Objective Biological age assessed by the Klemera and Doubal method (KDM) and phenotypic age (PhenoAge) was considered as a marker for ageing-related outcomes because it reflects different aspects of biological ageing and health, which are associated with increased risk of death. proBNPage based on N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a novel index for biological age estimation. However, the independence of its relationship with clinical outcomes from established risk factors, KDM or PhenoAge remains uncertain. Their identification could provide valuable information to prognosis.Design, setting and participants This study analysed data from the general population included in the National Health and Nutrition Examination Survey (NHANES). Participants who took part in the cross-sectional survey from 1999 to 2004 were included, and all-cause as well as cardiovascular mortality was recorded (up to 31 December 2019).Outcome measures All-cause and cardiovascular mortality were considered as outcomes. Clinical risk factors were collected, and biological age was estimated by proBNPage, KDM and PhenoAge. Cox proportional hazards models were used to determine the relationship between proBNPage and outcomes with adjustment for risk factors or other biological age indexes. Restricted cubic spline (RCS) analysis based on multivariate Cox regressions was performed to examine whether there was a non-linear relationship between proBNPage and outcomes.Results A total of 9 925 participants were included in this study. The association between proBNPage and outcomes remained significant after adjusting for risk factors, including NT-proBNP (for all-cause mortality, HR 1.14; 95% CI 1.10 to 1.17; for cardiovascular mortality, HR 1.20; 95% CI 1.14 to 1.27). Similar results were obtained after adjusting for KDM plus NT-proBNP (for all-cause mortality, HR 1.31; 95% CI 1.22 to 1.41; for cardiovascular mortality, HR 1.21; 95% CI 1.11 to 1.28) or PhenoAge plus NT-proBNP (for all-cause mortality, HR 1.21; 95% CI 1.16 to 1.28; for cardiovascular mortality, HR 1.35; 95% CI 1.24 to 1.47). These findings were confirmed in most subgroups. A non-linear relationship was observed between proBNPage and all-cause and cardiovascular mortality with an inflection point.Conclusions A non-linear positive relationship was observed between proBNPage and clinical outcomes. After adjusting for established risk factors and other biological age estimation indices (KDM or PhenoAge), proBNPage was significantly associated with mortality. The results remain similar after further adjustment for NT-proBNP. These results suggest that proBNPage is a useful surrogate for biological age estimation.

Objectives:To evaluate the prognostic value of lateral mitral annular plane systolic excursion (MAPSE) in the prediction of major adverse cardiology events (MACE) in patients with suspected coronary artery disease (CAD). Methods:233 consecutive patients were enrolled with suspected CAD from October 2012 to September 2013 and performed contrast-enhanced cardiac magnetic resonance (CMR) and two-dimensional echocardiogram studies no later than 72 h after admission. CMR imaging protocol included 4-chamber cine(cine-CMR), cardiovascular magnetic resonance angiography (CMRA) and late gadolinium enhancement (LGE). The primary endpoint is the time of first occurrence of a MACE The independent association between lateral MAPSE and MACE was evaluated by Kaplan-Meier analysis and multivariable Cox regression analysis. C statistic and net reclassification improvement (NRI) were used to evaluate the prognostic value of lateral MAPSE in MACE. Results:Forty-five MACE occurred during an average follow-up of 9.2 years. Patients with lateral MAPSE＜9.885 mm experienced a significantly higher incidence of MACE than patients with lateral MAPSE ≥ 9.885 mm (P＜0.001). After adjustment for established univariate predictors (age, diabetes, hypertension, hypercholesterolemia, transmural myocardial infarction), lateral MAPSE remained a significant independent predictor of MACE (HR = 1.373; P = 0.020). The incorporation of lateral MAPSE into the risk model resulted in significant improvement in C statistic (increasing from 0.668 to 0.844; P = 0.005). NRI improvement was 0.33 (P＜0.001). Conclusions:lateral MAPSE derived from cine-CMR is an independent predictor of MACE, and improve risk reclassification beyond traditional clinical and CMR risk factors in patients with suspected coronary disease.

