Non-obstructive Coronary Atherosclerosis Research Articles

Prevalence and prognostic relevance of non-obstructive coronary atherosclerosis in MINOCA: a meta-analysis of 35 studies

Abstract Background Myocardial infarction with non-obstructive coronary arteries (MINOCA) can result from a variety of pathological mechanisms, not always associated with atherosclerosis. It has been suggested to distinguish between patients without obstructive coronary artery disease (NObs-CAD, stenosis diameter 1-49%), and patients with smooth coronary arteries (NCA), but differences in terms of prognosis or therapeutic approaches have not been clearly elucidated. Objectives The aim of this study is to evaluate the prevalence and prognostic impact of NObs-CAD as assessed by invasive coronary angiography (ICA) in MINOCA. Methods A meta-analysis was performed including studies reporting the prevalence of NObs-CAD versus NCA in MINOCA patients. Data on prognosis stratified by the presence of NObs-CAD were collected. Random-effects models were used to estimate the prevalence of NObs-CAD. Pooled risk ratios (RR) with 95% confidence intervals (CI) for all-cause death, myocardial infarction (MI), and the composite of both outcomes of patients with NObs-CAD compared to NCA were calculated at short-term (<1 month), 1-year and long-term follow-up (more than 1 year). Results Thirty-five studies were analysed. The pooled prevalence of NObs-CAD estimated by ICA was 53% [95% CI 47-60%]. Heterogeneity was high (I2=98.0%), but none of the clinical and instrumental characteristics tested in meta-regression analyses had a significant impact on the I2, except for age (residual I2=97.2%, p=0.014) and geographical context. Specifically, studies conducted outside Europe reported a higher prevalence of NObs-CAD with lower I2 values. Thirteen studies provided prognostic data. The presence of NObs-CAD was associated with an increased risk of death or MI compared to NCA, as well as the risk of MI at 1-year follow-up (RR = 1.49 [95% CI 1.17-1.90] and RR = 1.80 [95% CI 1.26-2.59], respectively), whereas the risk of death was comparable. Similar results were observed at long-term, but not at short-term follow-up. Out of 13 studies, 4 provided information regarded the medications at discharge stratified by the presence or absence of NObs-CAD. NObs-CAD patients received more often aspirin (89% vs 69%; p<0.01), P2Y12-inhibitors (52% vs 29%; p<0.01), angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers (53% vs 40%; p<0.01), beta-blockers (70% vs 57%; p<0.01), and statins (86% vs 60%; p<0.01) compared to NCA. Conclusions Stratification of patients according to the degree of coronary stenosis has prognostic implications in the setting of MINOCA, since NObs-CAD patients present a higher risk of reinfarction. Further dedicated trials are needed to clarify whether these patients may benefit from a tailored approach in terms of secondary prevention strategies.Central illustration

Patients With Non-Obstructive Coronary Artery Disease and Polyvascular Disease. Sub-Analysis of the Real-World Registry KAMMA (Clinical Registry on Patient Population With Polyvascular Disease in the Russian Federation and Eurasian Countries).

To study the clinical status and data of laboratory and instrumental examination of patients with non-obstructive ischemic heart disease (IHD) and multifocal atherosclerosis (MFA) included in the KAMMA registry. The subanalysis included 1,893 IHD patients who underwent coronary angiography (CAG) and ultrasonic examination of peripheral arteries. Based on the CAG data, patients were divided into two groups: group 1, patients with obstructive coronary atherosclerosis (CA) (maximum stenosis ≥50% and/or history of percutaneous coronary intervention/coronary artery bypass grafting, n=1728; 91.3%) and group 2, patients with non-obstructive CA (maximum stenosis <50%, n = 165; 8.7%). A comparative analysis based on the degree of coronary obstruction in patients with verified IHD who were included in the KAMMA registry showed that 8.7% of them had coronary artery stenosis of less than 50%. The overwhelming majority of patients with non-obstructive CA had MFA affecting the brachiocephalic arteries in 94.3% and the lower extremity arteries in 40.2%. Among patients with non-obstructive IHD, women predominated; risk factors such as smoking and type 2 diabetes mellitus were less frequent in this group than in the obstructive IHD group. Patients with non-obstructive CA more frequently had a history of dyslipidemia; they had higher total cholesterol and non-high-density lipoprotein cholesterol; and they more frequently received moderate-intensity statin therapy than patients with obstructive CA (55.8% vs. 34.5%). Characteristic features of patients with non-obstructive CA were less severe IHD and less frequent history of acute coronary syndrome. However, the incidence of stroke, peripheral arterial thrombosis, and chronic arterial insufficiency of the lower extremities did not differ in groups 1 and 2, whereas the incidence of paroxysmal atrial fibrillation was higher in the non-obstructive IHD group. IHD patients without coronary obstruction also require assessment of the peripheral arterial status, as they may have advanced MFA, which should be taken into account when choosing the "aggressiveness" of therapy.

