Atherogenic responsibility of lipoprotein (a) and other apolipoprotein B-containing lipoproteins in acute coronary syndrome.

Background The TROPICAL-ACS trial showed that platelet function testing (PFT) guided de-escalation of P2Y12-inhibitor is a safe alternative treatment strategy in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). No specific data are available on the efficacy of this strategy in patients with multivessel coronary artery disease (CAD). Purpose To investigate the safety and efficacy of guided de-escalation of P2Y12-inhibitor treatment in patients with multivessel CAD. Methods Two-thousand six-hundred-two biomarker-positive ACS patients were 1:1 randomized to either conventional treatment with prasugrel for 12 months (control group) or to a PFT guided de-escalation treatment strategy (guided de-escalation group). The primary endpoint (net clinical benefit) was defined as the composite of cardiovascular mortality (CVM), myocardial infarction (MI), stroke, and clinically overt bleeding (bleeding ≥ grade 2 according to the BARC criteria). The ischemic endpoint was defined as the composite of CVM, MI or stroke. We used log-rank statistics and Cox regression analysis with interaction testing to assess the effect of multivessel CAD on the primary and ischemic endpoints. Results Patients with multivessel (n=709) versus single-vessel CAD (n=1,901) exhibited a higher risk for the primary endpoint (10.2% vs. 7.6%; HR 1.36; 95% CI 1.02–1.81; p=0.034). Guided de-escalation was non-inferior to conventional treatment for the primary endpoint in both patients with single-vessel CAD (6.7% vs. 8.5%; pnon-inferiority = 0.001; Figure 1A) and multivessel CAD (9,5% vs. 10.9%; pnon-inferiority=0.041; Figure 1B). Moreover, there was no significant interaction in the prognostic value of guided de-escalation between single-vessel and multivessel CAD for both the primary (HR 0.78 [0.56–1.08]; p=0.137 in patients with single-vessel CAD vs. 0.86 [0.54–1.37; p=0.524 in patients with multivessel CAD; pinteraction=0.732) and combined ischemic endpoints (HR 0.80 [0.44–1.45]; p=0.456 in patients with single-vessel CAD vs. 0.71 [0.35–1. 46]; p=0.356 in patients with multivessel CAD; pinteraction=0.823). Kaplan-Meier curves Conclusion A guided de-escalation of P2Y12-inhibitor appears to be safe and effective in ACS patients with both single-vessel and multivessel CAD. Acknowledgement/Funding Klinikum der Universität München, Roche Diagnostics, Eli Lilly, and Daiichi Sankyo.

Background Patients with multivessel or complex coronary artery disease (CAD) are at increased risk of atherothrombotic events. It has been suggested that these patients may derive an incremental benefit with more intense antiplatelet strategies, according to prior subgroup analyses from randomized clinical trials. However, whether there is any association between the presence and extension of multivessel CAD and platelet aggregability (PA) in patients with acute coronary syndromes (ACS) is unknown. Purpose To analyze the independent association between PA and presence of multivessel CAD in patients with ACS. Methods Patients with ACS on dual antiplatelet therapy (aspirin plus clopidogrel) were included in this study. Multivessel CAD was defined as the presence of significant ≥50% stenosis at two or more major epicardic vessels. Platelet aggregability was assessed by VerifyNow P2Y12 assay expressed in P2Y12 Reactivity Units (PRU) on the day of discharge from the coronary care unit. High On-treatment platelet reactivity (HPR) was defined as PRU ≥208. Stepwise linear and logistic regression models were applied to adjust for confounders. Models were adjusted for: age, sex, race, diabetes, hypertension, smoking, dyslipidemia, prior MI, prior PCI, prior CABG, prior HF, prior stroke and ACS phenotype (STEMI vs. Non-ST-segment elevation ACS). Results A total of 237 patients were included, among whom 143 (60.3%) had multivessel CAD at the coronary angiogram and 175 (73.8%) were submitted to PCI during index hospitalization. Patients with multivessel disease were older (mean age 64.8±12.1 vs. 58.9±11.2 years; p<0.001) and more likely to have a history of diabetes (47.6% vs. 29.8%; p=0.006) and non-ST-segment elevation ACS as the index event (55.2% vs. 28.7%; p<0.001), compared to patients without multivessel CAD. After adjustments, presence of multivessel CAD was associated with higher PA (mean 161.4±74 PRU in patients with versus 140.3±70.9 PRU in patients without multivessel CAD; adjusted mean difference 23.7 PRU; 95% CI 4.8 to 42.5; p=0.014). Additionally, there was an incremental of 12.5 PRU (95% CI 2.8 to 22.3; adj p=0.012) for each diseased vessel and of 4.67 PRU (95% CI 0.11 to 9.22; adj p=0.045) for each diseased coronary segment. Compared to patients with single-vessel disease, patients with three-vessel disease had higher rates of HPR. (Figure). Conclusion In patients with ACS, the presence and extension of multivessel CAD were associated with higher levels of platelet aggregability and higher rates of high on-treatment platelet reactivity with clopidogrel. This finding may explain the incremental benefit with more intense antiplatelet therapies seen in this particular subgroup in prior clinical trials. Prevalence of HPR and extension of CAD Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Sao Paulo Research Foundation (FAPESP)

