贾镭
中国医学科学院阜外医院
Coronary arteritis is a rare but life-threatening cause of coronary artery disease and could manifest as acute coronary syndrome in clinical scenarios. Coronary arteritis could occur in the setting of systematic vasculitis or being isolated. Most of these patients were lacking of conventional risk factors in atherosclerotic cardiovascular disease. Diagnosis of coronary arteritis still be difficult and often be delayed. Clinicians should take in account of comprehensive factors including the evidence of muti-organ involvement (mainly by symptoms, physical examination and radiology imaging findings) and specific laboratory test results. For the treatment of coronary arteritis, systematic drug therapy (i.e., corticosteroid and immunosuppressive therapy) combined with revascularization were applied in the most cases. However, problems of frequently in-stent restenosis and recurrent myocardial infarction still needed to be solved. It is still unclear whether revascularization is efficient and safe for these patients, and the strategy to prevent restenosis and re-ischemia still needs to be studied in the future. In this study, we reviewed the specific clinical manifestations, laboratory results, imaging findings, diagnosis criteria and therapeutic strategies for patients with coronary arteritis presented as acute coronary syndrome.
Current problems in cardiology 2023
Background Serum uric acid (UA) is correlated closely with traditional cardiovascular risk factors, which might interfere with the action of UA, in patients with coronary artery disease. We performed this study to evaluate the prognostic effect of UA levels in individuals with different numbers of standard modifiable cardiovascular risk factors (SMuRFs). Methods and Results In this prospective study, we consecutively enrolled 10 486 patients with coronary artery disease. They were stratified into 3 groups according to the tertiles of UA concentrations and, within each UA tertile, further classified into 3 groups by the number of SMuRFs (0-1 versus 2-3 versus 4). The primary end point was major adverse cardiovascular and cerebrovascular events (MACCEs), including death, myocardial infarction, stroke, and unplanned revascularization. Over a median follow-up of 2.4 years, 1233 (11.8%) MACCEs were recorded. Patients with high UA levels developed significantly higher risk of MACCEs than those with low UA levels. In addition, UA levels were positively associated with MACCEs as a continuous variable. More importantly, in patients with 0 to 1 SMuRF, the risks of MACCEs were significantly higher in the high-UA-level group (adjusted hazard ratio [HR], 1.469 [95% CI, 1.197-1.804]) and medium-UA-level group (adjusted HR, 1.478 [95% CI, 1.012-2.160]), compared with the low-UA-level group, whereas no significant association was found between UA levels and the risk of MACCEs in participants with 2 to 3 or 4 SMuRFs. Conclusions In patients with coronary artery disease who received evidence-based secondary prevention therapies, elevated UA levels might affect the prognosis of individuals with 0 to 1 SMuRF but not that of individuals with ≥2 SMuRFs.
