Artery Disease Events Research Articles

Abstract 9691: Lipoprotein Subclasses Are Associated With Hepatic Steatosis: Insights from the Prospective Multicenter Imaging Study for the Evaluation of Chest Pain (PROMISE) Clinical Trial

Introduction: Hepatic steatosis (HS) is associated with coronary artery disease (CAD) and cardiovascular (CV) events. Previously, we have demonstrated that granular measures of lipids (lipoprotein particle number/size) are associated with CAD and CV events and incremental to traditional lipid measures. Hypothesis: Granular measures of lipids are associated with HS detected by cardiac computed tomography (CT) and with HS detected by histopathology. Methods: We included 1524 subjects from the PROMISE trial. HS was defined as CT attenuation of the liver <40HU or liver<spleen HU on CT. Plasma lipoprotein particle parameters were measured by NMR. Principal components analysis was used for dimensionality reduction and logistic regression was used to test the association of lipoprotein factors and individual lipoproteins with HS cases and controls in uni/multivariable models. The association of lipoproteins with HS was validated in an independent cohort of 58 subjects (Laval U) with and without HS defined by histopathology on liver biopsy. Results: Subjects with HS (n=413) were slightly younger (59±8 vs 61±8 yrs) and more likely men (53 vs 44%) as compared to controls (n=1111). Three lipoprotein factors were associated with HS: LDL/LDL particle size (OR 1.36, 95%CI 1.21-1.53, p<0.001); HDL/HDL size (OR 1.75, 95%CI, 1.53-2.02, p<0.001), and TG-rich-lipoprotein particles (OR 0.74, 95% CI 0.65-0.84, p<0.002). Individual lipoproteins heavily loaded in these factors were also significant in multivariable analysis (Figure). These lipoproteins were also associated with HS in the validation cohort: small LDL (OR 6.36, p<0.05), large HDL (OR 0.29, p<0.05), and large TG particles (OR 13.83, p<0.05). Conclusions: We found association of small LDL, large HDL and large TG particles, previously associated with CV event risk, with HS phenotyped by CT and histopathology. These results suggest that use of lipoprotein subclasses may improve CV risk assessment in patients with HS.

Abstract 10363: Mitochondrial DNA Copy Number is Associated with Severe Coronary Artery Disease and Risk of Subsequent Long-Term Major Adverse Cardiovascular Events

Introduction: Mitochondrial DNA copy number (mtDNA-CN) is associated with cardiovascular disease (CVD) and mortality. Here we examine, in a high-risk CVD population, the association with prevalent coronary artery disease (CAD) and subsequent major adverse events (MACE) at 1-,5- and 10-year follow-up of mtDNA-CN. Methods: Consecutive subjects (n=2267) consenting to a blood sample drawn for the Intermountain INSPIRE biorepository at the time of a coronary angiogram from July 1994 to Sept 2003 were included. The mtDNA-CN was determined by multiplexed real-time polymerase chain reaction coamplifying a stable site of mt D- Loop and a region of a single copy genomic β-2-microglobulin gene(β2M). MtDNA-CN is given as the ratio of Mt to β2M DNA. The presence of severe CAD (>70% stenosis) was analyzed using multivariate logistic regression. The subsequent MACE (including all-cause mortality and non-fatal MI) outcomes were studied using multivariate Cox proportional hazard regression. Results: The average age of subjects was 62.3 ± 13.8, 35% were female, and 50% had prior CAD. Over half (55%) had severe CAD at the angiogram. As the mtDNA-CN increased, severe CAD decreased (58% for 1 st quartile vs. 51% for 4 th quartile). After adjustment for baseline differences, subjects with mtDNA-CN in the 1 st quartile were 1.31 times more likely to have severe CAD than subjects with mtDNA-CN in the 4 th quartile (95% CI: 1.01, 1.71; p=0.04). A total of 902(39.8%) had a subsequent MACE event within 10-years (193[8.5%] in 1-year and 548[24.2%] in 5-years). There was no association between mtDNA-CN and 1-year MACE. However, mtDNA-CN was associated with 5-year (p=0.006) and 10-year (p=0.003) MACE. After adjustment, subjects with mtDNA-CN in the 1 st quartile were at 1.29 increased risk of 10-year MACE than subjects with mtDNA-CN in the 4 th quartile (95% CI: 1.07, 1.56; p=0.008). Conclusions: In a coronary angiographic population, mtDNA-CN was associated with severe CAD and the risk of subsequent long-term MACE. These findings suggest that mtDNA-CN could be used as a clinical biomarker for risk. Moreover, understanding the factors impacting mtDNA-CN may also help in the prevention of secondary CVD outcomes.

