Regulation of interstitial fluid flow in adventitia along vasculature by heartbeat and respiration.

Converging studies showed interstitial fluid (ISF) adjacent to blood vessels flows in adventitia along vasculature into heart and lungs. We aim to reveal circulatory pathways and regulatory mechanism of such adventitial ISF flow in rat model. By MRI, real-time fluorescent imaging, micro-CT, and histological analysis, ISF was found to flow in adventitial matrix surrounded by fascia and along systemic vessels into heart, then flow into lungs via pulmonary arteries and back to heart via pulmonary veins, which was neither perivascular tissues nor blood or lymphatic vessels. Under physiological conditions, speckle-like adventitial ISF flow rate was positively correlated with heart rate, increased when holding breath, became pulsative during heavy breathing. During cardiac or respiratory cycle, each dilation or contraction of heart or lungs can generate to-and-fro adventitial ISF flow along femoral veins. Discovered regulatory mechanisms of adventitial ISF flow along vasculature by heart and lungs will revolutionize understanding of cardiovascular system.

Serum immunoglobulin M is associated with the severity of coronary artery disease in adults.

Purpose: The purpose of this study was to investigate the relationship between serum immunoglobulin M (IgM) and the severity of coronary artery disease in Chinese patients who underwent coronary angiography. Methods: A total of 2,045 patients who underwent coronary angiography (CAG) from March 2017 to March 2020 at Beijing Hospital were included in this study. Serum IgM concentration and biochemical indicators were measured before coronary angiography (CAG). The triquartile IgM levels at baseline in the population were analysed. Spearman rank correlation was used to analyse the association between IgM and traditional risk factors for coronary artery disease (CAD). CAD patients were divided into subgroups by affected area, number of affected vessels, and Gensini score to analyse the relationship between IgM and CAD severity. Multivariable logistic regression analysis was used to evaluate the association between IgM and CAD severity. Results: Serum IgM levels were significantly lower in the CAD group (63.5 mg/dL) than in the non-coronary artery disease (NCAD) group (72.3 mg/dL) (P < 0.001). Serum IgM levels were significantly associated with sex. Serum IgM levels were positively correlated with traditional CAD risk factors such as TG, TC and LDL-C (P < 0.05), and negatively associated with the number of obstructed vessels, the number of affected areas, and Gensini scores. After adjusting for age, sex, smoking status, hypertension, dyslipidaemia, diabetes, stroke, and statin use history, a high IgM level was independently negatively associated with the severity of CAD expressed by the Gensini score. Conclusion: We determined that serum IgM was independently negatively associated with the severity of CAD diagnosed by angiography in Chinese adults.

Precisión diagnóstica de la TC-RFF con un nuevo algoritmo de subpíxel grueso a fino en la detección de isquemia específica de lesión: un estudio multicéntrico prospectivo / Diagnostic accuracy of CT-FFR with a new coarse-to-fine subpixel algorithm in detecting lesion-specific ischemia: a prospective multicenter study

Introduction and objectives A new computed tomography-derived fractional flow reserve (CT-FFR) technique with a “coarse-to-fine subpixel” algorithm has been developed to generate precise lumen contours. The aim of this study was to assess the diagnostic performance of this new CT-FFR algorithm for discriminating lesion-specific ischemia using wire-based FFR ≤ 0.80 as the reference standard in patients with coronary artery disease. Methods This prospective, multicenter study screened 330 patients undergoing coronary CT angiography (CCTA) and invasive FFR (median interval 2 days) from 6 tertiary hospitals. CT-FFR was evaluated in a blinded fashion with a “coarse-to-fine subpixel” algorithm for lumen contour. Results Between March 2019 and May 2020, we included 316 patients with 324 vessels. There was a good correlation between CT-FFR and invasive FFR (r=0.76, P<.001). The diagnostic sensitivity, specificity, and accuracy on a per-vessel level were 95.3%, 89.8%, and 92.0% for CT-FFR, and 96.4%, 26.4%, and 53.1% for CCTA>50% stenosis, respectively. CT-FFR showed improved discrimination of ischemia compared with CCTA alone overall (AUC, 0.95 vs 0.74, P<.001) and in intermediate (AUC, 0.96 vs 0.62, P<.001) and “gray zone” lesions (AUC, 0.88 vs 0.61, P<.001). The diagnostic specificity, accuracy, and AUC for CT-FFR (71.9%, 82.8%, and 0.84) outperformed CCTA (9.4%, 48.3%, and 0.66) in patients or in vessels with severe calcification (all P<.05). Conclusions CT-FFR with a new “coarse-to-fine subpixel” algorithm showed high performance in identifying hemodynamically significant stenosis. The diagnostic performance of CT-FFR was superior to that of CCTA in intermediate lesions, “gray zone” lesions, and severely calcified lesions (AU)

