Chronic Chronic Coronary Artery Disease Research Articles

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.

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, 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 five years old. Over half 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 to 'usual care' (mean difference:0.620; 95%CI 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.

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

The impact of affective disorders on self-assessment of the quality of life in patients with chronic coronary artery disease

Aim. To determine the differences in self-assessment of social functioning by patients with chronic coronary artery disease (CAD), depending on the presence of comorbid affective disorders (ADs).Materials and methods. Using the Social Adaptation Self-Evaluation Scale (SASS), which makes it possible to assess the degree of social functioning and satisfaction with various aspects of social life, we studied the features of the social functioning of heart hospital patients with chronic CAD with (n = 248) and without AD (n = 291). In 290 patients (average age 56.6 ± 6.7 years) with chronic CAD, chronic ADs (45%) were revealed; depressive episodes (DEs) were diagnosed for the first time in 24% of patients, and 24.5% of patients had recurrent DEs. Bipolar disorder was found in 6.5% of cases. Qualitative and quantitative parameters were investigated using the Mann – Whitney U test and Student’s t-test. To assess the frequencies, the Pearson’s chi-squared test was used.Results. The mean total SASS score in the patients with chronic CAD with AD corresponded to difficult social adaptation (33.7 [29.5; 39]), while the patients without AD had good social adaptation score of 40.8 ± 6.3 (p &lt; 0.05). In the group without AD, patients with normal social adaptation prevailed (n = 215; 73.8%), while patients with AD more often had difficulties with social adaptation (n = 148; 59.7%). In the CAD patients, depending on the presence of AD, the frequency of disturbances in various spheres of social adaptation differed: employment, interest in and pleasure from activities, disposition of income, pleasure from and interest in seeking information, social support (p = 0.001).Conclusion. Higher frequency of pronounced impairment in social functioning in patients with chronic CAD with AD determines the need for taking this fact into consideration when planning rehabilitation measures in this group of patients.

Long-Term Treatment with the Combination of Rivaroxaban and Aspirin in Patients with Chronic Coronary or Peripheral Artery Disease: Outcomes During the Open Label Extension of the COMPASS trial.

To describe outcomes of patients with chronic coronary artery disease (CAD) and/or peripheral artery disease (PAD) enrolled in the Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) randomized trial who were treated with the combination of rivaroxaban 2.5mg twice daily and aspirin 100mg once daily during long-term open-label extension (LTOLE). Of the 27 395 patients enrolled in COMPASS, 12 964 (mean age at baseline 67.2 years) from 455 sites in 32 countries were enrolled in LTOLE and treated with the combination of rivaroxaban and aspirin for a median of 374 additional days (range 1-1191 days). During LTOLE, the incident events per 100 patient years were as follows: for the primary outcome [cardiovascular death, stroke, or myocardial infarction (MI)] 2.35 [95% confidence interval (CI) 2.11-2.61], mortality 1.87 (1.65-2.10), stroke 0.62 (0.50-0.76), and MI 1.02 (0.86-1.19), with CIs that overlapped those seen during the randomized treatment phase with the combination of rivaroxaban and aspirin. The incidence rates for major and minor bleeding were 1.01 (0.86-1.19) and 2.49 (2.24-2.75), compared with 1.67 (1.48-1.87) and 5.11 (95% CI 4.77-5.47), respectively, during the randomized treatment phase with the combination. In patients with chronic CAD and/or PAD, extended combination treatment for a median of 1 year and a maximum of 3 years was associated with incidence rates for efficacy and bleeding that were similar to or lower than those seen during the randomized treatment phase, without any new safety signals.

The Clinical Impact of β-Blocker Therapy on Patients With Chronic Coronary Artery Disease After Percutaneous Coronary Intervention.

The outcome benefits of β-blockers in chronic coronary artery disease (CAD) have not been fully assessed. We evaluated the prognostic impact of β-blockers on patients with chronic CAD after percutaneous coronary intervention (PCI). A total of 3,075 patients with chronic CAD were included from the Grand Drug-Eluting Stent registry. We analyzed β-blocker prescriptions, including doses and types, in each patient at 3-month intervals from discharge. After propensity score matching, 1,170 pairs of patients (β-blockers vs. no β-blockers) were derived. Primary outcome was defined as a composite endpoint of all-cause death and myocardial infarction (MI). We further analyzed the outcome benefits of different doses (low-, medium-, and high-dose) and types (conventional or vasodilating) of β-blockers. During a median (interquartile range) follow-up of 3.1 (3.0-3.1) years, 134 (5.7%) patients experienced primary outcome. Overall, β-blockers demonstrated no significant benefit in primary outcome (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.63-1.24), all-cause death (HR, 0.87; 95% CI, 0.60-1.25), and MI (HR, 1.25; 95% CI, 0.49-3.15). In subgroup analysis, β-blockers were associated with a lower risk of all-cause death in patients with previous MI and/or revascularization (HR, 0.38; 95% CI, 0.14-0.99) (p for interaction=0.045). No significant associations were found for the clinical outcomes with different doses and types of β-blockers. Overall, β-blocker therapy was not associated with better clinical outcomes in patients with chronic CAD undergoing PCI. Limited mortality benefit of β-blockers may exist for patients with previous MI and/or revascularization. ClinicalTrials.gov Identifier: NCT03507205.

