Project description:Background Plaque erosion is responsible for 25% to 40% of patients with acute coronary syndromes (ACS). Recent studies suggest that anti-thrombotic therapy without stenting may be an option for this subset of patients. Currently, however, an invasive procedure is required to make a diagnosis of plaque erosion. The aim of this study was to identify clinical or laboratory predictors of plaque erosion in patients with ACS to enable a diagnosis of erosion without additional invasive procedures. Methods and Results Patients with ACS who underwent optical coherence tomography imaging were selected from 11 institutions in 6 countries. The patients were classified into plaque rupture, plaque erosion, or calcified plaque, and predictors were identified using multivariable logistic modeling. Among 1241 patients with ACS, 477 (38.4%) patients were found to have plaque erosion. Plaque erosion was more frequent in non-ST-segment elevation-ACS than in ST-segment-elevation myocardial infarction (47.9% versus 29.8%, P=0.0002). Multivariable logistic regression models showed 5 independent parameters associated with plaque erosion: age <68 years, anterior ischemia, no diabetes mellitus, hemoglobin >15.0 g/dL, and normal renal function. When all 5 parameters are present in a patient with non-ST-segment elevation-ACS, the probability of plaque erosion increased to 73.1%. Conclusions Clinical and laboratory parameters associated with plaque erosion are explored in this retrospective registry study. These parameters may be useful to identify the subset of ACS patients with plaque erosion and guide them to conservative management without invasive procedures. The results of this exploratory analysis need to be confirmed in large scale prospective clinical studies. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT03479723.
Project description:Diabetes mellitus (DM) is a major risk factor for cardiovascular events. We aimed to investigate the coronary plaque phenotype of diabetic patients who presented with acute coronary syndromes by optical coherence tomography. A total of 322 patients with acute coronary syndromes who underwent preintervention optical coherence tomography imaging of the culprit lesion were included. Culprit plaque characteristics were compared between patients with DM (n=95) and those without DM (n=227). In the subgroup of 250 patients in whom sufficient length of nonculprit region in the culprit vessel was imaged by optical coherence tomography, the characteristics of nonculprit plaques were also evaluated. Patients with DM had a higher prevalence of lipid-rich plaque (58.9% versus 44.9%, P=0.030) and macrophage accumulation (60.0% versus 44.9%, P=0.019) in the culprit lesion compared with patients without DM. The prevalence of plaque rupture (33.7% versus 30.4%, P=0.896) and plaque erosion (21.1% versus 22.0%, P=0.458) was similar. In the nonculprit lesions, the DM group had greater maximal lipid arc (248.9°±83.9° versus 179.9°±58.3°, P=0.006), thinner fibrous cap thickness (103.3±56.2 μm versus 140.7±70.0 μm, P=0.013), and a higher prevalence of thin-cap fibroatheroma (17.2% versus 6.3%, P=0.031), compared with the non-DM group. Compared with patients without DM, those with DM had more vulnerable features in both culprit and nonculprit lesions, thus indicating a higher level of panvascular instability. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01110538.
Project description:BackgroundWe investigated the association of insulin resistance (IR) with coronary plaque morphology and the risk of cardiovascular events in patients enrolled in the Providing Regional Observations to Study Predictors of Events in Coronary Tree (PROSPECT) study.MethodsPatients with acute coronary syndromes (ACS) were divided based on DM status. Non-DM patients were further stratified according to homeostasis-model-assessment IR (HOMA-IR) index as insulin sensitive (IS; HOMA-IR ≤ 2), likely-IR (LIR; 2 < HOMA-IR < 5), or diabetic-IR (DIR; HOMA-IR ≥ 5). Coronary plaque characteristics were investigated by intravascular ultrasound. The primary endpoint was major adverse cardiac events (MACE); a composite of cardiac death, cardiac arrest, myocardial infarction, and rehospitalization for unstable/progressive angina.ResultsAmong non-diabetic patients, 109 patients (21.5%) were categorized as LIR, and 65 patients (12.8%) as DIR. Patients with DIR or DM had significantly higher rates of echolucent plaque compared with LIR and IS. In addition, DIR and DM were independently associated with increased risk of MACE compared with IS (adjusted hazard ratio [aHR] 2.29, 95% confidence interval [CI] 1.22-4.29, p = 0.01 and aHR 2.12, 95% CI 1.19-3.75, p = 0.009, respectively).ConclusionsIR is common among patients with ACS. DM and advanced but not early stages of IR are independently associated with increased risk of adverse cardiovascular events. Trial Registration ClinicalTrials.gov Identifier: NCT00180466.
