Atrial fibrillation incidence after coronary artery bypass graft surgery and percutaneous coronary intervention: the prospective AFAF cohort study.

Objectives. Atrial fibrillation is a common arrhythmia in patients with ischemic heart disease. This study aimed to determine the cumulative incidence of new-onset atrial fibrillation after percutaneous coronary intervention or coronary artery bypass grafting surgery during 30 days of follow-up. Design. This was a prospective multi-center cohort study on atrial fibrillation incidence following percutaneous coronary intervention or coronary artery bypass grafting for stable angina or non-ST-elevation acute coronary syndrome. Heart rhythm was monitored for 30 days postoperatively by in-hospital telemetry and handheld thumb ECG recordings after discharge were performed. The primary endpoint was the cumulative incidence of atrial fibrillation 30 days after the index procedure. Results. In-hospital atrial fibrillation occurred in 60/123 (49%) coronary artery bypass graft and 0/123 percutaneous coronary intervention patients (p < .001). The cumulative incidence of atrial fibrillation after 30 days was 56% (69/123) of patients undergoing coronary artery bypass grafting and 2% (3/123) of patients undergoing percutaneous coronary intervention (p < .001). CABG was a strong predictor for atrial fibrillation compared to PCI (OR 80.2, 95% CI 18.1-354.9, p < .001). Thromboembolic stroke occurred in-hospital in one coronary artery bypass graft patient unrelated to atrial fibrillation, and at 30 days in two additional patients, one in each group. There was no mortality. Conclusion. New-onset atrial fibrillation during 30 days of follow-up was rare after percutaneous coronary intervention but common after coronary artery bypass grafting. A prolonged uninterrupted heart rhythm monitoring strategy identified additional patients in both groups with new-onset atrial fibrillation after discharge.

The role of serum lipid in predicting coronary artery lesions and intravenous immunoglobulin resistance in Kawasaki disease: a cohort study.

OBJECTIVE: To assess the predictive value of the serum lipid profile for initial intravenous immunoglobulin (IVIG) resistance and coronary artery lesions (CALs) in patients with Kawasaki disease (KD). METHODS: This retrospective cohort study enrolled patients with KD and divided them into IVIG-responsive and IVIG-resistant groups. They were also stratified based on the presence of CALs (CALs and non-CALs groups). Clinical, echocardiographic and biochemical values were evaluated. A subgroup analysis was performed on complete and incomplete KD. Predictors of initial IVIG resistance and CALs were determined by multivariate logistic regression analysis. RESULTS: A total of 649 KD patients were enrolled: 151 had CALs and 76 had initial IVIG resistance. Low-density lipoprotein cholesterol (LDL-C) was significantly lower in the IVIG-resistant group than in the IVIG-responsive group. LDL-C and apolipoprotein (Apo) B were significantly lower in the CALs group compared with the non-CALs group. Multivariate logistic regression failed to identify the serum lipid profile (LDL-C, Apo A or Apo B) as an independent risk factor for initial IVIG resistance or CALs in KD patients. CONCLUSION: KD patients might have dyslipidaemia in the acute phase, but the serum lipid profile might not be suitable as a single predictor for initial IVIG resistance or CALs.

Assessment of the Level of Matrix Metalloproteinases, VEGF and MicroRNA-34a in Patients With Non-obstructive and Obstructive Lesions of the Coronary Arteries.