Clinical values of resting electrocardiography in patients with known or suspected chronic coronary artery disease: a stress perfusion cardiac MRI study

BackgroundElectrocardiography (ECG) is an essential investigation in patients with chronic coronary artery disease (CAD). However, evidence regarding the diagnostic and prognostic value of ECG in this population is limited. Therefore, we sought to determine whether baseline ECG abnormalities were associated with myocardial ischemia and cardiac events in patients with known or suspected chronic CAD.MethodsConsecutive patients with known (n = 146) or suspected chronic CAD (n = 349) referred for adenosine stress cardiac magnetic resonance (CMR) between 2011 and 2014 were enrolled. Resting ECGs were classified as major, minor, and no abnormalities. Predictors of myocardial ischemia on CMR and major adverse cardiac events (MACE) including cardiac death, nonfatal myocardial infarction, hospitalization for heart failure and late revascularization (> 180 days after CMR) were evaluated.ResultsAverage age was 69 ± 11 years (51% men). One hundred and eighty-five patients (37.4%) had major and 154 (31.1%) had minor ECG abnormalities. In patients with suspected CAD, myocardial ischemia was presented in 83 patients (23.8%). Multivariable analysis demonstrated major ECG abnormality as the strongest predictor of myocardial ischemia (HR 2.51; 95% CI 1.44–4.36; p = 0.001). Adding ECG to clinical pretest probability models improved the prediction of myocardial ischemia in ROC analyses (p = 0.04). In the whole cohort (n = 495), 91 MACE occurred during the median follow-up period of 4.8 years. Multivariable analysis showed that diabetes mellites, history of heart failure, prior revascularization, left ventricular ejection fraction, ischemia, and major ECG abnormality were independent predictors of MACE.ConclusionAbnormal resting ECG is common in patients with known or suspected chronic CAD. ECG had important diagnostic and prognostic values in this population.

MRI assessment of the abdominal adipose tissue and the state of the abdominal aorta in patients with coronary artery disease: association with metabolic disorders

Aim. To evaluate potential associations between quantitative features of visceral and subcutaneous adipose tissue (AT) and anthropometric characteristics of obesity, metabolic disorders, and the state of the abdominal aorta in patients with chronic coronary artery disease (CAD).Materials and methods. The study included 55 patients (average age 61.2 ± 7.2 years) with chronic CAD. Magnetic resonance imaging (MRI) was performed on a 1.5 T MRI scanner using T2-weighted spin-echo modes. The area and volume of abdominal subcutaneous (SAT) and visceral adipose tissue (VAT) were calculated at the L4–L5 level; the total volumes of abdominal SAT and VAT were determined. Parameters of lipid and carbohydrate metabolism, as well as adipokine profile were studied in the blood serum.Results. In the course of a multiple linear regression analysis, we detected the independent determinants, which described 95% of the total VAT volume variability and were represented by waist circumference (WC) and serum levels of high-density lipoprotein (HDL) cholesterol and adiponectin. The model was characterized by the significance level p &lt; 0.000001, the residuals of the model were normal. We calculated the coefficients in the model: 1.39 for WC, –0.26 for HDL cholesterol, and –0.19 for adiponectin. We detected a positive correlation between the abdominal aorta (AA) diameter and SAT area at the L4–L5 level (rs = 0.48; p = 0.0014), which does not depend on gender, and reverse correlations between the aorta diameter and glycated hemoglobin (HbA1c) level (rs = –0.40; p = 0.0359) and postprandial glycemia (rs = –0.40; p = 0.0273). The patients with a dilated aorta (group 2), when compared with the patients with a normal aorta diameter (group 1), did not differ in the AT accumulation, but demonstrated decreased levels of HbA1c and postprandial glycemia, which resulted in a smaller number of patients with type 2 diabetes mellitus.Conclusion. We identified independent determinants of an increase in the total volume of abdominal visceral AT, such as an increase in WC and a decrease in serum adiponectin and HDL cholesterol levels. Results of the study indicate the presence of a link between the AA remodeling, accumulation of subcutaneous AT, and impaired glucose metabolism.

