Future Adverse Cardiovascular Events Research Articles

Endothelial dysfunction as predictor of atherosclerosis during a translatitudinal sea voyage in the Arctic: prospective study

INTRODUCTION. Human labor activity in the Arctic takes place in severe climatic conditions associated with cooling, atmospheric pressure drops, high humidity, photoperiodicity, low oxygen content in the air. Endothelial dysfunction is an early pathophysiological sign and an independent predictor of poor prognosis in most cardiovascular diseases.
 OBJECTIVE.Тo analyze the dynamics of the level of metalloproteinase-9 and thrombin activity as predictors of the development of atherosclerosis in sailors during a translatitudinal sea voyage in the Arctic.
 MATERIALS AND METHODS. A prospective clinical and laboratory study of crew members was performed during the integrated marine research expedition “Transarctic-2019”. A clinical and laboratory study of the level of metalloprotease-9 (enzyme-linked immunosorbent assay), coagulation analysis of the parameters of the thrombin generation test, as well as ultrasonic dopplerography of the thickness of the intima-media complex were carried out. Statistical data processing was carried out using the methods of descriptive and analytical statistics in the StataCorp Stata 14.2 program. The study protocol was approved by the local ethical committee of the SSMU (protocol No. 03/5 dated May 27, 2015) and supported by the state task reg. No. NIOKTR 121030300111-7.
 RESULTS. A statistically significant increase in the level of MMP-9 in sailors after the expedition was noted, the relationship between the level of MMP-9, indicators of the thrombin generation test (lag time, min (p=0.0190), tPeak (p=0.0177), Peak (p= 0.0217) and KIM thickening.
 DISCUSSION. MMP-9 levels may be a predictor of early atherosclerosis and atherosclerotic plaque instability, as well as a risk factor for future adverse cardiovascular events. The relationship of MMP-9 with the kinetics of thrombin (one of the regulators of the antithrombotic state of the endothelium) during a translatitudinal voyage in sailors indicates the formation of readiness for prothrombotic events.
 CONCLUSION. Thus, in Arctic conditions, under conditions of chronic oxidative stress, which contribute to the progression of the development of endothelial dysfunction in the presence of external risk factors, the likelihood of progression of atherosclerotic vascular lesions increases, and, as a result, the development of vascular events.

Severity of obstructive sleep apnea is associated with left ventricular abnormality in patients with hypertension in the young

Abstract Background Hypertension in the young is defined as the presence of hypertension in individuals with an age of onset before 35 years. A previous study found that obstructive sleep apnea (OSA) may be a contributing factor of hypertension in the young up to 90% if other causes of secondary hypertension were excluded. Left ventricular (LV) abnormality is a marker of future cardiovascular consequences. There is limited data on risk factors of LV abnormality in patients with hypertension in the young with OSA. Objectives We aim to evaluate risk factors of LV abnormality in patients with hypertension in the young. Methods This study was a retrospective study. The eligible patients were adult patients who diagnosed as hypertension at age before 35 years and evaluated for echocardiogram. Those with causes of secondary hypertension or pregnant women were excluded. The study period was between October 2017 and January 2021. OSA was categorized as mild, moderate, and severe by an apnea-hypopnea index of 5-14.9, 15-29.9, and 30 or over times/hour. LV abnormality defined by relative wall thickness (RWT) over 0.42 mm. by a Doppler echocardiography. Other echocardiographic findings were also reported including left ventricular mass (LVM), left ventricular mass index (LVMI), and ejection fraction (EF). Differences of variables among severities of OSA were computed by a one-way ANOVA, while differences of proportions between groups were calculated by Chi square test. Multivariable analyses, linear and logistic regressions were performed to find the association between OSA and LV abnormality. Results There were 52 patients who met the study criteria. Mild OSA group had lower LVM, LVMI, and RWT than moderate OSA and severe OSA group (172.98 vs 232.16 vs 177.78 g; p 0.036 for LVMI; 83.03 vs 107.87 vs 84.99 g/m2; p 0.013 for LVMI; and 0.38 vs 0.45 vs 0.47 mm; p 0.010 for RWT). There was no significant difference in EF among the three groups. Severe OSA was found have an increased association with the presence of LV abnormality compared to patients with mild to moderate OSA (OR 3.28, 95% CI 0.96-12.5), however this was not statistically significant (p-value 0.07) Patients with severe OSA was found to have a correlation with RWT measurements of greater than 0.42 (correlation co-efficient 0.2, 95% CI 0.01-0.39, p-value 0.04). Conclusion Hypertensive patients under the age of 35 with severe OSA have a higher proportion of LV abnormality compared to mild and moderate OSA. Severe OSA was found to be correlated to RWT measurements of greater than 0.42. This finding might be one of prognostic indicators of the future adverse cardiovascular events and be required proper management. However, this relationship should be needed further study.

