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August 30, 2022; 99 (9) Research Articles

Plasma Soluble Dipeptidyl Peptidase-4 and Risk of Major Cardiovascular Events After Ischemic Stroke

Secondary Analysis of China Antihypertensive Trial in Acute Ischemic Stroke (CATIS)

Shoujiang You, Mengyuan Miao, Zian Lu, Anran Bao, Jigang Du, Bizhong Che, Tan Xu, Chongke Zhong, Yongjun Cao, Chun-Feng Liu, Yonghong Zhang, Jiang He
First published June 2, 2022, DOI: https://doi.org/10.1212/WNL.0000000000200784
Shoujiang You
From the Department of Neurology and Suzhou Clinical Research Center of Neurological Disease (S.Y., Y.C., C.-F.L.), The Second Affiliated Hospital of Soochow University; Department of Epidemiology (M.M., Z.L., A.B., J.D., B.C., T.X., C.Z., Y.Z.), School of Public Health, Medical College of Soochow University; Institutes of Neuroscience (Y.C., C.-F.L.), Soochow University, Suzhou, China; and Department of Epidemiology (J.H.), Tulane University School of Public Health and Tropical Medicine, New Orleans, LA.
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Mengyuan Miao
From the Department of Neurology and Suzhou Clinical Research Center of Neurological Disease (S.Y., Y.C., C.-F.L.), The Second Affiliated Hospital of Soochow University; Department of Epidemiology (M.M., Z.L., A.B., J.D., B.C., T.X., C.Z., Y.Z.), School of Public Health, Medical College of Soochow University; Institutes of Neuroscience (Y.C., C.-F.L.), Soochow University, Suzhou, China; and Department of Epidemiology (J.H.), Tulane University School of Public Health and Tropical Medicine, New Orleans, LA.
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Zian Lu
From the Department of Neurology and Suzhou Clinical Research Center of Neurological Disease (S.Y., Y.C., C.-F.L.), The Second Affiliated Hospital of Soochow University; Department of Epidemiology (M.M., Z.L., A.B., J.D., B.C., T.X., C.Z., Y.Z.), School of Public Health, Medical College of Soochow University; Institutes of Neuroscience (Y.C., C.-F.L.), Soochow University, Suzhou, China; and Department of Epidemiology (J.H.), Tulane University School of Public Health and Tropical Medicine, New Orleans, LA.
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Anran Bao
From the Department of Neurology and Suzhou Clinical Research Center of Neurological Disease (S.Y., Y.C., C.-F.L.), The Second Affiliated Hospital of Soochow University; Department of Epidemiology (M.M., Z.L., A.B., J.D., B.C., T.X., C.Z., Y.Z.), School of Public Health, Medical College of Soochow University; Institutes of Neuroscience (Y.C., C.-F.L.), Soochow University, Suzhou, China; and Department of Epidemiology (J.H.), Tulane University School of Public Health and Tropical Medicine, New Orleans, LA.
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Jigang Du
From the Department of Neurology and Suzhou Clinical Research Center of Neurological Disease (S.Y., Y.C., C.-F.L.), The Second Affiliated Hospital of Soochow University; Department of Epidemiology (M.M., Z.L., A.B., J.D., B.C., T.X., C.Z., Y.Z.), School of Public Health, Medical College of Soochow University; Institutes of Neuroscience (Y.C., C.-F.L.), Soochow University, Suzhou, China; and Department of Epidemiology (J.H.), Tulane University School of Public Health and Tropical Medicine, New Orleans, LA.
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Bizhong Che
From the Department of Neurology and Suzhou Clinical Research Center of Neurological Disease (S.Y., Y.C., C.-F.L.), The Second Affiliated Hospital of Soochow University; Department of Epidemiology (M.M., Z.L., A.B., J.D., B.C., T.X., C.Z., Y.Z.), School of Public Health, Medical College of Soochow University; Institutes of Neuroscience (Y.C., C.-F.L.), Soochow University, Suzhou, China; and Department of Epidemiology (J.H.), Tulane University School of Public Health and Tropical Medicine, New Orleans, LA.
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Tan Xu
From the Department of Neurology and Suzhou Clinical Research Center of Neurological Disease (S.Y., Y.C., C.-F.L.), The Second Affiliated Hospital of Soochow University; Department of Epidemiology (M.M., Z.L., A.B., J.D., B.C., T.X., C.Z., Y.Z.), School of Public Health, Medical College of Soochow University; Institutes of Neuroscience (Y.C., C.-F.L.), Soochow University, Suzhou, China; and Department of Epidemiology (J.H.), Tulane University School of Public Health and Tropical Medicine, New Orleans, LA.
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Chongke Zhong
From the Department of Neurology and Suzhou Clinical Research Center of Neurological Disease (S.Y., Y.C., C.-F.L.), The Second Affiliated Hospital of Soochow University; Department of Epidemiology (M.M., Z.L., A.B., J.D., B.C., T.X., C.Z., Y.Z.), School of Public Health, Medical College of Soochow University; Institutes of Neuroscience (Y.C., C.-F.L.), Soochow University, Suzhou, China; and Department of Epidemiology (J.H.), Tulane University School of Public Health and Tropical Medicine, New Orleans, LA.
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Yongjun Cao
From the Department of Neurology and Suzhou Clinical Research Center of Neurological Disease (S.Y., Y.C., C.-F.L.), The Second Affiliated Hospital of Soochow University; Department of Epidemiology (M.M., Z.L., A.B., J.D., B.C., T.X., C.Z., Y.Z.), School of Public Health, Medical College of Soochow University; Institutes of Neuroscience (Y.C., C.-F.L.), Soochow University, Suzhou, China; and Department of Epidemiology (J.H.), Tulane University School of Public Health and Tropical Medicine, New Orleans, LA.
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Chun-Feng Liu
From the Department of Neurology and Suzhou Clinical Research Center of Neurological Disease (S.Y., Y.C., C.-F.L.), The Second Affiliated Hospital of Soochow University; Department of Epidemiology (M.M., Z.L., A.B., J.D., B.C., T.X., C.Z., Y.Z.), School of Public Health, Medical College of Soochow University; Institutes of Neuroscience (Y.C., C.-F.L.), Soochow University, Suzhou, China; and Department of Epidemiology (J.H.), Tulane University School of Public Health and Tropical Medicine, New Orleans, LA.
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Yonghong Zhang
From the Department of Neurology and Suzhou Clinical Research Center of Neurological Disease (S.Y., Y.C., C.-F.L.), The Second Affiliated Hospital of Soochow University; Department of Epidemiology (M.M., Z.L., A.B., J.D., B.C., T.X., C.Z., Y.Z.), School of Public Health, Medical College of Soochow University; Institutes of Neuroscience (Y.C., C.-F.L.), Soochow University, Suzhou, China; and Department of Epidemiology (J.H.), Tulane University School of Public Health and Tropical Medicine, New Orleans, LA.
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Jiang He
From the Department of Neurology and Suzhou Clinical Research Center of Neurological Disease (S.Y., Y.C., C.-F.L.), The Second Affiliated Hospital of Soochow University; Department of Epidemiology (M.M., Z.L., A.B., J.D., B.C., T.X., C.Z., Y.Z.), School of Public Health, Medical College of Soochow University; Institutes of Neuroscience (Y.C., C.-F.L.), Soochow University, Suzhou, China; and Department of Epidemiology (J.H.), Tulane University School of Public Health and Tropical Medicine, New Orleans, LA.
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Citation
Plasma Soluble Dipeptidyl Peptidase-4 and Risk of Major Cardiovascular Events After Ischemic Stroke
Secondary Analysis of China Antihypertensive Trial in Acute Ischemic Stroke (CATIS)
Shoujiang You, Mengyuan Miao, Zian Lu, Anran Bao, Jigang Du, Bizhong Che, Tan Xu, Chongke Zhong, Yongjun Cao, Chun-Feng Liu, Yonghong Zhang, Jiang He
Neurology Aug 2022, 99 (9) e925-e934; DOI: 10.1212/WNL.0000000000200784

