Study design and participants
We performed a cross-sectional study on 241 HD patients who had received an MRI as a screening examination at Osaka City University Hospital and Ohno Memorial Hospital from November 2005 to November 2011. For patients who had received multiple MRIs, we used the results of the first MRI. This study protocol was approved by the ethics committee of Osaka City University (No. 1415). Informed consent was obtained from all subjects prior to their participation in the study.
Magnetic resonance imaging
The protocol for MRI was derived from our previous study [22]. All patients underwent brain MRI using a superconducting magnet at a field strength of 1.5 T for proton density, T1-, T2- weighted FLAIR MRI and two-dimensional (2D) gradient echo T2*-weighted MRI were performed in axial planes with 5-mm thick slices and an interslice gap of 1.5 mm. CMBs were defined as focal areas of signal loss consisting of homogeneous, rounded lesions with diameters of 2 to 5 mm on T2*-weighted MRI. Hypointensities of the globus pallidus, which are probably due to calcification or flow void artifacts of the pial vessel, were excluded. MR images were assessed independently by two neuroradiologists who were blinded to all clinical information.
Definition of risk factors
The background factors that needed to be adjusted when performing multivariable analysis on how much stroke history affects the presence of CMBs were selected from the available data on the risk factors of arteriosclerosis and CMBs. To evaluate factors associated with CMBs, we investigated history of stroke, age, sex, dialysis duration, hemoglobin, hypertension (HT), diabetes mellitus (DM), dyslipidemia (DL), current smoking, body mass index (BMI), albumin, cardiovascular disease (excluding stroke), use of antithrombotics, and use of statin. Stroke histories and patient histories were confirmed by checking all medical records.
Those with a clear episode of ICH or cerebral infarction were included, but patients with TIA were not included. Also, cardiovascular disease (excluding stroke) was defined as the following conditions: angina, myocardial infarction, the need for coronary angioplasty and coronary bypass surgery, congestive heart failure, valvular heart disease, atrial fibrillation, and peripheral arterial disease. HT was defined as (a) administration of antihypertensive agents and/or a history of this disorder; (b) systolic blood pressure > 140 mmHg; or (c) diastolic blood pressure > 90 mmHg, with blood pressure measured before HD. DM was defined as 1) administration of insulin or oral antidiabetic agents or 2) prior diagnosis according to the Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus of the American Diabetes Association [26]. DL was defined as low-density lipoprotein cholesterol > 140 mg/dl, triglyceride > 150 mg/dl, and high-density lipoprotein cholesterol < 40 mg/dl or medical treatment for hyperlipidemia. Blood samples were taken from the arterial line prior to HD sessions. BMI was calculated as weight (kg)/height2 (m2).
Statistical analysis
Baseline demographic and clinical characteristics were summarized using percentages and counts for categorical variables and medians and interquartile ranges [25th-75th percentile] for continuous variables. Differences of these variables between subjects with and without a history of stroke were examined by χ2 and Mann–Whitney U test for categorical and continuous variables, respectively. Multivariable logistic regression analysis was performed to examine the association of history of stroke with presence of CMBs with adjustment for age, sex, dialysis duration, HT, DM, DL, current smoking, use of antithrombotics, BMI, Hb, albumin, cardiovascular disease (excluding stroke), and use of statin. In the regression analysis, categorical variables were used as dummy variables (male = 0, female = 1; absence = 0, presence = 1; smoker = 1, non- smoker = 0; yes = 1, no = 0). All statistical tests were performed with a two-sided significance level of 5% using R ver. 4.0.2 (https://www.r-project.org/foundation/) with the “rms” package.