Journal of the American Heart Association 2023
Background:Social isolation and loneliness pose significant public health challenges globally. The objective of this study is to investigate the association between social isolation, loneliness, and the risk of type 2 diabetes mellitus (T2DM).Methods:423,503 UK adults from the UK Biobank (UKB) and 13,800 Chinese adults from the China Health and Retirement Longitudinal Study (CHARLS) were analyzed. The exposures of interest were social isolation and loneliness. Social isolation was evaluated based on the number of household members, frequency of social activities, contact with others, and marriage status (CHARLS only). Loneliness was evaluated by the subjective feeling of loneliness and the willingness to confide in others (UKB only). The primary endpoint was incident T2DM. The two-sample Mendelian randomization (MR) analysis was based on the genome-wide association studies of UKB (n = 463,010) and the European Bioinformatics Institute (n = 655,666).Findings:The UKB cohort study documented 15,072 T2DM cases during a mean follow-up of 13.5 years, and the CHARLS cohort study recorded 1,249 T2DM cases during a mean follow-up of 5.8 years. Social isolation and loneliness showed significant associations with an elevated risk of T2DM in both UKB (social isolation [most vs least]: HR 1.17, 95% CI 1.11-1.23; loneliness [yes vs no]: HR 1.21, 95% CI 1.13-1.30) and CHARLS cohorts (social isolation [yes vs no]: HR 1.22, 95% CI 1.06-1.40; loneliness [yes vs no]: HR 1.21, 95% CI 1.07-1.36). These associations remained significant after accounting for baseline glucose status and genetic susceptibility to T2DM. Two-sample MR analyses determined that feeling lonely (OR 1.04, 95% CI 1.02-1.06) and engaging in fewer leisure/social activities (OR 1.03, 95% CI 1.02-1.05) were associated with increased T2DM risk, whereas more contact with friends or family (OR 0.99, 95% CI 0.98-0.99) was associated with reduced T2DM risk.Interpretation:Social isolation and loneliness are each associated with an elevated risk of T2DM, with MR analyses suggesting potential causal links. These associations remain significant after considering genetic susceptibility to T2DM. The findings highlight the importance of promoting initiatives to address social isolation and loneliness as part of T2DM prevention strategies.Funding:CAMS Innovation Fund for Medical Sciences (No. 2021-I2M-1-008) and National Natural Science Foundation of China (No. 72103187).
EClinicalMedicine 2023
AIMS:To evaluate the impact of prediabetes identified by different glycemic thresholds (according to ADA or WHO/IEC criteria) and diagnostic tests (fasting plasma glucose [FPG] or hemoglobin A1c [HbA1c]) on clinical outcomes in patients with stable coronary artery disease (CAD).METHODS AND RESULTS:In this prospective cohort study, we consecutively enrolled 4088 stable CAD non-diabetic patients with a median follow-up period of 3.2 years. Prediabetes was defined according to ADA criteria as FPG 5.6∼6.9 mmol/L and/or HbA1c 5.7∼6.4%, and WHO/IEC criteria as FPG 6.1∼6.9 mmol/L and/or HbA1c 6.0∼6.4%. The primary endpoint was major adverse cardiovascular event (MACE), including all-cause death, myocardial infarction, or stroke. The prevalence of prediabetes defined according to ADA criteria (67%) was double that of WHO/IEC criteria (34%). Compared with patients with normoglycaemia, those with WHO/IEC-defined prediabetes were significantly associated with higher risk of MACE [adjusted hazard ratio (HR) 1.50, 95% confidence interval (CI) 1.10-2.06], mainly driven by the higher incidence of events in individuals with HbA1c-defined prediabetes. However, this difference was not found in patients with ADA-defined prediabetes and normoglycaemia (adjusted HR 1.17, 95% CI 0.81-1.68). Although FPG was not associated with cardiovascular events, HbA1c improved the risk prediction for MACE in a model of traditional risk factors. Furthermore, the optimal cutoff value of HbA1c for predicting MACE was 5.85%, which was close to the threshold recommended by IEC.CONCLUSION:This study supports the use of WHO/IEC criteria for the identification of prediabetes in stable CAD patients. Haemoglobin A1c, rather than FPG, should be considered as a useful marker for risk stratification in this population.REGISTRATION:Not applicable.
European journal of preventive cardiology 2023
The Mediterranean-DASH intervention for neurodegenerative delay (MIND) diet has been evaluated as a brain-protective diet pattern that contributes to better cognitive performance and attenuates dementia. Cardioprotective effects of the MIND diet have been demonstrated in the primary prevention of atherosclerotic cardiovascular disease (ASCVD), however, there is no exploration in patients with ASCVD. In this prospective cohort study, 943 patients with ASCVD or stroke from the National Health and Nutrition Examination Survey (NHANES) from 2003 to 2006 were enrolled and divided into three groups according to the MIND diet scores (≤7.0, 7.5-8.0, and ≥8.5). Compared with patients with low MIND diet scores (≤7.0), patients with better adherence to the MIND diet presented a significantly lower risk of all-cause and CV death, as results showed that the hazard ratio [HR] and 95% confidence interval [CI] were 1.09 (0.78, 1.52) in the group of 7.5-8.0, 0.66 (0.50, 0.87) in the group of ≥8.5 for all-cause mortality (P trend = 0.002); 0.70 (0.42, 1.17) in the group of 7.5-8.0 and 0.52 (0.35, 0.75) in the group of ≥8.5 for CV mortality (P for trend < 0.001). Besides, per one-score increase in the MIND diet score was associated with a 10% (HR = 0.90, 95% CI: 0.82, 0.99) lower risk of all-cause mortality and a 16% (HR = 0.84, 95% CI: 0.73, 0.97) lower risk of CV mortality in these patients. In conclusion, this study, for the first time, revealed that better adherence to the MIND diet was associated with improved outcomes in patients with ASCVD.
