Signaling Pathways Associated With Prior Cardiovascular Events in Hypertrophic Cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiomyopathy. A subset of patients experience major adverse cardiovascular events (MACEs), including arrhythmias, strokes and heart failure. However, the molecular mechanisms underlying MACEs in HCM are still not well understood. Therefore, we conducted a multicenter case-control study of patients with HCM, comparing those with and without prior histories of MACEs to identify dysregulated signaling pathways through plasma proteomics profiling. METHODS: We performed plasma proteomics profiling of 4986 proteins. We developed a proteomics-based discrimination model in patients enrolled at 1 institution (training set) and externally validated the model in patients enrolled at another institution (test set). We performed pathway analysis of proteins dysregulated in patients with prior MACEs. RESULTS: A total of 402 patients were included, with 278 in the training set and 124 in the test set. In this cohort, 257 (64%) patients had prior MACEs (172 in the training set and 85 in the test set). Using the proteomics-based model from the training set, the area under the receiver operating characteristic curve was 0.82 (95% confidence interval, 0.75-0.90) in the test set. Patients with prior MACEs demonstrated dysregulation in pathways known to be associated with MACEs (eg, TGF-ß) and novel pathways (eg, Ras-MAPK and associated pathways). CONCLUSIONS: In this multicenter study of 402 patients with HCM, we identified both known and novel pathways dysregulated in a subset of patients with more advanced disease.

Safety-Net Hospital Status Is Associated With Coronary Artery Bypass Grafting Outcomes at an Urban Academic Medical Center.

INTRODUCTION: Socioeconomic disparities impact outcomes after cardiac surgery. At our institution, cardiac surgery cases from the safety-net, county funded hospital (CH), which primarily provides care for underserved patients, are performed at the affiliated university hospital. We aimed to investigate the association of socioeconomic factors and CH referral status with outcomes after coronary artery bypass grafting (CABG). METHODS: The institutional Adult Cardiac Surgery database was queried for perioperative and demographic data from patients who underwent isolated CABG between January 2014 and June 2020. The primary outcome was major adverse cardiovascular event (MACE), a composite of postoperative myocardial infarction, stroke, or death. Secondary outcomes included individual complications. Chi-square, Wilcoxon rank-sum, and logistic regression analyses were used to compare differences between CH and non-CH cohorts. RESULTS: We included 836 patients with 472 (56.5%) from CH. Compared to the non-CH cohort, CH patients were younger, more likely to be Hispanic, non-English speaking, and be completely uninsured or require state-specific financial assistance. CH patients were more likely to have a history of tobacco and drug use, liver disease, diabetes, prior myocardial infarction, and greater degrees of left main coronary and left anterior descending artery stenosis. CH cases were less likely to be elective. The incidence of MACE was significantly higher in the CH cohort (16.3% versus 8.2%, P = 0.001). There were no significant differences in 30-d mortality, home discharge, prolonged mechanical ventilation, bleeding, sepsis, pneumonia, new dialysis requirement, cardiac arrest, or multiorgan system failure between cohorts. CH patients were more likely to develop renal failure and less likely to develop atrial fibrillation. On multivariable analysis, CH status (odds ratio 2.39, 95% confidence interval 1.25-4.55, P = 0.008) was independently associated with MACE. CONCLUSIONS: CH patients undergoing CABG presented with greater comorbidity burden, more frequently required nonelective surgery, and are at significantly higher risk of postoperative MACE.

Coronary Artery Calcification on Low-Dose Lung Cancer Screening CT in South Korea: Visual and Artificial Intelligence-Based Assessment and Association With Cardiovascular Events.

