Incidence Of Major Adverse Cardiovascular Events Research Articles

Trends in dual antiplatelet therapy regimens and clinical outcomes among patients with acute coronary syndrome undergoing percutaneous coronary intervention with drug‐eluting stents: A multicenter real‐world study

AbstractBackgroundThe patterns of dual antiplatelet therapy (DAPT) use and the associated clinical outcomes in current practice remain limited. This study evaluates DAPT regimen patterns and clinical outcomes among acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI).MethodsThis multicenter retrospective cohort study included ACS patients treated with PCI from January 2017 to February 2022 at five tertiary hospitals in Thailand. DAPT was categorized as nonpotent (NP‐DAPT) or potent (P‐DAPT). We described DAPT trends, with major adverse cardiovascular events (MACEs) and major bleeding, as primary efficacy and safety outcomes. Outcomes were assessed using inverse probability treatment weighting (IPTW) with Cox's proportional hazards model.ResultsThe study included 1877 patients with ACS undergoing PCI. The mean age was 64.51 years (standard deviation 11.34), with 639 (34.04%) female patients and 1159 (61.75%) presenting ST‐elevation myocardial infarction (STEMI). Of these, 924 (49.23%) received NP‐DAPT, and 953 (50.77%) were prescribed P‐DAPT. Crude MACE incidence was lower in the P‐DAPT compared to the NP‐DAPT group (6.82% vs. 10.28%). After applying IPTW and conducting Cox's proportional hazard analysis, no significant differences in MACE were observed between groups (hazard ratio [HR]: 0.85, 95% confidence interval [CI]: 0.58–1.25, p = 0.408), nor in major bleeding (HR: 0.80, 95% CI: 0.37–1.70, p = 0.555). P‐DAPT was associated with any higher bleeding risk (HR: 1.52, 95% CI: 1.13–2.03, p = 0.005).ConclusionStandard DAPT remains predominant among Thai ACS patients, with NP‐DAPT prescriptions approaching those of P‐DAPT. Despite similar rates of MACE and major bleeding between the groups, P‐DAPT was associated with a higher risk of any bleeding.

Clinical Significance of Undetectable High-sensitivity Cardiac Troponin I in Thai Individuals with Low Cardiovascular Risk

Background: The long-term prognosis in individuals who have undetectable high-sensitivity cardiac troponin I (hs-TnI) is poorly defined in those with low cardiovascular risk. We aimed to examine whether individuals with undetectable hs-TnI have better cardiovascular outcomes in the low-cardiovascular-risk population. Methods: Data from a low-cardiovascular-risk population (<7.5%) with no established atherosclerotic cardiovascular disease were derived from the Electricity Generating Authority of Thailand 2007–09 survey. Hs-TnI was measured using the Abbott ARCHITECT STAT assay. We categorised hs-TnI levels into undetectable hs-TnI, low hs-TnI and intermediate and higher hs-TnI by sex-specific cut-off. The low-cardiovascular-risk population was classified into extremely low risk (<5%) and low risk (5–7.5%). Data on major adverse cardiovascular events (MACE) and all-cause mortality were collected until 31 December 2019. Survival analysis and subgroup analysis were performed. Results: A total of 3,442 participants were eligible. Mean age was 43.6 years; 65.5% were male. Hs-TnI was detected in 79.8% (median hs-TnI 2.6 ng/l). During a median follow-up of 10.3 years, 52 events (1.5%) of MACE and 60 events (1.7%) of all-cause mortality occurred. After adjusting for conventional risk factors, an increasing level of hs-TnI was significantly associated with the incidence of MACE (HR 1.03; 95% CI [1.02–1.04]; p<0.001). Compared with the intermediate and higher hs-TnI group, the undetectable hs-TnI group and low hs-TnI group, respectively, had 79% and 52% lower incidences of MACE (HR 0.21; 95% CI [0.05–0.79] and HR 0.48; 95% CI [0.23–1.00]), p for trend 0.04. In subgroup analysis, the incidence of MACE remained higher in individuals with either extremely low or low CV risk with detectable hs-TnI compared with those undetectable hs-TnI (P for interaction 0.83). Conclusion: Among individuals with low cardiovascular risk, hs-TnI testing can provide risk prognostication. Undetectable hs-TnI could serve as a negative risk marker for adverse cardiovascular events.

Association among major adverse cardiovascular events with immune checkpoint inhibitors: A systematic review and meta-analysis.

This meta-analysis aimed to determine the incidence and overall risk of major adverse cardiovascular events (MACEs) related to immune checkpoint inhibitors (ICIs). We systematically searched all cohort studies, including the available MACE data in cancer patients receiving ICIs, in PubMed, Embase, and the Cochrane Library, from their inception to September 5, 2023. The primary outcome was the incidence of MACEs associated with ICI exposure, and the secondary outcome was the overall risk of MACEs associated with ICI exposure versus non-ICI exposure controls. Risk ratios with 95% confidence intervals were used in the random- or fixed-effects models. Overall, 26 cohort studies met the inclusion criteria, involving 109,883 cancer patients. In the median follow-up period ranging from 3.3 to 55.2 months, the incidence of MACEs associated with ICI exposure was 8.22%, ranging from 0.55% to 3.98%, among the nine MACEs, including myocarditis, tachyarrhythmia, pericarditis, pericardial effusions, cardiovascular death, myocardial infarction, heart failure, stroke, and conduction disorder. The incidence of MACE associated with non-ICI exposure was 3.84%, ranging from 0.81% to 4.72%. The risks of all-grade MACEs and pericardial effusions were significantly higher in the ICI group than in the non-ICI controls. ICI treatment, age, male sex, and prior radiation therapy were significantly associated with MACEs. The risk of MACEs during ICI treatment in patients with cancer is more common than is currently recognized. ICI use is closely associated with an increased risk of MACEs. Patients at risk were older, male, and had a history of radiation therapy.

