Crude HR Research Articles

Long-term outcomes in patients with dual pathology aortic stenosis and cardiac amyloidosis referred for valve intervention

Abstract Background The coexistence of aortic stenosis (AS) and cardiac amyloidosis (CA) is common. If treated with transcatheter aortic valve implantation (TAVI), patients with the combined phenotype (AS-CA) have a comparable short term survival to those with lone AS, whereas data on longer term outcomes is currently lacking. Purpose This study aimed to evaluate the clinical outcomes of AS-CA compared to lone AS over a 5-year follow-up. Methods Using a prospective, multicentre, observational, case-control design, we screened consecutive patients with severe AS referred for TAVI for co-existing CA. CA screening included blinded 99mTc-DPD bone scintigraphy (Perugini Grade-0 negative, 1-3 increasingly positive) with additional SPECT/CT and light chain assessment prior to intervention. Transthyretin CA (ATTR) was diagnosed by bone scintigraphy and unremarkable light chain assessment, light-chain CA (AL) by endomyocardial biopsy. Mortality (all-cause and cardiovascular [CV]) and hospitalisation for heart failure (HHF) were captured as clinical endpoints. Results 376 patients (83±7 years, 52% female, EuroSCORE-II 4.9±2.9) were recruited, of which 43 (11.4%) had AS-CA (42 ATTR, 1 AL). Compared to lone AS, patients with AS-CA were older with higher cardiac biomarkers (NT-proBNP, high-sensitive Troponin-T) and a higher prevalence of atrial fibrillation. Heart team decision yielded valve replacement in 320 (85%) and conservative management in 56 (15%) patients, without differences between AS-CA and lone AS. Over a median follow-up of 5.4 (Q1: 4.9; Q3: 5.7) years, 230 (61.1%) patients died and 67 (17.8%) experienced HHF (with a total HHF number of 91). AS-CA was associated with higher all-cause mortality (crude HR 1.64, 95%CI 1.15-2.35; log-rank, p=0.006), which remained significant after multivariate adjustment for clinical confounders (EuroSCORE-II, valve replacement; adjusted HR 1.63, 95%CI 1.15-2.32; p=0.006). AS-CA was not associated with CV mortality (log-rank, p=0.18) or time to first HHF (log-rank, p=0.43), but the rate of HHF was significantly higher in AS-CA compared to lone AS (5.7 versus 3.5 per 1,000 patient years, p=0.022). Conclusions Among elderly patients referred for TAVI, long-term outcomes of AS-CA are characterized by higher mortality and a higher rate of heart failure hospitalisations compared to patients with lone AS. Studies evaluating the role of CA-specific treatments are warranted in this population.

Neurodegeneration is highly associated with comorbidity burden in HFrEF patients

Abstract Background Heart failure (HF) is associated with cognitive decline and risk for dementia. Blood levels of amyloid beta 40 and 42 (Aβ40, Aβ42), tau protein (tau), and neurofilament light chain (NfL) have been found to be altered in neurodegenerative disease. Previous research has established a clear association between these neuromarkers and the risk of developing cognitive dysfunction and mortality in the general population. Objective The aim of this study was to investigate the association between the respective neuromarkers and comorbidity burden, as well as to explore whether comorbidity burden impacts the relationship between neuromarkers and outcome in HF patients. Methods Plasma levels of Aβ40, Aβ42, tau, and NfL were quantified using a single-molecule array assay. The primary outcome parameter was all-cause mortality. Results A total of 470 HFrEF patients were enrolled in the study, with a median age of 62 years (IQR: 52–72); 77% were male. Median NT-proBNP concentration was 1812 pg/ml (IQR: 718–3881). Elevated levels of all biomarkers were closely associated with comorbidity burden (Figure 1). All neuromarkers showed increased levels in individuals with chronic kidney disease (CKD) and known carotid artery stenosis (CAS), except for Aβ40, which did not show significant elevation in CAS (NfL: p<0.001 for both; t-tau: p<0.001 and p=0.041; Aβ40: p<0.001 and p=0.050; Aβ42: p<0.001 and p=0.033, respectively). In patients with type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD), only NfL levels were significantly elevated (p<0.001 for both), whereas atrial fibrillation (AF) was associated with higher levels of NfL and t-tau (p<0.001 for both). In individuals with iron deficiency, only Aβ42 levels were significantly higher (p=0.025). All biomarkers showed significant associations with all-cause mortality [crude HR for an increase in 1-log unit (95%CI): NfL 4.44 (3.02-6.53), t-tau 5.04 (2.97-8.58), Aβ40 3.90 (2.27-6.72), Aβ42 5.14 (2.84-9.32); p<0.001 for all] (Figure 2). These associations remained statistically significant after adjusting for comorbidity burden including AF, T2DM, CAD, CKD, CAS and ID [adjusted HR for an increase in 1-log unit (95%CI): NfL 3.28 (1.93-5.57), t-tau 3.96 (2.07-7.57), Aβ40 2.42 (1.34-4.38), Aβ42 3.05 (1.56-5.97); p<0.01 for all]. Conclusion The findings suggest a close connection between elevated levels of markers of neurodegeneration and increased comorbidity burden in HFrEF patients. While this association may indicate the cumulative risk leading to neuronal injury and HFrEF progression, a causal relationship cannot be excluded. The observed accelerated neurodegeneration in HFrEF underscores the need for further investigation into this complex interplay.Figure 1Figure 2

