Risk Of Major Adverse Cardiac Events Research Articles

Comparing the risk of death, major adverse cardiac events, and relapse in bullous pemphigoid patients treated with systemic or topical corticosteroids.

According to current guidelines, systemic or topical corticosteroids are recommended as first-line treatments for bullous pemphigoid (BP). There is evidence suggesting that topical application may be associated with a lower risk of mortality. However, there is a lack of comprehensive large-scale data comparing mortality rates, as well as the risk of major adverse cardiac events (MACE), infections, and relapse, between systemic and topical corticosteroid treatments. To evaluate the risk of death, MACE, infections, and relapse in BP patients treated with systemic or topical corticosteroids. A population-based retrospective cohort study was performed in the TriNetX US Collaborative Network. As a measure against bias, propensity-score matching for age, sex, ten diseases and six medications, and three sensitivity analyses were conducted. All-time risk of death was increased in US BP patients exposed to any dose of systemic corticosteroids (n=2,917) compared to topical clobetasol propionate treated patients (n=2,932, hazard ratio [HR], 1.43, 95% confidence interval [CI] 1.28-1.58, p<0.0001). This was consistent in time-stratified analysis (1- and 3-year mortality rates), and in analysis contrasting prednisone (equivalent) does of 1-10 mg (low) or 30-100 mg (medium-high) systemic corticosteroid to topical treatment. The increased risk of death in US BP patients exposed to any dose of systemic corticosteroids compared to topical treatment was accompanied by increased risks for MACE (HR 1.33, CI 1.08-1.64, p=0.0075) and infections (HR 1.33, CI 1.15-1.54, p=0.0001). The risk of continued disease or relapse was decreased in patients treated with systemic as opposed to topical corticosteroid (HR 0.85, CI 0.77-0.94, p=0.0016). Results regarding mortality and continued disease or relapse persisted in three of three sensitivity analyses. Potential limitations are the retrospective data collection, bias for treatment selection and miscoding. Pending validation in prospective studies, where feasible, and despite the heightened risk of relapse, topical corticosteroid treatment may be advantageous compared to systemic corticosteroid treatment due to its significantly lower risk of death.

Prognostic relevance of global work index and global constructive work in patients with non-ischemic dilated cardiomyopathy.

Myocardial work (MW) derived from pressure-strain loops is a novel non-invasive tool to assess left ventricular (LV) function, incorporating global longitudinal strain (GLS) by speckle tracking echocardiography and non-invasively assessed blood pressure. Studies on the role of MW in dilated cardiomyopathy (DCM) are still limited. Therefore, the aim of this study was to evaluate the potential value of MW for predicting adverse outcomes in patients with DCM. 116 consecutive patients with DCM who underwent heart catheterization were retrospectively recruited from June 2009 to July 2014. 34 patients (30%) met the composite endpoints for major adverse cardiac events (MACE) of cardiac transplantation, need for implantable cardioverter-defibrillator (ICD) therapy, heart failure hospitalization and all-cause mortality. Patients with DCM were followed up for a mean of 5.1 years (IQR: 2.2-9.1 years). Global work index (GWI) and global constructive work (GCW) were not only independent predictors but also provided incremental predictive values (Integrated discrimination improvement [IDI] > 0) of MACE in multivariate Cox models. Furthermore, Patients with GWI < 788mm Hg% (HR 5.46, 95%CI 1.66-17.92, p = 0.005) and GCW < 1,238mm Hg% (HR 4.46, 95%CI 1.53-12.98, p = 0.006) had higher risks of MACE. GWI and GCW assessed by strain imaging echocardiography may have an additional value beyond LV-EF and GLS for predicting adverse outcomes in DCM.

Prognostic role of serum albumin levels in patients with chronic heart failure.

Hypoalbuminemia is common in heart failure (HF) patients; however, there are no data regarding the possible long-term prognostic role of serum albumin (SA) in the younger population with chronic HF without malnutrition. The aim of this study was to examine the long-term prognostic role of SA levels in predicting major adverse cardiac events (MACE) in middle-aged outpatients with chronic HF. In the present retrospective analysis, 378 subjects with HF were enrolled. MACE (non-fatal ischemic stroke, non-fatal myocardial infarction, cardiac revascularization or coronary bypass surgery, and cardiovascular death), total mortality, and HF hospitalizations (hHF) occurrence were evaluated during a median follow-up of 6.1years. In all population, 152 patients had a SA value < 3.5g/dL and 226 had a SA value ≥ 3.5g/dL. In patients with SA ≥ 3.5g/dL, the observed MACE were 2.1 events/100 patient-year; while in the group with a worse SA levels, there were 7.0 events/100 patient-year (p < 0.001). The multivariate analysis model confirmed that low levels of SA increase the risk of MACE by a factor of 3.1. In addition, the presence of ischemic heart disease, serum uric acid levels > 6.0mg/dL, chronic kidney disease, and a 10-year age rise, increased the risk of MACE in study participants. Finally, patients with SA < 3.5g/dl had a higher incidence of hHF (p < 0.001) and total mortality (p < 0.001) than patients with SA ≥ 3.5g/dl. Patients with chronic HF that exhibits low SA levels show a higher risk of MACE, hHF and total mortality.