Introducción y objetivos Se ha desarrollado una nueva técnica basada en tomografía computarizada para la evaluación de la reserva fraccional de flujo (TC-RFF) con un algoritmo de subpíxel «de grueso a fino» para generar contornos luminales precisos. El objetivo de este estudio es evaluar el rendimiento diagnóstico de este nuevo algoritmo de TC-RFF para discriminar la isquemia específica de lesión utilizando la evaluación invasiva de la RFF ≤ 0,80 como referencia en pacientes con enfermedad coronaria. Métodos Este estudio prospectivo y multicéntrico evaluó a 330 pacientes sometidos a angiografía coronaria no invasiva con TC (ACTC) y evaluación invasiva de la RFF (mediana del intervalo, 2 días) en 6 hospitales terciarios. La TC-RFF se evaluó a ciegas con un algoritmo de subpíxel «de grueso a fino» para la evaluación de la luz. Resultado Entre marzo de 2019 y mayo de 2020, se incluyó a un total de 316 pacientes con 324 vasos. Hubo una buena correlación entre la TC-RFF y la evaluación invasiva de la RFF (r=0,76; p<0,001). La sensibilidad, la especificidad y la exactitud diagnóstica por vaso fueron, respectivamente, del 95,3, el 89,8 y el 92,0% para la TC-RFF y del 96,4, el 26,4 y el 53,1% para la ACTC para las estenosis>50%. La TC-RFF mostró mejor discriminación de la isquemia que la ACTC sola en general (ABC=0,95 frente a ABC=0,74; p<0,001) y en lesiones intermedias (ABC=0,96 frente a ABC=0,62; p<0,001) y en «zona gris» (ABC=0,88 frente a ABC=0,61; p<0,001). La especificidad, la exactitud y el ABC diagnóstica de la TC-RFF (el 71,9%, el 82,8% y 0,84) superaron las de la ACTC (el 9,4%, el 48,3% y 0,66) en pacientes o vasos con calcificación grave (todos, p<0,05). Conclusiones La TC-RFF con un algoritmo de subpíxel «de grueso a fino» proporcionó un alto rendimiento en la identificación de estenosis hemodinámicamente significativas. El rendimiento diagnóstico de la TC-RFF fue superior al de la ACTC en lesiones intermedias, de «zona gris» y con calcificación grave (AU)

Long-term all-cause death prediction by coronary, aortic, and valvular calcification in patients with acute ST-segment elevation myocardial infarction.

BACKGROUND: To determine the prognostic value of cumulative calcification score of coronary artery calcification (CAC), thoracic aortic calcification (TAC) and aortic valve calcification (AVC) in acute ST segment elevation myocardial infarction (STEMI) patients. METHODS: This was a retrospective, single-center cohort study. A total of 332 STEMI patients who received primary percutaneous coronary intervention (PPCI) were enrolled in this study between January 2010 to October 2018. We assessed the calcification in the left anterior descending branch (LAD), left circumflex branch (LCX), right coronary artery (RCA), thoracic aorta, and aortic valve. Calcification of each part was counted as 1 point, and the cumulative calcification score was calculated as the sum of all points. The primary endpoint was all-cause mortality. Multivariate Cox proportional hazards models were used to determine association of cumulative calcification score with end points. The performance of the score was evaluated by receiver operating characteristic (ROC) curve analysis and absolute net reclassification improvement (NRI), compared with the Global Registry of Acute Coronary Events (GRACE) risk score. RESULTS: The overall population's calcification score was 2.0 ± 1.6. During a mean follow-up time of 69.8 ± 29.3 months, the all-cause mortality rate was 12.1%. Kaplan-Meier curve showed that the score was significantly associated with mortality (log-rank p < 0.001). The multivariable Cox proportional hazard analyses showed that a calcification score of 4-5 was independently associated with all-cause death in STEMI patients [hazard ratio (HR) = 2.32, 95% confidence interval (CI): 1.01-5.31, p = 0.046]. The area under the ROC curve (AUC) of the calcification score was 0.67 (95% CI: 0.61-0.72), and the AUC of the GRACE score was 0.80 (95% CI: 0.75-0.84). There was no statistical difference in the predictive value between both scores for 3-year mortality in STEMI patients after PPCI (p = 0.06). Based on the NRI analysis, the calcification score showed better risk classification compared with the GRACE score (absolute NRI = 6.63%, P = 0.027). CONCLUSION: The cumulative calcification score is independently associated with the long-term prognosis of STEMI patients after PPCI.