Abstract 4137781: Relationship between Race, Predelivery Cardiology Care and Cardiovascular Outcomes in Pre-eclampsia/Eclampsia among a Commercially Insured Population

Background: Inequities in Preeclampsia/Eclampsia (PrE/E) persist. It is unknown if the receipt of cardiology care relates to future risk of major adverse cardiovascular events (MACE) in Black and White patients with PrE/E. We sought to determine the cumulative incidence of MACE by race and whether predelivery cardiology care was associated with the hazard of MACE up to 1-year post-delivery for Black and White patients with PrE/E. Methods: Using Optum’s Clinformatics® Data Mart Database (CDM), we identified Black and White patients with PrE/E who had a delivery between 2008 to 2019. MACE was defined as the composite of heart failure, acute myocardial infarction, stroke, and death. Cumulative incidence functions were used to compare the incidence of MACE by race. Cox regression models were used to assess the hazard of MACE by cardiology care for Black and White patients. Results: Among 29,336 patients (83.4% White, 16.6% Black, mean age of 30.9 years) with PrE/E, 11.2% received cardiology care (10.9% White, 13.0% Black). Black patients had a higher incidence of MACE than White patients at 1-yr post-delivery (2.7% vs 1.4%). After adjusting for age and clinical comorbidities, receipt of cardiology care was associated with lower hazard of MACE for White patients (HR= 0.68, 95%CI: 0.50-0.92 p=0.013) but not Black patients (HR: 1.22, 95% CI: 0.82-1.81; p= 0.328). The interaction effect between race and cardiology care was statistically significant (p=0.013) Conclusions: Among a well-insured population of patients with PrE/E, Black patients had a higher cumulative incidence of MACE up to a year post-delivery. However, cardiology care significantly lowered the hazard of MACE for only White women. This observation does not suggest that cardiology care is detrimental to Black individuals but underscores the necessity to investigate why outcomes are disparate among these racial groups.

Abstract 4124182: Depression Symptomatology as Predictor of Incident Major Vascular Outcomes: Results from the Hispanic Community Health Study/Study of Latinos

Background: Cardiovascular disease (CVD) has consistently been associated with higher depression symptoms and disorders. Conversely, fewer studies have shown that depression predicts risk of incident CVD and mortality. Objective: To examine the association of depression symptoms with incident major adverse cardiovascular events (MACE) among Hispanics/Latinos living in US. Methods: MACE-free Hispanic Community Health Study/Study of Latinos participants who underwent baseline evaluation between 2008-2011 (n=15,180) were included. MACE was defined as the composite of incident stroke, myocardial infarction (MI), or decompensated heart failure (HF), adjudicated using standard criteria up to year 2019. Depression symptoms were assessed at baseline with a 10-item Center for Epidemiological Studies Depression Scale (CES-D 10, range 0-30 points, 5 points increments), with clinically significant depression defined as CES-D 10 ≥10 points. The incident rate ratio (IRR) of MACE across CES-D 10 scores was determined using Poisson regression models, adjusting for baseline sociodemographic characteristics and Framingham Risk Scores. Analyses were weighted for complex survey design and non-response. Results: The mean age (95% CI) was 40.4 (39.9-40.9) years, and the mean CES-D 10 score was 8.4, 95%CI (7.2-9.5) for those with MACE vs 6.9, 95%CI (6.7-7.0) for individuals without MACE (p<0.05). Clinically significant depression symptoms were present in 29% of the population. There were 321 total MACE outcomes that occurred between baseline and year 2019, with 120 MACE occurrences in individuals with CES-D 10 ≥10 points. In the fully adjusted model, increasing CES-D 10 was associated with higher incidence of MACE (for all: IRR 1.22, 95% CI (1.10-1.36); for those with CES-D 10 scores ≥10: IRR 1.62, 95% CI (1.21-2.17). Additionally, participants with CES-D 10 scores ≥10 were 1.4 times more likely to develop MACE compared to those with CES-D 10 scores <10 (HR 1.41, 95% CI=1.13-1.83, Figure). Among MACE sub-components, incident HF was twice as high in the population with CES-D 10 ≥10 points versus those with CES-D 10 <10 points (HR 2.36, 95% CI (1.58-3.51)). Conclusion: The findings of this cohort study indicate that depression symptomatology is associated with incident overall MACE and HF, and that clinically significant depression symptoms further increased risk for MACE and HF, making early treatment of depression a possible target for decreasing CVD incidence.

Relationship Between Race, Predelivery Cardiology Care and Cardiovascular Outcomes in Pre-Eclampsia/Eclampsia Among a Commercially Insured Population.