Assessment of the visceral adipose tissue by magnetic resonance imaging in patients with coronary artery disease: link to metabolism disorders and condition of the abdominal aorta

Abstract Aim MRI-quantification of the visceral and subcutaneous adipose tissue (AT) and investigation of its interconnections with anthropometric parameters of obesity, carbohydrate metabolism and condition of abdominal aorta in patients with chronic coronary artery disease (CAD). Methods The study included 55 patients (mean age 61.2±7.2 y.o.) with chronic CAD. All patients underwent MRI of the abdominal AT and abdominal aorta segment on a 1.5 T MRI in standard modes. Calculation of the area and volume of abdominal subcutaneous (SAT) and visceral adipose tissue (VAT) was conducted at L4-L5 level; the total volumes of abdominal SAT and VAT were calculated. Parameters of lipid and carbohydrate metabolism as well adipokines' profile were measured in blood serum. Results To eliminate gender bias the data in the total group was corrected for the sex, height and body weight. In the course of the multiple linear regression analysis, we detected the independent determinants, which described 95% of the total VAT volume variability and were represented by waist circumference and serum levels of HDL cholesterol and adiponectin. The model was characterized by the significance level p&amp;lt;0,ehab724.116501, the residues of the model were normal. The evaluation of the coefficients in the model was as following: 1,39 for waist circumference, −0.26 for HDL cholesterol and −0,19 for adiponectin. We detected direct correlation between the aorta diameter and total SAT volume (rs=0.30), which was independent from sex; and reverse correlations between the aorta diameter and HbA1c level (rs=−0.40) and postprandial glycemia (rs=−0.40). Patients with dilated aorta when compared to the patients with normal aorta diameter did not differ in the AT accumulation, but demonstrated decreased levels of HbA1c and postprandial glycaemia, which was dependent upon the lower numbers of patients with diabetes mellitus type 2. Conclusion We have identified the independent determinants of the total volume of the abdominal visceral AT increase, which appeared to be increment of the waist circumference and decrease of the serum adiponectin and HDL cholesterol. Results of the study indicate the presence of the interconnection between the processes of the abdominal aorta remodeling, accumulation of subcutaneous adipose tissue and carbohydrate metabolism impairments. Funding Acknowledgement Type of funding sources: None. MRI of the abdominal tissueMRI of the abdominal aorta

Circulating FoxP3+ T-lymphocytes in chronic coronary artery disease: Associations with the severity of atherosclerosis and lipid metabolism

Introduction. The transcription factor forkhead box protein P3 (FoxP3) is a major regulator of T-regulatory (Treg) lymphocytes and may be expressed in T-conventional (Tconv) lymphocytes at the stage of their activation. The aim of the present study was to evaluate the quantities and features of FoxP3+ Tconv and Treg lymphocytes and their relationships with the parameters of lipid metabolism in patients with chronic coronary artery disease (CAD) depending on the severity of coronary atherosclerosis.Material and Methods. The study comprised 14 patients (8 men and 6 women) aged 66.5 ± 9.0 years with verified chronic CAD. All the patients underwent coronary angiography and assessment of atherosclerosis severity by calculation of Gensini Score index (GS). Patients were divided into the following groups: group 1 had GS &lt; 20; group 2 had GS ≥ 20. The absolute and relative counts of FoxP3+ Treg and Tconv lymphocytes and degree of FoxP3 nuclear translocation were evaluated in all patients by imaging flow cytometry. Concentrations of insulin, proprotein convertase subtilisin/kexin type 9 (PCSK9), and sortilin were assessed using enzyme-linked immunosorbent assay. Parameters of glucose metabolism and serum lipid spectrum were determined by the standard methods.Results. Counts of Treg and Tconv lymphocytes did not differ between groups of patients with different severity of atherosclerosis. However, patients with GS ≥ 20 had lower intensity of nuclear FoxP3 fluorescence in Treg and Tconv lymphocytes. GS index in the entire group of CAD patients tended to be negatively associated with the fluorescence intensity of FoxP3 in the nuclei of Treg (rs = –0.476) and Tconv lymphocytes (rs = –0.526). Multiple correlations existed between the quantitative and qualitative parameters of FoxP3+ Treg and FoxP3+ Tconv lymphocytes and metabolic parameters such as concentrations of PCSK9, sortilin, apolipoprotein B, and triglycerides/HDL cholesterol ratio.Conclusion. FoxP3 fluorescence intensity in the nuclei of T conventional lymphocytes was more sensitive marker of immunoregulatory imbalance in chronic CAD compared to counts of FoxP3+ T cells in the peripheral blood, which remained nearly unaltered with the increase in atherosclerosis severity. At the same time, markers of lipid metabolism were tightly associated with both quantitative and qualitative features of FoxP3+ T-lymphocytes.