Association between serum transthyretin and intracranial atherosclerosis in patients with acute ischemic stroke

So you described something, what the hell are we supposed to do with this information?  Since you had no objective for your research your mentors and senior researchers need to be fired.

Association between serum transthyretin and intracranial atherosclerosis in patients with acute ischemic stroke

Jinfeng He^1†, Jiamin Zhu^2†, Wenyuan Zhang^2,3, Zhenxiang Zhan², Fangwang Fu² and Qiongqiong Bao^3*

• ¹Department of Neurology, Taizhou Municipal Hospital, Taizhou, China
• ²Department of Neurology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China
• ³Department of Neurology, Affiliated Yueqing Hospital, Wenzhou Medical University, Yueqing, China

Background: Intracranial atherosclerotic stenosis (ICAS) is a primary cause of ischemic stroke. In addition to dyslipidemia, inflammation has been recognized as a potential pathogenesis of atherosclerosis. It remains unknown whether there is a link between transthyretin and ICAS as an inflammatory index.

Methods: Consecutive patients with acute ischemic stroke admitted to the Second Affiliated Hospital of Wenzhou Medical University between January 2019 and June 2020 were retrospectively analyzed. Blood samples were collected from all patients within 24 h of admission to detect their serum transthyretin levels. ICAS was defined as at least one intracranial artery stenosis on vascular examination with a degree of stenosis ≥50%. Multivariable logistic regression analysis was used to identify independent factors associated with ICAS. Restricted cubic spline models were used to depict patterns in the association between serum transthyretin levels and ICAS.

Results: In total, 637 patients with acute ischemic stroke were included in this study, of whom 267 (41.9%) had ICAS. Compared with the patients without ICAS, serum transthyretin levels in patients with ICAS were significantly lower (226.3 ± 56.5 vs. 251.0 ± 54.9 mg/L; p < 0.001). After adjusting for potential confounders, patients in the lowest tertile showed a significant increase in ICAS compared to those in the highest tertile (odds ratio, 1.85; 95% confidence interval, 1.12–3.05; p = 0.016). This negative linear association is also observed in the restricted cubic spline model. However, this association may only be observed in men. Age, National Institutes of Health Stroke Scale score, hemoglobin A1c level, and low-density lipoprotein cholesterol level were independently associated with ICAS.

Conclusions: Decreased serum transthyretin levels are associated with a more severe ICAS burden in patients with acute ischemic stroke. Our findings suggest that transthyretin may play a role in the pathogenesis of ICAS and provide insight into the control of inflammation for the treatment of ICAS.

Introduction

Acute ischemic stroke (AIS) is gradually becoming a major disease threatening the global population's health, particularly in China (1). As the dominant cause of stroke, large artery atherosclerosis is closely related to poor prognoses and high recurrence rates in patients with AIS (2–4). Due to differences in antioxidant content and susceptibility to hemodynamic pressure between the intracranial and extracranial arteries, their responses to different risk factors are inconsistent (5). Compared with Western individuals, intracranial atherosclerotic stenosis (ICAS) affects a larger proportion of Chinese patients than extracranial atherosclerotic stenosis (ECAS) (5). Currently, ICAS is the main cause of the high stroke burden in the Chinese population (6). Recent evidence suggests that inflammation plays a significant role in atherosclerotic disease and is expected to become a therapeutic target (7).

Transthyretin is mainly synthesized in the human liver and plays a role in transporting thyroxine and retinol (8). As a serum protein with a short half-life (approximately 2 days), transthyretin is an ideal index for assessing nutritional status (9). In addition, serum transthyretin concentration decreases in the acute phase of inflammation, malignant tumors, and trauma (8) and is thus a potent inflammatory marker. There is evidence that decreased serum transthyretin levels are associated with poor prognoses in stroke patients, even when stroke severity and vascular risk factors are considered (10–12). In patients with acute coronary syndrome, there is an independent negative relationship between transthyretin levels and coronary stenosis (13).

Consequently, it is speculated that transthyretin is associated with ICAS, although the pathogeneses of ICAS and ECAS are not identical. To our knowledge, no studies have investigated the relationship between transthyretin and ICAS. We aimed to determine whether low serum transthyretin levels are associated with ICAS in patients with AIS.

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