Background and Aims: Trimethylamine-N-oxide (TMAO) is recognized as a novel marker and mediator of atherosclerotic cardiovascular disease (ASCVD). Endothelial progenitor cells (EPCs) are crucial for maintaining vascular homeostasis. Impaired EPC numbers and function correlate with increased adverse cardiovascular events. The aim of this study was to decipher the effect of TMAO on late EPCs (LEPCs) and its underlying molecular mechanism. Methods and Results: In vitro migration and tubulogenic capacities of LEPCs were attenuated by TMAO in a dose-dependent manner, accompanied by inhibition of manganese superoxide dismutase (MnSOD) and mitochondrial damage. TMAO-induced mitochondrial damage provoked proinflammatory responses (increased levels of IL-6, IL-1b, ICAM-1, E-sel, and TNF-α) and autophagic cell death (confirmed by western blot immunofluorescent staining and transmission electron microscopy) in LEPCs. Overexpression of MnSOD through adenovirus transfection reversed TMAO-related LEPCs dysfunction. To study the effect of TMAO on LEPC-mediated vascular repair in vivo, a hind limb ischemia model was established in nude mice, and LEPCs were injected in the ischemic hind limb. Laser Doppler imaging of mouse ischemic hindlimbs at 21 days indicated that TMAO treatment inhibited LEPCs-mediated blood flow recovery, which was restored by MnSOD overexpression. Immunohistology analyses further revealed consistent alterations in capillary density determined by CD31 staining. Conclusions: TMAO induces mitochondrial damage in LEPCs via MnSOD suppression, which leads to cell dysfunction, proinflammatory activation, and autophagic cell death in vitro and impaired LEPCs-mediated revascularization in vivo. Overexpression of MnSOD restores TMAO-induced LEPCs dysfunction and further enhances LEPC-mediated revascularization in the ischemic hind limbs in nude mice.

BACKGROUND:Mobile stroke units (MSUs) improve outcomes in acute ischemic stroke (AIS), but their effectiveness is constrained by limited service radii. Integrating a rendezvous strategy with emergency medical services (EMS) may extend the operational reach of MSUs in rural areas. AIM:We evaluated whether a novel rendezvous approach between MSUs and EMS could enhance thrombolysis efficiency for rural AIS patients in a larger service area. METHODS:We conducted a single-center, pragmatic, non-randomized, operationally allocated comparative study in Suzhou, Anhui, from 1 January to 31 December 2024. When a suspected stroke call originated from a remote location, a nearby conventional ambulance was dispatched. Subsequently, the MSU was dispatched via an EMS call, met the EMS at a predetermined midway point en route to the stroke center, and treated the patient when MSU was available. Inclusion criteria were: age ⩾ 18 years; onset location ⩾ 20 km from the MSU center; and onset-to-call time ⩽ 4 h. Patients with a final diagnosis of cerebral ischemia were analyzed based on transport method (MSU rendezvous vs EMS only). The primary outcome was the thrombolysis rate; secondary outcomes included time metrics, 90-day functional prognosis, and incidence of symptomatic intracranial hemorrhage (sICH). Propensity score matching (PSM) was used to balance baseline characteristics. RESULTS:A total of 307 patients with AIS were included; the median age was 72 years (IQR, 63-79), and 192 (62.50%) were male. One hundred ninety-three patients were transferred through rendezvous transport, and 114 patients were transferred through EMS-only. The median distance from onset location to hospital in the rendezvous transport group was 39.00 km (24.23 miles) (IQR 30.00-47.00 km), with a maximum of 68.00 km (42.25 miles). Compared with EMS-only transfers, patients transferred through rendezvous transport had a nearly 3-fold increase in thrombolysis rates (68.90% vs 17.50%, p < 0.001), reduced dispatch-to-door time by 12.5 min, door-to-needle time by 46 min, and onset-to-needle time by 60 min (all p < 0.001). In addition, in terms of clinical outcomes, patients in the rendezvous group had lower median 90-day modified Rankin Scale scores (2.0 (1.0-3.0) vs 3.0 (1.5-5.0), p < 0.001). These findings remained consistent after PSM. CONCLUSION:Our study demonstrates that the novel MSU-EMS rendezvous approach significantly improves thrombolysis rates and functional outcomes, serving as a viable strategy to expand acute stroke care to remote populations.Data access statement:Data collected for the study may be made available from the corresponding author to others upon reasonable request.