Food & function 2023
Complete blood count (CBC)-derived indices have been proposed as reliable inflammatory biomarkers to predict outcomes in the context of coronary artery disease. These indices have yet to be thoroughly validated in patients with intermediate coronary stenosis. Our study included 1527 patients only with intermediate coronary stenosis. The examined variables were neutrophil-lymphocyte ratio (NLR), derived NLR, monocyte-lymphocyte ratio (MLR), platelet-lymphocyte ratio (PLR), systemic immune inflammation index (SII), system inflammation response index (SIRI), and aggregate index of systemic inflammation (AISI). The primary endpoint was the composite of major adverse cardiovascular events (MACEs), including all-cause death, non-fatal myocardial infarction, and unplanned revascularization. Over a follow-up of 6.11 (5.73-6.55) years, MACEs occurred in 189 patients. Receiver operator characteristic curve analysis showed that SIRI outperformed other indices with the most significant area under the curve. In the multivariable analysis, SIRI (hazard ratio [HR] 1.588, 95% confidence interval [CI] 1.138-2.212) and AISI (HR 1.673, 95% CI 1.217-2.300) were the most important prognostic factors among all the indices. The discrimination ability of each index was strengthened in patients with less burden of modifiable cardiovascular risk factors. SIRI also exhibited the best incremental value beyond the traditional cardiovascular risk model.
Angiology 2023
BACKGROUND:Prediabetes is common and associated with poor prognosis in patients with acute coronary syndrome and those undergoing revascularization. However, the impact of prediabetes on prognosis in patients with coronary intermediate lesions remains unclear. The objective of the current study is to explore the impact of prediabetes and compare the prognostic value of the different definitions of prediabetes in patients with coronary intermediate lesions.METHODS:A total of 1532 patients attending Fuwai hospital (Beijing, China), with intermediate angiographic coronary lesions, not undergoing revascularization, were followed-up from 2013 to 2021. Patients were classified as normal glucose tolerance (NGT), prediabetes and diabetes according to various definitions based on HbA1c or admission fasting plasma glucose (FPG). The primary endpoint was defined as major adverse cardiovascular events (MACE), the composite endpoint of all-cause death, non-fatal myocardial infarction and repeated revascularization therapy. Multivariate cox regression model was used to explore the association between categories of abnormal glucose category and MACE risk.RESULTS:The proportion of patients defined as prediabetes ranged from 3.92% to 47.06% depending on the definition used. A total of 197 MACE occurred during a median follow-up time of 6.1 years. Multivariate cox analysis showed that prediabetes according to the International Expert Committee (IEC) guideline (6.0 ≤ HbA1c < 6.5%) was associated with increased risk of MACE compared with NGT (hazard ratio [HR]: 1.705, 95% confidence interval [CI] 1.143-2.543) and after confounding adjustment (HR: 1.513, 95%CI 1.005-2.277). Consistently, the best cut-off point of glycated haemoglobin (HbA1c) identified based on the Youden's index was also 6%. Restricted cubic spline analysis delineated a linear positive relationship between baseline HbA1c and MACE risk. Globally, FPG or FPG-based definition of prediabetes was not associated with patients' outcome.CONCLUSIONS:In this cohort of patients with intermediate coronary lesions not undergoing revascularization therapy, prediabetes based on the IEC-HbA1c definition was associated with increased MACE risk compared with NGT, and may assist in identifying high-risk patients who can benefit from early lifestyle intervention.
