Serum 25-hydroxyvitamin D deficiency predicts poor outcomes among acute ischemic stroke patients receiving intravenous thrombolysis

Abstract

To the Editor: Ischemic stroke remains a major cause of death and disability worldwide and contributes to the rising costs of health care. Thrombolytic therapy with tissue plasminogen activator (tPA, alteplase) is beneficial for the treatment of acute ischemic stroke. However, only 40% to 50% of stroke patients show a significant improvement after treatment. In addition, the use of alteplase is restricted because symptomatic intracranial hemorrhage (sICH) occurs in 1.7% to 6.4% of treated patients.[1] 25-hydroxyvitamin D (25(OH)D), which is the major circulating metabolite of vitamin D, has been confirmed to be closely related to cerebrovascular disease (CVD). A series of studies indicated that vitamin D deficiency was associated with an increased risk of ischemic stroke, high stroke severity and poor functional outcomes.[2] The aim of this study was to examine the relationship between serum 25(OH)D levels and functional outcomes in patients treated with intravenous thrombolysis for acute ischemic stroke in a Chinese population. We retrospectively analyzed patients with acute ischemic stroke who were treated with intravenous alteplase in our stroke unit from February 2014 to January 2017. All 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 after obtaining informed consent. The inclusion and exclusion criteria for receiving alteplase, as well as the thrombolytic protocol, strictly followed the European Cooperative Acute Stroke Study (ECASS) II and ECASS III criteria. None of the patients had a history of 25(OH)D deficiency or received oral replenishment. Patients with incomplete baseline data (43 cases, 41 lacking 25(OH)D level data) or those that were lost to follow-up (13 cases) were excluded. As such, a total 208 patients were enrolled in this study. Data were collected by physicians with experience in acute stroke care using predefined criteria. The NIHSS and modified Rankin Scale (mRS) scores were evaluated by certified raters. This study was approved by the ethics committee of the Third Affiliated Hospital of Sun Yat-sen University. All subjects involved in the study provided written informed consent. Blood samples were collected within 24 hours of hospital admission and after at least 8 hours of fasting. Serum 25(OH)D levels were measured with a commercially available enzyme-linked immunosorbent assay kit (Immunodiagnostic Systems Limited, Bolton, UK) according to the manufacturer's instructions. A 25(OH)D level <50 nmol/L was defined as deficient. The season at blood sampling, which was defined as spring (March to May), summer (June to August), fall (September to November), or winter (December to February), 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 examined included blood cell count, C-reactive protein (CRP) level and 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 (including type and dose) was collected. Outcomes, which were defined as any intracerebral hemorrhage (ICH), symptomatic ICH (sICH), good functional outcome, all-cause death, and major disability, were assessed in the 3-month follow-up period after stroke onset. A sICH was defined as clinical neurological deterioration (an increment of the NIHSS scores of 4 or greater) in addition to any hemorrhage identified on CT/MRI. Outcomes were assessed by the mRS score at 3-month follow-up visit.