AIM: To assess the levels of matrix metalloproteinases (MMP), vascular endothelial growth factor (VEGF), and miRNA-34a expression in patients with ischemic heart disease (IHD) and obstructive and nonobstructive coronary artery (CA) disease. MATERIAL AND METHODS: This cross-sectional observational study included 64 patients with IHD (diagnosis verified by coronary angiography or multislice computed tomography coronary angiography), of which 33 (51.6%) were men aged 64.9±8.1 years. 20 patients had nonobstructive CA disease (stenosis <50%), and 44 had hemodynamically significant stenoses. The control group consisted of 30 healthy volunteers. MMP-1, -9, -13, and -14, miRNA-34a, and VEGF were measured in all patients. RESULTS: The concentration of MMP-1 was significantly higher in patients with ischemia and nonobstructive CA disease (INOCAD) (p=0.016), and the concentration of MMP-9 was the highest in the group with obstructive CA disease (p<0.001). The concentrations of MMP-13 and MMP-14 did not differ significantly between the groups. The highest VEGF concentrations were observed in the INOCAD group (p<0.001). The expression of miRNA-34a significantly differed between the IHD groups with different types of CA disease and controls (p <0.001). Patients with hemodynamically significant stenosis showed moderate relationships between the concentrations of MMP-14 and VEGF (ρ=0.418; p=0.024), as well as between VEGF and miRNA-34a (ρ=0.425; p=0.022). Patients with INOCAD had a significant negative correlation between the concentrations of MMP-13 and VEGF (ρ= -0.659; p=0.003). Correlation analysis showed in all IHD patients a moderate relationship of the concentrations of MMP-1 and MMP-14 with VEGF (ρ=0.449; p=0.002 and p=0.341; p=0.019, respectively). According to ROC analysis, a MMP-9 concentration above 4.83 ng/ml can be a predictor for the presence of hemodynamically significant CA obstruction in IHD patients; a VEGF concentration higher than 27.23 pg/ml suggests the absence of hemodynamically significant CA stenosis. CONCLUSION: IHD patients with INOCAD had the greatest increase in MMP-1, whereas patients with obstructive CA disease had the highest level of MMP-9. According to our data, concentrations of MMP-9 and VEGF can be used to predict the degree of CA obstruction. The expression of miRNA-34a was significantly higher in IHD patients with INOCAD and CA obstruction than in the control group, which suggested a miRNA-34a contribution to the development and progression of coronary atherosclerosis. In the future, it may be possible to use this miRNA as a diagnostic marker for IHD.

Coronary microvascular dysfunction and atrial reservoir function.

BACKGROUND: Coronary microvascular dysfunction (CMD) refers to structural and functional abnormalities of the coronary microcirculation, which may be diagnosed using invasive coronary physiology. CMD is responsible for impaired diastolic cardiac function. It has recently been suggested that left atrial strain (LASr) represents a highly sensitive tool for detecting cardiac diastolic function abnormalities. Accordingly, the aim of this study was to investigate the relationship between CMD and LASr. METHODS: Consecutively enrolled patients with non-obstructed coronary arteries (NOCA) underwent CMD and LASr evaluation by invasive thermodilution and noninvasive echocardiography, respectively. RESULTS: Forty-two (42) patients were included, out of which 26 presented with CMD. There were no significant differences between CMD-positive and negative patients in terms of clinical and echocardiographic characteristics. LASr was significantly reduced in patients with CMD (24.6% ± 6.1 vs. 30.3 ± 7.8%, p = 0.01). A moderate correlation was observed between coronary flow reserve and LAsr (r = 0.47, p = 0.002). A multivariate logistic regression analysis demonstrated that CMD was independently associated with LASr (OR = 0.88, 95%CI 0.78-0.99.135, p = 0.04). A LASr cut-off of 25.5% enabled an optimal classification of patients with or without CMD. CONCLUSION: Patients with NOCA and CMD had a significantly reduced LASr compared with patients without CMD, suggesting the early impairment of diastolic function in these patients.

The association between the triglyceride-glucose index and in-stent restenosis in patients undergoing percutaneous coronary intervention: a systematic review and meta-analysis.

