Chronic Chronic Coronary Artery Disease Research Articles

Abstract 4140139: Cardio-ankle vascular index (CAVI) in prediction of chronic coronary artery disease: risk, coronary artery lesions, and cardiovascular disease events

Introduction: The cardio-ankle vascular index (CAVI) is a significant metric for evaluating arterial function. The test measures the stiffness of the arteries from the beginning of the aorta to the ankle, and the algorithm used is not influenced by blood pressure. Recent statistics indicate that a high CAVI score has the potential to predict future cardiovascular disease (CVD) occurrences. However, no research has been conducted in Vietnam to investigate this matter. Methods: A prospective study was conducted on 222 patients. Out of these, 162 patients had chronic coronary artery disease (CAD), while the remaining 62 patients were free of CAD. The study took place between October 2019 and December 2022. Participants who fulfilled the criteria were evaluated using the CAVI baseline measurement and clinical and paraclinical parameters. A total of 162 patients with chronic coronary artery disease (CAD) were monitored for cardiovascular disease (CVD) events over a period of 2 years. Results: CAVI in chronic CAD patients (9.21±0.79) was significantly higher compared to those in free-CAD patients (8.48 ± 0.62) with p<0.001. CAVI with a cut-off point ≥ 8.83 was a significant predictor for chronic CAD (OR = 9.6; 95%CI: 4.0-18.8). The Area under the curve (AUC) of CAVI for chronic CAD was 0.796 (95% CI: 0.736-0.856 ; p<0.001). In addition, CAVI has a statistically significant increase in severe stenosis (≥75%) and multivessel coronary artery disease. CAVI in the CVD events group (9.77±1.06) was significantly higher than CAVI in the free–CVD events group (9.13±0.72) group (p=0.009). The patients with CAVI ≥9.63 have significantly higher CVD events (HR=6.4 ; 95% CI: 1.9-21.9, p=0.046). Conclusion: CAVI is higher in chronic CAD and can predict chronic CAD with a cut-off point ≥ 8.83. In chronic CAD, CAVI is higher in severe stenosis and multivessel coronary artery disease. Increased CAVI was significantly associated with CVD events.

Abstract 4122389: Accumulation of Epicardial Adipose Tissue as a Marker of Diastolic Dysfunction in Patients With Preserved Left Ventricular Ejection Fraction Undergoing Coronary Computed Tomography Angiograph

Background: Left ventricular diastolic dysfunction (LVDD) plays a major role in the pathophysiology of progression to heart failure with preserved left ventricular (LV) ejection fraction (EF). Although epicardial adipose tissue (EAT) is attracting attention for the underlying pathophysiology, whether increased EAT and coronary plaque burden are associated with LVDD is unclear in patients with chronic coronary artery disease (CAD) and preserved LVEF. Aims: To investigate the association between LVDD and EAT accumulation in chronic CAD patients with preserved LVEF. Methods: We included three hundred fourteen chronic CAD and preserved LVEF patients without history of heart failure (mean age: 66±13 years; 48% female). Thoracic tissue doppler echocardiography (TTDE) analysis included LVDD parameters, including left atrial volume index (LAVI), e’, E/e’ and tricuspid regurgitation (TR) velocity. LVDD was defined according to the American Society of Echocardiography guidelines. Coronary computed tomographic angiography (CCTA) analysis included EAT volume index (EAVi), coronary artery calcium score (CACS), and coronary plaque volume (%PV). Patients were divided into three groups according to EAVi: Group A as normal (<68.1 ml/m 2 , n=127), group B as low (68.1-89.4 ml/m 2 , n=95), and group C as high EATVi (>89.4 ml/m 2 , n=92). Multivariable logistic regression analysis was performed to investigate the association between the clinical parameters, TTDE and CCTA findings, and the presence of LVDD. Results: Compared with Group A, group C was older and more frequently suffered from renal dysfunction. Among the three groups, we observed significant differences in LV mass index, e’, E/e’, and CACS. The EAVi correlated with each LVDD diagnostic component, including e’, E/e’, left atrial volume index (all p<0.05), except for tricuspid regurgitation velocity. A multivariate model showed that age [odds ratio (OR), 1.13; 95% CI, 1.06-1.20; p<0.001] and EAVi (OR, 1.03; 95%CI, 1.01-1.04; p<0.05) were independently associated with LVDD, even after adjusting for LV mass index (OR, 1.1; p < 0.05). There was no independent association of CACS or %PV with LVDD (Table). Conclusion: This study demonstrates that accumulation of EAT and LV mass index but not plaque volume were independent predictors of LVDD in chronic CAD patients with preserved LVEF. Further study is needed to investigate whether EAT predicts the development to heart failure in this population.