Identification and Functional Assessment of Eight CYP3A4 Allelic Variants *39-*46 Detected in the Chinese Han Population.

Cytochrome P450 3A4 (CYP3A4), a key enzyme, is pivotal in metabolizing approximately half of the drugs used clinically. The genetic polymorphism of the CYP3A4 gene significantly influences individual variations in drug metabolism, potentially leading to severe adverse drug reactions (ADRs). In this study, we conducted a genetic analysis on CYP3A4 gene in 1163 Chinese Han individuals to identify the genetic variations that might affect their drug metabolism capabilities. For this purpose, a multiplex polymerase chain reaction (PCR) amplicon sequencing technique was developed, enabling us to perform the genotyping of CYP3A4 gene efficiently and economically on a large scale. As a result, a total of 14 CYP3A4 allelic variants were identified, comprising six previously reported alleles and eight new nonsynonymous variants that were nominated as new allelic variants *39-*46 by the PharmVar Association. Further, functional assessments of these novel CYP3A4 variants were undertaken by coexpressing them with cytochromes P450 oxidoreductase (CYPOR) in Saccharomyces cerevisiae microsomes. Immunoblot analysis indicated that with the exception of CYP3A4.40 and CYP3A4.45, the protein expression levels of most new variants were similar to that of the wild-type CYP3A4.1 in yeast cells. To evaluate their catalytic activities, midazolam was used as a probe drug. The results showed that variant CYP3A4.45 had almost no catalytic activity, whereas the other variants exhibited significantly reduced drug metabolism abilities. This suggests that the majority of the CYP3A4 variants identified in the Chinese population possess markedly altered capacities for drug metabolism. SIGNIFICANCE STATEMENT: In this study, we established a multiplex polymerase chain reaction (PCR) amplicon sequencing method and detected the maximum number of new CYP3A4 variants in a single ethnic population. Additionally, we performed the functional characterizations of these eight novel CYP3A4 allele variants in vitro. This study not only contributes to the understanding of CYP3A4 genetic polymorphism in the Chinese Han population but also holds substantial reference value for their potential clinical applications in personalized medicine.

Diagnostic accuracy of CT-FFR with a new coarse-to-fine subpixel algorithm in detecting lesion-specific ischemia: a prospective multicenter study.

INTRODUCTION AND OBJECTIVES: A new computed tomography-derived fractional flow reserve (CT-FFR) technique with a "coarse-to-fine subpixel" algorithm has been developed to generate precise lumen contours. The aim of this study was to assess the diagnostic performance of this new CT-FFR algorithm for discriminating lesion-specific ischemia using wire-based FFR ≤ 0.80 as the reference standard in patients with coronary artery disease. METHODS: This prospective, multicenter study screened 330 patients undergoing coronary CT angiography (CCTA) and invasive FFR (median interval 2 days) from 6 tertiary hospitals. CT-FFR was evaluated in a blinded fashion with a "coarse-to-fine subpixel" algorithm for lumen contour. RESULTS: Between March 2019 and May 2020, we included 316 patients with 324 vessels. There was a good correlation between CT-FFR and invasive FFR (r=0.76, P<.001). The diagnostic sensitivity, specificity, and accuracy on a per-vessel level were 95.3%, 89.8%, and 92.0% for CT-FFR, and 96.4%, 26.4%, and 53.1% for CCTA>50% stenosis, respectively. CT-FFR showed improved discrimination of ischemia compared with CCTA alone overall (AUC, 0.95 vs 0.74, P<.001) and in intermediate (AUC, 0.96 vs 0.62, P<.001) and "gray zone" lesions (AUC, 0.88 vs 0.61, P<.001). The diagnostic specificity, accuracy, and AUC for CT-FFR (71.9%, 82.8%, and 0.84) outperformed CCTA (9.4%, 48.3%, and 0.66) in patients or in vessels with severe calcification (all P<.05). CONCLUSIONS: CT-FFR with a new "coarse-to-fine subpixel" algorithm showed high performance in identifying hemodynamically significant stenosis. The diagnostic performance of CT-FFR was superior to that of CCTA in intermediate lesions, "gray zone" lesions, and severely calcified lesions. Clinical Trial Register: NCT04731285.

