Higher Risk Of MACE Research Articles

Socioeconomic and ethnical disparity in coronary heart disease outcomes in Denmark and the effect of cardiac rehabilitation-A nationwide registry study.

Cardiovascular patients with low socioeconomic status and non-western ethnic background have worse prognostic outcomes. The aim of this nationwide study was first to address whether short-term effects of hospital-based outpatient cardiac rehabilitation (CR) are similar across educational level and ethnic background, and secondly to study whether known disparity in long-term prognosis in patients with cardiovascular disese is diminished by CR participation. All patients with myocardial infarction and/or coronary revascularization from August 2015 until March 2018 in the Danish national patient registry or the Danish cardiac rehabilitation database (DHRD) were included. We used descriptive statistics to address disparity in achievement of quality indicators in CR, and Cox proportional hazard regression to examine the association between the disparity measures and MACE (cardiovascular hospitalization and all-cause mortality) with adjustment for age, gender, index-diagnose and co-morbidity. We identified 34,511 patients of whom 19,383 had participated in CR and 9,882 provided information on CR outcomes from the DHRD. We demonstrated a socioeconomic gradient in improvements in VO2peak, and non-western patients were less often screened for depression or receive dietary consulting. We found a strong socioeconomic gradient in MACE irrespective of CR participation, medication, and risk factor control (adjusted HR 0.65 (95% CI 0.56-0.77) for high versus low education). Non-western origin was associated with higher risk of MACE (adjusted HR 1.2 (1.1-1.4)). We found only minor socioeconomic and ethnic differences in achievement of CR quality indicators but strong differences in CHD prognosis indication that conventional risk factor control and medical treatment following CR do not diminish the socioeconomic and ethnical disparity in CHD prognosis.

Association of coagulation markers and antiphospholipid antibodies with ischemic and bleeding risk in patients with atrial fibrillation undergoing percutaneous coronary intervention

Abstract Background Antiphospholipid antibodies and other coagulation markers are associated with ischemic risk in patients with coronary artery disease without oral anticoagulation (OAC). Aim To assess the association of antiphospholipid antibodies (aPL) and conventional markers of coagulation with ischemic and bleeding risk in patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI). Patients and methods In this prospective single center observational cohort study, patients with AF and an indication for OAC were enrolled after PCI. Dilute Russell's viper venom time (DRVVT) was used to determine lupus anticoagulants (LA) in direct OAC-free plasma. Anti-cardiolipin IgG (aCL), IgM and anti-beta2GP-1-IgG (aβ2GP1) were analyzed by enzyme linked immunosorbent assay (ELISA). Fibrinogen C (FIBC), d-dimers and prothrombin fragments 1 and 2 (PF1+2) were measured in citrated plasma. Immature platelet fraction (IPF [%]) and absolute (IPF abs. [103/μl]) were measured in EDTA-blood. The primary ischemic outcome was defined as time to major adverse cardiovascular events (MACE: all-cause death, myocardial infarction, or stroke) assessed at 6 months. Bleeding was defined according to the International Society of Thrombosis and Haemostasis (ISTH) and the Bleeding Academic Research Consortium (BARC). Results 158 patients were enrolled between May 2020 and May 2021. The median age was 78 years (interquartile range, IQR 72–82), 111 (70%) were male, and 39 (25%) presented with acute coronary syndrome. All Patients were treated with clopidogrel and OAC, 145 (92%) in addition with acetylsalicylic acid (ASA). 32 patients (20%) had ≥1 antiphospholipid antibody (aPL; LA: 19 [12%], aCL: 14 [9%], aβ2GP1: 2 [1%]). D-dimers were elevated in 74 patients (47%), FIBC was increased in 40 (25%) and PF1+2 in 68 patients (43%). IPF [%] was elevated in 28 (18%) and IPF abs. [103/μl] in 11 (7%). The presence of aPL was neither significantly associated with MACE, nor with bleeding risk. Elevated d-dimers were significantly associated with higher risk for MACE (HR=5.1, 95% CI [1.1; 23.4], p=0.04), major ISTH bleeding events (HR= 6.9, 95% CI [1.5; 30.8], p=0.01) and BARC bleeding type 3 or 5 (HR=6.4, 95% CI [1.4; 28.7], p=0.02). Increased levels of FIBC were associated with risk of MACE (HR= 3.6, 95% CI [1.1; 12.0], p=0.03 (Table 1). Conclusion In patients with AF undergoing PCI, high levels of d-dimers and fibrinogen C indicate an increased ischemic risk. Elevated d-dimers are associated with higher risk for bleeding. aPL positivity was not significantly associated with outcome possibly due to low sample size. A combined panel of biomarkers might be suitable to assess ischemic and bleeding risk in patients with AF following PCI. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Faculty of Medicine, Freiburg

Lipoprotein(a), cardiovascular events, and benefit of P2Y12 inhibition: insights from the PEGASUS-TIMI 54 trial

