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Background: Type 2 myocardial infarction (T2MI) related to a supply/demand imbalance of coronary blood flow is common and associated with poor prognosis. Coronary artery disease (CAD) may predispose some individuals to T2MI and contribute to its high rate of recurrent cardiovascular events. Little is known about the presence and extent of CAD in this population., Objectives: The goal of this study was to evaluate the presence and characteristics of CAD among patients with T2MI., Methods: In this prospective study, consecutive eligible individuals with Fourth Universal Definition of Myocardial Infarction criteria for T2MI were enrolled. Participants underwent coronary computed tomography angiography (CTA), fractional flow reserve derived with coronary CTA (FFR CT ), and plaque volume analyses., Results: Among 50 participants, 25 (50%) were female, and the mean age was 68.0 ± 11.4 years. Atherosclerotic risk factors were common. Coronary CTA revealed coronary plaque in 46 participants (92%). A moderate or greater stenosis (≥50%) was identified in 42% of participants, and obstructive disease (≥50% left main stenosis or ≥70% stenosis in any other epicardial coronary artery) was present in 26%. Prevalence of obstructive CAD did not differ according to T2MI cause (P = 0.54). A hemodynamically significant focal stenosis identified by FFR CT was present in 13 participants (26%). Among participants with a stenosis ≥50% (n = 21), FFR CT excluded lesion-specific hemodynamically significant stenosis in 8 cases (38%)., Conclusions: Among individuals with adjudicated T2MI, CAD was prevalent, but the majority of patients had nonobstructive CAD. Mediators of ischemia are likely multifactorial in this population. (Defining the Prevalence and Characteristics of Coronary Artery Disease Among Patients with Type 2 Myocardial Infarction using CT-FFR [DEFINE TYPE 2 MI]; NCT04864119)., Competing Interests: Funding Support and Author Disclosures This work was supported by a grant from HeartFlow Inc. Dr McCarthy was supported by a National Heart, Lung, and Blood Institute T32 postdoctoral training grant (5T32HL094301-12); and has received consulting income from Abbott Laboratories and Roche Diagnostics. Dr Mohebi is supported by the Barry Fellowship. Dr Wasfy is supported by the American Heart Association (18 CDA 34110215); is chair of the New England Comparative Effectiveness Public Affairs Council (CEPAC); has received grant support from the American Heart Association and the National Institutes of Health; and has received consulting fees from Pfizer and Biotronik. Dr Januzzi is supported by the Hutter Family Professorship; is a Trustee of the American College of Cardiology; is a Director at Imbria Pharmaceuticals; is an advisor at Jana Care; has received grant support from Abbott, Applied Therapeutics, HeartFlow Inc, Innolife, and Roche Diagnostics; has received consulting income from Abbott, Janssen, Novartis, Merck, and Roche Diagnostics; and participates in clinical endpoint committees/data safety monitoring boards for Abbott, AbbVie, Bayer, CVRx, Intercept, Pfizer, and Takeda. Dr Ghoshhajra is on the Executive Committee of the Society of Cardiovascular Computed Tomography (President); has received grant support from Siemens Healthineers and the National Institutes of Health; and has received consulting fees from Siemens Healthineers, Philips Healthcare, and 3DR Labs (all unrelated to this work). Dr Rogers is an employee and shareholder of HeartFlow Inc. Dr Blankstein has received research support from Amgen Inc and Novartis Inc; and has served as a consultant/advisory board member for Caristo Inc, Elucid Inc, HeartFlow Inc, Beren Therapeutics, and Nanox.AI. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Inflammation, measured by traditional biomarkers such as C-reactive protein, has been linked to cardiovascular (CV) events. Recent technological advancement has allowed for measuring larger numbers of inflammatory biomarkers. A contemporary evaluation with established and novel biomarkers of inflammation is needed., Methods: 1,090 individuals who underwent coronary angiography were enrolled. Twenty-four inflammatory biomarkers were collected prior to angiography. Unsupervised machine learning cluster analyses determined unique patterns of inflammatory biomarkers. Cox proportional hazard regression assessed both association of inflammatory biomarker clusters and individual biomarker associations with major adverse cardiovascular events (MACE; non-fatal myocardial infarction or stroke, and CV death) during a median follow-up of 3.67 years., Results: Four distinct clusters were