In the present study, we demonstrated that BMI is a predictor of HT in older patients (≥ 73 years) with ischemic stroke treated with intravenous thrombolysis. In addition, fasting plasma glucose, atrial fibrillation, and NIHSS score at admission are also predictors of HT.
HT is a life-threatening complication in acute ischemic stroke patients treated with intravenous thrombolysis, which can worsen the clinical course and outcome. Furthermore, HT occurs in approximately 10% to 43% of patients after thrombolysis [16, 17]. In the present study, the rate of HT after thrombolysis was 15.3%, which was consistent with the findings of a previous investigation in China [17].
BMI is an established risk factor for stroke. Previously, we found that BMI (≥ 25 kg/m2) was associated with an increased risk of ischemic stroke [7]. However, its impact on HT after acute ischemic stroke is unclear. The present study indicates that a higher BMI can increase the risk of HT and its subtype (sICH and aSICH) after intravenous thrombolytic therapy in patients older than 73 years. In addition, patients with BMI ≥ 25 kg/m2 had an approximately 5.16-fold increased risk of developing HT compared to patients with BMI < 25 kg/m2, and this association was independent of age, fasting plasma glucose, atrial fibrillation and NIHSS score. In agreement with our findings, in the Safe Implementation of Treatments in Stroke symptomatic intracerebral hemorrhage risk score (The SITS SICH risk score), body weight was a predictor for sICH [12]. Moreover, Diedler J et al reported that the risk of sICH significantly increased in patients weighing > 100 kg who accepted intravenous r-tPA thrombolysis compared to those weighing ≤ 100 kg [13]. However, a meta-analysis across three studies in Europe reported that obesity (BMI ≥ 30 kg/m2 vs. BMI < 30 kg/m2) was not related to sICH risk with 3-month follow-up [8, 9], while others found inverse associations that may be related to obese patients receiving an intravenous r-tPA dose < 0.9 mg/kg [11]. These seemingly discrepant observations might be explained by differences in race, length of follow-up, sample size, or definition and subtype of HT. In one large study, body weight independently increased the risk of sICH when using the SITS-MOST (Safe implementation of thrombolysis in stroke-monitoring study) definition but not when using the ECASS II definition [9, 12]. When race was included in the GRASPS score, Asian race was an independent predictor of sICH [18].
Furthermore, our study showed a relationship among HT and different factors, such as NIHSS score, atrial fibrillation and fasting plasma glucose values, confirming the results of previous studies [4]. A higher NIHSS score was shown to increase the risk of HT in many studies [19, 20]. Severe ischemic stroke is reflected by large areas of injured brain tissue, including injured blood vessels, which are prone to bleeding after r-tPA treatment. Atrial fibrillation was also reported as an independent predictor of HT and sICH in many studies [4, 21]. This finding was confirmed in the present and our previous study assessing Chinese patients. Hyperglycemia is common in patients during the acute phase of stroke; however, the association between HT and blood glucose is controversial. In a meta-analysis of 11 studies on the associations between blood glucose and post r-tPA intracranial hemorrhage, the pooled OR associated with a per mmol/L increase in glucose level among patients treated with r-tPA was 1.10 (95% CI, 1.05-1.14) [4]. A previous Chineses study showed that elevated serum glucose on admission places a patient at increased risk for sICH following rt-PA [22]. In the present study, we confirmed that fasting plasma glucose was a predictor of HT in acute ischemic stroke patients after r-tPA treatment.
Although the mechanism of HT is not fully understood, several explanations may account for the observed association between these risk factors and HT in acute ischemic stroke after r-tPA treatment. First, obesity has been shown to be associated with a proinflammatory state, and participants with obesity more frequently had cardiovascular risk factors. The present study found that patients with higher BMI were likely to have lower platelet count. Certainly, the mechanism underlying this phenomenon requires further research. Second, interactions of multiple pathogenic factors, including hyperglycemia-mediated vascular oxidative stress and inflammation, ischemic insult, and r-tPA neurovascular toxicity, in concert, contribute to the blood-brain barrier damage-intracerebral hemorrhagic transformation process. The development of combination approaches targeting multiple pathological cascades may help to attenuate hemorrhagic complications [23].
There are some limitations of our study. First, the present study used a retrospective design, so some confounders were not available for control in our multivariate analyses. Second, the study included a single center‑based sample and a relatively small sample size, which might have limited the statistical power of the study. Third, body weight and height were self-reported by patients or caregivers in part, but these data were reassessed by the attending stroke physician.