Abstract Background Lp(a) plays a causal role in atherogenesis and may exert pro-thrombotic effects by inhibiting fibrinolysis owing to its structural homology with plasminogen. Patients with higher Lp(a) concentrations may derive greater benefit from anti-thrombotic therapy. Purpose We assessed whether patients with higher Lp(a) derive greater risk reduction from P2Y12 inhibition with ticagrelor vs. placebo on a background of aspirin therapy. Methods Lp(a) concentration was measured (Randox) in a prospective nested cohort of 8,967 pts enrolled in PEGASUS-TIMI 54, a randomized trial of ticagrelor vs. placebo in patients 1–3 years post MI (median follow-up: 2.7 y). Lp(a) was dichotomized at 200 nmol/L as an established threshold of risk. The prespecified MACE endpoint was CV death, MI or stroke, with KM rates reported at 3y. Cox proportional hazards were used to assess the relationship between Lp(a), MACE and treatment benefit. Models were adjusted for relevant baseline characteristics including apolipoprotein B. Results The median Lp(a) was 29 (25th-75th percentile: 12–137) nmol/L. A total of 1,053 pts (11.7%) had a high Lp(a) (≥200 nmol/L). In the pooled trial population, high Lp(a) concentration was associated with a 29% higher risk of MACE (9.1% vs 7.6%; adjusted hazard ratio [adj HR] 1.29, 95% confidence interval [CI] 1.02–1.62; p=0.03), including a 37% higher risk of MI (6.9% vs. 5.3%; adj HR 1.37, 95% CI 1.05–1.79; p=0.02). The hazard ratios for MACE with ticagrelor vs. placebo were 0.73 (95% CI 0.48–1.11) for patients with higher Lp(a) and 0.88 (95% CI 0.74–1.05) for patients with lower Lp(a) (p-interaction=0.41; Figure 1). The absolute risk reductions were 2.4% and 1.2%, respectively. Conclusion Lp(a) above 200 nmol/L identifies patients with prior MI at increased risk of MACE who may derive greater absolute risk reduction from treatment with ticagrelor. These exploratory observations provide insights for therapeutics that are evaluating the clinical benefit of Lp(a) reduction. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): The PEGASUS-TIMI 54 trial was funded by AstraZeneca

Cholesterol affects the relationship between albumin and major adverse cardiac events in patients with coronary artery disease: a secondary analysis

We aimed to examine whether the efficacy of the risk of poor prognosis in patients with coronary artery disease is jointly affected by total cholesterol and baseline serum albumin in a secondary analysis of previous study. We analyzed the data of 204 patients from October 2014 to October 2017 for newly diagnosed stable CAD. The outcome was major adverse cardiac events (MACE; defined as all cause mortality, non fatal myocardial infarction, and non fatal stroke). The median duration of follow-up was 783 days. Multivariable COX model was performed to revalidate the relationship between the sALB and MACE and interaction tests were conducted to find the effects of total cholesterol on their association. A total of 28 MACE occurred among the 204 participants. The risk of MACE varied by baseline serum albumin and total cholesterol. Specifically, lower serum albumin indicated higher risk of MACE (HR 3.52, 95% CI 1.30–9.54), and a test for interaction between baseline serum albumin and total cholesterol on MACE was significant (P = 0.0005). We suggested that baseline serum albumin and total cholesterol could interactively affect the risk of poor prognosis of patients with coronary artery diseases. Our findings need to be confirmed by further randomized trials.

Associations Among Depression, Hemoglobin A1c Level, and Prognosis in Patients With Coronary Artery Disease: A Prospective Study.

BackgroundDepression is ubiquitous in patients with coronary artery disease (CAD). The relationship between depression and hemoglobin A1c (HbA1c) is controversial. The combined effect of high HbA1c and depression on prognosis is unclear, especially in non-diabetic CAD patients. We sought to explore these associations.Methods558 CAD patients were included in this prospective study. Patients were grouped by HbA1c levels and the status of clinical depression. The average follow-up period was about 2.2 years, and Cox proportional hazards models were used to compare the differences of prognosis in all the groups.ResultsClinical depression had no associations with HbA1c in all CAD patients (P for Pearson correlation = 0.74). In the all four groups, compared to group 1 (patients without clinical depression and low HbA1c), group 3 (without clinical depression and high HbA1c) had a higher risk of MACE (adjusted hazard ratio [aHR], 1.97; 95% confidence interval [CI], 1.2–3.25) and composite events (aHR, 1.67; 95% CI, 1.09–2.053). Group 4 (patients with clinical depression and high HbA1c) had higher HRs for MACE (aHR, 2.9; 95%CI, 1.32–6.38) and composite events (aHR, 2.12; 95% CI, 1.06–4.25). In CAD patients without diabetes, patients with clinical depression and high HbA1c had a higher risk of MACE (HR, 2.71; 95% CI, 1.02–7.19), non-cardiac readmission (HR,3.48; 95% CI, 1.26–9.57) and composite events (HR,2.44; 95% CI, 1.08–5.53) than those with no clinical depression and low HbA1c. In patients with comorbidities of depression and diabetes, patients with depression and high HbA1c more likely to experienced non-cardiac readmissions (HR, 4.49; 95% CI, 1.31–15.38) than patients with no depression and low HbA1c only. In all the above analysis, p-values for interaction between clinical depression and HbA1c were not statistically significant.ConclusionsThe presence of both depression and high HbA1c lead to a worse prognosis in CAD patients than one risk factor alone, no matter with or without the comorbidity of diabetes in these CAD patients. For patients with CAD and depression, lower HbA1c may be required.

The comparative cardiovascular and renal effectiveness of sodium-glucose co-transporter-2 inhibitors and glucagon-like peptide-1 receptor agonists: A Scandinavian cohort study.

