Composite Endpoint Of Myocardial Infarction Research Articles

Cardiovascular safety of evogliptin dual and triple therapy in patients with type 2 diabetes: a nationwide cohort study

ObjectiveTo investigate the risk of cardiovascular events associated with commonly used dual and triple therapies of evogliptin, a recently introduced dipeptidyl peptidase-4 inhibitor (DPP4i), for managing type 2 diabetes in...

Abstract 12263: Inflammation and Cholesterol as Predictors of Cardiovascular Events and Risk Reduction With Bempedoic Acid Among Statin Intolerant Patients: An Analysis of the CLEAR Outcomes Trial

Introduction: Among contemporary statin-treated patients, residual inflammatory risk assessed by high-sensitivity C-reactive protein (hsCRP) is a stronger predictor of future cardiovascular (CV) events and all-cause mortality than residual cholesterol risk assessed by low density lipoprotein cholesterol (LDLC). Whether these relationships are present among statin-intolerant patients is unknown but has implications for the choice of preventive therapies including bempedoic acid, an agent that reduces both LDLC and hsCRP. Methods: In the multi-national CLEAR-Outcomes trial, 13,970 statin-intolerant patients were randomly allocated 1:1 to 180 mg oral bempedoic acid daily or matching placebo and followed for incident myocardial infarction (MI), stroke, coronary revascularization, CV death, and all-cause mortality. Quartiles of increasing baseline hsCRP and LDLC were assessed as predictors of future adverse CV events after adjustment for traditional risk factors and treatment (bempedoic acid vs. placebo). Results: Baseline hsCRP was significantly associated with incident composite endpoint of MI, stroke, coronary revascularization, and CV death (highest vs lowest hsCRP quartile, HR=1.43, 95% CI 1.24-1.65), CV mortality (HR=2.00, 95% CI 1.53-2.61), and all-cause mortality (HR=2.21, 95% CI 1.79-2.73). By contrast, the relationship of baseline LDLC quartile (highest vs. lowest) to future CV events was smaller for the composite endpoint (HR=1.19, 95% CI 1.04-1.37) and neutral for CV mortality (HR 0.90, 95% CI 0.70-1.17) and all-cause mortality (HR 0.95, 95% CI 0.78-1.16) such that risks were high for those with elevated hsCRP irrespective of LDLC level. Compared to placebo, bempedoic acid reduced median hsCRP by 21.6% and mean LDLC levels by 21.1% at 6 months and demonstrated similar efficacy in reducing major adverse CV events across all levels of hsCRP and LDLC. Interpretation: Among contemporary statin-intolerant patients, inflammation assessed by hsCRP was a stronger predictor of risk for future CV events and death than was hyperlipidemia assessed by LDLC. Compared to placebo, bempedoic acid had similar efficacy for reducing CV risk across hsCRP and LDLC strata.

Diagnostic and prognostic value of the sex-specific 99th percentile of four high-sensitivity cardiac troponin assays in patients with suspected myocardial infarction.

High-sensitivity cardiac troponin (hs-cTn) assays are used for detection of myocardial infarction (MI). Ninety-ninth percentiles show wide inter-assay variation. The use of sex-specific cut-offs is recommended as definitory cut-off for MI. We compared diagnostic performance and prognostic value of sex-specific 99th percentiles of four hs-cTn assays in patients with suspected MI. Concentrations of four hs-cTn assays were measured at presentation and after 3 h in patients with suspected MI. Final diagnoses were adjudicated according to the 4th Universal Definition of MI. Unisex and sex-specific 99th percentiles were evaluated as diagnostic cut-offs following the ESC 0/3 h algorithm. These cut-offs were used in Cox-regression analyses to investigate the association with a composite endpoint of MI, revascularization, cardiac rehospitalization, and death. Non-ST-elevation MI was diagnosed in 368 of 2718 patients. Applying the unisex 99th percentile, Elecsys hs-cTnT provided highest negative predictive value (NPV) of 99.7 and a positive predictive value (PPV) of 75.9. The analysed hs-cTnI assays showed slightly lower NPVs and comparable PPVs [Architect (NPV 98.0, PPV of 71.4); Atellica (NPV 97.7, PPV of 76.1); Pathfast (NPV 97.7, PPV of 66.6)]. Application of sex-specific 99th percentiles did not significantly affect diagnostic performance. Concentrations above 99th percentile were independent predictors for impaired long-term outcome (hazard ratios 1.2-1.5, P < 0.001). We describe a good diagnostic accuracy of four hs-cTn assays using the assay-specific 99th percentile for detection of MI. Application of sex-specific 99th percentiles did neither affect diagnostic performance nor prognostic value significantly. Finally, values above the 99th percentile were associated with poor long-term outcome.