Background: It is unknown whether predelivery cardiology care is associated with future risk of major adverse cardiovascular events (MACE) in Preeclampsia/Eclampsia (PrE/E). We sought to determine the cumulative incidence of MACE by race and whether predelivery cardiology care was associated with the hazard of MACE up to 1-year post-delivery for Black and White patients with PrE/E. Methods: Using Optum's de-identified Clinformatics® Data Mart Database, we identified Black and White patients with PrE/E who had a delivery between 2008 and 2019. MACE was defined as the composite of heart failure, acute myocardial infarction, stroke, and death. Cumulative incidence functions were used to compare incidence of MACE by race. Regression models were used to assess hazard of MACE by cardiology care for each race. Separate hazards were calculated for the first 14 days and the remainder of the year. Results: Among 29,336 patients (83.4% White, 16.6% Black, 99.5% commercially insured, mean age 30.9 years) with PrE/E, 11.2% received cardiology care (10.9% White, 13.0% Black). Black patients had higher incidence of MACE than White patients at 1-yr post-delivery (2.7% vs 1.4%) with the majority within 14 days of delivery (Black: 58.7%; White: 67.8%). After adjusting for age and comorbidities, receipt of cardiology care was associated with lower hazard of MACE for White patients within 14 days following delivery (HR 0.31, 95%CI: 0.21-0.46, p<0.001) but not Black patients (HR 1.00, 95%CI: 0.60-1.67; p= 0.999). The effect of the interaction between race and cardiology care was significant in the first 14 days (p<0.001) but not the remainder of the year (p=0.56). Conclusions: Among a well-insured population of patients with PrE/E, Black patients had a higher cumulative incidence of MACE up to a year post-delivery. Cardiology care was associated with a lower hazard of MACE only for White patients during the first 14 days following delivery.

Increased risk of major adverse cardiovascular events in patients with deep and infected diabetes-related foot ulcers.

Diabetes-related foot ulceration (DFU) is associated with increased cardiovascular risk, but the mechanisms remain unclear. Inflammation and infection are mediators of CVD, which may be important in DFU. Prospectively collected data from patients attending a multidisciplinary DFU service were analysed. A deep ulcer was defined as one that reached muscle, tendon or deeper structures. Patients were categorised into four DFU groups: not deep and no infection (D-/I-), not deep but infected (D-/I+), deep with no infection (D+/I-) or deep with infection (D+/I+). Incident major adverse cardiovascular events (MACE) were defined as hospitalisation for myocardial infarction, stroke or transient ischaemic attack, or heart failure. Survival analyses were performed using the logrank test and multivariate Cox regression. Of 513 patients, 241 (47.0%) were in the D-/I- group, 110 (21.4%) were in the D-/I+ group, 35 (6.8%) were in the D+/I- group and 127 (24.8%) were in the D+/I+ group. MACE or all-cause mortality occurred in 75 patients (14.6%), and MACE alone occurred in 46 patients (9.0%) after median follow-up of 381 days (IQR 220-551) and 404 days (IQR 228-576), respectively. Infection was associated with significantly higher MACE or all-cause mortality (21.5% vs 8.7%; p<0.001) and MACE alone (13.5% vs 5.1%; p=0.003). MACE or all-cause mortality was significantly higher in the D+/I+ group (D-/I- 7.9%; D-/I+ 15.5%; D+/I- 14.3%; D+/I+ 26.8%; p<0.001), as was MACE alone (D-/I- 5.0%; D-/I+ 10.9%; D+/I- 5.7%; D+/I+ 15.7%; p=0.017). Infection and a deep ulcer were independent predictors of adverse outcomes. Deep and/or infected DFUs are associated with increased cardiovascular risk compared with DFUs that are not deep or infected. These findings provide a potential mechanistic explanation that requires investigation.

Risk of Major Adverse Cardiovascular Outcomes in Families With MASLD: A Population-Based Multigenerational Cohort Study.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a risk factor for cardiovascular disease. However, whether family members of individuals with MASLD also share an increased cardiovascular risk is unknown. We created a nationwide multigenerational cohort study identifying all family members of Swedish adults diagnosed with biopsy-proven MASLD (1969-2017) and of matched general population comparators (by age, sex, calendar year, and county of residence). We calculated incidence rates and used Cox models to calculate adjusted hazard ratios (aHRs) and 95% CIs for incident major adverse cardiovascular events (MACE), including acute myocardial infarction, stroke, hospitalization for heart failure, or cardiovascular death. Cox models were adjusted for education, country of birth, diabetes, hypertension, obesity, dyslipidemia, chronic kidney disease, chronic obstructive pulmonary disease, and the Charlson comorbidity index. We identified 22 267 MASLD first-degree relatives (FDRs; parents, siblings, and offspring) and 5687 MASLD spouses, as well as 118 056 comparator FDRs and 29 389 comparator spouses without earlier cardiovascular disease. Overall, the mean age was 41.8 years (SD, 18.0), and 51.5% were females. Over a median of 24.6 years, the incidence rate for MACE was higher in MASLD FDRs than in comparator FDRs (65.0 versus 62.5/10 000 person-years; aHR, 1.06 [95% CI, 1.01-1.11]). MASLD FDRs had higher rates of acute myocardial infarction (23.0 versus 20.9/10 000 person-years; aHR, 1.09 [95% CI, 1.01-1.18]) and cardiovascular death (aHR, 1.09 [95% CI, 1.01-1.18]). Across generations of FDRs, the risk of MACE was uniformly increased with no differences by relationship (ie, parents, siblings, and offspring; Pinteraction>0.05). MASLD spouses were also at an increased risk of MACE (117.6 versus 103.5/10 000 person-years; aHR, 1.09 [95% CI, 1.01-1.18]). First-degree relatives of individuals with biopsy-proven MASLD are at slightly higher risk of incident MACE, but absolute risks do not support early screening for cardiovascular disease. Shared lifestyle factors may be the main contributors, as spouses of MASLD patients also had higher risks of MACE.