Project description:AimsUsing the principles of clinical governance, a patient-centred approach intended to promote holistic quality improvement, we designed a prospective, multicentre study in patients with acute coronary syndrome (ACS). We aimed to verify and quantify consecutive inclusion and describe relative and absolute effects of indicators of quality for diagnosis and therapy.Methods and resultsAdministrative codes for invasive coronary angiography and acute myocardial infarction were used to estimate the ACS universe. The ratio between the number of patients included and the estimated ACS universe was the consecutive index. Co-primary quality indicators were timely reperfusion in patients admitted with ST-elevation ACS and optimal medical therapy at discharge. Cox-proportional hazard models for 1-year death with admission and discharge-specific covariates quantified relative risk reductions and adjusted number needed to treat (NNT) absolute risk reductions. Hospital codes tested had a 99.5% sensitivity to identify ACS universe. We estimated that 7344 (95% CI: 6852-7867) ACS patients were admitted and 5107 were enrolled-i.e. a consecutive index of 69.6% (95% CI 64.9-74.5%), which varied from 30.7 to 79.2% across sites. Timely reperfusion was achieved in 22.4% (95% CI: 20.7-24.1%) of patients, was associated with an adjusted hazard ratio (HR) for 1-year death of 0.60 (95% CI: 0.40-0.89) and an adjusted NNT of 65 (95% CI: 44-250). Corresponding values for optimal medical therapy were 70.1% (95% CI: 68.7-71.4%), HR of 0.50 (95% CI: 0.38-0.66), and NNT of 98 (95% CI: 79-145).ConclusionA comprehensive approach to quality for patients with ACS may promote equitable access of care and inform implementation of health care delivery.RegistrationClinicalTrials.Gov ID NCT04255537.
Project description:BackgroundHigh cardiovascular mortality has been reported in young patients with diabetes. However, the underlying pathology in different age groups of patients with diabetes has not been studied.Methods and resultsThe aim of this study was to investigate the plaque characteristics and underlying pathology of acute coronary syndrome in different age groups of patients with or without diabetes in a large cohort. Patients who presented with acute coronary syndrome and underwent preintervention optical coherence tomography imaging were included. Culprit plaque was classified as plaque rupture, plaque erosion, or calcified plaque and stratified into 5 age groups. Plaque characteristics including features of vulnerability were examined by optical coherence tomography. Among 1394 patients, 482 (34.6%) had diabetes. Patients with diabetes, compared with patients without diabetes, had a higher prevalence of lipid-rich plaque (71.2% versus 64.8%, P=0.016), macrophage (72.0% versus 62.6%, P<0.001), and cholesterol crystal (27.6% versus 19.7%, P<0.001). Both diabetes and nondiabetes groups showed a decreasing trend in plaque erosion with age (patients with diabetes, P=0.020; patients without diabetes, P<0.001). Patients without diabetes showed an increasing trend with age in plaque rupture (P=0.004) and lipid-rich plaque (P=0.018), whereas patients with diabetes had a high prevalence of these vulnerable features at an early age that remained high across age groups.ConclusionsPatients without diabetes showed an increasing trend with age in plaque rupture and lipid-rich plaque, whereas patients with diabetes had a high prevalence of these vulnerable features at an early age. These results suggest that atherosclerotic vascular changes with increased vulnerability start at a younger age in patients with diabetes.RegistrationURL: https://www.clinicaltrials.gov; Unique identifiers: NCT04523194, NCT03479723. URL: https://www.umin.ac.jp/ctr/. Unique identifier: UMIN000041692.
Project description:Acute coronary syndromes (ACS) are frequently reported in patients with coronavirus disease 2019 (COVID-19) and may impact patient clinical course and mortality. Although the underlying pathogenesis remains unclear, several potential mechanisms have been hypothesized, including oxygen supply/demand imbalance, direct viral cellular damage, systemic inflammatory response with cytokine-mediated injury, microvascular thrombosis, and endothelial dysfunction. The severe hypoxic state, combined with other conditions frequently reported in COVID-19, namely sepsis, tachyarrhythmias, anemia, hypotension, and shock, can induce a myocardial damage due to the mismatch between oxygen supply and demand and results in type 2 myocardial infarction (MI). In addition, COVID-19 promotes atherosclerotic plaque instability and thrombus formation and may precipitate type 1 MI. Patients with severe disease often show decrease in platelets count, higher levels of d-dimer, ultralarge von Willebrand factor multimers, tissue factor, and prolongation of prothrombin time, which reflects a prothrombotic state. An endothelial dysfunction has been described as a consequence of the direct viral effects and of the hyperinflammatory environment. The expression of tissue factor, von Willebrand factor, thromboxane, and plasminogen activator inhibitor-1 promotes the prothrombotic status. In addition, endothelial cells generate superoxide anions, with enhanced local oxidative stress, and endothelin-1, which affects the vasodilator/vasoconstrictor balance and platelet aggregation. The optimal management of COVID-19 patients is a challenge both for logistic and clinical reasons. A deeper understanding of ACS pathophysiology may yield novel research insights and therapeutic perspectives in higher cardiovascular risk subjects with COVID-19.
