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Background: Matrix metalloproteinase-9 (MMP-9), a key determinant of extracellular matrix degradation, might cause cerebral damage after stroke and be involved in the development of depressive symptoms. This study aimed to evaluate the association of serum MMP-9 levels and post-stroke depression (PSD). Methods and Results: Serum MMP-9 levels were determined in 558 acute ischemic stroke patients from 7 hospitals comprising the China Antihypertensive Trial in Acute Ischemic Stroke. We assessed depression status using the 24-item Hamilton Depression Rating Scale and defined PSD as a cutoff score of 8. Logistic regression was performed to estimate the risk of PSD associated with serum MMP-9. Discrimination and reclassification for PSD by MMP-9 were analyzed. A total of 222 (39.8%) stroke patients were categorized as PSD within 3 months. Serum MMP-9 concentrations were higher among PSD patients than those without PSD (658.8 vs. 485.7 ng/mL; P<0.001). The multiple-adjusted odds ratio (95% confidence interval) for the highest MMP-9 quartile compared with the lowest quartile was 4.36 (2.49-7.65) for PSD, and 1 standard deviation higher log-MMP-9 was associated with 68% (37-106%) increased odds of PSD. Adding MMP-9 to the conventional risk factors model substantially improved discrimination and reclassification for PSD (all P<0.05). Conclusions: Elevated serum MMP-9 levels in the acute phase of ischemic stroke were associated with increased risk of PSD, suggesting an important prognostic role of MMP-9 for PSD.

The expression of tissue inhibitor metalloproteinase‐1 (TIMP‐1) significantly increased after acute cerebral ischaemia and involved in neurodegeneration. The purpose was to prospectively investigate the relationship between serum TIMP‐1 with post‐stroke cognitive impairment. Our participants were from an ancillary study of China Antihypertensive Trial in Acute Ischemic Stroke. 598 ischaemic stroke patients from seven participating hospitals were included. Cognitive impairment was evaluated using Mini‐Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) at 3 months. 316 (52.84%) or 384 (64.21%) participants had cognitive impairment according to MMSE or MoCA, respectively. Compared with the first quartile of TIMP‐1, the multivariate‐adjusted odds ratios (95% confidence intervals) for the highest quartile were 1.80 (1.09‐2.97) for cognitive impairment defined by MMSE and 2.55 (1.49‐4.35) by MoCA. Multiple‐adjusted spline regression models showed linear associations between TIMP‐1 concentrations and cognitive impairment ( P value for linearity < 0.01). The addition of TIMP‐1 to models including conventional factors improved reclassification for cognitive impairment, as shown by net reclassification index or integrated discrimination improvement ( P < 0.05). Participants with both higher TIMP‐1 and matrix metalloproteinase‐9 levels simultaneously had highest risk of cognitive impairment. Higher serum TIMP‐1 levels were associated with increased risk of cognitive impairment after acute ischaemic stroke, independently of established risk factors.

ObjectivesLittle is known about contemporary characteristics and management of valvular heart disease (VHD) in China. This study aimed to examine the clinical characteristics, aetiology and type of VHD, interventions and in-hospital outcomes of patients with VHD hospitalised in China.MethodsWe used a two-stage random sampling design to create a nationally representative sample of patients with VHD hospitalised in 2015 in China and included adult patients with mild, moderate or severe VHD. We abstracted data from medical records, including echocardiogram reports, on patient characteristics, aetiology, type and severity of VHD, interventions and in-hospital outcomes. We weighted our findings to estimate nationally representative hospitalisations. We performed multivariable logistic regression analysis to identify factors associated with valve intervention.ResultsIn 2015, 38 841 patients with VHD were hospitalised in 188 randomly sampled hospitals, representing 662 384 inpatients with VHD in China. We sampled 9363 patients, mean age 68.7 years (95% CI 42.2 to 95.2) and 46.8% (95% CI 45.8% to 47.8%) male, with an echocardiogram. Degenerative origin was the predominant aetiology overall (33.3%, 95% CI 32.3% to 34.3%), while rheumatic origin was the most frequent aetiology among patients with VHD as the primary diagnosis (37.4%, 95% CI 35.9% to 38.8%). Rheumatic origin was also the most common aetiology among patients with moderate or severe VHD (27.3%, 95% CI 25.6% to 29.0% and 33.6%, 95% CI 31.9% to 35.2%, respectively). The most common VHD was mitral regurgitation (79.1%, 95% CI 78.2% to 79.9%), followed by tricuspid regurgitation (77.4%, 95% CI 76.5% to 78.2%). Among patients with a primary diagnosis of severe VHD who were admitted to facilities capable of valve intervention, 35.6% (95% CI 33.1% to 38.1%) underwent valve intervention during the hospitalisation. The likelihood of intervention decreased significantly among patients with higher operative risk.ConclusionsAmong patients with VHD hospitalised in China, the predominant aetiology was degenerative in origin; among patients with moderate or severe VHD, rheumatic origin was the most common aetiology. Targeted strategies and policies should be promoted to address degenerative VHD. Patients with severe VHD may be undertreated, particularly those with high operative risk.