To assess the comparative cardiovascular and renal effectiveness of sodium-glucose co-transporter-2 (SGLT2) inhibitors versus glucagon-like peptide-1 (GLP-1) receptor agonists in routine clinical practice. A cohort study of nationwide registers from Sweden, Denmark, and Norway, including 87 525 new users of SGLT2 inhibitors and 63 921 new users of GLP-1 receptor agonists, was conducted using data from 2013-2018. Co-primary outcomes, analysed using an intention-to-treat exposure definition, were major adverse cardiovascular events (MACE; myocardial infarction, stroke, and cardiovascular death), heart failure (hospitalization or death because of heart failure), and serious renal events (renal replacement therapy, hospitalization for renal events, and death from renal causes). Use of SGLT2 inhibitors versus GLP-1 receptor agonists was associated with a higher risk of MACE (adjusted incidence rate: 15.2 vs. 14.4 events per 1000 person-years; HR 1.07 [95% CI 1.01-1.15]), a similar risk of heart failure (6.0 vs. 6.0 events per 1000 person-years; HR 1.02 [0.92-1.12]), and a lower risk of serious renal events (2.9 vs. 4.0 events per 1000 person-years; HR 0.76 [0.66-0.87]). In as-treated analyses, the HR (95% CI) was 1.11 (1.00-1.24) for MACE, 0.88 (0.74-1.04) for heart failure, and 0.60 (0.47-0.77) for serious renal events. In secondary outcome analyses, use of SGLT2 inhibitors versus GLP-1 receptor agonists was not associated with statistically significant differences for the risk of myocardial infarction (HR 1.09 [95% CI 1.00-1.19]), cardiovascular death (HR 0.97 [95% CI 0.84-1.12]), death from renal causes (HR 0.75 [95% CI 0.41-1.35]), or any cause death (HR 1.01 [95% CI 0.94-1.09]), while the risk of stroke was higher (HR 1.14 [95% CI 1.03-1.26]), and the risk of renal replacement therapy (HR 0.74 [95% CI 0.56-0.97]) and hospitalization for renal events (HR 0.75 [95% CI 0.65-0.88]) were lower among users of SGLT2 inhibitors. Use of SGLT2 inhibitors versus GLP-1 receptor agonists was associated with a similar risk of heart failure and a lower risk of serious renal events, while use of GLP-1 receptor agonists versus SGLT2 inhibitors was associated with a slightly lower risk of MACE. In as-treated analyses, the associations with MACE and serious renal events increased in magnitude, and the HR for heart failure tended towards a protective association for SGLT2 inhibitors.

Abstract 10416: Rising Trends in the Burden of Cardiovascular Comorbidities and Major Adverse Cardiovascular Events in Young Female Smokers Across Two Nationwide Cohorts Studied a Decade Apart (2017 vs. 2007)

Background: Ample evidence has suggested that female smokers are at a higher risk of smoking-related health problems compared to men. With the increasing number of young smokers in the US, there is limited data on the impact of smoking in young female smokers in the last decade. Methods: The National Inpatient Sample datasets (2007 and 2017) were utilized to identify hospitalizations among young (18-44 years) female tobacco smokers. We compared differences in frequency of admissions, comorbidity burden, and in-hospital outcomes (all-cause mortality and MACE) and resource utilization across two young cohorts 10-years apart. Results: A total of 1,224,479 (median age 32) admissions among young female smokers were identified in 2017 vs. 665,901 (median age 35) in 2007. Both cohorts showed the majority of admissions among white female smokers, followed by African Americans (Table 1) . Compared to the 2007 cohort, the rate of alcohol abuse, hyperlipidemia, uncomplicated diabetes and chronic pulmonary disease decreased inn 2017, whereas a rising trend was observed for deficiency and chronic blood loss anemias, diabetes with complications, drug abuse, hypertension, congestive heart failure, depression, liver disease, and obesity (p<0.001). On adjusted multivariable analysis, the 2017 cohort showed significantly higher odds of all-cause mortality [aOR 1.25 (95%CI: 1.16-1.35)] with a higher risk of MACE [aOR 1.17 (95%CI:1.14-1.20)] (p<0.001). There were fewer routine discharges and higher requirements of home health care in the 2017 cohort vs. 2007. Conclusion: The study reveals escalating trends in the burden of comorbidities, MACE and healthcare resource utilization in admissions (irrespective of primary cause) among young female smokers in this decade apart analysis. It is essential to raise awareness among young female smokers about the adverse impact of tobacco and associated polysubstance abuse on cardiovascular outcomes.

Abstract 12930: The Prognostic Value of Korean vs. Western Nomogram for Exercise Capacity in Korean Patients With Cardiovascular Disease

Background: Exercise capacity is known to be an independent predictor of cardiovascular events and mortality. However, most of previous studies were based on western population. Further study is warranted for Asian patients according to ethnic or national standard. We aimed to compare prognostic value of Korean and Western nomogram for exercise capacity in Korean patients with cardiovascular disease (CVD). Methods: In this retrospective cohort study, we enrolled 1178 patients (62 ± 11 years; 78 % male) who referred for cardiopulmonary exercise testing in cardiac rehabilitation program. Median follow-up was 1.6 years. Exercise capacity was measured in metabolic equivalents (MET) by direct gas exchange method during the treadmill test. The nomogram for exercise capacity from healthy Korean and previous landmark western study was used to determine the percentage of predicted exercise capacity. The endpoint was the composite of major adverse cardiovascular event (MACE; all-cause death, myocardial infarction, repeat revascularization and stroke) and hospital readmission for heart failure. Results: In multivariable cox proportional hazard analysis, the risk of primary endpoint was more than twice (hazard ratio [HR] 2.23, 95% confidence interval [CI] 1.12-4.46) in the patients with lower exercise capacity (<85% of predicted) by Korean nomogram. The lower exercise capacity was the most powerful predictor following age and left ventricular ejection fraction. However, the lower exercise capacity by Western nomogram could not predict the primary endpoint (HR 1.28, 95% CI 0.81-2.04). Conclusion: CVD patients with lower exercise capacity have higher risk of MACE and readmission for heart failure. Considering inter-ethnic differences in cardiorespiratory fitness, Korean nomogram provides more suitable reference values to determine lower exercise capacity to predict cardiovascular events in Korean patients with CVD.