Shorter (GT)n repeats in the haem-oxygenase 1 gene promoter are associated with better mid-term survival in subjects with coronary artery disease and abnormal ejection fraction

Background Haem oxygenase (HO)-1 is a rate-limiting enzyme for degrading haem into carbon monoxide. Subjects with longer GT repeats in the HO-1 gene (HMOX1) promoter are more likely to have coronary artery disease (CAD) and cardiovascular events. Methods We retrospectively enrolled CAD subjects with an abnormal ejection fraction (EF) <50% from our catheterisation data (N = 670). Polymerase chain reactions were performed for amplifying the HMOX1 promoter GT repeating segment to determine the number of repeats. Results In a median follow-up period of 40 months, 213 patients died. The distribution of genotype for HMOX1 promoter GT repeating segments SS, SL, and LL were significantly different (p < 0.001) between the dead (44.6%, 36.2%, 19.2%, respectively) and the survived (53.8%, 37.4%, 8.8%, respectively) (S allele: ≤30 repeats, L allele: >30 repeats). In Cox regression analysis, carrier of S allele (hazard ratio 0.665, p = 0.027), a higher EF (hazard ratio 0.037, p = 0.001), and revascularization with PCI were all negatively associated with all-cause death in subjects with CAD and abnormal EF. Conclusions Carrier of shorter (GT)n repeats of HMOX1 gene promoter was negatively correlated with death events in CAD patients with abnormal EF.

Percutaneous coronary intervention in patients with peripheral artery disease and adverse cardiovascular adverse event and bleeding

Abstract Background Peripheral artery disease (PAD) increase the risk of comorbidity and mortality in coronary artery disease (CAD). Objectives We evaluate influence of PAD on prognosis in patients undergoing percutaneous coronary intervention (PCI). Methods We analyzed all consecutive patients included in our dedicated local registry for PCI between January 2011 and December 2016. Presence of PAD was defined by decreased ankle-brachial index (&amp;lt;0.9). Major adverse cardiovascular event (MACE) was defined as a composite of cardiovascular death, non-fatal myocardial infarct, revascularization, and ischemic stroke. Major bleeding was defined as Bleeding Academic Research Consortium 3 or 5. Results Among the 4,747 patients who underwent the PCI, 12.9% (n=610) of PAD were identified. Old age (&amp;gt;60 years), renal dysfunction, reduced ejection fraction, and presence of PAD were predictors with both MACE and major bleeding event. Among them, presence of PAD was an independent risk factor of MACE and major bleeding (MACE, HR 8.26, 95% CI 2.33- 29.41, p=0.036; major bleeding, HR 3.11, 95% CI 1.10–10.63, p=0.040, respectively). The MACE and major bleeding rate at 5-year was significantly increased in patients with PAD (MACE, 30.0% vs. 15.8%, log rank test p&amp;lt;0.001; major bleeding, 6.7 vs. 3.6%, log rank test p=0.003, respectively) (Figure). Conclusion Presence of PAD was strongly associated with higher rate of long-term MACE and major bleeding. These findings could have a clinical relevance in requiring individualized pharmacologic strategies to reduce the burden of cardiovascular disease. Funding Acknowledgement Type of funding sources: None.

Abstract MP04: Single Cell Profiling Identifies IgM To MDA-LDL Producing Human B Cells And Atheroprotective Role Of CD24