BACKGROUND: Insulin resistance (IR) can lead to cellular metabolic disorders, activation of oxidative stress, and endothelial dysfunction, contributing to in-stent restenosis (ISR). The triglyceride-glucose index (TyG index), a new indicator reflecting IR, is extensively researched in the cardiovascular field. This study, through a meta-analysis, aimed to utilize a larger combined sample size and thereby enhance the overall test efficacy to explore the TyG index-ISR relationship. METHODS: A thorough search was conducted in the PubMed, EMBASE, Web of Science, and Cochrane Library databases to find original papers and their references published between 1990 and January 2024. This search included both prospective and retrospective studies detailing the correlation between the TyG index and ISR in individuals with coronary heart disease (CHD). OUTCOMES: The five included articles comprised 3,912 participants, and the odds ratio (OR) extracted from each study was combined using the Inverse Variance method. Results showed that, in the context of CHD patients, each incremental unit in the TyG index, when treated as a continuous variable, corresponded to a 42% elevation in ISR risk (95% CI 1.26-1.59, I²=13%, p < 0.005). When analyzing the TyG index categorically, the results revealed a higher ISR risk in the highest TyG index group compared to the lowest group (OR: 1.69, 95% CI 1.32-2.17, I²=0). Additionally, in patients with chronic coronary syndrome (CCS), each unit increase in the TyG index, the risk of ISR in patients increased by 37% (95% CI 1.19-1.57, I²=0%, p < 0.005). This correlation was also observable in acute coronary syndrome (ACS) patients (OR:1.48, 95% CI 1.19-1.85, I²=0, p < 0.005). CONCLUSIONS: The TyG index, an economical and precise surrogate for IR, is significantly linked with ISR. Furthermore, this correlation is unaffected by the type of coronary heart disease.

Insulin sensitivity estimates and their longitudinal association with coronary artery disease in type 1 diabetes. Does it matter?

BACKGROUND: Insulin resistance and chronic kidney disease are both associated with increased coronary artery disease risk. Many formulae estimating glucose disposal rate in type 1 diabetes infer insulin sensitivity from clinical data. We compare associations and performance relative to traditional risk factors and kidney disease severity between three formulae estimating the glucose disposal rate and coronary artery disease in people with type 1 diabetes. METHODS: The baseline glucose disposal rate was estimated by three (Williams, Duca, and Januszewski) formulae in FinnDiane Study participants and related to subsequent incidence of coronary artery disease, by baseline kidney status. RESULTS: In 3517 adults with type 1 diabetes, during median (IQR) 19.3 (14.6, 21.4) years, 539 (15.3%) experienced a coronary artery disease event, with higher rates with worsening baseline kidney status. Correlations between the three formulae estimating the glucose disposal rate were weak, but the lowest quartile of each formula was associated with higher incidence of coronary artery disease. Importantly, only the glucose disposal rate estimation by Williams showed a linear association with coronary artery disease risk in all analyses. Of the three formulae, Williams was the strongest predictor of coronary artery disease. Only age and diabetes duration were stronger predictors. The strength of associations between estimated glucose disposal rate and CAD incidence varied by formula and kidney status. CONCLUSIONS: In type 1 diabetes, estimated glucose disposal rates are associated with subsequent coronary artery disease, modulated by kidney disease severity. Future research is merited regarding the clinical usefulness of estimating the glucose disposal rate as a coronary artery disease risk factor and potential therapeutic target.

Temporal Relationship-Aware Treadmill Exercise Test Analysis Network for Coronary Artery Disease Diagnosis.

The treadmill exercise test (TET) serves as a non-invasive method for the diagnosis of coronary artery disease (CAD). Despite its widespread use, TET reports are susceptible to external influences, heightening the risk of misdiagnosis and underdiagnosis. In this paper, we propose a novel automatic CAD diagnosis approach. The proposed approach introduces a customized preprocessing method to obtain clear electrocardiograms (ECGs) from individual TET reports. Additionally, it presents TETDiaNet, a novel neural network designed to explore the temporal relationships within TET ECGs. Central to TETDiaNet is the TETDia block, which mimics clinicians' diagnostic processes to extract essential diagnostic information. This block encompasses an intra-state contextual learning module and an inter-state contextual learning module, modeling the temporal relationships within a single state and between states, respectively. These two modules help the TETDia block to capture effective diagnosis information by exploring the temporal relationships within TET ECGs. Furthermore, we establish a new TET dataset named TET4CAD for CAD diagnosis. It contains simplified TET reports for 192 CAD patients and 224 non-CAD patients, and each patient undergoes coronary angiography for labeling. Experimental results on TET4CAD underscore the superior performance of the proposed approach, highlighting the discriminative value of the temporal relationships within TET ECGs for CAD diagnosis.