Project description:RationaleCirculating progenitor cells (CPCs) mobilize in response to ischemic injury, but their predictive value remains unknown in acute coronary syndrome (ACS).ObjectiveWe aimed to investigate the number of CPCs in ACS compared with those with stable coronary artery disease (CAD), relationship between bone marrow PCs and CPCs, and whether CPC counts predict mortality in patients with ACS.Methods and resultsIn 2028 patients, 346 had unstable angina, 183 had an acute myocardial infarction (AMI), and the remaining 1499 patients had stable CAD. Patients with ACS were followed for the primary end point of all-cause death. CPCs were enumerated by flow cytometry as mononuclear cells expressing a combination of CD34+, CD133+, vascular endothelial growth factor receptor 2+, or chemokine (C-X-C motif) receptor 4+. CPC counts were higher in subjects with AMI compared those with stable CAD even after adjustment for age, sex, race, body mass index, renal function, hypertension, diabetes mellitus, hyperlipidemia, and smoking; CD34+, CD34+/CD133+, CD34+/CXCR4+, and CD34+/VEGFR2+ CPC counts were 19%, 25%, 28%, and 142% higher in those with AMI, respectively, compared with stable CAD. There were strong correlations between the concentrations of CPCs and the PC counts in bone marrow aspirates in 20 patients with AMI. During a 2 (interquartile range, 1.31-2.86)-year follow-up period of 529 patients with ACS, 12.4% died. In Cox regression models adjusted for age, sex, body mass index, heart failure history, estimated glomerular filtration rate, and AMI, subjects with low CD34+ cell counts had a 2.46-fold (95% confidence interval, 1.18-5.13) increase in all-cause mortality, P=0.01. CD34+/CD133+ and CD34+/CXCR4+, but not CD34+/VEGFR2+ PC counts, had similar associations with mortality. Results were validated in a separate cohort of 238 patients with ACS.ConclusionsCPC levels are significantly higher in patients after an AMI compared with those with stable CAD and reflect bone marrow PC content. Among patients with ACS, a lower number of hematopoietic-enriched CPCs are associated with a higher mortality.
Project description:ImportanceAt one end of the coronary artery disease (CAD) spectrum, there are patients with multiple recurrent acute coronary syndromes (rACS), and at the other end there are those with long-standing clinical stability. Predicting the natural history of these patients is challenging because unstable plaques often heal without resulting in ACS.ObjectiveTo assess in vivo the coronary atherosclerotic phenotype as well as the prevalence and characteristics of healed coronary plaques by optical coherence tomography (OCT) imaging in patients at the extremes of the CAD spectrum.Design, setting, and participantsThis is an observational, single-center cohort study with prospective clinical follow-up. From a total of 823 consecutive patients enrolled in OCT Registry of the Fondazione Policlinico A. Gemelli-IRCCS, Rome, Italy, from March 2009 to February 2016, 105 patients were included in the following groups: (1) patients with rACS, defined as history of at least 3 acute myocardial infarctions (AMIs) or at least 4 ACS with at least 1 AMI; (2) patients with long-standing stable angina pectoris (ls-SAP), defined as a minimum 3-year history of stable angina; and (3) patients with a single unheralded AMI followed by a minimum 3-year period of clinical stability (sAMI). Data were analyzed from January to August 2018.ExposuresIntracoronary OCT imaging of nonculprit coronary segments.Main outcomes and measuresCoronary plaque features and the prevalence of healed coronary plaques in nonculprit segments as assessed by intracoronary OCT imaging.ResultsOf 105 patients, 85 were men (81.0%); the median (interquartile range) age was 68 (63-75) years. Median (interquartile range) time of clinical stability was 9 (5.0-15.0) years in the ls-SAP group and 8 (4.5-14.5) years in the sAMI group. Patients in the rACS and sAMI groups showed similar prevalence of lipid-rich plaque and thin-cap fibroatheroma, which was significantly higher than in those with ls-SAP (lipid-rich plaque 80.0% [n = 24 of 30] vs 76.3% [n = 29 of 38] vs 37.8% [n = 14 of 37], respectively; P < .001; thin-cap fibroatheroma 40.0% [n = 12 of 30] vs 34.2% [n = 13 of 38] vs 8.1% [n = 3 of 37], respectively; P = .006). Spotty calcifications were more frequently observed in patients with rACS than in those with ls-SAP and sAMI (70.0% [n = 21 of 30] vs 40.5% [n = 15 of 37] vs 44.7% [n = 17 of 38], respectively; P = .04). Healed coronary plaques were rarely observed in patients with rACS, whereas their prevalence was significantly higher in patients with ls-SAP and sAMI (3.3% [n = 1 of 30] vs 29.7% [n = 11 of 37] vs 28.9% [n = 11 of 38], respectively; P = .01).Conclusions and relevancePatients with rACS have a distinct atherosclerotic phenotype compared with those with ls-SAP, including higher prevalence of thin-cap fibroatheroma and lower prevalence of healed coronary plaques, suggesting that atherosclerotic profile and plaque healing may play a role in leading the natural history of patients with CAD.