O054 What Measure of CPAP Treatment is most closely Associated with Reduced Risk of Future Major Cardiovascular Events (MACE)?

Abstract Introduction Obstructive sleep apnoea (OSA) is associated with future Major Adverse Cardiovascular Events (MACE). Continuous positive airway pressure (CPAP) is the standard treatment for OSA, but it is not known which measure of CPAP treatment is most closely associated with reduction in future MACE. We compared associations between a novel and a commonly used measure of CPAP treatment and future MACE. Materials and Methods Participants: 2717 adults with moderate-severe OSA attending a tertiary sleep clinic 2006-2010 completed baseline assessments and followed-up for 7years. CPAP treatment: Month-long CPAP trial and periodic review post-trial. Outcomes Time to cardiac death or non-fatal hospitalisations due to MACE, or end of follow-up, using Cox proportional hazards models. Predictors Average nightly CPAP use and the SARAH index (Sleep-Adjusted Residual AHI), using all available device downloads SARAH index=([AHITreatment×HoursTreatment]+[AHIUntreated×HoursUntreated])/HoursTotalSleepTime Covariates Demographics/comorbidities associated with MACE. Results MACE occurred in 18% participants. Average nightly use: Compared to zero use, each tertile of increasing use predicted reduction in risk of MACE (tertile-0:ref, tertile-I:HR 0.632, 95%CI 0.484-0.824, p<0.001, tertile-II:HR 0.772, 95%CI 0.602-0.990, p=0.042, tertile-III:HR 0.708, 95%CI 0.553-0.905, p=0.006). SARAH A dose-response decreasing risk of MACE with decreasing SARAH index tertiles (tertile-I:ref, tertile-II:HR 0.827, 95%CI 0.658-1.039, p= 0.102, tertile-III:HR 0.772, 95%CI 0.614-0.969, p=0.026). Conclusions Average nightly CPAP use and SARAH index were associated with a decreased risk of future MACE. The SARAH index showed a dose-response relationship with MACE; suggesting that it may be a better estimate of residual OSA-related cardiovascular stress.

Comparative Effectiveness of Aspirin Dosing in Cardiovascular Disease and Diabetes Mellitus: A Subgroup Analysis of the ADAPTABLE Trial.

Patients with diabetes mellitus (DM) and concomitant atherosclerotic cardiovascular disease (ASCVD) must be on the most effective dose of aspirin to mitigate risk of future adverse cardiovascular events. ADAPTABLE, an open-label, pragmatic study, randomized patients with stable, chronic ASCVD to 81 mg or 325 mg of daily aspirin. The effects of aspirin dosing was assessed on the primary effectiveness outcome, a composite of all-cause death, hospitalization for myocardial infarction, or hospitalization for stroke, and the primary safety outcome of hospitalization for major bleeding. In this prespecified analysis, we used Cox proportional hazards models to compare aspirin dosing in patients with and without DM for the primary effectiveness and safety outcome. Of 15,076 patients, 5,676 (39%) had DM of whom 2,820 (49.7%) were assigned to 81 mg aspirin and 2,856 (50.3%) to 325 mg aspirin. Patients with versus without DM had higher rates of the composite cardiovascular outcome (9.6% vs. 5.9%; P < 0.001) and bleeding events (0.78% vs. 0.50%; P < 0.001). When comparing 81 mg vs. 325 mg of aspirin, patients with DM had no difference in the primary effectiveness outcome (9.3% vs. 10.0%; hazard ratio [HR] 0.98 [95% CI 0.83-1.16]; P = 0.265) or safety outcome (0.87% vs. 0.69%; subdistribution HR 1.25 [95% CI 0.72-2.16]; P = 0.772). This study confirms the inherently higher risk of patients with DM irrespective of aspirin dosing. Our findings suggest that a higher dose of aspirin yields no added clinical benefit, even in a more vulnerable population.

BRAVEHEART: Open-source software for automated electrocardiographic and vectorcardiographic analysis

Background and ObjectivesElectrocardiographic (ECG) and vectorcardiographic (VCG) analyses are used to diagnose current cardiovascular disease and for risk stratification for future adverse cardiovascular events. With increasing use of digital ECGs, research into novel ECG/VCG parameters has increased, but widespread computer-based ECG/VCG analysis is limited because there are no currently available, open-source, and easily customizable software packages designed for automated and reproducible analysis. Methods and ResultsWe present BRAVEHEART, an open-source, modular, customizable, and easy to use software package implemented in the MATLAB programming language, for scientific analysis of standard 12-lead ECGs acquired in a digital format. BRAVEHEART accepts a wide variety of digital ECG formats and provides complete and automatic ECG/VCG processing with signal denoising to remove high- and low-frequency artifact, non-dominant beat identification and removal, accurate fiducial point annotation, VCG construction, median beat construction, customizable measurements on median beats, and output of measurements and results in numeric and graphical formats. ConclusionsThe BRAVEHEART software package provides easily customizable scientific analysis of ECGs and VCGs. We hope that making BRAVEHART available will allow other researchers to further the field of ECG/VCG analysis without having to spend significant time and resources developing their own ECG/VCG analysis software and will improve the reproducibility of future studies. Source code, compiled executables, and a detailed user guide can be found at http://github.com/BIVectors/BRAVEHEART. The source code is distributed under the GNU General Public License version 3.

