Chronic cerebral infarctions and white matter lesions link to long-term survival after a first ischemic event: A cohort study.

BACKGROUND AND PURPOSE: To investigate the association of different phenotypes, count, and locations of chronic covert brain infarctions (CBI) with long-term mortality in patients with first-ever manifest acute ischemic stroke (AIS) or transient ischemic attack (TIA). Additionally, to analyze their potential interaction with white matter hyperintensities (WMH) and predictive value in addition to established mortality scores. METHODS: Single-center cohort study including consecutive patients with first-ever AIS or TIA with available MRI imaging from January 2015 to December 2017. Blinded raters adjudicated CBI phenotypes and WMH (age-related white matter changes score) according to established definitions. We compared Cox regression models including prespecified established predictors of mortality using Harrell's C and likelihood ratio tests. RESULTS: A total of 2236 patients (median [interquartile range] age: 71 [59-80] years, 43% female, National Institutes of Health Stroke Scale: 2 [1-6], median follow-up: 1436 days, 21% death during follow-up) were included. Increasing WMH (per point adjusted Hazard Ratio [aHR] = 1.29 [1.14-1.45]), but not CBI (aHR = 1.21 [0.99-1.49]), were independently associated with mortality. Neither CBI phenotype, count, nor location was associated with mortality and there was no multiplicative interaction between CBI and WMH (p > .1). As compared to patients without CBI or WMH, patients with moderate or severe WMH and additional CBI had the highest hazards of death (aHR = 1.62 [1.23-2.13]). The Cox regression model including CBI and WMH had a small but significant increment in Harrell's C when compared to the model including 14 clinical variables (0.831 vs. 0.827, p < .001). DISCUSSION: WMH represent a strong surrogate biomarker of long-term mortality in first-ever manifest AIS or TIA patients. CBI phenotypes, count, and location seem less relevant. Incorporation of CBI and WMH slightly improves predictive capacity of established risk scores.

Chronic Covert Brain Infarctions and White Matter Hyperintensities in Patients With Stroke, Transient Ischemic Attack, and Stroke Mimic.

Background This study was conducted to compare frequencies of chronic brain infarctions (CBIs) and white matter hyperintensities (WMHs) as well as their associations with established early recurrence risk scores in patients with transient ischemic attack (TIA) and stroke mimics compared with ischemic stroke. Methods and Results Single-center cohort study including consecutive patients with TIA, stroke mimics, and acute ischemic stroke, with available magnetic resonance imaging from January 2015 to December 2017. Blinded raters adjudicated WMH (age-related white matter changes score) and CBI according to established definitions. A total of 2112 patients (median [Q1-Q3] age 71 [59-80] years, 43% women, National Institutes of Health Stroke Scale score of 2 [1-7], 80% ischemic stroke, 18% TIA, 2% stroke mimics) were included. While CBIs were present in only 10% of patients with stroke mimic, they were detected in 28% of TIAs and 38% of ischemic strokes (P<0.001). WMHs were less pronounced (0, 0-1) in patients with stroke mimic, but there was no difference between TIA (1, 1-2) and ischemic stroke (0, 1-2) patients. CBIs (adjusted odds ratio, 0.3; 95% CI, 0.1-0.9) were associated with a lower rate of stroke mimic as the final diagnosis, while WMHs were not (adjusted odds ratio per point, 1.3; 95% CI, 0.7-2.2). WMH (ß per point, 0.4; 95% CI, 0.3-0.6) and presence of CBI (ß, 0.6; 95% CI, 0.3-0.9) were associated with a higher cardiovascular risk profile according to the ABCD3-I score. The accuracy of prediction was good for high-risk TIA (cross-validated area under the receiver operating characteristic curve, 0.89; 95% CI, 0.79-0.93) on the basis of brain imaging, age, and sex. Conclusions CBI and WMH differ between patients with stroke mimic and patients with TIA/ischemic stroke and are closely associated with established recurrence risk scores. Prospective studies need to clarify whether including brain frailty markers may contribute to the refinement of current management algorithms and risk stratifications.

Placental Expression of Bile Acid Transporters in Intrahepatic Cholestasis of Pregnancy.

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-related condition characterized by increased maternal circulating bile acids (BAs) having adverse fetal effects. We investigated whether the human placenta expresses specific regulation patterns to prevent fetal exposition to harmful amounts of BAs during ICP. Using real-time quantitative PCR, we screened placentae from healthy pregnancies (n = 12) and corresponding trophoblast cells (n = 3) for the expression of 21 solute carriers and ATP-binding cassette transporter proteins, all acknowledged as BA- and/or cholestasis-related genes. The placental gene expression pattern was compared between healthy women and ICP patients (n = 12 each). Placental SLCO3A1 (OATP3A1) gene expression was significantly altered in ICP compared with controls. The other 20 genes, including SLC10A2 (ASBT) and EPHX1 (EPOX, mEH) reported for the first time in trophoblasts, were comparably abundant in healthy and ICP placentae. ABCG5 was undetectable in all placentae. Placental SLC10A2 (ASBT), SLCO4A1 (OATP4A1), and ABCC2 mRNA levels were positively correlated with BA concentrations in ICP. Placental SLC10A2 (ASBT) mRNA was also correlated with maternal body mass index. We conclude that at the transcriptional level only a limited response of BA transport systems is found under ICP conditions. However, the extent of the transcriptional response may also depend on the severity of the ICP condition and the magnitude by which the maternal BA levels are increased.