Abstract 12000: A Novel Human Arterial Transcriptomic Signature Associated With Major Adverse Cardiovascular Events and Oxidative Stress

Introduction: The biology of human vascular wall is implicated in cardiovascular pathology. We applied discovery transcriptomics to internal mammary arteries (IMAs) obtained from cardiac surgery patients, to identify pathways that can be treated therapeutically. Methods: Weighted correlation network analysis was conducted in sequencing data from IMAs RNA in 205 patients (Arm 1). Association with future incidence of major adverse cardiovascular events [MACE: cardiovascular death (CVD), non-fatal myocardial infarction or stroke, or new-onset heart failure] was assessed with Cox regression models (adjusted for age, sex, hypertension, dyslipidaemia, diabetes mellitus, and plasma TNFa). Arm 2 included 497 patients in whom segments of IMA were used for ex-vivo quantification of NADPH-stimulated superoxide by lucigenin chemiluminescence. Results: We identified 10 coexpressed gene ‘modules’ in the human arterial wall, through unsupervised transcriptomic analysis. The “red” module was found to cluster with arterial NADPH oxidase activity, while its eigengene values had the most significant correlation ( a ). Patients with high eigengene values for the “red” module showed a 3-fold higher risk of MACE ( b ), and enrichment analysis revealed top pathways ( c ). The Study Arm 2 population was followed up for a median of 6.35 years [IQR: 3.97-8.38], with 50 CVD and 101 MACE. High NADPH oxidases activity was independently predictive of cardiovascular mortality ( d ) and MACE (adj. hazard ratio 1.58 [1.07-2.36], p=0.02). Conclusion: We demonstrate that arterial oxidative stress leads to high risk of MACE in patients with atherosclerosis. We also identify a novel, redox-related arterial transcriptomic signature that predicts long-term cardiovascular risk. Pathways related with oxidative stress, or glucose metabolism or Hypoxia-Inducible Factor-1 in the human arterial wall, may be rational therapeutic targets to reduce cardiovascular risk in secondary prevention.

Abstract 11605: Analysis of 10-yr MACE Risk of LDL-C ≥160-189 Mg/dL Compared to <160 Mg/dL in Young Adults (ages 20-39) in an Integrated Healthcare System

Introduction: Adults <40-yrs (20-39) may have elevated cardiovascular risk based on higher LDL-C (e.g., ≥160 mg/dL). We sought to compare the risk of MACE (all-cause death, MI, ischemic stroke, heart failure hospitalization, and peripheral vascular disease [PVD]) in adults <40-yrs and LDL-C ≥160 to 189 compared with LDL-C <160 mg/dL. Hypothesis: Adults <40-yrs with LDL-C ≥160-189 mg/dL are minimally addressed in the current cholesterol management guidelines but may have a higher risk of MACE compared to other healthy controls. Methods: Patients (pts) from 20- 39 yrs of age with at least three lipid labs and outpatient primary care encounters at Intermountain Healthcare, a large integrated healthcare system, prior to January 2010 and an LDL-C measurement between January and December of 2020 (n=14,570) were included and followed for MACE until June 2021. Pts with LDL-C >190 or <160 on statin in 2010 but previously ≥160 were excluded. Pts were identified using MDClone (ADAMS self-service analytics platform). Outcome of interest was MACE during 10-yr follow-up, LDL-C was stratified as ≥160-189 vs <160 mg/dL. Baseline characteristics were compared by either a chi-squared or t-test, as appropriate. Multivariate logistic regression was used to identify the role of LDL-C as a predictor of outcome. A p-value of <0.05 was considered statistically significant. Results: Baseline characteristics are presented in the Table. MACE for LDL-C ≥160-189 mg/dL was not statistically significant compared to LDL-C <160 (OR 1.28, 95% CI 0.94 - 1.74, p<0.115). Conclusions: The risk of 10-yr MACE in adults <40 yrs of age with LDL-C ≥160-189 mg/dL did not confer a statistically significant elevated risk. Our findings are consistent with current guidelines that statin therapy is not mandated in these individuals.

Associations between changing patterns of ST-T waves morphologies in rest electrocardiography and cardiovascular risk in an asymptomatic low risk population: a report from Ansan-Ansung cohort study

Abstract Background While clinical significance of ST-T wave abnormalities (STA) in rest electrocardiography (ECG) on long-term cardiovascular outcomes has been on debate, few studies have been reported on the association between the changes in ST-T waves in rest ECG and cardiovascular outcomes in low risk populations. We investigate the changing patterns of STA in rest ECG and the predictive value of the changes in ST-T wave in rest ECG for cardiovascular events in an asymptomatic general population. Methods A longitudinal community-based cohort study was conducted for 12 years. Koreans aged 40–69 years were followed biennially through scheduled revisit for comprehensive assessments. Among 10,030 participants, 6,648 participants who did not have any cardiovascular diseases, angina-related symptoms or pathologic Q waves in rest ECG at baseline were included for analysis. Changes in STAs were defined using the changes between ECG at baseline and that at the first revisit. A major adverse cardiovascular events was defined as a composite of cardiac death, myocardial infarction, clinical diagnosis of coronary artery disease and stroke. Results Among 5,924 participants without STA at baseline, only 187 participants (3.2%) developed new STA. Among 724 patients (10.9%) with STA at baseline, 274 patients (37.8%) persistently showed STA at the first revisit. MACEs occurred more frequently in the participants persistently with STA and those with newly-developed STA than in the participants persistently without STA (Figure 1). Multivariate Cox-proportional hazard models showed that a higher risk of MACE was only associated with the persisted STA (HR 1.69; 95% CI 1.10–2.63). In participants with baseline STA, persisted T-wave flattening was associated with a higher risk of MACE, whereas T-wave inversion, either persisted or fluctuated was not associated with a higher risk of MACE, compared with persistent absence of STA (Figure 2). In the participants without baseline STAs, multivariate Cox-proportional hazard model showed that newly-developed T-wave flattening (HR 1.85; 95% CI 0.20–2.84), not T-wave inversion (HR 1.50; 95% CI 0.85–2.65) was associated with a higher risk of MACE. Survival receiver operating curve analysis showed that the changes in STAs had a C-index of 0.538 (95% CI 0.511–0.558), a sensitivity of 13.0% and a specificity of 92.5% and add only a small value to the predictive power of 10-year atherosclerotic cardiovascular diseases risk estimator (C-index without STA changes 0.708 [0.681–0.736] vs. C-index with STA changes 0.721 [0.694–0.748]). Conclusions STAs uncommonly developed while frequently disappeared spontaneously in the asymptomatic general population. Persisted STA and newly developed STA in rest ECG were predictive of future cardiovascular events in the asymptomatic general population. However, the changes in STAs did not significantly improve the predictive value of the conventional risk estimator, when added. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Research Foundation of Korea Figure 1Figure 2

