Unadjusted Hazard Ratio Research Articles

High ABCD2-score after transient ischemic attack is associated with a two-fold higher stroke-rate during long-term follow-up

Abstract Background The ABCD2-score is a validated risk score used to estimate the short-term risk of stroke after transient ischemic attack (TIA). However, "real-world" contemporary data on the long-term risk of stroke after TIA according to ABCD2-score are needed in order to guide preventive strategies. Purpose To determine the long-term risk of stroke after TIA according to modified ABCD2-score (high-risk (≥4 points) versus low-risk (<4 points)). Methods Patients aged ≥18 years with first-time TIA were included from the Danish Stroke Registry (2014-2020). The study population was stratified in high-risk (≥4 points) and low-risk (<4 points) ABCD2-score group. We utilized a modified ABCD2-score consisting of the following parameters: age ≥60 years, hypertension, clinical features, and diabetes. The 3-year risk of ischemic stroke and all-cause mortality was compared between the high-risk and low-risk group using the Aalen-Johansen and Kaplan-Meier estimator. A cox regression model was also conducted. Results In total, 21,433 patients with first-time TIA were included; 1,281 (6.0%) in the high-risk and 20,152 (94.0%) in the low-risk group. Patients in the high-risk group were older (77.5 years [interquartile range [IQR] 70.8-84.1] versus 70.3 years [IQR 60.1-78.2]), more often females (52.2% versus 46.6%) (p <0.001), more comorbid and received more medication compared with the low-risk group at baseline. The 3-year cumulative incidence of stroke was 6.0% [95% CI: 4.6-7.5] in the high-risk group and 4.2% [95% CI: 3.9-4.5] in the low-risk group, and the unadjusted hazard ratio (HR) was 1.6 (95% CI 1.2 – 2.0) (Figure 1). The cumulative incidence of all-cause mortality within three-years after TIA was 28.9% [95% CI: 26.1-31.7] in the high-risk group and 10.3% [95% CI: 9.9-10.8] in the low-risk group. The unadjusted HR was 3.2 (95% CI 2.8 – 3.6). Conclusions Patients with high-risk ABCD2-scores had an almost two-fold higher associated long-term stroke-rate compared to those with low-risk scores. Trials focusing on preventive measures, including evidence-based antithrombotic strategies, especially for the high-risk group are warranted.

Impact of body weight and body mass index on clinical outcomes of edoxaban therapy in atrial fibrillation patients included in the ETNA-AF-Global registry

Abstract Background In atrial fibrillation (AF) patients (pts) receiving non-vitamin K antagonist oral anticoagulant therapy, extreme body weights, both obesity and low body weight, may impact clinical outcomes. Purpose To determine the impact of body weight and body mass index (BMI) on clinical outcomes in AF pts receiving edoxaban from the Global ETNA program (Europe [NCT02944019], Japan [UMIN000017011], Korea/Taiwan [NCT02951039], Hong Kong [NCT03247582] and Thailand [NCT03247569]). Methods ETNA-AF-Global, a multinational, prospective, observational study collected demographic and clinical outcomes data for AF pts receiving edoxaban. In this subanalysis, pts were categorised into the following body weight groups: ≤60kg, >60 to 80kg (reference body weight), >80 to ≤100kg and >100kg; and BMI groups: <18.5kg/m², ≥18.5 to <25.0kg/m² (reference BMI), ≥25.0 to <30.0kg/m², ≥30.0 to <40.0kg/m² and ≥40.0kg/m². Clinical outcomes at 2-year follow-up were compared across body weight and BMI groups. Results 26,805 pts were included in this analysis. Mean ± standard deviation body weight was 72.2 ± 18.1kg and mean BMI was 26.4 ± 5.0kg/m². 43.7% of pts were categorised into the >60 to 80kg reference body weight group. [other groups: ≤60kg, 28.1%; >80 to ≤100kg, 21.7%; >100kg, 6.5%] and 40.0% of pts into the ≥18.5 to <25.0kg/m² reference BMI group [other groups: <18.5kg/m², 3.0%; ≥25.0 to <30.0kg/m², 37.3%; ≥30.0 to <40.0kg/m², 18.0%; ≥40.0kg/m², 1.7%]. Clinical outcomes are shown in Fig. 1 as unadjusted hazard ratios vs. reference group according to weight and in Fig. 2 according to BMI. Among body weight groups, pts weighing ≤60kg had the highest annualised rates of any stroke or systemic embolic event (SEE; 1.24%), ischemic stroke (0.97%), all-cause death (3.96%), major bleeding events (1.49%), and major bleeding or clinical-relevant non-major (CRNM) bleeding events (3.45%). Pts in the reference body weight group had the lowest annualised rates of all-cause death (2.81%). Annualised rates of major bleeding, major bleeding or CRNM bleeding events and any stroke or SEE were lowest in pts weighing >100kg. Among BMI groups, annualised rates of all effectiveness and safety outcomes were highest in pts with a BMI <18.5kg/m². Pts in the ≥25.0 to <30.0kg/m² BMI group had the lowest annualised rates of all-cause death (2.85%) and pts in the ≥18.5 to <25.0kg/m² BMI group had the lowest annualised rates of CV death (0.73%). Conclusions In the Global ETNA-AF program, clinical outcomes varied between different body weight and BMI subgroups. These findings highlight the need to consider the clinical implications of low body weight and/or low BMI, as AF pts who belong to these categories may be at higher risk of adverse outcomes during long-term anticoagulant treatment.Figure 1.Figure 2.