The Neutrophil to Lymphocyte Ratio Modifies Lipoprotein (a)-Related Poor Prognosis in Patients After Percutaneous Coronary Intervention.

Lipoprotein (a) [Lp(a)] could contribute to coronary artery disease (CAD) through proinflammatory effects. The neutrophil to lymphocyte ratio (NLR) is an inflammatory biomarker. We consecutively enrolled 7,922 CAD patients to investigate the synergistic association of Lp(a) and NLR with prognosis in patients undergoing percutaneous coronary intervention (PCI). NLR was calculated as the neutrophil count divided by the lymphocyte count. Cutoff for NLR was a median of 2.07. The threshold value was set at 30mg/dL for Lp(a). The primary endpoint was major adverse cardiac events (MACEs), including all-cause mortality and myocardial infarction. During 2 years follow-up, 111 (1.40%) MACEs occurred. Lp(a) > 30mg/dL was associated with an increased MACE risk in participants with NLR ≥2.07 [adjusted hazard ratio (HR), 1.84; 95% CI, 1.12-3.03], but not in participants with NLR <2.07 (adjusted HR, 0.74; 95% CI, 0.38-1.45) (Pinteraction = 0.021). Subgroup analysis demonstrated that the synergistic association of Lp(a) and NLR with prognosis was more pronounced in female patients (Pinteraction = 0.028). This study suggested that combining Lp(a) and NLR may be useful for risk stratification in CAD population.

Efficacy of revascularization in CTO patients based on hibernating myocardium therapy.

The effectiveness of percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) is still uncertain, especially for patients with ischemic left ventricular dysfunction. This study aimed to assess hibernating myocardium (HM), as determined by single-photon emission computed tomography (SPECT) and 18F-FDG positron emission tomography (PET), and to compare the benefits of PCI and optimal medical therapy (OMT). A retrospective study collected data from 332 patients with CTO and ischemic left ventricular dysfunction. The study compared patients who underwent PCI or OMT via propensity score matching (PSM) analysis which was performed with a 1:2 matching protocol using the nearest neighbour matching algorithm. The primary endpoint of the study was the occurrence of major adverse cardiac events (MACE), defined as a composite of cardiac death, readmission for worsening heart failure (WHF), revascularization and myocardial infarction (MI). After PSM, there were a total of 246 individuals in the PCI and OMT groups. Following Cox regression, hibernating myocardium/total perfusion defect (HM/TPD) was identified as an independent risk factor (hazard ratio (HR): 1.03, 95% confidence interval (CI): 1.008-1.052, p = .007). The cut-off value of HM/TPD was 38%. The results of the subgroup analysis suggest that for patients with HM/TPD >38%, the OMT group had a greater risk of MACE (p = .035). A sensitivity analysis restricting patients with single-vessel CTO lesions, HM/TPD remained an independent predictor (HR 1.025, 95% CI 1.008-1.043, p = .005). HM/TPD is an independent predictor of MACE, and for patients with HM/TPD > 38%, CTO-PCI had a lower risk of MACE compared with OMT. However, further validation is still needed through large-scale studies.

Long-Term Cardiovascular Outcomes in Children and Adolescents With Hypertension

Hypertension affects 6% of all children, and its prevalence is increasing. Childhood hypertension tracks into adulthood and is associated with subclinical cardiovascular disease; however, there is a lack of evidence linking childhood hypertension to cardiovascular outcomes, which may contribute to underdiagnosis and undertreatment. To determine the long-term associated risk of major adverse cardiac events (MACE) among children diagnosed with hypertension. This was a population-based, retrospective, matched cohort study conducted from 1996 to 2022. The study included all children (aged 3-18 years) alive in Ontario, Canada, from 1996 to 2021, who were identified using provincial administrative health databases. Children with prior kidney replacement therapy were excluded. Incident hypertension diagnosis, identified by validated case definitions using diagnostic and physician billing claims. Each case was matched with 5 controls without hypertension by age, sex, birth weight, maternal gestational hypertension, prior comorbidities (chronic kidney disease, diabetes, cardiovascular surgery), and a propensity score for hypertension. The primary outcome was MACE (a composite of cardiovascular death, stroke, hospitalization for myocardial infarction or unstable angina, or coronary intervention). Time to MACE was evaluated using the Kaplan-Meier method and Cox proportional hazards regression. A total of 25 605 children (median [IQR] age, 15 [11-17] years; 14 743 male [57.6%]) with hypertension were matched to 128 025 controls without hypertension. Baseline covariates were balanced after propensity score matching, and prior comorbidities were uncommon (hypertension vs control cohort: malignancy, 1451 [5.7%] vs 7908 [6.2%]; congenital heart disease, 1089 [4.3%] vs 5408 [4.2%]; diabetes, 482 [1.9%] vs 2410 [1.9%]). During a median (IQR) of 13.6 (7.8-19.5) years of follow-up, incidence of MACE was 4.6 per 1000 person-years in children with hypertension vs 2.2 per 1000 person-years in controls (hazard ratio, 2.1; 95% CI, 1.9-2.2). Children with hypertension were at higher associated risk of stroke, hospitalization for myocardial infarction or unstable angina, coronary intervention, and congestive heart failure, but not cardiovascular death, compared with nonhypertensive controls. Children diagnosed with hypertension had a higher associated long-term risk of MACE compared with controls without hypertension. Improved detection, follow-up, and control of pediatric hypertension may reduce the risk of adult cardiovascular disease.