Relationship between enteral nutrition timing and 28-day mortality in critically ill stroke patients in the MIMIC-IV database.

The ideal timing for commencing enteral nutrition (EN) in critically ill stroke patients in the intensive care unit (ICU) remains a subject of debate, with ongoing controversy regarding the impact of early EN (EEN) initiation. In this study, we investigated the association between the timing of EN initiation and 28-day mortality using data from the MIMIC-IV database. This study employed a retrospective cohort design using the MIMIC-IV database to identify stroke patients who received EN during their hospital stay. The main focus of this investigation was to examine 28-day mortality among these patients following hospital admission. Various demographic, clinical, laboratory, and intervention variables were considered as covariates. The Cox regression analysis was employed to assess the correlation between the timing of EN initiation and 28-day mortality, and restricted cubic splines (RCS) analysis was used to test for non-linear correlation. Patients were then stratified into two cohorts depending on the timing of EN initiation: within 2 days (n = 564) and beyond 2 days (n = 433). A multivariate Cox regression analysis was used to investigate the difference in 28-day mortality between the groups. A total of 997 participants were included in this study, with 318 (31.9%) dying within 28 days. We observed that the timing of EN initiation correlated with 28-day mortality, but this correlation was not significant after adjusting for covariates (crude HR: 0.94, 95% CI: 0.88-1, p = 0.044; adjusted HR: 0.96, 95% CI: 0.9-1.02, p = 0.178). The RCS analysis showed that the correlation was not non-linear. Notably, in the multivariate regression models, early EN initiation was associated with a higher mortality rate compared to late EN initiation [odds ratio (OR) = 1.34, 95% CI: 1.06-1.67, p = 0.012]. After adjusting for various confounding factors in the multivariate Cox regression models, we identified that patients in the early EN group had a 28% higher risk of mortality than those in the reference group (OR = 1.27, 95% CI: 1-1.61, p = 0.048). These associations remained consistent across various patient characteristics, as revealed through stratified analyses. Early commencement of EN in critically ill stroke patients may be linked to a higher risk of 28-day mortality, highlighting the need for further investigation and a more nuanced consideration of the optimal timing for commencing EN in this patient population.

Cardiovascular and All-Cause Mortality Is Affected by Serum Magnesium and Diet Pattern in a Cohort of Dialysis Patients.

Background: Hypomagnesaemia is associated with an increased overall mortality in patients with chronic kidney disease on dialysis (CKD-5D). Mediterranean-style diet (MD), having a high magnesium content, can serve as a form of dietary magnesium supplementation. We examined whether there is a potential link between increased Mediterranean Diet score (MDS) and elevated serum magnesium (sMg) to assess its impact on reducing mortality risk in CKD-5D patients. Methods: In this multi-center prospective observational study, 117 CKD-5D patients (66 on hemodialysis and 51 on peritoneal dialysis) with a mean age of 62 ± 15 years were studied for a median follow-up period of 68 months. After baseline assessment, including measurement of sMg and MDS, all patients were followed up for cardiovascular (CV) and all-cause mortality. Results: Forty deaths occurred, 58% of which were cardiovascular. Patients who were above the median value of sMg (2.2 mg/dL) had a 66% reduction in CV (crude HR, 0.34; 95% CI, 0.11-0.70), and 49% reduction in all-cause (crude HR, 0.51; 95% CI, 0.27-0.96) mortality, even after adjustment for age, malnutrition inflammation score, left ventricular mass index, peripheral vascular disease and diabetes. Similar results were obtained when sMg was analyzed as a continuous variable. sMg was associated directly with MDS (r = 0.230; p = 0.012). Conclusions: Higher sMg levels are strongly and independently associated with reduced CV and all-cause mortality in CKD-5D patients. A strong correlation exists between MDS and sMg. Elevated sMg levels, achieved through MD adherence, can significantly reduce CV mortality, implicating MD as a mediator of the association between sMg and CV mortality.