Murine B-1 cells produce IgMs that inactivate oxidation-specific epitopes and protect against atherosclerosis. Despite compelling data that IgM to MDA-LDL (IgM MDA-LDL ) is inversely associated with coronary artery disease (CAD) and cardiovascular (CV) events in human, the human B cell subtype that produces IgM MDA-LDL is unknown. Here, we utilized mass cytometry to identify the 11 circulating human B cell subtypes and discovered that only the frequency of CD20 + CD27 + IgM + cells was associated with IgM MDA-LDL levels. Notably, high expression of CD24, a GPI-anchored sialoglycoprotein, was associated with IgM MDA-LDL (r = 0.57, p = 0.002) and inversely associated with CAD severity (r = -0.58, p=0.001). Adoptive transfer (AT) of sorted CD20 + CD27 + IgM + CD24hi (B 27+IgM+CD24hi ) and CD24lo/- (B 27+IgM+CD24lo/- ) human B cells into humanized mice demonstrated that CD24 is critical for trafficking to the spleen and IgM production. Bulk RNAseq coupled with pathway analysis of B 27+IgM+CD24hi and B 27+IgM+CD24lo/- cells revealed enhanced BCR and CCR6 signaling in B 27+IgM+CD24hi . Imaging flow cytometry indicated colocalization between CD24 and CCR6 which was abrogated by CD24 blocking antibody (CD24mAb). Trans-well migration and internalization assays demonstrated that CD24 blockade increased CCL20-induced CCR6 internalization (p &lt; 0.05, n =4), and reduced CCL20-induced migration of B 27+IgM+CD24hi cells (p &lt; 0.05, n =4). CD24mAb treatment of B 27+IgM+CD24hi cells prior to AT into humanized mice also reduced the amount of surface CCR6 on B 27+IgM+CD24hi cells in vivo (p &lt; 0.05, n = 4). Both CCR6 knockout and CD24 inhibition of B 27+IgM+CD24hi cells reduced migration to the spleen (p &lt; 0.05, n = 4), and plasma level of human IgM (p = 0.057, n = 4). Lastly, single cell multi-omics sequencing of PBMCs from 60 CAD subjects revealed elevated CCR6 and IgM signaling in B 27+IgM+CD24hi cells in subjects with less severe CAD. Results provide the first evidence for a role for CD24 in regulating CCR6-mediated B cell homing to the spleen, IgM production and CAD in humans. Findings may have important implications for the new CD24 immunotherapy entering clinical trials and raise the possibility that augmenting CD24 and/or CCR6 on B 27+IgM+ cells may be an effective atheroprotective strategy.

Parenteral anticoagulation in non-ST segment elevation acute coronary syndromes: which option to pick?

Abstract Background According to the 2015 European Society of Cardiology's non-ST segment elevation acute coronary syndrome (NSTE-ACS) clinical practice guideline, fondaparinux is the parenteral anticoagulant with the most favorable efficacy/safety profile. Thus, it is recommended over enoxaparin, for instance, in that setting. However, its use and performance in a contemporary portuguese cohort has not been fully described. Purpose To assess fondaparinux utilization degree and to compare its in-hospital efficacy and safety profiles with those of enoxaparin, in a contemporary portuguese cohort of NSTE-ACS patients. Methods Patients consecutively admitted with NSTE-ACS, between October 2010 and January 2019, were retrospectively identified from a national registry of acute coronary syndromes and were further divided in two groups, as per parenteral anticoagulation strategy (fondaparinux vs. enoxaparin). Key exclusion criteria were specific contraindications to both agents, recent hemorrhagic stroke and indications for anticoagulation other than ACS. The primary efficacy endpoint was a composite of in-hospital reinfarction and mortality, whereas the primary safety endpoint was moderate-to-severe bleeding, as defined by the GUSTO criteria. Results A total of 5843 NSTE-ACS patients (mean age 65±13 years, 72.4% males) were included. Of these, 89.2% had a myocardial infarction, while the remaining 10.8% were diagnosed with unstable angina. The most frequent cardiovascular comorbidities were hypertension (71.3%), dyslipidemia (63.0%) and diabetes mellitus (31.7%). Fondaparinux was the anticoagulant of choice in 27.5% of patients, whereas the remainder were treated with enoxaparin. Compared with patients receiving enoxaparin, those in the fondaparinux group were younger, had less hypertension or diabetes mellitus and exhibited a less severe presentation; nonetheless, they had more often a previous history of coronary artery disease or hemorrhagic events. An invasive approach in terms of revascularization was adopted in 87.7% of the cohort (79.1% in the fondaparinux group vs. 90.9% in the enoxaparin group, p&amp;lt;0.001). The primary efficacy and safety endpoints occurred in 2.4% and 4.7% of patients, respectively. After adjustment for relevant covariates, the use of fondaparinux was independently associated with a lower rate of both the primary efficacy (OR 0.56 [0.32–0.95], p=0.034) and the primary safety endpoints (OR 0.37 [0.23–0.59], p&amp;lt;0.001). Conclusion In a contemporary portuguese cohort of NSTE-ACS patients, fondaparinux was underused but still independently associated with a lower risk of both a composite of in-hospital reinfarction or mortality event and major hemorrhage. Funding Acknowledgement Type of funding source: None

Rationale and Design of the ACS-BP Study: Prognostic Value of In-Hospital Blood Pressure and Indices of Atherosclerosis in Acute Coronary Syndromes.