Clinical impact of complex percutaneous coronary intervention in the pre-TAVR workup

Introduction and objectivesIn patients undergoing percutaneous coronary intervention (PCI) in the workup for transcatheter aortic valve replacement (TAVR), the clinical impact of coronary revascularization complexity remains largely unknown. This study sought to examine the impact of PCI complexity on clinical outcomes after TAVR in patients undergoing PCI in the preprocedural workup. MethodsThis was a multicenter study including consecutive patients scheduled for TAVR with concomitant significant coronary artery disease. Complex PCI was defined as having at least 1 of the following features: 3 vessels treated, ≥ 3 stents implanted, ≥ 3 lesions treated, bifurcation with 2 stents implanted, total stent length >60mm, or chronic total occlusion. The rates of major adverse cardiac events (MACE), including cardiovascular mortality, myocardial infarction, and coronary revascularization were evaluated. ResultsA total of 1550 patients were included, of which 454 (29.3%) underwent complex PCI in the pre-TAVR workup. After a median follow-up period of 2 [1-3] years after TAVR, the incidence of MACE was 9.6 events per 100 patients-years. Complex PCI significantly increased the risk of cardiovascular death (HR, 1.44; 95%CI, 1.01-2.07), nonperiprocedural myocardial infarction (HR, 1.52; 95%CI, 1.04-2.21), and coronary revascularization (HR, 2.46; 95%CI, 1.44-4.20). In addition, PCI complexity was identified as an independent predictor of MACE after TAVR (HR, 1.44; 95%CI, 1.09-1.83; P=.009). ConclusionsIn TAVR candidates with significant coronary artery disease requiring percutaneous treatment, complex revascularization was associated with a higher risk of MACE. The degree of procedural complexity should be considered a strong determinant of prognosis in the PCI-TAVR population.

Association of the longitudinal trajectory of urinary albumin/creatinine ratio in diabetic patients with adverse cardiac event risk: a retrospective cohort study.