A novel index reflecting both anatomical and physiologic parameters in coronary artery disease, the FFR adjusted SYNTAX score (FaSs)

Abstract Background Various physiology-based indices have been proposed to predict adverse clinical events in patients with coronary artery disease (CAD), such as the sum of three vessel-fractional flow reserve (3v-FFR), and the functional SYNTAX score (fSS). However, these values could not fully reflect the anatomical factors, which remains as a barrier for clinical application of these indices. Purpose To propose a novel index which can reflect both anatomical and physiologic features in CAD patients, and evaluate the additional predictive value for cardiovascular adverse events compared to previous indices. Methods For an index which can reflect both anatomical and physiologic features, we proposed the FFR adjusted SYNTAX score (FaSs). The FaSs is calculated by adding the product of the SYNTAX score and `1-FFR', for all three major coronary arteries. Among the 1136 patients who enrolled at 3V FFR-FRIENDS study, we investigated 866 patients, after excluding those who had missing variables. The 3v-FFR, fSS and FaSs were calculated, derived from the baseline FFR and SYNTAX score. Patients were divided into two groups according to the median value of each index. The primary endpoint was major adverse cardiac events (MACE, a composite of cardiac death, myocardial infarction and ischemia-driven revascularization) at 2 years follow-up. Results Among the total population, MACE occurred in 35 (4.04%) patients. Using the median value in a multivariable COX regression model, only FaSs was associated with an increased risk of MACE, (Hazard Ratio [HR] 5.256, 95% confidence interval [CI] 2.014–13.720), while 3v-FFR (HR 1.383, 95% CI 0.685–2.790) and fSS (HR 1.640, 95% CI 0.830–3.243) were not significantly associated with a higher risk of MACE. This was also observed in the Kaplan Meier survival curve analysis (log-rank p value: p<0.001 for FaSs, 0.153 for 3v-FFR, and 0.061 for fSS; Figure 1) The sensitivity and specificity of the FaSs was 85.7% and 51.6%, which was higher compared to the 3v-FFR (62.9% and 49.3%, respectively) and fSS (57.1% and 58.5%, respectively). When these indices were combined with clinical risk factors (age, sex, hypertension, diabetes, hyperlipidemia, chronic renal failure, LVEF<40%), FaSs was superior compared with 3v-FFR and fSS assessed in regards of the predictive accuracy for MACE (Figure 2). Conclusion The FaSs, which is a novel index calculated by a formula using the SYNTAX score and FFR, showed a superior predictive value for MACE compared to previous indices. Our results confirm the importance of considering both anatomical and physiologic parameters in evaluating the patient's risk for cardiovascular adverse outcomes. Funding Acknowledgement Type of funding sources: None.

Predictors of adverse clinical outcomes in atrial fibrillation patients with concomitant renal impairment under rivaroxaban therapy

Abstract Background Atrial fibrillation (AF) increases the risk of stroke and mortality, and concomitant renal impairment confers a worse prognosis. However, those factors that may limit the use of direct-acting oral anticoagulants in AF patients with renal impairment have not been further investigated, as they confer a higher risk of adverse events in this patient population. Purpose To investigate predictors of adverse clinical outcomes in AF patients with renal impairment who were treated with rivaroxaban. Methods The EMIR study is an observational, multicenter study including patients with AF treated with rivaroxaban for at least the previous 6 months. During 2.5 years of follow-up, the occurrence of thromboembolic events (the composite of isquemic stroke, transient ischemic attack, systemic embolism and myocardial infarction [MI]), major bleeding (ISTH definition) and major adverse cardiovascular events (MACE: fatal/non-fatal MI, myocardial revascularization and cardiovascular death) were recorded. For the present analysis, creatinine clearance (CrCl) was estimated by using the Cockroft-Gault equation and renal impairment was defined as a CrCl <60 mL/min. Results 1433 patients were included (44.5% female; mean age 74.2±9.7 years), of which 498 (35.1%) had CrCl <60 mL/min. The mean CHA2DS2-VASc and HAS-BLED were 3.5±1.5 and 1.6±1.0, respectively. During the follow-up, 7 (1.4%) patients with CrCl <60 mL/min suffered a thromboembolic event, 16 (3.2%) suffered major bleeding, and 19 (3.8%) suffered a MACE. Compared to patients with normal renal function, patients with CrCl <60 mL/min showed a higher annual rate of major bleeding (0.62%/year vs. 1.87%/year; p=0.003) and MACE (0.62%/year vs. 1.97%/year; p=0.002). Multivariate analyses demonstrated that the CHA2DS2-VASc score (OR 1.84; 95% CI 1.11–3.07) was associated with a higher risk of thromboembolic events; whereas the HAS-BLED score (OR 2.25; 95% CI 1.41–3.59) and any dependency level (OR 3.42; 95% CI 1.17–9.98) were associated with a higher risk of major bleeding; and male sex (OR 3.55; 95% CI 1.08–11.63) and heart failure (OR 4.67; 95% CI 1.62–13.51) with a higher risk of MACE. The use of antiplatelet agents was also independently associated with an increased risk of thromboembolic events and MACE (OR 12.28; 95% CI 2.50–60.18; and OR 8.72; 95% CI 2.86–26.59; respectively). Conclusions Rivaroxaban showed excellent results in moderate renal impairment. However, the annual rate of major bleeding and MACE was higher in AF patients with impaired renal function. In patients with AF and renal impairment, male sex, the presence of heart failure, dependency, the concomitant use of antiplatelets, and greater comorbidity according to the CHA2DS2-VASc and HAS-BLED, were associated with higher risk of adverse clinical outcomes. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Bayer