High blood pressure (BP) is a leading risk factor for coronary artery disease and other major cardiovascular events. Blood pressure variability (BPV), ambulatory arterial stiffness index (AASI) and ankle- brachial index (ABI) have been proposed as indices that can improve risk stratification for an adverse cardiac outcome. However, their utility in the setting of acute coronary syndromes (ACS) is unclear. The ACS-BP study is a single-centre observational cohort study designed to investigate the prognostic role of haemodynamic load and arterial stiffness indices for cardio-renal outcomes in patients with acute myocardial infarction (AMI). All consecutive patients admitted with a diagnosis of acute AMI with or without ST segment elevation were screened for inclusion in the study. The management of AMI will follow current guidelines. Data from baseline clinical and laboratory parameters during their hospitalization were collected. The haemodynamic load of each patient was determined by clinical BP values as well as 24-h ambulatory BP monitoring. The AASI was calculated from the raw 24-h BP data and ABI was measured after the third day of hospitalization using a certified device. Patients were followed-up for 12 months in order to collect data for hard cardiovascular and renal endpoints. The study results should clarify the role of these non-invasive tools in secondary risk stratification of such patients.

Relationship between ABO blood groups and cardiovascular disease in type 1 diabetes according to diabetic nephropathy status

BackgroundABO blood groups have previously been associated with cardiovascular disease (CVD) in the general population. This study aimed to investigate the potential relationship between ABO blood groups and CVD in individuals with type 1 diabetes according to diabetic nephropathy (DN) status.MethodsAdults with type 1 diabetes (4531 individuals) from the FinnDiane Study were evaluated. DN was determined by two out of three measurements of urinary albumin excretion rate. Albuminuria was defined as an excretion rate above 20 µg/min. CVD events were identified by linking the data with the Finnish Care Register for Health Care and the Finnish Cause of Death Register. Follow-up ranged from the baseline visit until a CVD event, death or the end of 2017. The impact of ABO blood groups on CVD risk was estimated by multivariable Cox-regression analyses adjusted for traditional risk factors.ResultsAt baseline, the median age was 38.5 (IQR 29.2–47.9) years, 47.5% were female and median duration of diabetes was 20.9 (11.4–30.7) years. There were 893 incident ischemic heart disease (IHD) events, 301 ischemic strokes (IS), and 415 peripheral artery disease (PAD) events during a median follow up of 16.5 (IQR 12.8–18.6) years. The A blood group showed the highest risk of IHD versus the O blood group, when microalbuminuria was present. Comparing the population with microalbuminuria with those with normoalbuminuria, only the A blood group elevated the risk of IHD. This increased risk was neither explained by the FUT2 secretor phenotype nor by the A-genotype distribution. The risk of IS or PAD was no different among the ABO blood groups regardless of diabetic nephropathy stage.ConclusionThe A blood group is a risk factor for IHD in individuals with type 1 diabetes and microalbuminuria.

Early diastolic strain rate by two-dimensional speckle tracking echocardiography is a predictor of coronary artery disease and cardiovascular events in stable angina pectoris.

This study aimed to clarify the diagnostic and prognostic potential of strain rate in patients with suspected stable angina pectoris (SAP). Strain rate by 2-dimensional speckle tracking echocardiography (2DSTE) has been suggested to be able to diagnose coronary artery disease (CAD) and predict cardiovascular events in various patient groups. Prospectively enrolled patients (n = 296) with suspected SAP, no previous cardiac disease, and normal left ventricular ejection fraction were examined by 2DSTE, exercise ECG, and coronary angiography. Obstructive CAD was defined as stenosis ≥ 70% in ≥ 1 coronary artery on coronary angiography (n = 107). Major adverse cardiac events (MACE) included myocardial infarction, heart failure, atrial fibrillation, and stroke. In multivariable analysis adjusted for baseline data, conventional echocardiography, and Duke score, early diastolic strain rate (SRe) was independently associated with significant CAD with a 1.35 increased risk of having CAD per 0.1 decrease in SRe (OR = 1.35, 95% CI 1.03-1.76, P = 0.027). Peak velocity of early diastolic filling (E)/SRe was not associated with significant CAD (OR = 1.14, 95% CI 0.81-1.62, P = 0.445). MACE occurred in 34 patients (12%) during follow-up (median 3.5years) and both SRe (HR 1.26, 95% CI (1.07-1.49), P = 0.006) and E/SRe (HR 1.24, 95% CI (1.04-1.47), P = 0.017) were independent predictors after multivariable adjustment. In patients with suspected SAP, SRe by 2DSTE was independently associated with presence of CAD. In addition, SRe and E/SRe provided independent and incremental prognostic value for predicting future MACE.

