Prognostic value of plasma fibroblast growth factor 21 among patients with acute ischemic stroke
Xiaowei Zheng
Department of Epidemiology, School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Medical College of Soochow University, Jiangsu, China
Search for more papers by this authorZhengbao Zhu
Department of Epidemiology, School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Medical College of Soochow University, Jiangsu, China
Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana, USA
Search for more papers by this authorDaoxia Guo
Department of Epidemiology, School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Medical College of Soochow University, Jiangsu, China
Search for more papers by this authorChongke Zhong
Department of Epidemiology, School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Medical College of Soochow University, Jiangsu, China
Search for more papers by this authorTan Xu
Department of Epidemiology, School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Medical College of Soochow University, Jiangsu, China
Search for more papers by this authorYanbo Peng
Department of Neurology, Affiliated Hospital of North China University of Science and Technology, Hebei, China
Search for more papers by this authorAili Wang
Department of Epidemiology, School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Medical College of Soochow University, Jiangsu, China
Search for more papers by this authorHao Peng
Department of Epidemiology, School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Medical College of Soochow University, Jiangsu, China
Search for more papers by this authorZhong Ju
Department of Neurology, Kerqin District First People’s Hospital of Tongliao City, Tongliao City, China
Search for more papers by this authorDeqin Geng
Department of Neurology, Affiliated Hospital of Xuzhou Medical University, Jiangsu, China
Search for more papers by this authorCorresponding Author
Yonghong Zhang
Department of Epidemiology, School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Medical College of Soochow University, Jiangsu, China
Correspondence
Yonghong Zhang, Department of Epidemiology, School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Medical College of Soochow University, 199 Renai Road, Industrial Park District, Suzhou, Jiangsu Province 215123, China.
Email: [email protected]
Search for more papers by this authorJiang He
Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana, USA
Search for more papers by this authorXiaowei Zheng
Department of Epidemiology, School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Medical College of Soochow University, Jiangsu, China
Search for more papers by this authorZhengbao Zhu
Department of Epidemiology, School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Medical College of Soochow University, Jiangsu, China
Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana, USA
Search for more papers by this authorDaoxia Guo
Department of Epidemiology, School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Medical College of Soochow University, Jiangsu, China
Search for more papers by this authorChongke Zhong
Department of Epidemiology, School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Medical College of Soochow University, Jiangsu, China
Search for more papers by this authorTan Xu
Department of Epidemiology, School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Medical College of Soochow University, Jiangsu, China
Search for more papers by this authorYanbo Peng
Department of Neurology, Affiliated Hospital of North China University of Science and Technology, Hebei, China
Search for more papers by this authorAili Wang
Department of Epidemiology, School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Medical College of Soochow University, Jiangsu, China
Search for more papers by this authorHao Peng
Department of Epidemiology, School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Medical College of Soochow University, Jiangsu, China
Search for more papers by this authorZhong Ju
Department of Neurology, Kerqin District First People’s Hospital of Tongliao City, Tongliao City, China
Search for more papers by this authorDeqin Geng
Department of Neurology, Affiliated Hospital of Xuzhou Medical University, Jiangsu, China
Search for more papers by this authorCorresponding Author
Yonghong Zhang
Department of Epidemiology, School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Medical College of Soochow University, Jiangsu, China
Correspondence
Yonghong Zhang, Department of Epidemiology, School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Medical College of Soochow University, 199 Renai Road, Industrial Park District, Suzhou, Jiangsu Province 215123, China.
Email: [email protected]
Search for more papers by this authorJiang He
Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana, USA
Search for more papers by this authorAbstract
Background and purpose
To evaluate the association between plasma fibroblast growth factor 21 (FGF-21) and clinical outcomes in patients with acute ischemic stroke.
Methods
A total of 3412 acute ischemic stroke patients from the China Antihypertensive Trial in Acute Ischemic Stroke with plasma FGF-21 measurements were included in this analysis. The primary outcome was a combination of death or major disability (modified Rankin Scale score ≥3) within 1 year after stroke.