Cardiac rehabilitation do not diminish the socioeconomic and ethnical disparity in patients with coronary heart disease

Abstract Aims Cardiac patients with low socioeconomic status and non-western ethnic background have worse outcomes. The aim of this nationwide study was to determine whether the immediate effect of CR differs between groups defined by socioeconomic status and ethnic background, and whether disparity in the prognosis of cardiac patients is diminished by CR participation. Methods We included all patients in Denmark with myocardial infarction and/or coronary revascularization from August 2015 until March 2018. Level of education, as a marker for socioeconomic status, was divided into four groups, and ethnicity into Danish, non-Western and Western. Participation in CR was identified through the Danish Cardiac Rehabilitation Database (DHRD) and the Danish National Patient Register. Primary outcome was achievement of CR quality indicators, including risk factor control and medication, from DHRD, and secondary outcome a composite endpoint of cardiovascular disease hospitalization and all-cause mortality (MACE). Results We identified 34,511 patients of whom 19,383 had participated in CR and 9,882 provided information on CR data from DHRD. Higher education was associated with greater improvement in VO2peak and non-western patients were less likely to be screened for depression or receive dietary consulting. No other significant disparity in CR quality indicators, was found across education and ethnicity. There was a strong socioeconomic gradient in MACE irrespective of CR participation, medication and risk factor control (adjusted HR 0.71 (0.58–0.86) for high versus low education). Similarly, non-western origin was associated with higher risk of MACE (adjusted HR 1.2 (1.1–1.4). Conclusion We found strong socioeconomic and ethnic disparity in prognosis of CHD patients which were unaffected by CR participation. The results indicate that CR, conventional risk factor control and medical treatment have limited impact on these disparities. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): The Danish Heart Foundation Figure 1Figure 2

A human arterial transcriptomic signature predicts major adverse cardiac events and identifies novel, redox-related therapeutic targets within the vascular wall

Abstract Background The transcriptomic profile of the human vascular wall is implicated in a range of pathologies. RNA sequencing technologies allow for interrogation of gene expression patterns that are associated with clinical outcomes and can guide future research and drug development. Purpose To apply discovery network transcriptomics to internal mammary arteries (IMAs) obtained from patients undergoing cardiac surgery, in order to identify redox-related molecular pathways within the vascular wall that can be treated therapeutically. Methods Arm 1 included 377 patients in whom segments of IMA were used for ex-vivo quantification of NADPH-stimulated superoxide production by lucigenin-enhanced chemiluminescence. Arm 2 included 205 patients in whom bulk RNA sequencing was performed in RNA isolated from IMA, and the WGCNA package used for the analyses. The association with future incidence of major adverse cardiac events (MACE: cardiovascular death, non-fatal myocardial infarction, and stroke) was assessed using Cox regression models (adjusted for age, sex, hypertension, dyslipidaemia, diabetes mellitus, body mass index, smoking, and plasma TNFa). Results Over a median follow-up of 4.84 years [IQR: 2.03–7.14], 38 (11.2%) MACE occurred in Arm 1. High arterial NADPH-stimulated superoxide was independently associated with MACE risk (Adj. HR [95% CI]: 2.62 [1.13–6.07] high group, p=0.02). Unsupervised transcriptomic analysis in Arm 2 allowed identification of 10 coexpressed gene “modules”. Eigengenes summarising modular coexpression signatures were then correlated with NADPH-stimulated superoxide revealing the red module (a) as the most significant (rho=0.19, p=0.01). In survival analysis the red module showed significant correlation with MACE (Adj. HR [95% CI]: 1.40 [1.00–1.95] per SD, p=0.04). For an optimal cut-off, patients with high eigengene values for the red module showed a 4-fold higher risk of MACE (b), and significantly higher arterial oxidative stress (c). Enrichment analysis (performed with Enrichr) of genes in the red module revealed “Electron Transport Chain”, “Oxidative phosphorylation”, “Striated Muscle Contraction Pathway”, and “Glycolysis and Gluconeogenesis” amongst the top enriched pathways (d). Conclusion We present for the first time a novel human arterial transcriptomic signature reflecting changes in redox state, which identifies long-term cardiovascular risk. Targeting pathways in the vasculature related with the mitochondrial electron transport chain, the contractile mechanism, or glucose metabolism may lead to the development of novel therapeutics in cardiovascular disease. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): EPSRC-EP/N509711/1-2119518British Heart Foundation Figure 1

Association between phosphate and long-term outcome in CAD patients underwent coronary intervention