Abstract 4120670: Pericoronary Adipose Tissue Inflammation as a Marker of Increased Coronary Plaque Burden in Patients With Chronic Coronary Artery Disease With Zero Calcium Score

Background: Dysfunctional or excess adiposity plays pivotal role in the development of coronary atherosclerosis. It remains unclear whether pericoroanry adipose tissue (PCAT) inflammation is associated with increased coronary plaque burden in its early stage of atherosclerosis, independent of traditional coronary risks or cardiovascular-kidney metabolic health. Purpose: To investigate the association of PCAT inflammation with coronary plaque burden in patients with newly suspected with chronic coronary artery disease (CAD) and zero calcium score who underwent coronary computed tomography angiography (CCTA). Methods: This retrospective CCTA study consists of 294 chronic CAD patients with zero calcium score (59 years, male 51 %). Chronic CAD was defined as stable condition with presence of increased non-calcified plaque burden on CCTA (Figure 1A-D). PCAT attenuation (PCATA) was assessed by fat attenuation index in the major three coronary arteries (right coronary artery, RCA; left anterior descending artery; LAD, and left circumflex coronary artery, LCX)(Figure 1C and D). Multivariable analysis using linear regression model was performed to determine independent predictors of increased %PV by adjusting for traditional coronary risks, metabolic risks, and chronic kidney disease (CKD). Hisayama Risk Score (HRS) was calculated to estimate 10-year cardiovascular risks. Results: Mean %plaque volume (PV) and PCATA-RCA was 44±4.0％ and -77±8.8 HU. %PV was correlated with age (p<0.05), systolic blood pressure (p<0.05), non-HDL cholesterol (p<0.05), Hisayama risk score (p<0.05, Figure 2), PCATA-RCA (p<0.001, Figure 3), PCATA-LAD (p<0.001), and LCX-PCATA (p<0.001). In a multivariable linear regression model adjusting for age, sex, hypertension, diabetes, dyslipidemia, and current smoking (model 1), PCATA-RCA was independently associated with %PV [beta, 0.17; 95% confidential interval (CI) 0.115-0.217, p < 0.001]. In a model adjusting for age, sex, metabolic syndrome, body mass index ≥23kg/mm 2 , and CKD (model 2), PCATA-RCA (beta, 0.18; 95% CI 0.128-0.232, p<0.001) and high-risk HRS (beta, 3.1; 95% CI 1.35−4.87, p<0.001) were independently associated with %PV. Similarly, independent associations of PCATA in LAD and LCX with %PV was observed. Conclusion: This study demonstrates that PCATA is a robust marker related to increased burden of coronary atherosclerosis even in the early stage of atherosclerosis as defined by zero coronary artery calcium score.

Homocysteine Blood Levels and Mandatory Folic Acid Fortification in Serbia.

The current study aims to investigate the blood Hcy levels in patients with CAD and hypertension in Serbia, a country with a high incidence and mortality of both diseases. The level of Hcy in the Serbian population was assessed in 123 patients with chronic coronary artery disease (CAD) and hypertension. There were 53 patients with chronic CAD and 70 patients with hypertension (HTA), but without CAD. The Hcy levels were high in both groups of patients (the mean Hcy level of 16.0 ± 7.0 μmol/L) without a statistical difference between the patients in the CAD (14.9 ± 7.3 μmol/L) and hypertension (16.7 ± 6.7 μmol/L) groups. Hypercholesterolemia was found in 81% of the patients with CAD and 92.0% of the patients with HTA, as a common concern across both clinical conditions. It was also found that not a single conventional risk factor (diabetes, hypertension, the smoking status, the family history of CAD, and hyperlipidemia) may individually influence Hcy levels. By contrast, the low levels of vitamin B12 may be related to the high levels of Hcy. Given the fact that it is known that various factors interact and influence Hcy levels and associated cardiovascular risks, specific dietary habits, lifestyle and the other Serbia-specific possible factors were done.

Мікроциркуляція та варіабельність серцевого ритму при хронічній ішемічній хворобі серця і COVID-19

COVID-19 is associated with a wide range of negative effects on the cardiovascular system. The aim of our study was to investigate the impact of COVID-19 on the interdependence of changes in the microcirculation system and heart rate variability in patients with chronic coronary artery disease (CAD). An ECG study was performed in 12-lead leads, as well as 24-hour Holter ECG monitoring and laser Doppler flowmetry (LDF). Patients were divided into 3 groups. Group 1 included patients with coronary artery disease (n = 32), group 2 - with coronary artery disease in combination with COVID-19 (n = 35), and group 3 - with COVID-19 (n = 35). The control group consisted of 30 conditionally healthy individuals. All subjects were determined: microcirculation index, capillary blood flow reserve of the occlusion test, as well as nitroglycerin test and wavelet transform indicators (the relationship between the frequency and amplitude of microcirculatory oscillations, which are divided into endothelial, neurogenic, myogenic, respiratory and cardiac mechanisms of microcirculation regulation). The deterioration of endothelial function, as measured by the maximum amplitude of endothelial flux motions, should be noted, and a decrease in the endotheliumdependent and endothelium-independent components of microcirculation regulation. The capillary blood flow reserve of the occlusion test in patients with CAD in combination with COVID-19 was lower than in patients with CAD (group 1) and COVID-19 (group 3). In patients of the study groups, the total heart rate variability decreased, parasympathetic activity was weakened, and the QT interval duration and its variability increased compared with controls. These changes were most pronounced in patients with coronary artery disease in combination with COVID-19 in terms of the standard deviation of all intervals, the parasympathetic component of regulation, and both characteristics of the QT interval. Thus, patients with chronic CAD and concomitant COVID-19, along with endothelial dysfunction and worsening venous outflow, showed signs of autonomic dysregulation and increased QT interval duration and variability. Additional consideration of the characteristics of the microcirculatory bed, heart rate variability and QT interval is advisable in the examination system of such patients.