Red cell distribution width and prognosis in myelofibrosis patients treated with ruxolitinib.

We evaluated RDW in a single-center series of 61 consecutive patients with primary and secondary MF at diagnosis and during treatment with ruxolitinib (RUX) and examined any possible prognostic impact. Elevated RDW values were present in all but 4 patients at diagnosis with a median RDW of 18.9%. RDW was higher in subjects with palpable splenomegaly (p = 0.02), higher ferritin, as well as among those cases who did not receive any cytoreduction before RUX (p = 0.04). Interestingly, higher RDW at diagnosis also correlated with a shorter time from MF diagnosis to RUX start (-4.1 months per one RDW unit; p = 0.03). We observed a modest increase (< 1%) in RDW during the first 6 months of RUX treatment. In a multivariable random-intercept model that considered all time points and contained the covariates time and RUX dose, we also observed a clear decrease in RDW with increasing hemoglobin (Hb) during RUX (slope: -0.4% per g/dL of Hb; p < 0.001). The median RDW at diagnosis of 18.9% was used as a cut-off to identify two subgroups of patients [Group 1: RDW 19.0-25.7%; Group 2: RDW 13.1-18.7%], showing a difference in mortality [Group 1 vs. 2: crude HR 2.88; p = 0.01]. Using continuous RDW at diagnosis, the crude HR was 1.21 per RDW unit (p = 0.002). In a Cox model adjusted for gender, age and Hb at diagnosis, the HR was 1.13 per RDW unit (p = 0.07). RDW may have prognostic significance at MF diagnosis and during RUX, helping in the rapid detection of patients with poor prognosis.

Prospective risk of Type 2 diabetes in 99892 Nordic women with polycystic ovary syndrome and 446055 controls: national cohort study from Denmark, Finland, and Sweden.

What is the prospective risk of Type 2 diabetes (T2D) in Nordic women with polycystic ovary syndrome (PCOS) compared to controls? A diagnosis of PCOS and BMI ≥30 kg/m2 is a high-risk phenotype for a prospective risk of T2D diagnosis across Nordic countries. The risk of T2D in women with PCOS is increased. The risk of T2D is related to BMI and the magnitude of risk in normal weight women with PCOS has been discussed. However, prospective data regarding risk of T2D in population-based cohorts of women with PCOS are limited. This national register-based study included women with PCOS and age-matched controls. The main study outcome was T2D diagnosis occurring after PCOS diagnosis. T2D was defined according to ICD-10 diagnosis codes and/or filled medicine prescriptions of anti-diabetic medication excluding metformin. The study cohort included women originating from Denmark (PCOS Denmark, N = 27016; controls, N = 133994), Finland (PCOS Finland, N = 20467; controls, N = 58051), and Sweden (PCOS Sweden, N = 52409; controls, N = 254010). The median age at cohort entry was 28 years in PCOS Denmark, Finland, and Sweden with a median follow-up time (interquartile range) in women with PCOS of 8.5 (4.0-14.8), 9.8 (5.1-15.1), and 6.0 (2.0-10.0) years, respectively. Cox regression analyses were adjusted for BMI and length of education. The crude hazard ratio (HR, 95% CI) for T2D diagnosis in women with PCOS was 4.28 (3.98-4.60) in Denmark, 3.40 (3.11-3.74) in Finland, and 5.68 (5.20-6.21) in Sweden. In adjusted regression analyses, BMI ≥30 vs <25 kg/m2 was associated with a 7.6- to 11.3-fold risk of T2D. In a combined meta-analysis (PCOS, N = 99892; controls, N = 446055), the crude HR for T2D in PCOS was 4.64 (3.40-5.87) and, after adjustment for BMI and education level, the HR was 2.92 (2.32-3.51). Inclusion of more severe cases of PCOS in the present study design could have lead to an overestimation of risk estimates in our exposed population. However, some women in the control group would have undiagnosed PCOS, which would lead to an underestimation of T2D risk in women with PCOS. BMI data were not available for all participants. The present study should be repeated in study cohorts with higher background risks of T2D, particularly in populations of other ethnicities. The prospective risk for diagnosis of T2D is increased in women with PCOS, and the risk is aggravated in women with BMI ≥30 kg/m2. Funding in Denmark was from the Region of Southern Denmark, Overlægerådet, Odense University Hospital. Funding in Finland was from Novo Nordisk Foundation, Finnish Research Council and Sigrid Juselius Foundation, the National Regional Fund, Sakari Alhopuro Foundation and Finnish Diabetes Research Foundation. E.E. has received a research grant from Ferring Pharmaceuticals (payment to institution) and serves as medical advisor for Tilly AB, not related to this manuscript. The remaining authors declare no conflict of interest. N/A.

