Major Adverse Cardiovascular Events Events Research Articles

Effect of distal ischemic preconditioning on cardiovascular events in adult patients with hip fracture one year after operation

To investigate the effect of remote ischemic preconditioning (RIPC) on major adverse cardiovascular events (MACE) in elderly patients with hip fracture 1 year after operation. Total of 314 elderly patients with hip fracture of gradeⅡand Ⅲ for American Society of Anesthesiologists (ASA) were treated by surgical operation from April 2015 to May 2020 including 116 males and 198 females, the age ranged from 60 to 76 years old. The subjects were divided into intervention group and control group according to whether received RIPC. Among them, 157 cases in intervention group included 56 males and 101 females with an average age of (68.12±7.13) years old and 157 cases in control group included 60 males and 97 females with an average age of (68.24±7.05) years old. Both groups were given routine anesthesia. The intervention group was treated with RIPC on the basis of routine anesthesia. The MACE events 1 year after operation in two groups were compared and analyzed. The OR values of RIPC for myocardial infarction, heart failure, stroke, nonfatal cardiac arrest, coronary revascularization, severe arrhythmia, peripheral artery thrombosis, readmission of cardiovascular disease, and all-cause death in patients with hip fracture one year after operation were 1.269, 1.304, 0.977, 1.089, 1.315, 1.335, 0.896, 0.774, 1.191, respectively, but there was no significant difference (P>0.05). RIPC did not significantly affect and change the occurrence of major cardiovascular adverse events within 1 year after hip fracture surgery. The long term impact of RIPC on clinical cardiovascular outcomes in non cardiac surgery needs to be confirmed in appropriate randomized clinical trials.

Enhancing cardiovascular risk prediction through AI-enabled calcium-omics

Whole-heart coronary calcium Agatston score is a well-established predictor of major adverse cardiovascular events (MACE), but it does not account for individual calcification features related to the pathophysiology of the disease (e.g., multiple-vessel disease, spread of the disease along the vessel, stable calcifications, numbers of lesions, and density). We used novel, hand-crafted calcification features (calcium-omics); Cox time-to-event modeling; elastic net; and up and down synthetic sampling methods for imbalanced data, to assess MACE risk. We used 2457 CT calcium score (CTCS) images enriched for MACE events from our large no-cost CLARIFY program (ClinicalTrials.gov Identifier: NCT04075162). Among calcium-omics features, numbers of calcifications, LAD mass, and diffusivity (a measure of spatial distribution) were especially important determinants of increased risk, with dense calcification (> 1000HU, stable calcifications) associated with reduced risk Our calcium-omics model with (training/testing, 80/20) gave C-index (80.5%/71.6%) and 2-year AUC (82.4%/74.8%). Although the C-index is notoriously impervious to model improvements, calcium-omics compared favorably to Agatston and gave a significant difference (P < 0.001). The calcium-omics model identified 73.5% of MACE cases in the high-risk group, a 13.2% improvement as compared to Agatston, suggesting that calcium-omics could be used to better identity candidates for intensive follow-up and therapies. The categorical net-reclassification index was NRI = 0.153. Our findings from this exploratory study suggest the utility of calcium-omics in improved risk prediction. These promising results will pave the way for more extensive, multi-institutional studies of calcium-omics.

Impact of Polyvascular Disease in Patients Undergoing Unprotected Left Main Percutaneous Coronary Intervention

Percutaneous coronary intervention (PCI) has demonstrated its safety and efficacy in treating left main coronary artery disease (LM-CAD) in select patients. Polyvascular disease (PolyVD) is associated with adverse events in all-comers with CAD. However, there is little data examining the interplay between PolyVD and LM-PCI, which we sought to investigate in a retrospective single-center study. We included patients undergoing unprotected LM-PCI at a tertiary center from 2012-2019. The patient population was stratified based on the presence or absence of PolyVD (i.e. medical history of cerebrovascular and/or peripheral artery disease in addition to LM-CAD). The primary outcome was major adverse cardiovascular events (MACE) combining all-cause mortality and spontaneous myocardial infarction within one year after index PCI. Overall, 869 patients were included, and 23.8% of the population had PolyVD. Individuals with PolyVD were older and had a greater burden of comorbidities. After 1 year follow-up individuals with PolyVD exhibited significantly higher rates of both MACE (22.8% vs. 9.4%; p<0.001) and bleeding events compared to those without PolyVD. MACE was primarily driven by an increase in all-cause mortality (18.3% vs. 7.1%; p<0.001). Results persisted after adjusting for confounders. In conclusion, among patients undergoing LM-PCI, the presence of PolyVD is linked to an increased risk of MACE and bleeding after 1 year of follow-up, which highlights the vulnerability of this patient population.

Immune-inflammatory biomarkers for the occurrence of MACE in patients with myocardial infarction with non-obstructive coronary arteries.