The HALP score predicts no-reflow phenomenon and long-term prognosis in patients with ST-segment elevation myocardial infarction after primary percutaneous coronary intervention.

Despite recent advances in the management of ST-segment elevation myocardial infarction (STEMI), the clinical outcome of some patients is still unsatisfactory. Therefore, early evaluation to identify high-risk individuals in STEMI patients is essential. The hemoglobin, albumin, lymphocyte, and platelet (HALP) score, as a new indicator that can reflect both nutritional status and inflammatory state of the body, can provide prognostic information. In this context, the present study was designed to investigate the relationship between HALP scores assessed at admission and no-reflow as well as long-term outcomes in patients with STEMI. A total of 1040 consecutive STEMI patients undergoing primary PCI were enrolled in this retrospective study. According to the best cutoff value of HALP score of 40.11, the study samples were divided into two groups. The long-term prognosis was followed up by telephone. Long-term mortality was significantly higher in patients with HALP scores lower than 40.11 than in those higher than 40.11. The optimal cutoff value of HALP score for predicting no-reflow was 41.38, the area under the curve (AUC) was 0.727. The best cutoff value of HALP score for predicting major adverse cardiovascular events (MACE) was 40.11, the AUC was 0.763. The incidence of MACE and all-cause mortality was higher in the HALP score <40.11 group. HALP score can independently predict the development of no-reflow and long-term mortality in STEMI patients undergoing PCI.

Temporal Trends in Atrial Fibrillation Ablation in the Elderly: Incidence of MACE and Recurrence Rates.

The elderly population with atrial fibrillation (AF) is growing. There is limited evidence to suggest AF ablation as an effective treatment for the elderly. This study aimed to investigate the temporal trends of first-time ablations in the elderly, the impact of age on major adverse cardiovascular events (MACE), and a composite endpoint of AF-related hospitalizations, repeat AF ablation, or use of antiarrhythmic drugs (AADs). Utilizing the Danish administrative registers, we incorporated individuals undergoing their first-time AF ablation from 2001 to 2020. Our cohort was divided into 3 age groups (<60, 60-74, and≥75 years) and scrutinized across 4 consecutive 5-year intervals. Cox proportional-hazard multivariable analyses and cumulative incidences were used to evaluate the endpoints of 5-year MACE incidence and a 1-year composite endpoint of AF-related hospitalizations, repeat AF ablation, or use of antiarrhythmic drugs. Elderly patients who underwent AF ablation increased significantly, from none in 2001 to 9% in 2020. The 5-year incidence of MACE in the elderly decreased from 61.9% (95%CI: 41.1%-82.7%) to 38.1% (95%CI: 31.9%-44.2%). The HR for age≥75 years in the last time period was 1.52 (95%CI: 1.26-1.83). The 1-year composite outcome varied from 35.6% to 52.0%; age was not a consistent predictor. AF ablation use in the elderly has significantly increased over time. A notable decrease in MACE was evident across all age cohorts, with a particularly pronounced trend observed among the elderly population. Age was not an independent predictor of the composite endpoint.

Presence of Patent Foramen Ovale Does Not Increase Cerebrovascular Event Rates in Patients with Atrial Fibrillation Following Left Atrial Appendage Closure

ObjectiveBoth atrial fibrillation (AF) and patent foramen ovale (PFO) has been associated with occurrences of ischemic stroke. The aim of this study was to investigate whether patients with concomitant AF and PFO were at an increased risk of stroke, and whether PFO closure was necessary for the prevention of stroke in AF patients who underwent left atrial appendage closure (LAAC). MethodWe retrospectively analyzed 614 patients who underwent LAAC at Wuhan Asia Heart Hospital from May 2014 to April 2021. We compared the baseline clinical characteristics and ischemic stroke rates before LAAC, major adverse cardiovascular events (MACEs) and other long-term outcomes between AF patients with and without PFO after LAAC. The predictor for ischemic stroke or TIA after LAAC was analyzed with univariate and multivariable Cox regression, and the long-term cumulative survival rates of AF patients with PFO compared to those without PFO after LAAC were analyzed with the Kaplan–Meier graph. ResultsA total of 614 patients who underwent LAAC and had completed follow-up data were included in our study. Among them, 74 patients were diagnosed with AF with PFO, and 540 with AF without PFO. There was no significant difference between their baseline clinical data, including ischemic stroke rates (p = 0.961). Patients with and without PFO had similar device implantation success rates (98.6% vs 99.4%, P=0.403) and procedure-related complications. During follow-up (medium follow-up period 36.9 months), no significant difference was observed in the incidence of MACEs (8.1% in PFO group vs 5.7% in non-PFO group, P=0.432) or the cumulative ischemic stroke/TIA rates (5.4% in PFO group vs 4.3% in non-PFO group, P = 0.554). The Cox multivariable regression analysis indicated that the presence of PFO in patients with AF had no correlation with ischemic stroke or TIA after LAAC implantation (HR 1.685, 95% CI 0.570-4.978, P = 0.345). The only predictor for ischemic stroke/TIA events after LAAC was major leakage (>5mm) seen on transesophageal echocardiography (TEE) or left atrial CTA at the 45-day follow-up (HR 10.352, 95% CI 1.221-87.736, P = 0.032). ConclusionAF patients with PFO are not at increased risk for ischemic stroke or TIA before LAAC. The presence of PFO in AF patients did not affect the success rate and safety of LAAC. The presence of mild PFO is not a viable predictor of stroke events in AF patients who underwent LAAC during long-term follow-up. Major leakage (>5 mm) is associated with a higher ischemic stroke/TIA rate in AF patients who underwent LAAC.