Cardiovascular diabetology 2023
Ahead of Print article withdrawn by the publisher.
Journal of medical Internet research 2023
Background:DNA methylation plays a key role in establishing cell type-specific gene expression profiles and patterns in atherosclerosis. The underlying mechanism remains unclear. Previous studies have shown that DNA methyltransferase 3b (DNMT3b) may play an important role in atherosclerosis. This study aimed to establish the regulatory role of DNMT3b in the development of atherosclerosis.Methods:We constructed a viral vector carrying Dnmt3b shRNA to transduce ApoE-/- mice. Meanwhile, healthy human peripheral blood Treg cells were treated with inhibitor of DNMT3b (AZA and EGCG) or transduced with DNMT3b shRNA.Results:It showed that Dnmt3b silencing attenuated atherosclerosis, including decreased lesion size and macrophage content and increased collagen and smooth muscle cells content in ApoE-/- mice. To further investigate the possible mechanisms, combined with previous studies by our group, we showed that Foxp3-TSDR methylation level was significantly reduced Foxp3 expression and peripheral blood Treg levels were significantly increased by Dnmt3b shRNA vector transduction in animals committed to western diet for 12 and 18 weeks. Consistently, inhibition of DNMT3b (AZA and EGCG) decreased the expression levels of DNMT3b, which can increase the expression levels of FOXP3, and increase the levels of TGF-β and IL-10 and decrease the levels of IL-β and IFN-γ. After transduction with DNMT3b shRNA, the effect was more obvious.Conclusions:DNMT3b accelerated atherosclerosis, and may be associated with FOXP3 hypermethylation status in regulatory T cells.
Oxidative medicine and cellular longevity 2022
Purpose:The specific mechanisms and biomarkersunderlying the progression of stable coronary artery disease (CAD) to acute myocardial infarction (AMI) remain unclear. The current study aims to explore novel gene biomarkers associated with CAD progression by analyzing the transcriptomic sequencing data of peripheral blood monocytes in different stages of CAD.Material and Methods:A total of 24 age- and sex- matched patients at different CAD stages who received coronary angiography were enrolled, which included 8 patients with normal coronary angiography, 8 patients with angiographic intermediate lesion, and 8 patients with AMI. The RNA from peripheral blood monocytes was extracted and transcriptome sequenced to analyze the gene expression and the differentially expressed genes (DEG). A Gene Oncology (GO) enrichment analysis was performed to analyze the biological function of genes. Weighted gene correlation network analysis (WGCNA) was performed to classify genes into several gene modules with similar expression profiles, and correlation analysis was carried out to explore the association of each gene module with a clinical trait. The dynamic network biomarker (DNB) algorithm was used to calculate the key genes that promote disease progression. Finally, the overlapping genes between different analytic methods were explored.Results:WGCNA analysis identified a total of nine gene modules, of which two modules have the highest positive association with CAD stages. GO enrichment analysis indicated that the biological function of genes in these two gene modules was closely related to inflammatory response, which included T-cell activation, cell response to inflammatory stimuli, lymphocyte activation, cytokine production, and the apoptotic signaling pathway. DNB analysis identified a total of 103 genes that may play key roles in the progression of atherosclerosis plaque. The overlapping genes between DEG/WGCAN and DNB analysis identified the following 13 genes that may play key roles in the progression of atherosclerosis disease: SGPP2, DAZAP2, INSIG1, CD82, OLR1, ARL6IP1, LIMS1, CCL5, CDK7, HBP1, PLAU, SELENOS, and DNAJB6.Conclusions:The current study identified a total of 13 genes that may play key roles in the progression of atherosclerotic plaque and provides new insights for early warning biomarkers and underlying mechanisms underlying the progression of CAD.
Frontiers in immunology 2022