Phase 3 Trial of Stereotactic Body Radiotherapy in Localized Prostate Cancer

BackgroundWhether stereotactic body radiotherapy (SBRT) is noninferior to conventionally or moderately hypofractionated regimens with respect to biochemical or clinical failure in patients with localized prostate cancer is unclear.MethodsWe conducted a phase 3, international, open-label, randomized, controlled trial. Men with stage T1 or T2 prostate cancer, a Gleason score of 3+4 or less, and a prostate-specific antigen (PSA) level of no more than 20 ng per milliliter were randomly assigned (in a 1:1 ratio) to receive SBRT (36.25 Gy in 5 fractions over a period of 1 or 2 weeks) or control radiotherapy (78 Gy in 39 fractions over a period of 7.5 weeks or 62 Gy in 20 fractions over a period of 4 weeks). Androgen-deprivation therapy was not permitted. The primary end point was freedom from biochemical or clinical failure, with a critical hazard ratio for noninferiority of 1.45. The analysis was performed in the intention-to-treat population.ResultsA total of 874 patients underwent randomization at 38 centers (433 patients in the SBRT group and 441 in the control radiotherapy group) between August 2012 and January 2018. The median age of the patients was 69.8 years, and the median PSA level was 8.0 ng per milliliter; the National Comprehensive Cancer Network risk category was low for 8.4% of the patients and intermediate for 91.6%. At a median follow-up of 74.0 months, the 5-year incidence of freedom from biochemical or clinical failure was 95.8% (95% confidence interval [CI], 93.3 to 97.4) in the SBRT group and 94.6% (95% CI, 91.9 to 96.4) in the control radiotherapy group (unadjusted hazard ratio for biochemical or clinical failure, 0.73; 90% CI, 0.48 to 1.12; P=0.004 for noninferiority), which indicated the noninferiority of SBRT. At 5 years, the cumulative incidence of late Radiation Therapy Oncology Group (RTOG) grade 2 or higher genitourinary toxic effects was 26.9% (95% CI, 22.8 to 31.5) with SBRT and 18.3% (95% CI, 14.8 to 22.5) with control radiotherapy (P<0.001), and the cumulative incidence of late RTOG grade 2 or higher gastrointestinal toxic effects was 10.7% (95% CI, 8.1 to 14.2) and 10.2% (95% CI, 7.7 to 13.5), respectively (P=0.94).ConclusionsFive-fraction SBRT was noninferior to control radiotherapy with respect to biochemical or clinical failure and may be an efficacious treatment option for patients with low-to-intermediate-risk localized prostate cancer as defined in this trial. (Funded by Accuray and others; PACE-B ClinicalTrials.gov number, NCT01584258.)

Cardiovascular health metrics and all-cause mortality in osteoarthritis, inflammatory arthritis, and unclassified arthritis patients: a national prospective cohort study

BackgroundArthritis notably elevates mortality risk. It remains unclear whether the cardiovascular health (CVH) metrics improves the risk of all-cause mortality in patients with all types of arthritis.MethodsThis study data from the National Health and Nutrition Examination Survey to probe the link between CVH and all-cause mortality among arthritis sufferers in the United States. CVH evaluation employed the Life's Essential 8 metrics. Mortality outcomes were scrutinized using Cox proportional hazard regression models. Additionally, a restricted cubic spline analysis delineated the linear relationship between CVH and mortality. The study also delved into the singular impact of each CVH component on mortality.ResultsIn the cohort of 5919 patients with arthritis, improved CVH was linked to lower all-cause mortality. Specifically, each 10-point increment in CVH score was associated with a substantial decline in all-cause mortality risk [unadjusted hazard ratio (HR): 0.77, 95% Confidence Interval (95% CI): 0.71–0.83, P < 0.001]. Adjustments for age, sex, race, and social determinants of health further refined the HR to 0.72 (95% CI: 0.67–0.79, P < 0.001). Higher versus lower CVH scores at baseline markedly reduced mortality risk, with the most substantial decrease seen in those with ideal CVH metrics (HR: 0.39, 95% CI: 0.26–0.59, P < 0.001). Similar results were not observed in patients with inflammatory arthritis, but were seen in those with osteoarthritis or degenerative arthritis, and unknown types of arthritis.ConclusionIdeal CVH substantially decreases all-cause mortality risk among patients with arthritis, confirming the critical role of CVH in arthritis management. This study advocates for CVH interventions as part of comprehensive arthritis treatment plans.

Association between PaO2/(FiO2*PEEP) ratio and in-hospital mortality in COVID-19 patients: A reanalysis of published data from Peru using PaO2/(FiO2*PEEP) ratio in place of PaO2/FaO2 ratio.