The baseline urinary albumin/creatinine ratio (uACR) has been proven to be significantly associated with the risk of major adverse cardiac events (MACE). However, data on the association between the longitudinal trajectory patterns of uACR, changes in glycated hemoglobin A1c (HbA1c), and the subsequent risk of MACE in patients with diabetes are sparse. This is a retrospective cohort study including 601 patients with type 2 diabetes mellitus (T2DM; uACR < 300 mg/g) admitted to The First Hospital of Shanxi Medical University and The Second Hospital of Shanxi Medical University from January 2015 to December 2018. The uACR index was calculated as urinary albumin (in milligrams)/creatinine (in grams), and latent mixed modeling was used to identify the longitudinal trajectory of uACR during the exposure period (2016-2020). The deadline for follow-up was December 31, 2021. The primary outcome was the MACE [a composite outcome of cardiogenic death, hospitalization related to heart failure (HHF), non-fatal acute myocardial infarction, non-fatal stroke, and acute renal injury/dialysis indications]. The Kaplan-Meier survival analysis curve was used to compare the risk of MACE among four groups, while univariate and multivariate Cox proportional hazards models were employed to calculate the hazard ratio (HR) and 95% confidence interval (CI) for MACE risk among different uACR or HbA1c trajectory groups. The predictive performance of the model, both before and after the inclusion of changes in the uACR and HbA1c, was evaluated using the area under the receiver operating characteristic (ROC) curve (AUC). Four distinct uACR trajectories were identified, namely, the low-stable group (uACR = 5.2-38.3 mg/g, n = 112), the moderate-stable group (uACR = 40.4-78.6 mg/g, n = 229), the high-stable group (uACR = 86.1-153.7 mg/g, n = 178), and the elevated-increasing group (uACR = 54.8-289.4 mg/g, n = 82). In addition, five distinct HbA1c trajectories were also identified: the low-stable group (HbA1c = 5.5%-6.8%, n = 113), the moderate-stable group (HbA1c = 6.0%-7.9%, n = 169), the moderate-decreasing group (HbA1c = 7.4%-6.1%, n = 67), the high-stable group (HbA1c = 7.7%-8.9%, n = 158), and the elevated-increasing group (HbA1c = 8.4%-10.3%, n = 94). Compared with the low-stable uACR group, patients in the high-stable and elevated-increasing uACR groups were more likely to be older, current smokers, and have a longer DM course, higher levels of 2-h plasma glucose (PG), HbA1c, N-terminal pro-B-type natriuretic peptide (NT-proBNP), uACR, and left ventricular mass index (LVMI), while featuring a higher prevalence of hypertension and a lower proportion of β-receptor blocker treatment (p < 0.05). During a median follow-up of 45 months (range, 24-57 months), 118 cases (19.6%) of MACE were identified, including 10 cases (1.7%) of cardiogenic death, 31 cases (5.2%) of HHF, 35 cases (5.8%) of non-fatal acute myocardial infarction (AMI), 18 cases (3.0%) of non-fatal stroke, and 24 cases (4.0%) of acute renal failure/dialysis. The Kaplan-Meier survival curve showed that, compared with that in the low-stable uACR group, the incidence of MACE in the high-stable (HR = 1.337, 95% CI = 1.083-1.652, p = 0.007) and elevated-increasing (HR = 1.648, 95% CI = 1.139-2.387, p = 0.009) uACR groups significantly increased. Similar results were observed for HHF, non-fatal AMI, and acute renal injury/dialysis indications (p < 0.05). The multivariate Cox proportional hazards models indicated that, after adjusting for potential confounders, the HRs for the risk of MACE were 1.145 (p = 0.132), 1.337 (p = 0.007), and 1.648 (p = 0.009) in the moderate-stable, high-stable, and elevated-increasing uACR groups, respectively. In addition, the HRs for the risk of MACE were 1.203 (p = 0.028), 0.872 (p = 0.024), 1.562 (p = 0.033), and 2.218 (p = 0.002) in the moderate-stable, moderate-decreasing, high-stable, and elevated-increasing groups, respectively. The ROC curve showed that, after adding uACR, HbA1c, or both, the AUCs were 0.773, 0.792, and 0.826, which all signified statistically significant improvements (p = 0.021, 0.035, and 0.019, respectively). A long-term elevated uACR is associated with a significantly increased risk of MACE in patients with diabetes. This study implies that regular monitoring of uACR could be helpful in identifying diabetic patients with a higher risk of MACE.

Proarrhythmic major adverse cardiac events with donepezil: A systematic review with meta-analysis.

Cholinesterase inhibitors (ChEIs) are regularly used in Alzheimer's disease. Of the three ChEIs approved for dementia, donepezil is among the most prescribed drugs in the United States with nearly 6 million prescriptions in 2020; however, it is classified as a "known risk" QT interval-prolonging medication (QTPmed). Given this claim is derived from observational data including single case reports, we aimed to evaluate high-quality literature on the frequency and nature of proarrhythmic major adverse cardiac events (MACE) associated with donepezil. We searched Medline, Embase, International Pharmaceutical Abstracts, and Cochrane Central from 1996 onwards for randomized controlled trials (RCTs) involving patients age ≥18 years comparing donepezil to placebo. The MACE composite included mortality, sudden cardiac death, non-fatal cardiac arrest, Torsades de pointes, ventricular tachyarrhythmia, seizure or syncope. Random-effects meta-analyses were performed with a treatment-arm continuity correction for single and double zero event studies. Sixty RCTs (n = 12,463) were included. Twenty-five of 60 trials (n = 5886) investigated participants with Alzheimer's disease and 33 trials monitored electrocardiogram data. The mean follow-up duration was 31 weeks (SD = 36). Mortality was the most commonly reported MACE (252/331, 75.8% events), the remainder were syncope or seizures, with no arrhythmia events. There was no increased risk of MACE with exposure to donepezil compared to placebo (risk ratio [RR] 1.08, 95% CI 0.88-1.33, I2 = 0%) and this was consistent in the subgroup analysis of trials including participants with cardiovascular morbidities (RR 1.14, 95% CI 0.88-1.47). Subgroup analysis suggested a trend toward more events with donepezil with follow-up ≥52 weeks (RR: 1.32, 0.98-1.79). This systematic review with meta-analysis found donepezil may not be arrhythmogenic. Donepezil was not associated with mortality, ventricular arrhythmias, seizure or syncope, although longer durations of therapy need more study. Further research to clarify actual clinical outcomes related to QTPmed is important to inform prescribing practices.

The prognostic value of visual and automatic coronary calcium -scoring from low dose CT-[15O]-water PET.

