Unruptured intracranial aneurysm (UIA) is a life-threatening cerebrovascular condition. Whether changes in gut microbial composition participate in the development of UIAs remains largely unknown. We perform a case-control metagenome-wide association study in two cohorts of Chinese UIA patients and control individuals and mice that receive fecal transplants from human donors. After fecal transplantation, the UIA microbiota is sufficient to induce UIAs in mice. We identify UIA-associated gut microbial species link to changes in circulating taurine. Specifically, the abundance of Hungatella hathewayi is markedly decreased and positively correlated with the circulating taurine concentration in both humans and mice. Consistently, gavage with H. hathewayi normalizes the taurine levels in serum and protects mice against the formation and rupture of intracranial aneurysms. Taurine supplementation also reverses the progression of intracranial aneurysms. Our findings provide insights into a potential role of H. hathewayi-associated taurine depletion as a key factor in the pathogenesis of UIAs.

Background and Purpose—: This study aimed to investigate the association between carotid plaque progression and subsequent recurrent events using magnetic resonance imaging. Methods—: Sixty-three symptomatic patients with ipsilateral carotid atherosclerotic stenosis (30%–69% stenosis) determined by ultrasound underwent first and second carotid artery magnetic resonance imaging for carotid artery at baseline and ≥6 months after the first scan, respectively. All the patients had clinical follow-up after the second magnetic resonance scan for ≤5 years until the onset of recurrent transient ischemic attack or stroke. Presence/absence of carotid plaque compositional features, particularly intraplaque hemorrhage and fibrous cap rupture was identified. The annual progression of carotid wall volume between 2 magnetic resonance scans was measured. Univariate and multivariate Cox regression was used to calculate the hazard ratio and corresponding 95% confidence interval of carotid plaque features in discriminating recurrent events. Receiver-operating-characteristic-curve analysis was conducted to determine the area-under-the-curve of carotid plaque features in predicting recurrent events. Results—: Sixty-three patients (mean age: 66.5±10.0 years old; 54 males) were eligible for final statistics analysis. During a mean follow-up duration of 55.1±13.6 months, 14.3% of patients (n=9) experienced ipsilateral recurrent transient ischemic attack/stroke. The annual progression of carotid wall volume was significantly associated with recurrent events before (hazard ratio, 1.14 per 10 mm ³ ; 95% confidence interval, 1.02–1.27; P =0.019) and after (hazard ratio, 1.19 per 10 mm3; 95% confidence interval, 1.03–1.37; P =0.022) adjusted for confounding factors. In discriminating the recurrence of transient ischemia attack/stroke, receiver–operator curve analysis indicated that combined with annual progression of wall volume, there was a significant incremental improvement in the area-under-the-curve of intraplaque hemorrhage (area-under-the-curve: 0.69–0.81) and fibrous cap rupture (area-under-the-curve: 0.73–0.84). Conclusions—: The annual progression of carotid wall volume is independently associated with recurrent ischemic cerebrovascular events, and this measurement has added value for intraplaque hemorrhage and fibrous cap rupture in predicting future events.

As a systemic disease, atherosclerosis commonly affects intracranial and extracranial carotid arteries simultaneously which is defined as co-existing plaques. Previous studies demonstrated that co-existing atherosclerotic diseases are significantly associated with ischemic cerebrovascular events. The aim of this study was to investigate the characteristics of co-existing intracranial and extracranial carotid atherosclerotic plaques and their relationships with recurrent stroke by using 3D multi-contrast magnetic resonance (MR) vessel wall imaging. Patients with recent cerebrovascular symptoms in anterior circulation and at least one carotid plaque were recruited. All patients underwent cardiovascular magnetic resonance (CMR) for brain and intracranial and extracranial arteries. Presence/absence of atherosclerotic plaque at each arterial segment was identified. The maximum wall thickness (Max WT), length, stenosis of each plaque was measured. The presence/absence of calcification, lipid-rich necrotic core (LRNC), and intraplaque hemorrhage (IPH) was assessed. Cerebral old and acute infarcts in anterior circulation were evaluated. Fifty-eight patients (mean age: 58.0 ± 8.5 years old, 34 males) were recruited. Of the 58 patients, co-existing intracranial and extracranial carotid artery plaques were found in 45 patients (77.6%), of which 7 (15.6%) had first time acute stroke and 26 (57.8%) had recurrent stroke. For these 33 patients with stroke, the number of intracranial plaques (OR = 11.26; 95% CI, 1.27–100; p = 0.030) and co-existing intracranial and extracranial carotid artery plaques (OR = 2.42; 95% CI, 1.04–5.64; p = 0.040) was significantly associated with recurrent stroke. After adjusting for traditional risk factors, the number of co-existing plaques was still significantly correlated with recurrent stroke (OR = 3.31; 95% CI, 1.09–10.08; p = 0.035). No correlations were found between recurrent stroke and Max WT, length, stenosis, and compositions of plaques. Co-existing intracranial and extracranial carotid artery plaques are prevalent in symptomatic patients and the number of co-existing plaques is independently associated with the risk of recurrent stroke.