Characterization of 15 CYP2J2 variants identified in the Chinese Han population on the metabolism of ebastine and terfenadine in vitro.

Genetic polymorphism of the cytochrome P450 (CYP) gene can significantly influence the metabolism of endogenous and xenobiotic compounds. However, few studies have focused on the polymorphism of CYP2J2 and its impact on drug catalytic activity, especially in the Chinese Han population. In this study, we sequenced the promoter and exon regions of CYP2J2 in 1,163 unrelated healthy Chinese Han individuals using the multiplex PCR amplicon sequencing method. Then, the catalytic activities of the detected CYP2J2 variants were evaluated after recombinant expression in S. cerevisiae microsomes. As a result, CYP2J2*7, CYP2J2*8, 13 variations in the promoter region and 15 CYP2J2 nonsynonymous variants were detected, of which V15A, G24R, V68A, L166F and A391T were novel missense variations. Immunoblotting results showed that 11 of 15 CYP2J2 variants exhibited lower protein expression than wild-type CYP2J2.1. In vitro functional analysis results revealed that the amino acid changes of 14 variants could significantly influence the drug metabolic activity of CYP2J2 toward ebastine or terfenadine. Specifically, 4 variants with relatively higher allele frequencies, CYP2J2.8, 173_173del, K267fs and R446W, exhibited extremely low protein expression and defective catalytic activities for both substrates. Our results indicated that a high genetic polymorphism of CYP2J2 could be detected in the Chinese Han population, and most genetic variations in CYP2J2 could influence the expression and catalytic activity of CYP2J2. Our data significantly enrich the knowledge of genetic polymorphisms in CYP2J2 and provide new theoretical information for corresponding individualized medication in Chinese and other Asian populations.

Effectiveness and safety of Shexiang Baoxin Pill (MUSKARDIA) in patients with stable coronary artery disease and concomitant diabetes mellitus: a subgroup analysis of a randomized clinical trial.

BACKGROUND: Preliminary studies have indicated that Shexiang Baoxin Pill (MUSKARDIA) has a coronary artery dilation effect and increases the coronary blood flow, relieving the symptoms of angina. This study aimed to evaluate the benefit of MUSKARDIA on patients with stable coronary artery disease (CAD) and diabetes mellitus (DM). METHODS: This was a subgroup analysis of a multicenter, randomized, placebo-controlled phase IV trial. CAD patients with a medical history of DM or baseline fasting blood glucose (FBG) ≥7.0 mmol/L were grouped according to the treatment (standard therapy plus MUSKARDIA or placebo). The primary outcome was major adverse cardiovascular events (MACEs), which was the composite outcome of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. The secondary outcome was the composite outcome of all-cause death, non-fatal myocardial infarction, non-fatal stroke, hospitalization for unstable angina or heart failure, and coronary angioplasty. RESULTS: MACEs occurred in 2.6% (9/340) and 4.8% (18/376) of patients in the MUSKARDIA and placebo groups, respectively ( P  = 0.192). Secondary composite outcome was significantly less frequent with MUSKARDIA than with placebo (15.3% [52/340] vs . 22.6% [85/376], P  = 0.017). Risk of MACEs (hazard ratio [HR] = 0.69, 95% confidence interval [CI]: 0.31-1.57) was comparable between two groups. In patients with uncontrolled DM (≥4 measurements of FBG ≥7 mmol/L in five times of follow-up), the risk of secondary outcome was significantly lower with MUSKARDIA (5/83, 6.0%) than with placebo (15/91, 16.5%) (HR = 0.35, 95%CI: 0.13-0.95). CONCLUSION: As an add-on to standard therapy, MUSKARDIA shows a trend of reduced MACEs in patients with stable CAD and DM. Furthermore, MUSKARDIA may reduce the frequency of all-cause death, hospitalization, and coronary angioplasty in this population, especially in those with uncontrolled DM. TRIAL REGISTRATION: ChiCTR.org.cn, ChiCTR-TRC-12003513.

Drug-coated balloon for the treatment of small vessel disease: 9 months of angiographic results and 12 months of clinical outcomes of the PEPCAD China SVD study.