Abstract 2194: Association of metabolic syndrome conditions with risk of second primary cancer of any organ in breast cancer survivors

Abstract Purpose: Breast cancer survivors are at increased risk of developing second primary cancers; however, factors attributing to increased risk of second primary cancer in breast cancer survivors are under-studied. We evaluated the association of metabolic syndrome conditions with second primary cancer of any organ in breast cancer survivors. Methods: In this retrospective cohort study, we included 37,222 patients diagnosed with breast cancer between 2008-2020 at Kaiser Permanente Southern California (KPSC), an integrated healthcare system. We extracted data on cancer-related variables, sociodemographic and clinical variables from KPSC’s cancer registry and electronic health records. Among the metabolic conditions, we identified diabetes, hypertension, and dyslipidemia using ICD-10 diagnosis codes at or 1-year prior to breast cancer diagnosis; obesity was based on body mass index (BMI≥30kg/m2). We included metabolic syndrome as a categorical variable: 0, 1-2, and 3+ metabolic conditions. We followed patients electronically from breast cancer diagnosis until patients developed second primary cancer of any organ, died, disenrolled from the health plan, or reached study’s end (12/31/2021), whichever occurred first. Proportional hazards regression was used to report association [HR (95%CI)] between metabolic conditions and any second primary cancer. Results: During a median (IQR) follow-up of 5.17 (2.75-8.58) years, 1701 (4.6%) patients developed any second primary cancer. More than half (53.1%) of the breast cancer survivors had 1-2 metabolic conditions at baseline; 19.4% had 3+ metabolic conditions, and the rest 27.5% did not have any metabolic condition. Hypertension was the most common metabolic condition (45.5%), followed by obesity (38.9%), dyslipidemia (36.5%), and diabetes (19.0%). Survivors with 0 and 1-2 metabolic conditions were 35% and 19% less likely to develop any second primary cancer than survivors with 3+ metabolic conditions, respectively [crude HR (95%CI): 0.65 (0.57-0.75) and 0.81 (0.72-0.91), respectively]. Reduced risk in survivors with 1-2 metabolic conditions persisted adjusting for age, race and ethnicity, breast cancer diagnosis year, breast tumor SEER summary stage, breast tumor estrogen-progesterone status, smoking status, and breast tumor treatment [adjusted HR (95%CI): 0.87 (0.77-0.99)]. Conclusion: Risk of second primary cancer of any organ was elevated in breast cancer survivors with three or more metabolic conditions. Citation Format: Amrita Mukherjee, Zheng Gu, Lie Hong Chen, Arnold L. Potosky, Reina Haque. Association of metabolic syndrome conditions with risk of second primary cancer of any organ in breast cancer survivors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2194.