Imaging Acute and Chronic Cardiac Complications of COVID-19 and after COVID-19 Vaccination.

COVID-19 is associated with acute and longer-term cardiovascular manifestations including myocardial injury, myopericarditis, stress-induced cardiomyopathy, myocardial infarction, and thromboembolic disease. Although the morbidity and mortality related to acute COVID-19 have decreased substantially, there is growing concern about the longer-term cardiovascular effects of the disease and postacute sequelae. Myocarditis has also been reported after messenger ribonucleic acid (mRNA)-based COVID-19 vaccination, with the highest risk among adolescent boys and young adult men. Noninvasive imaging including cardiac MRI has a key role in identifying the presence of cardiovascular disease, evaluating for potential mechanisms of injury, stratifying risk of future adverse cardiovascular events, and potentially guiding treatment in patients with suspected cardiovascular injury after COVID-19 and vaccination. Patterns of injury identified at cardiac MRI after COVID-19 include myocarditis and pericarditis, myocardial ischemia, and infarction. Myocardial edema and late gadolinium enhancement have been described months after the initial infection in a minority of patients with persistent cardiac symptoms after COVID-19. In patients with myocarditis after receiving a COVID-19 vaccination, the most common pattern of late gadolinium enhancement is subepicardial at the basal inferolateral wall, and patients tend to have milder imaging abnormalities compared with those from other causes of myocarditis. This article describes the role of multimodality cardiac imaging and imaging findings in patients with acute and longer-term cardiovascular manifestations of COVID-19 and in patients with myocarditis after receiving an mRNA-based COVID-19 vaccination. ©RSNA, 2023 Online supplemental material is available for this article. Quiz questions for this article are available through the Online Learning Center.

1071 Examining Blood Lipid Profiles and Lipid Lowering Therapy in Carotid Surgery Patients in a 1-Year Follow-Up Study

Abstract Aim Stroke patients are at a high risk of future major adverse cardiovascular events. Focusing on lipid lowering therapy (LLT), current ESVS and NICE guidelines advise high intensity statin (HIS) treatment with a target LDL-C of less than 1.8mmol/L. Method This is a retrospective cohort study on 205 patients who underwent carotid endarterectomy or stenting from 01/01/18 to 31/12/20 at Leeds Vascular Institute. Prescriptions and lipid profiles prior to intervention, at discharge, and 1-year post-intervention were recorded. Differences between time points were assessed using the McNemar test. Results There were 137 men, the median age was 73, and 175 patients underwent carotid endarterectomy. Increases in prescriptions of statins (65%vs93%, p&amp;lt;0.001) and HIS (47%vs83%, p&amp;lt;0.001) were observed at discharge compared to pre-intervention but no differences were seen at 1 year. At 1 year, 8 patients were not on statin therapy; 6 were intolerant and 3 were prescribed Ezetimibe. At 1 year, there was a significant improvement in median LDL-C (2.4mmol/L IQR (1.9-3.3) vs. 1.6mmol/L (1.2-2.0)), and proportion of patients reaching target LDL-C of &amp;lt;1.8mmol/L (21%vs59%,p = 0.003) compared to pre-admission. In patients with LDL-C≥1.8mmol/L, 92% had scope for LLT up-titration. No significant differences were noted in the proportion of patients who underwent lipid profile monitoring prior to admission and at 1 year. Conclusions Admission to our local vascular unit is associated with an increase in the guideline-directed prescription of LLT, and subsequently attainment of target LDL-C. Reasons for suboptimal lipid monitoring in the community need to be understood to allow for optimal risk reduction.