Cerebrovascular disease frequently co-occurs with amyloid-β (Aβ) plaques and tau tangles, the pathological hallmarks of Alzheimer's disease (AD), compounding cognitive decline. Aβ deposition is also central to cerebral amyloid angiopathy (CAA), yet peripheral biomarkers that specifically reflect CAA-related vascular pathology remain elusive. Here, we integrated proteomic, imaging, clinical, neuropathological, and genomic data from brain and cerebrospinal fluid (CSF) to define molecular signatures distinguishing CAA from plaque pathology. Proteomic profiling of 118 cerebrovascular-enriched brain samples quantified over 11,000 proteins, revealing co-expression modules enriched for extracellular matrix (ECM) components strongly linked to CAA. In CSF proteomes from 1,104 individuals, vascular ECM module proteins (e.g., CRIP1, LTBP1, PRSS23) were associated with CAA, white matter hyperintensities (WMH), microbleeds, and infarcts but not Aβ plaque burden. Integrating AD genome-wide association studies and CSF protein quantitative trait loci (pQTLs) identified CRIP1 as a candidate causal protein for AD. Carriers of the minor allele at the CRIP1 pQTL exhibited reduced CRIP1 levels, less WMH, and lower CSF levels of ECM proteins linked to CAA. In vitro, CRIP1 bound Aβ and accelerated fibril formation, providing a mechanistic link to vascular amyloid pathology. These findings establish overlapping brain and CSF biomarkers for CAA and identify CRIP1 and vascular ECM pathways as candidate targets for precision diagnostics and therapeutic intervention.

The rupture of vulnerable plaques is the principal cause of luminal thrombosis in acute ischemic stroke. The identification of plaque features that indicate risk for disruption may predict cerebrovascular events. Here, we aimed to build a high-risk intracranial plaque model that differentiates symptomatic from asymptomatic plaques using radiomic features based on high-resolution magnetic resonance imaging (HRMRI). One hundred and seventy-two patients with 188 intracranial atherosclerotic plaques (100 symptomatic and 88 asymptomatic) with available HRMRI data were recruited. Clinical characteristics and conventional plaque features on HRMRI were measured, including high signal on T1-weighted images (HST1), the degree of stenosis, normalized wall index, remodeling index, and enhancement ratio (ER). Univariate and multivariate analyses were performed to build a traditional model to differentiate between symptomatic and asymptomatic plaques. Radiomic features were extracted from pre-contrast and post-contrast HRMRI. A radiomic model based on HRMRI was constructed using random forests, ridge, least absolute shrinkage and selection operator, and deep learning (DL). A MIX model was constructed based on the radiomic model and the traditional model. Gender, HST1, and ER were associated with symptomatic plaques and were included in the traditional model, which had an area under the curve (AUC) of 0.697 in the training set and 0.704 in the test set. The radiomic model achieved an AUC of 0.982 in the training set and 0.867 in the test dataset for identifying symptomatic plaques. In the training set, the MIX model showed an AUC of 0.977. In the test set, the MIX model exhibited an improved AUC of 0.895, which outperformed the traditional model (p = 0.032). Radiomic analysis based on DL and machine learning can accurately identify high-risk intracranial plaques.

Vascular aging increases the susceptibility to cardio-cerebrovascular conditions, such as atherosclerotic diseases and hypertension, the leading causes of global disability and mortality. Dietary citrate extends the lifespan of Drosophila melanogaster and Caenorhabditis elegans as well as improves the memory of mice injured by a high-fat diet (HFD); whether it alleviates vascular aging and age-related vascular diseases; however, remains unknown. Here, we showed that dietary supplementation of citrate delayed vascular aging, as evidenced by maintaining the integrity of elastic fibers and decreasing the level of the aging-related marker, CDKN1A (p21). Functionally, citrate improved the sensitivity to endothelial-dependent vasodilators and lowered blood pressure, and in HFD-fed ApoE-/- mice, it reduced the size of atherosclerotic plaques, decreased the necrotic core area and vulnerability index in aortic root plaques. Additionally, citrate decreased the frailty index, increased bone density, and improved maximal grip strength and balance speed in both aged and HFD-fed ApoE-/- mice. Mechanistically, we showed that citrate exposure delayed human umbilical vein endothelial cell senescence with a decreased percentage of cells stained with senescence-associated β-galactosidase and p21 levels. Moreover, citrate activated AMPK-related pathways and reversed senescence-related mitochondrial dysfunction in basal respiration, maximal respiration, and ATP production and reduced the production of reactive oxygen species (ROS). The citrate-promoted beneficial effects were abolished due to inactivated AMPK and the increased mitochondrial ROS. Thus, we demonstrate that dietary citrate delays vascular aging and alleviates age-related vascular diseases by improving mitochondrial function via activation of AMPK-related pathways. Citrate may have potential clinical implications for interventions against vascular aging and age-related vascular diseases.