Elevated plasma factor XI predicts cardiovascular events in patients with type 2 diabetes: a long-term observational study

Background Type 2 diabetes mellitus (T2DM) patients are at high risk of cardiovascular (CV) events. Factor XI (FXI) is associated with arterial thromboembolism, including myocardial infarction (MI), stroke, and CV mortality. The role of FXI in T2DM is unknown. We investigated whether plasma FXI is associated with CV events in T2DM patients in long-term observation.MethodsIn 133 T2DM patients (aged 66 ± 8 years, 40.6% women, median T2DM duration 5 [2–10] years) we assessed plasma FXI levels, along with fibrin clot properties, thrombin generation, and fibrinolysis proteins. A composite endpoint of MI, stroke, or CV death, as well as CV mortality alone were assessed during a median follow-up of 72 months.ResultsPlasma FXI above the 120% upper normal limit was detected in 25 (18.8%) patients and showed positive association with LDL cholesterol and thrombin activatable fibrinolysis inhibitor, but not glycated hemoglobin, inflammatory markers or thrombin generation. The composite endpoint (n = 21, 15.8%) and CV death alone (n = 16, 12%) were more common in patients with elevated FXI (hazard ratio [HR] 10.94, 95% confidence interval [CI] 4.46–26.87, p < 0.001 and HR 7.11, 95% CI 2.61–19.31, p < 0.001, respectively). On multivariable analysis, FXI remained an independent predictor of the composite endpoint and CV death, regardless of concomitant coronary artery disease.ConclusionsTo our knowledge, this study is the first to show that in T2DM patients, elevated FXI could predict major CV events, including mortality, which suggest that anti-FXI agents might be a potential novel antithrombotic option in this disease.

Elevated factor XIa as a modulator of plasma fibrin clot properties in coronary artery disease.

Patients with coronary artery disease (CAD) display a prothrombotic fibrin clot phenotype, involving low permeability and resistance to lysis. The determinants of this phenotype remain elusive. Circulating tissue factor (TF) and activated factor XI (FXIa) are linked to arterial thromboembolism. We investigated whether detectable active TF and FXIa influence fibrin clot properties in CAD. In 118 CAD patients (median age 65 years, 78% men), we assessed Ks, an indicator of clot permeability, and clot lysis time (CLT) in plasma-based assays, along with the presence of active TF and FXIa. We also analysed proteins involved in clotting and thrombolysis, including fibrinogen, plasminogen activator inhibitor-1 (PAI-1) and thrombin activatable thrombolysis inhibitor (TAFI). During a median 106 month (interquartile range 95-119) follow-up, myocardial infarction (MI), stroke, systemic thromboembolism (SE) and cardiovascular (CV) death were recorded. Circulating TF and FXIa, detected in 20.3% and 39.8% of patients, respectively, were associated with low Ks and prolonged CLT. Solely FXIa remained an independent predictor of low Ks and high CLT on multivariable analysis. Additionally, fibrinogen and PAI-1 were associated with low Ks, while PAI-1 and TAFI-with prolonged CLT. During follow-up low Ks and prolonged CLT increased the risk of MI and the latter also a composite endpoint of MI, stroke/SE or CV death. To our knowledge, this study is the first to show that circulating FXIa is associated with prothrombotic fibrin clot properties in CAD, suggesting additional mechanisms through which FXIa inhibitors could act as novel antithrombotic agents in CAD.

1129 IMAGING STRESS TEST OR CORONARY COMPUTED TOMOGRAPHY PRIOR TO NON-CARDIAC SURGERY? A SEVEN YEARS SINGLE CENTRE EXPERIENCE