Liraglutide treatment improves the coronary microcirculation in insulin resistant Zucker obese rats on a high salt diet

BackgroundObesity, hypertension and prediabetes contribute greatly to coronary artery disease, heart failure and vascular events, and are the leading cause of mortality and morbidity in developed societies. Salt sensitivity exacerbates endothelial dysfunction. Herein, we investigated the effect of chronic glucagon like peptide-1 (GLP-1) receptor activation on the coronary microcirculation and cardiac remodeling in Zucker rats on a high-salt diet (6% NaCl).MethodsEight-week old Zucker lean (+/+) and obese (fa/fa) rats were treated with vehicle or liraglutide (LIRA) (0.1 mg/kg/day, s.c.) for 8 weeks. Systolic blood pressure (SBP) was measured using tail-cuff method in conscious rats. Myocardial function was assessed by echocardiography. Synchrotron contrast microangiography was then used to investigate coronary arterial vessel function (vessels 50–350 µm internal diameter) in vivo in anesthetized rats. Myocardial gene and protein expression levels of vasoactive factors, inflammatory, oxidative stress and remodeling markers were determined by real-time PCR and Western blotting.ResultsWe found that in comparison to the vehicle-treated fa/fa rats, rats treated with LIRA showed significant improvement in acetylcholine-mediated vasodilation in the small arteries and arterioles (< 150 µm diameter). Neither soluble guanylyl cyclase or endothelial NO synthase (eNOS) mRNA levels or total eNOS protein expression in the myocardium were significantly altered by LIRA. However, LIRA downregulated Nox-1 mRNA (p = 0.030) and reduced ET-1 protein (p = 0.044) expression. LIRA significantly attenuated the expressions of proinflammatory and profibrotic associated biomarkers (NF-κB, CD68, IL-1β, TGF-β1, osteopontin) and nitrotyrosine in comparison to fa/fa-Veh rats, but did not attenuate perivascular fibrosis appreciably.ConclusionsIn a rat model of metabolic syndrome, chronic LIRA treatment improved the capacity for NO-mediated dilation throughout the coronary macro and microcirculations and partially normalized myocardial remodeling independent of changes in body mass or blood glucose.

P938Extensive formation of atherosclerotic cardiovascular disease in subjects with severe familial hypercholesterolemia defined by the international atherosclerosis society criteria

Abstract Introduction The International Atherosclerosis Society (IAS) has proposed “severe familial hypercholesterolemia (FH)” as a FH phenotype with the highest cardiovascular risk. Coronary artery disease (CAD) represents a major atherosclerotic change in FH patients. Given their higher LDL-C level and atherogenic clinical features, more extensive formation of atherosclerosis cardiovascular disease including not only CAD but stroke/peripheral artery disease (PAD) may more frequently occur in severe FH. Methods 481 clinically-diagnosed heterozygous FH subjects were analyzed. Severe FH was defined as untreated LDL-C&gt;10.3 mmol/l, LDL-C&gt;8.0 mmol/l+ 1 high-risk feature, LDL-C&gt;4.9 mmol/l + 2 high-risk features or presence of clinical ASCVD according to IAS proposed statement. Cardiac (cardiac death and ACS) and non-cardiac (stroke and peripheral artery disease) events were compared in severe and non-severe FH subjects. Results Severe FH was identified in 50.1% of study subjects. They exhibit increased levels of LDL-C and Lipoprotein (a) with a higher frequency of LDLR mutation. Furthermore, a proportion of %LDL-C reduction&gt;50% was greater in severe FH under more lipid-lowering therapy (Table). However, during the observational period (median=6.3 years), severe FH was associated with a 5.9-fold (95% CI, 2.05–25.2; p=0.004) and 5.8-fold (95% CI, 2.02–24.7; p=0.004) greater likelihood of experiencing cardiac-death/ACS and stroke/PAD, respectively (picture). Multivariate analysis demonstrated severe FH as an independent predictor of both cardiac-death/ACS (hazard ratio=3.39, 95% CI=1.12–14.7, p=0.02) and stroke/PAD (hazard ratio=3.38, 95% CI=1.16–14.3, p=0.02) events. Clinical characteristics of severe FH Non-severe FH Severe FH P-value Baseline LDL-C (mmol/l) 5.3±1.5 6.6±2.0 &lt;0.0001 Lp(a) (mg/dl) 15 [8–28] 21 [10–49] &lt;0.0001 LDLR mutation (%) 49.6% 58.9% 0.00398 On-treatment LDL-C (mmol) 133 [106–165] 135 [103–169] 0.9856 %LDL-C reduction&gt;50% 21.3% 49.8% &lt;0.0001 High-intensity statin (%) 13.3% 42.3% &lt;0.0001 PCSK9 inhibitor (%) 6.3% 21.2% &lt;0.0001 Clinical outcome Conclusions Severe FH subjects exhibit substantial atherosclerotic risks for coronary, carotid and peripheral arteries despite lipid lowering therapy. Our finding underscore the screening of systemic arteries and the adoption of further stringent lipid management in severe FH patients.