The gut microbial metabolite trimethylamine N-oxide (TMAO) is regarded as a novel risk factor for hypertension. Berberine (BBR) exerts cardiovascular protective effects by regulating the gut microbiota-metabolite production pathway. However, whether and how BBR alleviates TMAO-induced vascular dysfunction in hypertension remains unclear. In the present study, we observed that plasma TMAO and related bacterial abundance were significantly elevated and negatively correlated with vascular function in 86 hypertensive patients compared with 46 normotensive controls. TMAO activated endoplasmic reticulum stress (ERS) signaling pathway to promote endothelial cell dysfunction and apoptosis in vitro. BBR (100, 200 mg · kg-1 ·d-1) for 4 weeks ameliorates TMAO-induced vascular dysfunction and ERS activation in a choline-angiotensin II hypertensive mouse model. We found that plasma TMAO levels in 15 hypertensive patients treated with BBR (0.4 g, tid) were reduced by 8.8 % and 16.7 % at months 1 and 3, respectively, compared with pretreatment baseline. The oral BBR treatment also improved vascular function and lowered blood pressure. Faecal 16 S rDNA showed that BBR altered the gut bacterial composition and reduced the abundance of CutC/D bacteria in hypertensive mice and patients. In vitro bacterial cultures and enzyme reaction systems indicated that BBR inhibited the biosynthesis of TMAO precursor in the gut microbiota by binding to and inhibiting the activity of CutC/D enzyme. Our results indicate that BBR improve vascular dysfunction at least partially by decreasing TMAO via regulation of the gut microbiota in hypertension.

BACKGROUND:We aimed to investigate the association of characteristics of lenticulostriate artery (LSA) morphology and parental atheromatous disease (PAD) with single subcortical infarction (SSI) and to explore whether the LSA morphology is correlated with proximal plaque features in asymptomatic PAD. METHODS AND RESULTS:Patients with acute SSI were prospectively enrolled and classified as large- and small-SSI groups. The clinical data and imaging features of LSA morphology (branches, length, dilation, and tortuosity) and middle cerebral artery plaques (normalized wall index, remodeling index, enhancement degree, and hyperintense plaques) were evaluated. Logistic regression was performed to determine the association of large SSIs with morphologic features of LSAs and plaques. The Spearman correlation between the morphologic characteristics of LSAs and plaque features in asymptomatic PAD was analyzed. Of the 121 patients recruited with symptomatic PAD, 102 had coexisting asymptomatic contralateral PAD. The mean length of LSAs (odds ratio, 0.84 [95% CI, 0.73-0.95]; P=0.007), mean tortuosity of LSAs (odds ratio, 1.13 [95% CI, 1.05-1.22]; P=0.002), dilated LSAs (odds ratio, 22.59 [95% CI, 2.46-207.74]; P=0.006), and normalized wall index (odds ratio, 1.08 [95% CI, 1.01-1.15]; P=0.022) were significantly associated with large SSIs. Moreover, the normalized wall index was negatively correlated with the mean length of LSAs (r=-0.348, P<0.001), and the remodeling index was negatively correlated with the mean tortuosity of LSAs (r=-0.348, P<0.001) in asymptomatic PAD. CONCLUSIONS:Our findings suggest that mean length of LSAs, mean tortuosity of LSAs, dilated LSAs, and normalized wall index are associated with large SSIs. Moreover, plaque features in asymptomatic PAD are correlated with morphologic features of LSAs.

This study aimed to investigate the dilation of lenticulostriate artery (LSA) identified by whole-brain vessel wall imaging (WB-VWI) in differentiating the etiologic subtypes of single subcortical infarction (SSI) and to determine whether the appearance of dilated LSA was associated with 90-day clinical outcomes in parental atherosclerotic disease (PAD)-related SSI. Patients with acute SSI were prospectively enrolled and categorized into PAD-related SSI and cerebral small-vessel disease (CSVD)-related SSI groups. The imaging features of LSA morphology (branches, length, dilation, and tortuosity), plaques (burden, remodeling index, enhancement degree, and hyperintense plaque), and CSVD (white matter hyperintensity, lacunes, cerebral microbleed, and enlarged perivascular space) were evaluated. The logistic regression was performed to determine the association of dilated LSA with PAD-related SSI and 90-day clinical outcomes. In total, 131 patients (mean age, 52.2 ± 13.2 years; 99 men) were included. The multivariate logistic regression analysis revealed that the presence of dilated LSAs (odds ratio (OR), 7.40; 95