Abstract Introduction Recent published ESC guidelines on non-cardiac surgery suggest the use of imaging stress test in patients with poor functional capacity and high likelihood of coronary artery disease or high clinical risk (class I, level B), while the use of coronary computed tomography has lower evidence (class IIa, level B). Witch test has the best performance in the clinical contest of pre-operative risk assessment is a matter of debate. Aim The aim of our single centre, retrospective study was to compare the prognostic role of the three main cardiac imaging modalities (CCT: Cardiac computed tomography, sCMR: stress cardiac magnetic resonance, SPECT MPI:single photon emission computed tomography myocardial perfusion imaging) in relation to 30 days post-surgery cardiac events (composite endpoint of myocardial infarction, unstable angina, cardiac death, cardiogenic shock, pulmonary oedema, life threatening cardiac arrythmias). Method Clinical data of patients from January 2015 to December 2021 were retrospectively collected from review of electronical medical records. Recorded data included demographic characteristics, clinical risk factors, results from laboratory tests, results from cardiac imaging tests, pharmacological therapy, type of intervention, cardiac complication within 30 days after surgery. Results Eight-hundred eighty-three patients were included (287 sCMR, 382 SPECT-MPI, 214 CCT). Rate of 30-days myocardial infarction was not significantly different between different modalities (CMR 1.1%, SPECT 1.3%; CT 0.5%; CMR vs SPECT p 0.998; sCMR vs CT p 0.639; SPECT vs CT 0.427); while planned invasive coronary angiography (ICA) was more common in CT group (CT 34%, CMR 16%, SPECT 10%, p&amp;lt;0,001). Absence of ischemia on stress test and absence of relevant coronary artery disease on CT are associate to lower cardiac events at follow-up (0.67%). Conclusions The use of imaging stress test and coronary CT are both associated to low incidence of cardiac events and should be recommended in risk assessment before non-cardiac surgery, in the appropriate clinical context.

704 STRESS TEST STRATEGY WITH CMR AND SPECT-MPI REDUCES CARDIAC EVENTS IN CANDIDATES TO NON-CARDIAC SURGERIES

Abstract Introduction . Cardiac complications related to non-cardiac surgery have a variable incidence, from less than 1% to more than 5% with a great variability depending on type of intervention, patient's risk factors and results from tests performed during the pre-operative evaluation. The aim of our single centre retrospective study was to evaluate the prognostic role of stress cardiac magnetic resonance (sCMR) and single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI) in relation to 30 days post-surgery cardiac events. Method Clinical data of patients from January 2015 to December 2021 were retrospectively collected from review of electronical medical records. Only intermediate and high risk surgeries were included. All patients underwent to cardiologic, electrocardiographic and echocardiographic evaluation before surgery. Stress test was performed according to cardiologist judgment. Primary endpoint was a composite endpoint of myocardial infarction, unstable angina, cardiac death, cardiogenic shock, pulmonary oedema and life threatening cardiac arrythmias. Secondary endpoint were the research of ischemia predictors and the rate of revascularization. Results One-thousand-five-hundred-ninety patients were included, 669 stress tests were performed (287 sCMR, 382 SPECT-MPI). Rate of 30-days cardiac events was lower in the stress test group vs non-stress test group (1,2% vs 3,4%; p 0,006). Imaging stress test strategy showed a significant reduction of composite endpoint at multivariate analysis (OR: 0.334, IC: 0.155–0.766, p 0.009). Predictors of ischemia were hypertension, coronary artery disease and diastolic dysfunction. SCMR was non inferior to SPECT with regard the risk of cardiac events, while showed a greater accuracy to predict coronary revascularization (AUC for sCMR: 0.94). Conclusions Stress test strategy reduces cardiac events in high risk patients candidate to moderate- to high- risk surgeries. Stress CMR is non-inferior to SPECT with regards to the risk of cardiac events, but has a greater accuracy to predict the need for revascularization.

Fish intake and risk of cardiovascular events: an analysis of the VITAL cohort.

Dietary habits with fish consumption have been associated with a lower risk of cardiovascular (CV) disease, based on heterogenous observational studies. Current recommendations suggest eating at least 1-2 fish servings per week for CV prevention. We conducted a retrospective evaluation of a cohort study that enrolled a large primary prevention population to determine the potential benefit of fish intake ≥1.5 serving per week, through a multivariate Cox regression model. The outcomes of interest included all-cause mortality, cardiovascular mortality, MACE (composite endpoint of myocardial infarction, stroke, and death from cardiovascular causes), expanded MACE (MACE plus coronary revascularization), total myocardial infarction (MI), total coronary heart disease (CHD) and total stoke. The estimates were reported using hazard ratio (HR) with 99% confidence intervals (99% CI). A total of 25,435 patients were evaluated (11,921 individuals ≥1.5 fish servings/week; 13,514 < 1.5 fish servings per week). Intake ≥1.5 servings/week was not independently associated with CV outcomes reduction, such as CV mortality, MI risk MACE, expanded MACE outcomes, CHD or stroke (HR 0.78, 99% CI 0.57-1.07). Fish intake ≥1.5 servings/week was not associated with CV outcomes improvement in this analysis, but potential benefit cannot be ruled out.