recognized. Incremental increases in inflammatory biomarkers were observed from cluster 1 to cluster 4. During follow-up, 263 MACE were ascertained. Considering cluster 1 as a reference, study participants with inflammatory cluster 2 (Hazard ratio [HR] 1.55, 95% confidence interval [CI]: 1.01-2.37), cluster 3 (HR 1.89, CI: 1.25-2.85), and cluster 4 (HR 2.93, CI: 1.95-4.42) were at increased risk of MACE. Interleukin (IL)-1α IL-6, IL-8, IL-10, IL-12, Adhesion molecule-1 high-sensitivity C-reactive protein, ferritin, myeloperoxidase, macrophage inflammatory protein (MIP)-1a, MIP 3, and macrophage colony-stimulating factor-1 were independently associated with MACE., Conclusions: Among persons undergoing coronary angiography procedures, distinct clusters of inflammatory biomarker distributions with significant prognostic meaning may be identified. These results may identify unique targets for anti-inflammatory treatments aimed at CV disease., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The relation of high-sensitivity cardiac troponin I (hs-cTnI) concentration and presence of obstructive coronary artery disease (CAD) in patients without myocardial infarction (MI) is unclear. Study participants selected from patients free of MI who underwent coronary angiography with or without intervention were enrolled, and hs-cTnI measured. A gradient boosting model was implemented to build a model for detection of CAD. Cox proportional hazard regression was used to assess the association of hs-cTnI and adverse cardiovascular (CV) outcome. Among 978 study participants, 607 patients (62%) had CAD. Higher concentrations of hs-cTnI were associated with chronic kidney disease, heart failure, CAD, male gender, current tobacco use, anemia, age, and low-density lipoprotein cholesterol. History of CAD, male gender, type 2 diabetes mellitus, hs-cTnI, anemia, age, and high-density lipoprotein cholesterol were the most influential factors for detection of CAD. The gradient boosting model had an area under the curve of 0.82, accuracy of 75%, sensitivity of 88%, specificity of 52%, positive predictive value of 76%, and negative predictive value of 72% for detection of CAD. Increase in 1 log unit of hs-cTnI was significantly associated with increased risk of incident MI (hazard ratio [HR] 1.34, 95% confidence interval [CI] 1.22 to 1.47, p <0.001), CV mortality (HR 1. 24, 95% CI 1.11 to 1.39, p <0.001), and composite of incident MI or CV mortality (HR 1.29, 95% CI 1.20 to 1.40, p <0.001). In conclusion, among patients without acute MI and CAD, higher concentrations of hs-cTnI were associated with the presence of CAD and linked to increased risk of future CV events. ClinicalTrials.gov Identifier: NCT00842868., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background Current noninvasive modalities to diagnose coronary artery disease (CAD) have several limitations. We sought to derive and externally validate a hs-cTn (high-sensitivity cardiac troponin)-based proteomic model to diagnose obstructive coronary artery disease. Methods and Results In a derivation cohort of 636 patients referred for coronary angiography, predictors of ≥70% coronary stenosis were identified from 6 clinical variables and 109 biomarkers. The final model was first internally validated on a separate cohort (n=275) and then externally validated on a cohort of 241 patients presenting to the ED with suspected acute myocardial infarction where ≥50% coronary stenosis was considered significant. The resulting model consisted of 3 clinical variables (male sex, age, and previous percutaneous coronary intervention) and 3 biomarkers (hs-cTnI [high-sensitivity cardiac troponin I], adiponectin, and kidney injury molecule-1). In the internal validation cohort, the model yielded an area under the receiver operating characteristic curve of 0.85 for coronary stenosis ≥70% ( P <0.001). At the optimal cutoff, we observed 80% sensitivity, 71% specificity, a positive predictive value of 83%, and negative predictive value of 66% for ≥70% stenosis. Partitioning the score result into 5 levels resulted in a positive predictive value of 97% and a negative predictive value of 89% at the highest and lowest levels, respectively. In the external validation cohort, the score performed similarly well. Notably, in patients who had myocardial infarction neither ruled in nor ruled out via hs-cTnI testing ("indeterminate zone," n=65), the score had an area under the receiver operating characteristic curve of 0.88 ( P <0.001). Conclusions A model including hs-cTnI can predict the presence of obstructive coronary artery disease with high accuracy including in those with indeterminate hs-cTnI concentrations.