The relationship between workload and exercise-induced cardiac troponin elevations is influenced by non-obstructive coronary atherosclerosis.

The relationship between exercise-induced troponin elevation and non-obstructive coronary artery disease (CAD) is unclear. This observational study assessed non-obstructive CAD's impact on exercise-induced cardiac Troponin I (cTnI) elevation in middle-aged recreational athletes. cTnI levels of 40 well-trained recreational athletes (73% males, 50 ± 9 years old) were assessed by a high-sensitive cTnI assay 24 h before, and at 3 and 24 h following two high-intensity exercises of different durations; a cardiopulmonary exercise test (CPET), and a 91-km mountain bike race. Workload was measured with power meters. Coronary computed tomography angiography was used to determine the presence or absence of non-obstructive (<50% obstruction) CAD. A total of 15 individuals had non-obstructive CAD (Atherosclerotic group), whereas 25 had no atherosclerosis (normal). There were higher post-exercise cTnI levels following the race compared with CPET, both at 3 h (77.0 (35.3-112.4) ng/L vs. 11.6 (6.4-22.5) ng/L, p < 0.001) and at 24 h (14.7 (6.7-16.3) vs. 5.0 (2.6-8.9) ng/L, p < 0.001). Absolute cTnI values did not differ among groups. Still, the association of cTnI response to power output was significantly stronger in the CAD versus Normal group both at 3 h post-exercise (Rho = 0.80, p < 0.001 vs. Rho = -0.20, p = 0.33) and 24-h post-exercise (Rho = 0.87, p < 0.001 vs. Rho = -0.13, p = 0.55). Exercise-induced cTnI elevation was strongly correlated with exercise workload in middle-aged athletes with non-obstructive CAD but not in individuals without CAD. This finding suggests that CAD influences the relationship between exercise workload and the cTnI response even without coronary artery obstruction.

Single-Cell RNA Sequencing of Coronary Perivascular Adipose Tissue From End-Stage Heart Failure Patients Identifies SPP1+ Macrophage Subpopulation as a Target for Alleviating Fibrosis.

Perivascular adipose tissue (PVAT) is vital for vascular homeostasis, and PVAT dysfunction is associated with increased atherosclerotic plaque burden. But the mechanisms underlining coronary PVAT dysfunction in coronary atherosclerosis remain elusive. We performed single-cell RNA sequencing of the stromal vascular fraction of coronary PVAT from 3 groups of heart transplant recipients with end-stage heart failure, including 3 patients with nonobstructive coronary atherosclerosis, 3 patients with obstructive coronary artery atherosclerosis, and 4 nonatherosclerosis control subjects. Bioinformatics was used to annotate the cellular populations, depict the cellular developmental trajectories and interactions, and explore the differences among 3 groups of coronary PVAT at the cellular and molecular levels. Pathological staining, quantitative real-time polymerase chain reaction, and in vitro studies were performed to validate the key findings. Ten cell types were identified among 67 936 cells from human coronary PVAT. Several cellular subpopulations, including SPP1+ (secreted phosphoprotein 1) macrophages and profibrotic fibroadipogenic progenitor cells, were accumulated in PVAT surrounding atherosclerotic coronary arteries compared with nonatherosclerosis coronary arteries. The fibrosis percentage was increased in PVAT surrounding atherosclerotic coronary arteries, and it was positively associated with the grade of coronary artery stenosis. Cellular interaction analysis suggested OPN (osteopontin) secreted by SPP1+ macrophages interacted with CD44 (cluster of differentiation 44)/integrin on fibroadipogenic progenitor cells. Strikingly, correlation analyses uncovered that higher level of SPP1 in PVAT correlates with a more severe fibrosis degree and a higher coronary stenosis grade. In vitro studies showed that conditioned medium from atherosclerotic coronary PVAT promoted the migration and proliferation of fibroadipogenic progenitor cells, while such effect was prevented by blocking CD44 or integrin. SPP1+ macrophages accumulated in the PVAT surrounding atherosclerotic coronary arteries, and they promoted the migration and proliferation of fibroadipogenic progenitor cells via OPN-CD44/integrin interaction and thus aggravated the fibrosis of coronary PVAT, which was positively correlated to the coronary stenosis burden. Therefore, SPP1+ macrophages in coronary PVAT may participate in the progression of coronary atherosclerosis.