Firstly, to validate automatically and visually scored coronary artery calcium (CAC) on low dose CT (LDCT) scans with a dedicated calcium scoring CT (CSCT) scan. Secondly, to assess the added value of CAC scored from LDCT scans acquired during [15O]-water-PET myocardial perfusion imaging (MPI) on prediction of major adverse cardiac events (MACE). 572 consecutive patients with suspected coronary artery disease, who underwent [15O]-water-PET MPI with LDCT and a dedicated CSCT scan were included. In the reference CSCT scans, manual CAC scoring was performed, while LDCT scans were scored visually and automatically using deep learning approach. Subsequently, based on CAC score results from CSCT and LDCT scans, each patient's scan was assigned to one out of five cardiovascular risk groups (0; 1-100; 101-400; 401-1000; >1000) and the agreement in risk group classification between CSCT and LDCT scans was investigated. MACE was defined as a composite of all-cause death, nonfatal myocardial infarction, coronary revascularization, and unstable angina. The agreement in risk group classification between reference CSCT manual scoring and visual/automatic LDCT scoring from LDCT was 0.66 (95% CI: 0.62-0.70) and 0.58 (95% CI: 0.53-0.62), respectively. Based on visual and automatic CAC scoring from LDCT scans, patients with CAC>100 and CAC>400, respectively, were at increased risk of MACE, independently of ischemic information from the [15O]-water-PET scan. There is a moderate agreement in risk classification between visual and automatic CAC scoring from LDCT and reference CSCT scans. Visual and automatic CAC scoring from LDCT scans improve identification of patients at higher risk of MACE.

Association of Anxiety and Recurrent Cardiovascular Events: Investigating Different Aspects of Anxiety.

While elevated levels of anxiety are associated with worse prognosis of cardiovascular disease (CVD), this association may vary between different aspects of anxiety. The aim of this study was to analyse self-reported behavioural, physiological, affective, and cognitive aspects of anxiety and their relation to the risk of recurrent CV events. This prospective cohort study utilized data from the U-CARE Heart trial. Participants (N = 935, post myocardial infarction) answered the Hospital Anxiety and Depression Scale (HADS: Anxiety subscale) and the Cardiac Anxiety Questionnaire (CAQ: Fear, Avoidance & Attention subscales). HADS Anxiety reflected physiological aspects, CAQ Fear reflected cognitive and affective aspects, CAQ Avoidance reflected behavioural aspects, and CAQ Attention reflected cognitive aspects of anxiety. Cox Regression was used to estimate the risk between anxiety and recurrent major adverse cardiac event (MACE). During the follow-up period (mean 2.9 years), 124 individuals (13%) experienced a specified MACE endpoint. HADS Anxiety and CAQ Total were both associated with increased risk of MACE (HR = 1.52, 95% CI: 1.15-2.02 and HR = 1.30, 95% CI: 1.04-1.64, respectively). Among the CAQ subscales, there was support for an association between Avoidance and risk of MACE (HR = 1.37, 95% CI 1.15-1.64), but not for Attention and Fear. The results support that anxiety is associated with an increased risk of recurrent MACE in post-MI patients. The association between anxiety and risk was strong for the aspects of anxiety relating to behaviour and physiology, while the support for an association with cognitive and affective aspects was lacking.

Diabetic kidney disease as an independent predictor of long-term adverse outcomes in patients with coronary artery disease and diabetic mellitus.

Diabetic kidney disease (DKD) had been proposed as a contributor in the pathogenesis of coronary artery disease (CAD). However, the relationship of DKD and the long-term adverse outcomes in patients with CAD after percutaneous coronary intervention (PCI) was still undiscovered. Approximately 892 patients with CAD enrolled from January 2012 to December 2016. The patients were divided into two groups, the DKD group (n = 341) and the None DKD group (n = 551). The primary outcome was major adverse cardiac events (MACE) after PCI. The average follow-up time was 1,897 ± 1,276 days. Baseline data showed that some factors were significantly different between the two groups, including age, body mass index, gender (female), hypertension, smoking, stroke history, heart failure, duration of diabetic mellitus (DM), low-density lipoprotein cholesterol, urinary protein/creatinine ratio, serum creatinine, hemoglobin, platelet, antiplatelet, beta blocker, statin, antihypertensive drugs, and insulin (all p < 0.005). There were significant differences between the two groups in MACE, 40.3% vs. 52.2% (p = 0.001), and in cardiovascular death events and all-cause death events (5.6% vs. 20.5%, p < 0.001 and 4.4% vs. 13.5%, p < 0.001, respectively). In the DKD group, the risk of MACE was elevated to 141.9% [hazard ratio (HR) = 1.419, 95% confidence interval (CI): 1.164-1.730, p = 0.001] in the Cox univariable regression analyses; after adjusting co-variables, the Cox multivariable regression analyses demonstrated that DKD was an independent predictor for MACE (HR = 1.291, 95% CI: 1.027-1.624, p = 0.029) in patients with CAD after PCI, as well as in cardiovascular death events (HR = 2.148, 95% CI: 1.292-3.572, p = 0.003) and all-cause death events (HR = 2.229, 95% CI: 1.325-3.749, p = 0.003). This study suggests that DKD is an independent and novel predictor of long-term adverse outcomes in patients with CAD and DM who underwent PCI.