Neutrophil-to-high-density lipoprotein cholesterol ratio (NHR), monocyte-to-high-density lipoprotein cholesterol ratio (MHR), lymphocyte-to-high-density lipoprotein cholesterol ratio (LHR), platelet-to-high-density lipoprotein cholesterol ratio (PHR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), and aggregate index of systemic inflammation (AISI) have been identified as immune-inflammatory biomarkers associated with the prognosis of cardiovascular diseases. However, the relationship of these biomarkers with the prognosis of myocardial infarction with non-obstructive coronary arteries (MINOCA) remains unclear. Patients with MINOCA who underwent coronary angiography at the 920th Hospital of Joint Logistics Support Force were included in our study. Clinical baseline characteristics and laboratory testing data were collected from the hospital record system. The patients were divided into two groups on the basis of major adverse cardiovascular events (MACE) occurrence. Multiple logistic regression analysis was conducted to assess the relationship between NHR, MHR, LHR, PHR, SII, SIRI, AISI, and MACE. Receiver operating characteristic (ROC) curves were generated to evaluate the predictive value of NHR, MHR, LHR, PHR, SII, SIRI, and AISI for MACE in patients with MINOCA. The accuracy of the prediction was indicated by the area under the curve (AUC) value. The study included 335 patients with MINOCA. (81 in the MACE group and 254 in the No-MACE group). The MACE group had higher levels of NHR, MHR, LHR, PHR, SII, SIRI, and AISI than the No-MACE group. Multiple logistic regression analysis adjusted for confounding factors indicated that the higher levels of NHR, MHR, PHR, SII, SIRI, and AISI were associated with the occurrence of MACE in patients with MINOCA (P < 0.001). The AUC values for NHR, MHR, PHR, SII, SIRI, and AISI were 0.695, 0.747, 0.674, 0.673, 0.688, and 0.676, respectively. The combination of NHR, MHR, PHR, SII, SIRI, and AISI improved the accuracy of predicting MACE in patients with MINOCA (AUC = 0.804). Higher levels of NHR, MHR, PHR, SII, SIRI, and AISI were associated with the occurrence of MACE, and the combination of NHR, MHR, PHR, SII, SIRI, and AISI improved the accuracy for predicting the incidence of MACE events in patients with MINOCA.

Alirocumab and cardiovascular outcomes according to sex and lipoprotein(a) after acute coronary syndrome: ODYSSEY OUTCOMES

BackgroundThe ODYSSEY OUTCOMES trial (NCT01663402) compared the effects of the proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab with placebo on major adverse cardiovascular events (MACE) in patients with recent acute coronary syndrome (ACS). ObjectiveWe assessed efficacy and safety of alirocumab versus placebo according to sex and lipoprotein(a) level. MethodsThis prespecified analysis compared the effects of alirocumab versus placebo on lipoproteins, MACE (coronary heart disease death, non-fatal myocardial infarction, fatal/non-fatal ischemic stroke, unstable angina requiring hospitalization), death, total cardiovascular events, and adverse events in 4762 women and 14,162 men followed for a median of 2.8 years. In post-hoc analysis, we evaluated total cardiovascular events according to sex, baseline lipoprotein(a), and treatment. ResultsWomen were older, had higher baseline LDL-C levels (89.6 vs 85.3 mg/dL) and lipoprotein(a) (28.0 vs 19.3 mg/dL) and had more co-morbidities than men. At 4 months, alirocumab lowered LDL-C by 49.4 mg/dL in women and 54.0 mg/dL in men and lipoprotein(a) by 9.7 and 8.1 mg/dL, respectively (both p < 0.0001). Alirocumab reduced MACE, death, and total cardiovascular events similarly in both sexes. In the placebo group, lipoprotein(a) was a risk factor for total cardiovascular events in women and men. In both sexes, reduction of total cardiovascular events was greater at higher baseline lipoprotein(a), but this effect was more evident in women than men (pinteraction=0.08). Medication adherence and adverse event rates were similar in both sexes. ConclusionsAlirocumab improves cardiovascular outcomes after ACS irrespective of sex. SummaryAfter recent ACS, addition of alirocumab to GDMT improves outcomes consistently in women and men. Reduction of total cardiovascular events was greater at higher baseline Lp(a).

Evidence that tirzepatide protects against diabetes-related cardiac damages

BackgroundGlucagon-like peptide-1 receptor agonists (GLP-1RAs) are effective antidiabetic drugs with potential cardiovascular benefits. Despite their well-established role in reducing the risk of major adverse cardiovascular events (MACE), their impact on heart failure (HF) remains unclear. Therefore, our study examined the cardioprotective effects of tirzepatide (TZT), a novel glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) receptor agonist.MethodsA three-steps approach was designed: (i) Meta-analysis investigation with the primary objective of assessing major adverse cardiovascular events (MACE) occurrence from major randomized clinical trials.; (ii) TZT effects on a human cardiac AC16 cell line exposed to normal (5 mM) and high (33 mM) glucose concentrations for 7 days. The gene expression and protein levels of primary markers related to cardiac fibrosis, hypertrophy, and calcium modulation were evaluated. (iii) In silico data from bioinformatic analyses for generating an interaction map that delineates the potential mechanism of action of TZT.ResultsMeta-analysis showed a reduced risk for MACE events by TZT therapy (HR was 0.59 (95% CI 0.40–0.79, Heterogeneity: r2 = 0.01, I2 = 23.45%, H2 = 1.31). In the human AC16 cardiac cell line treatment with 100 nM TZT contrasted high glucose (HG) levels increase in the expression of markers associated with fibrosis, hypertrophy, and cell death (p < 0.05 for all investigated markers). Bioinformatics analysis confirmed the interaction between the analyzed markers and the associated pathways found in AC16 cells by which TZT affects apoptosis, fibrosis, and contractility, thus reducing the risk of heart failure.ConclusionOur findings indicate that TZT has beneficial effects on cardiac cells by positively modulating cardiomyocyte death, fibrosis, and hypertrophy in the presence of high glucose concentrations. This suggests that TZT may reduce the risk of diabetes-related cardiac damage, highlighting its potential as a therapeutic option for heart failure management clinical trials. Our study strongly supports the rationale behind the clinical trials currently underway, the results of which will be further investigated to gain insights into the cardiovascular safety and efficacy of TZT.Graphical

Major adverse cardiovascular events related to phosphodiesterase 5 inhibitors: analysis of real-life data from Eudra-Vigilance database.