P/FP [PaO2/(FiO2*PEEP)] is associated with in-hospital mortality in patients with acute respiratory distress syndrome (ARDS). However, to the best of our knowledge, the association between P/FP after 24 hours of invasive mechanical ventilation (IMV) and in-hospital mortality in patients with ARDS due to Coronavirus Disease 2019 (COVID-19) remained unclear. This study aimed to evaluate the relationship between the P/FP after 24 hours of IMV and in-hospital mortality in patients with ARDS due to COVID-19. We reanalyzed previously published data from Peru. Hueda-Zavaleta et al conducted a retrospective cohort study between April 2020 and April 2021 in southern Peru. A total of 200 hospitalized COVID-19 patients requiring IMV were included in this analysis. We used Cox proportional hazard regression models and Kaplan-Meier survival analysis to investigate the effect of P/FP after 24 hours of IMV on in-hospital mortality. We used a restricted cubic spline regression and a two-piecewise Cox proportional hazards model to explore the relationship between P/FP after 24 hours of IMV and in-hospital mortality in patients with ARDS due to COVID-19. Of the 200 patients, 51 (25.50%) died in hospital. The median P/FP was 20.45 mm Hg/cmH2O [interquartile range 15.79-25.21 mm Hg/cmH2O], with a range of 5.67 mm Hg/cmH2O to 51.21 mm Hg/cmH2O. Based on the P/FP ratio, patients were equally divided into 2 groups (low group [P/FP < 20.50 mm Hg/cmH2O] and high group [P/FP ≥ 20.50 mm Hg/cmH2O]). In-hospital mortality was lower in the high P/FP group than in the low P/FP group (12 [12%] vs 39 [39%]; unadjusted hazard ratio [HR]: 0.33, 95% confidence interval [CI]: 0.17-0.63; adjusted HR: 0.10, 95% CI: 0.02-0.47). We also found a nonlinear relationship between P/FP and in-hospital mortality. After adjusting for potential confounders, the HR was 0.67 (95% CI: 0.56-0.79) for P/FP ≤ 22 mm Hg/cmH2O and 1.10 (95% CI: 0.83-1.47) for P/FP > 22 mm Hg/cmH2O. In addition, lymphocytes ≤ 1 × 109/L and acute kidney failure had a higher risk of death. After adjusting for potential confounders, the P/FP after 24 hours of IMV was nonlinearly associated with in-hospital mortality in patients with ARDS due to COVID-19.

Clinical importance of cerebrospinal fluid protein levels in HIV-associated cryptococcal meningitis: Insights from a prospective cohort study in Uganda.

Cerebrospinal fluid (CSF) protein levels exhibit high variability in HIV-associated cryptococcal meningitis; however, its clinical implications remain unclear. We analyzed data from 890 adults with HIV-associated cryptococcal meningitis randomized into two clinical trials in Uganda between 2015 and 2021. CSF protein was grouped into < 100mg/dl (72%, n =641) and ≥ 100mg/dl (28%, n =249). We described baseline clinical variables and 18-week mortality by CSF protein groups. Those with CSF protein ≥ 100mg/dl were more likely to present with Glasgow coma scale score<15 (P < .01), self-reported seizures at baseline (P = .02), higher CD4 T-cell count (P < .001), and higher CSF white blood cells (P < .001). Moreover, those with a baseline CSF protein ≥ 100mg/dl also had a lower baseline CSF fungal burden (P < .001) and a higher percentage of sterile CSF cultures at day 14 (P = .02). Individuals with CSF protein ≥ 100mg/dl demonstrated a more pronounced immune response consisting of upregulation of immune effector molecules, pro-inflammatory cytokines, T-helper cell type 1 and 17 cytokines, and immune-exhaustion marker (P < .05). 18-week mortality risk in individuals with a CSF protein < 100mg/dl was 34% higher (unadjusted Hazard Ratio 1.34; 95% Confidence Interval, 1.05-1.70; P = .02) than those with CSF protein ≥ 100mg/dl. In HIV-associated cryptococcal meningitis, individuals with baseline CSF protein ≥ 100mg/dl more frequently presented with neurological symptoms, higher CSF inflammatory cytokines, reduced fungal burden, and lower mortality risk. The findings underscore the prognostic significance of baseline CSF protein levels in predicting disease severity and mortality risk in cryptococcal meningitis.

The Updated Registry of Fast Myocardial Perfusion Imaging with Next-Generation SPECT (REFINE SPECT 2.0).

The Registry of Fast Myocardial Perfusion Imaging with Next-Generation SPECT (REFINE SPECT) has been expanded to include more patients and CT attenuation correction imaging. We present the design and initial results from the updated registry. Methods: The updated REFINE SPECT is a multicenter, international registry with clinical data and image files. SPECT images were processed by quantitative software and CT images by deep learning software detecting coronary artery calcium (CAC). Patients were followed for major adverse cardiovascular events (MACEs) (death, myocardial infarction, unstable angina, late revascularization). Results: The registry included scans from 45,252 patients from 13 centers (55.9% male, 64.7 ± 11.8 y). Correlating invasive coronary angiography was available for 3,786 (8.4%) patients. CT attenuation correction imaging was available for 13,405 patients. MACEs occurred in 6,514 (14.4%) patients during a median follow-up of 3.6 y (interquartile range, 2.5-4.8 y). Patients with a stress total perfusion deficit of 5% to less than 10% (unadjusted hazard ratio [HR], 2.42; 95% CI, 2.23-2.62) and a stress total perfusion deficit of at least 10% (unadjusted HR, 3.85; 95% CI, 3.56-4.16) were more likely to experience MACEs. Patients with a deep learning CAC score of 101-400 (unadjusted HR, 3.09; 95% CI, 2.57-3.72) and a CAC of more than 400 (unadjusted HR, 5.17; 95% CI, 4.41-6.05) were at increased risk of MACEs. Conclusion: The REFINE SPECT registry contains a comprehensive set of imaging and clinical variables. It will aid in understanding the value of SPECT myocardial perfusion imaging, leverage hybrid imaging, and facilitate validation of new artificial intelligence tools for improving prediction of adverse outcomes incorporating multimodality imaging.