BACKGROUND. Coronary artery calcification (CAC) on lung cancer screening low-dose chest CT (LDCT) is a cardiovascular risk marker. South Korea was the first Asian country to initiate a national LDCT lung cancer screening program, although CAC-related outcomes are poorly explored. OBJECTIVE. The purpose of this article is to evaluate CAC prevalence and severity using visual analysis and artificial intelligence (AI) methods and to characterize CAC's association with major adverse cardiovascular events (MACEs) in patients undergoing LDCT in Korea's national lung cancer screening program. METHODS. This retrospective study included 1002 patients (mean age, 62.4 ± 5.4 [SD] years; 994 men, eight women) who underwent LDCT at two Korean medical centers between April 2017 and May 2023 as part of Korea's national lung cancer screening program. Two radiologists independently assessed CAC presence and severity using visual analysis, consulting a third radiologist to resolve differences. Two AI software applications were also used to assess CAC presence and severity. MACE occurrences were identified by EMR review. RESULTS. Interreader agreement for CAC presence and severity, expressed as kappa, was 0.793 and 0.671, respectively. CAC prevalence was 53.4% by consensus visual assessment, 60.1% by AI software I, and 56.6% by AI software II. CAC severity was mild, moderate, and severe by consensus visual analysis in 28.0%, 10.3%, and 15.1%; by AI software I in 39.9%, 14.0%, and 6.2%; and by AI software II in 34.9%, 14.3%, and 7.3%. MACEs occurred in 36 of 625 (5.6%) patients with follow-up after LDCT (median, 1108 days). MACE incidence in patients with no, mild, moderate, and severe CAC for consensus visual analysis was 1.1%, 5.0%, 2.9%, and 8.6%, respectively (p < .001); for AI software I, it was 1.3%, 3.0%, 7.9%, and 11.3% (p < .001); and for AI software II, it was 1.2%, 3.4%, 7.7%, and 9.6% (p < .001). CONCLUSION. For Korea's national lung cancer screening program, MACE occurrence increased significantly with increasing CAC severity, whether assessed by visual analysis or AI software. The study is limited by the large sex imbalance for Korea's national lung cancer screening program. CLINICAL IMPACT. The findings provide reference data for health care practitioners engaged in developing and overseeing national lung cancer screening programs, highlighting the importance of routine CAC evaluation.

Glycemic control target for liver and cardiovascular events risk in metabolic dysfunction-associated steatotic liver disease.

AIMS: Optimizing glycemic control may prevent liver-related events and major adverse cardiovascular events (MACE) in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). However, the optimal hemoglobin A1c (HbA1c) threshold associated with a lower risk of complications, particularly liver-related events as well as MACE is unknown. METHODS: We investigated a nationwide population-based cohort and identified 633 279 patients with MASLD, with a mean follow-up of 4.2 years. Hemoglobin A1c levels were measured annually. The primary endpoint was the risk of liver-related events and MACE and to determine the optimal HbA1c level associated with the risk of complications. RESULTS: Mean HbA1c (per 1%) was associated with liver-related events (subdistribution hazard ratio [sHR] 1.26; 95% confidence interval [CI], 1.12-1.42) as well as MACE (sHR 1.36; 95% CI, 1.32-1.41) after adjustment for confounders. Multivariable sHR (95% CI) for HbA1c of <5.0%, 6.0%-6.9%, 7.0%-7.9%, 8.0%-8.9%, and ≥9.0% (reference, 5.0%-5.9%) were 14 (9.1-22), 1.70 (1.2-2.3), 3.32 (2.3-4.8), 3.81 (2.1-6.8), and 4.83 (2.4-9.6) for liver-related events, and 1.24 (0.8-1.8), 1.27 (1.2-1.4), 1.70 (1.5-2.0), 2.36 (1.9-2.9), and 4.17 (3.5-5.0) for MACE. An HbA1c level of 7% was selected as the optimal threshold for predicting complications (sHR 2.40 [1.8-3.2] for liver-related events and 1.98 [1.8-2.2] for MACE). CONCLUSION: The risk of liver-related events as well as MACE increased in a dose-dependent fashion with an increase in HbA1c levels, except for patients with HbA1c <5.0% for liver-related events. An HbA1c level of 7% was the optimal threshold associated with a lower risk of complications and may be utilized as a target for glycemic control in patients with MASLD.

Improving cardiovascular risk prediction with machine learning: a focus on perivascular adipose tissue characteristics.

BACKGROUND: Timely prevention of major adverse cardiovascular events (MACEs) is imperative for reducing cardiovascular diseases-related mortality. Perivascular adipose tissue (PVAT), the adipose tissue surrounding coronary arteries, has attracted increased amounts of attention. Developing a model for predicting the incidence of MACE utilizing machine learning (ML) integrating clinical and PVAT features may facilitate targeted preventive interventions and improve patient outcomes. METHODS: From January 2017 to December 2019, we analyzed a cohort of 1077 individuals who underwent coronary CT scanning at our facility. Clinical features were collected alongside imaging features, such as coronary artery calcium (CAC) scores and perivascular adipose tissue (PVAT) characteristics. Logistic regression (LR), Framingham Risk Score, and ML algorithms were employed for MACE prediction. RESULTS: We screened seven critical features to improve the practicability of the model. MACE patients tended to be older, smokers, and hypertensive. Imaging biomarkers such as CAC scores and PVAT characteristics differed significantly between patients with and without a 3-year MACE risk in a population that did not exhibit disparities in laboratory results. The ensemble model, which leverages multiple ML algorithms, demonstrated superior predictive performance compared with the other models. Finally, the ensemble model was used for risk stratification prediction to explore its clinical application value. CONCLUSIONS: The developed ensemble model effectively predicted MACE incidence based on clinical and imaging features, highlighting the potential of ML algorithms in cardiovascular risk prediction and personalized medicine. Early identification of high-risk patients may facilitate targeted preventive interventions and improve patient outcomes.