Results
During the 1-year of follow-up, 745 (21.83%) patients experienced the primary outcome; 550 had a major disability and 195 died. After multivariate adjustment, higher plasma FGF-21 was significantly associated with increased risk of the primary outcome (odds ratio = 1.52, 95% confidence interval = 1.11–1.29). Each 1-SD increase of log-transformed FGF-21 (0.67 pg/ml) was associated with 19%, 3%, and 33% increased risk of the primary outcome, major disability, and death, respectively. The addition of FGF-21 to the conventional risk factors significantly improved prediction of the primary outcome in ischemic stroke patients (net reclassification index = 10.8%, p = 0.011; integrated discrimination improvement = 0.3%, p = 0.038).
Conclusions
Higher plasma FGF-21 was associated with poor prognosis in acute ischemic stroke patients, suggesting that FGF-21 may be a prognostic marker for ischemic stroke.
CONFLICT OF INTERESTS
The authors declare no financial or other conflicts of interest.
Open Research
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.
Supporting Information
| Filename | Description |
|---|---|
| ene14683-sup-0001-TableS1-S2.docxWord document, 22.4 KB | Table S1-S2 |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
REFERENCES
- 1Krishnamurthi RV, Feigin VL, Forouzanfar MH, et al. Global and regional burden of first-ever ischaemic and haemorrhagic stroke during 1990–2010: findings from the Global Burden of Disease Study 2010. Lancet Glob Health. 2013; 1: e259-e281.
- 2Zhang LF, Yang J, Hong Z, et al. Proportion of different subtypes of stroke in China. Stroke. 2003; 34: 2091-2096.
- 3Liu L, Wang D, Wong KS, Wang Y. Stroke and stroke care in China: huge burden, significant workload, and a national priority. Stroke. 2011; 42: 3651-3654.
- 4Wu S, Wu B, Liu M, et al. Stroke in China: advances and challenges in epidemiology, prevention, and management. Lancet Neurol. 2019; 18: 394-405.
- 5Slot KB, Berge E, Dorman P, Lewis S, Dennis M, Sandercock P. Impact of functional status at six months on long term survival in patients with ischaemic stroke: prospective cohort studies. BMJ. 2008; 336: 376-379.
- 6Seo JA, Kim NH. Fibroblast growth factor 21: a novel metabolic regulator. Diabetes Metab J. 2012; 36: 26-28.
- 7Badman MK, Pissios P, Kennedy AR, Koukos G, Flier JS, Maratos-Flier E. Hepatic fibroblast growth factor 21 is regulated by PPARalpha and is a key mediator of hepatic lipid metabolism in ketotic states. Cell Metab. 2007; 5: 426-437.
- 8Kharitonenkov A, Shiyanova TL, Koester A, et al. FGF-21 as a novel metabolic regulator. J Clin Invest. 2005; 115: 1627-1635.
- 9Kharitonenkov A, Wroblewski VJ, Koester A, et al. The metabolic state of diabetic monkeys is regulated by fibroblast growth factor-21. Endocrinology. 2007; 148: 774-781.
- 10Coskun T, Bina HA, Schneider MA, et al. Fibroblast growth factor 21 corrects obesity in mice. Endocrinology. 2008; 149: 6018-6027.
- 11Badman MK, Koester A, Flier JS, Kharitonenkov A, Maratos-Flier E. Fibroblast growth factor 21-deficient mice demonstrate impaired adaptation to ketosis. Endocrinology. 2009; 150: 4931-4940.
- 12Li H, Bao Y, Xu A, et al. Serum fibroblast growth factor 21 is associated with adverse lipid profiles and gamma-glutamyltransferase but not insulin sensitivity in Chinese subjects. J Clin Endocrinol Metab. 2009; 94: 2151-2156.
- 13Zhang X, Yeung DCY, Karpisek M, et al. Erratum. Serum FGF21 levels are increased in obesity and are independently associated with the metabolic syndrome in humans. Diabetes 2008;57:1246–1253. Diabetes. 2019; 68: 235.
- 14Chavez AO, Molina-Carrion M, Abdul-Ghani MA, Folli F, Defronzo RA, Tripathy D. Circulating fibroblast growth factor-21 is elevated in impaired glucose tolerance and type 2 diabetes and correlates with muscle and hepatic insulin resistance. Diabetes Care. 2009; 32: 1542-1546.
- 15Semba RD, Crasto C, Strait J, Sun K, Schaumberg DA, Ferrucci L. Elevated serum fibroblast growth factor 21 is associated with hypertension in community-dwelling adults. J Hum Hypertens. 2013; 27: 397-399.