ObjectiveThe impact of serum uric acid (sUA) levels on the clinical prognosis and severity of coronary artery disease in patients with acute coronary syndrome (ACS) and hypertension after percutaneous coronary...

Reply: The forced correlation between ISCHEMIA and the inaccurate CABG recommendations of the 2021 American College of Cardiology/American Heart Association/Society for cardiovascular Angiography coronary revascularization guidelines

The relationship between autoantibodies to oxidized low density lipoprotein (OxLDL) and coronary artery disease (CAD) remains controversial. IgM and IgG OxLDL autoantibodies to malondialdehyde (MDA)-modified LDL, copper oxidized low density lipoprotein (CuOxLDL), and oxidized cholesterol linoleate (OxCL), as well as apolipoprotein B-100 immune complexes (apoB-ICs), were measured in 504 patients undergoing clinically indicated coronary angiography. Patients were followed for cardiovascular events for a median of 4 years. In univariate analysis, IgM OxLDL autoantibodies and IgM apoB-ICs were inversely associated with the presence of angiographically determined CAD, whereas IgG OxLDL autoantibodies and IgG apoB-ICs were positively associated. In logistic regression analysis, compared with the first quartile, patients in the fourth quartile of IgM OxLDL autoantibodies and apoB-ICs showed a lower probability of angiographically determined CAD (>50% diameter stenosis). Odds ratios and (95% confidence intervals) were as follows: MDA-LDL, 0.51 (0.32-0.82; P = 0.005); CuOxLDL, 0.63 (0.39-1.01; P = 0.05); OxCL, 0.63 (0.39-1.01; P = 0.05); and apoB-IC, 0.55 (0.34-0.88; P = 0.013). These relationships were accentuated in the setting of hypercholesterolemia, with the highest IgM levels showing the lowest risk of CAD for the same level of hypercholesterolemia. Multivariable analysis revealed that neither IgM or IgG OxLDL autoantibodies nor apoB-ICs were independently associated with angiographically determined CAD or cardiovascular events. In conclusion, IgG and IgM OxLDL biomarkers have divergent associations with CAD in univariate analysis but are not independent predictors of CAD or clinical events.

To evaluate the relationship between an incremental model including cardiovascular risk factors, carotid disease, and inflammatory biomarkers to predict the presence of obstructive coronary artery disease (CAD). A total of 134 consecutive and asymptomatic intermediate-risk patients (mean age 61 ± 9 years, 52% men) were enrolled. Each subject underwent circulating levels assessment of interleukin (IL)-2r, IL-6, IL-8, IL-10, high-sensitivity C-reactive protein (hs-CRP) and carotid and coronary artery evaluation using carotid ultrasound and coronary computed tomography angiography (CCTA), respectively. Carotid disease was diagnosed in 71 (53%) patients. Obstructive and multi-vessel CAD were found in 50 (37%) and 18 (14%) patients, respectively. Patients in whom CCTA showed multi-vessel CAD had a higher rate of carotid disease (89 vs. 46%, P = 0.001) and increased values of all interleukins when compared with patients without multi-vessel obstructive CAD. The univariate and multivariate analysis showed that male gender, diabetes, carotid disease, and IL-6 were independently associated with obstructive CAD. At receiver operating characteristic curve analysis, the multivariate model (including male gender, carotid disease, IL-6 > 5.9 pg/mL, and diabetes) showed the highest area under the curve for prediction of obstructive CAD, multi-vessel CAD, and high-risk plaque defined as mixed and/or remodelled plaque when compared with all other models (P < 0.001). Among asymptomatic intermediate-risk patients, the presence of increased IL6 levels in addition to traditional risk factors (male gender with diabetes) and carotid artery disease predicts higher rates of obstructive CAD and it could be of help to identify which subset of asymptomatic patients could be referred to CCTA for screening.

