statin use predicts improved ischemic stroke discharge disposition. Neurology 2012; 78(21): 1678-83.
[http://dx.doi.org/10.1212/WNL.0b013e3182575142] [PMID: 22614435]
[50]
Vitturi BK, Gagliardi RJ. The influence of statin withdrawal and adherence on stroke outcomes. Neurol Sci 2021; 42(6): 2317-23.
[http://dx.doi.org/10.1007/s10072-020-04790-y] [PMID: 33037514]
[51]
Vitturi BK, Gagliardi RJ. Effects of statin therapy on outcomes of ischemic stroke: a real-world experience in Brazil. Arq Neuropsiquiatr 2020; 78(8): 461-7.
[http://dx.doi.org/10.1590/0004-282x20200027] [PMID: 32627806]
[52]
Amarenco P, Benavente O, Goldstein LB, et al. Results of the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial by stroke subtypes. Stroke 2009; 40(4): 1405-9.
[http://dx.doi.org/10.1161/STROKEAHA.108.534107] [PMID: 19228842]
[53]
An SJ, Kim TJ, Yoon BW. Epidemiology, risk factors, and clinical features of intracerebral hemorrhage: An update. J Stroke 2017; 19(1): 3-10.
[http://dx.doi.org/10.5853/jos.2016.00864] [PMID: 28178408]
[54]
Endres M, Nolte CH, Scheitz JF. Statin treatment in patients with intracerebral hemorrhage. Stroke 2018; 49(1): 240-6.
[http://dx.doi.org/10.1161/STROKEAHA.117.019322] [PMID: 29191849]
[55]
Collins R, Armitage J, Parish S, Sleight P, Peto R. 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(9411): 757-67.
[http://dx.doi.org/10.1016/S0140-6736(04)15690-0] [PMID: 15016485]
[56]
Van Matre ET, Sherman DS, Kiser TH. Management of intracerebral hemorrhage--use of statins. Vasc Health Risk Manag 2016; 12: 153-61.
[PMID: 27143909]
[57]
Hackam DG, Woodward M, Newby LK, et al. Statins and intracerebral hemorrhage: collaborative systematic review and meta-analysis. Circulation 2011; 124(20): 2233-42.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.111.055269] [PMID: 22007076]
[58]
McKinney JS, Kostis WJ. Statin therapy and the risk of intracerebral hemorrhage: a meta-analysis of 31 randomized controlled trials. Stroke 2012; 43(8): 2149-56.
[http://dx.doi.org/10.1161/STROKEAHA.112.655894] [PMID: 22588266]
[59]
Judge C, Ruttledge S, Costello M, et al. Lipid lowering therapy, low-density lipoprotein level and risk of intracerebral hemorrhage- a meta-analysis. J Stroke Cerebrovasc Dis 2019; 28(6): 1703-9.
[http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2019.02.018] [PMID: 30878368]
[60]
Pandit AK, Kumar P, Kumar A, Chakravarty K, Misra S, Prasad K. High-dose statin therapy and risk of intracerebral hemorrhage: a meta-analysis. Acta Neurol Scand 2016; 134(1): 22-8.
[http://dx.doi.org/10.1111/ane.12540] [PMID: 26647879]
[61]
Newman CB, Preiss D, Tobert JA, et al. Statin safety and associated adverse events: A scientific statement from the American heart association. Arterioscler Thromb Vasc Biol 2019; 39(2): e38-81.
[http://dx.doi.org/10.1161/ATV.0000000000000073] [PMID: 30580575]
[62]
Siddiqui FM, Langefeld CD, Moomaw CJ, et al. Use of statins and outcomes in intracerebral hemorrhage patients. Stroke 2017; 48(8): 2098-104.
[http://dx.doi.org/10.1161/STROKEAHA.117.017358] [PMID: 28663510]
[63]
Tapia-Perez JH, Zilke R, Schneider T. Match-study of statin therapy in spontaneous intracerebral hemorrhage: is the discontinuation reasonable? J Neurosurg Sci 2016; 60(3): 301-12.
[PMID: 25501007]
[64]
Dowlatshahi D, Demchuk AM, Fang J, Kapral MK, Sharma M, Smith EE. Association of statins and statin discontinuation with poor outcome and survival after intracerebral hemorrhage. Stroke 2012; 43(6): 1518-23.
[http://dx.doi.org/10.1161/STROKEAHA.111.645978] [PMID: 22442172]
[65]
Flint AC, Conell C, Rao VA, et al. Effect of statin use during hospitalization for intracerebral hemorrhage on mortality and discharge disposition. JAMA Neurol 2014; 71(11): 1364-71.