Plasma Gut Microbe-Derived Metabolites Associated with Peripheral Artery Disease and Major Adverse Cardiac Events.

Cardiovascular diseases are associated with gut dysbiosis, but the role of microbe-derived metabolites as biomarkers or modulators of cardiovascular disease are not well understood. This is a targeted metabolomics study to investigate the association of nine microbe-derived metabolites with lower extremity peripheral artery disease (PAD), a form of atherosclerosis, and major adverse cardiac events (MACE). The study cohort consists of individuals with intermittent claudication and ankle-brachial index (ABI) < 0.9 (N = 119) and controls without clinically-apparent atherosclerosis (N = 37). The primary endpoint was MACE, a composite endpoint of myocardial infarction, coronary revascularization, stroke, transient ischemic attack, or cardiac-related death. Plasma metabolite concentrations differed significantly between the PAD and control groups. After adjustment for traditional atherosclerosis risk factors, kynurenine, hippuric acid, indole-3-propionic acid (IPA), and indole-3-aldehyde (I3A) concentrations were negatively associated with PAD, whereas indoxyl sulfate and 3-hydroxyanthranilic acid were positively associated. Hippuric acid, IPA, and I3A correlated with ABI, a surrogate for atherosclerotic disease burden. Those in the highest I3A concentration quartile had significantly improved freedom from MACE during follow-up compared to those in the lowest quartile. This study identifies specific indole- and phenyl-derived species impacted by gut microbial metabolic pathways that could represent novel microbiome-related biomarkers of PAD.

Incident atrial fibrillation and heart failure in treated hypertensive patients with left ventricular hypertrophy

Abstract Background Hypertension and left ventricular hypertrophy (LVH) are predictors of atrial fibrillation (AF) and heart failure (HF). The incidence rates of AF and HF and especially the combination of these two complications in hypertensive patients with LVH receiving antihypertensive treatment are unknown, and so are the association with risk levels of other cardiovascular diseases and death in hypertensive patients with LVH who develop new onset AF and HF. Purpose We aimed to investigate the appearance and severity of AF and HF in 8,702 hypertensive patients aged 55–80 years with LVH receiving antihypertensive treatment in a prospective and randomized clinical trial primarily designed to investigate the preventive effect on a composite endpoint of myocardial infarction, stroke and cardiovascular death. Methods Included were patients who had sinus rhythm in ECG and no history of AF or HF when they were randomly allocated to blinded study medication with losartan or atenolol. Additional medication was given with hydrochlorothiazide and calcium antagonist if needed to gain blood pressure control. Incident AF was detected by annual ECGs and from adverse event reports submitted by the 930 clinical investigators. Incident HF was diagnosed according to Framingham criteria. Endpoints including incident HF, myocardial infarction, stroke and cardiovascular death were reported with relevant documentation by the investigators, and adjudicated by an expert endpoint committee. Results Incident AF occurred in 679 patients (7.8%) and HF in 246 patients (2.8%) during 4.7±1.1 years mean follow-up. Incident AF was associated with a &amp;gt;4-fold increased risk of developing subsequent HF (HR=4.7; 95% CIs, 3.1–7.0; P&amp;lt;0.001) in multivariable Cox analyses adjusting for age, sex, race, randomized treatment, standard cardiovascular risk factors and incident myocardial infarction. The development of HF as a time-dependent variable was associated with a multivariable-adjusted 3-fold increase of the primary study endpoint (HR=3.11; 95% CIs, 1.52 to 6.39; P&amp;lt;0.001) which was the composite of myocardial infarction, stroke or cardiovascular death. Incident HF was associated with a &amp;gt;3-fold increased risk of developing subsequent AF (HR=3.3; 95% CIs, 2.3–4.9; P&amp;lt;0.001). This development of AF was associated with more than a 2-fold increase of the composite of myocardial infarction, stroke or cardiovascular death in multivariable Cox analysis (HR=2.26; 95% CIs, 1.09–4.67; P=0.028). Conclusions Incident atrial fibrillation and heart failure are associated with increased risk of the other in treated hypertensive patients with left ventricular hypertrophy. These hypertensive patients who subsequently develop both atrial fibrillation and heart failure during antihypertensive treatment have particularly high risk of an additional composite endpoint consisting of myocardial infarction, stroke or cardiovascular death. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): The study originally received support from Merck &amp; Co., Inc.

Activated factor XI is associated with increased factor VIIa - Antithrombin complexes in stable coronary artery disease: Impact on cardiovascular outcomes.