Recovery time is associated with the onset of cardiovascular disease in Japanese patients undergoing maintenance hemodialysis.

Cardiovascular disease (CVD) is the leading cause of mortality in patients undergoing maintenance hemodialysis (HD), with various reported risk factors. Recovery time (RT) is a valuable indicator of post-dialysis fatigue. However, the association between RT and the onset of CVD remains unexplored. As such, this study aimed to determine the effect of RT on the onset of CVD. Data from 620 patients undergoing maintenance HD at Yabuki Hospital and 3 related facilities (Yamagata Prefecture, Japan) as of December 31, 2020, were retrospectively analyzed. Patients were asked to respond to the question "How long does it take you to recover from a dialysis session?"; the response was defined as RT. The analysis was performed by categorizing patients into 2 groups according to RT: short RT (< 2h); and long RT (≥ 2h). The primary outcome was major adverse cardiovascular events (MACE). Secondary outcomes included all-cause death and hospitalization. During the 24-month follow-up, 70 (11.3%) patients developed MACE. The long RT group exhibited a higher incidence of MACE; multivariate analysis revealed that age and long RT were associated with the onset of MACE. All-cause death was observed in 45 (7.3%) patients, with no significant difference between the 2 groups. Hospitalization occurred in 252 (40.6%) patients and was more frequent in the long RT group. Multivariate analysis revealed that age, sex, duration of HD, intact parathyroid hormone level, and long RT were associated with hospitalization. Long RT was an independent risk factor for the onset of CVD.

Cardiovascular effects of obstructive sleep apnoea and effects of continuous positive airway pressure therapy: evidence from different study models

INTRODUCTIONCardiovascular consequences of obstructive sleep apnoea (OSA) and the effects of continuous positive airway pressure (CPAP) therapy on blood pressure, endothelial dysfunction, and MACE (major adverse cardiovascular events) have been studied over decades using different study designs. However, clinical findings from different study models on cardiovascular outcomes are sometimes contradictory.METHODSA literature search was conducted in PubMed for randomised controlled trials, meta-analyses, population-based epidemiological studies and OSA cohort studies up to September 2023 investigating the cardiovascular effect of OSA and CPAP in adults with OSA on the following cardiovascular endpoints: blood pressure, arterial hypertension, endothelial function, and MACE (myocardial infarction, stroke, transient ischemic attack, cardiovascular death). The level of evidence for these outcomes was discussed on the basis of different study models.RESULTS AND CONCLUSIONSThere is high-level evidence of a causal relationship between OSA and arterial hypertension and endothelial dysfunction, as well as on higher MACE incidence among subgroups of patients with untreated OSA. The cardiovascular effects of OSA depend on the severity of OSA, symptoms, phenotype, and comorbidities. The blood pressure-lowering effect of CPAP is mainly observed in uncontrolled and treatment-resistant hypertension. The MACE risk reduction in OSA depends on good long-term CPAP adherence. Younger, sleepy patients with more severe OSA, higher hypoxaemic burden and without overt cardiovascular end-organ disease may particularly benefit from CPAP treatment in terms of cardiovascular risk reduction. Randomised controlled trials of CPAP or other effective OSA treatments in primary cardiovascular prevention and in patients at highest risk are lacking.

TM6SF2-rs58542926 genotype has opposing effects on incidence of hepatic and cardiac events in a community cohort: TM6SF2 effects on liver and cardiac outcomes.

TM6SF2-rs58542926-T is associated with increased cirrhosis and modestly decreased coronary artery disease prevalence. However, relative effects of TM6SF2 genotype on major adverse cardiovascular events (MACE) vs. liver-related events (LRE) is not known. We utilized the UK Biobank, a prospective cohort with genetic and inpatient diagnosis data. The primary predictor was TM6SF2-rs58542926 genotype and the primary outcomes were MACE and LRE. Effects were reported as subhazard ratios (sHR) and 10-year cumulative incidence by Fine-Gray competing risk analyses. >430,000 individuals met inclusion criteria. TM6SF2-rs58542926-TT genotype (vs. CC) was associated with higher incidence of LRE (adjusted sHR 3.16, 95% confidence interval [CI] 1.86-5.37) and lower incidence of MACE (adjusted sHR for TT vs. CC genotype 0.76, 95% CI 0.63-0.91 ). In individuals with Fibrosis-4 (FIB4) <1.3, 1.3-2.67, and >2.67, 10-year LRE incidence in TM6SF2-rs58542926-TT vs. CC individuals was 0.08% vs. 0.06% (p>0.05), 0.81% vs. 0.20% (p<0.0001), and 10.5% vs. 3.4% (p=0.00094), respectively. The corresponding values for MACE were 3.8% vs. 5.1% (p=0.032), 6.4% vs. 8.2% (p=0.040), and 17.1% vs. 12.4% (p>0.05). The absolute decrease in MACE with rs58542926-TT (vs. CC) genotype exceeded the absolute increase in LRE in all groups but FIB4>2.67. Associations of TM6SF2 genotype with LRE/MACE were significant in men but not women. TM6SF2-rs58542926-T allele was also associated with increased hepatic steatosis and corrected T1 time by magnetic resonance imaging, with greater effect sizes in men than women. TM6SF2 genotype has opposite effects on LRE vs. MACE incidence, and absolute effects on MACE were greater except in those with highest FIB4 scores. Effects were strongest in men. These findings clarify implications of TM6SF2 genotype based on personalized clinical risk.