Patients With Coronary Microvascular Dysfunction Have Less Circulating α-Klotho.

BACKGROUND: Coronary microvascular dysfunction (CMD) represents an early functional characteristic of coronary vascular aging. Klotho (α-klotho) is a circulating protein inversely linked to physiological aging. We examined low klotho as a potential marker for vascular aging in patients with CMD and no coronary artery disease. METHODS AND RESULTS: Patients undergoing nonurgent angiogram for chest pain who had no coronary artery disease underwent invasive coronary microvascular and endothelial function testing. CMD was defined by ≤50% increase in coronary blood flow (percentage change in coronary blood flow) in response to intracoronary acetylcholine or coronary flow reserve ≤2. Fresh arterial whole blood was used to analyze circulating endothelial progenitor cells with flow cytometry. Stored arterial plasma was used for klotho analysis by ELISA. Participants with CMD (n=62) were compared with those without CMD (n=36). Those with CMD were age 55±10 years (versus 51±11 years; P=0.07) and 73% women (versus 81%; P=0.38). Traditional risk factors for coronary artery disease were similar between groups. Patients with CMD had less klotho (0.88±1.50 versus 1.75±2.38 ng/mL; P=0.03), and the odds of low klotho in CMD were significant in a logistic regression model after adjusting for traditional cardiovascular risk factors (odds ratio [OR], 0.80 [95% CI, 0.636-0.996]; P=0.05). Higher klotho was associated with higher numbers of endothelial progenitor cells with vascular regenerative potential (CD34+ and CD34+CD133+KDR+). Among a subgroup of patients with atherosclerotic cardiovascular disease risk <5% (n=58), CMD remained associated with lower klotho (OR, 0.80 [95% CI, 0.636-0.996]; P=0.047). CONCLUSIONS: Klotho may be a biomarker for CMD and may be a therapeutic target for groups of patients without significant traditional cardiovascular risk.

Identification of diagnostic biomarkers and immune cell infiltration in coronary artery disease by machine learning, nomogram, and molecular docking.

Background: Coronary artery disease (CAD) is still a lethal disease worldwide. This study aims to identify clinically relevant diagnostic biomarker in CAD and explore the potential medications on CAD. Methods: GSE42148, GSE180081, and GSE12288 were downloaded as the training and validation cohorts to identify the candidate genes by constructing the weighted gene co-expression network analysis. Functional enrichment analysis was utilized to determine the functional roles of these genes. Machine learning algorithms determined the candidate biomarkers. Hub genes were then selected and validated by nomogram and the receiver operating curve. Using CIBERSORTx, the hub genes were further discovered in relation to immune cell infiltrability, and molecules associated with immune active families were analyzed by correlation analysis. Drug screening and molecular docking were used to determine medications that target the four genes. Results: There were 191 and 230 key genes respectively identified by the weighted gene co-expression network analysis in two modules. A total of 421 key genes found enriched pathways by functional enrichment analysis. Candidate immune-related genes were then screened and identified by the random forest model and the eXtreme Gradient Boosting algorithm. Finally, four hub genes, namely, CSF3R, EED, HSPA1B, and IL17RA, were obtained and used to establish the nomogram model. The receiver operating curve, the area under curve, and the calibration curve were all used to validate the accuracy and usefulness of the diagnostic model. Immune cell infiltrating was examined, and CAD patients were then divided into high- and low-expression groups for further gene set enrichment analysis. Through targeting the hub genes, we also found potential drugs for anti-CAD treatment by using the molecular docking method. Conclusions: CSF3R, EED, HSPA1B, and IL17RA are potential diagnostic biomarkers for CAD. CAD pathogenesis is greatly influenced by patterns of immune cell infiltration. Promising drugs offers new prospects for the development of CAD therapy.