Predictors of non-calcified plaque presence and future adverse cardiovascular events in symptomatic rural Appalachian patients with a zero coronary artery calcium score

BackgroundCoronary artery calcium (CAC) scoring is a proven predictor for future adverse cardiovascular events (CVE) in asymptomatic individuals. Data is emerging regarding the usefulness of non-calcified plaque (NCP) assessment on cardiac computed tomography (CCT) angiography in symptomatic patients with a zero CAC score for further risk assessment. MethodsA retrospective review from January 2019 to January 2022 of 696 symptomatic patients with no known CAD and a zero CAC score identified 181 patients with NCP and 515 patients without NCP by a visual assessment on CCT angiography. The primary endpoint was to identify predictors for NCP presence and adverse CVEs (death, myocardial infarction, or cerebrovascular accident) within two years. ResultsBased on logistic regression, age (OR 1.039, 95% CI [1.020–1.058], p ​< ​0.001), diabetes mellitus (OR 2.192, 95% CI [1.307–3.676], p ​< ​0.003), tobacco use (OR 1.748, 95% CI [1.157–2.643], p ​< ​0.008), low-density lipoprotein cholesterol level (OR 1.009, 95% CI [1.003–1.015], p ​< ​0.002), and hypertension (OR 1.613, 95% CI [1.024–2.540], p ​< ​0.039) were found to be predictors of NCP presence. NCP patients had a higher pretest probability for CAD using the Morise risk score (p ​< ​0.001∗), with NCP detection increasing as pretest probability increased from low to high (OR 55.79, 95% CI [24.26–128.26], p ​< ​0.001∗). 457 patients (66%) reached a full two-year period after CCT angiography completion, with NCP patients noted to have shorter follow-up times and higher rates of elective coronary angiography, intervention, and CVEs. The presence of NCP (aOR 2.178, 95% CI [1.025–4.627], p ​< ​0.043) was identified as an independent predictor for future adverse CVEs when adjusted for diabetes mellitus, age, and hypertension. ConclusionNCP was identified at high rates (26%) in our symptomatic Appalachian population with no known CAD and a zero CAC score. NCP was identified as an independent predictor of future adverse CVEs within two years.

Machine learning for abdominal aortic calcification assessment from bone density machine-derived lateral spine images.

Lateral spine images for vertebral fracture assessment can be easily obtained on modern bone density machines. Abdominal aortic calcification (AAC) can be scored on these images by trained imaging specialists to assess cardiovascular disease risk. However, this process is laborious and requires careful training. Training and testing of model performance of the convolutional neural network (CNN) algorithm for automated AAC-24 scoring utilised 5012 lateral spine images (2 manufacturers, 4 models of bone density machines), with trained imaging specialist AAC scores. Validation occurred in a registry-based cohort study of 8565 older men and women with images captured as part of routine clinical practice for fracture risk assessment. Cox proportional hazards models were used to estimate the association between machine-learning AAC (ML-AAC-24) scores with future incident Major Adverse Cardiovascular Events (MACE) that including death, hospitalised acute myocardial infarction or ischemic cerebrovascular disease ascertained from linked healthcare data. The average intraclass correlation coefficient between imaging specialist and ML-AAC-24 scores for 5012 images was 0.84 (95% CI 0.83, 0.84) with classification accuracy of 80% for established AAC groups. During a mean follow-up 4 years in the registry-based cohort, MACE outcomes were reported in 1177 people (13.7%). With increasing ML-AAC-24 scores there was an increasing proportion of people with MACE (low 7.9%, moderate 14.5%, high 21.2%), as well as individual MACE components (all p-trend <0.001). After multivariable adjustment, moderate and high ML-AAC-24 groups remained significantly associated with MACE (HR 1.54, 95% CI 1.31-1.80 & HR 2.06, 95% CI 1.75-2.42, respectively), compared to those with low ML-AAC-24. The ML-AAC-24 scores had substantial levels of agreement with trained imaging specialists, and was associated with a substantial gradient of risk for cardiovascular events in a real-world setting. This approach could be readily implemented into these clinical settings to improve identification of people at high CVD risk. The study was supported by a National Health and Medical Research Council of Australia Ideas grant and the Rady Innovation Fund, Rady Faculty of Health Sciences, University of Manitoba.

Patterns of Circulating Microbiota during the Acute Phase Following ST-Segment Elevation Myocardial Infarction Predict Long-Term Cardiovascular Events.

Limited information exists regarding whether circulating microbiota could predict long-term clinical outcomes following ST-segment elevation myocardial infarction (STEMI). A total of 244 consecutive patients with STEMI were followed for 2.8 years, and 64 first major adverse cardiovascular events (MACEs) were recorded. Both microbiota abundance [Corynebacterium tuberculostearicum (HR, 1.28; 95% CI, 1.03-1.58) and Staphylococcus aureus (S. aureus) (HR, 1.16; 95% CI, 1.02-1.33) ] and microbiota clusters (Cluster 2 versus Cluster 1: HR, 1.84; 95% CI, 1.04-3.27) could independently predict MACE. Furthermore, a model based on established independent predictors alone was significantly improved by the addition of different microbiota patterns. In addition, CD14++CD16+ monocytes (Mon2) had a significant mediation effect on the microbiota patterns → MACE association. The present study demonstrated that the abundance and clusters of circulating microbiota are associated with future adverse cardiovascular events independent of traditional risk factors, which were partially mediated by an increase in Mon2.