Phosphate has been linked to higher cardiovascular (CV) risk. However, whether phosphate is associated with poor outcomes for patients with coronary artery disease (CAD) after percutaneous coronary interventions (PCIs) remained undetermined. 2,894 CAD patients (2,220 male, aged 71.6 ± 12.2), who received PCI at TVGH from 2006 to 2015, with phosphate measurement, were enrolled. The primary outcome was the composite of major adverse CV events [MACE, comprising of CV death, nonfatal MI, and nonfatal stroke] and heart failure hospitalization (HHF). The key secondary outcome was MACE. There was a J-curve association between phosphate and CV events after adjusted for comorbidities and renal function. Phosphate around 3.2 ± 0.1 mg/dL was associated with the lowest CV risk. In Cox analysis, each 1 mg/dL increases in phosphate was associated with a higher risk of MACE + HHF (HR: 1.12, 95% CI: 1.05–1.21): CV death (HR: 1.37, 95% CI: 1.22–1.55) and HHF (HR: 1.12, 95% CI: 1.02–1.23). Subgroup analyses showed more prominent association between phosphate and MACE + HHF in male, age > 65, bare-metal stents (BMSs), LVEF < 50%, eGFR < 60, LDL > 70 mg/dL, and emergent PCI. Phosphate has a significant association with the risk of CV events in CAD patients undergoing PCI that was independent of comorbidities and renal function.

Survival benefit of coronary revascularization after myocardial perfusion SPECT: The role of ischemia

BackgroundSurvival benefit of revascularization over medical therapy (MT) in patients with stable ischemic heart disease (SIHD) is uncertain. We evaluated the prognostic effects of revascularization in patients with SIHD undergoing single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI). MethodsOf 47,894 patients, 7973 had ischemia ≥ 5% of the left ventricle. Of these, 1837 underwent early revascularization (≤ 60 days after SPECT-MPI). The rest were MT subgroup. Follow-up period was 4.04 ± 1.86 years. Statin therapy intensity and adherence were assessed. Outcomes were all-cause mortality, death + non-fatal myocardial infarction (MI), and MACE [major adverse cardiac event = death + MI + late revascularization (> 60 days after SPECT-MPI)]. ResultsAmong patients with moderate-severe ischemia (≥ 10%), death rate was lower in early revascularization compared to MT subgroup (1.42%/year vs 3.12%/year, adjusted hazard ratio (HR) 0.67 (95% CI 0.50-0.90, P = .008). Death + MI and MACE rates were also lower, adjusted HR 0.69 (0.55-0.88, P = .003) and 0.80 (0.69-0.92, P = .003). Revascularization was beneficial in optimal statin therapy subgroup (death rate 1.04%/year vs 2.36%/year, adjusted HR 0.51 (0.30-0.86, P = .012). In mild ischemia (5%-9%), revascularization did not improve survival or MI-free survival, and was associated with higher MACE rate (8.86%/year vs 7.67%/year, adjusted HR 1.30 (1.12-1.52, P < .001). ConclusionCompared to MT, revascularization was associated with reduced risk of death, death + MI, and MACE in patients with moderate-severe ischemia, incremental over optimal statin therapy. In mild ischemia, revascularization was associated with higher risk of MACE, driven by late revascularization, with no impact on death and death + MI.

Impact of HIV on Treatment and Outcome After Acute Myocardial Infarction: A Swedish Nationwide Observational Cohort Study

Background: People living with HIV (PLHIV) on antiretroviral treatment (ART) may have unfavourable cardiovascular outcomes compared to people without HIV. A potential explanation could be differences in acute treatment and in-hospital management. This study aimed to compare patients with and without HIV experiencing an acute myocardial infarction (MI) in relation to baseline characteristics, treatment, and cardiovascular outcomes. Methods: Two Swedish disease registry cohorts were used to identify patients with and without HIV experiencing MI. The primary outcome was the occurrence of a combined composite endpoint of major adverse cardiovascular events (MACE: reinfarction, stroke, or all-cause mortality) within 5 years in PLHIV versus patients without HIV presenting with MI. Cox regression models were used to compare populations. Findings: We identified all PLHIV (n=191; 89% male) and people without HIV (n=324,635; 64% male) who experienced a MI during 1996–2017 in Sweden. PLHIV presented with MI more than 15 years earlier (median age 55 vs 72 years), had a higher prevalence of smoking, and a lower prevalence of hypertension. PLHIV with MI had higher risks of MACE (adjusted hazard ratio (aHR) 2·01 [1·56-2·58]), reinfarction (aHR 2·06 [1·46–2·91]), stroke (aHR 2·00 [1·11–3·62]), and all-cause mortality (aHR 2·07 [1·45–2·94]) at 5 years. Interpretation: HIV was independently associated with higher risk of MACE and more than doubled the risk of all-cause mortality at 5 years after MI. This study indicates that HIV is an independent risk factor for worse outcomes following MI. Funding Information: This work was supported by a Gilead Science Fellowship and the Public Health Agency of Sweden to GM. Declaration of Interests: Dr. Jernberg reports grants from MSD, grants from Novartis, and that his employer has received reimbursement from Astra Zeneca, Bayer, MSD, Novartis and Sanofi for lecturing. Dr. Elvstam reports grants from Pfizer, outside the submitted work. The other authors declare that there is no conflict of interest. Ethics Approval Statement: The study is ethically approved by the ethical review board of Stockholm, Sweden (reference number: 2018/1957-32). The ethical review board waived the need for consent for this study.