Long-term prognostic value of thyroid hormones in left ventricular noncompaction.

PURPOSE: Thyroid function is closely related to the prognosis of cardiovascular diseases. This study aimed to explore the predictive value of thyroid hormones for adverse cardiovascular outcomes in left ventricular noncompaction (LVNC). METHODS: This longitudinal cohort study enrolled 388 consecutive LVNC patients with complete thyroid function profiles and comprehensive cardiovascular assessment. Potential predictors for adverse outcomes were thoroughly evaluated. RESULTS: Over a median follow-up of 5.22 years, primary outcome (the combination of cardiovascular mortality and heart transplantation) occurred in 98 (25.3%) patients. For secondary outcomes, 75 (19.3%) patients died and 130 (33.5%) patients experienced major adverse cardiovascular events (MACE). Multivariable Cox analysis identified that free triiodothyronine (FT3) was independently associated with both primary (HR 0.455, 95%CI 0.313-0.664) and secondary (HR 0.547, 95%CI 0.349-0.858; HR 0.663, 95%CI 0.475-0.925) outcomes. Restricted cubic spline analysis illustrated that the risk for adverse outcomes increased significantly with the decline of serum FT3. The LVNC cohort was further stratified according to tertiles of FT3 levels. Individuals with lower FT3 levels in the tertile 1 group suffered from severe cardiac dysfunction and remodeling, resulting in higher incidence of mortality and MACE (Log-rank P < 0.001). Subgroup analysis revealed that lower concentration of FT3 was linked to worse prognosis, particularly for patients with left atrial diameter ≥ 40 mm or left ventricular ejection fraction ≤ 35%. Adding FT3 to the pre-existing risk score for MACE in LVNC improved its predictive performance. CONCLUSION: Through the long-term investigation on a large LVNC cohort, we demonstrated that low FT3 level was an independent predictor for adverse cardiovascular outcomes.

Clinical impact of Academic Research Consortium for High Bleeding-Risk scores on clinical outcomes in patients with stable coronary artery disease undergoing percutaneous coronary intervention.

High bleeding risk (HBR), as defined by the Academic Research Consortium for High Bleeding Risk (ARC-HBR) criteria, has been recently reported to be associated with an increased risk of major bleeding events and cardiovascular events. We investigated the association between the ARC-HBR score and clinical outcomes in patients with stable coronary artery disease (CAD) who underwent percutaneous coronary intervention (PCI). We assessed 328 consecutive patients with stable CAD who underwent PCI between January 2017 and December 2020. We scored the ARC-HBR criteria by assigning 1 point to each major criterion and 0.5 points to each minor criterion. Patients were stratified into low (ARC-HBR score < 1), intermediate (1 ≤ ARC-HBR score < 2), and high (ARC-HBR score ≥ 2) bleeding-risk groups. The primary outcome measure was major adverse cardiovascular events (MACE), defined as a composite of all-cause death, nonfatal myocardial infarction, and nonfatal stroke. We compared the discriminative abilities of the ARC-HBR score with the Thrombolysis in Myocardial Infarction Risk Score for Secondary Prevention (TRS2°P) and ARC-HBR score with Coronary Revascularization Demonstrating Outcome Study in Kyoto (CREDO-Kyoto) thrombotic risk score. The mean patient age was 70.1 ± 10.2 years (males, 76.8%). During the median follow-up period of 983 (618-1338) days, 44 patients developed MACE. Kaplan-Meier curves showed that a stepwise significant increase in the cumulative incidence of MACE as the ARC-HBR score increased (log-rank p < 0.001). In the time-dependent receiver-operating characteristic curve analysis for predicting MACE within 2 years, the area under the curve (AUC) of the ARC-HBR score was significantly higher than that of the TRS2°P (AUC: 0.825 vs. 0.725, p value for the difference = 0.023) and similar to that of CREDO-Kyoto thrombotic risk score (AUC: 0.825 vs. 0.813, p value for the difference = 0.627). Conclusions: The ARC-HBR score adequately stratified future risk of MACE in patients with stable CAD who underwent PCI. The ARC-HBR score showed a higher discriminative ability for predicting mid-term MACE than the TRS2°P.

Predicting major adverse cardiovascular events within 3 years by optimization of radiomics model derived from pericoronary adipose tissue on coronary computed tomography angiography: a case-control study.