BACKGROUND: Whether the drug-coated balloons (DCBs)-alone strategy was superior to plain old balloon angioplasty (POBA) in treating SVD remains unknown. AIMS: We aimed to evaluate the efficacy and safety of DCBs for the treatment of coronary de novo small vessel disease (SVD) and provide further evidence for extending the clinical indications of DCBs. (ChiCTR1800014966). METHODS: Eligible patients were randomized at a 2:1 ratio to receive DCB treatment or POBA in this prospective, multicenter clinical trial. The reference vessel diameter of lesions was visually assessed to be 2.0 to 2.75 mm. The primary endpoint of the study was angiographic in-segment late luminal loss (LLL) at the 9-month follow-up to demonstrate the superiority of DCB treatment to POBA in SVD. The composite clinical endpoints included clinically driven target lesion revascularization (CD-TLR), target lesion failure (TLF), major adverse cardiac events (MACEs), and thrombosis at the 12-month follow-up. RESULTS: A total of 270 patients were enrolled (181 for DCB, 89 for POBA) at 18 centers in China. The primary endpoint of 9-month in-segment LLL in the intention-to-treat population was 0.10 ± 0.33 mm with DCB and 0.25 ± 0.38 mm with POBA (p = 0.0027). This difference indicated significant superiority of DCB treatment (95% CI: -0.22, -0.04, psuperiority = 0.0068). The rates of the clinical endpoints-CD-TLR, TLF, and MACEs-were comparable between groups. No thrombosis events were reported. CONCLUSIONS: DCB treatment of de novo SVD was superior to POBA with lower 9-month in-segment LLL. The rates of clinical events were comparable between the two devices.

Establishment of a Nomogram for Predicting the Suboptimal Angiographic Outcomes of Coronary De Novo Lesions Treated with Drug-Coated Balloons.

INTRODUCTION: Factors affecting the angiographic outcomes of coronary de novo lesions treated with drug-coated balloons (DCBs) have not been well illustrated. The aim of the study is to establish a nomogram for predicting the risk of suboptimal diameter stenosis (DS) at angiographic follow-up. METHODS: A retrospective analysis was performed on a cohort of patients who underwent DCB intervention for coronary de novo lesions with angiographic follow-up data. Multivariable logistic regression analysis was applied to determine the independent predictors of DS ≥ 30% at follow-up, and then a nomogram model was established and validated. RESULTS: A total of 196 patients (313 lesions) were divided into the suboptimal (DS ≥ 30%) and optimal (DS < 30%) DS groups according to quantitative coronary angiography (QCA) measurements of the target lesions at follow-up. Seven independent factors including calcified lesions, true bifurcation lesions, immediate lumen gain rate (iLG%) < 20%, immediate diameter stenosis (iDS) ≥ 30%, DCB diameter/reference vessel diameter ratio (DCB/RVD) < 1.0, DCB length and mild dissection were identified. The area under the curve (AUC) (95% CI) of the receiver-operating characteristic (ROC) curve of the nomogram was 0.738 (0.683, 0.794). After the internal validation, the AUC (95% CI) was 0.740 (0.685, 0.795). The Hosmer-Lemeshow goodness of fit (GOF) test (χ2 = 6.57, P = 0.766) and the calibration curve suggested a good predictive consistency of the nomogram. CONCLUSIONS: The well-calibrated nomogram could efficiently predict the suboptimal angiographic outcomes at follow-up. This model may be helpful to optimize lesion preparation to achieve optimal outcomes.

Evaluating the value of anti-SARS-CoV-2 antibody detection and neutralizing responses with euvirus: A population of 10776 close contacts in the epidemic of Fujian.

BACKGROUND: Nucleic acid detection represents limitations due to its false-negative rate and technical complexity in the COVID-19 pandemic. Anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody tests are widely spread all over the world presently. However, there is no report on the effectiveness of anti-SARS-CoV-2 antibody testing methods in China. METHODS: We gathered 10776 serum samples from close contacts of the SARS-CoV-2 infections in Fujian of China and used 2 chemiluminescence immunoassays (Wantai Bio., Yahuilong Bio.) and 2 lateral flow immunoassays (Lizhu Bio. and Dongfang Bio.) to perform the anti-SARS-CoV-2 antibody tests in China. RESULTS: The 4 antibody tests have great diagnostic value for infected or uninfected, especially in the neutralizing antibodies tests, the AUC can reach 0.939 (Wantai Bio.) and 0.916 (Yahuilong Bio.). Furthermore, we used pseudoviruses and euvirus neutralization assay to validate the effectiveness of these antibody test, the results of pseudoviruses neutralization assay or euvirus neutralization assay shows a considerable correlation with the 4 antibody detection respectively, particularly in euvirus neutralization assay, neutralizing antibodies detected by Wantai Bio. or Yahuilong Bio., the correlation can get the level of 0.93 or 0.82. CONCLUSIONS: The findings of this study demonstrate that the detections of antibodies have profound value in the diagnosis of COVID-19.

