Intestinal farnesoid X receptor (FXR) signaling is involved in the development of obesity, fatty liver disease, and type 2 diabetes. However, the role of intestinal FXR in atherosclerosis and its potential as a target for clinical treatment have not been explored. The serum levels of fibroblast growth factor 19 (FGF19), which is encoded by an FXR target gene, were much higher in patients with hypercholesterolemia than in control subjects and were positively related to circulating ceramide levels, indicating a link between intestinal FXR, ceramide metabolism, and atherosclerosis. Among ApoE^–/– mice fed a high-cholesterol diet (HCD), intestinal FXR deficiency (in Fxr^ΔIE ApoE^–/– mice) or direct FXR inhibition (via treatment with the FXR antagonist glycoursodeoxycholic acid [GUDCA]) decreased atherosclerosis and reduced the levels of circulating ceramides and cholesterol. Sphingomyelin phosphodiesterase 3 (SMPD3), which is involved in ceramide synthesis in the intestine, was identified as an FXR target gene. SMPD3 overexpression or C16:0 ceramide supplementation eliminated the improvements in atherosclerosis in Fxr^ΔIE ApoE^–/– mice. Administration of GUDCA or GW4869, an SMPD3 inhibitor, elicited therapeutic effects on established atherosclerosis in ApoE^–/– mice by decreasing circulating ceramide levels. This study identified an intestinal FXR/SMPD3 axis that is a potential target for atherosclerosis therapy.

Epidemiological data of cerebral small vessel disease (CSVD) in the general population of China are lacking. We report on the prevalence of lacunes, white matter hyperintensity (WMH), and cerebral microbleeds (CMBs) in a community-based sample in China and compare the results with those of other studies. This was a cross-sectional analysis of the population-based Shunyi Study in China. A total of 1,211 stroke-free participants (mean age, 55.6±9.3 years; 37.4% men) with available 3 Tesla (3T) magnetic resonance images were included in this analysis. Demographic information and risk factor data were assessed. The overall and age-specific prevalence of lacunes, WMH, and CMBs was evaluated. Associations between cardiovascular risk factors and the presence of these lesions were analyzed by multiple logistic regression. Our study showed a prevalence of 14.5% for lacunes, 72.1% for periventricular hyperintensity (PVH), 65.4% for deep white matter hyperintensity (DWMH), and 10.6% for CMBs. When compared with other community-based samples, individuals in the same age group showed a higher burden of lacunes and a relatively lower prevalence of CMBs. Advanced age was independently associated with the prevalence of these CSVD markers, while the presence of hypertension increased the risk of lacunes, PVH/DWMH, and CMBs in deep or infratentorial locations. A higher burden of lacunes but a relatively lower prevalence of CMBs was observed in this Chinese population. This notable result highlights the challenge of CSVD prevention in China. Chinese have a risk factor profile for CSVD similar to those in other populations.

Background and purpose: Although inflammation has been proposed to be a candidate risk factor for cerebral small vessel disease (CSVD), previous findings remain largely inconclusive and vary according to disease status and study designs. The present study aimed to investigate possible associations between inflammatory biomarkers and MRI markers of CSVD. Methods: A group of 15 serum inflammatory biomarkers representing a variety of those putatively involved in the inflammatory cascade was grouped and assessed in a cross-sectional study involving 960 stroke-free subjects. The biomarker panel was grouped as follows: systemic inflammation (high-sensitivity C reactive protein (hsCRP), interleukin 6 and tumour necrosis factor α), endothelial-related inflammation (E-selectin, P-selectin, intercellular adhesion molecule 1, vascular cell adhesion molecule 1 (VCAM-1), CD40 ligand, lipoprotein-associated phospholipase A2, chitinase-3-like-1 protein and total homocysteine (tHCY)) and media-related inflammation (matrix metalloproteinases 2, 3 and 9, and osteopontin). The association(s) between different inflammatory groups and white matter hyperintensity (WMH), lacunes, cerebral microbleeds (CMBs), enlarged perivascular space (PVS) and the number of deep medullary veins (DMVs) were investigated. Results: High levels of serum endothelial-related inflammatory biomarkers were associated with both increased WMH volume (R²=0.435, p=0.015) and the presence of lacunes (R²=0.254, p=0.027). Backward stepwise elimination of individual inflammatory biomarkers for endothelial-related biomarkers revealed that VCAM-1 was significant for WMH (β=0.063, p=0.005) and tHCY was significant for lacunes (β=0.069, p<0.001). There was no association between any group of inflammatory biomarkers and CMBs or PVS. Systemic inflammatory biomarkers were associated with fewer DMVs (R²=0.032, p=0.006), and backward stepwise elimination of individual systemic-related inflammatory biomarkers revealed that hsCRP (β=−0.162, p=0.007) was significant. Conclusion: WMH and lacunes were associated with endothelial-related inflammatory biomarkers, and fewer DMVs were associated with systemic inflammation, thus suggesting different underlying inflammatory processes and mechanisms.