Aetiology and predictors of major bleeding events in patients with heart failure with reduced ejection fraction undergoing percutaneous coronary intervention.

OBJECTIVES: We sought to determine the relationship between the degree of left ventricular ejection fraction (LVEF) impairment and the frequency and type of bleeding events after percutaneous coronary intervention (PCI). DESIGN: This was an observational retrospective cohort analysis. Patients who underwent PCI from 2009 to 2017 were identified from our institutional National Cardiovascular Disease Registry (NCDR) CathPCI database. Patients were stratified by pre-PCI LVEF: preserved (≥50%), mildly reduced (41%-49%) and reduced (≤40%) LVEF. PRIMARY OUTCOME MEASURES: The outcome was major bleeding, defined by NCDR criteria. Events were classified based on bleeding aetiology and analysed by multivariable logistic regression. RESULTS: Among 13 537 PCIs, there were 817 bleeding events (6%). The rate of bleeding due to any cause, blood transfusion, gastrointestinal bleeding and coronary artery perforation or tamponade each increased in a stepwise fashion comparing preserved, mildly reduced and reduced LVEF reduction (p<0.05 for all comparisons). However, there were no differences in bleeding due to asymptomatic drops in haemoglobin, access site haematoma or retroperitoneal bleeding. After multivariable adjustment, mildly reduced and reduced LVEF remained independent predictors of bleeding events (OR 1.36, 95% CI 1.06 to 1.74, p<0.05 and OR 1.73, 95% CI 1.45 to 2.06, p<0.0001). CONCLUSIONS: The degree of LV dysfunction is an independent predictor of post-PCI major bleeding events. Patients with mildly reduced or reduced LVEF are at greatest risk of post-PCI bleeding, driven by an increased need for blood transfusion, major GI bleeding events and coronary artery perforation or tamponade. Pre-PCI LV dysfunction does not predict asymptomatic declines in haemoglobin, access site haematoma or retroperitoneal bleeding.

Interplay Between Systemic Inflammation, Myocardial Injury, and Coronary Microvascular Dysfunction in Rheumatoid Arthritis: Results From the LiiRA Study.

BACKGROUND: Coronary microvascular dysfunction as measured by myocardial flow reserve (MFR) is associated with increased cardiovascular risk in rheumatoid arthritis (RA). The objective of this study was to determine the association between reducing inflammation with MFR and other measures of cardiovascular risk. METHODS AND RESULTS: Patients with RA with active disease about to initiate a tumor necrosis factor inhibitor were enrolled (NCT02714881). All subjects underwent a cardiac perfusion positron emission tomography scan to quantify MFR at baseline before tumor necrosis factor inhibitor initiation, and after tumor necrosis factor inhibitor initiation at 24 weeks. MFR <2.5 in the absence of obstructive coronary artery disease was defined as coronary microvascular dysfunction. Blood samples at baseline and 24 weeks were measured for inflammatory markers (eg, high-sensitivity C-reactive protein [hsCRP], interleukin-1b, and high-sensitivity cardiac troponin T [hs-cTnT]). The primary outcome was mean MFR before and after tumor necrosis factor inhibitor initiation, with Δhs-cTnT as the secondary outcome. Secondary and exploratory analyses included the correlation between ΔhsCRP and other inflammatory markers with MFR and hs-cTnT. We studied 66 subjects, 82% of which were women, mean RA duration 7.4 years. The median atherosclerotic cardiovascular disease risk was 2.5%; 47% had coronary microvascular dysfunction and 23% had detectable hs-cTnT. We observed no change in mean MFR before (2.65) and after treatment (2.64, P=0.6) or hs-cTnT. A correlation was observed between a reduction in hsCRP and interleukin-1b with a reduction in hs-cTnT. CONCLUSIONS: In this RA cohort with low prevalence of cardiovascular risk factors, nearly 50% of subjects had coronary microvascular dysfunction at baseline. A reduction in inflammation was not associated with improved MFR. However, a modest reduction in interleukin-1b and no other inflammatory pathways was correlated with a reduction in subclinical myocardial injury. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02714881.