Shexiang Baoxin Pill (MUSKARDIA) reduces major adverse cardiovascular events in women with stable coronary artery disease: A subgroup analysis of a phase IV randomized clinical trial.

Background: A previous phase IV trial revealed sex as a potential effect modifier of MUSKARDIA efficacy in stable coronary artery disease (CAD). Objective: To assess the clinical effect of MUSKARDIA as a supplemental treatment to optimal medical therapy (OMT) in stable CAD cases. Methods: This study was a subgroup analysis of a multicenter, randomized, double-blinded, placebo-controlled phase IV clinical study. Eligible individuals underwent randomization to the oral MUSKARDIA and placebo groups and were treated for 24 months. All participants received OMT according to existing guidelines. The primary composite outcome was the major adverse cardiovascular event (MACE), included cardiovascular death, non-fatal myocardial infarction (MI), or non-fatal stroke. The secondary composite outcome encompassed all-cause mortality, non-fatal MI, non-fatal stroke, hospitalization for unstable angina and/or heart failure, and undergoing coronary procedure/surgery during treatment. Safety signals, especially cardiovascular adverse events (AEs), were analyzed. Results: The female subgroup included 776 participants (384 and 392 in the MUSKARDIA and placebo groups, respectively). The occurrence of the primary composite outcome was lower in the MUSKARDIA group compared with placebo-treated individuals (HR = 0.27, 95%CI: 0.09-0.83; P = 0.02), but the secondary composite outcome showed no significant difference (HR = 0.77, 95%CI: 0.47-1.25; P = 0.29). The MUSKARDIA group had reduced incidence of cardiovascular AEs compared with placebo-treated cases (2.9% vs. 5.6%). Conclusion: As a supplemental treatment to OMT, 24-month administration of MUSKARDIA is effective and safe in female stable CAD cases. Clinical trial registration: [https://clinicaltrials.gov/], identifier [NCT01897805].

Nonlinear association of 1,5-anhydroglucitol with the prevalence and severity of coronary artery disease in chinese patients undergoing coronary angiography.

Background: Postprandial hyperglycemia plays an important role in the pathogenesis of coronary artery disease (CAD). The aim of this study is to determine the associations of 1,5-Anhydroglucitol (1,5-AG), which reflects circulating glucose fluctuations, with the prevalence of CAD and CAD severity in coronary angiography defined Chinese patients. Methods: 2970 Chinese patients undergoing coronary angiography were enrolled. Baseline demographics and medical history data was recorded. Serum 1,5-AG levels and biochemical parameters were measured. Baseline characteristics were compared across 1,5-AG categories in diabetes (DM) and non-DM groups. Logistic regression analysis was performed to evaluate the associations of 1,5-AG with the prevalence and severity of CAD. Results: Lower 1,5-AG was significantly associated with higher Gensini scores in both DM and non-DM groups. Logistic regression analysis demonstrated that the associations of low 1,5-AG with the prevalence of CAD, elevated Gensini score and severe CAD robustly dose-response increased from undiagnosed DM with 1,5-AG ≥ 14µg/mL to DM with 1,5-AG < 14µg/mL even after adjusting for fasting blood glucose (FBG) or Hemoglobin A1c (HbA1c). The associations were more significant in persons with DM. Significant modification effect of DM on the relationship of 1,5-AG with elevated Gensini score was found. In addition, nonlinear relationship and threshold effects of 1,5-AG with CAD and severity were observed. Conclusion: Low 1,5-AG is significantly and independently associated with CAD and CAD severity in Chinese patients undergoing coronary angiography. Measurement of 1,5-AG is useful to differentiate subjects with extensive glucose fluctuations and high CAD risks, especially in DM patients. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT03072797.

Design, methods and baseline characteristics of the Beijing Hospital Atherosclerosis Study: a prospective dynamic cohort study.