Chronic coronary artery disease: aspects of recording and coding in clinical practice (results of a survey of physicians)

Aim. To study the opinion of doctors about the applicability, frequency and criteria for practical use of codes of the International Classification of Diseases, 10th revision (ICD-10) from the group of chronic coronary artery disease (CAD) — I25.0, I25.1, I25.8, I25.9.Material and methods. This cross-sectional study was conducted in the period from February 27, 2024 to March 11, 2024 on a continuous sample of medical workers who agreed to participate in an anonymous survey as respondents. The questionnaire consisted of an introductory, personal and main part, which consisted of 19 questions devoted to various aspects of chronic CAD coding at the doctor’s appointment and during preparing medical death certificate. This article presents the results of a survey of cardiologists (group 1) and internists/general practitioners/family physicians (group 2). The χ2 test was used to compare two groups. The Friedman test was used to test the hypothesis that the physicians' opinion about the use of different chronic CAD codes was random. The Kendall test was used to assess the agreement between physicians. Calculations were carried out using Microsoft Office Excel 2021 and SPSS-26.0.Results. A total of 883 doctors from 47 constituent entities of the Russian Federation took part in the survey. Half of the respondents believed that there are differences between the codes I25.0, I25.1, I25.8, I25.9 and that they are necessary for statistical recording. Although cardiologists (59,2%) were less likely than internists/general practitioners/family doctors (65,9%) to believe that one or more of the 4 codes analyzed could be used only on the basis of risk factors, differences did not reach significance (p=0,1). The need to confirm chronic CAD using paraclinical research methods varied from 57,3% for code I25.9 to 83,1% for code I25.1. In case of death of a patient from chronic CAD, almost a third of respondents do not see the differences between the 4 specified codes, but are ready to use them in different clinical setting. In addition, 14,6% responded that when filling out medical death certificates they would not use any of the 4 specified codes. There is no agreement among physicians regarding the use of codes in clinical practice (Kendall's coefficient of concordance 0,084; p<0,001) and as a cause of death (0,148; p<0,001).Conclusion. There is no unified stance among doctors on the rules and applicability of using at least 4 codes (I25.0, I25.1, I25.8, I25.9). To correctly assess morbidity and mortality rates from individual forms of chronic ACAD based on ICD-10 codes, guidelines that should include a description and consideration of all the most significant clinical scenarios of chronic CAD should be developed.

Influence of multimorbidity on the risk of events in men with chronic coronary artery disease after myocardial infarction and percutaneous coronary intervention

Aim. To study the effect of multimorbidity on the risk of cardiovascular events (CVEs) in men with chronic coronary artery disease (CAD) after myocardial infarction (MI) and percutaneous coronary intervention (PCI).Material and methods. A total of 101 men with chronic CAD after MI and PCI were included in the study (mean age 60,5±6,1 years). Of these, taking into account the non-inclusion criteria and consent to examination, 2 following groups were formed: first (n=39) — men without CVEs; 2nd (n=39) — men with CVEs. In both groups, we studied the detection rate of grade I hypertension (HTN), class I obesity, hypercholesterolemia (HCE), and type 2 diabetes (T2D). The influence of HTN, obesity, HCE, and T2D on the risk of cardiovascular events was analyzed based on the calculation of contingency tables and Pearson's χ2, as well as odds ratios (OR) with 95,0% confidence intervals (CI). The follow-up period for patients averaged 3,6±0,5 years.Results. In men of group 2, compared with group 1 patients, grade I HTN, class I obesity, HCE were diagnosed more often in 1,3 (p=0,044), 1,4 (p=0,047), 1,2 (p=0,059) times, respectively. An increase in the risk of CVEs in men with chronic CAD, who underwent MI and PCI was associated with the detection of grade I HTN, class I obesity, HCE — OR 2,44 (CI: 1,88-6,75), OR 1,78 (CI: 1,56-4,62), OR 1,37 (CI: 1,11-4,17), respectively.Conclusion. Thus, the detection rate of grade I HTN, class I obesity and HCE in men with chronic CAD and CVEs at long-term follow-up after MI and PCI was significantly higher compared to patients with chronic CAD without CVEs after PCI. At the same time, the detection of grade I HTN, class I obesity and HCE were associated with an increased risk of cardiovascular events.

Incremental prognostic utility of left ventricular and left atrial strains in coronary artery disease patients with reduced systolic function.

This study aimed to investigate the predictive value of left ventricular global longitudinal strain (GLS) and left atrial reservoir strain (LARS) on adverse events in chronic coronary artery disease (CAD) patients with reduced systolic function. A total of 192 consecutive patients clinically diagnosed with chronic CAD and left ventricular ejection fraction (LVEF)≤50% were finally included. Multiple strain parameters were analyzed with speckle tracking echocardiography. The composite endpoint included all-cause mortality, rehospitalization due to heart failure, myocardial infarction, and stroke. Patients experiencing the endpoint showed lower LVEF, lower absolute GLS and LARS than those without events. Both GLS (AUC=0.82 [GLS] vs. 0.58 [LVEF], p < 0.001) and LARS (AUC=0.71 [LARS] vs. 0.58 [LVEF], p=0.033) were superior to LVEF in predicting adverse events. Multivariate cox regression analysis showed that both GLS (hazard ratio, 0.71; 95% CI, 0.63-0.79; p < 0.001) and LARS (hazard ratio, 0.96; 95% CI, 0.93-0.98; p < 0.001) were independent predictors for the endpoint. The addition of LARS (global chi-squared, 35.7vs. 17.4; p < 0.05), GLS (global chi-squared, 58.6vs. 17.4; p < 0.05) or both LARS and GLS (global chi-squared, 79.6vs. 17.4; p < 0.05) to LVEF in the prediction model significantly improved its performance. The same significant improvement was also shown in the subgroups of mild (30%<LVEF≤50%) and severe (LVEF≤30%) reduced systolic function. Regarding CAD patients with reduced LVEF, both GLS and LARS are superior to LVEF in predicting adverse events, providing significant incremental value to LVEF.