Factors associated with major adverse cardiovascular events among Arabs and Jews in Israel: a population-based cohort study

Abstract Introduction Arabs in Israel are at higher risk of cardiovascular mortality; however, there are no data on factors associated with disparities in major adverse cardiovascular events (MACE) incidence among Arabs and Jews. Purpose To study factors associated with MACE incidence among Arabs and Jews in Israel. Materials and Methods This is a cohort study carried out in urban localities of Hadera District in Israel. The study sample included 1,100 participants, stratified in equal numbers by ethnicity (Arab and Jewish), sex, and five 10-year age group (mean age: 51 years, range: 26-77). Data collected via in-person interviews conducted between 2001-2006 included socio-demographic characteristics and health-related behaviors (smoking, physical activity, and diet). Data on baseline diabetes, hypertension, dyslipidemia, and cardiovascular disease were collected from interviews and participants' health records. Information on MACE occurring during follow-up was determined based on hospital discharge diagnoses, recorded in the Israel Ministry of Health hospital admission database. MACE was defined as an acute coronary, cerebrovascular or peripheral artery event, or invasive procedure for its treatment. Factors associated with the time to first MACE were tested in Cox proportional hazards models. Sensitivity analysis included death from any cause as a competing risk, using Fine and Gray’s model. Results During a median follow-up period of 20 years, there were 221 first MACE during follow-up; 91 among Jewish participants and 130 among Arab participants, hazard ratio (HR) Arab vs. Jewish: 1.59; 95% confidence interval (CI) 1.22, 2.09, adjusted for age and sex. Arab ethnicity was no longer significantly associated with MACE, following further adjustment for years of education; HR: 1.32; 95%CI 0.95, 1.84. The HR (95%CI) associated with ethnicity after additional adjustment for health-related behaviors, body weight and baseline chronic morbidity was 1.02 (95%CI: 0.73, 1.42). A subgroup analysis among 950 participants, who did not have a baseline diagnosis of cardiovascular disease, produced similar results. These participants experience 147 first MACE during follow-up. The age and sex-adjusted HR (95%CI) associated with Arab ethnicity was 1.72 (1.23, 2.40), compared to 1.08 (0.72, 1.64) in a fully adjusted model. Competing risk analysis did not materially change these results. Conclusions Arabs in Israel are at higher risk for MACE. Lower socioeconomic position and higher prevalence of unhealthy lifestyle and cardiovascular risk factors may explain the excess risk of MACE among Arabs. Improving cardiovascular health among Arabs should consider social determinants of health and cultural aspects.

Nomogram-based prediction of MACE in older adults with STEMI

Abstract Introduction Despite the significant progress made in diagnosing and treating patients with ST elevation myocardial infarction (STEMI), high-risk subgroups such as older adults (those over 65 years-old) still face considerable residual risk of major adverse cardiovascular events (MACE) following treatment for their index event. Thus, it is crucial to create accurate, validated, and actionable tools to stratify patients according to their risk of MACE after admission for STEMI. Purpose Utilizing clinical data obtained from a registry of patients diagnosed with STEMI, this study aims to develop a nomogram that can reliably predict the likelihood of MACE incidence. Methods Using a large electronic single-center registry, all consecutive patients with STEMI, undergoing primary percutaneous coronary intervention (PCI), and aged 65 and above were identified. Demographic, laboratory, clinical and intra-procedural variables were examined. Univariate and multivariate logistic regression analyses were utilized to identify those factors which were independently associated with MACE incidence in the post PCI follow-up period. A nomogram was developed in a training set, and performance metrics such as receiver operating curves (ROC), calibration plots, and decision curve analysis were used for validation in a testing set. Analyses were performed using tidyverse and rms packages in R programming language. Results 1946 patients were included in the study and split into 70% training and 30% testing sets. Both groups were similar in terms of baseline demographic and clinical characteristics. Mean follow-up period was 17 months. Total MACE incidence in the post PCI follow-up period was 18%. Thirty-eight factors with limited missing information (&amp;lt;5%) were examined for their relationship with MACE incidence and after performing univariate and multivariate analysis 8 were selected for construction of the nomogram: left-ventricular ejection fraction (LVEF), serum creatinine, hemoglobin and fasting blood glucose levels, presence of valvular heart disease, post PCI TIMI flow grade, diameter of the stent placed in the culprit lesion, and presence of shock in the post PCI setting. The area under the curve (AUC) for MACE prediction in post PCI follow-up period showed acceptable discrimination (c-statistic=73%, 95%CI 71.2% to 76.3%). Calibration plots demonstrated that the nomogram model was well-calibrated, and its predictions were closely aligned with observed outcomes. Additionally, decision curve analysis indicated that the model exhibited strong discriminatory ability in predicting MACE. Conclusions A nomogram developed using a combination of laboratory, clinical, and procedural parameters reliably predicts future risk for MACE in older adults following STEMI. Future implementation of this model may identify the highest risk individuals to target more aggressive preventive efforts in a vulnerable cohort of patients.Plot 1Plot 2