BACKGROUND: Coronary inflammation induces changes in pericoronary adipose tissue (PCAT) can be detected by coronary computed tomography angiography (CCTA). Our aim was to investigate whether different PCAT radiomics model based on CCTA could improve the prediction of major adverse cardiovascular events (MACE) within 3 years. METHODS: This retrospective study included 141 consecutive patients with MACE and matched to patients with non-MACE (n = 141). Patients were randomly assigned into training and test datasets at a ratio of 8:2. After the robust radiomics features were selected by using the Spearman correlation analysis and the least absolute shrinkage and selection operator, radiomics models were built based on different machine learning algorithms. The clinical model was then calculated according to independent clinical risk factors. Finally, an overall model was established using the radiomics features and the clinical factors. Performance of the models was evaluated for discrimination degree, calibration degree, and clinical usefulness. RESULTS: The diagnostic performance of the PCAT model was superior to that of the RCA-model, LAD-model, and LCX-model alone, with AUCs of 0.723, 0.675, 0.664, and 0.623, respectively. The overall model showed superior diagnostic performance than that of the PCAT-model and Cli-model, with AUCs of 0.797, 0.723, and 0.706, respectively. Calibration curve showed good fitness of the overall model, and decision curve analyze demonstrated that the model provides greater clinical benefit. CONCLUSION: The CCTA-based PCAT radiomics features of three major coronary arteries have the potential to be used as a predictor for MACE. The overall model incorporating the radiomics features and clinical factors offered significantly higher discrimination ability for MACE than using radiomics or clinical factors alone.

Early coronary angiography in NSTEMI: a regional Victorian perspective.

BACKGROUND: Current guidelines highlight a paucity of evidence guiding optimal timing for non-ST-elevation myocardial infarction (NSTEMI) in high-risk and non-high-risk cases. AIM: We assessed long-term major adverse cardiovascular events (MACEs) in NSTEMI patients undergoing early (<24 h) versus delayed (>24 h) coronary angiography at 6 years. Secondary end-points included all-cause mortality and cumulative MACE outcomes. METHODS: Baseline characteristics and clinical outcomes were assessed among 355 patients presenting to a tertiary regional hospital between 2017 and 2018. Cox proportional hazard models were generated for MACE and all-cause mortality outcomes, adjusting for the Global Registry of Acute Coronary Events (GRACE) score, patient demographics, biomarkers and comorbidities. RESULTS: Two hundred and seventy patients were included; 147 (54.4%) and 123 (45.6%) underwent early and delayed coronary angiography respectively. Median time to coronary angiography was 13.3 and 45.4 h respectively. At 6 years, 103 patients (38.1%) experienced MACE; 41 in the early group and 62 in the delayed group (hazard ratio (HR) = 2.23; 95% confidence interval (CI) = 1.50-3.31). After multivariable adjustment, the delayed group had higher rates of MACE (HR = 1.79; 95% CI = 1.19-2.70), all-cause mortality (HR = 2.76; 95% CI = 1.36-5.63) and cumulative MACE (incidence rate ratio = 1.54; 95% CI = 1.12-2.11). Subgroup analysis of MACE outcomes in rural and weekend NSTEMI presentations was not significant between early and delayed coronary angiography (HR = 1.49; 95% CI = 0.83-2.62). CONCLUSION: Higher MACE rates in the delayed intervention group suggest further investigation is needed. Randomised control trials would be well suited to assess the role of early invasive intervention across all NSTEMI risk groups.

The Impact of Systemic Inflammation Response Index on the Prognosis of Patients with ST-Segment Elevation Myocardial Infarction Undergoing Percutaneous Coronary Intervention.

Background: Inflammation is essential in cardiovascular disease (CVD) development and progression. A novel inflammatory parameter, the systemic inflammation response index (SIRI), has been proven to predict cancer prognosis strongly. Little is known about the relationship between SIRI and outcomes in patients with ST-segment elevation myocardial infarction (STEMI). Methods: 1312 STEMI patients who underwent percutaneous coronary intervention (PCI) in Beijing Anzhen hospital from January 2019 to December 2021 were analyzed. SIRI was calculated as neutrophils × monocytes/lymphocytes. Our primary outcome was a 30-day major adverse event (MACE), including all-cause mortality, non-fatal myocardial infarction (MI), stroke, incident heart failure (HF), cardiogenic shock, and cardiac arrest. Results: Patients were stratified into four groups according to quartiles of SIRI: SIRI < 1.58 (n = 328), 1.58 ≤ SIRI < 3.28 (n = 328), 3.28 ≤ SIRI < 7.80 (n = 328), SIRI ≥ 7.80 (n = 328). Higher SIRI was associated with a higher incidence of the 30-day MACE. The rates of 30-day MACE were 6.1%, 8.8%, 12.8%, and 17.1% (p < 0.001) for the lowest SIRI quartile to the highest quartile, respectively. This association was consistent in the outcome of HF but no other components. Higher SIRI indicated higher 30-day MACE incidence in most participants except in those with very high inflammatory indicators. Subgroup analysis showed this correlation was consistent in various subgroups (p for interaction > 0.05). Conclusions: In patients with STEMI, higher SIRI indicated a higher incidence of 30-day MACE, except for those with very high inflammatory indicators. In most STEMI patients, SIRI might be a trustworthy indicator of short-term prognosis.