Enhancing Prediction of Myocardial Recovery After Coronary Revascularization: Integrating Radiomics from Myocardial Contrast Echocardiography with Machine Learning.

Chronic coronary artery disease (CAD) management often relies on myocardial contrast echocardiography (MCE), yet its effectiveness is limited by subjective interpretations and difficulty in distinguishing hibernating from necrotic myocardium. This study explores the integration of machine learning (ML) with radiomics to predict functional recovery in dyskinetic myocardial segments in CAD patients undergoing revascularization, aiming to overcome these limitations. This prospective study enrolled 55 chronic CAD patients, dividing into training (39 patients, 205 segments) and testing sets (16 patients, 68 segments). Dysfunctional myocardial segments were identified by initial wall motion scores (WMS) of ≥2 (hypokinesis or higher). Functional recovery was defined as a decrease of ≥1 grade in WMS during follow-up echocardiography. Radiomics features were extracted from dyssynergic segments in end-systolic phase MCE images across five cardiac cycles post- "flash" impulse and processed through a five-step feature selection. Four ML classifiers were trained and compared using these features and MCE parameters, to identify the optimal model for myocardial recovery prediction. Functional improvement was noted in 139 out of 273 dyskinetic segments (50.9%) following revascularization. Receiver Operating Characteristic (ROC) analysis determined that myocardial blood flow (MBF) was the most precise clinical predictor of recovery, with an area under the curve (AUC) of 0.770. Approximately 1.34 million radiomics features were extracted, with nine features identified as key predictors of myocardial recovery. The random forest (RF) model, integrating MBF values and radiomics features, demonstrated superior predictive accuracy over other ML classifiers. Validation of the RF model on the testing dataset demonstrated its effectiveness, evidenced by an AUC of 0.821, along with consistent calibration and clinical utility. The integration of ML with radiomics from MCE effectively predicts myocardial recovery in CAD. The RF model, combining radiomics and MBF values, presents a non-invasive, precise approach, significantly enhancing CAD management.

Patient decision aids for aortic stenosis and chronic coronary artery disease: a systematic review and meta-analysis.

Shared decision-making is recommended for patients considering treatment options for severe aortic stenosis (AS) and chronic coronary artery disease (CAD). This review aims to systematically identify and assess patient decision aids (PtDAs) for chronic CAD and AS and evaluate the international evidence on their effectiveness for improving the quality of decision-making. Five databases (Cochrane, CINAHL, Embase, MEDLINE, and PsycInfo), clinical trial registers, and 30 PtDA repositories/websites were searched from 2006 to March 2023. Screening, data extraction, and quality assessments were completed independently by multiple reviewers. Meta-analyses were conducted using Stata statistical software. Eleven AS and 10 CAD PtDAs were identified; seven were less than 5 years old. Over half of the PtDAs were web based and the remainder paper based. One AS and two CAD PtDAs fully/partially achieved international PtDA quality criteria. Ten studies were included in the review; four reported on the development/evaluation of AS PtDAs and six on CAD PtDAs. Most studies were conducted in the USA with White, well-educated, English-speaking participants. No studies fulfilled all quality criteria for reporting PtDA development and evaluation. Meta-analyses found that PtDAs significantly increased patient knowledge compared with 'usual care' (mean difference: 0.620; 95% confidence interval 0.396-0.845, P < 0.001) but did not change decisional conflict. Patients who use PtDAs when considering treatments for AS or chronic CAD are likely to be better informed than those who do not. Existing PtDAs may not meet the needs of people with low health literacy levels as they are rarely involved in their development. PROSPERO: CRD42021264700.

Developing and evaluating a chronic ischemic cardiomyopathy in swine model by rest and stress CMR.