Unleashing the potential: early evaluation of blood pressure control with novel measurements in patients with hypertension

Abstract Objective To assess the prognostic value of two novel blood pressure measurements——short-term cumulative systolic blood pressure (SBP) load and Time in Target Rang (TTR) in major adverse cardiovascular outcomes and all-cause mortality. Method This is a post-hoc analysis of the SPIRNT (Systolic Blood Pressure Intervention Trial). Participants with complete record of BP values and no adverse events occurred in the initial 90-days follow-up were enrolled. Short-term cumulative SBP load and TTR were calculated by the 3-month SBP values in the follow-up period (Fig 1). The primary outcome was major adverse cardiovascular events (MACEs), defined as the composite of myocardial infarction, stroke, heart failure and cardiovascular death. Secondary outcomes were the components of the primary outcomes and all-cause mortality. Results The study population included 8639 adults (median [IQR]or mean (%) baseline age, 67 [61,76] years; 2940 women (35.1%); Median follow-up time 3.8[3.3-4.4] years). 559 MACEs were occurred. Participants categorized by tertiles of cumulative SBP Load (T1: [0,0.1572]; T2: (0.1572 ,3.5946]; T3: (3.5946 ,30.2949]) showed a significant increase hierarchical trend (P for trend &amp;lt;0.05) in the incidence of MACEs and stroke. For Participants grouped by SBP TTR (T1: [0,21.2657]; T2: (21.2657 ,71.1462]; T3: (71.1462 ,100]), it indicated a decrease hierarchical trend (P for trend &amp;lt;0.05) in the incidence of MACEs and MI (Fig2 and Fig3). Both short-term cumulative SBP Load (HR: 1.117(1.033-1.208)) and TTR (HR: 0.861(0.785-0.945)) were correlated with MACEs independently(tabal1). According to C-statistics and Net Reclassification Indexes (NRI), short-term cumulative SBP Load and TTR both outperformed mean SBP and SBP standard derivation (SD) on the prognosis value of MACEs. Moreover, our results showed that the coefficient of cumulative SBP Load under penalty decreased to 0 with the largest log(lambda),which indicted a major role across 4 different measures in models. (Fig 4). Conclusions Both short-term cumulative SBP load and TTR had an independent prognosis value for MACEs superior to mean SBP and SBP SD in hypertension patients without diabetes. This study provided the evidence of novel BP measurements for early assessment of BP levels after antihypertensive treatment.

A systematic assessment of myocardial involvement and cardiovascular events up to six months in patients hospitalised with COVID-19

Abstract Background Retrospective cohort studies indicate that myocardial injury occurs in approximately 25% of patients hospitalised with COVID-19. However, prospective studies with a systematic assessment of myocardial involvement and major adverse cardiovascular events (MACE) after COVID-19 are scarce. Purpose The primary objective was to determine the incidence of MACE within six months of hospitalisation. MACE was defined as a composite of cardiac death, sudden death, life-threatening ventricular arrhythmia's, heart failure, non-fatal myocardial infarction, and/or non-fatal stroke. The main secondary objective was to determine the frequency of other cardiac complications not covered by this definition. Methods We conducted a prospective multicenter cohort study in 13 Dutch medical centers. Adult patients hospitalised with COVID-19 were consecutively recruited (May 2021-April 2023). Exclusion criteria were age ≥70 years, a history of new cardiac disease in the past six months, or dependency in the activities of daily living. Cardiac involvement was evaluated by a standardised healthcare pathway that was implemented in participating hospitals. All patients received an electrocardiogram, transthoracic echocardiogram, and troponin measurement at admission and at six months follow-up. Furthermore, a questionnaire was distributed at three and six months after admission to collect information on post-COVID symptomatology. Results In total 190 patients were included, median age of 57 years [IQR 48; 64], mostly male (n=110, 60%) and white (n=136, 72%). Cardiovascular risk factors were present in 116 (61.1%) patients and 33 (17.4%) had a history of cardiac disease. At admission, troponin was above the upper limit of normal in 68 (35.8%) patients. Seven (3.7%) patients died during follow-up. The cumulative incidence of MACE was 2.6% at discharge with no additional events during follow-up. Other cardiac complications were detected in 18 (9.5%) patients during admission with 3 (1.6%) additional events at six months follow-up. Supraventricular tachycardias (n=8, 4.2%) were the most common cardiac complication. Other complications were myocarditis (n=2, 1.1%), pericarditis (n=1, 0.5%), non-sustained ventricular tachycardia (n=1, 0.5%), and other arrhythmias or conduction disorders (n=5, 2.6%). At six months follow-up, three (2.3%) patients reported chest pain, with one requiring a percutaneous coronary intervention. Palpitations and dizziness were experienced by 88.9% and 83.3% of patients three months after admission but the prevalence of these symptoms decreased to 9.8% and 11.8% at six months. Conclusion With a systematic assessment, one in three patients hospitalized with COVID-19 have elevated troponin levels at admission. However, the overall incidence of MACE within six months is low. Palpitations and dizziness are commonly reported after discharge but these symptoms disappeared for most participants within six months.