Background: Concentrations of circulating apolipoproteins are strongly linked to risk for coronary artery disease (CAD). The relative importance of the additional knowledge of apolipoprotein concentrations within specific lipoprotein species for CAD risk prediction is limited., Objectives: This study sought to evaluate the performance of a high-density lipoprotein (HDL) apolipoproteomic score, based on targeted mass spectrometry of HDL-associated apolipoproteins, for the detection of angiographic CAD and outcomes., Methods: HDL-associated apolipoprotein (apo) A-1, apoC-1, apoC-2, apoC-3, and apoC-4 were measured in 943 participants without prevalent myocardial infarction (MI) referred for coronary angiography in the CASABLANCA (Catheter Sampled Blood Archive in Cardiovascular Diseases) study. A composite HDL apolipoproteomic score (pCAD) was associated with likelihood of obstructive CAD (≥70% lesion in ≥1 vessel) and with incident cardiovascular outcomes over 4-year follow-up., Results: There were 587 (62.2%) patients with coronary stenosis. The pCAD score was associated with the presence of obstructive CAD (odds ratio: 1.39; 95% confidence interval [CI]: 1.14 to 1.69; p < 0.001), independently of conventional cardiovascular risk factors including circulating plasma apoA-1 and apoB. The C-index for pCAD was 0.63 (95% CI: 0.59 to 0.67) for the presence of obstructive CAD. Although pCAD was not associated with cardiovascular mortality among all individuals (hazard ratio: 1.24; 95% CI: 0.93 to 1.66; p = 0.15), there was evidence of association for individuals with obstructive CAD (hazard ratio: 1.48; 95% CI: 1.07 to 2.05; p = 0.019)., Conclusions: An HDL apolipoproteomic score is associated with the presence of CAD, independent of circulating apoA-1 and apoB concentrations and other conventional cardiovascular risk factors. Among individuals with CAD, this score may be independently associated cardiovascular death. (The CASABLANCA Study: Catheter Sampled Blood Archive in Cardiovascular Diseases [CASABLANCA]; NCT00842868)., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The meaning of high-sensitivity troponin I (hsTnI) concentrations in patients without acute myocardial infarction (MI) requires clarity. We hypothesized that among patients referred for diagnostic coronary angiography without acute MI, hsTnI concentrations would correlate with prevalent coronary artery disease (CAD) and predict incident cardiovascular events and mortality., Methods and Results: We measured hsTnI using a single-molecule counting assay (99th percentile, 6 ng/L) in samples from 991 patients obtained at the time of angiography. Concentrations of hsTnI were assessed relative to the severity of CAD and prognosis during mean follow-up of 3.7 years. Median hsTnI concentration was 4.19 ng/L; 38% of patients had hsTnI concentrations ≥99th percentile. Across increasing hsTnI quartiles, patients had higher prevalence of angiographic CAD; in multivariate models, hsTnI ≥99th percentile independently predicted obstructive CAD (odds ratio: 2.57; P <0.001) and incident MI (hazard ratio [HR]: 2.68; P <0.001), cardiovascular death (HR: 2.29; P =0.001), and all-cause death (HR: 1.84; P =0.004). In those with >70% coronary stenosis, hsTnI ≥99th percentile independently predicted incident MI (HR: 1.87; P =0.01), cardiovascular mortality (HR: 2.74; P =0.001), and the composite end point of MI and all-cause death (HR: 2.06; P <0.001). In participants with coronary stenosis <70%, hsTnI ≥99th percentile even more strongly predicted incident MI (HR: 8.41; P <0.001), cardiovascular mortality (HR: 3.60; P =0.03), and the composite end point of MI and all-cause death (HR: 3.62; P <0.001)., Conclusions: In a large prospective cohort of patients who were free of prevalent MI and undergoing diagnostic coronary angiography, hsTnI concentrations were associated with higher prevalence of CAD and predicted incident MI, cardiovascular death, and all-cause death., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00842868., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Introduction: Concentrations of circulating apolipoproteins are strongly linked to risk for coronary artery disease (CAD). However, relative importance of the additional knowledge of apolipoprotein concentrations within specific lipoprotein species for CAD risk prediction is limited. Hypothesis: Apolipoproteins (apo) directly within high density lipoprotein (HDL) particles among patients undergoing coronary angiography associate with CAD quantitative measures and outcomes. Methods: HDL-associated apoA-1, apoC-1, apoC-2, apoC-3, and apoC-4 were measured in 938 participants without prevalent myocardial infarction (MI) referred for coronary angiography in the Catheter Sampled Blood Archive in Cardiovascular Diseases (CASABLANCA, NCT00842868) study. A composite score (pCAD) was calculated using these features based on a model to predict angiographic CAD from an independent set of patients. The pCAD score was then associated with likelihood of prevalent CAD (>=70% lesion in >=1 vessel) and with incident cardiovascular outcomes over a 4-year follow up period. Results: There were 587 (62.6%) patients with prevalent CAD. The pCAD HDL-specific proteomic score was associated with the presence of CAD (odds ratio per standard deviation [OR/SD]: 1.44; 95% confidence interval [CI]: 1.29-1.60). Association was independent of conventional cardiovascular risk factors, including circulating plasma apoA-1 and apoB measures. The C-statistic for CAD odds was 0.64 (95% CI 0.60-0.68). Additionally, pCAD was associated with the composite endpoint of incident MI and cardiovascular mortality (hazard ratio per SD [HR/SD]: 1.18, 95% CI: 1.01-1.38), in a model adjusting for conventional risk factors, including circulating plasma apoA-1 and apoB concentrations. In stratified analyses, the association with incident MI and cardiovascular mortality was similar (P for interaction = 0.41) in those with prevalent CAD (HR/SD: 1.21, 95% CI: 1.01-1.44) and those without prevalent CAD (HR/SD: 1.07, 95% CI: 0.73-1.58). Conclusions: An HDL proteomic score, independent of circulating apoA-1 and apoB concentrations, is strongly associated with the prevalence of CAD. Among those with CAD, this score predicted risk of future MI and cardiovascular death. [ABSTRACT FROM AUTHOR]