A large animal model of chronic coronary artery disease (CAD) is crucial for the understanding the underlying pathophysiological processes of chronic CAD and consequences for cardiac structure and function. The goal of this study was to develop a chronic model of CAD in a swine model and to evaluate the changes of myocardial structure, myocardial motility, and myocardial viability during coronary stenosis. A total of 30 swine (including 24 experimental animals and 6 controls) were enrolled. The chronic ischemia model was constructed by using Ameroid constrictor in experimental group. The 24 experimental animals were further divided into 4 groups (6 animals in each group) and were sacrificed at 1, 2, 3 and 4 weeks after operation for pathological examination, respectively. Cardiac magnetic resonance (CMR) was performed preoperatively and weekly postoperatively until sacrificed both in experimental and control group. CMR cine images, rest/adenosine triphosphate (ATP) stress myocardial contrast perfusion and LGE were performed and analyzed. The rest wall thickening (WT) score was calculated from rest cine images. The MPRI (myocardial perfusion reserve index) and MPR (myocardial perfusion reserve) were calculated based on rest and stress perfusion images. Pathology staining including triphenyltetrazolium chloride, HE and picrosirus red staining were performed after swine were sacrificed and collagen volume fraction (CVF) was calculated. The time to formation of ischemic, hibernating, and infarcted myocardium was recorded. In experimental group, from 1w to 4w after surgery, the rest WT score decreased gradually from 35.2 ± 2.0%, 32.0 ± 2.9% to 30.5 ± 3.0% and finally 29.06 ± 1.78%, p < 0.001. Left ventricular ejection fraction was gradually impaired after modeling (58.9 ± 12.6%, 56.3 ± 10.1%, 55.3 ± 9.0%, 53.8 ± 9.9%, respectively). And the MPR and MPRI also decreased stepwise with extent of surgery time (MPRI dropped from 2.1 ± 0.4, 2.0 ± 0.2 to 1.8 ± 0.3 and finally 1.7 ± 0.1, p = 0.004; MPR dropped from 2.3 ± 0.4, 2.1 ± 0.2 to 1.9 ± 0.4 and finally 1.8 ± 0.1, p < 0.001). Stronger associations between MPR, MPRI and CVF were paralleled lower wall thickening scores in fibrosis-affected areas. The ischemic myocardium was first appeared in the first week after surgery (involving ten segments), hibernated myocardium was first appeared in the second week after surgery (involving seventeen segments). LGE was first appeared in eight swine in the third weeks after surgery (16 segments). At 4w after surgery, average 9.6g scar tissue was found among 6 swine. At the same time, histological analysis established the presence of fibrosis and ongoing apoptosis in the infarcted area. In conclusion, our study provided valuable insights into the pathophysiological processes of chronic CAD and its consequences for cardiac structure and function in a large animal model through combining myocardial motion and stress perfusion.

Clinical efficacy of permanent internal mammary artery occlusion in chronic coronary artery disease: a double-blind, randomized, sham-controlled trial

Abstract Introduction Natural internal mammary artery (IMA) bypasses to the coronary circulation have been shown to act as extracardiac sources of myocardial blood supply, which has been found augmented by right IMA device occlusion. The goal of this randomized, sham-controlled trial was to test the efficacy of permanent right or left IMA device occlusion on symptoms of chronic coronary artery disease (CAD), on coronary artery occlusive blood supply, as well as on myocardial ischemia. Methods This was a prospective superiority trial in 100 patients with chronic CAD randomly allocated (1:1) to IMA permanent vascular device occlusion (verum group) or to IMA sham intervention (placebo group). The primary study endpoint was the change in treadmill exercise time (DET in seconds, s) during 6 weeks of follow-up after trial intervention. Secondary study endpoints were the changes in simultaneously obtained collateral flow index (CFI), and angina pectoris during a 1-minute proximal balloon occlusion of the coronary artery of interest. CFI is the ratio between simultaneous mean coronary occlusive divided by mean aortic pressure both subtracted by central venous pressure. Results In the verum and placebo group, exercise time changed from 398±176s to from 421±198s in the verum group (p=0.1745), and from 426±162s to 430±166s in the placebo group (p=0.55); DET was +23±116s and +4±120s, respectively (p=0.44). CFI change during follow-up was +0.022±0.061 in the verum and -0.039±0.072 in the placebo group (p&amp;lt;0.0001). Angina pectoris at follow-up during the coronary balloon occlusion for CFI measurement had decreased or disappeared in 20/48 patients of the verum group, and in 10/47 patients of the placebo group (p=0.0336). Conclusion Permanent IMA device occlusion tends to augment treadmill exercise time in response to heightened coronary artery occlusive blood supply, the fact of which is reflected by mitigated signs of myocardial ischemia.

Colchicine and diabetes in patients with chronic coronary artery disease: insights from the LoDoCo2 randomized controlled trial.

Despite optimal treatment, patients with chronic coronary artery disease (CAD) and diabetes mellitus (DM) are at high risk of cardiovascular events, emphasizing the need for new treatment options. The Low-Dose Colchicine 2 (LoDoCo2) trial demonstrated that colchicine reduces cardiovascular risk in patients with chronic CAD. This analysis determines the efficacy of colchicine in patients with chronic CAD and DM as well as the effect of colchicine on the development of new-onset type 2 diabetes mellitus (T2DM). The LoDoCo2 trial randomized 5,522 patients to placebo or colchicine 0.5 mg once daily, with a median follow-up of 28.6 months. The primary composite endpoint was cardiovascular death, spontaneous myocardial infarction, ischemic stroke, or ischemia-driven revascularization. The effect of its treatment in patients with and without DM was evaluated by including an interaction term in the model. A total of 1,007 participants (18.2%) had T2DM at baseline. The adjusted hazard ratio (HR) [(95% confidence interval (CI)] for the primary endpoint in the T2DM group was 1.52 (1.15-2.01, p < 0.01) compared with the group without T2DM. The HR for the treatment effect on the primary endpoint was 0.87 (0.61-1.25) in participants with T2DM and 0.64 (0.51-0.80) in participants without diabetes (pinteraction = 0.14). The incidence of new-onset T2DM was 1.5% (34 out of 2,270) in the colchicine group and 2.2% (49 out of 2,245) in the placebo group (p = 0.10). In conclusion, based on the current evidence, the beneficial effects of colchicine on cardiovascular endpoints are consistent regardless of DM status. The potential benefits of colchicine in preventing new-onset DM need further investigation. These findings are only hypothesis-generating and require larger prospective trials to confirm the results.