The association between C-reactive protein and coronary artery calcification: a systematic review and meta-analysis.

BACKGROUND: While coronary artery calcification (CAC) is recognized as a reliable marker for coronary atherosclerosis, the relationship between the concentration of C-reactive protein (CRP) and the incidence and progression of CAC remains controversial. METHOD: PubMed, Embase, Web of Science, and Scopus were systematically searched to identify relevant observational studies until October 2023. The methodological quality of the included studies was evaluated using the Newcastle-Ottawa Scale (NOS). A random-effects meta-analysis was employed to calculate pooled odd ratios (OR) and corresponding 95% confidence intervals, considering heterogeneity among the studies. RESULTS: Out of the 2545 records, 42 cross-sectional and 9 cohort studies were included in the systematic review. The meta-analysis on 12 eligible cross-sectional studies revealed no significant association between CAC and CRP [pooled OR: 1.03 (1.00, 1.06)]. Additionally, an insignificant association was found between CAC and CRP through meta-analysis on three eligible cohort studies [pooled OR: 1.05 (0.95, 1.15)] with no considerable heterogeneity across studies. Sensitivity analyses indicated that the meta-analysis models were robust. There was no evidence of publication bias. CONCLUSION: Based on the meta-analysis findings, elevated levels of CRP did not emerge as a valuable prognostic maker for CAC incidence and progression prediction.

Health information-seeking behavior in patients with coronary artery disease: Activating methods.

INTRODUCTION: Coronary artery disease (CAD) has a high mortality rate worldwide, and continuous health behavior practice and careful management are required owing to risks such as rapid changes in symptoms and emergency hospitalization. The utilization of health-related information is an important factor for long-term disease management in patients with CAD. For this purpose, an understanding of health information-seeking behavior is needed first. METHODS: This study analyzed data from the 2021 Korea Medical Panel Survey, and logistic regression analysis was conducted to confirm the factors influencing the health information-seeking behavior of patients with CAD. RESULTS: The health information-seeking behavior of patients with CAD differed according to demographic characteristics, and differences in preferred information use were confirmed. Finally, it was identified that insufficient levels of health literacy were a major reason for CAD patients not engaging in health information-seeking behaviors (OR, 0.17; 95% CI, 0.09-0.33; p < 0.001). CONCLUSION: This study suggests that to improve health information-seeking behaviors, the application of education and intervention programs to increase the level of health literacy is necessary.

Acute myocardial infarction due to giant coronary artery aneurysm and arteriovenous fistula: a challenging case report and review of the literature.

BACKGROUND: A coronary artery aneurysm (CAA) is an abnormal dilation of a coronary artery segment often accompanied by coronary artery fistula (CAF), leading to communication between a coronary artery and a cardiac chamber or a part of the coronary venous system. Both CAAs and CAFs can present with symptoms and signs of myocardial ischemia and infarction. CASE PRESENTATION: We describe the case of a 46-year-old woman with non-ST-elevation myocardial infarction (NSTEMI) caused by a "giant" CAA. Various imaging modalities revealed a thrombus-containing aneurysm located at the right-posterior cardiac border, with established arteriovenous communication with the distal part of left circumflex artery (LCx). After initial treatment with dual antiplatelet therapy, a relapse of pain was reported along with a new increase in troponin levels, electrocardiographic abnormalities, reduced left ventricular ejection fraction (LVEF) and thrombus enlargement. Surgical excision of the aneurysm was favored, revealing its true size of 6 cm in diameter. Τhe aneurysm was excised without complications. The patient remained asymptomatic during follow-up. CONCLUSIONS: Management of rare entities such as "giant" CAAs and CAFs can be challenging. Cases such as this can serve as precedents to facilitate treatment plans and develop consistent recommendations, emphasizing the importance of personalized strategies for future patients.