Remnant Cholesterol to Lymphocyte Ratio as a New Predictor of Prognosis in Patients with Unstable Angina Undergoing Percutaneous Coronary Intervention.

Background: Inflammatory cells and remnant cholesterol (RC) play an important role in the development and progression of cardiovascular diseases. In order to understand their contribution to cardiovascular diseases, we proposed the RC to lymphocyte ratio (RCLR) that reflects the level of serum lipid and inflammation as a predictive indicator. In this study, we explored the correlation between RCLR and major adverse cardiovascular events (MACEs) in patients with unstable angina (UA) treated with percutaneous coronary intervention (PCI). Methods: RCLR was calculated by dividing RC by lymphocyte percentage. Patients were divided into four groups according to RCLR quartiles. The endpoint of the study was MACE, a composite endpoint including all-cause mortality, non-fatal myocardial infarction (MI), and ischemia­driven revascularization. The multivariable Cox proportional hazard model was used to determine the exclusive effect of RCLR on MACE. Results: The study was conducted on 1092 patients with UA. The rate of MACE increased as RCLR quartiles increased (quartile 4 vs quartile 1: 40.9% vs 9.2%, p < 0.001). An adjustment for confounding variables revealed that an increase in the rate of MACE was directly proportional to RCLR (quartile 4 vs quartile 1: HR - 5.85 [95% CI, 3.77-9.08], p < 0.001, p for trend < 0.001). Conclusions: RCLR independently correlated with the incidence of MACE in patients with UA treated with PCI.

Long-term outcomes of COVID-19 survivors with hospital AKI: association with time to recovery from AKI.

BACKGROUND: Although coronavirus disease 2019 (COVID-19) patients who develop in-hospital acute kidney injury (AKI) have worse short-term outcomes, their long-term outcomes have not been fully characterized. We investigated 90-day and 1-year outcomes after hospital AKI grouped by time to recovery from AKI. METHODS: This study consisted of 3296 COVID-19 patients with hospital AKI stratified by early recovery (<48 hours), delayed recovery (2-7 days) and prolonged recovery (>7-90 days). Demographics, comorbidities and laboratory values were obtained at admission and up to the 1-year follow-up. The incidence of major adverse cardiovascular events (MACE) and major adverse kidney events (MAKE), rehospitalization, recurrent AKI and new-onset chronic kidney disease (CKD) were obtained 90-days after COVID-19 discharge. RESULTS: The incidence of hospital AKI was 28.6%. Of the COVID-19 patients with AKI, 58.0% experienced early recovery, 14.8% delayed recovery and 27.1% prolonged recovery. Patients with a longer AKI recovery time had a higher prevalence of CKD (P < .05) and were more likely to need invasive mechanical ventilation (P < .001) and to die (P < .001). Many COVID-19 patients developed MAKE, recurrent AKI and new-onset CKD within 90 days, and these incidences were higher in the prolonged recovery group (P < .05). The incidence of MACE peaked 20-40 days postdischarge, whereas MAKE peaked 80-90 days postdischarge. Logistic regression models predicted 90-day MACE and MAKE with 82.4 ± 1.6% and 79.6 ± 2.3% accuracy, respectively. CONCLUSION: COVID-19 survivors who developed hospital AKI are at high risk for adverse cardiovascular and kidney outcomes, especially those with longer AKI recovery times and those with a history of CKD. These patients may require long-term follow-up for cardiac and kidney complications.

The clinical utility of circulating cell division control 42 in small-vessel coronary artery disease patients undergoing drug-coated balloon treatment.