Differential prediction of high-sensitivity cardiac troponin-I, but not N-terminal pro-brain natriuretic peptide, in different pitavastatin doses on cardiovascular events in stable coronary artery disease

BackgroundThis study aimed to examine whether high-sensitivity cardiac troponin-I (hsTnI) and N-terminal pro-brain natriuretic peptide (NT-proBNP) could predict future major adverse cardiovascular events (MACE) in stable coronary artery disease (CAD) patients with high- or low-dose of pitavastatin. MethodsThis was a case-cohort analysis of the REAL-CAD study, a randomized trial of high- or low-dose (4 or 1 mg/day) pitavastatin therapy in patients with stable CAD. We examined the MACE risk according to the quartile of hsTnI and NT-proBNP at baseline. ResultsA total of 1336 and 1396 patients including 582 MACE cases were randomly examined into the hsTnI and NT-proBNP cohort, respectively. Both higher levels of hsTnI and NT-proBNP at baseline were significantly associated with increased risk of MACE (p < 0.001, respectively). When separately analyzed in statin dose, the higher marker levels were significantly associated with higher MACE risk in all cohorts (p < 0.001 in all cohorts). After multivariable adjustment, hsTnI levels were significantly associated with MACE risk in low-dose statin group (HR 2.54, p = 0.0001); however, in high-dose pitavastatin therapy, a significant association was diminished in MACE risk among the quartiles of baseline hsTnI levels (p = 0.154). Conversely in the NT-proBNP cohort, the association between NT-proBNP levels and MACE risk was constantly observed regardless of pitavastatin dose even after multivariable adjustment (both p < 0.0001). ConclusionsPatients with high hsTnI levels had high risk of MACE in low-dose statin group, but not in high-dose, suggesting that high-dose statin treatment might decrease MACE risk in stable CAD patients with high hsTnI levels.

157-OR: Cystatin C Predicts Major Cardiovascular Events in Patients with Coronary Artery Disease Both among Patients With and among Those Without the Metabolic Syndrome

Cystatin C is an established biomarker for renal function, and, given the close association of chronic kidney disease and cardiovascular disease might indicate new-onset or deteriorating cardiovascular disease. However, evidence for cystatin C as a predictor of cardiovascular events is limited and controversial. We therefore aimed at investigating the role of cystatin C as a predictor of future major adverse cardiovascular events (MACE) in a high risk-cohort of patients with established coronary artery disease (CAD). We prospectively recorded cardiovascular events in 1481 patients with angiographically verified CAD over a mean follow-up of 10.0±5.2 years. At baseline, 684 patients had the metabolic syndrome (MetS) and 797 did not have the MetS. During follow-up, 578 (39%) of our patients suffered MACE. Cystatin C proved to be a strong and independent predictor for MACE in the total study cohort (standardized adjusted HR 1.56 [1.34-1.83], p&amp;lt;0.001). When MetS status was taken into account, cystatin C significantly predicted major cardiovascular events both in patients with the MetS (HR 1.56 [1.28-1.90], p&amp;lt;0.001) and in non-MetS patients (HR 1.44 [1.12-1.84], p=0.004). We conclude that cystatin C predicts major cardiovascular events in patients with coronary artery disease both among patients with the MetS and in non-MetS individuals. Disclosure A.Mader: None. C.H.Saely: None. M.Maechler: None. B.Larcher: None. L.Sprenger: None. A.Leiherer: None. A.Muendlein: None. A.Vonbank: None. T.Plattner: None. H.Drexel: None.

Near-infrared spectroscopy-intravascular ultrasound to improve assessment of coronary artery disease severity in patients referred for transcatheter aortic valve implantation (The IMPACTavi registry): Design and rationale

Transcatheter aortic valve implantation (TAVI) was established as a standard treatment for high-operative risk patients with severe aortic stenosis (AS). Although coronary artery disease (CAD) often co-exists with AS, clinical and angiographic evaluations of stenosis severity are unreliable in this specific setting. To provide precise risk stratification of coronary lesions, combined near-infrared spectroscopy and intravascular ultrasound (NIRS-IVUS) was developed to integrate morphological and molecular information on plaque composition. However, there is a lack of evidence on the association between NIRS-IVUS derived findings such as maximum 4mm lipid core burden index (maxLCBI4mm) and clinical outcomes in AS patients undergoing TAVI. This registry aims to assess feasibility and safety of NIRS-IVUS imaging in the setting of routine pre-TAVI coronary angiography to improve assessment of CAD severity. The registry is designed as a non-randomized, prospective, observational, multi-center cohort registry. Patients referred for TAVI with angiographic evidence of CAD receive NIRS-IVUS imaging and are followed up to 24 months. Enrolled patients are classified as NIRS-IVUS positive and NIRS-IVUS negative, respectively, based on their maxLCBI4mm to compare their clinical outcomes. The primary endpoint of the registry is major adverse cardiovascular events over a 24-month follow-up period. Identification of patients likely or unlikely to benefit from revascularization prior to TAVI represents an important unmet clinical need. This registry is designed to investigate whether NIRS-IVUS-derived atherosclerotic plaque characteristics can identify patients and lesions at risk for future adverse cardiovascular events after TAVI, in order to refine interventional decision-making in this challenging patient population.