P5515Circulating galectin 1 is associated with severity of coronary artery disease and adverse cardiovascular events in patients undergoing coronary angiography

Abstract Background Galectin-1, a β-galactoside-binding lectin, was reported to attenuate the cardiac inflammation and ventricular remodeling after AMI. Its role in stable CAD was not fully elaborated. This study aimed to identify the relationship between galectin-1 and severity of CAD in patients with stable angina. Methods Totally 834 subjects underwent elective CAG were enrolled. Pre-procedure galectin-1 and hsCRP concentrations were determined. Subjects were grouped into tertiles according to their galectin-1 concentrations. SYNTAX scores were calculated to evaluate the severity of CAD. All patients were followed until January 2019, or the occurrence of major adverse cardiovascular events (MACE). Results Patients with higher galectin-1 concentrations were older and had higher prevalence of hypertension, diabetes, heart failure, and with higher levels of hsCRP and STNYAX scores. Patients with the highest tertile of galectin-1 were associated with higher risk of MACE (Fig 1A), even after adjusting age, gender, hypertension, diabetes, hemoglobin, creatinine, and LVEF (aHR: 2.13, 95% CI: 1.04–4.33, p=0.038). Gelection-1 (AUC: 0.802) showed better discriminatory performance than hsCRP (AUC: 0.696) in prediction the incidence of MACE (Fig 1B). Table 1 Tertile 1 (n=278) Tertile 2 (n=278) Tertile 3 (n=278) P Age (years) 61.0 (54.8–71.0) 67.0 (60.0–75.0) 72.0 (61.0–80.3) &lt;0.001 Male, n (%) 188 (67.6) 184 (66.2) 197 (70.9) 0.479 Hypertension, n (%) 153 (55.0) 185 (66.5) 219 (78.8) &lt;0.001 Diabetes, n (%) 67 (24.1) 90 (32.4) 123 (44.2) &lt;0.001 Heart failure, n (%) 10 (3.6) 8 (2.9) 44 (15.8) &lt;0.001 Hemoglobin (g/dL) 13.5 (12.5–14.3) 13.4 (12.4–14.3) 12.3 (10.8–13.7) &lt;0.001 Creatinine (mg/dL) 0.9 (0.8–1.1) 1.0 (0.9–1.2) 1.3 (1.1–1.9) &lt;0.001 Hs-CRP (mg/dL) 0.1 (0.0–0.2) 0.1 (0.0–0.3) 0.2 (0.1–0.7) &lt;0.001 Galectin 1 (ng/mL) 13.3 (10.2–14.7) 18.7 (17.4–20.5) 29.3 (25.5–38.5) &lt;0.001 SYNTAX score 0.0 (0.0–5.0) 0.0 (0.0–7.0) 7.0 (0.0–16.1) &lt;0.001 LVEF (%) 59.0 (54.6–62.2) 58.0 (52.0–63.0) 55.9 (49.0–60.9) 0.009 MACE: revascularization, n (%) 17 (6.1) 13 (4.7) 43 (15.5) &lt;0.001 MACE: nonfatal MI, n (%) 1 (0.4) 1 (0.4) 7 (2.5) 0.018 MACE: nonfatal stroke, n (%) 0 (0.0) 1 (0.4) 2 (0.7) 0.367 MACE: death, n (%) 4 (1.4) 1 (0.4) 13 (4.7) 0.001 Conclusion Serum galectin-1 levels were associated with the severity of CAD and subsequent MACE in patients with stable angina. Acknowledgement/Funding This study was supported in part by research grants from the Taipei Veterans General Hospital and Taiwan Ministry of Science and Technology Academic E

Comparing the Modified History, Electrocardiogram, Age, Risk Factors, and Troponin Score and Coronary Artery Disease Consortium Model for Predicting Obstructive Coronary Artery Disease and Cardiovascular Events in Patients With Acute Chest Pain.