Testosterone therapy in females is not associated with increased cardiovascular or breast cancer risk: a claims database analysis.

Testosterone therapy (TTh) has been shown to improve libido in women with sexual dysfunction, but its utilization has been limited due to concern for cardiovascular events and past studies reporting highly variable results. To assess the association of TTh in women with major adverse cardiac events (MACEs), including heart attack, stroke, or death, using a large database. The TriNetX Diamond Network was queried from 2009 to 2022. Our study cohort included adult females with ≥3 systemic testosterone prescriptions within a year. Our control cohort excluded females with any testosterone prescriptions, polycystic ovary syndrome, or androgen excess. Both cohorts excluded females with prior heart failure, unstable angina, intersex surgery (female to male), personal history of sex reassignment, or gender identity disorders. Propensity matching between the cohorts was performed. A subanalysis by age was conducted (18-55 and >55 years). We evaluated the association of TTh to the following: MACE, upper or lower emboli or deep vein thrombosis (DVT), pulmonary embolism (PE), breast neoplasm, and hirsutism within 3 years of TTh. When compared with propensity-matched controls, adult females with TTh had a lower risk of MACE (risk ratio [RR], 0.64; 95% CI, 0.51-0.81), DVT (RR, 0.61; 95% CI, 0.42-0.90), PE (RR, 0.48; 95% CI, 0.28-0.82), and malignant breast neoplasm (RR, 0.48; 95% CI, 0.37-0.62). Similarly, females aged 18 to 55 years with TTh had a lower risk of MACE (RR, 0.49; 95% CI, 0.28-0.85) and DVT (RR, 0.48; 95% CI, 0.25-0.93) and a similar risk of malignant breast neoplasm (RR, 0.62; 95% CI, 0.34-1.12). Females aged ≥56years with TTh had a similar risk of MACE (RR, 0.84; 95% CI, 0.64-1.10), DVT (RR, 0.82; 95% CI, 0.50-1.36), and PE (RR, 0.52; 95% CI, 0.26-1.05) and a significantly lower risk of malignant breast neoplasm (RR, 0.51; 95% CI, 0.38-0.68). Risk of hirsutism was consistently higher in those with TTh as compared with propensity-matched controls. Our results contribute to safety data on TTh, a therapy for sexual dysfunction in women. The TriNetX Diamond Network allows for significant generalizability but has insufficient information for some factors. We found a decreased risk of MACE among women with TTh as compared with matched controls and a similar risk of MACE in postmenopausal women while demonstrating a similar or significantly lower risk of breast cancer on age-based subanalysis.

The transition of metabolic phenotypes and cardiovascular events: Panasonic cohort study 16.

The study objective was to investigate whether changes in metabolic phenotype affect the risk of cardiovascular events. All 117,589 participants were included in this retrospective cohort study. The metabolic phenotypes of the participants were assessed at two points (the second evaluation was set 2 years after the first evaluation), and the incidence rate of cardiovascular events was observed for 11 years. The main outcome was 3-point major adverse cardiac events (MACE), which comprises cardiovascular death, nonfatal coronary artery disease, and nonfatal stroke incidence. Of the participants, 2748 (2.3%) cases of 3-point MACE were identified during follow-up. The stable metabolically healthy obesity group had a higher risk of 3-point MACE than those with stable metabolically healthy nonobesity (MHNO). Additionally, the change from metabolically healthy obesity to MHNO for 2 years decreased the risk of 3-point MACE (hazard ratio [HR], 1.12: 95% CI: 0.84-1.47) to the same level as stable MHNO. However, the change from metabolically abnormal nonobesity and metabolically abnormal obesity to MHNO for 2 years maintained a higher risk of 3-point MACE (HR, 1.66 [95% CI: 1.36-2.01]; HR, 1.91 [95% CI: 1.22-2.81]) than those with stable MHNO. Change in metabolic phenotype is associated with incident 3-point MACE.