Percutaneous Coronary Intervention Versus Robotic Coronary Bypass for Left Anterior Descending Artery Chronic Total Occlusion

BackgroundBoth percutaneous coronary interventions (PCIs) and robotic-assisted coronary artery bypass (CAB) offer viable options for left anterior descending (LAD) chronic total occlusion (CTO) revascularization. Our study aims to compare long-term clinical outcomes associated with these 2 strategies. MethodsIn this retrospective study, we analyzed data from 273 patients diagnosed with LAD CTO who underwent either PCI (n = 129) or CAB (n = 144) at a single institution. Long-term follow-up was available for 96 PCI and 125 CAB patients. We employed Kaplan-Meier curves and the log-rank test to conduct cumulative survival analyses free of major adverse cardiovascular events (MACE), cumulative survival, survival free of myocardial infarction, and repeat revascularization. ResultsIn the study cohort, patients who underwent PCI exhibited a higher prevalence of comorbidities including diabetes (48.9% vs 24.6%; P < .001), lower ejection fraction (44 ± 14 vs 52 ± 10; P < .001), prior heart failure (36.6% vs 22.2%; P = .02), and prior bypass surgery (16% vs 0, P < .001). PCI to non-LAD vessels was performed as part of initial complete revascularization in 40.3% of PCI and 40.6% of CAB patients. Upon a median 3.4 years of follow-up, CAB patients had significantly higher rates of survival free of MACE compared to PCI patients (unadjusted hazard ratio, 2.39; 95% CI, 1.13-5.03). Although PCI patients had similar unadjusted mortality, they experienced higher myocardial infarction and repeat revascularizations compared to CAB. However, the risk of repeat revascularization was attenuated after adjusting for prior bypass, diabetes, and ejection fraction. ConclusionsAmong patients with LAD CTO, those undergoing robotic-assisted CAB had a higher 5-year overall survival free of MACE compared to those who underwent PCI. This discrepancy in outcomes can be attributed in part to the greater burden of comorbidities among PCI patients.

Risk of Dementia Diagnosis After Injurious Falls in Older Adults

Emerging evidence suggests that mild cognitive impairment, which is a precursor to Alzheimer disease and related dementias (ADRD), places older adults at increased risk for falls. However, the risk that an older adult develops dementia after experiencing a fall is unknown. To determine the risk of new ADRD diagnosis after a fall in older adults. This retrospective cohort study examined Medicare Fee-for-Service data from 2014 to 2015, with follow-up data available for at least 1 year after the index encounter. Participants included adults aged 66 years and older who experienced a traumatic injury that resulted in an emergency department (ED) or inpatient encounter and did not have a preexisting diagnosis of dementia. Data analysis was performed from August 2023 to July 2024. Experiencing a fall compared with other mechanisms of injury, defined by International Classification of Diseases, Ninth Revision (ICD-9) and ICD-10 external cause of injury codes. The hazard of new ADRD diagnosis within 1 year of a fall, assessed by performing a Cox multivariable competing risk model that controlled for potential confounders while accounting for the competing risk of death. The study included 2 453 655 older adult patients who experienced a traumatic injury; 1 522 656 (62.1%) were female; 124 396 (5.1%) were Black and 2 232 102 (91.0%) were White; and the mean (SD) age was 78.1 (8.1) years. The mechanism of injury was a fall in 1 228 847 incidents (50.1%). ADRD was more frequently diagnosed within 1 year of a fall compared with other injury mechanisms (10.6% [129 910 of 1 228 847] vs 6.1% [74 799 of 1 224 808]; P < .001). The unadjusted hazard ratio (HR) of incident dementia diagnosis after a fall was 1.63 (95% CI, 1.61-1.64; P < .001). On multivariable Cox competing risk analysis, falling was independently associated with an increased risk of dementia diagnosis among older adults (HR, 1.21 [95% CI, 1.20-1.21]; P < .001) after controlling for patient demographics, medical comorbidities, and injury characteristics, while accounting for the competing risk of death. Among the subset of older adults without a recent skilled nursing facility admission, the HR was 1.27 (95% CI, 1.26-1.28; P < .001). In this cohort study, new ADRD diagnoses were more common after falls compared with other mechanisms of injury, with 10.6% of older adults being diagnosed with ADRD in the first year after a fall. To improve the early identification of ADRD, this study's findings suggest support for the implementation of cognitive screening in older adults who experience an injurious fall that results in an ED visit or hospital admission.