Coronary artery disease (CAD) is associated with a prothrombotic tendency including increased factor (F) VIIa-antithrombin (FVIIa-AT) complexes, a measure of tissue factor (TF) exposure, and activated FXI (FXIa). We investigated whether increased FVIIa-AT complexes are associated with FXIa and active TF and if major adverse clinical outcomes are predicted by the complexes in CAD. In 120 CAD patients, we assessed FVIIa-AT complex concentrations and the presence of circulating FXIa and active TF. Levels of 8-iso-prostaglandin F2α (8-iso-PGF2α), interleukin-6, high-sensitivity C reactive protein, prothrombin fragment 1 + 2, and free Tissue Factor Pathway Inhibitor were determined. Myocardial infarction (MI), ischemic stroke, systemic thromboembolism (SE), and cardiovascular (CV) death were recorded separately and as a composite endpoint, during follow-up. FVIIa-AT complexes were positively associated with current smoking and multivessel CAD. Elevated FVIIa-AT complexes characterized patients with circulating FXIa and/or active TF in association with increased plasma isoprostanes but not with thrombin generation or inflammatory markers. During a median follow-up of 106 months (interquartile range 95-119), high baseline levels of FVIIa-AT complexes predicted ischemic stroke/SE (HR 4.61 [95% CI 1.48-18.42]) and a composite endpoint of MI, stroke/SE, and CV death (HR 7.47 [95% CI 2.81-19.87]). This study is the first to show that high FVIIa-AT complexes characterize advanced CAD patients with detectable FXIa and active TF, which is, in part, driven by oxidative stress. High FVIIa-AT complexes were associated with the risk of ischemic stroke/SE during long-term follow-up, highlighting the need for effective antithrombotic agents in CAD.

The association of long-acting insulin analogue use versus neutral protamine Hagedorn insulin use and the risk of major adverse cardiovascular events among individuals with type 2 diabetes: A population-based cohort study.

To compare the risk of cardiovascular outcomes associated with long-acting insulin analogues versus neutral protamine Hagedorn (NPH) insulin among patients with type 2 diabetes. We conducted a population-based retrospective cohort study using the UK Clinical Practice Research Datalink Aurum, linked with hospitalization and vital statistics data. Patients with type 2 diabetes who initiated basal insulin treatment between 2002 and 2018 were included in the study. Exposure was defined as current use of long-acting insulin analogues or NPH insulin, defined using a time-varying approach. The primary outcome was major adverse cardiovascular events (MACE; a composite endpoint of myocardial infarction, ischaemic stroke and cardiovascular death). We used a marginal structural Cox proportional hazards model to estimate the hazard ratio (HR) and 95% confidence interval (CI) for MACE with current use of long-acting insulin analogues versus NPH insulin, and in secondary analyses, by long-acting insulin molecule. Our cohort included 57 334 patients. A total of 3494 MACE occurred over a mean follow-up of 1.6 years (incidence rate 37.4, 95% CI 36.2 to 38.7 per 1000 person-years). Long-acting insulin analogues were associated with a decreased risk of MACE compared to NPH insulin (HR 0.89, 95% CI 0.83 to 0.96). Current use of long-acting insulin analogues is associated with a modestly reduced risk of MACE compared to current use of NPH insulin among patients with type 2 diabetes. This study could have important implications for drug plan managers and guideline-writing committees for recommendations of insulin treatment for type 2 diabetes.

Cardiovascular safety associated with febuxostat versus allopurinol among patients with gout: Update with accumulated use of febuxostat

BackgroundTo re-evaluate comparative cardiovascular (CV) safety of febuxostat versus allopurinol among patients with gout following recent accumulated use of febuxostat. MethodsUsing 2011-2019 Korea National Health Insurance database, we conducted a cohort study comparing gout patients initiating febuxostat versus allopurinol, 1:1 matched on a propensity-score (PS) for >60 covariates. The primary outcome was a composite endpoint of myocardial infarction, coronary revascularization, and stroke. Secondary outcomes were individual components of the primary outcome, hospitalized heart failure, and all-cause mortality. Subgroup analyses were done for those at high CV risk, long-term users (follow-up >3 years), and those without chronic kidney disease. We used Cox proportional hazard models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). ResultsWe included 160,930 PS-matched pairs of febuxostat and allopurinol users (mean age 59.3 years, 79.6% male). Incidence rates of the primary outcome were 2.06 and 2.27 per 100 person-years for febuxostat and allopurinol users, respectively, with a HR [95% CI] of 1.03 [0.95-1.12] comparing febuxostat versus allopurinol initiators. We also observed similar risks for secondary outcomes, except for reduced all-cause mortality among febuxostat users (HR [95% CI] of 0.84 [0.78-0.91]). Subgroup analyses also showed non-inferior CV safety of febuxostat. ConclusionIn this population-based cohort study including the largest number of febuxostat users to date, we found non-inferior CV safety of febuxostat versus allopurinol. There was a 16% reduction in all-cause mortality among febuxostat users.