ObjectivesCardiovascular magnetic resonance-feature tracking (CMR-FT) enables quantification of myocardial deformation and may be used as an objective measure of myocardial involvement in ST-elevation myocardial infarction (STEMI). We sought to investigate the associations between myocardial dyssynchrony parameters and myocardium damage for STEMI.MethodsWe analyzed 65 patients (45–80 years old) with anterior STEMI after primary percutaneous coronary intervention during 3–7 days [observational (STEMI) group] and 60 healthy volunteers [normal control (NC) group]. Myocardial dyssynchrony parameters were derived, including global and regional strain, radial rebound stretch and displacement, systolic septal time delay, and circumferential stretch.ResultsCMR characteristics, including morphologic parameters such as left ventricular ejection fraction (LVEF) (45.3% ± 8.2%) and myocardium damage in late gadolinium enhancement (LGE) (19.4% ± 4.7% LV), were assessed in the observation group. The global radial strain (GRS) and global longitudinal strain (GLS) substantially decreased in anterior STEMI compared with the NC group (GRS: 19.4% ± 5.1% vs. 24.8% ± 4.0%, P < 0.05; GLS: −10.1% ± 1.7% vs. −13.7% ± 1.0%, P < 0.05). Among 362 infarcted segments, radial and circumferential peak strains of the infarcted zone were the lowest (14.4% ± 3.2% and −10.7% ± 1.6%, respectively). The radial peak displacement of the infarct zone significantly decreased (2.6 ± 0.4 mm) (P < 0.001) and manifested in the circumferential displacement (3.5° ± 0.7°) in the STEMI group (P < 0.01). As microvascular occlusion (MVO) was additionally present, some strain parameters were significantly impaired in LGE+/MVO+ segments (radial strain [RS]: 12.2% ± 2.1%, circumferential strain [CS]: −9.6% ± 0.7%, longitudinal strain [LS]: −6.8% ± 1.0%) compared to LGE+/MVO− (RS: 14.6% ± 3.2%, CS: −10.8% ± 1.8%, LS: −9.2% ± 1.3%) (P < 0.05). When the extent of transmural myocardial infarction is greater than 75%, the parameter of the systolic septal delay (mean, 148 ms) was significantly reduced compared to fewer degrees of infarction (P < 0.01).ConclusionIn anterior STEMI, the infarcted septum swings in a bimodal mode, and myocardial injury reduces the radial strain contractility. A more than 75% transmural degree was the septal strain-contraction reserve cut-off point.

目的 分析头颈动脉MRI血管壁成像(VW-MRI)的临床适应证、图像质量以及VW-MRI常规临床检查对诊断和治疗的影响.资料与方法 回顾性分析首都医科大学宣武医院2016年4月—2018年5月因神经系统症状就诊并行头颈动脉VW-MRI检查患者,评价指标包括人口学数据、病史、治疗过程、VW-MRI检查适应证、图像质量、病变特征、管腔成像诊断、管腔成像+VW-MRI成像诊断.分析管腔成像、管腔成像+VW-MRI成像对每种病因诊断的差异.结果 共纳入241例患者(255个VW-MRI检查),VW-MRI临床适应证包括:病因诊断占76.5％(195/255),评估颅内血管成形术风险占18.0％(46/255),评估治疗效果占5.5％(14/255).行VW-MRI评估病因的195例中,179例(91.8％)有明确诊断,VW-MRI改变了34.9％的患者(68/195)的病因诊断,其中管腔成像+VW-MRI诊断头颈动脉夹层比例高于单纯管腔成像诊断[19.0％(37/195)比9.2％(18/195);χ2=12.960,P<0.001].46例颅内动脉狭窄患者行VW-MRI评估颅内血管成形术风险,其中16例(34.8％)由于颅内血管成形术风险较高放弃手术.结论 VW-MRI作为非侵袭性检查,对病因诊断、临床干预及疗效评估具有一定价值.