Background and Purpose—: Intracranial arterial dolichoectasia (IADE) is a poorly understood arteriopathy compared with intracranial atherosclerotic stenosis (ICAS). We aimed to investigate the risk factors of IADE and ICAS and their relationship with neuroimaging markers of cerebral small vessel disease in a population-based study. Methods—: This study comprised 1237 participants (aged 57.2±9.4 years, 37.6% men) who underwent brain magnetic resonance imaging and magnetic resonance angiography. IADE was assessed based on basilar artery dolichoectasia (diameter, height of bifurcation, and laterality of basilar artery) and dilation of basilar artery and internal carotid artery (intracranial volume-adjusted diameter ≥2 SD). ICAS was defined as any degree of stenosis in at least 1 intracranial artery. The neuroimaging markers of cerebral small vessel disease, including lacunes, white matter hyperintensities, microbleeds, dilated perivascular spaces, and brain atrophy, were evaluated. Results—: Basilar arterial dolichoectasia was observed in 3.6% (45/1237); intracranial arterial dilation in 5.9% (67/1142); and ICAS in 15.7% (194/1237). Older age, higher systolic blood pressure, diabetes mellitus, higher LDL-C (low-density lipoprotein cholesterol) and lower HDL-C (high-density lipoprotein cholesterol) were associated with the presence of ICAS (all P <0.001), whereas only older age was associated with IADE. ICAS was associated with lacunes (odds ratio, 2.91; 95% confidence interval, 1.96–4.34; P <0.001), increased white matter hyperintensities volume (β±SE, 0.54±0.13; P <0.001), and brain atrophy (β±SE, −1.16±0.21; P <0.001), whereas basilar arterial dolichoectasia was mainly associated with dilated perivascular spaces in basal ganglia (odds ratio, 2.20; 95% confidence interval, 1.20–4.02; P =0.01) and, to a lesser extent, associated with lacunes and microbleeds. Conclusions—: IADE and ICAS had different risk factor profiles and associated with different imaging phenotypes of cerebral small vessel disease, suggesting different underlying mechanisms.

In recent years, a series of initiatives have been launched to promote intravenous thrombolysis (IVT) and endovascular therapy (EVT) for acute ischaemic stroke (AIS) in China. We aimed to update the rates of IVT and EVT in China between 2019 and 2020 and to evaluate the current IVT and EVT according to hospital grades. Cross-sectional data on patients receiving IVT/EVT were derived from the Bigdata Observatory platform for Stroke of China (BOSC). The monthly number of discharged patients with a principal diagnosis of AIS was derived from the first pages of medical records of each hospital. The rates and information of IVT and EVT were analysed according to hospital grades. During this period, 938 tertiary hospitals and 786 secondary hospitals from 31 provinces continuously reported data to the BOSC. The overall IVT rate for AIS was 5·64%, and the EVT rate was 1·45%. The IVT rate in secondary hospitals was higher than that in tertiary hospitals (6·39% vs. 5·39%, P < 0·001), whereas the EVT rate in secondary hospitals was much lower than that in tertiary hospitals (0·29% vs. 1·84%, P < 0·001). Significant differences in demographic and clinical characteristics of patients receiving IVT/EVT were also shown between tertiary and secondary hospitals. The rates of IVT and EVT for AIS have greatly increased in China, but there is still a large gap compared with developed countries. Hospital inhomogeneity in IVT and EVT suggests the importance of developing a region-specific network for stroke treatment. None.