Association between duration of gonadotrophin-releasing hormone agonist use and cardiovascular risks: A population-based competing-risk analysis.

Although androgen deprivation therapy has known cardiovascular risks, it is unclear if its duration is related to cardiovascular risks. This study thus aimed to investigate the associations between gonadotrophin-releasing hormone (GnRH) agonist use duration and cardiovascular risks. This retrospective cohort study included adult patients with prostate cancer receiving GnRH agonists in Hong Kong during 1999-2021. Patients who switched to GnRH antagonists, underwent bilateral orchidectomy, had <6 months of GnRH agonist, prior myocardial infarction (MI), or prior stroke was excluded. All patients were followed up until September 2021 for a composite endpoint of MI and stroke. Multivariable competing-risk regression using the Fine-Gray subdistribution model was used, with mortality from any cause as the competing event. In total, 4038 patients were analyzed (median age 74.9 years old, interquartile range (IQR) 68.7-80.8 years old). Over a median follow-up of 4.1 years (IQR 2.1-7.5 years), longer GnRH agonists use was associated with higher risk of the endpoint (sub-hazard ratio per year 1.04 [1.01-1.06], p = 0.001), with those using GnRH agonists for ≥2 years having an estimated 23% increase in the sub-hazard of the endpoint (sub-hazard ratio 1.23 [1.04-1.46], p = 0.017). Longer GnRH agonist use may be associated with greater cardiovascular risks.

C67 CARDIOVASCULAR RISK CLASSIFICATION AND LIPID LOWERING TREATMENT PRESCRIPTIONS IN A REAL–WORLD: INSIGHT FROM ITALIAN COMMUNITY COHORT

Abstract Background Lipid lowering treatment (LLT) and LDL–C target across CV risk categories might prompt consideration on further lower LDL–C levels advocated by last EAS/ESC guidelines. Aim The aim of the study was to provide current prevalence, clinical characteristics, LLT across different CV risk classes at the time of publication of current ESC/EAS Guidelines. Short–term prognosis was also addressed. Methods and Results This community–based study enrolled 6851 patients (mean age 71 years) with an LDL–C measurement and cardiological evaluation from 01–Jan–2018 until 31–Dec–2018. Of those, 4578 (67%) patients were at very high risk, 1494 (22%) at high risk, 420 (6%) at moderate risk, and 359 (5%) at low risk according to EAS/ESC 2019 guidelines. Dyslipidemia was present in three quarter of patients, and 3888 (57%) received LLT. High Efficacy (potency to reduce LDL–C ≥ 50%) LLT was prescribed in 21% of patients (23% and 10% in very high and high risk categories). There was a statistically significant difference between CV categories with respect to demographic, CV risk factors, and comorbidities. Patients at very high risk were more frequently elderly with a high proportion of patients affected by atherosclerotic CVD (ASCVD) and non–cardiac comorbidities. 394 (9%) patients at very high risk and 102 (7%) patients at high risk presented LDL–C at target. Among very high risk patients, 439 (10%) were treated with ezetimibe. At 24 months of follow–up, death occurred in 676 (8%) patients. In survival curves, adjusted for age and comorbidities, an increased risk of death and CV hospitalization was confirmed in the high risk and very high risk categories. Similar trend was confirmed considering composite endpoint of myocardial infarction and stroke. Conclusion In a contemporary population the strategy to achieve the ambitious LDL–C target of current Guidelines continue to be largely suboptimal and LLT is widely underused. This underlines the huge unmet need when assessed more aggressive LDL–C target advocated in current EAS/ESC guidelines.