Body mass components affecting low-attenuation noncalcified coronary plaque burden

Abstract Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): National Institute of Cardiology in Warsaw, Poland Background Weight control is a major risk modifier for coronary artery disease. However, the effect exerted by individual body mass components on coronary plaque may not be uniform. Low-attenuation noncalcified plaque (LAP) has been recently identified as an independent predictor of cardiovascular outcomes [1]. Purpose To determine the relationship between changes in body mass composition and LAP burden. Methods 89 participants of Dietary Intervention to Stop Coronary Atherosclerosis in Computed Tomography (DISCO-CT) were enrolled into the analysis (40% women, mean age 60±7.7 years). Patients with non-obstructive (stenosis&amp;lt;70%) coronary atherosclerosis confirmed in coronary computed tomography angiography (CCTA) and qualified to conservative treatment were randomized (1:1) to intensive diet and lifestyle intervention atop optimal medical therapy (OMT) versus OMT alone over 66.8±13.7 months [2]. Body mass (BM) and body mass components including total body fat (TBF), skeletal muscle mass (SMM), visceral cell mass (VCM), and extracellular mass (ECM) were measured at baseline and follow-up (InBody S10 analyser, South Korea). LAP burden was defined as the volume of coronary plaque &amp;lt;30 Hounsfield units divided by the vessel volume, and expressed in %. Changes in body components were compared with changes in LAP measured in serial CCTA scans (QAngioCT, Medis Medical Imaging Systems, the Netherlands). Results Reduction in BM was significantly higher in the experimental (∆BM=-3.6±4.9 kg) vs control arm (∆BM=-1.4±2.9 kg; p = 0.016) and so was the reduction in TBF (∆TBF=-4.2±5.3 kg vs ∆TBF=0.2±4.3 kg, respectively; p&amp;lt;0.001). SMM increased by 0.4±2.6 kg in the experimental arm and decreased by 1.0±2.1 kg in the control arm (p = 0.006). No significant interarm differences were observed for changes in VCM and ECM. Reduction in LAP was higher in the experimental vs control arm (∆LAP=-0.42±1.4% vs ∆LAP=-0.03±0.45%, respectively; p = 0.078). In the entire study population, a significant positive correlation between LAP reduction and BM reduction was revealed (r=0.45, p&amp;lt;0.001). Multivariate regression model incorporating the investigated body mass components identified TBF as the only component associated with LAP reduction (table). Conclusions Body mass reduction may decrease LAP burden due to body fat reduction.

Invasive Evaluation for Coronary Vasospasm.

Vasospastic angina (VSA) occurs at rest and on exertion, with transient electrocardiographic ischemic changes. VSA presents with spontaneous coronary artery spasm (CAS); it has been associated with stable angina, acute coronary syndromes, and sudden cardiac death. CAS can be identified in normal arteries or non-obstructive coronary atherosclerosis, but is also prevalent in patients with coronary artery disease. The diagnosis is made with invasive coronary reactivity testing with provocation using acetylcholine (Ach). Epicardial spasms can be visualized through coronary angiography as a reversible epicardial vessel narrowing, while the diagnosis of microvascular spasm can be made when angina symptoms and ECG changes happen following intracoronary Ach without epicardial spasm. Identification of CAS allows for risk stratification and specific therapies targeting endothelial dysfunction and paradoxical vascular smooth muscle cell constriction. Therapies include calcium channel blockers as monotherapy or in a combination of a dihydropyridine and non-dihydropyridine. Short-acting nitrates offer acute symptomatic relief but long-acting nitrates should be used sparingly. This current update on invasive evaluation of VSA discusses unified Ach protocols.

Prevalence of angina pectoris and association with coronary atherosclerosis in a general population

ObjectiveTo assess the contemporary prevalence of, and factors associated with angina pectoris symptoms, and to examine the relationship to coronary atherosclerosis in a middle-aged, general population.MethodsData were based on the...

Positive Stress Electrocardiography in Patients With Non-obstructive Coronary Disease.