Identification of leptin resistance in patients with coronary artery disease and heart defects

Aim. To compare the incidence of leptin resistance (LR) in patients with acute and chronic coronary artery disease (CAD) and patients with acquired heart defects (AHD).Material and methods. The study included 234 patients: 114 patients with acute myocardial infarction (MI) and 120 patients with chronic CAD. The comparison group consisted of 48 patients with degenerative non-rheumatic AHD — aortic stenosis (AS). The control group consisted of 40 healthy volunteers. On the 1st day of hospitalization, the concentration of leptin and leptin receptor was measured, and the free leptin index (FLI) was assessed. LR was recorded at leptin &gt;6,45 ng/ ml and FLI &gt;25. Statistical data processing was carried out using the software package Statistica 10.0 and SPSS 17.0 for Windows.Results. Initially, LR in MI, chronic CAD and non-coronary disease was revealed in 64%, 56,2% and 25%, respectively. Significant differences in the incidence of LR were observed between patients with MI and chronic CAD relative to patients with AHD (p=0,02 and p=0,03, respectively), while no differences were found between patients with coronary pathology (p=0,82). Equation of patients for body mass index (BMI) did not affect the incidence of LR. High incidence of LR remained for patients with acute and chronic CAD, and amounted to 63% and 57,3%, respectively, while for patients with AS — 25%.Conclusion. Patients with acute and chronic CAD are characterized by a high LR incidence, in contrast to patients with AHD. The number of LR cases in patients with coronary pathology did not depend on BMI values, which indicates possible alternative leptin sources contributing the development of hyperleptinemia. In addition, studying the mechanisms underlying the leptin receptor decrease in CAD is necessary for adequate leptin effects and the prevention of LR.

Monocyte-to-High Density Lipoprotein Cholesterol Ratio Positively Predicts Coronary Artery Disease and Multi-Vessel Lesions in Acute Coronary Syndrome.

We investigated the hypothesis that MHR (monocyte-to-high density lipoprotein cholesterol ratio) is related to the severity of coronary artery in ACS (acute coronary syndrome). In this case-control study, we recruited 15,853 participants undergoing the first time percutaneous coronary intervention (PCI) including 4093 normal controls, 10,518 chronic coronary artery disease (CAD), and 1242 ACS cases. Examination of demographic clinical data and biochemical profiles, as well as MHR values, were performed before PCI. The relationship between MHR and severity of coronary artery lesion in ACS was analyzed. We also used a flow cytometric assay to distinguish CD14+/CD16- classical monocyte subsets in peripheral blood mononucleated cells from CAD patients. MHR was higher in patients with ACS compared with MHR in normal control and chronic CAD (normal control vs chronic CAD vs ACS: 0.46 ± 0.27 × 109/mmol vs 0.53 ± 0.29 × 109/mmol vs 0.73 ± 0.47 × 109/mmol, P < 0.001). MHR showed a significantly progressive increase as the angiographic severity of coronary lesions increased (single vessel lesion vs multi-vessel lesions in ACS: 0.54 ± 0.31 × 109/mmol vs 0.58 ± 0.35 × 109/mmol, P < 0.001), and classical monocyte subset to HDL-C ratio (CMHR) was increased in with CAD patients compared with control [4.69 (IQR, 1.06, 2.97) × 103/mmol vs 1.92 (IQR, 0.92, 3.04) × 103/mmol, P = 0.02]. Using a multivariate analysis, after adjusting for age, gender, body mass index (BMI), diabetes, and dyslipidemia, MHR was positively associated with multi-vessel lesions in ACS [OR (odds ratio): 1.28 (95% CI: 1.03-1.59, P = 0.029)]. MHR level could be a potential predictor of coronary artery lesion severity in ACS.

The Presence of Residual Vascular and Adipose Tissue Inflammation on 18F-FDG PET in Patients with Chronic Coronary Artery Disease

PurposeWe evaluated the residual vascular and adipose tissue inflammation in patients with chronic coronary artery disease (CAD) using positron emission tomography (PET).MethodsOur study population consisted of 98 patients with known CAD and 94 control subjects who had undergone 18F-fluorodeoxyglucose (18F-FDG) PET due to non-cardiac reasons. Aortic root and vena cava superior 18F-FDG uptake were measured to obtain the aortic root target-to-background ratio (TBR). In addition, adipose tissue PET measurements were done in pericoronary, epicardial, subcutaneous, and thoracic adipose tissue. Adipose tissue TBR was calculated using the left atrium as a reference region. Data are presented as mean ± standard deviation or as median (interquartile range).ResultsThe aortic root TBR was higher in CAD patients compared to control subjects, 1.68 (1.55–1.81) vs. 1.53 (1.43–1.64), p < 0.001. Subcutaneous adipose tissue uptake was elevated in CAD patients 0.30 (0.24–0.35) vs. 0.27 (0.23–0.31), p < 0.001. Metabolic activity of CAD patients and control subjects was comparable in the pericoronary (0.81 ± 0.18 vs. 0.80 ± 0.16, p = 0.59), epicardial (0.53 ± 0.21 vs. 0.51 ± 0.18, p = 0.38) and thoracic (0.31 ± 0.12 vs. 0.28 ± 0.12, p = 0.21) adipose tissue regions. Aortic root or adipose tissue 18F-FDG uptake was not associated with the common CAD risk factors, coronary calcium score, or aortic calcium score (p value > 0.05).ConclusionPatients with a chronic CAD had a higher aortic root and subcutaneous adipose tissue 18F-FDG uptake compared to control patients, which suggests residual inflammatory risk.