Patient-Specific Myocardial Infarction Risk Thresholds From AI-Enabled Coronary Plaque Analysis

BACKGROUND: Plaque quantification from coronary computed tomography angiography has emerged as a valuable predictor of cardiovascular risk. Deep learning can provide automated quantification of coronary plaque from computed tomography angiography. We determined per-patient age- and sex-specific distributions of deep learning–based plaque measurements and further evaluated their risk prediction for myocardial infarction in external samples. METHODS: In this international, multicenter study of 2803 patients, a previously validated deep learning system was used to quantify coronary plaque from computed tomography angiography. Age- and sex-specific distributions of coronary plaque volume were determined from 956 patients undergoing computed tomography angiography for stable coronary artery disease from 5 cohorts. Multicenter external samples were used to evaluate associations between coronary plaque percentiles and myocardial infarction. RESULTS: Quantitative deep learning plaque volumes increased with age and were higher in male patients. In the combined external sample (n=1847), patients in the ≥75th percentile of total plaque volume (unadjusted hazard ratio, 2.65 [95% CI, 1.47–4.78]; P =0.001) were at increased risk of myocardial infarction compared with patients below the 50th percentile. Similar relationships were seen for most plaque volumes and persisted in multivariable analyses adjusting for clinical characteristics, coronary artery calcium, stenosis, and plaque volume, with adjusted hazard ratios ranging from 2.38 to 2.50 for patients in the ≥75th percentile of total plaque volume. CONCLUSIONS: Per-patient age- and sex-specific distributions for deep learning–based coronary plaque volumes are strongly predictive of myocardial infarction, with the highest risk seen in patients with coronary plaque volumes in the ≥75th percentile.

Myocardial Scarring and Sudden Cardiac Death in Young Patients With Hypertrophic Cardiomyopathy

The ability to predict sudden cardiac death (SCD) in children and adolescents with hypertrophic cardiomyopathy (HCM) is currently inadequate. Late gadolinium enhancement (LGE) by cardiovascular magnetic resonance (CMR) imaging is associated with SCD events in adults with HCM. To examine the prognostic significance of LGE in patients with HCM who are younger than 21 years. This multicenter, retrospective cohort study was conducted from April 8, 2015, to September 12, 2022, in patients with HCM who were younger than 21 years and had undergone CMR imaging across multiple sites in the US, Europe, and South America. Observers of CMR studies were masked toward outcomes and demographic characteristics. Natural history of HCM. The primary outcome was SCD and surrogate events, including resuscitated cardiac arrest and appropriate discharges from an implantable defibrillator. Continuous and categorical data are expressed as mean (SD), median (IQR), or number (percentage), respectively. Survivor curves comparing patients with and without LGE were constructed by the Kaplan-Meier method, and likelihood of subsequent clinical events was further evaluated using univariate and multivariable Cox proportional hazards models. Among 700 patients from 37 international centers, median (IQR) age was 14.8 (11.9-17.4) years, and 518 participants (74.0%) were male. During a median (IQR) [range] follow-up period of 1.9 (0.5-4.1) [0.1-14.8] years, 35 patients (5.0%) experienced SCD or equivalent events. LGE was present in 230 patients (32.9%), which constituted an mean (SD) burden of 5.9% (7.3%) of left ventricular myocardium. The LGE amount was higher in older patients and those with greater left ventricular mass and maximal wall thickness; patients with LGE had lower left ventricular ejection fractions and larger left atrial diameters. The presence and burden of LGE was associated with SCD, even after correcting for existing risk stratification tools. Patients with 10% or more LGE, relative to total myocardium, had a higher risk of SCD (unadjusted hazard ratio [HR], 2.19; 95% CI, 1.59-3.02; P < .001). Furthermore, the addition of LGE burden improved the performance of the HCM Risk-Kids score (before LGE addition: 0.66; 95% CI, 0.58-0.75; after LGE addition: 0.73; 95% CI, 0.66-0.81) and Precision Medicine in Cardiomyopathy score (before LGE addition: 0.68; 95% CI, 0.49-0.77; after LGE addition: 0.73; 95% CI, 0.64-0.82) SCD predictive models. In this retrospective cohort study, quantitative LGE was a risk factor for SCD in patients younger than 21 years with HCM and improved risk stratification.

In-Hospital Mortality and Treatment in Patients With Acute Coronary Syndrome With and Without Standard Modifiable Cardiovascular Risk Factors: Findings From the CCC-ACS Project.