Phosphodiesterase 5 inhibitors (PDE5i) are the standard medical treatment for erectile dysfunction. Aim of our study was to evaluate the rate of major adverse cardiovascular events (MACE) reported during PDE5i treatment based on Eudra-Vigilance (EV) reports. EV database is the system for managing and analyzing data on suspected adverse reactions to medicines which have been authorized or being studied in clinical trials in the European Economic Area. MACE are defined as non-fatal stroke, non-fatal myocardial infarction, non-fatal congestive heart failure, revascularization after aorto-coronary graft bypass and cardiovascular death. We recorded the number of MACE for sildenafil, tadalafil, vardenafil, avanafil per category and severity until 1st July 2023. Pooled Relative Risk (PRR) was used to compare data between drugs. Overall, 951 MACE events were reported. Most of them were observed in younger patients <65 years old (452/951 events, 48%). Overall, 377/8939 (4%) MACE events were observed for sildenafil, 221/5213 (4%) for tadalafil, 50/1029 (4%) for vardenafil and no events for avanafil. No significative differences were reported comparing sildenafil and tadalafil (PRR 0.71-0.99, IQR 0.61-1.35, P>0.05), neither sildenafil vs. vardenafil (PRR 0.68-0.79, IQR 0.43-1.55, P>0.05), neither tadalafil vs. vardenafil (PRR 0.77-0.95, IQR 0.64-1.30. P>0.05) even when compared for age. Comparison between different classes of age showed MACE were more frequent in patients younger than 65 years old taking sildenafil and tadalafil when compared to patients older than 85 years old (PRR 0.02-0.11. IQR 0.01-0.40. P<0.01) and when compared to patients in 65-85 class of age (PRR 0.02-0.12, IQR 0.01-0.95, P<0.01). Real life data is consistent with MACE related to PDE5i. PDE5is are infrequently (<5%) associated with MACE. However, risk seems higher in younger patients, particularly for sildenafil (452/951 events, 48%). Clinicians should consider these data when prescribing PDE5i especially in young patients.

Clinical impact of preemptive pharmacogenomic testing on antiplatelet therapy in a real-world setting.

CYP2C19 genotyping to guide antiplatelet therapy after patients develop acute coronary syndromes (ACS) or require percutaneous coronary interventions (PCIs) reduces the likelihood of major adverse cardiovascular events (MACE). Evidence about the impact of preemptive testing, where genotyping occurs while patients are healthy, is lacking. In patients initiating antiplatelet therapy for ACS or PCI, we compared medical records data from 67 patients who received CYP2C19 genotyping preemptively (results >7 days before need), against medical records data from 67 propensity score-matched patients who received early genotyping (results within 7 days of need). We also examined data from 140 patients who received late genotyping (results >7 days after need). We compared the impact of genotyping approaches on medication selections, specialty visits, MACE and bleeding events over 1 year. Patients with CYP2C19 loss-of-function alleles were less likely to be initiated on clopidogrel if they received preemptive rather than early or late genotyping (18.2%, 66.7%, and 73.2% respectively, p = 0.001). No differences were observed by genotyping approach in the number of specialty visits or likelihood of MACE or bleeding events (all p > 0.21). Preemptive genotyping had a strong impact on initial antiplatelet selection and a comparable impact on patient outcomes and healthcare utilization, compared to genotyping ordered after a need for antiplatelet therapy had been identified.

Effects of Non-Face-to-Face Chronic Care Management on Service Utilization and Outcomes Among US Medicare Beneficiaries with Diabetes.

Type 2 diabetes mellitus (T2DM) results in heavy economic and disease burdens in Louisiana. The Centers for Medicare and Medicaid Services has reimbursed non-face-to-face chronic care management (NFFCCM) for patients with two or more chronic conditions since 2015. To assess the impacts of NFFCCM on healthcare utilization and health outcomes. This retrospective cohort study included Medicare fee-for-service beneficiaries with T2DM and at least one additional chronic disease between 2014 and 2018. At least one record of NFFCCM Current Procedural Terminology codes. The health outcomes in the study included major adverse cardiovascular events (MACE), all-cause mortality, and heart failure. The monthly service utilization and continuity of care index for primary care were also included. The propensity score method was used to balance the baseline differences between the two groups. Weighted multivariate regression models were developed using propensity score weights to assess the impacts of NFFCCM on outcomes. During the 5years of study period, 8415 patients among the 118,643 Medicare beneficiaries received at least one NFFCCM. Patients receiving any NFFCCM had reduced healthcare utilization compared with patients not receiving NFFCCM, including 0.012 (95% CI - 0.014 to - 0.011; p < 0.001) fewer monthly hospital admissions, 0.017 (95% CI - 0.019 to - 0.016; p < 0.001) fewer monthly ED visits, and 0.399 (95% CI 0.375 to 0.423; p < 0.001) more monthly outpatient encounters. Patients receiving NFFCCM services had lower MACE event rates of 7.4% (95% CI 7.1 to 7.8%; p < 0.001), all-cause mortality rate of 7.8% (95% CI 7.4 to 8.1%; p < 0.001), and heart failure rate of 0.3% (95% CI 0.2 to 0.5%; p < 0.001), respectively. These findings suggest that reimbursement for NFFCCM was associated with the shifting high-cost utilization to lower-cost primary health care settings among patients with diabetes in Louisiana.