POS-154 ASSOCIATION OF ANCA VASCULITIS AND CARDIOVASCULAR EVENTS: A POPULATION-BASED COHORT STUDY

ANCA associated vasculitis (AAV) increases the risk for cardiovascular (CV) disease; whether the elevated risk applies to all types of CV diseases or specific types is unclear. The objective of this study was to examine the association of AAV and adverse CV outcomes compared to the non-AAV population. We conducted a population-based, retrospective cohort study of adults (mean age 61 years, 51% female) with a new diagnosis of AAV in Ontario, Canada from 2007 to 2017. AAV was defined as receiving during a hospital encounter an ICD10 code for AAV (M313 granulomatous polyangiitis, M3131 granulomatous polynagiitis with renal involvement, M317 microscopic polyangiitis, or M301 allergic granulomatous angiitis). The main outcomes were major adverse CV events (MACE defined as myocardial infarction (MI), stroke or CV death), its individual components, atrial fibrillation (AF), and congestive heart failure (CHF), and were ascertained through hospital encounter ICD10 codes. Overlap propensity score weighting along with Cox proportional hazards models accounting for the competing risk of death were used to examine the association of AAV (n=1,520) and CV events in a matched (1:4) control cohort (n=5,834). Study participants were followed until first event of study outcome, death or end of the study period (31st March 2019). Over a mean follow-up of 3.8 years, individuals with AAV had a high cumulative incidence of MACE (15.4%), MI (6.6%), stroke (7.0%), AF (16.4%) and CHF (20.8%). AAV (compared to non-AAV) was not associated with a higher risk of MACE (sub-distribution hazard ratio [sHR] 1.05 95%CI 0.89-1.23), MI (sHR 1.15 95%CI 0.90 -1.47) or CV death (sHR 0.66 95%CI 0.49-0.89) but a higher risk of stroke (sHR 2.92 95%CI 1.76-4.85), AF (sHR 1.51 95%CI 1.30 to 1.75) and CHF (sHR 1.41 95%CI 1.22 to 1.63). The risks for all CV events (except CV death) were significantly elevated in the early period (90 days and 1 year) after AAV diagnosis compared to the non-AAV controls. Table. Cumulative incidences and risks for cardiovascular outcomes Tabled 1Follow-upGroupEvents (%)Cumulative incidence (%)sHR (95% CI)MACEFull studyControl642 (11.0)15.1AAV192 (12.6)15.41.05 (0.89 to 1.23)365-dayControl326 (5.6)5.6AAV126 (8.3)8.31.31 (1.07 to 1.62)90-dayControl162 (2.8)2.8AAV89 (5.9)5.91.87 (1.42 to 2.46)MIFull studyControl234 (4.0)5.8AAV77 (5.1)6.61.15 (0.90 to 1.47)365-dayControl115 (2.0)2.0AAV54 (3.6)3.61.52 (1.10 to 2.10)90-dayControl53 (0.9)0.9AAV42 (2.8)2.82.52 (1.63 to 3.88)Stroke/TIAFull studyControl205 (3.5)5.2AAV85 (5.6)7.01.49 (1.10 to 2.02)365-dayControl85 (1.5)1.5AAV47 (3.1)3.11.87 (1.25 to 2.80)90-dayControl37 (0.6)0.6AAV37 (2.4)2.42.92 (1.76 to 4.85)CV deathFull studyControl285 (4.9)6.2AAV54 (3.6)4.10.66 (0.49 to 0.89)365-dayControl158 (2.7)2.7AAV34 (2.2)2.20.81 (0.55 to 1.20)90-dayControl85 (1.5)1.5AAV17 (1.1)1.10.85 (0.46 to 1.56)AFFull studyControl460 (7.9)11.5AAV205 (13.5)16.41.51 (1.30 to 1.75)365-dayControl236 (4.1)4.1AAV148 (9.7)9.82.06 (1.71 to 2.48)90-dayControl131 (2.3)2.2AAV124 (8.2)8.23.33 (2.66 to 4.18)CHFFull studyControl598 (10.3)13.3AAV240 (15.8)20.81.41 (1.22 to 1.63)365-dayControl350 (6.0)6.0AAV177 (11.6)11.71.75 (1.48 to 2.07)90-dayControl170 (2.9)2.9AAV143 (9.4)9.42.65 (2.15 to 3.26) Open table in a new tab ANCA vasculitis is associated with a high risk of certain types of cardiovascular events, particularly in the early period following diagnosis.

Optimal duration and combination of antiplatelet therapies following percutaneous coronary intervention: a meta-analysis

IntroductionThe ideal duration of dual antiplatelet therapy (DAPT) following percutaneous coronary intervention (PCI) is still unknown. In this meta-analysis, we aimed to compare very short-term (1–3 months), short-term (6 months), standard-term (12 months) and long-term (>12 months) DAPT durations for efficacy and safety. MethodsOverall DAPT comparisons were classified as “any shorter-term”/”any longer-term” DAPT. The primary outcome was a composite of major adverse cardiovascular events (MACE: non-fatal myocardial infarction, non-fatal stroke and cardiovascular death). The primary safety outcome was major bleeding. ResultsTwenty-six studies comprising 103.394 patients were included. Compared with standard-term DAPT duration, very short-term DAPT duration with subsequent drop of aspirin (RR 1.06, 95% CI, 0.95–1.18, p = 0.26) or drop of the P2Y12 inhibitor (RR 0.92, 95% CI, 0.72-1.16, p = 0.47) was not associated with a higher risk of MACE. Any longer-term compared with any shorter-term DAPT durations led to a significantly lower risk of MACE (RR 0.88, 95% CI, 0.81–0.96, p = 0.002), but a significantly higher risk of BARC 3-5 major bleeding events (RR 1.63, 95% CI, 1.22–2.17, p = 0.001). In the ACS subgroup receiving prasugrel or ticagrelor but not clopidogrel, any longer-term DAPT duration was associated with a significantly lower risk of MACE compared to any shorter-term DAPT duration (RR 0.84, 95% CI, 0.77–0.92, p = 0.0001). ConclusionDAPT may be shortened to 1-3 months in patients with low ischemic but high bleeding risk followed by aspirin or P2Y12 monotherapy. Prasugrel or ticagrelor based DAPT may be extended to >12 months in case of high ischemic and low bleeding risk. PROSPERO registration noCRD42020163719.