Patients with acute coronary syndrome without standard modifiable cardiovascular risk factors (SMuRFs; hypertension, smoking, dyslipidemia, diabetes) have not been well studied, with little known about their characteristics, quality of care, or outcomes. We sought to systematically analyze patients with ACS without SMuRFs, especially to evaluate the effectiveness of guideline-directed medical therapy for these patients. In the CCC-ACS (Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome) project (2014-2019), we examined the presence and absence of SMuRFs and features among 89 462 patients with initial acute coronary syndrome. The main outcome was in-hospital all-cause mortality. Among eligible patients, 11.0% had none of the SMuRFs (SMuRF-less). SMuRF-less patients had higher in-hospital mortality (unadjusted hazard ratio [HR], 1.49 [95% CI, 1.19-1.87]). After adjustment for clinical characteristics and treatments, the associations between SMuRF status and in-hospital mortality persisted (adjusted HR, 1.35 [95% CI, 1.07-1.70]). Guideline-directed optimal medical therapy (receiving angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, β-blockers, and statins) was not associated with lower mortality (adjusted HR, 0.98 [95% CI, 0.58-1.67]) in SMuRF-less patients, unlike the association in patients with SMuRFs (adjusted HR, 0.80 [95% CI, 0.66-0.98]). Sensitivity analyses were consistent with these results. SMuRF-less patients were associated with an increased risk of in-hospital mortality. Guideline-directed medical therapy was less effective in SMuRF-less patients than in patients with SMuRFs. Dedicated studies are needed to confirm the optimal therapy for SMuRF-less patients. URL: https://www.clinicaltrials.gov; Unique identifier: NCT02306616.

Endometriosis and Long-Term Cardiovascular Risk: A Nationwide Danish study.

Endometriosis, a systemic gynecological disease affecting 10% of women in reproductive age, shares pathophysiological characteristics with cardiovascular disease. However, data on the relationship between endometriosis and cardiovascular outcomes are scarce, prompting this study to address the knowledge-gap. Using Danish nationwide registries, women diagnosed with endometriosis (1977-2021) were identified and matched with controls in a 1:4 ratio based on year of birth. The primary outcome was a composite of acute myocardial infarction and ischemic stroke. The secondary outcomes were arrhythmias, heart failure, and mortality. In total, 60,508 women with endometriosis and 242,032 matched controls were included (median age 37.3 years). Women with endometriosis were more comorbid and used more medications than controls. The incidence rates of the composite outcomes were 3.2 (95% confidence interval [CI] 3.2-3.3) and 2.7 (95% CI 2.7-2.8) per 1000 person-years among women with and without endometriosis, respectively. Women with endometriosis had a significantly higher associated rate of the composite outcome compared with controls (unadjusted hazard ratio [HR] 1.18 [95% CI 1.14-1.23], adjusted HR 1.15 [95% CI 1.11-1.20]). Likewise, women with endometriosis were also at significantly increased associated risk of arrhythmias (unadjusted HR 1.24 [95% CI 1.20-1.28], adjusted HR 1.21 [95% CI 1.17-1.25]) and heart failure (unadjusted HR 1.16 [95% CI 1.09-1.22], adjusted HR 1.11 [95% CI 1.05-1.18]) but at decreased risk of mortality (unadjusted HR 0.95 [95% CI 0.92-0.97], adjusted HR 0.93 [95% CI 0.91-0.96]). Women with endometriosis have a higher associated long-term risk of cardiovascular outcomes compared with controls. Despite subtle absolute risk-differences, the high prevalence of endometriosis underscores the importance of these findings.

The Association between Preserved Ratio Impaired Spirometry and Depression: Results from a Prospective Population-Based Study

Introduction: The relationship between preserved ratio impaired spirometry (PRISm) and depression remains unclear. This study aimed to assess the bidirectional relationship between PRISm and depression using data from a national cohort. Methods: Data from wave 2 (2004–2005) to wave 4 (2008–2009) of the English Longitudinal Study of Ageing (ELSA) were analyzed. Lung function and depressive symptoms were measured at baseline and follow-up. Cox proportional hazard models were used to calculate the hazard ratio (HR) of PRISm with depression (study 1) and depression with PRISm (study 2). Results: Studies 1 and 2 included 2,934 and 2,277 participants, respectively. The follow-up period extended from wave 2 to wave 4. In univariate analyses, a bidirectional association between PRISm and depression was observed, with unadjusted HRs of 1.49 (95% confidence interval [CI], 1.12–1.99; p = 0.007) in study 1 and 1.69 (95% CI, 1.13–2.52; p = 0.010) in study 2. However, in multivariable Cox models, baseline PRISm was not associated with subsequent depression development (adjusted HR 1.26; 95% CI, 0.94–1.69; p = 0.128). Conversely, participants with depression had a significantly higher risk of developing PRISm compared to those without depression (adjusted HR 1.54; 95% CI, 1.03–2.32; p = 0.038). These findings were consistent with z-score-based interpretive strategies, with an adjusted HR of 1.30 (95% CI, 0.95–1.77; p = 0.105) in study 1 and 1.59 (95% CI, 1.03–2.47; p = 0.038) in study 2. Conclusions: Depression was associated with an increased risk of developing PRISm, whereas PRISm did not increase the risk of developing depression. Physicians should be vigilant for potential PRISm development in patients with depression.

Causes of Excess Mortality in Diabetes Patients Without Coronary Artery Disease: A Cohort Study Revealing Endocrinologic Contributions.