[http://dx.doi.org/10.1001/jamaneurol.2014.2124] [PMID: 25244578]
[66]
Woo D, Deka R, Falcone GJ, et al. Apolipoprotein E, statins, and risk of intracerebral hemorrhage. Stroke 2013; 44(11): 3013-7.
[http://dx.doi.org/10.1161/STROKEAHA.113.001304] [PMID: 24008570]
[67]
Haussen DC, Henninger N, Kumar S, Selim M. Statin use and microbleeds in patients with spontaneous intracerebral hemorrhage. Stroke 2012; 43(10): 2677-81.
[http://dx.doi.org/10.1161/STROKEAHA.112.657486] [PMID: 22829545]
[68]
Jung JM, Choi JY, Kim HJ, Seo WK. Statin use in spontaneous intracerebral hemorrhage: a systematic review and meta-analysis. Int J Stroke 2015; 10(Suppl. A100): 10-7.
[http://dx.doi.org/10.1111/ijs.12624] [PMID: 26306674]
[69]
Chen PS, Cheng CL, Chang YC, Kao Yang YH, Yeh PS, Li YH. Early statin therapy in patients with acute intracerebral hemorrhage without prior statin use. Eur J Neurol 2015; 22(5): 773-80.
[http://dx.doi.org/10.1111/ene.12649] [PMID: 25623473]
[70]
Seyfried D, Han Y, Lu D, Chen J, Bydon A, Chopp M. Improvement in neurological outcome after administration of atorvastatin following experimental intracerebral hemorrhage in rats. J Neurosurg 2004; 101(1): 104-7.
[http://dx.doi.org/10.3171/jns.2004.101.1.0104] [PMID: 15255259]
[71]
Karki K, Knight RA, Han Y, et al. Simvastatin and atorvastatin improve neurological outcome after experimental intracerebral hemorrhage. Stroke 2009; 40(10): 3384-9.
[http://dx.doi.org/10.1161/STROKEAHA.108.544395] [PMID: 19644071]
[72]
FitzMaurice E, Wendell L, Snider R, et al. Effect of statins on intracerebral hemorrhage outcome and recurrence. Stroke 2008; 39(7): 2151-4.
[http://dx.doi.org/10.1161/STROKEAHA.107.508861] [PMID: 18436876]
[73]
Ribe AR, Vestergaard CH, Vestergaard M, et al. Statins and risk of intracerebral hemorrhage in individuals with a history of stroke. Stroke 2020; 51(4): 1111-9.
[http://dx.doi.org/10.1161/STROKEAHA.119.027301] [PMID: 32114928]
[74]
Westover MB, Bianchi MT, Eckman MH, Greenberg SM. Statin use following intracerebral hemorrhage: a decision analysis. Arch Neurol 2011; 68(5): 573-9.
[http://dx.doi.org/10.1001/archneurol.2010.356] [PMID: 21220650]
[75]
Wang X, Dong Y, Qi X, Huang C, Hou L. Cholesterol levels and risk of hemorrhagic stroke: a systematic review and meta-analysis. Stroke 2013; 44(7): 1833-9.
[http://dx.doi.org/10.1161/STROKEAHA.113.001326] [PMID: 23704101]
[76]
Hartz J, Hegele RA, Wilson DP. Low LDL cholesterol-Friend or foe? J Clin Lipidol 2019; 13(3): 367-73.
[http://dx.doi.org/10.1016/j.jacl.2019.05.006] [PMID: 31130490]
[77]
Undas A, Brummel-Ziedins KE, Mann KG. Statins and blood coagulation. Arterioscler Thromb Vasc Biol 2005; 25(2): 287-94.
[http://dx.doi.org/10.1161/01.ATV.0000151647.14923.ec] [PMID: 15569822]
[78]
Ma C, Gurol ME, Huang Z, et al. Low-density lipoprotein cholesterol and risk of intracerebral hemorrhage: A prospective study. Neurology 2019; 93(5): e445-57.
[http://dx.doi.org/10.1212/WNL.0000000000007853] [PMID: 31266905]
[79]
Iyengar SS, Puri R, Narasingan SN, et al. Lipid Association of India (LAI) expert consensus statement on management of dyslipidemia in Indians 2017: part 2. Clin Lipidol 2017; 12: 56-109.