Objective—: Carotid intraplaque hemorrhage (IPH) is associated with cardiovascular events. Calcification, which frequently accompanies IPH, may play a role in IPH occurrence. In this study, we aimed to investigate the associations between calcification characteristics and IPH in carotid plaques. Approach and results—: One hundred seventeen patients with cerebrovascular symptoms and carotid plaques detected by ultrasound were recruited and underwent multicontrast magnetic resonance imaging. Advanced carotid plaques with composition measured by magnetic resonance imaging were included in the analysis. Carotid calcifications were divided into the following categories: surface, mixed, and deep calcification. They were also classified into single and multiple calcifications according to quantity. Logistic regression models utilizing generalized estimating equations were performed to evaluate the relationship between calcification and IPH. Of 117 subjects, 85 with 142 plaques were included in the final analysis, whereas 32 were excluded because of lack of plaque compositions. Of the 142 plaques, 40 (28.2%) had IPH. Plaques with IPH showed greater prevalence of calcification than those without (87.5% versus 55.9%; P =0.005). After adjusting for age, low-density lipoprotein, maximum wall thickness, and maximum soft plaque thickness, multiple calcifications (odd ratio, 10.1; 95% confidence interval, 3.3–30.4), surface calcification (odd ratio, 29.4; 95% confidence interval, 4.1–210.8), and mixed calcifications (odd ratio, 27.9; 95% confidence interval, 7.3–107.1) were found to be strongly associated with the presence of IPH (all P <0.05). Conclusions—: Surface calcification and multiple calcifications in carotid atherosclerotic plaques are independently associated with the presence of IPH, suggesting that both quantity and location of calcification may play important roles in the occurrence of IPH. These findings may provide novel insights for understanding mechanisms of IPH.

Type 2 diabetes mellitus (T2DM) might aggravate the carotid plaque vulnerability, and increase the risk for ischemic stroke. Few studies reported the acute stroke subtype with carotid plaque characteristics in T2DM patients. This study aimed to investigate the association between carotid plaque characteristics and acute cerebral infarct (ACI) lesion features determined by MRI in T2DM patients. Patients with acute cerebrovascular syndrome in internal carotid artery territory were recruited. All patients were stratified into T2DM and non-T2DM groups and underwent both carotid and brain MRI scans. Ipsilateral carotid plaque morphological and compositional characteristics, intracranial and extracranial carotid artery stenosis were also determined. Stroke subtype based on the Trial of ORG 10172 in Acute Stroke Treatment classification and ACI lesion patterns were evaluated. Of the recruited 140 patients, 68 (48.6%) patients had T2DM (mean age 64.16 ± 11.38 years, 40 males). T2DM patients exhibited higher prevalence of carotid type IV–VI lesions, larger plaque burden as well as larger lipid-rich necrotic core (LRNC) compared with non-T2DM patients. Among the patients with carotid LRNC on symptomatic side, more concomitant large perforating artery infarct patterns and larger ACI size in the internal carotid artery territory were found in T2DM group than those in non-T2DM group. Carotid plaque with LRNC% > 22.0% was identified as an independent risk factor for the presence of ACI lesions confined to the carotid territory in T2DM patients, regardless of other risk factors. This study shows that more concomitant large perforating artery infarct patterns and larger ACI size in the internal carotid artery territory were found in the T2DM patients with ipsilateral carotid LRNC plaque than those in non-T2DM patients. Quantification of the carotid plaque characteristics, particularly the LRNC% by MRI has the potential usefulness for stroke risk stratification.