Diagnostic and prognostic value of ECG-predicted hypertension mediated left ventricular hypertrophy using machine learning

Abstract Background Hypertension is the commonest cause of left ventricular hypertrophy (LVH). Using cardiac magnetic resonance (CMR) imaging, four distinct hypertension mediated LVH phenotypes have been reported: normal LV, LV remodelling, eccentric LVH and concentric LVH. Early detection of hypertensives with LVH can enable timely initiation of therapy however a CMR based screening strategy is costly, particularly in low resource settings. The electrocardiogram (ECG) is an inexpensive screening tool and can detect LVH but its capacity to discriminate between the 4 phenotypes is unknown. Purpose To classify hypertension mediated LVH phenotypes from the ECG using machine learning (ML) and test for associations of ECG predicted LVH phenotypes with incident cardiovascular outcomes. Methods ECG markers with a known physiological association with LVH (including QRS markers, Sokolow-Lyon, and Cornell) were extracted from the 12-lead ECG of 20,439 hypertensive participants in UK Biobank. Three classification models, logistic regression, support vector machine (SVM) and random forest, were trained in 80% of the participants using extracted ECG markers and clinical variables. The remaining 20% individuals were included in the test set for performance measurement. External validation was sought in 877 hypertensives from the Study of Health in Pomerania (SHIP). Subsequently, we tested for associations between the four ECG-predicted LVH phenotypes and incident major adverse cardiovascular events (MACE) and heart failure using Cox proportional hazard regression in the UK Biobank test set with median follow-up of 4.2 years. Results Among UK Biobank participants (mean age ± standard deviation 65 ± 7.4 years), 23,190 had normal LV, 894 LV remodelling, 218 eccentric and 103 concentric LVH. Classification performance of the three models was comparable, but SVM showed consistent results (accuracy 0.79, sensitivity 0.59, specificity 0.87, AUC 0.69) and superior prediction of eccentric LVH (AUC 0.86). In SHIP (55 ± 12.7 years), 704 had normal LV, 134 LV remodelling, 12 eccentric and 24 concentric LVH. In the external validation performed in SHIP, SVM had accuracy of 0.75 (sensitivity 0.51, specificity 0.85, AUC 0.65), with superior prediction of eccentric LVH (AUC 0.76), as shown in Figure 1. Ventricular rate and QRS amplitude (P&amp;lt;0.001) were the features most strongly associated with LVH. In the test set of UK Biobank, setting normal LV as the reference group, the ECG predicted eccentric LVH group was associated with heart failure (Hazard Ratio 3.42, confidence interval 1.06-9.86), there were no associations with MACE (Figure 2). Conclusions ECG-based ML classifiers were able to discriminate the four hypertension mediated LVH phenotypes with external validation demonstrating robustness. This automated approach enhances capabilities of non-specialists and potentially represents an accessible screening strategy for the early detection of hypertensives with LVH.

Safety and effectiveness of glycoprotein IIb/IIIa inhibitors in acute coronary syndromes: insights from the SPUM-ACS study

Abstract Aims Data on Glycoprotein IIb/IIIa inhibitors (GPI) use in real world ACS patients following the introduction of potent P2Y12 inhibitors and newer generation stents are scant. Here, we aimed to assess the utilization, effectiveness, and safety of GPI in a large prospective cohort of contemporary ACS patients. Methods SPUM-ACS is a prospective, multicentre study in which ACS patients between 2009 and 2017 were recruited. The primary endpoint of the present study was major adverse cardiovascular events (MACE), a composite of all-cause death, non-fatal myocardial infarction (MI) and non-fatal stroke at one year. Any bleeding events, BARC 3-5 bleeding, and net adverse cardiovascular events (NACE) comprised the secondary endpoints. Results A total of 4395 ACS patients were included in the analysis. GPI-treated patients had more total coronary artery occlusion (56% vs 35%, p&amp;lt;0.001) and thrombus (60% vs 35%, p&amp;lt;0.001) at angiography. Among the propensity score matched (PSM) population (1992 patients equally split into two groups), GPI-treated patients showed lower MACE risk (PSM adjusted HR 0.70, 95% CI 0.49-0.99) but a higher risk of any (PSM adj HR 1.46, 95% CI 1.06-1.99) and major bleedings (PSM adj HR 1.73, 95% CI 1.09-2.76), resulting in a neutral effect on NACE (PSM adj HR 0.87, 95% CI 0.65-1.17). These results remained consistent across all subgroups. When including only patients treated with potent P2Y12, the incidence of MACE was not different between the two groups, (log rank p=0.50 and PSM adjusted HR 0.94, 95% CI 0.60-1.48). In the PSM population, GPI use (HR 0.76, 95% CI 0.59-0.99, p=0.04), TIMI 3 at the end of the procedure (HR 0.16, 95% CI 0.08-0.30, p&amp;lt;0.001) and potent P2Y12 inhibitor use (HR 0.70, 95% CI 0.49-0.99, p=0.04) were protective independent predictors of MACE at follow-up, while oral anticoagulation at discharge (4.48, 95% CI 2.10-9.52, p&amp;lt;0.001), multivessel disease (HR 1.95, 95% CI 1.09-3.48, p=0.02) and KILLIP class ≥ 2 at admission (HR 1.98, 95% CI 0.99-3.95, p=0.05) were adverse independent predictors. Conclusion In ACS patients undergoing PCI and broadly treated with potent P2Y12 inhibitors, GPI use reduced the risk of MACE at 1 year, while increasing the risk of major bleedings, with a neutral effect on NACE. The routine use of these pharmacological agents should be discouraged, while in selected patients GPI use should be considered following personalized balancing between ischaemic and bleeding risk.Events in PSM populationEvents in PSM population