Introduction The episodes of myocardial ischemia in patients with non-obstructive coronary disease are extremely variable in provoking factors and presentation. Purpose We investigated the significance of coronary blood flow velocity and epicardial diameter as correlates of a positive electrocardiographic exercise stress test (ExECG) in hospitalized patients with unstable angina and non-obstructive coronary artery disease. Methods The study was a single-center cohort retrospective. ExECG was performed and analyzed in a group of 79 patients with non-obstructive coronary disease (coronary stenoses < 50%). Thirty-one percent of the patients (n=25) were diagnosed with slow coronary flow phenomenon, SCFP; 40.5% (n=32) - patients with hypertensive disease, left ventricular hypertrophy (LVH), and slow epicardialflow; 27.8% (n=22) with hypertension, left ventricular hypertrophy and normal coronaryflow. The patients were hospitalized in University Hospital "Alexandrovska," Sofia in the period 2006-2008. Results The frequency of positive ExECG is increased as a trend was associated with smaller epicardial diameters and pronounced delay in epicardial coronaryflow.In the subgroup with SCFP, the risk for a positive ExECG test was determined by slower coronary flow (36.5±7.7 frames vs. 30.3±4.4 frames, p=0.044) and borderline significant by epicardial lumen diameters (3.3±0.8 mm vs. 4.1±1.0 mm, p=0.051) and greater myocardial mass (92.8±12.6 g/m2 vs. 82.9±8.6 g/m2, p=0.054). In cases of left ventricular hypertrophy, which included both patients with the normal and slow epicardialflow, there were no statistically significant correlates of an abnormal exercise stress ECG test. Conclusions In patients with non-obstructive coronary atherosclerosis and predominantly slow epicardial coronary flow, the provoking of ischemia at an electrocardiographic exercise stress test is associated with the lower epicardial flow velocity at rest and with the smaller epicardial diameter. In SCFP, the risk for an abnormal stress test is determined by slower coronary flow, smaller epicardial lumen diameter, and greater myocardial mass.The presence and size of the plaque burden are not associated with a greater risk of a positive ExECG in these patients.

Nonobstructive coronary atherosclerosis is associated with adverse prognosis among patients diagnosed with myocardial infarction without obstructive coronary arteries

Background and aimsThe prognostic impact of nonobstructive coronary artery disease (CAD), as opposed to normal coronary arteries, on long-term outcomes of patients with myocardial infarction with no obstructive coronary arteries (MINOCA) is unclear. We aimed to address the association between nonobstructive-CAD and major adverse events (MAE) following MINOCA. MethodsWe conducted a retrospective cohort study of consecutive MINOCA patients admitted to a large referral medical center between 2005 and 2018. Patients were classified according to coronary angiography as having either normal-coronaries or nonobstructive-CAD. The primary outcome was MAE, defined as the composite of all-cause mortality and recurrent acute coronary syndrome (ACS). ResultsOf the 1544 MINOCA patients, 651 (42%) had normal coronaries, and 893 (58%) had CAD. The mean age was 61.2 ± 12.6 years, and 710 (46%) were females. Nonobstructive-CAD patients were older and less likely to be females, with higher rates of diabetes, hypertension, dyslipidemia, atrial fibrillation, and chronic renal-failure (p < 0.05). At a median follow-up of 7 years, MAE occurred in 203 (23%) patients and 67 (10%) patients in the nonobstructive-CAD and normal-coronaries groups, respectively (p < 0.01). In multivariable models, nonobstructive -CAD was significantly associated with long-term MAE [adjusted-hazard-ratio (aHR):1.67, 95% confidence-interval (95%CI):1.25–2.23; p < 0.001]. Other factors associated with a higher MAE-risk were older-age (aHR:1.05,95%CI:1.03–1.06; p < 0.001) and left ventricular ejection-fraction<40% (aHR:3.04,95%CI:2.03–4.57; p < 0.001), while female-sex (aHR:0.72, 95%CI: 0.56–0.94; p=0.014) and sinus rhythm at presentation (aHR:0.66, 95%CI: 0.44–0.98; p=0.041) were associated with lower MAE-risk. ConclusionsIn MINOCA, nonobstructive-CAD is independently associated with a higher MAE-risk than normal-coronaries. This finding may promote risk-stratification of patients with nonobstructive-CAD-MINOCA who require tighter medical follow-up and treatment optimization.

Impact of Nonobstructive Left Main Coronary Artery Atherosclerosis on Long-Term Mortality

