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Atherosclerosis. 2019 May 30;287:30-37. doi: 10.1016/j.atherosclerosis.2019.05.028. [Epub ahead of print]

Multiple biomarkers covering several pathways improve predictive ability for cognitive impairment among ischemic stroke patients with elevated blood pressure.

Author information

1
Department of Epidemiology, School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Medical College of Soochow University, Suzhou, China; Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA.
2
Department of Epidemiology, School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Medical College of Soochow University, Suzhou, China.
3
Department of Neurology, Siping Central Hospital, Jilin, China.
4
Department of Neurology, Jilin Central Hospital, Jilin, China.
5
Department of Neurology, The 88th Hospital of PLA, Shandong, China.
6
Department of Internal Medicine, Feicheng City People's Hospital, Shandong, China.
7
Department of Neurology, Tongliao Municipal Hospital, Inner Mongolia, China.
8
Department of Neurology, Kerqin District First People's Hospital of Tongliao City, Inner Mongolia, China.
9
Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA.
10
Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA; Department of Medicine, Tulane University School of Medicine, New Orleans, LA, USA.
11
Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA; Department of Medicine, Tulane University School of Medicine, New Orleans, LA, USA. Electronic address: jhe@tulane.edu.
12
Department of Epidemiology, School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Medical College of Soochow University, Suzhou, China. Electronic address: yhzhang@suda.edu.cn.

Abstract

BACKGROUND AND AIMS:

We aimed to evaluate the ability of multiple novel biomarkers representing several pathophysiological pathways to improve risk prediction of post-stroke cognitive impairment.

METHODS:

We conducted a prospective multicenter study in 638 ischemic stroke patients with elevated blood pressure based on a random subsample from China Antihypertensive Trial in Acute Ischemic Stroke and measured 12 circulating biomarkers in these participants. Cognitive impairment was assessed at 3 months after stroke with definitions of Mini-Mental State Examination (MMSE) score <27 or Montreal Cognitive Assessment (MoCA) score <25.

RESULTS:

According to MMSE score, 1 SD increase of rheumatoid factor (odds ratio [OR] 1.22, 95% confidence interval [CI] 1.02-1.46), matrix metalloproteinase-9 (OR 1.47, 95% CI 1.22-1.77) and total homocysteine (OR 1.22, 95% CI 1.01-1.49) after log transformation was significantly associated with the risk of post-stroke cognitive impairment. The ORs associated with their simultaneously high levels were 4.89 (95% CI, 2.31-10.35; ptrend<0.001) and 3.09 (95% CI, 1.60-5.98; ptrend<0.001) for cognitive impairment and the severity of cognitive impairment, respectively. Adding these 3 biomarkers to conventional model significantly improved the risk prediction of cognitive impairment (C statistic 0.729 vs. 0.688, p = 0.004; net reclassification improvement = 33.67%, p < 0.001; integrated discrimination index = 4.61%; p < 0.001). Similar significant findings were observed when cognitive impairment was defined by MoCA score.

CONCLUSIONS:

Combination of rheumatoid factor, matrix metalloproteinase-9 and total homocysteine can improve the risk prediction of cognitive impairment among ischemic stroke patients with elevated blood pressure. Further studies are warranted to validate our findings and explore their roles as potential therapeutic targets.

KEYWORDS:

Biomarkers; Cognitive impairment; Ischemic stroke; Prevention; Risk prediction

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