The incorporation of repeated measurements of risk factors at current and previous visits improves the accuracy of cardiovascular risk assessment: an analysis of the EXSCEL trial

Abstract Funding Acknowledgements Type of funding sources: None. Background Risk prediction tools play an important role in cardiovascular risk stratification. One major limitation of most of these tools is their use of only single values of each risk factor, measured usually at a particular clinical visit, ignoring measurements made at previous visits. Purpose The aim of this study is to demonstrate the gain in predictive performance when CVD risk prediction tools incorporate repeated, rather than only single, measurements of risk factors. Methods We used data from the Exenatide Study of Cardiovascular Event Lowering (EXSCEL) randomized controlled trial to compare the quality of predictions of future major adverse cardiovascular events (MACE) in the Cox proportional hazards model that uses single values of risk factors, compared to the Bayesian joint model that uses repeated measures of risk factors. The risk of MACE was calculated in patients with type 2 diabetes with and without established CVD. We assessed the predictive ability of the following cardiovascular risk factors: glycated haemoglobin (HbA1c), high-density lipoprotein cholesterol (HDL-C), non-HDL-C, triglycerides, estimated glomerular filtration rate, low-density lipoprotein cholesterol (LDL-C), total cholesterol, and systolic blood pressure (SBP) using the time-dependent area under the receiver operating characteristic curve (aROC) for discrimination and the time-dependent Brier score for calibration. Results In participants without history of CVD, the aROC of systolic blood pressure increased from 0.62 to 0.69 when repeated, rather than only single, measurements of SBP were incorporated into the predictive model. Similarly, the aROC increased from 0.67 to 0.80 when repeated, rather than only single, measurements of both SBP and LDL-C were incorporated into the predictive model. For all other investigated cardiovascular risk factors, the measures of discrimination and calibration both improved when using the joint model as compared to the Cox proportional hazards model. The improvement was evident in participants with and without history of CVD but was more pronounced in the latter group. Conclusion This analysis demonstrates that the joint modeling approach, considering trajectories of cardiovascular risk factors, provides superior predictive performance of CVD risk stratification compared to standard risk prediction tools, using only a single time point.

Utilization Rates of SGLT2 Inhibitors Among Patients With Type 2 Diabetes, Heart Failure, and Atherosclerotic Cardiovascular Disease: Insights From the Department of Veterans Affairs

BackgroundMultiple clinical trials have demonstrated significant cardiovascular benefit with use of sodium-glucose cotransporter-2 (SGLT2) inhibitors in patients with type 2 diabetes (T2DM) and heart failure (HF) irrespective of ejection fraction. There are limited data evaluating real-world prescription and practice patterns of SGLT2 inhibitors. ObjectivesThe authors sought to assess utilization rates and facility-level variation in the use among patients with established atherosclerotic cardiovascular disease (ASCVD), HF, and T2DM using data from the nationwide Veterans Affairs health care system. MethodsThe authors included patients with established ASCVD, HF, and T2DM seen by a primary care provider between January 1, 2020, and December 31, 2020. They assessed the use of SGLT2 inhibitors and the facility-level variation in their use. Facility-level variation was computed using median rate ratios, a measure of likelihood that 2 random facilities differ in use of SGLT2 inhibitors. ResultsAmong 105,799 patients with ASCVD, HF, and T2DM across 130 Veterans Affairs facilities, 14.6% received SGLT2 inhibitors. Patients receiving SGLT2 inhibitors were younger men with higher hemoglobin A1c and estimated glomerular filtration rate and were more likely to have HF with reduced ejection fraction and ischemic heart disease. There was significant facility-level variation of SGLT2 inhibitor use, with an adjusted median rate ratio of 1.55 (95% CI: 1.46-1.64), indicating a 55% residual difference in SGLT2 inhibitor use among similar patients with ASCVD, HF, and T2DM receiving care at 2 random facilities. ConclusionsUtilization rates of SGLT2 inhibitors are low in patients with ASCVD, HF, and T2DM, with high residual facility-level variation. These findings suggest opportunities to optimize SGLT2 inhibitor use to prevent future adverse cardiovascular events.