Background. Diabetes is a known independent risk factor for stroke. However, whether higher glucose levels (126–139.9 mg/dl) can increase the risk of stroke in people without diabetes is still unknown. Moreover, as a fluctuating parameter, long-term glucose levels may also be related to the risk of stroke outcome. It is important to explore the correlation between long-term average blood glucose, as well as its variability, and stroke. Methods. We used 40,975 clinical measurements of glucose levels and 367 measurements of glycated hemoglobin A1c levels from 12,321 participants without stroke to examine the relationship between glucose levels and the risk of stroke. Participants were from the Weitang Geriatric Diseases study, including 5,707 men and 6,614 women whose mean age at baseline was 60.8 years; 1,011 participants had diabetes, and 11,310 did not. We estimated the long-term average blood glucose level based on the multilevel Bayesian model and fit in Cox regression models, stratified according to diabetes status. Results. Over a median follow-up period of 5 years, stroke developed in 279 of the 12,321 participants (244 without diabetes and 35 with). For people with an average glucose level of 126–139.9 mg per deciliter, compared with 90–99.9 mg per deciliter, the adjusted hazard ratio (HR) for total stroke was 1.78 (95% confidence interval (CI), 1.16–2.75), and the HR for levels higher than 140 mg per deciliter was 1.89 (95% CI, 1.09–3.29). Among those without diabetes whose glucose level was higher than 140 mg per deciliter, compared with 90–99.9 mg per deciliter, the adjusted HRs for total stroke and fatal stroke were 3.66 (95% CI, 1.47–9.08) and 5 (95% CI, 1.77–14.15), respectively. For a glucose standard deviation level higher than 13.83 mg per deciliter, compared with that lower than 5.91 mg per deciliter, the adjusted HR for total stroke was 2.31 (95% CI, 1.19–4.48). Conclusions. Our results suggest that higher average glucose levels (126–139.9 mg/dl) and variance may be risk factors for stroke, even among people without diabetes diagnosis.

Background The age‐related trends in the predictive ability of carotid intima‐media thickness (CIMT) for cardiovascular risk remain unclear. We aimed to identify the age‐related trends in the predictive value of CIMT for cardiovascular death. Methods and Results In a prospective cohort of adults aged 35 to 75 years without history of cardiovascular disease who were enrolled between 2014 and 2020, we measured CIMT at baseline and collected the vital status and cause of death. We divided the study population into 4 age groups (35–44, 45–54, 55–64, and 65–75 years). Competing risk models were fitted to estimate the associations between CIMT and cardiovascular death. The added values of CIMT in prediction were assessed by the differences of the Harrell's concordance index and the net reclassification improvement index. We included 369 478 adults and followed them for a median of 4.7 years. A total of 4723 (1.28%) cardiovascular deaths occurred. After adjusting for the traditional risk factors, the hazard ratios for CIMT mean per SD decreased with age, from 1.27 (95% CI, 1.17–1.37) in the 35 to 44 years age group to 1.14 (95% CI, 1.10–1.19) in the 65 to 75 years age group ( P for interaction <0.01). Meanwhile, the net reclassification improvement indexes for CIMT mean were attenuated with age, from 22.60% (95% CI, 15.56%–29.64%) in the 35 to 44 years age group to 7.00% (95% CI, −6.82% to 20.83%) in the 65 to 75 years age group. Similar results were found for maximum CIMT in all age groups. Conclusions CIMT may improve cardiovascular risk prediction in the young and middle‐aged populations, rather than those aged ≥55 years.

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