BackgroundAlthough the presence of severe stenosis in the left main coronary artery (LMCA) is a well-established predictor of mortality, whether this extends to nonobstructive atherosclerosis in the LMCA is unknown. ObjectivesThe aim of this study was to evaluate the association between LMCA disease by intravascular ultrasound (IVUS) and long-term mortality. MethodsBetween 2005 and 2013, 3,239 patients with LMCA IVUS imaging without LMCA revascularization (either before angiography or scheduled based on index angiography or IVUS) were included. The primary and secondary endpoints were all-cause and cardiac mortality at a minimum of 5 years obtained from the National Death Index. ResultsThe IVUS-measured LMCA minimum lumen area (MLA) and plaque burden were 13.1 ± 5.0 mm2 and 41.7% ± 15.6%, respectively. The median follow-up was 8.2 years. The Kaplan-Meier estimated 12-year all-cause and cardiac death rates were 37.5% and 17.0%, respectively. Greater plaque burden (unadjusted HR per 10%: 1.17; 95% CI: 1.12-1.22; P < 0.0001) and smaller IVUS MLA (unadjusted HR per 1 mm2: 0.98; 95% CI: 0.96-0.99; P = 0.0008) were associated with all-cause death. After adjusting for clinical, angiographic, and IVUS factors, plaque burden (adjusted HR per 10%: 1.12; 95% CI: 1.04-1.21; P = 0.003) but not MLA (adjusted HR per 1 mm2: 1.02; 95% CI: 0.99-1.04; P = 0.18) was associated with long-term all-cause death. These findings were also consistent for long-term cardiac mortality. ConclusionsIn the present large-scale study with a 12-year follow-up, increasing LMCA plaque burden was associated with long-term all-cause and cardiac mortality in patients not undergoing LMCA revascularization, even when the lumen area was preserved.

Coronary Artery Embolism: a Rare Cause of ST Segment Elevation Myocardial Infarction

Acute myocardial infarction (AMI) is a fatal clinical disease, and is often caused by thrombotic occlusion, secondary to coronary artery atherosclerotic plaque erosion or rupture [1]. But about 1-14% of AMI is caused by myocardial infarction with non-obstructive coronary atherosclerosis (MINOCA [2], which is characterized by evidence of myocardial infarction, normal coronary angiography or coronary artery stenosis of &lt;50&gt;]. The causes of MINOCA vary from person to person [4], such as coronary artery spasm [5], Stress cardiomyopathy [6], Thrombophilia [7], coronary artery embolism(CE) [8,9]. CE is a rare cause of AMI in clinical practice. We had presented a female patient who had left anterior descending artery embolism, with dilated cardiomyopathy and paroxysmal atrial flutter [10]. CE, while rare, is now recognized as an important non-atherosclerotic cause of AMI. In the past, the description of clinical features about CE was little or just case reports [8-9]. A recent study involving 1776 patients evaluated the clinical features of CE-related myocardial infarction. It is pointed out that the prevalence rate is 2.9% in the initial AMI. and atrial fibrillation is the most important cause of CE (73%). Other causes include cardiomyopathy and valvular heart disease. And proposed CE diagnostic criteria [11]. In recent years, thrombus aspiration devices have been widely used in AMI patients with angiographically confirmed thrombosis and have proved to be a viable and effective strategy for the treatment of thrombotically burdened AMI, including CE-related infarction. Moreover, histological examination of aspiration thrombus provides additional information for the diagnosis of CE. Although thrombus aspiration is an effective method for treating patients with CE, Stoel et al [12] reported that the diameter of the lumen of the aspiration catheter is small and useless for aspirating large thrombi. In addition, it is challenging to access to the distal lumen through the suction device. In fact, 42% of existing patients are treated conservatively because of distal occlusion or small vessel with a criminal lesion. The treatment of CE-related risk factors is also very important. Including atrial fibrillation, cardiomyopathy, rheumatic heart valve disease, prosthetic heart valve, patent foramen ovale, atrial septal defect, history of cardiac surgery, infective endocarditis or hypercoagulable state. The patient in this case was dilated cardiomyopathy with paroxysmal atrial flutter, both of which were high risk for CE. She had chest pain, typical changes in the ECG, coronary angiography revealed coronary embolization of the LAD. that are consistent with acute myocardial infarction. Intravascular ultrasound (IVUS) or optical coherence Tomography (OCT) is an effective method to detect the atherosclerotic plaque erosion or rupture of coronary artery. This patient was proved to be CE by IVUS. It is very important to given sufficient anticoagulant therapy to prevent CE in clinical practice.

Association of Circulating Heme Oxygenase-1, Lipid Profile and Coronary Disease Phenotype in Patients with Chronic Coronary Syndrome.