(294) Revisiting Risk of Testosterone Therapy: Assessing the Impact of Supratherapeutic Levels on MACE and Mortality

Abstract Introduction The benefits and risks of testosterone therapy (TT) have been a subject of long-standing debate. The recent TRAVERSE trial demonstrated that men who received TT did not show an increased risk of major adverse cardiovascular events (MACE) or mortality. However, it is essential to note that the median post-treatment testosterone levels were found to be less than 400ng/dL. Therefore, our investigation aims to assess whether supra-therapeutic T levels (&amp;gt;1000ng/dL) are associated with an elevated risk of MACE and/or mortality. Objective To use data from the National Health and Nutrition Examination Survey (NHANES) 2011-2016 to determine whether supratherapeutic testosterone levels (&amp;gt; 1000 ng/dL) are associated with higher rates of all-cause mortality or MACE. Additionally, to determine whether there was a higher rate of MACE among patients who died. Methods We collected data from the NHANES 2011-2016 Continuous Files and linked them to the National Death Index (NDI) through 2019. The NHANES is a national survey run by the Center for Disease Control that assesses the health status of United States residents by sampling of populations across the country. The survey collects socio-demographic data, lab values, dietary health, clinical variables and body measurements. NDI is a centralized database of United States death record information on file in state vital statistics offices. We included male participants aged 18 years and older with data on total testosterone and who were eligible for mortality data. We compared participants with testosterone &amp;gt; 1000 ng/dL against those with &amp;lt;1000 ng/dL, with the assumption that those &amp;gt; 1000 ng/dL had supratherapeutic levels of testosterone from testosterone therapy. Our primary outcome was mortality, with secondary outcomes of mortality due to MACE. We additionally analyzed association with MACE as the primary cause of mortality among participants who had died. MACE was determined by those who were categorized as dying of “diseases of the heart” or “cerebrovascular diseases.” We used binary logistic regression and controlled for age, race, body mass index, and history of myocardial infarction. Statistical significance was assessed at p&amp;lt;0.05. All analyses were performed on STATA MP 17. Results We identified 7,790 males aged 18 or older with mortality data. Of those, 7,715 had testosterone &amp;lt;1000 and 75 men had testosterone &amp;gt; 1000. Among all patients in our cohort, 643 died of all causes, and 199 died of MACE. In the multivariable logistic regression adjusted for potentially confounding variables, we found testosterone &amp;gt;1000 was associated with all-cause mortality (OR 2.59, 95% CI 1.29-5.20, p=0.007). There was no association with mortality from MACE in either all participants (OR 0.60, 95% CI 0.08-4.45, p=0.615) or among those who died (OR 0.28, 95% CI 0.03-2.17, p=0.221). Conclusions Supratherapeutic levels of testosterone are associated with all-cause mortality by 2019 in NHANES participants from 2011-2016. There were no associations with MACE in this population, although overall numbers of death from MACE were low in this data set. Future studies should examine longitudinal data across a greater duration and consider non-fatal MACE events in men who achieve supra-therapeutic levels on TT. Disclosure No.

Impact of Bempedoic Acid on Total Cardiovascular Events

The ATP citrate lyase (ACL) inhibitor, bempedoic acid, reduces low-density lipoprotein cholesterol (LDL-C) level and major adverse cardiovascular events (MACE) by 13% in patients at high cardiovascular risk with intolerance of statin and high-intensity statin medications. The effects of bempedoic acid on total cardiovascular events remain unknown. To determine the impact of bempedoic acid on the total incidence of MACE. Included in this prespecified analysis of the Cholesterol Lowering via Bempedoic Acid, an ACL-Inhibiting Regimen (CLEAR) Outcomes trial were patients with, or at high risk for, cardiovascular disease, with hypercholesterolemia and inability to take guideline-recommended statins. Study data were analyzed from December 2016 to November 2022. Patients were randomly assigned to treatment with bempedoic acid or placebo daily. The primary end point was the time to first event for a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization (MACE-4). The key secondary end point was time to first event for cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke (MACE-3). This prespecified analysis compared the total number of cardiovascular events in the treatment groups. A total of 13 970 patients (mean [SD] age, 65 [9] years; 7230 male [51.8%]) were included in the study. A total of 9764 participants (69.9%) had prior atherosclerotic cardiovascular disease and a baseline LDL-C level of 139 mg/dL; treatment with bempedoic acid resulted in a 21% reduction in LDL-C level and a 22% reduction in high-sensitivity C-reactive protein (hsCRP) level at 6 months. Median (IQR) follow-up was 3.4 (3.1-3.9) years. A total of 1746 positively adjudicated first MACE-4 events and 915 additional MACE events in 612 patients were recorded, with coronary revascularization representing 32.8% (573 of 1746) of first events and 69.4% (635 of 915) of additional events. For the total incidence of cardiovascular events, treatment with bempedoic acid was associated with a reduction in risk of MACE-4 (hazard ratio [HR], 0.80; 95% CI, 0.72-0.89; P <.001), MACE-3 (HR, 0.83; 95% CI, 0.73-0.93; P = .002), myocardial infarction (HR, 0.69; 95% CI, 0.58-0.83; P < .001), and coronary revascularization (HR, 0.78; 95% CI, 0.68-0.89; P <.001), although no statistically significant difference was observed for stroke (HR, 0.80; 95% CI, 0.63-1.03). A lower HR for protection with bempedoic acid was observed with increasing number of MACE events experienced by patients. Lowering LDL-C level with bempedoic acid reduced the total number of cardiovascular events in patients with high cardiovascular risk, statin therapy intolerance, and elevated LDL-C levels.