BACKGROUND: Cell division control 42 (CDC42) regulates atherosclerosis, blood lipids, and inflammation and thus affects coronary artery disease (CAD), but its utility in drug-coated balloon (DCB)-treated small-vessel CAD (SV-CAD) patients is unclear. This study intended to evaluate the change and prognostic role of CDC42 in SV-CAD patients underwent DCB. METHODS: Serum CDC42 was measured by enzyme-linked immunosorbent assay in 211 SV-CAD patients underwent DCB at baseline, day (D) 1, D3, and D7, as well as in 50 healthy controls (HCs). RESULTS: CDC42 was decreased in SV-CAD patients compared to HCs (P < 0.001), and it was negatively associated with total cholesterol (P = 0.015), low-density lipoprotein cholesterol (P = 0.003), C-reactive protein (P = 0.001), multivessel disease (P = 0.020), and American college of cardiology/American heart association type B2/C lesions (P = 0.039) in SV-CAD patients. Longitudinally, CDC42 decreased from baseline to D1 and then gradually increased to D7 (P < 0.001) in SV-CAD patients after DCB. Interestingly, high CDC42 (cut-off value = 500 pg/mL) at baseline (P = 0.047), D3 (P = 0.046), and D7 (P = 0.008) was associated with a lower accumulating target lesion failure (TLF) rate; high CDC42 at D3 (P = 0.037) and D7 (P = 0.041) was related to a lower accumulating major adverse cardiovascular event (MACE) rate in SV-CAD patients underwent DCB. Importantly, CDC42 at D7 (high vs. low) independently predicted lower accumulating TLF (hazard ratio (HR) = 0.145, P = 0.021) and MACE (HR = 0.295, P = 0.023) risks in SV-CAD patients underwent DCB. CONCLUSIONS: Circulating CDC42 level relates to milder disease conditions and independently estimates lower risks of TLF and MACE in SV-CAD patients underwent DCB, but further validation is still needed.

Comparison of two diagnostic strategies for patients with stable chest pain suggestive of chronic coronary syndrome: rationale and design of the double-blind, pragmatic, randomized and controlled OPERATE Trial.

BACKGROUND: To achieve potential financial savings and avoid exposing the patients to unnecessary risk, an optimal diagnostic strategy to identify low risk individual who may derive minimal benefit from further cardiac imaging testing (CIT) is important for patients with stable chest pain (SCP) suggestive of chronic coronary syndrome (CCS). Although several diagnostic strategies have been recommended by the most recent guidelines, few randomized controlled trials (RCTs) have prospectively investigated the actual effect of applying these strategies in clinical practice. METHODS: OPERATE (OPtimal Evaluation of stable chest pain to Reduce unnecessAry utilization of cardiac imaging TEsting) trial is an investigator-initiated, multicenter, coronary computed tomography angiography (CCTA)-based, 2-arm parallel-group, double-blind, pragmatic and confirmative RCT planning to include 800 subjects with SCP suggestive of CCS. After enrollment, all subjects will be randomized to two arms (2016 U.K. National Institute of Health and Care Excellence guideline-determined and 2019 European Society of Cardiology guideline-determined diagnostic strategy) on a 1:1 basis. According to each strategy, CCTA should be referred and deferred for a subject in high and low risk group, respectively. The primary (effectiveness) endpoint is CCTA without obstructive coronary artery disease. Safety of each strategy will be mainly assessed by 1-year major adverse cardiovascular event rates. DISCUSSION: The OPERATE trial will provide comparative effectiveness and safety evidences for two different diagnostic strategies for patients with SCP suggestive of CCS, with the intension of improving the diagnostic yield of CCTA at no expense of safety. CLINICAL TRIAL REGISTRATION: ClinicalTrial.org Identifier NCT05640752.

Time-dependent changes in P2Y12 reaction unit values for predicting the different types of cardiovascular events in patients with ischemic heart disease.

Several studies have investigated the association between P2Y12 reaction unit (PRU) value and major adverse cardiovascular events (MACEs) in patients with ischemic heart disease, but there is no well-established consensus on the utility of PRU value. Furthermore, the optimal PRU cut-off value varied with studies. One reason may be that the endpoints and observation periods differed, depending on the study. This study aimed to investigate the optimal cut-off and predictive ability of the PRU value for predicting cardiovascular events, while considering different endpoints and observation periods. We surveyed a total of 338 patients receiving P2Y12 inhibitors and measured PRU during cardiac catheterization. Using time-dependent receiver operating characteristic analysis, we evaluated the cut-off and area under curve (AUC) of the PRU value for two MACEs (MACE ①: composite of death, myocardial infarction, stent thrombosis, and cerebral infarction; MACE ②: composite of MACE ① and target vessel revascularization) at 6, 12, 24 and 36 months after cardiac catheterization. MACE ① occurred in 18 cases and MACE ② in 32 cases. The PRU cut-off values at 6, 12, 24, and 36 months were 257, 238, 217, and 216, respectively, for MACE ① and 250, 238, 209, and 204, respectively, for MACE ②. The AUCs at 6, 12, 24, and 36 months were 0.753, 0.832, 0.718, and 0.717, respectively, for MACE ① and 0.724, 0.722, 0.664, and 0.682, respectively, for MACE ②. The optimal cut-off and predictive ability of PRU values for cardiovascular events varied depending on different endpoints and duration of the observation periods. A relatively high PRU value is effective for short-term event suppression, but a low value is required for long-term event suppression.

The clinical role of serum cell division control 42 in coronary heart disease.

