Reduction in the Ratio of Low-density Lipoprotein Cholesterol to Highdensity Lipoprotein Cholesterol is Associated with Increased Risks of Hemorrhagic Transformation in Patients with Acute Ischemic Stroke

Author(s): Yanan Wang, Chenchen Wei, Quhong Song, Junfeng Liu, Yajun Cheng, Yisong Li, Bo Wu, Ming Liu*

Journal Name: Current Neurovascular Research

Volume 16 , Issue 3 , 2019

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Background and Purpose: Hemorrhagic transformation (HT) is a potentially serious complication in patients with acute ischemic stroke (AIS). Whether the ratio of low-density lipoprotein cholesterol to high-density lipoprotein cholesterol (LDL-C/HDL-C) is associated with HT remains unclear.

Methods: Ischemic stroke patients within 7 days of stroke onset from January 2016 to November 2017 were included in this study. Lipid profiles were measured within 24h after admission. HT was determined by a second computed tomography or magnetic resonance imaging within 7 days after admission. Univariate and multivariate logistic regression analysis was used to assess the association between LDL-C/HDL-C and HT.

Results: We enrolled 1239 patients with AIS (788 males; mean age, 64 ± 15 years), of whom 129 (10.4%) developed HT. LDL-C/HDL-C was significantly lower on admission in patients with HT than those without HT (2.00 ± 0.89 vs. 2.25 ± 1.02, P=0.009). The unadjusted odds ratio (OR) of low LDL-C/HDL-C for HT was 2.07 (95% confidence interval [CI] 1.42-3.01, P<0.001). After adjustment for possible confounders, lower LDL-C/HDL-C (≤1.52) was significantly associated with HT (OR 1.53, 95% CI: 1.02-2.31, P=0.046). Similar results were observed between lower LDL-C (≤ 4 mmol/L) and HT (OR 4.17, 95% CI: 1.25-13.90, P=0.02). However, no significant association was found between HT and high HDL-C, low triglycerides or low total cholesterol.

Conclusion: Lower LDL-C/HDL-C and LDL-C were significantly associated with increased risk of HT after AIS. Further investigations are warranted to confirm these findings and then optimize lipid management in stroke patients with lower LDL/HDL-C or LDL-C.

Keywords: LDL-C/HDL-C, hemorrhagic transformation (HT), acute ischemic stroke, LDL-C, HDL-C, lipid profiles.