Background: Carotid atherosclerotic plaque inflammation plays a critical role in guiding the prevention of secondary stroke. Increased perivascular adipose tissue attenuation observed on computed tomography angiography (CTA) may indicate local inflammation. Our objective was to investigate whether pericarotid adipose tissue (PCAT), as a local inflammation biomarker, could distinguish between different stages of carotid atherosclerotic disease plaques.Methods: We prospectively enrolled 45 consecutive acute stroke patients with carotid artery stenosis from September 2019 to September 2021. We then matched them to non-stroke patients (n=67) and no carotid atherosclerotic disease controls (n=65) based on gender, age, and cardiovascular risk factors. We compared PCAT attenuation, carotid plaque features on CTA, clinical risk factors, and serum inflammatory factors across the different groups. To detect the association of PCAT attenuation with stage of carotid atherosclerotic disease, we used multivariable logistic regression analysis.Results: Patients with acute stroke had a higher PCAT attenuation (-78.80 +/- 11.62 HU) than patients with non-stroke (-89.01 +/- 10.81 HU, P<0.001) and no carotid atherosclerotic disease controls (-95.24 +/- 10.81 HU, P<0.001). PCAT attenuation was significantly increased in non-stroke patients compared to non-stroke patients over no carotid atherosclerotic disease controls (P=0.004). The association between PCAT attenuation and the stage of carotid atherosclerotic disease was independent of age, gender, cardiovascular risk factors, and CTA plaque characteristics. No interaction was observed between clinical features and CTA plaque characteristics on PCAT attenuation.Conclusions: PCAT attenuation, which is an imaging biomarker of local inflammation, independently distinguishes patients with different stages of carotid atherosclerotic disease. Quantitative evaluation of PCAT attenuation in carotid atherosclerotic disease is expected to guide targeted surgical treatment of carotid plaque.

Purpose: To elucidate the vessel wall changes of vertebrobasilar dolichoectasia (VBD) with ischemic stroke, using vessel wall magnetic resonance imaging (VW-MRI).Method: Thirty-four patients with VBD (22 with stroke and 12 without stroke) who underwent VW-MRI were recruited. Forty-one patients without VBD who underwent VW-MRI were also recruited if they had a recent stroke due to atherosclerosis in the basilar artery or the intracranial vertebral artery. The vessel wall features of VBD were compared between stroke and non-stroke groups. The plaque characteristics were compared between VBD and non-VBD stroke patients.Results: The frequency of plaques was higher (54.5% vs. 8.3%, P = 0.011) in VBD patients with stroke than that in non-stroke patients, while the frequencies of aneurysm, dissection, intraluminal thrombus, and diffuse/ concentric wall enhancement did not differ. When the plaque features were compared between plaque-positive stroke patients with and without VBD, the degree of stenosis (31.0% & PLUSMN; 26.8% vs. 71.5% & PLUSMN; 19.0%, P < 0.001), normalized wall index (NWI) (0.7 & PLUSMN; 0.1 vs. 0.9 & PLUSMN; 0.1, P < 0.001), and remodeling index (RI) (1.0 & PLUSMN; 0.4 vs. 1.3 & PLUSMN; 0.4, P = 0.023) were lower in the VBD group, while intraplaque hemorrhage, and enhancement ratio showed no difference.Conclusions: This preliminary study suggests that atherosclerosis may be an important cause of stroke in VBD patients. Symptomatic plaques in VBD patients have a lower degree of stenosis, NWI, and RI than that in nonVBD patients. VW-MRI may help to assess stroke mechanisms and identify VBD patients at high risk.

Hypertension is associated with intracranial atherosclerosis (ICAS) and is a leading cause of acute ischemic stroke (AIS). Given sex-differences in the severity of hypertension, we hypothesized sex-differences in ICAS burden among hypertensive patients with AIS. Results show males have significantly higher adjusted total plaque burdens than females. Subgroup analyses show treated hypertensive males with AIS have higher total proximal and bifurcation plaques than treated females. Untreated hypertensive females have significantly higher total proximal and bifurcation plaques compared to untreated males. The results suggest attention to differential hypertension management by sex may be warranted to reduce ICAS burden and AIS risk.