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Abstract

Background and Objectives Recent studies have suggested that plasma soluble dipeptidyl peptidase-4 (sDPP4) have important physiologic effects, which may influence the prognosis of ischemic stroke. Our study aimed to examine the relationship between plasma sDDP4 levels and long-term clinical outcomes among patients with acute ischemic stroke.

Methods Secondary analysis was conducted among 3,564 participants (2,270 men and 1,294 women) from the China Antihypertensive Trial in Acute Ischemic Stroke with baseline measurement of plasma sDPP4 levels. We evaluated the associations between plasma sDPP4 levels and 2-year clinical outcomes using logistic regression and Cox regression models. We further investigated the predictive utility of sDPP4 by calculating net reclassification index and integrated discrimination improvement.

Results The highest plasma sDPP4 quartile was associated with lower risk of cardiovascular events (hazard ratio [HR] 0.62, 95% confidence interval [CI] 0.45–0.87), recurrent stroke (HR 0.70, 95% CI 0.49–0.99), all-cause mortality (HR 0.62, 95% CI 0.44–0.87), stroke-specific mortality (HR 0.65, 95% CI 0.44–0.94), and poor functional outcomes (odds ratio 0.66, 95% CI 0.53–0.82) at 2 years compared with the lowest sDPP4 category in multivariable models. The addition of plasma sDPP4 to conventional risk factors model significantly improved risk prediction of all outcomes.

Discussion In this study, we found that higher plasma sDPP4 levels in patients with acute ischemic stroke were associated with decreased risks of cardiovascular events, recurrent stroke, all-cause mortality, and poor functional outcomes after ischemic stroke. These findings suggest that plasma sDPP4 may be a potential prognostic marker for initial risk stratification in patients with acute ischemic stroke.

Glossary

BP=
blood pressure;
CATIS=
China Antihypertensive Trial in Acute Ischemic Stroke;
CIs=
confidence intervals;
DPP4=
dipeptidyl peptidase-4;
eGFR=
estimated glomerular filtration rate;
HRs=
hazard ratios;
IDI=
integrated discrimination improvement;
LDL-C=
low-density lipoprotein cholesterol;
NIHSS=
NIH Stroke Scale;
NRI=
net reclassification index;
ORs=
odds ratios;
sDPP4=
soluble dipeptidyl peptidase-4;
TLR=
toll-like receptor

Footnotes

  • ↵* These authors contributed equally to this work as co-first authors.

  • Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Submitted and externally peer reviewed. The handling editor was Brad Worrall, MD, MSc, FAAN.

  • Received November 4, 2021.
  • Accepted in final form April 11, 2022.
  • © 2022 American Academy of Neurology
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