Alvarez-Sabin J, Maisterra O, Santamarina E, et al. Factors influencing haemorrhagic transformation in ischaemic stroke. Lancet Neurol 2013; 12(7): 689-705.
Yaghi S, Willey JZ, Cucchiara B, et al. Treatment and outcome of hemorrhagic transformation after intravenous alteplase in acute ischemic stroke: A scientific statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2017; 48(12): e343-61.
Wu S, Wu B, Liu M, et al. Stroke in China: Advances and challenges in epidemiology, prevention, and management. Lancet Neurol 2019; 18(4): 394-405.
Rothwell PM, Algra A, Amarenco P. Medical treatment in acute and long-term secondary prevention after transient ischaemic attack and ischaemic stroke. Lancet 2011; 377(9778): 1681-92.
Bang OY, Saver JL, Liebeskind DS, et al. Cholesterol level and symptomatic hemorrhagic transformation after ischemic stroke thrombolysis. Neurology 2007; 68(10): 737-42.
D’Amelio M, Terruso V, Famoso G, et al. Cholesterol levels and risk of hemorrhagic transformation after acute ischemic stroke. Cerebrovascular diseases (Basel, Switzerland) 2011; 32(3): 234-8.
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(5): 1627-32.
Lin TC, Lin YK, Chen CI, et al. Serum lipid level is not associated with symptomatic intracerebral hemorrhage after intravenous thrombolysis for acute ischemic stroke. PeerJ 2018; 6: e6021.
Messe SR, Pervez MA, Smith EE, et al. Lipid profile, lipid-lowering medications, and intracerebral hemorrhage after tPA in get with the guidelines-stroke. Stroke 2013; 44(5): 1354-9.
Nardi K, Leys D, Eusebi P, et al. Influence of lipid profiles on the risk of hemorrhagic transformation after ischemic stroke: Systematic review. Cerebrovasc Dis Extra 2011; 1(1): 130-41.
Kannel WB. Risk stratification of dyslipidemia: Insights from the Framingham Study. Curr Med Chem Cardiovasc Hematol Agents 2005; 3(3): 187-93.
Barter P, Gotto AM, LaRosa JC, et al. HDL cholesterol, very low levels of LDL cholesterol, and cardiovascular events. N Engl J Med 2007; 357(13): 1301-10.
Nicholls SJ, Tuzcu EM, Sipahi I, et al. Statins, high-density lipoprotein cholesterol, and regression of coronary atherosclerosis. JAMA 2007; 297(5): 499-508.
Lei C, Wu B, Liu M, et al. Totaled health risks in vascular events score predicts clinical outcomes in patients with cardioembolic and other subtypes of ischemic stroke. Stroke 2014; 45(6): 1689-94.
Aho K, Harmsen P, Hatano S, et al. Cerebrovascular disease in the community: Results of a WHO collaborative study. Bull World Health Organ 1980; 58(1): 113-30.
Brott T, Adams HP Jr, Olinger CP, et al. Measurements of acute cerebral infarction: A clinical examination scale. Stroke 1989; 20(7): 864-70.
Tan S, Wang D, Liu M, et al. Frequency and predictors of spontaneous hemorrhagic transformation in ischemic stroke and its association with prognosis. J Neurol 2014; 261(5): 905-12.
Choi KH, Park MS, Kim JT, et al. The serum ferritin level is an important predictor of hemorrhagic transformation in acute ischaemic stroke. Eur J Neurol 2012; 19(4): 570-7.
Tan G, Lei C, Hao Z, et al. Liver function may play an uneven role in haemorrhagic transformation for stroke subtypes after acute ischaemic stroke. Eur J Neurol 2016; 23(3): 597-604.
Liu B, Wang D, Hao Z, et al. Reduction in Estimated Glomerular Filtration Rate (eGFR) results in an increased risk of spontaneous hemorrhagic transformation in patients with large-artery atherosclerosis stroke. Curr Neurovasc Res 2016; 13(1): 75-81.
Lokeskrawee T, Muengtaweepongsa S, Patumanond J, et al. Prediction of symptomatic intracranial hemorrhage after intravenous thrombolysis in acute ischemic stroke: The symptomatic intracranial hemorrhage score. J Stroke Cerebrovasc Dis 2017; 26(11): 2622-9.
Kalinin MN, Khasanova DR, Ibatullin MM. The hemorrhagic transformation index score: A prediction tool in middle cerebral artery ischemic stroke. BMC Neurol 2017; 17(1): 177.
Zhang J, Yang Y, Sun H, et al. Hemorrhagic transformation after cerebral infarction: Current concepts and challenges. Annals of translational medicine 2014; 2(8): 81.
Lin SF, Chao AC, Hu HH, et al. Low cholesterol levels increase symptomatic intracranial hemorrhage rates after intravenous thrombolysis: A multicenter cohort validation study. J Atheroscler Thromb 2018; 26(6): 513-27.
Hong CT, Chiu WT, Chi NF, et al. Low-density lipoprotein level on admission is not associated with postintravenous thrombolysis intracranial hemorrhage in patients with acute ischemic stroke. J Investig Med 2018; 67(3): 659-62.
You S, Zhong C, Xu J, et al. LDL-C/HDL-C ratio and risk of all-cause mortality in patients with intracerebral hemorrhage. Neurol Res 2016; 38(10): 903-8.
Thrift A, McNeil J, Donnan G. Reduced frequency of high cholesterol levels among patients with intracerebral haemorrhage. J Clin Neurosci 2002; 9(4): 376-80.
Presta V, Figliuzzi I, Miceli F, et al. Achievement of low density lipoprotein (LDL) cholesterol targets in primary and secondary prevention: Analysis of a large real practice database in Italy. Atherosclerosis 2019; 285: 40-8.
Guedeney P, Claessen BE, Kalkman DN, et al. Residual inflammatory risk in patients with low LDL cholesterol levels undergoing percutaneous coronary intervention. J Am Coll Cardiol 2019; 73(19): 2401-9.
Calabresi L, Gomaraschi M, Simonelli S, et al. HDL and atherosclerosis: Insights from inherited HDL disorders. Biochim Biophys Acta 2015; 1851(1): 13-8.
Rosenson RS, Shott S, Tangney CC. Hypertriglyceridemia is associated with an elevated blood viscosity Rosenson: Triglycerides and blood viscosity. Atherosclerosis 2002; 161(2): 433-9.
Millan J, Pinto X, Munoz A, et al. Lipoprotein ratios: Physiological significance and clinical usefulness in cardiovascular prevention. Vasc Health Risk Manag 2009; 5: 757-65.
Zeng N, Wang A, Xu T, et al. Co-effect of serum Galectin-3 and high-density lipoprotein cholesterol on the prognosis of acute ischemic stroke. J Stroke Cerebrovasc Dis 2019; 28(7): 1879-85.
Jickling GC, Liu D, Stamova B, et al. Hemorrhagic transformation after ischemic stroke in animals and humans. J Cereb Blood Flow Metab 2014; 34(2): 185-99.
Song Q, Li Y, Wang Y, et al. Increased neutrophil-to-lymphocyte ratios are associated with greater risk of hemorrhagic transformation in patients with acute ischemic stroke. Curr Neurovasc Res 2018; 15(4): 326-35.
Kapourchali FR, Surendiran G, Goulet A, et al. The Role of dietary cholesterol in lipoprotein metabolism and related metabolic abnormalities: A mini-review. Crit Rev Food Sci Nutr 2016; 56(14): 2408-15.

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Article Details

Year: 2019
Published on: 19 June, 2019
Page: [266 - 272]
Pages: 7
DOI: 10.2174/1567202616666190619151914
Price: $65

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