Background. The NF-E2–related factor 2 (Nrf2)/Heme Oxygenase-1 (HO-1) pathway has an emerging role in atherosclerosis. Activated by oxidative stress, it is deemed to exert athero-protective effects. We aimed at evaluating the relationships between plasma HO-1, clinical/molecular profiles and coronary disease patterns in patients with chronic coronary syndromes (CCS). Methods. HO-1 was measured in 526 patients (60 ± 9 years, 318 males) with CCS. Coronary computed tomography angiography (CTA) and stress imaging were used to assess the disease phenotype (coronary atherosclerosis and myocardial ischemia) in a subgroup of 347 patients. Results. In the overall population, HO-1 median value (25–75 percentile) was 5.195 (1.75–8.25) ng/mL. Patients with higher HO-1 were more frequently male, had a higher BMI and lower LVEF%, but otherwise similar risk factors than the other patients. Their bio-humoral profile was characterized by higher markers of endothelial/myocardial dysfunction, but lower levels of cholesterol lipoproteins. Coronary artery disease was characterized by more diffuse atherosclerosis, with mainly non-obstructive and calcified plaques, and a higher prevalence of functional ischemia. Conclusion: In patients with CCS, higher plasma HO-1 levels are associated with lower cholesterol and a more diffuse but mainly non-obstructive coronary atherosclerosis, confirming a potential role for the Nrf2/HO-1 pathway as a protective feedback.

Non-Invasive Scintigraphy in the Identification of Treatable Transthyretin Cardiac Amyloid

<h3>Introduction</h3> The previous gold standard for diagnosing transthyretin amyloid cardiomyopathy (ATTR-CM) was cardiac biopsy. Nuclear scintigraphy using technetium-99m-pyrophosphate (Tc-99m-PYP) is a non-invasive underutilized method of diagnosing this condition <h3>Case Report</h3> An 83 year old man with a past medical history of hyperlipidemia and paroxysmal atrial fibrillation presented with dyspnea and volume overload on physical examination. Echocardiogram showed a left ventricular ejection fraction of 47%, severe diastolic dysfunction, increased left ventricular wall thickness, and bi-atrial enlargement. Non-ischemic evaluation was unremarkable including negative serum/urine protein electrophoresis and immunofixation. Left heart catheterization showed mild non-obstructive coronary artery atherosclerosis. Cardiac MRI revealed late gadolinium enhancement consistent with amyloidosis. Nuclear scintigraphy (Figure 1) was consistent with ATTR-CM. The patient was referred to a cardiac amyloid specialist for further care. <h3>Summary</h3> While cardiac biopsies are classically recommended for diagnosing ATTR-CM, bone scintigraphy offers a non-invasive method to attain the same diagnosis. If incorporated into the algorithm for initial non-ischemic cardiomyopathy evaluation, Tc-99m-PYP scintigraphy can quickly and safely identify patients with ATTR-CM who would benefit from the newer transthyretin stabilizer tafamidis, which halts the progression of ATTR-CM.

High-Risk Coronary Plaque Regression After Intensive Lifestyle Intervention in Nonobstructive Coronary Disease: A Randomized Study

ObjectivesThe authors sought to study the impact of diet and lifestyle intervention on changes in atherosclerotic plaque volume and composition. BackgroundLifestyle and diet modification are the leading strategies to manage coronary artery disease; however, their direct impact on atherosclerosis remains unknown. Coronary plaque composition is related to the risk of future cardiovascular events independent of stenosis severity and can be conveniently evaluated with computed tomography angiography (CTA). MethodsWe enrolled 92 patients (41% women; mean age 60 ± 7.7 years) with nonobstructive (<70% stenosis) coronary atherosclerosis identified by CTA. Participants were randomized (1:1) to either the DISCO (Dietary Intervention to Stop Coronary Atherosclerosis in Computed Tomography) intervention group (systematic follow-up by a dietitian to adhere to the Dietary Approaches to Stop Hypertension nutrition model together with optimal medical therapy [OMT]) or the control group (OMT alone). In all patients, CTA was repeated after 66.9 ± 13.7 weeks. The outcome was change (Δ) in atheroma volume and plaque composition. Based on atherosclerotic tissue attenuation ranges in Hounsfield units (HU), the following components of coronary plaque were distinguished: dense calcium (>351 HU), fibrous plaque (151 to 350 HU), and fibrofatty plaque combined with necrotic core (-30 to 150 HU), referred to as noncalcified plaque. ResultsPercent atheroma volume increased in the control arm (Δ = +1.1 ± 3.4%; p = 0.033) versus no significant change in the experimental arm (Δ = +1.0% ± 4.2%; p = 0.127; intergroup p = 0.851). There was a reduction in noncalcified plaque in both the experimental arm (Δ = −51.3 ± 79.5 mm3 [−1.7 ± 2.7%]; p < 0.001) and the control arm (Δ = −21.3 ± 57.7 [−0.7 ± 1.9%]; p = 0.018), which was greater in the DISCO intervention group (intergroup p = 0.045). No differences in fibrous component or dense calcium changes were observed between the groups. ConclusionsControlled diet and lifestyle intervention together with OMT may slow the progression of atherosclerosis and reduce noncalcified plaque volume compared to OMT alone. (Dietary Intervention to Stop Coronary Atherosclerosis in Computed Tomography [DISCO-CT]; NCT02571803)

Epidemiology and pathophysiologic insights of coronary atherosclerosis relevant for contemporary non-invasive imaging.