Background Studies suggest the presence of sex differences in hypertension prevalence and its associated outcomes in atherosclerosis and stroke. We hypothesized a higher intracranial atherosclerosis burden among men with hypertension and acute ischemic stroke compared with women. Methods and Results A multicenter retrospective study was performed from a prospective database identifying patients with hypertension presenting with intracranial atherosclerosis‐related acute ischemic stroke and imaged with intracranial vessel wall magnetic resonance imaging. Proximal and distal plaques on vessel wall magnetic resonance imaging were scored. Negative binomial models assessed the associations between plaque‐count and sex and the interaction between sex and treatment. Covariates were selected by a least absolute shrinkage and selection operator procedure. Sixty‐one patients (n=42 men) were included. There were no significant differences in demographic or cardiovascular risk factors except for smoking history ( P =0.002). Adjusted total and proximal plaque counts for men were 1.6 (95% CI, 1.2–2.1; P <0.01) and 1.4 (95% CI, 1.0–1.9; P =0.03) times as high as women, respectively. Female sex was more protective for proximal plaque if treated for hypertension. The risk ratio of men versus women was 1.5 (95% CI, 1.0–2.1) for treated patients. The risk ratio of men versus women was 0.7 (95% CI, 0.4–1.3) for untreated patients. The relative difference between these 2 risk ratios was 2.0 (95% CI, 1.1–3.9), which was statistically significant from the interaction test, P =0.04. Conclusions Men with hypertension with acute ischemic stroke have significantly higher total and proximal plaque burdens than women. Women with hypertension on anti‐hypertensive medication showed a greater reduction in proximal plaque burden than men. Further confirmation with a longitudinal cohort study is needed and may help evaluate whether different treatment guidelines for managing hypertension by sex can help reduce intracranial atherosclerosis burden and ultimately acute ischemic stroke risk.

目的:探讨心血管磁共振(CMR)黑血、亮血T2加权序列对急性心肌梗死患者再灌注血管开通后水肿心肌的诊断效能.方法:回顾分析2016年9月至2018年12月就诊于首都医科大学宣武医院的76例首次发作急性心肌梗死患者的临床影像资料.患者平均年龄(57±11)岁,其中男性66例.全部患者于1周内行CMR检查.收集并分析CMR黑血T2加权黑血反转恢复(T2-STIR)序列、亮血T2预脉冲自由呼吸平衡稳态进动(T2p-SSFP)序列图像,以定量T2-MAP序列为"金标准"评价识别水肿心肌的诊断效能.图像质量分析包含患者水平图像伪影识别,层面水平图像信噪比,对比噪声比比较;诊断效能包含节段水平水肿心肌识别的敏感度、特异度和准确度.结果:在患者水平,黑血T2-STIR和亮血T2p-SSFP产生运动伪影分别有24例和5例,磁敏感伪影分别有17例和2例,差异有统计学意义(P<0.05).层面水平,黑血T2-STIR序列显示远端心肌、水肿心肌信噪比是亮血T2p-SSFP序列的2倍(P<0.05),水肿心肌与远端心肌、与血池的对比噪声比黑血T2-STIR序列强于亮血T2p-SSFP序列,差异有统计学意义(P<0.05).在节段水平,黑血T2-STIR对水肿心肌识别的敏感度高[87.4％(83.3％,90.8％)],亮血T2p-SSFP的特异度高[95.4％(89.5％,98.5％)],两者相结合可显著提升水肿心肌识别效能,敏感度达[93.7％(90.5,96.1)],约登指数提升至0.86.结论:心血管磁共振T2加权序列的优质图像质量,对急性心肌梗死后水肿心肌的识别具备临床实用价值,黑血T2-STIR和亮血T2p-SSFP序列相结合可显著提升识别敏感度和准确性.

Introduction: We hypothesized sex-differences in the prevalence of intracranial atherosclerosis (ICAS) among hypertensive patients with ischemic stroke due to ICAS. Methods: Subjects with ischemic stroke secondary to ICAS underwent MR vessel wall imaging (VWI) within 8 weeks of symptom onset. Demographic data, cardiovascular risk factors, and medication history were recorded. A neuroradiologist blinded to clinical history scored proximal (A1/M1/P1) and distal (A2/M2-3/P2) plaques involving the anterior/middle/posterior cerebral arteries. The most stenotic vessel lesion with wall thickening/enhancement and supplying the ischemic territory was defined as a culprit plaque. Continuous variables are summarized by medians and interquartile ranges. Chi square and Mann Whitney U-tests compared categorical and continuous variables, respectively. Results: Sixty-one subjects (male, N=42) with a diagnosis of hypertension and ischemic stroke due to ICAS were included. There were no significant sex-differences in demographic or cardiovascular risk factors except for smoking history (p=0.002). Hypertensive males with ischemic stroke due to ICAS had a significantly higher number of proximal plaques than females [males=8 (4, 10) vs females=5 (3, 7); p=0.03; Figure] but not distal plaques [males=3 (1, 5) vs females=2 (0, 5); p=0.33]. Among subjects on an anti-hypertensive prior to admission (N=35), males with ischemic stroke had a significantly higher proximal plaque burden than females [males=8 (4, 10) vs females=4 (3, 6); p=0.05]. The culprit plaque was proximal in 95% and 92% of cases in males and females treated for hypertension and with ischemic stroke, respectively. Conclusions: Attention to differential management of hypertension for males versus females may be warranted to reduce ischemic stroke risk given significantly higher proximal ICAS burden in hypertensive males than females despite medical treatment.