MO517: A Polygenic Risk Score for Reduced EGFR is Associated With Adverse Events in a Chronic Kidney Disease Cohort —the German Chronic Kidney Disease Study

Abstract BACKGROUND AND AIMS Over 10% of the adult population worldwide is affected by chronic kidney disease (CKD). CKD is associated with an increased risk of kidney failure (KF), cardiovascular events and mortality. CKD is defined and staged by estimated glomerular filtration rate (eGFR), the most common measure of kidney function. Genome-wide association studies enable the calculation of polygenic risk scores (PRSs), e.g. for eGFR. The aim of this study was to investigate if a polygenic predisposition to lower eGFR is associated with KF, cardiovascular events and mortality in people with CKD, and if the eGFR PRS carries predictive ability. METHOD A PRS for log(eGFR) was developed and tuned in independent, general population-based study samples consisting of European ancestry participants of the UK Biobank and the CKDGen Consortium via the LDpred algorithm [1]. Using genetic information and follow-up data of 4873 participants with moderate CKD enrolled in the German Chronic Kidney Disease study, we calculated, standardized and evaluated the association of the PRS with adverse endpoints. Main endpoints included KF, a composite endpoint of myocardial infarction, cerebral haemorrhage and stroke (3P-MACE), and overall mortality. Cox proportional hazard regression was conducted to estimate (cause-specific) hazard ratios (HRs). Predictive performance of the PRS for KF and 3P-MACE was assessed using prediction error curves and time-dependent c-index. The statistical significance level was Bonferroni-corrected for three main endpoints (P &amp;lt; .05/3). RESULTS After a median follow-up time of 6.5 years, 619 patients died, 466 experienced KF, and 545 3P-MACE. Higher levels of the PRS, corresponding to a genetic predisposition to lower eGFR, were associated with higher risk for all three endpoints {KF: HR 1.23, [95% confidence interval (95% CI) 1.12–1.35], 3MACE: 1.15 (1.06–1.25), mortality: 1.12 (1.04;1.22)} after adjusting for baseline age, sex and two principal components. Across deciles of the eGFR PRS, participants in the highest decile, corresponding to the genetically lowest eGFR, had a &amp;gt;2-fold increased risk of KF compared with those in the lowest decile [HR = 2.13 (1.39–3.27), Fig. 1]. No distinct improvement in the prediction performance for KF was observed when adding the PRS to the well-established KF risk equation by Tangri et al. [2]. This also held true for the added predictive ability of the PRS for 3P-MACE when compared with a model with established cardiovascular risk factors. CONCLUSION Our study revealed a significant association between a polygenic predisposition to lower eGFR and KF, cardiovascular events, and mortality among people with moderate CKD, emphasizing the importance of genetic background even after disease onset. The eGFR PRS carried no added predictive ability with regard to KF and 3P-MACE beyond established risk factors.

Neutrophil extracellular traps (NETs) in patients with STEMI. Association with percutaneous coronary intervention and antithrombotic treatments

BackgroundNeutrophil extracellular traps (NETs) are formed by DNA, histones and proteolytic enzymes, and are produced by activated neutrophils through different mechanisms. In turn, NETs can activate platelets and coagulation cascade favoring thrombotic processes. The aims of this study were to analyze levels and kinetics of NETs in ST-segment elevation myocardial infarction (STEMI) patients and correlate them with antithrombotic therapy and cardiovascular outcomes at follow-up. Methods150 consecutive STEMI patients referred to primary percutaneous coronary intervention (pPCI) were included. Citrate anticoagulated blood was extracted immediately before pPCI, 30 min and 24 h after the procedure. As markers of NETS cell free DNA (cfDNA), nucleosomes and citrullinated Histone 3 (citH3) were determined. 46 healthy subjects were included as controls. Patients were follow-up for 1.4 ± 0.56 years. ResultsBefore pPCI, NETs markers were elevated in STEMI patients compared to healthy controls (p < 0.05); these increased significantly 30 min post pPCI (p ≤ 0.001) and decreased at 24 h but remained elevated compared with the control group (p < 0.05). Patients treated with bivalirudin presented a lower increase of NETs 30 min post pPCI compared to patients treated with heparin (p < 0.05). Cardiovascular risk factors or type of stent implanted did not modify NETs levels. Cit3H (HR = 3.74; 95%CI 1.05–13.4; p = 0.042) and left ventricular ejection fraction ≤35% (HR = 6.84; 95%CI 2–23; p = 0.002) were independent predictors of composite endpoint of myocardial infarction, stroke, stent thrombosis and/or cardiovascular-cause death. ConclusionsNETs were elevated in STEMI patients, increased by pPCI and decreased thereafter. One of the most specific NETs markers was associated with cardiovascular outcomes.