In the past few years significant changes have taken place in the diagnostic and therapeutic approach to patients with coronary artery disease (CAD) and/or ischemic heart disease (IHD). New discoveries about the development and progression of coronary atherosclerosis have changed the clinical landscape. At the same time a marked decrease in cardiovascular (CV) mortality and CAD incidence have been observed in many Countries but particularly in the most industrialized ones. This fall has been also observed in the incidence of stroke, sudden death, myocardial ischemia, myocardial infarction (MI), and prevalence of CAD. As a consequence, an increasing number of patients with chest pain exhibits non-significant stenosis at both invasive and non-invasive coronary angiography and the rate of coronary vessels revascularizations has greatly reduced. Coronary atherosclerosis and its characteristics have shown to be both diagnostic and therapeutic targets beyond obstructive CAD. The decreased prevalence of CAD in the general population has modified the pre-test probability (PTP) of disease. In this landscape the conventional stress imaging tests appear to have limited accuracy making the diagnosis of obstructive CAD very challenging. These diagnostic tests have been introduced and tested in a population with a much higher probability of disease and therefore the contemporary accuracy of these old tests appear much lower than in the past. In addition, in the past few years the relevance of the traditional ischemia guided coronary intervention strategy has been questioned. Given the low CV events granted by an optimal medical therapy in CAD the major attention has been directed on detecting coronary atherosclerosis. The earlier the better. At the same time, a growing number of data from clinical studies have shown a significant prognostic role for non-obstructive CAD and coronary atherosclerosis. All these facts have shifted the clinicians' attention from the functional evaluation of the coronary circulation to the anatomic burden of disease.

Long non-coding RNA expression profiles in peripheral blood mononuclear cells of patients with coronary artery disease

BackgroundCoronary artery disease (CAD) is a leading cause of death and often presents as a complex systemic disease. The aim of the presents study was to determine the expression profiles of long non-coding RNAs (lncRNAs) in peripheral blood mononuclear cells (PBMC) of CAD patients and controls.MethodsThe lncRNA expression profiling of PBMC obtained from 40 CAD patients and 10 non-obstructive coronary atherosclerosis (NOCA) subjects were analyzed using the Illumina Hiseq 4000 sequencer. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to validate the differentially expressed lncRNAs. Gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of mRNA were conducted to predict biologic functions.ResultsOur results indicated that lncRNAs were differentially expressed; 83 were upregulated lncRNAs and 114 were downregulated lncRNAs (P<0.05). A horizontal comparison of lncRNA expression indicated that the change in the expression profile of 48 lncRNAs was consistent with the degree of CAD. Six lncRNAs were validated using qRT-PCR, confirming the accuracy of the RNA sequencing analysis. GO analysis indicated that these dysregulated lncRNA transcripts were related to chromatin organization, cell and cell part, and protein heterodimerization activity. Pathway analysis indicated that these differentially expressed genes mainly included viral carcinogenesis, systemic lupus erythematosus and alcoholism.ConclusionsOur preliminary findings indicate that lncRNAs could be used as potential biomarkers of subclinical cardiac abnormalities in the PBMC of CAD patients. However, further studies are needed to verify our findings and hypothesis.

Long-Term Prognostic Significance of High-Sensitive Troponin I Increase during Hospital Stay in Patients with Acute Myocardial Infarction and Non-Obstructive Coronary Arteries.

Background and Objectives: A topic already widely investigated is the negative prognostic value regarding the extent of high sensitive troponin I (hs-TnI) increases among patients with myocardial infarction (MI) and obstructive coronary atherosclerosis compared to a group of patients with MI and non-obstructive coronary atherosclerosis (MINOCA). Thus, the aim of this study was to evaluate the prognostic value concerning the extent of hs-TnI increase on clinical outcomes among patients with a MINOCA working diagnosis. Materials and Methods: We selected 337 consecutive patients admitted to hospital with a working diagnosis of MINOCA. The patients were divided in three groups according to the extent of hs-TnI increase during hospitalization (increase ≤5-times above the limit of the upper norm, >5 and ≤20-times, and >20-times). The study endpoints included all-cause mortality and major adverse cardiac and cerebrovascular events (MACCE; cerebral stroke and transient ischemic attacks, MI, coronary artery revascularization, either percutaneous coronary intervention or coronary artery bypass grafting and all-cause mortality). Results: During the mean follow-up period of 516.1 ± 239.8 days, using Kaplan–Meier survival curve analysis, significantly higher mortality rates were demonstrated among patients from the group with the greatest hs-TnI increase compared to the remaining groups (p = 0.01) and borderline values for MACCE (p = 0.053). Multivariable cox regression analysis did not confirm hs-TnI among factors related to increased MACCE or all-cause mortality rates. Conclusion: While a relationship between clinical outcomes and the extent of the hs-TnI increase among patients with a MINOCA working diagnosis remains, it does not seem to be not as strong as it is in patients with obstructive coronary atherosclerosis.