Analysis of myocardial revascularization and endpoints after a 1-year follow-up of patients with acute and chronic coronary artery disease, depending on diabetes presence

Aim. To analyze myocardial revascularization in patients with acute and chronic coronary artery disease (CAD) and with different glycemic status, as well as to evaluate complications after a 1-year follow-up.Material and methods. This prospective comparative clinical study included 202 patients of both sexes with acute and chronic coronary artery disease. Depending on the glycemic status and CAD type, the patients were divided into four groups: acute CAD and type 2 diabetes (T2D); acute CAD without T2D (control group); chronic CAD and T2D; chronic CAD without DM2 (control group). Depending on the clinical condition and the results of coronary angiography, patients underwent various types of myocardial revascularization: balloon angioplasty without stenting, stenting, coronary artery bypass grafting, stenting + coronary artery bypass grafting. One year after discharge, all patients were contacted to evaluate complications and endpoints, which included recurrent myocardial infarction, cerebrovascular accident, readmission, revascularization, and death. Total indicator of endpoints was assessed.Results. Up to 80% of patients with acute and chronic CAD, regardless of glycemic status, underwent revascularization, mainly stenting. The prevalence of stenting among persons without T2D with acute and chronic CAD was significantly higher compared with patients with T2D. The absolute number of patients with coronary artery bypass grafting, including in combination with stenting, was higher in the T2D groups. In groups without T2D, the number of patients with one stent was 2-2,5 times higher compared to groups with T2D — acute CAD (p=0,041) and chronic CAD (p=0,017). The prevalence of implantation of ≥2 stents did not differ between the groups. Within 1 year after discharge, there were more hospitalizations and reoperations among people with acute and chronic CAD and T2D. The groups did not differ in the number of non-fatal and fatal complications, although the absolute numbers of these indicators were higher in patients with T2D. The total number of endpoints in T2D people, regardless of the CAD type, were 2 times higher compared to the corresponding control groups (p&lt;0,001).Conclusion. Most patients with acute and chronic CAD, regardless of glycemic status, underwent myocardial revascularization. In patients without T2D, stenting prevailed, most often of one coronary artery. Patients with T2D, along with stenting, underwent coronary bypass grafting, as well as a combination of these two procedures. After a year of follow-up, the number of complications in patients with T2D was 2 times higher compared to patients without type 2 diabetes, which emphasizes the importance of secondary prevention, including complex drug treatment.

The effects of colchicine in patients with diabetes mellitus and chronic coronary artery disease: a post-hoc analysis of the LoDoCo2-trial

Abstract Background Atherosclerosis is an inflammatory disease and is accelerated by diabetes mellitus (DM). Patients with chronic coronary artery disease (CAD) who also have DM are at high risk of recurrent cardiovascular events. The role of inflammation in atherosclerosis is well established, whereas the role of inflammation on incident and progression of DM has been hypothesized. The nucleotide-binding oligomerization domain-, leucine-rich repeat-, and pyrin domain-containing protein 3 (NLRP3) inflammasome in particular, may play an important role in the onset and progression of T2DM. The anti-inflammatory drug colchicine attenuates the NLRP3-inflammasome. The Low-Dose Colchicine 2 (LoDoCo2) trial showed that colchicine reduces cardiovascular risk in patients with chronic CAD. Purpose The purpose of this study was to assess the effects of colchicine in patients with chronic CAD and DM on cardiovascular events as well as the effect of colchicine on the development of new-onset DM. Methods The LoDoCo2 trial randomized 5522 to placebo or colchicine, with a median follow-up of 28.6 months (interquartile range 20.5–44.4). The primary endpoint was a composite of cardiovascular death, spontaneous myocardial infarction, ischaemic stroke, or ischaemia-driven revascularization. Secondary outcomes consisted of the aforementioned events, separately. Cox proportional hazards models were used to investigate univariable associations between DM status for all endpoints in the placebo group. The interactions between treatment group and DM status were evaluated with the addition of treatment and the treatment-by-DM variable interaction. Results In total, 1007 participants (18.2%) had DM at baseline. The hazard ratio for the primary endpoint was 0.87 (95% CI, 0.61–1.25) in those with DM and 0.64 (95% CI, 0.51–0.80) in those without DM (p for interaction&amp;gt;0.05). Treatment effects of colchicine were consistent over all secondary endpoints (p for interaction&amp;gt;0.05). The incidence of new-onset DM was 1.5% (34/2270) in the colchicine group and 2.2% (49/2245) in the placebo group (p=0.10). Participants with DM were at higher risk for all endpoints. The primary composite end point in the placebo group occurred in 13.0% (67/515) patients with DM and in 8.8% (197/2245) of the patients without DM (unadjusted hazard ratio 1.54 [95% CI 1.16–2.03, p&amp;lt;0.01]) compared to the group without DM. DM was also strongly associated with the occurrence of all secondary end points. Conclusion This study shows that the beneficial effects of colchicine on cardiovascular endpoints are consistent regardless of DM status. The data indicate that larger trials are needed to assess whether colchicine reduces the incidence of new-onset DM. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): National Health Medical Research Council of Australia and the Netherlands Organization for Health Research and Development