Active factor XI is associated with the risk of cardiovascular events in stable coronary artery disease patients

Background and aimsTissue factor (TF) and activated factor XI (FXIa) have been associated with acute coronary syndrome, ischemic stroke and venous thromboembolism. Their predictive value in stable coronary artery disease (CAD) is unclear. We investigated whether active TF and FXIa were associated with clinical outcomes in CAD patients in long-term observation. MethodsIn 124 stable patients with multivessel CAD, we assessed the presence of circulating, active TF and FXIa by measuring a response of thrombin generation to respective inhibitory antibodies. We recorded the composite endpoint of myocardial infarction (MI), stroke, systemic thromboembolism and cardiovascular death during follow-up (median 106 months, interquartile range 95–119). ResultsCirculating FXIa and active TF were detected in 40% and 20.8% of the 120 patients (aged 65.0 [57.0–70.3] years, men, 78.3%), who completed follow-up. The composite endpoint occurred more frequently in patients with detectable active TF and FXIa present at baseline (hazard ratio [HR] 4.02, 95% confidence interval [CI] 2.26–7.17, p < 0.001 and HR 6.21, 95% CI 3.40–11.40, p < 0.001, respectively). On multivariate analysis FXIa, but not active TF, was an independent predictor of the composite endpoint, as well as MI, stroke/systemic thromboembolism, and cardiovascular death, when analyzed separately. ConclusionsTo our knowledge, this study is the first to show that circulating FXIa predicts arterial thromboembolic events in advanced CAD, supporting a growing interest in FXIa inhibitors as novel antithrombotic agents.

Usefulness of Cardiac Computed Tomography in Coronary Risk Prediction: A Five-Year Follow-Up of the SPICA Study (Secure Prevention with Imaging of the Coronary Arteries).

Accurate identification of individuals at high coronary risk would reduce acute coronary syndrome incidence and morbi-mortality. We analyzed the effect on coronary risk prediction of adding coronary artery calcification (CAC) and Segment Involvement Score (SIS) to cardiovascular risk factors. This was a prospective cohort study of asymptomatic patients recruited between 2013–2017. All participants underwent a coronary computed tomography angiography to determine CAC and SIS. The cohort was followed-up for a composite endpoint of myocardial infarction, coronary angiography and/or revascularization (median = five years). Discrimination and reclassification of the REGICOR function with CAC/SIS were examined with the Sommer’s D index and with the Net reclassification index (NRI). Nine of the 251 individuals included had an event. Of the included participants, 94 had a CAC = 0 and 85 a SIS = 0, none of them had an event. The addition of SIS or of SIS and CAC to the REGICOR risk function significantly increased the discrimination capacity from 0.74 to 0.89. Reclassification improved significantly when SIS or both scores were included. CAC and SIS were associated with five-year coronary event incidence, independently of cardiovascular risk factors. Discrimination and reclassification of the REGICOR risk function were significantly improved by both indexes, but SIS overrode the effect of CAC.

Abstract 6919: Comparative Effectiveness of Long-Acting Insulin Analogs and Neutral Protamine Hagedorn (nph) Insulin for the Reduction of Major Adverse Cardiovascular Events Among Patients With Type 2 Diabetes

Introduction: Although long-acting insulin analogs (glargine, detemir, and degludec) and neutral protamine Hagedorn (NPH) insulin show similar efficacy for glycemic control among patients with type 2 diabetes, their comparative effectiveness in reducing cardiovascular events is unclear. Objective: To compare the risk of major adverse cardiovascular events (MACE) with the use of long-acting insulin analogs versus NPH among patients with type 2 diabetes. Methods: We conducted a retrospective cohort study using the Clinical Practice Research Datalink, a primary care database from the United Kingdom, linked with hospitalization and vital statistics data. The cohort included adults with type 2 diabetes initiating basal insulin therapy between 2002 and 2018. Exposure was defined as time-varying where each person-month of follow-up was classified as either current use of long-acting insulin analogs or NPH; patients who discontinued insulin treatment or were exposed to both insulin analogs and NPH in the same month were censored. The primary endpoint was MACE, a composite endpoint of myocardial infarction, ischemic stroke, and cardiovascular death. We used inverse probability of treatment and censoring weighting to estimate the adjusted hazard ratio (HR) and 95% confidence interval (CI) for MACE associated with current use of long-acting insulin analogs versus NPH. We also conducted secondary analyses stratified by age, sex, history of cardiovascular disease . Results: A total of 57,334 patients entered our cohort (31,136 using a long-acting analog and 26,198 using NPH. Mean age was 63.8 years, and 44.3% of patients were female. A total of 3,494 MACE events occurred over a mean follow-up of 1.62 years. Long-acting insulin analogs were not associated with a decreased risk of MACE compared to NPH (Table). Conclusions: Current use of long-acting insulin analogs is not associated with a reduced risk of MACE compared to use of NPH insulin among patients with type 2 diabetes.