For decades, coronary artery bypass grafting (CABG) has been the main method of myocardial revascularization in patients with coronary artery disease, including those with acute coronary syndrome (ACS). Over the past decades, with the development of endovascular interventions and the development of drug-eluting stents, percutaneous coronary intervention (PCI) has become the main method of revascularization after ACS. [1,6]. Acute coronary syndrome (ACS) includes clinical manifestations such as unstable angina pectoris (NS), acute non-ST-segment elevation myocardial infarction (STEMI), and ST-segment elevation myocardial infarction (STEMI). Approximately 40% of all patients diagnosed with ACS have multivessel coronary artery disease, for which coronary artery bypass grafting (CABG) is better than PCI. [2]. The majority of studies comparing PCI and CABG have mainly included patients with stable coronary artery disease who underwent planned myocardial revascularization, rather than those requiring emergency or urgent myocardial revascularization. Thus, the results of these studies have limited applicability to patients with ACS. However, the long-term results of these studies, in particular the low need for re-revascularization, a lower rate of re-myocardial infarction, and the survival benefits of CABG, still need to be considered when determining the best course of treatment for ACS. The current recommendations for treatment in most patients with ACS give preference to early revascularization using PCI or CABG [3, 4]. Thus, our main goal here is to provide the current indications and options for surgical revascularization of the coronary arteries, including current guidelines and the latest published literature. In STEMI patients, early PCI of the main lesion remains the gold standard because it provides the fastest revascularization of the ischemic myocardium and is generally better tolerated than emergency CABG [5]. Since up to 50% of STEMI patients have multivessel coronary artery disease, early arterial revascularization without myocardial infarction has been recommended to provide optimal opportunities for myocardial rescue, reduction of ischemic watershed and improvement of left ventricular function [6,7]. A clinical case of successful beating coronary artery bypass grafting in a patient with ST-segment elevation myocardial infarction, multivessel coronary artery disease and low ejection fraction. The patient was discharged on the 11th day after surgery without complications.

Background Artificial intelligence (AI)-based quantitative computed tomography (AI-QCT) is a novel tool for automated plaque characterization and quantification from coronary computed tomography angiography (CCTA). The prognostic value of various AI-QCT plaque types on top of the presence of obstructive or ischemic coronary artery disease (CAD) is unknown. Purpose To investigate the added prognostic value for acute coronary syndrome (ACS) of AI-QCT total plaque burden (percent atheroma volume (PAV) %), and its subcomponents non-calcified plaque burden (NCPB), low-attenuation plaque burden (LAP), and calcified plaque burden (CPB) (%) on top of obstructive or ischemic CAD. Methods A cohort of 2007 symptomatic patients having undergone CCTA and selective downstream PET perfusion for suspected CAD was analyzed. Patients with prior or early elective revascularization within 6 months from CCTA were excluded. Obstructive CAD was defined as ≥1 vessel with &amp;gt;50% visual stenosis, and ischemic CAD as absolute hyperemic myocardial blood flow ≤2.3 ml/g/min in ≥2 adjacent segments on 15O-H2O PET. Multivariable Cox regressions adjusted for clinical confounders (age, sex hypertension, typical angina) including each plaque type separately (per 1.0%) on top of obstructive or ischemic CAD, respectively, were performed. The amount of LAP was &amp;lt;1% and therefore pooled together with NCPB. Results Throughout a median follow-up of 7 years, 72/2007 patients experienced ACS (50 myocardial infarction, 22 unstable angina). On top of obstructive CAD, all plaque types were independent predictors of ACS (Figure 1A), however according to the C-indexes (p-value vs. obstructive CAD), only PAV (C-index=0.814, p=0.010) and NCPB+LAP (C-index=0.818, p=0.014), but not CPB (C-index=0.800, p=0.066) significantly improved the prediction of ACS on top of obstructive CAD (C-index=0.790) (Figure 2A). On top of ischemic CAD (1967 patients, 66 events), all plaque types were also independent predictors of ACS (Figure 1B). But, similarly, according to the C-indexes (p-value vs. ischemic CAD), only PAV (C-index=0.818, p=0.003), and NCPB+LAP (C-index=0.818, p=0.005), but not CPB (C-index=0.798, p=0.054) significantly improved the prediction of ACS on top of ischemic CAD (C-index=0.776) (Figure 2B). NCPB+LAP alone performed similarly as PAV on top of obstructive (p=0.554) and ischemic CAD (p=0.991) (Figure 2). Conclusions Among patients with native coronary arteries treated medically, AI-based plaque quantification significantly improved the prediction of ACS on top of obstructive or ischemic CAD. The risk of ACS was largely related to NCPB+LAP, whereas CPB did not significantly improve risk stratification.Adjusted HR for ACS per plaque typeC-indexes for ACS