BackgroundPrevious studies have demonstrated that patients with a cancer diagnosis have an elevated risk of suicide and cardiovascular death. However, the effects of the diagnosis of multiple primary cancers (MPCs) on the risk of suicide and cardiovascular death remain unclear. This study aimed to identify the risk of suicide and cardiovascular death among patients with MPCs in the United States.MethodsPatients with a single or MPC(s) between 1975 and 2016 were selected from the Surveillance, Epidemiology, and End Results database in a retrospective cohort study. Mortality rates and standardized mortality ratios (SMRs) of suicides and cardiovascular diseases among patients with MPCs were estimated.ResultsOf the 645,818 patients diagnosed with MPCs included in this analysis, 760 and 36,209 deaths from suicides and cardiovascular diseases were observed, respectively. The suicide and cardiovascular-disease mortality rates were 1.89- (95% CI, 1.76–2.02) and 1.65-times (95% CI, 1.63–1.67), respectively, that of the general population. The cumulative mortality rate from both suicides and cardiovascular diseases among patients with MPCs were significantly higher than those of patients with a single primary cancer (Both p < 0.001). In patients with MPCs diagnosed asynchronously, the cumulative incidence rates of suicides and cardiovascular deaths were higher than those diagnosed synchronously. Among all MPCs, cancers of the pancreas and esophagus had the highest SMRs of suicide (5.98 and 5.67, respectively), while acute myeloid leukemia and brain cancer had the highest SMRs of cardiovascular diseases (3.87 and 3.62, respectively). The SMR of suicide was highest within 1 year after diagnosis, while that of cardiovascular diseases was highest 5 years after diagnosis.ConclusionsThis study showed that the mortality rates from suicides and cardiovascular diseases among patients with MPCs were higher than those with a single primary cancer. Therefore, our results underscore the need for psychological assessment and targeted preventive interventions for suicides and cardiovascular diseases among patients with MPCs.

Berberine (BBR) has been demonstrated to exert cardiovascular protective effects by regulating gut microbiota. However, few studies examine the effect of BBR on the gut microbiota in hypertension. This study aims to investigate the role of BBR in regulating microbial alterations and vascular function in hypertension. C57BL/6 J mice were infused with Ang II (0.8 mg/kg/day) via osmotic minipumps and treated with BBR (150 mg/kg/day) or choline (1%) for 4 weeks. Blood pressure was detected by tail-cuff measurement once a week. Abdominal aorta pulse wave velocity (PWV) and endothelium dependent vasodilatation were measured to evaluate vascular function. Vascular remodeling was assessed by histological staining of aortic tissue. The fecal microbiota was profiled using 16S ribosomal DNA (rDNA) sequencing. Plasma trimethylamine (TMA)/trimethylamine-N-oxide (TMAO) and hepatic FMO3 expression were measured. We found that BBR treatment significantly alleviated the elevated blood pressure, vascular dysfunction, and pathological remodeling in Ang II-induced hypertensive mice, while choline treatment aggravated hypertension-related vascular dysfunction. 16S rDNA gene sequencing results showed that BBR treatment altered gut microbiota composition (reduced the Firmicutes/Bacteroidetes (F/B) ratio and increased the abundances of Lactobacillus). Moreover, BBR inhibited FMO3 expression and plasma TMA/TMAO production in hypertensive mice. TMAO treatment increased the apoptosis and oxidative stress of human aortic endothelial cells (HAECs) and aggravated Ang II-induced HAECs dysfunction in vitro. These results indicate that the protective effect of BBR in hypertension might be attributed (at least partially) to the inhibition of TMAO production via regulating the gut microbiota.