Serum 25-Hydroxyvitamin D Deficiency Predicts Poor Outcomes Among Acute Ischemic Stroke Patients Receiving Intravenous Thrombolysis
Ischemic stroke remains a leading cause of death and disability worldwide, contributing significantly to the rising costs of healthcare. Intravenous thrombolysis with tissue plasminogen activator (tPA, alteplase) is a widely used treatment for acute ischemic stroke. However, only 40% to 50% of stroke patients show significant improvement after treatment, and the use of alteplase is limited by the risk of symptomatic intracranial hemorrhage (sICH), which occurs in 1.7% to 6.4% of treated patients. Recent research has highlighted the role of 25-hydroxyvitamin D (25(OH)D), the major circulating metabolite of vitamin D, in cerebrovascular disease (CVD). Studies have shown that vitamin D deficiency is associated with an increased risk of ischemic stroke, higher stroke severity, and poor functional outcomes. This study aimed to examine the relationship between serum 25(OH)D levels and functional outcomes in Chinese patients treated with intravenous thrombolysis for acute ischemic stroke.
Study Design and Methodology
The study retrospectively analyzed patients with acute ischemic stroke who were treated with intravenous alteplase in a stroke unit from February 2014 to January 2017. Patients with a clinical diagnosis of ischemic stroke and a National Institutes of Health Stroke Scale (NIHSS) score of less than 24 received IV alteplase (0.9 mg/kg) within 4.5 hours of stroke onset. The inclusion and exclusion criteria for receiving alteplase strictly followed the European Cooperative Acute Stroke Study (ECASS) II and ECASS III criteria. Patients with a history of 25(OH)D deficiency or those who received oral vitamin D replenishment were excluded. Additionally, patients with incomplete baseline data or those lost to follow-up were excluded, resulting in a final cohort of 208 patients.
Data were collected by physicians experienced in acute stroke care using predefined criteria. The NIHSS and modified Rankin Scale (mRS) scores were evaluated by certified raters. Blood samples were collected within 24 hours of hospital admission after at least 8 hours of fasting. Serum 25(OH)D levels were measured using a commercially available enzyme-linked immunosorbent assay (ELISA) kit. A 25(OH)D level of less than 50 nmol/L was defined as deficient. The season of blood sampling (spring, summer, fall, or winter) was also recorded for analysis.
Baseline characteristics, including age, sex, body mass index (BMI), and medical history (atrial fibrillation, coronary artery disease, current smoking, diabetes mellitus, hypertension, and previous stroke/transient ischemic attack [TIA]), were collected. Onset-to-treatment time and blood pressure (BP) on admission were recorded. Laboratory data included blood cell count, C-reactive protein (CRP) level, glucose level on admission, and total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), and homocysteine (HCY) levels within 24 hours after admission. Information on previous use of antiplatelet, anticoagulant, antidiabetic, and statin drugs was also collected.
Outcomes were assessed during a 3-month follow-up period and included any intracerebral hemorrhage (ICH), symptomatic ICH (sICH), good functional outcome, all-cause death, and major disability. Symptomatic ICH was defined as clinical neurological deterioration (an increase in NIHSS score of 4 or greater) in addition to any hemorrhage identified on CT/MRI. Good functional outcome was defined as an mRS score of 0–1, and major disability was defined as an mRS score of 3–5.
Results
Of the 208 participants, 71.6% were male, and the mean age was 63.5 years. The mean serum 25(OH)D level was 56.0 nmol/L. Patients with low 25(OH)D levels were more likely to be female, non-smokers, and have higher baseline glucose levels. The median mRS score was significantly higher in patients with low 25(OH)D levels at discharge (4 vs. 3) and at 3 months (3 vs. 2). Patients in the high 25(OH)D level group were more likely to have a low mRS score, indicating better functional outcomes.
There were 21 cases of hemorrhagic transformation, with no significant difference between the high and low 25(OH)D level groups. However, there was a trend toward more sICH cases in the low 25(OH)D level group (10.9% vs. 4.7%). At 3 months, 44.2% of patients had good functional outcomes, with a higher proportion in the high 25(OH)D level group (49.5% vs. 38.6%). Major disability was observed in 40.3% of patients, with a higher proportion in the low 25(OH)D level group (47.3% vs. 34.3%). All-cause death occurred in 6.7% of patients, with a significantly higher proportion in the low 25(OH)D level group (10.9% vs. 2.8%).
After adjusting for age, sex, BMI, BP, blood glucose, blood lipid levels, smoking status, admission NIHSS, and season, the differences in outcomes were no longer statistically significant. However, patients with low 25(OH)D levels displayed a trend toward higher leucocyte counts and significantly higher CRP levels, indicating an increased inflammatory response.
Subgroup Analysis Based on Blood Lipid Levels
The study also analyzed the impact of blood lipid components on clinical outcomes in 25(OH)D deficient patients. According to Chinese guidelines, the cutoff points for normal lipid levels were TC, 5.2 mmol/L; LDL-c, 3.4 mmol/L; and HDL-c, 1.0 mmol/L. Detrimental effects of 25(OH)D deficiency on clinical outcomes were observed in patients with TC ≥ 5.2 mmol/L and LDL-c ≥ 3.4 mmol/L. In these subgroups, patients with 25(OH)D deficiency had a lower chance of good functional outcomes and a higher risk of all-cause death. After adjustment for confounding factors, only patients with LDL-c ≥ 3.4 mmol/L had a significantly higher rate of all-cause death at 3 months.
Discussion
This study demonstrated that low serum 25(OH)D levels are associated with worse functional outcomes at 3 months in Chinese patients treated with intravenous thrombolysis for acute ischemic stroke. Additionally, high TC or LDL-c levels contributed to a lower chance of good functional outcomes and a higher risk of all-cause death in these patients.
Vitamin D has been suggested to have neuroprotective properties, and its deficiency is associated with an increased risk of ischemic stroke, severe stroke, and high mortality. Although there are no previous studies on mortality and ischemic stroke with 25(OH)D deficiency after intravenous thrombolysis, the results of this study are consistent with previous research on stroke patients, regardless of the acute treatment administered.
The study also found an increased inflammatory response in patients with low 25(OH)D levels, as indicated by higher CRP levels and leucocyte counts. This suggests that 25(OH)D may exert protective effects by regulating the inflammatory response in the early stages of stroke. Furthermore, the interaction between 25(OH)D and blood lipid levels may play a role in the pathophysiological process of stroke, particularly in patients treated with intravenous thrombolysis.
Conclusion
In conclusion, this study highlights the significant association between low serum 25(OH)D levels and worse outcomes at 3 months in Chinese patients treated with intravenous thrombolysis for acute ischemic stroke. Patients with 25(OH)D deficiency and high LDL-c levels are at a higher risk of all-cause mortality. These findings underscore the importance of monitoring and addressing vitamin D deficiency in stroke patients, particularly those undergoing thrombolytic therapy.
doi.org/10.1097/CM9.0000000000000084
Was this helpful?
0 / 0