Ethnic Differences in Thrombotic Profiles of Acute Coronary Syndrome Patients and Relationship to Cardiovascular Outcomes: A Comparison of East Asian and White subjects.

East Asians (EAs), compared to white Caucasians (W), have a lower risk of ischemic heart disease and a higher risk of bleeding with antithrombotic medications. The underlying mechanisms are incompletely understood. We sought to compare thrombotic profiles of EA and W patients with myocardial infarction (MI) and relate these to cardiovascular outcomes. In a prospective study in the United Kingdom and Korea, blood samples from patients (n = 515) with ST- or non-ST-elevation MI (STEMI and NSTEMI) were assessed using the Global Thrombosis Test, measuring thrombotic occlusion (OT) and endogenous fibrinolysis (lysis time [LT]). Patients were followed for 1 year for major adverse cardiovascular events (MACE) and bleeding. EA patients showed reduced OT (longer OT) compared to W (646 seconds [470-818] vs. 436 seconds [320-580], p < 0.001), with similar LT. In STEMI, OT (588 seconds [440-759] vs. 361 seconds [274-462], p < 0.001) and LT (1,854 seconds [1,389-2,729] vs. 1,338 seconds [1,104-1,788], p < 0.001) were longer in EA than W. In NSTEMI, OT was longer (OT: 734 seconds [541-866] vs. 580 seconds [474-712], p < 0.001) and LT shorter (1519 seconds [1,058-2,508] vs. 1,898 seconds [1,614-2,806], p = 0.004) in EA than W patients. MACE was more frequent in W than EA (6.3 vs. 1.9%, p = 0.014) and bleeding infrequent. While OT was unrelated, LT was a strong independent predictor of MACE event after adjustment for risk factors (hazard ratio: 3.70, 95% confidence interval: 1.43-9.57, p = 0.007), predominantly in W patients, and more so in STEMI than NSTEMI patients. EA patients exhibit different global thrombotic profiles to W, associated with a lower rate of cardiovascular events.

Risk Factors Associated with Major Adverse Cardiovascular Events after Ischemic Stroke: A Linked Registry Study

Introduction: Survivors of stroke are at risk of experiencing subsequent major adverse cardiovascular events (MACE). We aimed to determine the incidence of, and risk factors for, MACE after first-ever ischemic stroke, by age group (18–64 years vs. ≥65 years). Methods: Observational cohort study using patient-level data from the Australian Stroke Clinical Registry (2009–2013), linked with hospital administrative data. We included adults with first-ever ischemic stroke who had no previous acute cardiovascular admissions and followed these patients for 2 years post-discharge, or until the first post-stroke MACE event. A Fine-Gray sub-distribution hazard model, accounting for the competing risk of non-cardiovascular death, was used to determine factors for incident post-stroke MACE. Results: Among 5,994 patients with a first-ever ischemic stroke (median age 73 years, 45% female), 17% were admitted for MACE within 2 years (129 events per 1,000 person-years). The median time to first post-stroke MACE was 117 days (89 days if aged <65 years vs. 126 days if aged ≥65 years; p = 0.025). Among patients aged 18–64 years, receiving intravenous thrombolysis (sub-distribution hazard ratio [SHR] 0.51 [95% CI, 0.28–0.92]) or being discharged to inpatient rehabilitation (SHR 0.65 [95% CI, 0.46–0.92]) were associated with a reduced incidence of post-stroke MACE. In those aged ≥65 years, being unable to walk on admission (SHR 1.33 [95% CI 1.15–1.54]), and history of smoking (SHR 1.40 [95% CI 1.14–1.71]) or atrial fibrillation (SHR 1.31 [95% CI 1.14–1.51]) were associated with an increased incidence of post-stroke MACE. Acute management in a large hospital (>300 beds) for the initial stroke event was associated with reduced incidence of post-stroke MACE, irrespective of age group. Conclusions: MACE is common within 2 years of stroke, with most events occurring within the first year. We have identified important factors to consider when designing interventions to prevent MACE after stroke, particularly among those aged <65 years.