[80]
Tai SY, Lin FC, Lee CY, Chang CJ, Wu MT, Chien CY. Statin use after intracerebral hemorrhage: a 10-year nationwide cohort study. Brain Behav 2016; 6(8): e00487.
[http://dx.doi.org/10.1002/brb3.487] [PMID: 27247857]
[81]
Quinn KL, Macdonald EM, Mamdani MM, Diong C, Juurlink DN. Lipophilic statins and the risk of intracranial hemorrhage following ischemic stroke: A population-based study. Drug Saf 2017; 40(10): 887-93.
[http://dx.doi.org/10.1007/s40264-017-0552-z] [PMID: 28620871]
[82]
Freiberg JJ, Tybjaerg-Hansen A, Jensen JS, Nordestgaard BG. Nonfasting triglycerides and risk of ischemic stroke in the general population. JAMA 2008; 300(18): 2142-52.
[http://dx.doi.org/10.1001/jama.2008.621] [PMID: 19001625]
[83]
Bonaventure A, Kurth T, Pico F, et al. Triglycerides and risk of hemorrhagic stroke vs. ischemic vascular events: The Three-City Study. Atherosclerosis 2010; 210(1): 243-8.
[http://dx.doi.org/10.1016/j.atherosclerosis.2009.10.043] [PMID: 19963214]
[84]
Shahar E, Chambless LE, Rosamond WD, et al. Plasma lipid profile and incident ischemic stroke: the Atherosclerosis Risk in Communities (ARIC) study. Stroke 2003; 34(3): 623-31.
[http://dx.doi.org/10.1161/01.STR.0000057812.51734.FF] [PMID: 12624282]
[85]
Kayran Y, Yayla V, Çabalar M, et al. LDL subclasses in ischemic stroke: A risk factor? Noro Psikiyatri Arsivi 2019; 56(1): 13-7.
[PMID: 30911231]
[86]
Bhatt DL, Steg PG, Miller M, et al. Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia. N Engl J Med 2019; 380(1): 11-22.
[http://dx.doi.org/10.1056/NEJMoa1812792] [PMID: 30415628]
[87]
Di Angelantonio E, Sarwar N, Perry P, et al. Major lipids, apolipoproteins, and risk of vascular disease. JAMA 2009; 302(18): 1993-2000.
[http://dx.doi.org/10.1001/jama.2009.1619] [PMID: 19903920]
[88]
Sanossian N, Saver JL, Navab M, Ovbiagele B. High-density lipoprotein cholesterol: an emerging target for stroke treatment. Stroke 2007; 38(3): 1104-9.
[http://dx.doi.org/10.1161/01.STR.0000258347.19449.0f] [PMID: 17255541]
[89]
Kontush A, Chantepie S, Chapman MJ. Small, dense HDL particles exert potent protection of atherogenic LDL against oxidative stress. Arterioscler Thromb Vasc Biol 2003; 23(10): 1881-8.
[http://dx.doi.org/10.1161/01.ATV.0000091338.93223.E8] [PMID: 12920049]
[90]
Chei CL, Yamagishi K, Kitamura A, et al. High-density lipoprotein subclasses and risk of stroke and its subtypes in Japanese population: the Circulatory Risk in Communities Study. Stroke 2013; 44(2): 327-33.
[http://dx.doi.org/10.1161/STROKEAHA.112.674812] [PMID: 23321451]
[91]
Reina SA, Llabre MM, Allison MA, et al. HDL cholesterol and stroke risk: The Multi-Ethnic Study of Atherosclerosis. Atherosclerosis 2015; 243(1): 314-9.
[http://dx.doi.org/10.1016/j.atherosclerosis.2015.09.031] [PMID: 26425994]
[92]
Wilson DP, Jacobson TA, Jones PH, et al. Use of Lipoprotein(a) in clinical practice: A biomarker whose time has come. A scientific statement from the National Lipid Association. J Clin Lipidol 2019; 13(3): 374-92.
[http://dx.doi.org/10.1016/j.jacl.2019.04.010] [PMID: 31147269]
[93]
Kamstrup PR, Tybjærg-Hansen A, Nordestgaard BG. Elevated lipoprotein(a) and risk of aortic valve stenosis in the general population. J Am Coll Cardiol 2014; 63(5): 470-7.