Plasma asymmetric dimethylarginine is associated with vulnerable plaque and long-term outcomes in stable coronary artery disease

Asymmetric dimethylarginine (ADMA) is considered to be an atherogenic molecule. We aimed to investigate the relationship between ADMA and plaque vulnerability assessed by optical coherence tomography (OCT) in patients with stable coronary artery disease (CAD). Two hundred and forty-five patients with stable CAD undergoing OCT-guided percutaneous coronary intervention were included in this study and were divided into two groups according to their ADMA levels. Micro-vessel, macrophage accumulation, thin-cap fibroatheroma, intra-plaque calcium and lipid core content, and vulnerable score (VS) were evaluated by OCT analysis. The patients with higher ADMA levels had significantly higher calcium and lipid content (p < 0.001, respectively). There were significantly more micro-vessel and macrophage (32.8%, p = 0.004 and 52.5%, p < 0.001, respectively) and higher VS (87.7 ± 17.6, p < 0.001) in the higher ADMA group. Moreover, plasma ADMA level was significantly correlated with the intra-plaque lipid, calcium content and VS (p < 0.001, respectively). Plasma ADMA level was identified as an independent predictor of future adverse cardiovascular events, following OCT-guided PCI. In patients with stable CAD, higher plasma ADMA levels were significantly associated with the presence of intra-plaque lipid, calcification, vulnerable plaque, and poor long-term outcomes.

Soluble interleukin-2 receptor combined with interleukin-8 is a powerful predictor of future adverse cardiovascular events in patients with acute myocardial infarction.

Little is known about the role of interleukin (IL) in patients with acute myocardial infarction (MI), especially soluble IL-2 receptor (sIL-2R) and IL-8. We aim to evaluate, in MI patients, the predictive value of serum sIL-2R and IL-8 for future major adverse cardiovascular events (MACEs), and compare them with current biomarkers reflecting myocardial inflammation and injury. This was a prospective, single-center cohort study. We measured serum concentrations of IL-1β, sIL-2R, IL-6, IL-8 and IL-10. Levels of current biomarkers for predicting MACEs were measured, including high-sensitivity C reactive protein, cardiac troponin T and N-terminal pro-brain natriuretic peptide. Clinical events were collected during 1-year and a median of 2.2 years (long-term) follow-up. Twenty-four patients (13.8%, 24/173) experienced MACEs during 1-year follow-up and 40 patients (23.1%, 40/173) during long-term follow-up. Of the five interleukins studied, only sIL-2R and IL-8 were independently associated with endpoints during 1-year or long-term follow-up. Patients with high sIL-2R or IL-8 levels (higher than the cutoff value) had a significantly higher risk of MACEs during 1-year (sIL-2R: HR 7.7, 3.3-18.0, p < 0.001; IL-8: HR 4.8, 2.1-10.7, p < 0.001) and long-term (sIL-2R: HR 7.7, 3.3-18.0, p < 0.001; IL-8: HR 4.8, 2.1-10.7, p < 0.001) follow-up. Receiver operator characteristic curve analysis regarding predictive accuracy for MACEs during 1-year follow-up showed that the area under the curve for sIL-2R, IL-8, sIL-2R combined with IL-8 was 0.66 (0.54-0.79, p = 0.011), 0.69 (0.56-0.82, p < 0.001) and 0.720 (0.59-0.85, p < 0.001), whose predictive value were superior to that of current biomarkers. The addition of sIL-2R combined with IL-8 to the existing prediction model resulted in a significant improvement in predictive power (p = 0.029), prompting a 20.8% increase in the proportion of correct classifications. High serum sIL-2R combined with IL-8 levels was significantly associated with MACEs during follow-up in patients with MI, suggesting that sIL-2R combined with IL-8 may be a helpful biomarker for identifying the increased risk of new cardiovascular events. IL-2 and IL-8 would be promising therapeutic targets for anti-inflammatory therapy.

Heterogeneous plaque-lumen geometry is associated with major adverse cardiovascular events.

Prospective studies show that only a minority of plaques with higher risk features develop future major adverse cardiovascular events (MACE), indicating the need for more predictive markers. Biomechanical estimates such as plaque structural stress (PSS) improve risk prediction but require expert analysis. In contrast, complex and asymmetric coronary geometry is associated with both unstable presentation and high PSS, and can be estimated quickly from imaging. We examined whether plaque-lumen geometric heterogeneity evaluated from intravascular ultrasound affects MACE and incorporating geometric parameters enhances plaque risk stratification. We examined plaque-lumen curvature, irregularity, lumen aspect ratio (LAR), roughness, PSS, and their heterogeneity indices (HIs) in 44 non-culprit lesions (NCLs) associated with MACE and 84 propensity-matched no-MACE-NCLs from the PROSPECT study. Plaque geometry HI were increased in MACE-NCLs vs. no-MACE-NCLs across whole plaque and peri-minimal luminal area (MLA) segments (HI curvature: adjusted P = 0.024; HI irregularity: adjusted P = 0.002; HI LAR: adjusted P = 0.002; HI roughness: adjusted P = 0.004). Peri-MLA HI roughness was an independent predictor of MACE (hazard ratio: 3.21, P < 0.001). Inclusion of HI roughness significantly improved the identification of MACE-NCLs in thin-cap fibroatheromas (TCFA, P < 0.001), or with MLA ≤ 4 mm2 (P < 0.001), or plaque burden (PB) ≥ 70% (P < 0.001), and further improved the ability of PSS to identify MACE-NCLs in TCFA (P = 0.008), or with MLA ≤ 4 mm2 (P = 0.047), and PB ≥ 70% (P = 0.003) lesions. Plaque-lumen geometric heterogeneity is increased in MACE vs. no-MACE-NCLs, and inclusion of geometric heterogeneity improves the ability of imaging to predict MACE. Assessment of geometric parameters may provide a simple method of plaque risk stratification.