Coffee consumption and adverse outcome events in patients with atrial fibrillation

Abstract Background/Introduction Moderate coffee consumption has been associated with a lower risk of major adverse cardiovascular events (MACE) in the general population. However, there are some concerns that coffee consumption might be harmful for patients with atrial fibrillation (AF). Purpose The aim of this study was to investigate the association of coffee consumption with MACE and other adverse outcome events in AF patients. Methods Data of AF patients from two large prospective, multicenter cohort studies (yearly based follow-up data from Swiss-AF and Beat-AF) were used for this analysis. Coffee consumption was assessed and categorized into two main groups "not-daily" and "daily" consumers and subcategories (&amp;lt;1, 1, 2-3 and ≥4cups/day). The primary endpoint was defined as a composite of stroke or systemic embolism, myocardial infarction, hospitalization for acute heart failure and cardiovascular death (MACE). We performed time-updated multivariable adjusted Cox regression analyses to investigate the association of coffee consumption with MACE and other adverse outcome events. Results Among 3,835 patients (mean age 71.4 years, 28.0% females), 3,095 (80.7%) reported daily coffee consumption. The incidence rate for MACE was 5.09 in daily and 7.49 per 100py in not-daily consumers. Cumulative incidence curves are presented in Figure 1. After comprehensive multivariable adjustment, daily coffee consumption was associated with a 23% relative risk reduction for MACE compared to not-daily consumption (hazard ratio (HR) (95% confidence interval (CI)) 0.77 (0.67-0.89), p&amp;lt;0.001;). Compared to patients with not-daily coffee consumption, patients with moderate coffee consumption (2-3 cups/day) had the lowest hazard for MACE (HR (95%CI) 0.73 (0.62; 0.85), p&amp;lt;0.001). The associations between coffee consumption and all adverse outcome events are presented in Figure 2. Conclusion In a population of AF patients, daily coffee consumption was associated with a lower risk of MACE and other adverse outcomes. These findings seem to be similar to those in the general population.

Kidney function by creatinine and cystatin c and adverse cardiovascular outcomes in patients with atrial fibrillation

Abstract Background Atrial fibrillation (AF) patients with chronic kidney disease are at an increased risk for ischemic and bleeding events and all-cause mortality. Accurate kidney function estimation is key for risk assessment. Creatinine is commonly used to calculate the Glomerular Filtration Rate (GFR). However, cystatin c has been described to be more sensitive than creatinine independent of muscle mass, autoimmune disease, inflammation or consuming diseases. Thus, cystatin C might be superior for risk assessment in patients with AF. Aim We aimed to investigate the associations between kidney function, assessed by creatinine and cystatin c, and major adverse cardiovascular events (MACE), its individual components, and major bleedings. Methods We enrolled 3865 AF patients into two prospective, multicenter cohort studies. Creatinine and cystatin c were measured at baseline and clinical outcome events were assessed yearly. We calculated GFR using the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] formula based on either creatinine (GFRcr), cystatin c (GFRcy) or both (GFRc2). Primary outcome was MACE, defined as a composite of stroke or systemic embolism, myocardial infarction and cardiovascular death. Secondary outcomes were the individual components of MACE and major bleeding. Multivariable adjusted Cox regression analyses were built to investigate the associations between kidney function and adverse outcome events. Results Mean age was 71 ± 10 years and 28% were female. Mean creatinine and cystatin levels were 103 ± 32 μmol/l and 1.2 ± 0.4 mg/l, respectively, translating to a GFRc2 of 63.8 ± 21.7 ml/min/1.73 m2. Over a median follow-up of 6 years, the incidence rates for MACE (per 100 person-years) across quartiles (Q1-Q4) of GFRc2 were 22.0, 19.6, 17.4 and 15.9, respectively (Figure). When using multivariable adjusted Cox regression analysis, MACE was significantly associated with GFRcr (per 1 standard deviation: HR 0.87 (95%CI 0.77; 0.97) p=0.01), GFRcy (HR 0.68 (CI 0.58; 0.78), p&amp;lt;0.001) and GFRc2 (HR 0.75 (CI 0.66; 0.86), p&amp;lt;0.001). This association was mainly driven by cardiovascular death (Table). Major bleeding was associated with GFRcy (HR 0.73 (0.60-0.88) p=0.001) and GFRc2 (HR 0.80 (0.67-0.95), p=0.01), but not with GFRcr (HR 0.91 (95% CI 0.78-1.07) p=0.25). Conclusion Among AF patients, GFR equations including cystatin c were associated both with MACE and bleeding events, while creatinine based GFR equations were only associated with MACE. Therefore, Cystatin c based GFR equations might offer more comprehensive risk stratification in AF patients.Figure 1Table 1

Effects of icosapent ethyl on residual cardiovascular risk according to predicted baseline risk: results from REDUCE-IT