Individual lifetime benefit from low-dose colchicine in chronic coronary artery disease patients

Abstract Background Low-dose colchicine reduces the risk of cardiovascular events in patients with chronic coronary artery disease (CAD), but the absolute benefit may vary between patients. Individual benefit from preventive therapies can be estimated using the guideline-recommended SMART-REACH model. Purpose This study aimed to assess the range of individual absolute 10-year and lifetime benefit from low-dose colchicine according to patient risk profile. Methods The SMART-REACH model was combined with the relative treatment effect of low-dose colchicine, and applied to all participants from the LoDoCo2 trial (n=5,522), and patients with chronic CAD from the UCC-SMART cohort (n=5,308). Individual treatment benefit was expressed as (i) 10-year absolute risk reductions (ARRs) for myocardial infarction, ischemic stroke, or cardiovascular death (MACE), and (ii) life-years gained free of MACE. Predictions were also performed for MACE plus ischemia-driven coronary revascularization (MACE+), through development of a new competing risk-adjusted lifetime prediction model in data from the REACH registry (n=14,522). Low-dose colchicine was compared to alternative intensive prevention goals, i.e. low density lipoprotein-cholesterol (LDL-c) reduction to &amp;lt;1.4 mmol/L, and systolic blood pressure (SBP) reduction to &amp;lt;130 mmHg. Results Median individual 10-year ARR for MACE from low-dose colchicine therapy was 4.6% (interquartile range [IQR] 3.6–6.0%), and median gain in life expectancy free of MACE was 2.0 (IQR 1.6–2.5) years. Median 10-year ARR for MACE+ was 8.6% (IQR 7.6–9.8%), and median gain in MACE+-free life expectancy was 3.4 (IQR 2.6–4.2) years. For intensified LDL-c and SBP reduction respectively, median 10-year ARRs were 3.0% (IQR 1.5–5.1%) and 1.7% (IQR 0.0–5.7%) for MACE, and 5.2% (IQR 2.5–8.7%) and 2.9% (IQR 0.0–9.5%) for MACE+. Median life-years gained from LDL-c and SBP reduction were 1.2 (IQR 0.6–2.1) and 0.7 (IQR 0.0–2.3) years free of MACE, and 1.8 (IQR 0.8–3.3) and 0.9 (IQR 0.0–3.4) years free of MACE+. Conclusion The individual absolute benefit from low-dose colchicine varies between patients. In an era where lipid- and blood pressure-lowering therapies are already routinely used, the benefits of low-dose colchicine are expected to be of at least similar magnitude to those of intensified LDL-c and SBP reduction in patients with chronic CAD. Funding Acknowledgement Type of funding sources: None.

End-of-trial inflammatory biomarkers, lipid levels, creatine kinase and markers of renal and liver function in the LoDoCo2 trial

Abstract Background The Low-Dose Colchicine 2 (LoDoCo2) trial demonstrated that colchicine reduced major cardiovascular events in patients with chronic coronary artery disease (CAD). The effect of long-term colchicine treatment on inflammatory biomarkers and markers reflecting renal and liver function have not been investigated yet. Purpose This substudy examines levels of inflammatory biomarkers, lipid fractions, creatine kinase (CK) and markers of renal and liver function at close-out of the trial. Methods The LoDoCo2 trial randomly assigned patients with chronic CAD to colchicine 0.5 mg once daily or placebo. Blood samples were drawn during close-out visits after a median follow-up of 32.7 (interquartile range [IQR] 24.0–48.6) months. Results Assignment to colchicine was associated with lower levels of high-sensitivity C-Reactive Protein (0.94 mg/L [0.53–1.93] vs. 1.24 mg/L [0.73–2.55]; −24.2%; p&amp;lt;0.01) and interleukin-6 (2.70 ng/L [1.79–4.18] vs. 3.16 ng/L [2.07–4.95]; −14.9%; p&amp;lt;0.01), but was not associated with any differences in lipid fractions or markers of renal function. Although CK levels were higher after colchicine (123.0 U/L, [84.0–184.0] vs. 110.0 U/L, [77.0–164.0], p&amp;lt;0.01), the number of participants with marked elevations of CK (&amp;gt;5 times upper limit of normal [ULN]) was low and not different between treatment groups. Levels of alanine aminotransferase (ULN 40 U/L) and albumin (ULN 50 U/L) were higher (p&amp;lt;0.01) in the colchicine group compared to placebo (30.0 U/L [22.0–40.0] vs. 26.0 U/L [19.0–34.0] and 43.01 g/L±2.39 vs. 42.64 g/L±2.48, respectively). There were no differences in gamma-glutamyl transferase or bilirubin. Conclusion Long-term low-dose colchicine in patients with chronic CAD was associated with lower levels of hs-CRP and IL-6 but was not associated with clinically important differences in lipid fractions, CK, renal or liver function. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): The National Health Medical Research Council of AustraliaThe Netherlands Organization for Health Research and Development