[http://dx.doi.org/10.1016/j.jacc.2013.09.038] [PMID: 24161338]
[94]
Kamstrup PR, Benn M, Tybjaerg-Hansen A, Nordestgaard BG. Extreme lipoprotein(a) levels and risk of myocardial infarction in the general population: the Copenhagen City Heart Study. Circulation 2008; 117(2): 176-84.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.107.715698] [PMID: 18086931]
[95]
Nave AH, Lange KS, Leonards CO, et al. Lipoprotein (a) as a risk factor for ischemic stroke: a meta-analysis. Atherosclerosis 2015; 242(2): 496-503.
[http://dx.doi.org/10.1016/j.atherosclerosis.2015.08.021] [PMID: 26298741]
[96]
Lange KS, Nave AH, Liman TG, Grittner U, Endres M, Ebinger M. Lipoprotein(a) Levels and recurrent vascular events after first ischemic stroke. Stroke 2017; 48(1): 36-42.
[http://dx.doi.org/10.1161/STROKEAHA.116.014436] [PMID: 27856951]
[97]
Langsted A, Nordestgaard BG, Kamstrup PR. Elevated lipoprotein(a) and risk of ischemic stroke. J Am Coll Cardiol 2019; 74(1): 54-66.
[http://dx.doi.org/10.1016/j.jacc.2019.03.524] [PMID: 31272552]
[98]
Meyers CD, Kamanna VS, Kashyap ML. Niacin therapy in atherosclerosis. Curr Opin Lipidol 2004; 15(6): 659-65.
[http://dx.doi.org/10.1097/00041433-200412000-00006] [PMID: 15529025]
[99]
Tsimikas S, Karwatowska-Prokopczuk E, Gouni-Berthold I, et al. AKCEA-APO(a)-LRx Study Investigators. Lipoprotein(a) reduction in persons with cardiovascular disease. N Engl J Med 2020; 382(3): 244-55.
[http://dx.doi.org/10.1056/NEJMoa1905239] [PMID: 31893580]
[100]
Madsen CM, Kamstrup PR, Langsted A, Varbo A, Nordestgaard BG. Lipoprotein(a)-lowering by 50 mg/dL (105 nmol/L) may be needed to reduce cardiovascular disease 20% in secondary prevention: A population-based study. Arterioscler Thromb Vasc Biol 2020; 40(1): 255-66.
[http://dx.doi.org/10.1161/ATVBAHA.119.312951] [PMID: 31578080]
[101]
Paré G, Çaku A, McQueen M, et al. INTERHEART Investigators. Lipoprotein(a) levels and the risk of myocardial infarction among 7 ethnic groups. Circulation 2019; 139(12): 1472-82.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.118.034311] [PMID: 30667276]
[102]
Choi KH, Seo WK, Park MS, et al. Effect of statin therapy on outcomes of patients with acute ischemic stroke and atrial fibrillation. J Am Heart Assoc 2019; 8(24): e013941.
[http://dx.doi.org/10.1161/JAHA.119.013941] [PMID: 31826725]
[103]
Park HK, Lee JS, Hong KS, et al. Statin therapy in acute cardioembolic stroke with no guidance-based indication. Neurology 2020; 94(19): e1984-95.
[http://dx.doi.org/10.1212/WNL.0000000000009397] [PMID: 32273430]
[104]
Amarenco P, Labreuche J, Lavallée P, Touboul PJ. Statins in stroke prevention and carotid atherosclerosis: systematic review and up-to-date meta-analysis. Stroke 2004; 35(12): 2902-9.
[http://dx.doi.org/10.1161/01.STR.0000147965.52712.fa] [PMID: 15514180]
[105]
Perler BA. The effect of statin medications on perioperative and long-term outcomes following carotid endarterectomy or stenting. Semin Vasc Surg 2007; 20(4): 252-8.
[http://dx.doi.org/10.1053/j.semvascsurg.2007.10.008] [PMID: 18082842]
[106]
Gröschel K, Ernemann U, Schulz JB, Nägele T, Terborg C, Kastrup A. Statin therapy at carotid angioplasty and stent placement: effect on procedure-related stroke, myocardial infarction, and death. Radiology 2006; 240(1): 145-51.
[http://dx.doi.org/10.1148/radiol.2401050603] [PMID: 16793975]
[107]
Patti G, Tomai F, Melfi R, et al. Strategies of clopidogrel load and atorvastatin reload to prevent ischemic cerebral events in patients undergoing protected carotid stenting. Results of the randomized ARMYDA-9 CAROTID (Clopidogrel and Atorvastatin Treatment During Carotid Artery Stenting) study. J Am Coll Cardiol 2013; 61(13): 1379-87.