Background: The atherosclerotic coronary artery disease (CAD) risk assessment based on conventional risk factors have only moderate performance, and residual risks still exist. Thus, we reported here a cohort study that aims to identify and validate the new biosignatures (especially the metabolomics, lifestyle biomarkers and biological age), and elucidate their predictive effect on CAD and subsequent cardiovascular events. Methods: This prospective, single-center, cohort study commenced in March 2017 and seeks to examine patients undergoing coronary angiography (CAG) at the Beijing Hospital. Patients' baseline demographic and medical history data are captured by questionnaires. Blood samples are taken before CAG for clinical laboratory tests and metabolomics analyses. Traditional CAD risk factors are analyzed by routine assays. CAD-related metabolites from different metabolic pathways and lifestyle biomarkers are measured by liquid chromatography-tandem mass spectrometry methods. Biological ages are calculated based on the laboratory and metabolomics data. The enrolled patients attend annual follow-up examinations for 10 years. The primary end points are the composite end points of major adverse cardiovascular events, including death from any cause, non-fatal myocardial infarction, and non-fatal stroke. Quality management and control are carried out through the entire research process, including standardized baseline and follow-up investigation, intra- and inter-run quality controls for laboratory measurements, etc. Results: Baseline data of the enrolled 2,970 patients from 2017 to 2020 were collected and are presented in this article. Among them, there were more males (62.5%) than females, and the patients tended to be old and overweight. The percentages of diagnosed hypertension and diabetes were 67.3% and 35.2%, respectively. A total of 8.5% had a family history of premature CAD. Their lipid profiles were within the normal range, probably due to the use of statins. Conclusions: This study has successfully initiated an investigation into the roles of new biosignatures in predicting CAD among Chinese Han patients undergoing CAG. To the best of our knowledge, this cohort is the first study systematically focusing on the association of lifestyle biomarkers and biological age with CAD risk. Findings from this study will provide biomarkers to discriminate the presence of CAD and to predict subsequent cardiovascular events.

Mechanistic insight into premature atherosclerosis and cardiovascular complications in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is associated with a significant risk of cardiovascular disease (CVD), which substantially increases disease mortality and morbidity. The overall mechanisms associated with the development of premature atherosclerosis and CVD in SLE remain unclear, but has been considered as a result of an intricate interplay between the profound immune dysregulation and traditional CVD risk factors. Aberrant systemic inflammation in SLE may lead to an abnormal lipid profile and dysfunction, which can further fuel the pro-atherosclerotic environment. The existence of a strong imbalance between endothelial damage and vascular repair/angiogenesis promotes vascular injury, which is the early step in the progression of atherosclerotic CVD. Profound innate and adaptive immune dysregulation, characterized by excessive type I interferon burden, aberrant macrophage, platelet and complements activation, neutrophil dysregulation and neutrophil extracellular traps formation, uncontrolled T cell activation, and excessive autoantibody production and immune complex formation, have been proposed to promote accelerated CVD in SLE. While designing targeted therapies to correct the dysregulated immune activation may be beneficial in the treatment of SLE-related CVD, much additional work is needed to determine how to translate these findings into clinical practice. Additionally, a number of biomarkers display diagnostic potentials in improving CVD risk stratification in SLE, further prospective studies will help understand which biomarker(s) will be the most impactful one(s) in assessing SLE-linked CVD. Continued efforts to identify novel mechanisms and to establish criteria for assessing CVD risk as well as predicting CVD progression are in great need to improve CVD outcomes in SLE.

Retrospective study of treatment with a drug-coated balloon alone is beneficial for ostial coronary lesions.

Background: The effects of ostial coronary lesion (OCL) treatment with a drug-coated balloon (DCB) alone remain controversial. This retrospective study assessed the effectiveness and safety with DCB only strategy for OCL and the factors associated with target lesion revascularization (TLR) in these patients. Methods: The study retrospectively included patients whom had OCLs treated with a paclitaxel-eluting DCB only strategy from 1 May 2014 to 1 May 2017. Patients were divided into in-stent restenosis (ISR) and de novo (primary) groups. And all patients came back to hospital, and underwent clinical and also angiographic follow-up. Results: Among the 44 patients with 55 OCLs, 12 (27.3%) were assigned to the ISR group and 32 (72.7%) to the de novo group. The outcomes included TLR, post-interventional lumen gain, and late lumen loss (LLL). Only 8 TLRs (7 ISR and 1 de novo) were observed after a mean follow-up of 16 months. The TLR rate in the de novo group was significantly lower than the ISR group (2.4% vs. 50%, P<0.001). The LLL was 0.07±0.63 mm. Logistic regression analysis showed that the TLR incidence was independently associated with the type of stenosis (ISR vs. de novo) after adjusting for sex [odds ratio (OR), 58.72; 95% confidence interval (CI): 4.42-779.94, P=0.002]. Conclusions: Treatment with DCB alone was beneficial to patients with OCLs, particularly those with de novo lesions.

Association of Serum ß-Hydroxybutyrate and Coronary Artery Disease in an Urban Chinese Population.