Predictability of noninvasive liver fibrosis score for cardiac events in patients with nonalcoholic fatty liver disease

Background and aimsPatients with nonalcoholic fatty liver disease (NAFLD) have a higher risk of cardiac events. However, although the severity of liver fibrosis is related to worsening prognosis in patients with NAFLD, it is unclear whether the noninvasive liver fibrosis score has a predictive value for cardiac events. Methods and resultsWe evaluated 4071 patients with NAFLD diagnosed using ultrasonography. Liver fibrosis was assessed and divided into three groups based on the Fibrosis-4 (FIB4) index and NAFLD fibrosis score (NFS). The primary outcome of this study was major adverse cardiac events (MACE), including cardiac death, nonfatal myocardial infarction, and revascularization due to coronary artery disease. The median age of the evaluated patients was 61 (52–69) years, and 2201 (54.1%) were male. During the median follow-up period of 6.6 years, 179 (4.4%) patients experienced MACE. Kaplan–Meier survival analysis demonstrated that MACE increased progressively with the FIB4 index (log-rank, p < 0.001) and NFS (log-rank, p < 0.001). Multivariable analysis showed that the higher the FIB4 index, the higher the risk for MACE (low group as reference vs. intermediate group, hazard ratio [HR]: 1.860 [95% confidence interval (CI), 1.326–2.610; p < 0.001]; vs. high group, HR:3.325 [95% CI, 2.017–5.479; p < 0.001]), as well as NFS (low NFS group as reference vs. intermediate group, HR: 1.938 [95% CI, 1.391–2.699; p < 0.001]; vs. high group, HR: 3.492 [95% CI, 1.997–6.105; p < 0.001]). ConclusionsThe FIB4 index and NFS are associated with the probability of MACE in patients with NAFLD. Clinical trialsThe study design was approved by the ethics review board of Ogaki Municipal Hospital (approval number: 20221124–12, registration date: November 28th, 2022). https://www.ogaki-mh.jp/chiken/kenkyu.html.

Circulating osteoprotegerin levels and cardiovascular outcomes in patients with pre-dialysis chronic kidney disease: results from the KNOW-CKD study.

While the relationship between circulating osteoprotegerin (OPG) and cardiovascular events is well-established in the general population, its association with cardiovascular risks in chronic kidney disease (CKD) patients remains less robust. This study hypothesized that elevated circulating OPG levels might be associated with an increased risk of major adverse cardiac events (MACE) in CKD patients, a total of 2,109 patients with CKD stages 1 through pre-dialysis 5 from the KNOW-CKD cohort were categorized into quartiles based on serum OPG levels. The primary outcome of the study was 3-point MACE, defined as a composite of nonfatal myocardial infarction, nonfatal stroke, or cardiac death. The median follow-up duration was 7.9years. The cumulative incidence of 3-point MACE significantly varied across serum OPG levels in Kaplan-Meier curve analysis (P < 0.001, log-rank test), with the highest incidence observed in the 4th quartile. Cox regression analysis indicated that, relative to the 1st quartile, the risk of 3-point MACE was significantly higher in the 3rd (adjusted hazard ratio 2.901, 95% confidence interval 1.009 to 8.341) and the 4th quartiles (adjusted hazard ratio 4.347, 95% confidence interval 1.410 to 13.395). In conclusion, elevated circulating OPG levels are associated with adverse cardiovascular outcomes in pre-dialysis CKD patients.

Impact of diabetes mellitus on clinical outcomes after first episode in-stent restenosis PCI: Results from a large registry

BackgroundDiabetes mellitus (DM) is associated with a high rate of major adverse cardiac events (MACE) after de novo coronary artery percutaneous coronary intervention (PCI). Whether patients with DM undergoing PCI for in-stent restenosis (ISR) experience a similar heightened risk of MACE is not known. Hence, we sought to compare the clinical outcomes of patients with and without DM undergoing PCI for ISR. MethodsPatients undergoing first episode ISR PCI between January 2015 and December 2021 were included. The primary outcome of interest was MACE (all-cause death, myocardial infarction [MI], and target lesion revascularization [TVR]) at 1-year. ResultsA total of 3156 patients (56.7% with DM) underwent PCI for ISR during the study period. Patients with DM were younger, more likely to be female, and had a higher prevalence of comorbidities.At 1-year follow-up, DM was associated with a higher rate of MACE (22.4% vs. 18.7%, unadjusted HR 2.03, 95%CI(1.27–3.25), p = 0.003). All-cause mortality and MI were significantly more frequent among people with DM at 1-year follow-up. The rate of TVR was similar in both groups (17.9% vs. 16.0%, unadjusted HR 1.14, 95%CI (0.94–1.37), p = 0.180). On adjusted analysis, there was no significant difference in the rate of MACE (AHR 1.07, 95%CI(0.90 ‐ –1.29), p = 0.444), all-cause death (AHR 1.54, 95%CI(0.93–2.54), p = 0.095) or MI (AHR 1.10, 95%CI(0.74–1.63), p = 0.652). ConclusionISR PCI in patients with DM was associated with a higher rate of MACE at 1-year follow-up. However, this increased risk was no longer significant after adjusting for baseline characteristics.