Background Metabolic syndrome is associated with increased incidence of diabetes and cardiovascular diseases in patients initially free from these diseases. However, its prognostic value in patients with established coronary artery diseases remains controversial. Purpose Therefore, we aimed to illustrate the prevalence and investigate the impact of metabolic syndrome in patients with multivessel coronary artery disease and acute coronary syndrome. Methods We conducted a large registry of consecutive patients with acute coronary syndrome referred to primary percutaneous coronary intervention and those with multivessel diseases were eligible for this analysis. Metabolic syndrome was defined using modified criteria based on the Adult Treatment Panel III definition from the National Cholesterol Education Program. The primary outcome was major adverse cardiovascular events (MACE), a composite of all-cause death, myocardial infarction, and stroke. Results A total of 2532 patients were included in current analysis and 993 (39.2%) of them had metabolic syndrome while 1539 (60.8%) did not. The prevalence of metabolic syndrome increased over the study period (p for trend = 0.005). There was a significant decline of metabolic syndrome prevalence in patients over 60 years old (p for trend = 0.002) and females had a higher prevalence than their male counterparts (61.5% verse 32.9%, p&amp;lt;0.001). Over a median follow-up of 2.3 years, metabolic syndrome was not significantly associated with MACE (adjusted 95% CI 0.92 to 1.54). In addition, there was no significant difference observed between two groups in other individual outcomes, namely all-cause death, cardiac death, stroke, myocardial infarction, and any revascularization. Conclusions Metabolic syndrome was frequently observed in patients with multivessel coronary artery disease and acute coronary syndrome. Patients with metabolic syndrome were more likely to be young and female. However, it was not an independent predictor for MACE after primary percutaneous coronary intervention in those patients. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences Metabolic syndrome distribution in MVDOutcome according to metabolic syndrome

This study evaluates the association between high sensitivity troponin I (hsTnI) and T (hsTnT) in patients with suspected stable Coronary Artery Disease (CAD) undergoing Coronary Computed Tomography Angiography (CCTA). Patients undergoing CCTA were enrolled prospectively. CCTA was indicated in patients with angina and a low to intermediate pre-test probability for CAD during routine clinical care. Blood samples were taken at the time of CCTA to measure cardiac biomarkers. A total of 99 patients were enrolled with 43 % revealing no CAD, 30 % with non-obstructive and 26 % with obstructive CAD. Out of these, 61 % had single-vessel and 39 % had multi-vessel CAD. Both hsTnI and hsTnT levels increased significantly according to the presence and extent of CAD (p = 0.0001) and were able to discriminate the presence of both obstructive (AUC range: 0.775 - 0.785; p = 0.0001) and multi-vessel CAD (AUC range: 0.740 - 0.749; p = 0.01). In multivariate logistic regression models adjusted for cardiovascular risk factors and NT-proBNP, both hsTn were still associated significantly with obstructive CAD (range of odds ratios (OR): 8.3-32.3; p < 0.02). This study shows that high sensitivity troponin I and T reflect the presence and extent of CAD being diagnosed by CCTA in patients with a low to intermediate pretest probability for CAD.

792 Acute Coronary Syndrome in Patients With Normal or Non-Obstructive Coronary Artery Disease: Patient Characteristics and Long-Term Outcomes

Objectives The aim of this study was to evaluate all-cause mortality in patients aged greater than 80 years old with multi-vessel (MV) coronary artery disease (CAD) presenting with an acute...

Although risk factors for acute coronary syndrome (ACS) and atherothrombotic cerebral infarction (ACI) are common, it is unknown if the risk factors for these two conditions are similar. The purpose of our study was to elucidate differences in carotid artery atherosclerotic features between ACS and ACI. We measured carotid artery ultrasound-based atherosclerotic parameters in 61 ACS and 33 ACI patients. In the ACS patients, 31 had single-vessel coronary artery disease (SVD) and 30 had multivessel coronary artery disease (MVD). The maximum intima-media thickness (IMT) of the common carotid artery was higher in ACS patients with MVD than in ACS patients with SVD (P<0.05), and tended to be higher than that in ACI patients (P=0.085). The values in ACS patients with SVD and ACI patients were similar. The maximum IMT of the carotid artery bulb in ACS patients with MVD was similar to that in both ACS patients with SVD and ACI patients. The plaque score was higher in ACS patients with MVD than in ACS patients with SVD (P<0.01), but similar to that in ACI patients. ACS and ACI show common atherosclerotic features as assessed by carotid artery ultrasonography.

Treatment Strategies in CKD Patients With Suspected Coronary Artery Disease

Commentary: Does the SYNTAX (Synergy between PCI with Taxus and Cardiac Surgery) score even matter?