Ketone bodies, including ß-hydroxybutyrate (BHB), acetoacetate (AA), and acetone, can substitute and alternate with glucose under conditions of fuel/food deficiency. Ketone-body metabolism is increased in a myriad of tissue-metabolism disorders. Perturbations in metabolism are major contributors to coronary artery disease (CAD). We investigated the association of BHB with CAD. A total of 2,970 people of Chinese Han ethnicity were enrolled. The Gensini score was calculated for all patients who had positive findings. The serum level of BHB and other laboratory parameters were measured. The association of serum levels of metabolites with traditionally risk factors and CAD severity was analyzed. The BHB was found to be associated with some traditional risk factors of CAD and CAD severity, as determined by the Gensini score or the number of diseased regions. Moreover, BHB was associated with the T3/T1 tertiles of the Gensini score after the adjustment for traditional risk factors by multivariable logistic regression analysis. The association of BHB with CAD severity was more obvious in women. Taken together, these data suggest that the circulating BHB level is independently associated with CAD severity, and that this association is more pronounced in women.

Serum glutamate and glutamine-to-glutamate ratio are associated with coronary angiography defined coronary artery disease.

BACKGROUND AND AIMS: Serum concentrations of glutamate (Glu), Glutamine (Gln) and Gln/Glu ratio have consistently been reported to be associated with metabolic disorders and diabetes. The aim of this study was to examine the relationship between these metabolites with the presence of coronary artery disease (CAD) and CAD severity in Chinese patients. METHODS AND RESULTS: 2970 Chinese patients undergoing coronary angiography (CAG) in Beijing Hospital were enrolled. Baseline demographics and medical history data was recorded by questionnaires. Serum Glu and Gln concentrations were analyzed by isotope dilution liquid chromatography-tandem mass spectrometry (LC-MS/MS). Statistical analysis showed that CAD patients had significantly higher levels of Glu and lower Gln/Glu ratios compared with non-CAD control group. Glu was significantly positively associated with body mass index (BMI), fasting blood glucose (FBG), triglycerides (TG), creatinine (Crea), and uric acid (UA), and negatively associated with high-density lipoprotein cholesterol (HDL-C), while inverse associations between Gln/Glu ratio and these risk factors were observed. Glu levels increased and Gln/Glu decreased with the increase of CAD severity as represented by either the number of stenosed vessels or the Gensini scores. Logistic regression analysis demonstrated that, after adjusting for smoking status, obesity or overweight, hypertension, dyslipidemia, diabetes, stroke and family history of premature CAD, high Glu level and low Gln/Glu ratio were positively associated with CAG defined CAD as well as CAD severity expressed by Gensini score. CONCLUSIONS: We identified Glu and Gln/Glu ratio independently associated with CAG defined CAD as well as CAD severity in Chinese patients undergoing CAG.

A Non-inferiority, Randomized Clinical Trial Comparing Paclitaxel-Coated Balloon Versus New-Generation Drug-Eluting Stents on Angiographic Outcomes for Coronary De Novo Lesions.

BACKGROUND: Drug-coated balloon (DCB) has been proved efficacy for coronary small vessel disease, but data regarding outcomes of DCB in common de novo lesions (including reference vessel diameter more than 3.0mm) compared with new-generation drug-eluting stent (DES) are lacking. We hypothesized that a DCB-only strategy for coronary de novo lesions would be non-inferior to DES treatment on angiographic outcomes. METHODS: In this randomized controlled trial, we compared the effect of DCB with DES on late lumen loss (LLL) at 9-month angiographic follow-up and 12-month major adverse cardiac events (MACEs), including death, non-fatal myocardial infarction, target lesion revascularization (TLR), and target vessel revascularization (TVR). RESULTS: From July 2017 to July 2018, 288 consecutive patients with reference vessel diameter (RVD) between 2.25 and 4.0mm were screened. After proper pre-dilation, 170 patients were enrolled and randomized to the DCB and the DES groups at 1:1 ratio. Seven patients withdrew the consent forms during hospital stay (1 in DCB group, 6 in DES group). Two patients in DCB group underwent bailout stenting due to severe dissection after DCB release. The primary endpoint of 9-month LLL was -0.19±0.49mm with the DCB versus 0.03±0.64mm with the DES. The one-sided 97.5% upper confidence limit of the difference was -0.04mm, achieving non-inferiority of the DCB compared with the DES (P=0.019). The 12-month cumulative MACE rate was similar in the DCB and DES groups (2.44% vs. 6.33%, P=0.226). CONCLUSIONS: In this prospective study, the DCB only strategy for de novo lesion was non-inferior to the new-generation DES in terms of 9-month late lumen loss.