(089) Greater Changes in Hematocrit Predict More Frequent Major Adverse Cardiac Events in Men Receiving Testosterone Therapy - A Retrospective Cohort Claims Database Analysis

Abstract Introduction While recent studies have shown that Testosterone therapy (TTh)-induced secondary polycythemia, Hematocrit (Hct) &amp;gt; 52%, is an independent risk factor for major adverse cardiac events (MACE) within the first year of treatment, it is not clear whether erythrocytosis – i.e., degree of change in Hct from baseline Hct after starting TTh confers additional risk for MACE. Objective The objective of this study is to determine the incidence of MACE associated with the degree of Hct change from baseline in adult men receiving testosterone therapy for hypogonadism. Methods To assess whether an increase in Hct after initiating TTh is associated with an increased risk of MACE within 3 and 24 months of initiating TTh, we queried the TriNetX Research network database for men over the age of 18 with Hct values obtained within six months before starting TTh, and who had follow-up Hct measurements within three and 24 months after beginning TTh from 2010 through 2021. Men with and without a subsequent increase in Hct after initiating TTh were propensity matched. MACE was defined as myocardial infarction, stroke, or death. Results After matching, 10,291 men who experienced an any increase in Hct after initiating TTh and 6,320 controls who did not were included. Compared to controls who did not have an increase in Hct, the majority of men who had an increase in subsequent Hct had a statistically significant increased risk of major adverse cardiac events with greater change being associated with increase risk of MACE. Conclusions We demonstrate that increases in Hct from baseline are associated with increased risk of MACE, compared to men whose Hct remains stable while receiving TTh. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Boston Scientific, Coloplast, Endo Pharmaceuticals, Antares Pharma.

Prognostic impact of peripheral artery disease in patients with and without high bleeding risk undergoing percutaneous coronary intervention.

Peripheral artery disease (PAD) is associated with worse outcomes after percutaneous coronary intervention (PCI). The aim of this study was to assess the prognostic impact of PAD according to high bleeding risk (HBR) status. Consecutive patients undergoing PCI with drug-eluting stent implantation at a tertiary-care center (Mount Sinai Hospital) between 2012 and 2019 were stratified according to HBR and PAD status. The primary outcome was major adverse cardiac events (MACE), a composite of all-cause death, myocardial infarction (MI), and stroke 1 year after PCI. Secondary outcomes included major bleeding. Out of 16,750 patients, 43% were HBR and 57% were no-HBR. Within the two groups, PAD patients were 14% and 6%, respectively, and were more likely to have comorbidities and to undergo complex PCI than no-PAD patients. Within the HBR group, PAD was associated with an increased risk of MACE (11.4% vs. 7.3%, hazard ratio [HR]: 1.59, 95% confidence interval [CI]: 1.27-1.99, p < 0.001) and a numerical nonsignificant increase of major bleeding (8.5% vs. 6.9%, HR: 1.25, 95% CI: 0.98-1.59, p = 0.066) as compared with no-PAD. Among no-HBR patients, rates of MACE and major bleeding were numerically but not significantly higher in the PAD group. After multivariable adjustment, PAD was no longer a predictor of adverse outcomes, irrespective of HBR status. At 1-year after PCI, PAD was associated with increased 1-year risks of MACE in HBR patients. After adjustment for cardiovascular risk factors and comorbidities, the effect of PAD on adverse events was largely attenuated.

Fractal Analysis of Left Ventricular Trabeculae in Patients with End-Stage Renal Disease: A Random Survival Tree Analysis.

The complexity of left ventricular (LV) trabeculae is related to the prognosis of several cardiovascular diseases. To evaluate the prognostic value of LV trabecular complexity in patients with end-stage renal disease (ESRD). Prospective outcome study. 207 participants on maintenance dialysis, divided into development (160 patients from 2 centers) and external validation (47 patients from a third center) cohorts, and 72 healthy controls. 3.0T, steady-state free precession (SSFP) and modified Look-Locker imaging sequences. All participants had their trabecular complexity quantified by fractal analysis using cine SSFP images. Patients were followed up every 2 weeks until April 2023, or endpoint events happened. Random Forest (RF) and Cox regression models including age, diabetes, LV mass index, mean basal fractal dimension (FD), and left atrial volume index, were developed to predict major adverse cardiac events (MACE). Patients were divided into low- and high-risk groups based on scores derived from the RF model and survival compared. Receiver operating characteristic curve analysis; Kaplan-Meier survival analysis with log rank tests; Harrel's C-index to assess model performance. A P value <0.05 was considered statistically significant. Fifty-five patients (26.57%) experienced MACE during a median follow-up time of 21.83 months. An increased mean basal FD (≥1.324) was associated with a significantly higher risk of MACE. The RF model (C-index: 0.81) had significantly better discrimination than the Cox regression model (C-index: 0.74). Participants of the external validation dataset classified into the high-risk group had a hazard of experiencing MACE increased by 12.29 times compared to those in the low-risk group. LV basal FD was an independent predictor for MACE in patients with ESRD. Reliable risk stratification models could be generated based on LV basal FD and other MRI variables using RF analysis. 2 TECHNICAL EFFICACY: Stage 2.