The objective of this study was to compare the History, Electrocardiogram, Age, Risk factors, and Troponin (HEART) score and clinical coronary artery disease (CAD) consortium (CADC) model for predicting obstructive CAD (≥50% stenosis on coronary computed tomographic angiography) and 30-day major adverse cardiovascular events (MACE, composite of acute myocardial infarction, revascularization, and mortality). We studied 1981 patients with no known CAD who presented with acute chest pain and had negative initial troponin and electrocardiogram. Chest pain was classified as typical, atypical, and nonanginal and used to score the history component of the modified HEART score. The C-statistic for predicting obstructive CAD was 0.747 [95% confidence interval (CI), 0.712-0.783] for the HEART score and 0.792 (95% CI, 0.762-0.823) for the CADC model (P = 0.0005). The C-statistic for predicting 30-day MACE was 0.820 (95% CI, 0.774-0.864) for the HEART score and 0.850 (95% CI, 0.800-0.891) for the CADC model (P = 0.11). Among the 48.3% of patients for whom the CADC model predicted ≤5% probability of obstructive CAD, the observed 30-day MACE was 0.6%; among the 48.9% of patients for whom the HEART score was ≤2, the 30-day MACE was 0.6%. In conclusion, the CADC model was more effective at predicting obstructive CAD compared to the HEART score. The HEART score and CADC model were equally effective to safely identify low-risk patients by achieving <1% missed 30-day MACE.

THE IMPACT OF ATRIAL FIBRILLATION AT TIME OF CARDIAC PET STRESS TESTING ON RESULTS, CORONARY OUTCOMES, AND MACE

Atrial fibrillation (AF) is associated with coronary artery disease (CAD) and major cardiovascular adverse events (MACE); cardiac PET imaging may be used to determine the risk of these outcomes. However, it is unclear whether having AF at the time of the PET will impact the results and subsequent

P1554A non-invasive vascular multi-marker approach for the detection of coronary artery disease and future adverse events in high cardiovascular risk patients

P1554A non-invasive vascular multi-marker approach for the detection of coronary artery disease and future adverse events in high cardiovascular risk patients

Performance of Clinical/Proteomic Biomarker Panels to Predict Coronary Artery Disease Presence or Cardiovascular Prognosis in Patients With and Without Diabetes Mellitus

Background: Patients with diabetes mellitus (DM) are at increased risk for prevalent coronary artery disease (CAD) and incident major adverse cardiac events (MACE) such as cardiovascular death, myocardial infarction, and stroke. Prediction of risk in those with DM may be challenging. Using unbiased proteomics we recently described biomarker panels to predict prevalent CAD (HART-CAD) and incident MACE (HART-CVE; both Prevencio, Kirkland, WA) in unselected patients undergoing diagnostic coronary angiography. In this study, we sought to compare accuracy of these panels in patients with and without DM. Methods: The HART-CAD panel includes 2 clinical variables (male sex and prior PCI) and 4 biomarkers: adiponectin, apolipoprotein CI, kidney injury molecule 1 (KIM 1), and midkine. The HART-CVE panel includes 4 biomarkers (amino-terminal pro-B type natriuretic peptide, KIM 1, osteopontin, and tissue inhibitor of matrix metalloproteinase-1). These panels were derived in 167 DM and 482 non-DM patients; performance of each was validated in a second cohort of patients (N=278) with and without DM. Results: In patients with DM, the HART-CAD panel had excellent performance for prediction of coronary stenosis ≥ 70%, with area under the curve (AUC) of 0.81 (p&amp;lt;0.001), sensitivity 85%, specificity 69%, positive predictive value (PPV) 90%, and negative predictive value (NPV) 58% for detection of CAD, results comparable to those without DM. HART-CVE was highly predictive of incident 1 year MACE in those with DM: AUC of 0.80 (p=0.002), sensitivity 78%, specificity 69%, PPV 47%, and NPV of 90%, again, comparable to those without DM. In Kaplan-Meier analyses, an elevated HART-CVE score predicted shorter time to first MACE (p&amp;lt;0.001). Conclusion: Previously described multivariate proteomic biomarker panels effectively predict prevalent CAD and risk for incident MACE in at-risk patients with DM. Disclosure S. Shrestha: None. C.P. McCarthy: None. N.E. Ibrahim: None. R. van Kimmenade: None. H. Gaggin: Research Support; Self; Roche Diagnostics Corporation, Portola. Consultant; Self; Roche Diagnostics Corporation, Amgen Inc., Ortho clinical. Other Relationship; Self; EchoSense, Radiometer. R. Mukai: None. C.A. Magaret: Consultant; Self; Prevencio. G. Barnes: Employee; Self; Prevencio. R.F. Rhyne: None. J. Januzzi: Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc.. Board Member; Self; Jana Care Inc.. Research Support; Self; Prevencio.