Abstract Background Icosapent ethyl is recommended by the ESC CVD Prevention Guidelines as one of the intensified prevention strategies to be considered in patients with established CVD and a high residual risk.[1] Treatment effects of icosapent ethyl may vary between individual patients. This study aimed to determine the relative and absolute treatment effects of icosapent ethyl according to baseline CVD risk. Methods Participants from the REDUCE-IT trial with established CVD were included (n = 5,785).[2] Baseline 5-year risk of major adverse cardiovascular events (MACE), defined here as cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke was estimated using the ESC guideline-recommended SMART2 risk score.[3] Modification of the relative treatment effect of icosapent ethyl by baseline risk was assessed using a Cox proportional hazards model including a treatment-by-risk interaction. Next, relative treatment effects were derived stratified by quartiles of baseline risk. The observed 5-year absolute risk reduction (ARR) with icosapent ethyl within each risk quartile was assessed based on Kaplan-Meier estimates of the cumulative incidence of MACE. Results During a median follow-up of 4.8 years (interquartile range 3.2-5.3), 361 MACE events occurred in the icosapent ethyl group vs 489 in the placebo group (hazard ratio [HR] 0.72; 95% confidence interval [CI] 0.63-0.82). Mean predicted vs observed 5-year risk of MACE was 9.1% vs 10.2% in the first quartile (range 3.6-11.4%), 13.8% vs 14.6% in the second quartile (range 11.5-16.0%), 19.2% vs 19.5% in the third quartile (range 16.1-23.4%), and 33.4% vs 32.2% in the fourth quartile (range 23.5-83.0%). Icosapent ethyl significantly reduced MACE in all risk quartiles, with an HR (95% CI) of 0.62 (0.43-0.88), 0.66 (0.48-0.92), 0.69 (0.53-0.90), and 0.78 (0.63-0.96) respectively (p for treatment-by-risk interaction = 0.06). The 5-year ARR (95% CI) with icosapent ethyl increased across risk quartiles, i.e. was 5.3% (1.8-8.7%), 5.6% (1.9-9.4%), 7.4% (3.0-11.8%), and 10.8% (5.3-16.2%) respectively (Figure). This translates to a number needed to treat (NNT; 95% CI) of 19 (11-54), 18 (11-52), 14 (8-34), and 9 (6-19). Conclusions Among CVD patients with elevated triglyceride levels, icosapent ethyl significantly reduces the risk of MACE in individuals with a low, moderate, and high baseline risk. Absolute treatment benefits are largest for patients at the highest risk, as reflected by the twofold increase in ARR and decrease in NNT in the highest as compared to the lowest risk quartile.Icosapent ethyl effect in risk quartiles

Long-term outcomes of patients with ischemia and no obstructive coronary artery disease (INOCA) - a systematic review and meta-analysis

Abstract Background Myocardial ischemia with no obstructive coronary artery disease (INOCA) is an increasingly recognized syndrome that encompasses coronary vasomotor disorders such as coronary microvascular dysfunction (CMD) and coronary vasospasm. However, the prognosis of patients with INOCA is not well defined. Purpose To perform a systematic review and meta-analysis of previous studies evaluating the long-term prognosis of patients with INOCA stratified by the underlying vasomotor disorder. Methods We searched Medline, Embase, Web of Science, and Cochrane databases combining terms for INOCA and outcomes to identify observational studies evaluating the prognosis of patients with INOCA published between 1984 and 2021. The primary outcomes were composite of all-cause death and MI, and major adverse cardiovascular events (MACE) at annual intervals for up to 5-year follow-up. Meta-analytic averages with 95% confidence intervals (CI) of the incidence of primary outcomes for INOCA, each INOCA endotype, and by method used to determine the diagnosis were calculated using the random effect models. Results We identified a total of 52 studies (19765 patients) meeting eligibility criteria. Of those, 22 included patients with vasospastic angina and 34 with microvascular angina. The rate of all-cause death and MI in the vasospastic angina group was 0.7 (95% CI 0.4-1.0)/100 patient-years [Figure 1] and the rate of MACE was 1.1 (95% CI 0.6-1.9)/100 patient-years [Figure 2]. For patients with microvascular angina the rate of all cause death and MI was 1.2 (95% CI 0.7-1.7)/100 patient-years [Figure 1] and the rate of MACE was 2.8 (95% CI 1.8-4.0)/100 patient-years [Figure 2]. Patients with evidence of microvascular dysfunction by non-invasive (CFR) or invasive (CFR, IMR, TIMI frame count) criteria had 2.7 times higher all-cause death and MI rates than patients whose diagnosis was established solely based on an abnormal exercise or imaging stress test (2.6 (95% CI, 0.8-5.1) vs. 0.7(95% CI, 0.4-1.2)/100 patient-years, p=0.034). Conclusions Overall, patients with INOCA have a low rate of MACE events or death, although there is heterogeneity based on the underlying phenotype. Patients with vasospastic angina have a relatively benign long-term prognosis, whereas patients with microvascular angina have a significantly higher rate of MACE at long-term follow-up. Among patients with microvascular angina, those with objective evidence of abnormal microvascular function (such as reduced CFR) had 2.7 times higher rates of all-cause death and MI.Incidence of all cause death and MIIncidence of MACE

Abstract 15319: Impact of Atherosclerotic Cardiovascular Disease Risk Factors on Pregnancy Outcomes in Women With Heart Disease

