Residual Inflammatory Risk Predicts Poor Prognosis in Acute Ischemic Stroke or Transient Ischemic Attack Patients

Abstract

Background and Purpose: It is still unclear whether the residual cholesterol and inflammatory risk in the acute phase is associated with prognosis of stroke. We aimed to investigate the proportion and relative contribution of residual cholesterol and inflammatory risk, determined by baseline low-density lipoprotein cholesterol (LDL-C) and high-sensitivity C-reactive protein (hsCRP) levels, to the risk of recurrent stroke and poor functional outcome at 1 year. Methods: In this prospective multicenter cohort study, 10 499 consecutive acute ischemic stroke and transient ischemic attack patients with levels of LDL-C and hsCRP were enrolled. Patients were divided into 4 groups: residual cholesterol risk only (LDL-C ≥2.6 mmol/L and hsCRP <3 mg/L), residual inflammatory risk (RIR) only (LDL-C <2.6 mmol/L and hsCRP ≥3 mg/L), both risk (LDL-C ≥2.6 mmol/L and hsCRP ≥3 mg/L), and neither risk (LDL-C <2.6 mmol/L and hsCRP <3 mg/L). The primary outcomes consisted of stroke recurrence and a modified Rankin Scale score of 2 to 6 within 1 year. Results: The relative proportions of patients with RIR only, residual cholesterol risk only, both risk, and neither were 21.3%, 23.7%, 14.4%, and 40.6%, respectively. RIR only was independently associated with recurrent stroke (adjusted hazard ratio, 1.18 [95% CI, 1.00–1.40]; P =0.05). The association was slightly attenuated after further adjusting for usage of antiplatelet agent and statin during 1-year follow-up in addition to the traditional risk factors (hazard ratio, 1.31 [95% CI, 0.99–1.76]; P =0.07). When applying the LDL-C cutoff value of 1.8 mmol/L in the sensitivity analyses, such association in large-artery atherosclerosis subtype was more significant (adjusted hazard ratio, 1.69 [95% CI, 1.06–2.67]; P =0.03). Patients with RIR only also had increased risk of poor functional outcome (adjusted odds ratio, 1.43 [95% CI, 1.24–1.64]; P <0.0001). Conclusions: In the patients with acute ischemic stroke or transient ischemic attack, RIR only could be predictive for recurrent stroke, especially for those with large-artery atherosclerosis, and poor functional outcome.

Association of residual inflammatory risk with stroke recurrence in patients with acute ischaemic stroke or transient ischaemic attack

“…Patients with no hsCRP measurements or only one blood hsCRP measurement were excluded from the analysis. High inflammatory status was defined as hsCRP ≥3 mg/l according to previous studies [4,10,12]. Patients were classified into four groups according to two hsCRP values at baseline and 3 months: (i) persistent high RIR-high values of hsCRP at baseline and 3 months; (ii) attenuated RIR-high hsCRP at baseline and low hsCRP at 3 months; (ii) increased RIR-low hsCRP at baseline and high hsCRP at 3 months; and (iv) persistent low RIR-low hsCRP values at baseline and 3 months.…”

“…Indeed, CRP is relatively stable in healthy individuals [11] but can be increased transiently as an acute phase reactant. Our recent study showed that baseline RIR was associated with 1‐year stroke recurrence and poor functional outcome [12]. A previous study showed that longitudinal increases in hsCRP were also associated with an increased risk of adverse cardiovascular outcomes in patients with acute coronary syndrome [13].…”

Brain-derived programmed death-ligand 1 mediates immunosuppression post intracerebral hemorrhage

“…Programed death-ligand 1 (PD-L1) is a membrane-bound protein that exerts immune checkpoint roles by binding to programed death-1 (PD-1) receptor; PD-L1 has long been known for its involvement in escaping immune surveillance of tumor cells. 7,8 Recent report identified PD-L1 released by tumor cells into the circulation to mediate systemic immunosuppression. 8 We here find that neurons of healthy humans and mice express high basal levels of PD-L1, which are significantly reduced in the perihematomal area upon hemorrhagic stroke.…”

LncRNA KCNQ1OT1 predicts further cerebral events in patients with transient ischemic attack

“…Both clinical evidence and laboratory evidence suggested that anti-inflammatory therapies effectively decreased vascular damages and suppressed cerebral ischemic stroke (Kelly et al, 2018). Moreover, a high level of residual inflammatory risk (RIR) was proven to imply patients' poor prognosis of acute cerebral ischemic stroke (Li et al, 2021a), while high-sensitivity C-reactive protein (hs-CRP), which represented early inflammatory response, was addressed as a decisive factor of RIR (Ridker et al, 2017). Low-level inflammation reflected by hs-CRP indicated recurrent ischemic events independently (Mengozzi et al, 2020;Coveney et al, 2021).…”