Coronary Artery Calcium Trajectory Predicts Coronary Artery Disease Events—The CACTI Study

Coronary artery calcium (CAC), a marker of subclinical atherosclerosis, predicts coronary artery disease (CAD) events, but the best use of CAC in risk prediction remains unclear. We examined whether group-based trajectory modeling of CAC in the Coronary Artery Calcification in Type 1 Diabetes (CACTI) study could independently predict CAD events. Four CAC trajectory groups (Figure 1a) were identified using longitudinal CAC in people free from CAD (Proc TRAJ in SAS Version 9.4), and these groups were used to predict a subsequent CAD event (myocardial infarction or coronary revascularization) using survival analysis. People with type 1 diabetes (T1D) were more likely to be in higher CAC trajectory groups than those without diabetes (non-DM, p&amp;lt;0.0001). Over 17,417 person-years of follow-up, 75 CAD events occurred (56 in T1D and 19 in non-DM individuals). Higher CAC trajectory group predicted CAD events in a dose-response manner (Figure 1b). In cox proportional hazards adjusted for age, sex, T1D, smoking, LDL, HDL, triglycerides and systolic blood pressure, being in a higher CAC group increased CAD risk, with a 33-fold increased risk in Group 4 (95% CI 12-91). A 3.3-fold excess risk (95% CI 1.7-6.4) for CAD remained for people with T1D. CAC trajectory group modeling can identify individuals at very high risk for a CAD event. However, T1D increases CAD risk independently of traditional risk factors and CAC trajectory. Disclosure J.K. Snell-Bergeon: Stock/Shareholder; Self; Abbott. Research Support; Self; Roche Diagnostics Corporation. A. Keshawarz: None. G.L. Kinney: None. I.E. Schauer: None. V.N. Shah: None. L. Pyle: None.

Lipoprotein(a) Cholesterol But Not Lipoprotein(a) Mass is Significantly Correlated with Angiographic Coronary Artery Disease and Major Adverse Events

Lipoprotein(a) Cholesterol But Not Lipoprotein(a) Mass is Significantly Correlated with Angiographic Coronary Artery Disease and Major Adverse Events

P1761Diabetic status influences the effect of pro-inflammatory interleukin-1 genotypes on lipoprotein(a) mediated risk of coronary artery disease and cardiovascular events

P1761Diabetic status influences the effect of pro-inflammatory interleukin-1 genotypes on lipoprotein(a) mediated risk of coronary artery disease and cardiovascular events

Lack of association between cystatin C and different coronary atherosclerotic manifestations

Cystatin C (CysC) is known to be related to cardiovascular disease (CVD), including the presence and severity of coronary artery disease (CAD) and future clinical events. In this study, the association between CysC levels and (1) coronary artery calcification (CAC) in asymptomatic individuals from the general population as well as (2) different subgroups of patients with suspected or definite acute myocardial infarction (MI) was investigated. CysC levels were measured in serum from asymptomatic individuals as part of a screening study for CAC using non-contrast cardiac CT scan (N = 1039) as well as in subgroups of hospitalized patients with a suspected MI (N = 769). CysC was not associated with CAC in asymptomatic individuals after adjusting for relevant risk factors. No difference in CysC levels was observed between patients with type 1 MI (1.07 mg/L) and patients with normal troponin (with or without prior CAD: 1.14 and 1.01 mg/L, respectively). However, patients with type 2 MI and patient subgroups with elevated troponin but without MI had significantly higher CysC levels (1.24, 1.23 and 1.31 mg/L), even after adjusting for other risk factors. CysC was not associated with CAC in middle-aged asymptomatic individuals from the general population. Furthermore, CysC levels were found to be significantly lower in patients with type 1 MI compared to patients with type 2 MI and patients with elevated troponins but without MI. Thus, in two independent and clinically different populations, no association between CysC and coronary atherosclerotic manifestations could be demonstrated.