Mechanisms of myocardial infarction with nonobstructive coronary atherosclerosis: a multifaceted play of different actors with guarded prognosis.

Myocardial infarction (MI) with nonobstructive coronary atherosclerosis (MINOCA) on invasive angiography (stenosis severity <50%) is a heterogenous clinical entity with a prevalence between 6 and 8% of all MI. Whereas the long-term prognosis of MINOCA is not benign, the identification of its underlying mechanism is critical for appropriate risk stratification and tailored secondary prevention strategies. The current review summarizes the contemporary data on the mechanisms, diagnosis, management strategies and outcomes of MINOCA. MINOCA is a relatively common form of MI with guarded prognosis. The use of additional diagnostic tests (particularly intracoronary imaging and cardiac magnetic resonance) is paramount to determine the exact cause of MINOCA and implement tailored medical interventions.

The Natural history of Epicardial Adipose Tissue Volume and Attenuation: A long-term prospective cohort follow-up study

Epicardial adipose tissue (EAT) is associated with cardiovascular risk. The longitudinal change in EAT volume (EATv) and density (EATd), and potential modulators of these parameters, has not been described. We prospectively recruited 90 patients with non-obstructive coronary atherosclerosis on baseline computed tomography coronary angiography (CTCA) performed for suspected coronary artery disease to undergo a repeat research CTCA. EATv in millilitres (mL) and EATd in Hounsfield units (HU) were analysed and multivariable regression analysis controlling for traditional cardiovascular risk factors (CVRF) performed to assess for any predictors of change. Secondary analysis was performed based on statin therapy. The median duration between CTCA was 4.3years. Mean EATv increased at follow-up (72 ± 33 mL to 89 ± 43 mL, p < 0.001) and mean EATd decreased (baseline −76 ± 6 HU vs. −86 ± 5 HU, p < 0.001). There were no associations between baseline variables of body mass index, age, sex, hypertension, hyperlipidaemia, diabetes or smoking on change in EATv or EATd. No difference in baseline, follow-up or delta EATv or EATd was seen in patients with (60%) or without baseline statin therapy. In this select group of patients, EATv consistently increased and EATd consistently decreased at long-term follow-up and these changes were independent of CVRF, age and statin use. Together with the knowledge of strong associations between EAT and cardiac disease, these findings may suggest that EAT is an independent parameter rather than a surrogate for cardiovascular risk.

Influencing factors of vascular endothelial function in patients with non-obstructive coronary atherosclerosis: a 1-year observational study

BackgroundEndothelial dysfunction may play a key role in non-obstructive coronary artery atherosclerosis. Our study aimed to evaluate the vascular endothelial function and its influencing factors in patients with non-obstructive coronary artery atherosclerosis.MethodsA total of 131 consecutive patients with non-obstructive coronary artery atherosclerosis were enrolled. Flow-mediated dilatation (FMD) was measured at baseline and 1-year follow-up. Endothelial progenitor cells (EPCs) were counted by staining the fasting venous blood with antibodies against CD34 and vascular endothelial growth factor receptor 2.ResultsSystolic blood pressure, pulse pressure and the levels of HbA1c in participants with baseline FMD < 6% (n = 65) were significantly higher than those with baseline FMD ≥ 6% (n = 66). Baseline FMD was negatively associated with EPC counts (r = − 0.199, P < 0.05) and systolic blood pressure (r = − 0.315, P < 0.01). The 1-year FMD was significantly increased compared to the baseline FMD [(9.31 ± 5.62) % vs (7.31 ± 5.26) %, P < 0.001]. Independent predictors of FMD improvement included elevated EPC counts (OR = 1.104, 95% CI: 1.047–1.165, P < 0.001) and decreased levels of serum creatinine (OR = 0.915, 95% CI: 0.843–0.993, P = 0.034).ConclusionsFamily history of premature cardiovascular diseases, hypertension, elevated systolic pressure, and HbA1c > 6.5% are independent risk factors for endothelial dysfunction in non-obstructive atherosclerotic patients. Elevated peripheral blood EPC counts and decreased levels of serum creatinine are independent predictors of endothelial function improvement.