Cell division control 42 (CDC42) regulates blood lipids, atherosclerosis, T cell differentiation and inflammation, which is involved in the process of coronary heart disease (CHD). This study aimed to evaluate the CDC42 level and its correlation with clinical features, the T-helper 17 (Th17)/regulatory-T (Treg) cell ratio and prognosis in CHD patients. In total, 210 CHD patients, 20 healthy controls and 20 disease controls were enrolled. Serum CDC42 levels of all participants were measured by enzyme-linked immunosorbent assay. In CHD patients, Th17 and Treg cells were discovered by flow cytometry; CHD patients were followed-up for a median of 16.9 months (range of 2.5-38.2 months). CDC42 level was lowest in CHD patients (median (interquartile range (IQR)): 402.5 (287.3-599.0) pg/mL), moderate in disease controls (median (IQR): 543.5 (413.0-676.3) pg/mL) and highest in healthy controls (median (IQR): 668.0 (506.5-841.3) pg/mL) (p < .001). Moreover, in CHD patients, lower CDC42 level was related to more prevalent diabetes mellitus (p = .021), and higher levels of C-reactive protein (p = .001), Gensini score (p = .006), Th17 cells (p = .001) and Th17/Treg ratio (p < .001) but was associated with lower Treg cells (p = .018). Furthermore, CDC42 low level [below the median level (402.5 pg/mL) of CDC42 in CHD patients] was correlated with higher accumulating major adverse cardiovascular event (MACE) risk (p = .029), while no correlation was found between the quartile of CDC42 level and accumulating MACE risk in CHD patients (p = .102). The serum CDC42 level is decreased and its low level is related to higher Th17/Treg ratio and increased accumulating MACE risk in CHD patients.

Clinical value of long non-coding RNA KCNQ1OT1 in estimating the stenosis, lipid level, inflammation status, and prognostication in coronary heart disease patients.

OBJECTIVE: Long non-coding RNA KQT-like subfamily, member 1 opposite strand/antisense transcript 1 (KCNQ1OT1) could regulate lipid metabolism, vascular smooth muscle cell function, inflammation, and atherosclerosis. This study aimed to evaluate whether lncRNA KCNQ1OT1 could serve as a biomarker for reflecting coronary heart disease (CHD) patients' disease situation and prognosis. METHODS: LncRNA KCNQ1OT1 expression was determined in peripheral blood mononuclear cells from 267 CHD patients, 50 disease controls (DCs) (unexplained chest pain), and 50 healthy controls (HCs) by the RT-qPCR method. TNF-α, IL-17A, VCAM-1, and ICAM-1 were determined by the ELISA procedure in serum from CHD patients only. The mean (95% confidential interval) follow-up duration was 16.0 (15.3-16.8) months. RESULTS: LncRNA KCNQ1OT1 was highest in CHD patients, followed by DCs, and lowest in HCs (p < 0.001). LncRNA KCNQ1OT1 could distinguish the CHD patients from DCs (area under the curve [AUC]: 0.757) and from the HCs (AUC: 0.880). LncRNA KCNQ1OT1 was positively associated with triglyceride (p = 0.026), low-density lipoprotein cholesterol (p = 0.023), cardiac troponin I (p = 0.023), and C-reactive protein (p = 0.001). Besides, lncRNA KCNQ1OT1 was also positively linked with the Gensini score (p = 0.008). Furthermore, lncRNA KCNQ1OT1 was positively related to the TNF-α (p < 0.001), IL-17A (p = 0.008), and VCAM-1 (p = 0.003). LncRNA KCNQ1OT1 was elevated in CHD patients with MACE compared to those without MACE (p = 0.006); moreover, lncRNA KCNQ1OT1 high was associated with shorter MACE-free survival (p = 0.018). CONCLUSION: Circulating lncRNA KCNQ1OT1 expression not only reflects the stenosis degree, blood lipid level, and inflammation status but also predicts the MACE risk, while a large-scale study is needed for verification.

Prognostic Value of Brachial-Ankle Pulse Wave Velocity According to Subjects' Clinical Characteristics: Data From Analysis of 10,597 Subjects.