Introduction: The impact of atherosclerotic cardiovascular disease (ASCVD) risk factors on pregnancy outcomes in women with pre-existing heart disease (HD) has not been examined. Aim: To determine the risk of major adverse cardiovascular events (MACE), preeclampsia and fetal events in women with HD stratified according to the presence of ASCVD risk factors. Methods: We studied a consecutive cohort of pregnant women with heart disease. ASCVD risk factors included any of the following: obesity, hypertension, dyslipidemia, diabetes or smoking. Primary outcomes were MACE (heart failure, cardiac arrest, CV death, stroke and myocardial infarction), preeclampsia and adverse fetal events (pre-term birth, small for gestational age, intraventricular hemorrhage, neonatal death and respiratory distress syndrome). Univariate logistic regression was used to determine the odds of adverse outcomes. Results: In total, 1656 pregnancies (congenital heart disease n=1041, acquired heart disease n= 420, isolated arrhythmia n=195) were included. At least one ASCVD risk factor was present in 24% of pregnancies. Overall, MACE occurred in 7.1%, preeclampsia in 4.3% and adverse fetal events in 30.1% of the pregnancies. Compared to pregnancies in women without ASCVD risk factors, those with ASCVD risk factors were more likely to have pregnancies complicated by MACE (9.7% vs 6.3%, p= 0.025), preeclampsia (8.3% vs 3.4%, p &lt; 0.001), and fetal events (38.5% vs 27.5%, p &lt;0.001). There were differences in maternal and fetal outcomes with or without ASCVD risk factors when stratified by diagnosis (acquired heart disease, congenital heart disease, isolated arrhythmias) (Figure 1). Conclusions: The presence of ASCVD risk factors in women with heart disease is associated with worse maternal and fetal outcomes. Modification of ASCVD risk factors may improve pregnancy outcomes.

Abstract 13237: The Combined Effect of Triglyceride-Glucose Index and High Sensitivity C-reactive Protein on Cardiovascular Outcomes in Patients With Chronic Coronary Syndrome: A Multicenter Cohort Study

Background: Triglyceride-glucose (TyG) index is a proven non-invasive alternative indicator of insulin resistance. There is an interconnection between insulin resistance and inflammation, and high sensitivity C-reactive protein (hsCRP) is one of the most commonly used biomarkers of systemic inflammation. We aimed to investigate the combined association of TyG and hsCRP with adverse outcomes in patients with chronic coronary syndrome (CCS). Methods: A total of 9421 patients with CCS were finally included in this study. The primary endpoint was defined as a composite of the major adverse cardiovascular events (MACE) covering all-cause death, non-fatal myocardial infarction, and revascularization. Kaplan-Meier analysis and Cox regression models were used to evaluate the relationship between TyG, hsCRP, and cardiovascular events. Results: During the 2-year follow-up period, 660 (7.0%) cases of MACE were recorded. Participants were divided equally into 3 groups according to TyG levels. Compared to the TyG T1 group, the risk of MACE was significantly higher in the TyG T3 group (adjusted HR 1.283, 95% CI 1.037-1.587, P=0.022). In addition, there was a significantly higher risk of MACE in the TyG T3 group with a higher level of hsCRP (&gt; 3 mg/l) (adjusted HR 1.735,95% CI 1.126-2.674, P=0.012). However, the association between TyG and MACE events was attenuated with hsCRP ≤ 3 mg/l (adjusted HR 1.077,95% CI 0.834-1.391, P=0.568). When patients were divided into 6 groups according to hsCRP and TyG, the Cox regression analysis showed that patients in the TyG T3&amp;hsCRP&gt;3 mg/l group had a significantly higher risk of MACE than those in the TyG T1&amp;hsCRP≤3 mg/l group (adjusted HR: 1.577, 95%CI: 1.180-2.108, P=0.002). The Cox regression analysis of secondary endpoints showed that all-cause mortality and myocardial infarction appeared to be the main contributors to the increased risk of MACE. Conclusion: Elevated TyG index serves as a strong predictor of poor prognosis in patients with CCS. Additionally, participants with concurrently elevated hsCRP and TyG had worse clinical outcomes. The concurrent assessment of TyG and hsCRP may be valuable in identifying high-risk groups among CCS patients.

Abstract 13144: High Polygenic Risk Score is a Predictor for Major Adverse Cardiac Event

Background: The polygenic risk score for coronary artery disease (CAD PRS) is an emerging CAD risk assessment tool. It is unclear if it improves predictive value for major adverse cardiovascular events (MACE). This study aims to investigate the value of PRS as predictor for MACE. Methods: Patients who had coronary calcium score (CAC) within the Sanford Heart Screening Program were enrolled in the study from 2011-2021. They were genotyped using Illumina Global Screening Array version 1. PRS was calculated using a literature derived list of 180 single nucleotide polymorphisms. Patients were classified into 3 groups based on CAD PRS: high PRS (&gt; 85 th percentile), moderate PRS (15 th to 85 th percentile) or low PRS (&lt;15 th percentile). MACE was defined as the composite of death, myocardial infarction, coronary revascularization and heart failure hospitalization. Results: A total of 1,380 patients with mean age of 57.76± 9.76 were analyzed of which 6.6% had MACE. Chi-square test revealed a significant relationship between PRS (low, moderate, high) and a future MACE event, [X 2 (N=1380) = 9.9,p &lt; .01]. Post-hoc testing showed that those with high PRS(standardized residuals = 3.14, p &lt; .01) were more likely to have a future MACE event than those with a moderate (standardized residuals =1.59, p=.68) or low PRS (standardized residuals =1.11, p = 1) (Figure 1). Conclusions: This study shows that high CAD PRS has an added value in predicting future MACE in general population as represented in our Sanford Heart Screening Program.