Diabetes mellitus (DM) patients without coronary artery disease (CAD) have a higher all-cause mortality rate than patients with neither DM nor CAD. We examined cause-specific death of DM patients with and without CAD. We conducted a cohort study of all patients who underwent CAG in Western Denmark between 2003 and 2016. Using Danish health registries, patients were followed for a maximum of 10 years and stratified according to their DM and CAD status. Outcomes included all-cause-, cancer-, circulatory-, and endocrinologic death. Ten-year cumulative risks were computed as well as adjusted and unadjusted hazard ratios (aHR and HR). A total of 132,432 patients (28,524 deaths, median follow-up of 6.2 years) were included. Compared to patients with neither DM nor CAD, DM patients without CAD had a higher 10-year risk of all-cause death (27.9% versus 19.7%, aHR 1.43 [95% CI 1.35-1.52]), cancer death (7.2% versus 5.4%, aHR 1.29 [95% CI 1.15-1.46]), circulatory death (9.1% versus 6.9%, aHR 1.35 [95% CI 1.22-1.49]), and endocrinologic death (3.9% versus 0.3%, aHR 14.02 [95% CI 10.95-17.95]). Among endocrinologic deaths, 87% were due to classical complications of DM, such as diabetic nephropathy and ketoacidosis, in DM patients without CAD. Diabetes patients without CAD exhibit a higher risk of all-cause mortality, driven primarily by elevated rates of cancer, circulatory, and endocrinologic deaths, particularly related to diabetic microvascular complications.

Beta-blocker use and outcomes in patients with heart failure and mildly reduced and preserved ejection fraction.

In the absence of randomized trial evidence, we performed a large observational analysis of the association between beta-blocker (BB) use and clinical outcomes in patients with heart failure (HF) and mildly reduced (HFmrEF) and preserved ejection fraction (HFpEF). We pooled individual patient data from four large HFmrEF/HFpEF trials (I-Preserve, TOPCAT, PARAGON-HF, and DELIVER). The primary outcome was the composite of cardiovascular death or HF hospitalization. Among the 16 951 patients included, the mean left ventricular ejection fraction (LVEF) was 56.8%, and 13 400 (79.1%) had HFpEF (LVEF ≥50%). Overall, 12 812 patients (75.6%) received a BB. The median bisoprolol-equivalent dose of BB was 5.0 (Q1-Q3: 2.5-5.0) mg with BB continuation rates of 93.1% at 2 years (in survivors). The unadjusted hazard ratio (HR) for the primary outcome did not differ between BB users and non-users (HR 0.98, 95% confidence interval [CI] 0.91-1.05), but the adjusted HR was lower in BB users than non-users (0.81, 95% CI 0.74-0.88), and this association was maintained across LVEF (pinteraction = 0.88). In subgroup analyses, the adjusted risk of the primary outcome was similar in BB users and non-users with or without a history of myocardial infarction, hypertension, or a baseline heart rate <70 bpm. By contrast, a better outcome with BB use was seen in patients with atrial fibrillation compared to those without atrial fibrillation (pintreraction = 0.02). In this observational analysis of non-randomized BB treatment, there was no suggestion that BB use was associated with worse HF outcomes in HFmrEF/HFpEF, even after extensive adjustment for other prognostic variables.

Overcoming the Disparity in Mitral Valve Repair: A Sex-based Analysis of Long-term Outcomes

Sex-disparities remain pervasive across most cardiovascular diseases and continue to demonstrate significantly worse early and late outcomes for women, especially after surgical repair. This study aims to investigate outcomes of mitral valve (MV) repair by sex and identify opportunities for improvement. A single-centre retrospective analysis of consecutive patients undergoing MV repair was conducted, from May 2008 - February 2023. In-hospital and long-term outcomes, including survival and symptomatic disease recurrence (sMR) were examined by sex. Adjusted outcome analysis was performed using inverse-probability treatment weighting (IPTW). In total, 490 patients underwent MV repair (Median age 65 years [IQR 57-73 years] sternotomy n=128 [26%], minimally-invasive n=362 [74%]), including 343 males and 147 females. Median follow-up time was 5.4 years, with an interquartile range of 3.1 to 8.4 years. IPTW-adjusted 30-day outcomes for female versus males, including death (1.4% vs 0.6%, p=0.59) and MACE (8.2% vs 7.6%, p=0.81), were not significantly different. Survival for females vs males after mitral valve repair was 94.9% vs 98.0% at 2 years, 91.4% vs 97.8% at 4 years and 87.2 % vs 88.7% at 8 years (HR 0.52 [0.19-1.44]). Both unadjusted and IPTW-adjusted Cox-regression hazard ratios for survival and freedom from sMR demonstrated no significant difference between sexes at long-term follow up. These contemporary results are encouraging and suggest that a critical "bridging of the gap" between sexes is possible with comprehensive efforts including earlier detection and awareness and improved surgical techniques, though other factors may be important to explore further.