BACKGROUND: To make good use of the prognostic value of arterial stiffness, it is important to identify the population with the greatest benefit. In this study, we compared the prognostic value of brachial-ankle pulse wave velocity (baPWV) according to various clinical characteristics. METHODS: A total of 10,597 subjects who underwent baPWV measurement (mean age, 61.4 ± 9.5 years; female proportion, 42.5%) were retrospectively analyzed. Major adverse cardiovascular events (MACEs), defined as a composite of cardiac death, non-fatal myocardial infarction, coronary revascularization, and ischemic stroke were assessed during the clinical follow-up period. RESULTS: In the multivariate analysis, clinical variables with more than 4,000 subjects were selected as grouping variables, which were sex (men and women), age (≥ 65 and < 65 years), body mass index (BMI) (≥ 25 and < 25 kg/m²), hypertension (presence and absence), estimated glomerular filtration rate (≥ 90 and < 90 mL/min/1.73 m²), and statin use (user and non-user). During the median clinical follow-up duration of 3.58 years (interquartile range, 1.43-5.38 years), there were 422 MACEs (4.0%). In total study subjects, baseline higher baPWV was associated with increased risk of MACE occurrence (hazard ratio for baPWV ≥ 1,800 cm/s compared to baPWV < 1,400 cm/s, 4.04; 95% confidence interval, 2.62-6.21; P < 0.001). The prognostic value of baPWV was statistically significant regardless of sex, age, BMI, hypertension, renal function, and statin use. CONCLUSION: Our results suggest that baPWV is not only effective in specific clinical situations, but can be effectively applied to predict cardiovascular prognosis in various clinical situations.

Risk of major adverse cardiovascular events in patients initiating biologics/apremilast for psoriatic arthritis: a nationwide cohort study.

OBJECTIVE: Several biological DMARDs (bDMARDs) have demonstrated anti-inflammatory effects in PsA. However, their comparative cardiovascular safety profiles remain unknown. We evaluated the risk of major adverse cardiovascular events (MACEs) in PsA patients on therapy with different classes of bDMARDs and apremilast. METHODS: This nationwide cohort study involved the administrative healthcare database of the French health insurance scheme linked to the hospital discharge database. All adults with PsA who were new users of bDMARDs/apremilast (neither in the year before the index date) during 2015-19 were included. Patients with previous cardiovascular diseases were excluded. End of follow-up was 31 December 2019. The primary endpoint was an occurrence of MACEs in a time-to-event analysis with propensity score-weighted Cox and Fine-Gray models. RESULTS: Between 2015 and 2019, we included 9510 bDMARD new users [mean age 48.5 (s.d. 12.7) years; 42% men], including 7289 starting a TNF inhibitor, 1058 an IL-12/23 inhibitor and 1163 an IL-17 inhibitor, with 1885 apremilast new users [mean age 54.0 (s.d. 12.5) years; 44% men]. MACEs occurred in 51 (0.4%) patients. After propensity score weighting, the risk of MACEs was significantly greater with IL-12/23 (weighted hazard ratio 2.0, 95% CI 1.3, 3.0) and IL-17 (weighted hazard ratio 1.9, 95% CI 1.2, 3.0) inhibitors than TNF inhibitors, with no significant increased risk with apremilast (weighted hazard ratio 1.3, 95% CI 0.8, 2.2). Similar results were observed with the Fine-Gray competing risks survival model. CONCLUSION: Analysis of a large database revealed a small overall number of MACEs, and the risk of MACEs was greater for PsA new users of IL-12/23 and IL-17 vs TNF inhibitors.

Semaglutide reduces cardiovascular events regardless of metformin use: a post hoc subgroup analysis of SUSTAIN 6 and PIONEER 6.

BACKGROUND: Cardiovascular outcome trials (CVOTs) are conducted on a background of standard of care including metformin. These analyses sought to determine whether the cardiovascular (CV) effects of semaglutide and other glucagon-like peptide-1 receptor agonists (GLP-1RAs) vary according to baseline metformin use. METHODS: A post hoc analysis was conducted using pooled SUSTAIN 6 and PIONEER 6 CVOT data in subjects with and without metformin use at baseline. Additionally, a trial-level meta-analysis was conducted using data from seven CVOTs with GLP-1RAs-SUSTAIN 6, PIONEER 6, HARMONY OUTCOMES, LEADER, REWIND, EXSCEL and AMPLITUDE-O-including adults with type 2 diabetes at high CV risk, and a primary endpoint of time to first major adverse CV event (MACE). RESULTS: In the post hoc analysis, the no-metformin subgroup was older, with a higher body mass index, lower estimated glomerular filtration rate and higher CV risk at baseline vs the metformin subgroup. Hazard ratios (95% confidence intervals) for the reduction in risk of MACE with semaglutide vs placebo in the metformin and no-metformin subgroups were 0.70 (0.55;0.89) and 0.86 (0.60;1.22), respectively. No significant interaction between the treatment effect on MACE and metformin subgroup was observed. Findings for other CV endpoints were similar. In the meta-analysis, treatment effect (GLP-1RA vs placebo) on CV outcomes was no different with vs without baseline metformin (overall ratio between the hazard ratios for metformin vs no-metformin 1.09 [0.96;1.22]). CONCLUSION: These findings indicate that the CV outcomes for semaglutide were similar regardless of baseline metformin use, which may also apply to all GLP-1RAs. Trial registration SUSTAIN 6 (NCT01720446), PIONEER 6 (NCT02692716).