The absence of a widely available and sensitive diagnostic and prognostic test for acute cerebral ischemia remains a significant limitation in the diagnosis, prognosis, and management of stroke. At most medical institutions, CT scans of the brain are performed as part of the initial evaluation of a patient with suspected stroke. The main advantage of this imaging modality is its widespread availability and sensitivity for hemorrhage. However, it is insensitive to early ischemic changes during acute cerebral ischemia and is usually of little value for establishing the diagnosis of acute stroke [5].
This raises the need to improve the prediction and diagnosis of stroke motivating the search for sensitive biomarkers. Research on the identification of novel blood-borne markers that are associated with cerebral ischemia is continuing at a rapid pace, and it is likely that in the future, a biomarker or panel of biomarkers will play a role in facilitating the management of patients with cerebral ischemia. Such biomarkers may ultimately be used in a fashion similar to the use of troponin in the early diagnosis and management of patients with suspected myocardial ischemia or B-type natriuretic peptide in the diagnosis of congestive heart failure. Biomarkers may also be useful in the individualization of treatment decisions, determining etiology and providing prognostic information [6].
Ideally, a biomarker for diagnosing and monitoring prognosis of stroke should include at least the following characteristics. It should be brain specific. Because of obvious difficulties to obtain CSF samples in patients with acute stroke, detection in serum is highly desirable. It should appear very early, hours at the most, after the insult. Its peak level should reflect the extension of brain damage. It should possibly distinguish between stroke and stroke mimics, between transient and established stroke, and between hemorrhage and ischemia. Finally, it should be indicative of functional outcome [7].
That is why we decided to study apolipoprotein A1 in serum of stroke patients, because apart from differentiation between hemorrhage and ischemia, all the previous rules are applied to this specific marker.
Our main finding in this study is that low serum ApoA1 level is associated with an increased risk of ischemic cerebrovascular events. The cutoff value of ApoA1 level to discriminate between cases and controls was 6.2 μg/ml, with 94.9% sensitivity and 86.6% specificity. The mean value of ApoA1 in stroke patients versus healthy controls matched in age and sex revealed high statistical significance.
The previous finding is consistent with the results of a study by Kim and colleagues who reported that high serum ApoB level and low serum ApoA1 level are associated with increased risk of ischemic cerebrovascular events [8]. Also, it is consistent with the results of another study by Kostapanos and colleagues who reported that ApoB/ApoA1 ratio may represent a predictor of a first-ever ischemic non-embolic stroke in elderly subjects which was evident after adjustment for other cardiovascular risk factors and confounders, including lipid parameters [9].
As an exploratory analysis, we further correlate the level of ApoA1 with the clinical outcome of the patient, recurrence of the stroke, and mortality. In AMORIS prospective study done by Walldius and colleagues, they showed that there is a strong direct relationship between the increasing values of ApoB, decreasing values of ApoA1, and the risk of fatal stroke [10]. Another study done by Bhatia and colleagues showed that there is an association between apolipoproteins and long-term risk of ischemic stroke in patients with previous transient ischemic attack [11]. Other recent studies strengthened the notion of the ApoB/ApoA1 ratio as a useful indicator of ischemic stroke risk in patients with preexisting atherothrombotic disease [12, 13]. These results are consistent with our findings.
In our study, we found that there is an inverse relationship between the level of ApoA1 and the clinical outcome expressed by NIHSS score. Also, cases who showed recurrence of stroke in the first 3 months after the incident of the first stroke had low ApoA1 level compared to those who did not show recurrence. Furthermore, cases that had low level of ApoA1 showed high mortality risk than cases of high ApoA1 level. However, all these correlations did not reach statistical significance. This could be explained by some reasons. First, we excluded severe stroke with NIHSS score > 20, so we did not know the level of ApoA1 in such cases and we did not follow-up them. Secondly, due to ethical issues, we could not prevent the cases during follow-up from taking statin which increases the level of ApoA1 and reduces the risk of stroke. Finally, the small size of the sample can be an important factor.
Wallenfeldt and colleagues in their study approved that the ApoB/ApoA1 ratio was associated with metabolic syndrome and with the change in carotid artery intima medial thickness during 3 years of follow-up [14]. In addition, Park and colleagues in their study concluded that higher ApoB/ApoA1 ratio is a predictor of ICAS rather than of ECAS and that ApoB/ApoA1 ratio might be a biomarker for ICAS in patients with stroke [15].
These findings were present in our study. The mean level of ApoA1 in patients with no intracranial atherosclerotic stenosis was 5.08 ± 4.67 μg/ml, and it decreased in patients with mild ICAS and decreased with increasing stenosis till reaching its lowest level in patients with severe stenosis or occlusion. Also, in patients with ECAS, it was 5.06 ± 5.11 μg/ml in patients with no stenosis and it further decreased with the appearance of plaques. But in general, ApoA1 level was lower in patients with ICAS than patients with ECAS. However, all these correlations did not reach statistical significance, and this could be explained by the small size of the sample.