Impact of cigarette smoking on the outcomes of ST-elevation myocardial infarction after primary percutaneous coronary intervention in metropolitan Tehran

Objective: Although the adverse effects of smoking are well-established, evidence shows a longer survival rate following an acute myocardial infarction (MI) among smokers or the so-called “smoker's paradox”. This study aimed to determine the impact of smoking on the one-year clinical outcomes of ST-elevation myocardial infarction (STEMI) after primary percutaneous coronary intervention (PPCI) in a large registry of the Iranian population. Methods: A total of 3087 patients diagnosed with acute STEMI who underwent PPCI between 2013 and 2018 were enrolled in the study. Patients' smoking status was determined based on self-reported history and categorized into two groups: current smokers and non-smokers. Clinical and angiographic data were collected from the Tehran Heart Center (THC) registry. The primary outcome was one-year of major adverse cardiac and cerebrovascular events (MACCE). The effect of smoking on MACCE was evaluated using a Cox model. Results: From the study population, 1967 (63.7%) were non-smokers, and 1120 (36.3%) were current smokers. Non-smokers had higher rates of prior CABG (5.3%) as well as a higher history of co-morbidities, including a history of diabetes mellitus (46.0%), hypertension (52.7%) and hyperlipidemia (55.4%) than smokers (2.3%, 30.4%, 35.7%, and 49.8% respectively). Smokers had a higher reference vessel diameter than non-smokers (P=0.005). The unadjusted hazard ratios (HRs) for MACCE within one year were significantly lower in smokers than non-smokers (0.73, 95% CI: [0.58,0.92]; P=0.009); however, after adjustment for confounders, the HRs for MACCE in smokers were similar to non-smokers (HR: 1.00, 95% CI: [0.73,1.38]). Conclusion: The study found that smoking had no significant impact on the one-year clinical outcomes of STEMI patients after PPCI in the Iranian population. This study is the first of its kind to assess the effect of smoking on STEMI patients in Iran and highlights the need for further research in this area.

Decreasing chronic graft-versus-host disease rates in all populations

AbstractSince 2005, there has been a steady decline in chronic graft-versus-host disease (cGVHD) at the Fred Hutchinson Cancer Center. To better understand this phenomenon, we studied the risk of cGVHD requiring systemic immunosuppression (cGVHD-IS) as a function of hematopoietic cell transplantation (HCT) date in 3066 survivors from 2005 through 2019. Cox regression models were fit to assess associations of HCT date (as a continuous linear variable) with cause-specific hazards of cGVHD using unadjusted and adjusted models. Median follow-up for study subjects was 7.0 years (range, 1.0-17.2). Two-year probabilities of cGVHD-IS declined among all survivors from 45% to 52% (2005-2007) to ∼40% (2008-2012) and then further to ∼26% by 2017. A decline was also observed when the analysis was restricted to 502 pediatric survivors, with cGVHD-IS probabilities <10% since 2013. Among 305 adult and pediatric survivors who underwent transplantation for nonmalignant diseases, cGVHD rates showed greater fluctuation but remained <20% after 2016. Each 5-year increase in HCT date was associated with a 27% decrease in the cause-specific hazard of cGVHD (unadjusted hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.68-0.78; P < .0001); the HR was 0.81 (95% CI, 0.75-0.87; P < .0001) even after adjusting for various factors (age, donor/stem-cell source, race, sex, conditioning intensity, GVHD prophylaxis, among others) that could lead to cGVHD reduction. The decline in cGVHD was not fully explained by demographic shifts and greater use of HCT approaches that are generally associated with lower cGVHD rates. This observation underscores that single-cohort cGVHD prevention studies should use contemporaneous and not historical controls for comparison.

Elevated plasma hepcidin concentrations are associated with an increased risk of mortality and nonfatal cardiovascular events in patients with type 2 diabetes: a prospective study

BackgroundThe effect of plasma hepcidin concentrations on the long-term risk of developing adverse cardiovascular outcomes in people with type 2 diabetes mellitus (T2DM) is unclear.MethodsWe followed for a median of 55.6 months 213 outpatients with established T2DM (45.5% women, mean age 69 ± 10 years; BMI 28.7 ± 4.7 kg/m2; median diabetes duration 11 years). Baseline plasma ferritin and hepcidin concentrations were measured with an electrochemiluminescence immunoassay and mass spectrometry-based assay, respectively. The primary study outcome was a composite of all-cause mortality or incident nonfatal cardiovascular events (inclusive of myocardial infarction, permanent atrial fibrillation, ischemic stroke, or new hospitalization for heart failure).Results42 patients developed the primary composite outcome over a median follow-up of 55.6 months. After stratifying patients by baseline hepcidin tertiles [1st tertile: median hepcidin 1.04 (IQR 0.50–1.95) nmol/L, 2nd tertile: 3.81 (IQR 3.01-4-42) nmol/L and 3rd tertile: 7.72 (IQR 6.37–10.4) nmol/L], the risk of developing the primary composite outcome in patients in the 3rd tertile was double that of patients in the 1st and 2nd tertile combined (unadjusted hazard ratio [HR] 2.32, 95%CI 1.27–4.26; p = 0.007). This risk was not attenuated after adjustment for age, sex, adiposity measures, smoking, hypertension, statin use, antiplatelet medication use, plasma hs-C-reactive protein and ferritin concentrations (adjusted HR 2.53, 95%CI 1.27–5.03; p = 0.008).ConclusionsIn outpatients with T2DM, higher baseline hepcidin concentrations were strongly associated with an increased long-term risk of overall mortality or nonfatal cardiovascular events, even after adjustment for established cardiovascular risk factors, plasma ferritin concentrations, medication use, and other potential confounders.