The major findings of our study were that the degree of oxLDL level change is related to the neurological improvement at discharge and favorable functional prognosis at 90 days for patients with acute atherosclerosis related ischemic stroke, but was not correlated with infarct volume on DWI.
Previous researches demonstrated that oxLDL level in the acute phase was not only related to poor functional outcome after stroke[2, 7], but also can predict recurrent stroke in patients with minor stroke or transient ischemic attack independently. However, the level of oxLDL is fluctuant in circulation. Study showed that it increased to peak level at the third day, and decreased gradually to the premorbid state . To date, previous studies just focused on oxLDL at the acute stage of stroke[7, 8, 10], only limited research has been conducted on relationship between the change of oxLDL level with the prognosis of stroke. Our study extended previous studies, and firstly reported that significant change of oxLDL level is related with favorable functional prognosis at 90 days for patients with acute atherosclerosis related ischemic stroke.
The mechanism of these association between oxidative lipoprotein markers and prognosis of stroke remains unclear. The potential reasons were as follows. Firstly, oxLDL as the result of oxidative modification of low-density lipoprotein, has pro-inflammatory and pro-atherosclerotic properties by inducing endothelial dysfunction. Endothelial dysfunction may contribute to the blood-brain barrier (BBB) impairment, leading to the permeability of the BBB increased, circulatory immune cells permeate and infiltrate the surrounding brain parenchyma. These immune cells secrete pro-inflammatory cytokines, deteriorating the injurious damage following stroke as result. Which was confirmed by many studies, because they all showed a positive relationship between oxLDL level and severe neurological deficits in patients with acute ischemic stroke [19-22]. Secondly, endothelial dysfunction and continuous neuroinflammation state caused by oxLDL may accelerate atherosclerosis progression, promote the formation of unstable plaque, contributing to clinical events onset[4-6]. Studies suggested that there was a significant correlation between plasma and plaque oxLDL level, and high plasma levels of oxLDL were correlated with the vulnerability to rupture of atherosclerotic lesions [23, 24]. Therefore, oxLDL can be used as a biomarker of atherosclerotic plaque stability . Given the volatility of oxLDL levels in the cycle. We only recruited acute ischemic stroke patients within 3 days after onset in order to ensure the initial level of oxLDL is its peak level. In our study, Compared to patients with mild change of oxLDL level, patients with significant change were more likely to have favorable functional prognosis at 90 days (OR=6.67, 95%CI, 2.15-20.73, p <0.01) and neurological improvement at discharge(OR=7.21,95%, 3.09-16.80, p <0.01).Therefore, the more the level of oxLDL decreased, the more likely the plaque tends to be stable, and the more likely the neurological function will be improved.
We found the change of oxLDL level is not related with infarct volume on DWI. The median DWI volumes in patients with different oxLDL changes groups were 4.21cm3, 3.08 cm3, and 2.38 cm3 respectively, although presented reduced gradually, no statistical difference. Nai-Wen Tsai et al demonstrated the oxLDL level in acute phase was positively correlated with infarct volume. Uno et al  evaluated oxLDL levels and ischemic lesions in acute stroke, and confirmed that a persistent plasma oxLDL elevation was associated with enlargement of the ischemic lesion in the early phase after acute ischemic stroke. But as far as we know, we are the first to explore the relationship between change of oxLDL level and infarct volume on DWI.
Our study had some limitations. First , Our sample size is relatively small, so in view of the biological characteristics of oxLDL, we only focus on acute ischemic stroke associated with atherosclerosis, namely large artery atherosclerotic and small-artery occlusion cerebral infarction. Secondly, we recruited acute ischemic stroke patients within 3 days after onset , the initial oxLDL level was not the time of stroke onset. What’s more, our oxLDL level for the second time was before discharge(10-14days after stroke onset), it has not reached the level before the stroke onset , so the change of oxLDL level was between acute phase and subacute phase, but not the acute phase and premorbid state.
Despite all this, we evaluated changes of plasma oxLDL level and their impact on stroke prognosis over time, and confirmed that significant change of oxLDL level is related to the neurological improvement at discharge and favorable functional prognosis at 90 days for patients with acute ischemic stroke associated with atherosclerosis, but is not correlated with infarct volume on DWI.
These findings shed new light on oxLDL level as a therapeutic target in improving functional outcomes after acute ischemic stroke.