Influence of BMI on adenosine deaminase and stroke outcomes in mechanical thrombectomy subjects

Benton Maglinger, Christopher J McLouth, Jacqueline A Frank, Chintan Rupareliya, Madison Sands, Lila Sheikhi, Shivani Pahwa, David Dornbos 3rd, Jordan P Harp, Amanda L Trout, Jadwiga Turchan-Cholewo, Ann M Stowe, Justin F Fraser, Keith R Pennypacker, Benton Maglinger, Christopher J McLouth, Jacqueline A Frank, Chintan Rupareliya, Madison Sands, Lila Sheikhi, Shivani Pahwa, David Dornbos 3rd, Jordan P Harp, Amanda L Trout, Jadwiga Turchan-Cholewo, Ann M Stowe, Justin F Fraser, Keith R Pennypacker

Abstract

Background: Emergent Large Vessel Occlusion (ELVO) strokes are ischemic vascular events for which novel biomarkers and therapies are needed. The purpose of this study is to investigate the role of Body Mass Index (BMI) on protein expression and signaling at the time of ELVO intervention. Additionally, we highlight the protein adenosine deaminase (ADA), which is a deaminating enzyme that degrades adenosine, which has been shown to be neuroprotective in ischemia. We investigate the relationship between ADA and BMI, stroke outcomes, and associated proteomic networks which might aid in personalizing prognosis and future treatment of ELVO stroke.

Methods: The Blood And Clot Thrombectomy And Collaboration (BACTRAC) study is a continually enrolling tissue bank (clinicaltrials.gov NCT03153683) and registry from stroke patients undergoing mechanical thrombectomy (MT). N ​= ​61 human carotid plasma samples were analyzed for inflammatory and cardiometabolic protein expression by Olink Proteomics. Statistical analyses used t-tests, linear, logistic, and robust regressions, to assess the relationship between BMI, proteomic expression, and stroke-related outcomes.

Results: The 61 subjects studied were broken into three categories: normal weight (BMI 18.5-24.9) which contained 19 subjects, overweight (BMI 25-30) which contained 25 subjects, and obese (BMI ≥30) which contained 17 subjects. Normal BMI group was a significantly older population (mean 76 years) when compared to overweight (mean 66 years) and obese (mean 61 years) with significance of p ​= ​0.041 and p ​= ​0.005, respectively. When compared to normal weight and overweight categories, the obese category had significantly higher levels of adenosine deaminase (ADA) expression (p ​= ​0.01 and p ​= ​0.039, respectively). Elevated levels of ADA were found to have a significant positive correlation with both infarct volume and edema volume (p ​= ​0.013 and p ​= ​0.041, respectively), and were associated with a more severe stroke (NIHSS on discharge) and greater stroke related disability (mRS on discharge) with significance of p ​= ​0.053 and p ​= ​0.032, respectively.

Conclusions: When examined according to BMI, subjects undergoing MT for ELVO demonstrate significant differences in the expression of certain plasma proteins, including ADA. Levels of ADA were found to be significantly higher in the obese population when compared to normal or overweight groups. Increased levels of ADA in the obese group were predictive of increased infarct volume, edema volume, and worse NIHSS scores and mRS at discharge. These data provide novel biomarker candidates as well as treatment targets while increasing the personalization of stroke prognosis and treatment.

Keywords: Adenosine deaminase; Ischemic stroke; Mechanical thrombectomy; Obesity.

Conflict of interest statement

Authors KRP, AMS, and JFF are co-founders/equity holders in Cerelux, LLC.

© 2022 The Authors.

Figures

Fig. 1
Fig. 1
STRING-generated proteomic network webs for proteins with significant expression differences across BMI categories (A), proteins most predictive of infarct volume (B), and proteins most predictive of edema volume (C).
Fig. 2
Fig. 2
Overweight BMI category had significantly higher infarct volumes than Obese BMI group with p ​= ​0.017 (A). Significant positive correlation between systemic ADA expression and infarct volume with p ​= ​0.008 (B).

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