- 16Chow WS, Xu A, Woo YC, et al. Serum fibroblast growth factor-21 levels are associated with carotid atherosclerosis independent of established cardiovascular risk factors. Arterioscler Thromb Vasc Biol. 2013; 33: 2454-2459.
- 17Fisher FM, Chui PC, Antonellis PJ, et al. Obesity is a fibroblast growth factor 21 (FGF21)-resistant state. Diabetes. 2010; 59: 2781-2789.
- 18Mraz M, Bartlova M, Lacinova Z, et al. Serum concentrations and tissue expression of a novel endocrine regulator fibroblast growth factor-21 in patients with type 2 diabetes and obesity. Clin Endocrinol (Oxf). 2009; 71: 369-375.
- 19Lin Z, Wu Z, Yin X, et al. Serum levels of FGF-21 are increased in coronary heart disease patients and are independently associated with adverse lipid profile. PLoS One. 2010; 5:e15534.
- 20Ong KL, Januszewski AS, O'Connell R, et al. The relationship of fibroblast growth factor 21 with cardiovascular outcome events in the Fenofibrate Intervention and Event Lowering in Diabetes study. Diabetologia. 2015; 58: 464-473.
- 21Lenart-Lipinska M, Matyjaszek-Matuszek B, Gernand W, Nowakowski A, Solski J. Serum fibroblast growth factor 21 is predictive of combined cardiovascular morbidity and mortality in patients with type 2 diabetes at a relatively short-term follow-up. Diabetes Res Clin Pract. 2013; 101: 194-200.
- 22He J, Zhang Y, Xu T, et al. Effects of immediate blood pressure reduction on death and major disability in patients with acute ischemic stroke: the CATIS randomized clinical trial. JAMA. 2014; 311: 479-489.
- 23Kurtz TW, Griffin KA, Bidani AK, Davisson RL, Hall JE. Recommendations for blood pressure measurement in animals: summary of an AHA scientific statement from the Council on High Blood Pressure Research, Professional and Public Education Subcommittee. Arterioscler Thromb Vasc Biol. 2005; 25: 478-479.
- 24Durrleman S, Simon R. Flexible regression models with cubic splines. Stat Med. 1989; 8: 551-561.
- 25DeLong ER, DeLong DM, Clarke-Pearson DL. Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics. 1988; 44: 837-845.
- 26Pencina MJ, D'Agostino RB Sr, D'Agostino RB Jr, Vasan RS. Evaluating the added predictive ability of a new marker: from area under the ROC curve to reclassification and beyond. Stat Med. 2008; 27: 157-172; discussion 207–112.
- 27Kohara M, Masuda T, Shiizaki K, et al. Association between circulating fibroblast growth factor 21 and mortality in end-stage renal disease. PLoS One. 2017; 12:e0178971.
- 28Gomez-Samano MA, Grajales-Gomez M, Zuarth-Vazquez JM, et al. Fibroblast growth factor 21 and its novel association with oxidative stress. Redox Biol. 2017; 11: 335-341.
- 29Allen CL, Bayraktutan U. Oxidative stress and its role in the pathogenesis of ischaemic stroke. Int J Stroke. 2009; 4: 461-470.
- 30Zhao L, Wang Y, Ma X, Wang Y, Deng X. Oxidative stress impairs IKCa- and SKCa-mediated vasodilatation in mesenteric arteries from diabetic rats. Nan Fang Yi Ke Da Xue Xue Bao. 2013; 33: 939-944.
- 31Janyou A, Wicha P, Jittiwat J, Suksamrarn A, Tocharus C, Tocharus J. Dihydrocapsaicin attenuates blood brain barrier and cerebral damage in focal cerebral ischemia/reperfusion via oxidative stress and inflammatory. Sci Rep. 2017; 7: 10556.
- 32Wang Y, Liao X, Zhao X, et al. Using recombinant tissue plasminogen activator to treat acute ischemic stroke in China: analysis of the results from the Chinese National Stroke Registry (CNSR). Stroke. 2011; 42: 1658-1664.
- 33Wang Z, Leng Y, Wang J, et al. Tubastatin A, an HDAC6 inhibitor, alleviates stroke-induced brain infarction and functional deficits: potential roles of α-tubulin acetylation and FGF-21 up-regulation. Sci Rep. 2016; 6: 19626. Published 2016 Jan 21.