AttGRU-HMSI: enhancing heart disease diagnosis using hybrid deep learning approach.

Heart disease is a major global cause of mortality and a major public health problem for a large number of individuals. A major issue raised by regular clinical data analysis is the recognition of cardiovascular illnesses, including heart attacks and coronary artery disease, even though early identification of heart disease can save many lives. Accurate forecasting and decision assistance may be achieved in an effective manner with machine learning (ML). Big Data, or the vast amounts of data generated by the health sector, may assist models used to make diagnostic choices by revealing hidden information or intricate patterns. This paper uses a hybrid deep learning algorithm to describe a large data analysis and visualization approach for heart disease detection. The proposed approach is intended for use with big data systems, such as Apache Hadoop. An extensive medical data collection is first subjected to an improved k-means clustering (IKC) method to remove outliers, and the remaining class distribution is then balanced using the synthetic minority over-sampling technique (SMOTE). The next step is to forecast the disease using a bio-inspired hybrid mutation-based swarm intelligence (HMSI) with an attention-based gated recurrent unit network (AttGRU) model after recursive feature elimination (RFE) has determined which features are most important. In our implementation, we compare four machine learning algorithms: SAE + ANN (sparse autoencoder + artificial neural network), LR (logistic regression), KNN (K-nearest neighbour), and naïve Bayes. The experiment results indicate that a 95.42% accuracy rate for the hybrid model's suggested heart disease prediction is attained, which effectively outperforms and overcomes the prescribed research gap in mentioned related work.

Matrix metallopeptidase 9 contributes to the beginning of plaque and is a potential biomarker for the early identification of atherosclerosis in asymptomatic patients with diabetes.

Aims: To determine the roles of matrix metallopeptidase-9 (MMP9) on human coronary artery smooth muscle cells (HCASMCs) in vitro, early beginning of atherosclerosis in vivo in diabetic mice, and drug naïve patients with diabetes. Methods: Active human MMP9 (act-hMMP9) was added to HCASMCs and the expressions of MCP-1, ICAM-1, and VCAM-1 were measured. Act-hMMP9 (n=16) or placebo (n=15) was administered to diabetic KK.Cg-Ay/J (KK) mice. Carotid artery inflammation and atherosclerosis measurements were made at 2 and 10 weeks after treatment. An observational study of newly diagnosed drug naïve patients with type 2 diabetes mellitus (T2DM n=234) and healthy matched controls (n=41) was performed and patients had ultrasound of carotid arteries and some had coronary computed tomography angiogram for the assessment of atherosclerosis. Serum MMP9 was measured and its correlation with carotid artery or coronary artery plaques was determined. Results: In vitro, act-hMMP9 increased gene and protein expressions of MCP-1, ICAM-1, VCAM-1, and enhanced macrophage adhesion. Exogenous act-hMMP9 increased inflammation and initiated atherosclerosis in KK mice at 2 and 10 weeks: increased vessel wall thickness, lipid accumulation, and Galectin-3+ macrophage infiltration into the carotid arteries. In newly diagnosed T2DM patients, serum MMP9 correlated with carotid artery plaque size with a possible threshold cutoff point. In addition, serum MMP9 correlated with number of mixed plaques and grade of lumen stenosis in coronary arteries of patients with drug naïve T2DM. Conclusion: MMP9 may contribute to the initiation of atherosclerosis and may be a potential biomarker for the early identification of atherosclerosis in patients with diabetes. Clinical trial registration: https://clinicaltrials.gov, identifier NCT04424706.