[http://dx.doi.org/10.1016/j.jacc.2013.01.015] [PMID: 23490041]
[108]
Verzini F, De Rango P, Parlani G, et al. Effects of statins on early and late results of carotid stenting. J Vasc Surg 2011; 53(1): 71-9.
[http://dx.doi.org/10.1016/j.jvs.2010.08.024] [PMID: 20961727]
[109]
Hussain MA, Saposnik G, Raju S, et al. Association between statin use and cardiovascular events after carotid artery revascularization. J Am Heart Assoc 2018; 7(16): e009745.
[http://dx.doi.org/10.1161/JAHA.118.009745] [PMID: 30369318]
[110]
Naylor AR, Ricco JB, de Borst GJ, et al. Editor’s Choice - Management of Atherosclerotic Carotid and Vertebral Artery Disease: 2017 Clinical Practice Guidelines of the European Society for Vascular Surgery (ESVS). Eur J Vasc Endovasc Surg 2018; 55(1): 3-81.
[http://dx.doi.org/10.1016/j.ejvs.2017.06.021] [PMID: 28851594]
[111]
Ward NC, Watts GF, Eckel RH. Statin Toxicity. Circ Res 2019; 124(2): 328-50.
[http://dx.doi.org/10.1161/CIRCRESAHA.118.312782] [PMID: 30653440]
[112]
Sattar N, Preiss D, Murray HM, et al. Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials. Lancet 2010; 375(9716): 735-42.
[http://dx.doi.org/10.1016/S0140-6736(09)61965-6] [PMID: 20167359]
[113]
Ridker PM, Pradhan A, MacFadyen JG, Libby P, Glynn RJ. Cardiovascular benefits and diabetes risks of statin therapy in primary prevention: an analysis from the JUPITER trial. Lancet 2012; 380(9841): 565-71.
[http://dx.doi.org/10.1016/S0140-6736(12)61190-8] [PMID: 22883507]
[114]
Orth M, Bellosta S. Cholesterol: its regulation and role in central nervous system disorders. Cholesterol 2012; 19.
[115]
Zhang J, Liu Q. Cholesterol metabolism and homeostasis in the brain. Protein Cell 2015; 6(4): 254-64.
[http://dx.doi.org/10.1007/s13238-014-0131-3] [PMID: 25682154]
[116]
Sezer K, Emral R, Corapcioglu D, Gen R, Akbay E. Effect of very low LDL-cholesterol on cortisol synthesis. J Endocrinol Invest 2008; 31(12): 1075-8.
[http://dx.doi.org/10.1007/BF03345655] [PMID: 19246973]
[117]
O’Keefe JH Jr, Cordain L, Harris WH, Moe RM, Vogel R. Optimal low-density lipoprotein is 50 to 70 mg/dl: lower is better and physiologically normal. J Am Coll Cardiol 2004; 43(11): 2142-6.
[http://dx.doi.org/10.1016/j.jacc.2004.03.046] [PMID: 15172426]
[118]
Freedman DS, Srinivasan SR, Cresanta JL, Webber LS, Berenson GS. Cardiovascular risk factors from birth to 7 years of age: the Bogalusa Heart Study. Serum lipids and lipoproteins. Pediatrics 1987; 80(5 Pt 2): 789-96.
[PMID: 3478647]
[119]
Brown MS, Goldstein JL. A receptor-mediated pathway for cholesterol homeostasis. Science 1986; 232(4746): 34-47.
[http://dx.doi.org/10.1126/science.3513311] [PMID: 3513311]
[120]
Giugliano RP, Pedersen TR, Park JG, et al. Clinical efficacy and safety of achieving very low LDL-cholesterol concentrations with the PCSK9 inhibitor evolocumab: a prespecified secondary analysis of the FOURIER trial. Lancet 2017; 390(10106): 1962-71.
[http://dx.doi.org/10.1016/S0140-6736(17)32290-0] [PMID: 28859947]
[121]
Wong ND, Puri R, Mehta V, Duell PB. When is it appropriate to lower low density lipoprotein-cholesterol levels to <30 mg/dL? Am J Cardiol 2021; 157: 142-4.
[http://dx.doi.org/10.1016/j.amjcard.2021.06.041] [PMID: 34344510]
[122]
Puri R, Mehta V, Iyengar SS, et al. Low density lipoprotein cholesterol targets in secondary prevention of atherosclerotic cardiovascular disease. J Assoc Physicians India 2020; 68(11[Special]): 21-34.
[PMID: 33350612]

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