Identification of vulnerable non-culprit lesions by coronary computed tomography angiography in patients with chronic coronary syndrome and diabetes mellitus.

Among patients with diabetes mellitus (DM) and chronic coronary syndrome (CCS), non-culprit lesions (NCLs) are responsible for a substantial number of future major adverse cardiovascular events (MACEs). Thus, we aimed to establish the natural history relationship between adverse plaque characteristics (APCs) of NCLs non-invasively identified by coronary computed tomography angiography (CCTA) and subsequent MACEs in these patients. Between January 2016 and January 2019, 523 patients with DM and CCS were included in the present study after CCTA and successful percutaneous coronary intervention (PCI). All patients were followed up for MACEs (the composite of cardiac death, myocardial infarction, and unplanned coronary revascularization) until January 2022, and the independent clinical event committee classified MACEs as indeterminate, culprit lesion (CL), and NCL-related. The primary outcome was MACEs arising from untreated NCLs during the follow-up. The association between plaque characteristics detected by CCTA and primary outcomes was determined by Marginal Cox proportional hazard regression. Overall, 1,248 NCLs of the 523 patients were analyzed and followed up for a median of 47 months. The cumulative rates of indeterminate, CL, and NCL-related MACEs were 2.3%, 14.5%, and 20.5%, respectively. On multivariate analysis, NCLs associated with recurrent MACEs were more likely to be characterized by a plaque burden >70% [hazard ratio (HR), 4.35, 95% confidence interval (CI): 2.92-6.44], a low-density non-calcified plaque (LDNCP) volume >30 mm3 (HR: 3.40, 95% CI: 2.07-5.56), a minimal luminal area (MLA) <4 mm2 (HR: 2.30, 95% CI: 1.57-3.36), or a combination of three APCs (HR: 13.69, 95% CI: 9.34-20.12, p < 0.0001) than those not associated with recurrent MACEs. Sensitivity analysis regarding all indeterminate MACEs as NCL-related ones demonstrated similar results. In DM patients who presented with CCS and underwent PCI, half of the MACEs occurring during the follow-up were attributable to recurrence at the site of NCLs. NCLs responsible for unanticipated MACEs were frequently characterized by a large plaque burden and LDNCP volume, a small MLA, or a combination of these APCs, as determined by CCTA.

Synergistic role of circulating CD14++CD16+ monocytes and fibrinogen in predicting the cardiovascular events after myocardial infarction

Monocytes and fibrinogen (FIB) play important roles in driving acute and reparative inflammatory pathways after myocardial infarction (MI). In humans, there are three subsets of monocytes, namely, CD14++CD16- (Mon1), CD14++CD16+ (Mon2), and CD14+CD16++ (Mon3). During the inflammatory response, monocyte subsets express high levels of integrin αM β2 and protease-activated receptors 1 and 3 to interact with FIB. However, whether there is a synergistic role of FIBcombined with Mon2 counts in prioritizing patients at high risk of future major adverse cardiovascular events (MACEs) after MI remains unknown. The MI patients who treated with primary percutaneous coronary intervention were enrolled. MI patients were categorized into four groups, that is, low FIB/low Mon2, low FIB/high Mon2, high FIB/low Mon2, and high FIB/high Mon2, according to cutoff values of 3.28 g/L for FIB and 32.20 cells/μL for Mon2. Kaplan-Meier survival analysis and Cox proportional hazards models were used to estimate the risk of MACEs of MI patients during a median follow-up of 2.7 years. Mediating effects of high FIB levels and MACEs associated with high monocyte subsets were calculated by mediation analysis. High FIB/high Mon2 group had the highest risk of MACEs during a median follow-up of 2.7 years. Moreover, mediation analysis showed that a high FIB level could explain 24.9% (p < .05) of the increased risk of MACEs associated with Mon2. This work provides evidence indicating the translational potential of a synergistic role of FIB combined with Mon2 in prioritizing patients at high risk of future MACEs after MI.