BIRC5 expression by race, age and clinical factors in breast cancer patients

PurposeSurvivin/BIRC5 is a proliferation marker that is associated with poor prognosis in breast cancer and an attractive therapeutic target. However, BIRC5 has not been well studied among racially diverse populations where aggressive breast cancers are prevalent.Experimental designWe studied BIRC5 expression in association with clinical and demographic variables and as a predictor of recurrence in 2174 participants in the Carolina Breast Cancer Study (CBCS), a population-based study that oversampled Black (n = 1113) and younger (< 50 years; n = 1137) participants with breast cancer. For comparison, similar analyses were conducted in The Cancer Genome Atlas [TCGA N = 1094, Black (n = 183), younger (n = 295)]. BIRC5 was evaluated as a continuous and categorical variable (highest quartile vs. lower three quartiles).ResultsUnivariate, continuous BIRC5 expression was higher in breast tumors from Black women relative to non-Black women in both estrogen receptor (ER)-positive and ER-negative tumors and in analyses stratified by stage (i.e., within Stage I, Stage II, and Stage III/IV tumors). Within CBCS and TCGA, BIRC5-high was associated with young age (< 50 years) and Black race, as well as hormone receptor-negative tumors, non-Luminal A PAM50 subtypes, advanced stage, and larger tumors (> 2 cm). Relative to BIRC5-low, BIRC5-high tumors were associated with poor 5-year recurrence-free survival (RFS) among ER-positive tumors, both in unadjusted models [HR (95% CI): 2.7 (1.6, 4.6)] and after adjustment for age and stage [Adjusted HR (95% CI): 1.87 (1.07, 3.25)]. However, this relationship was not observed among ER-negative tumors [Crude HR (95% CI): 0.7 (0.39, 1.2); Adjusted HR (95% CI): 0.67 (0.37, 1.2)].ConclusionBlack and younger women with breast cancer have a higher burden of BIRC5-high tumors than older and non-Black women. Emerging anti-survivin treatment strategies may be an important future direction for equitable breast cancer outcomes.

Prognostic implication of residual inflammatory trajectories in acute type I aortic dissection: dual-center prospective cohort study.

Peripheral platelet-white blood cell ratio (PWR) integrating systemic inflammatory and coagulopathic pathways is a key residual inflammatory measurement in the management of acute DeBakey type I aortic dissection (AAD); however, trajectories of PWR in AAD is poorly defined. Two AAD cohorts were included in two cardiovascular centers (2020-2022) if patients underwent emergency total arch replacement with frozen elephant trunk implantation. PWR data were collected over time at baseline and five consecutive days after surgery. Trajectory patterns of PWR were determined using the latent class mixed modelling (LCMM). Cox regression was used to determine independent risk factors. By adding PWR Trajectory, a user-friendly nomogram was developed for predicting mortality after surgery. Two hundred forty-six patients with AAD were included with a median follow-up of 26 (IRQ 20-37) months. Three trajectories of PWR were identified [cluster α 45(18.3%), β105 (42.7%), and γ 96 (39.0%)]. Cluster γ was associated with higher risk of mortality at follow-up (crude HR, 3.763; 95% CI: 1.126-12.574; P =0.031) than cluster α. By the addition of PWR trajectories, an inflammatory nomogram, composed of age, hemoglobin, estimated glomerular filtration rate, and cardiopulmonary time was developed and internally validated, with adequate discrimination [the area under the receiver-operating characteristic curve 0.765, 95% CI: 0.660-0.869)], calibration, and clinical utility. Based on PWR trajectories, three distinct clusters were identified with short-term outcomes, and longitudinal residual inflammatory shed some light to individualize treatment strategies for AAD.

A retrospective cohort study on early antibiotic use in vaccinated and unvaccinated COVID-19 patients.

The bacteriophage behavior of SARS-CoV-2 during the acute and post-COVID-19 phases appears to be an important factor in the development of the disease. The early use of antibiotics seems to be crucial to inhibit disease progression-to prevent viral replication in the gut microbiome, and control toxicological production from the human microbiome. To study the impact of specific antibiotics on recovery from COVID-19 and long COVID (LC) taking into account: vaccination status, comorbidities, SARS-CoV-2 wave, time of initiation of antibiotic therapy and concomitant use of corticosteroids and nonsteroidal anti-inflammatory drugs (NSAIDs). A total of 211 COVID-19 patients were included in the study: of which 59 were vaccinated with mRNA vaccines against SARS-CoV-2 while 152 were unvaccinated. Patients were enrolled in three waves: from September 2020 to October 2022, corresponding to the emergence of the pre-Delta, Delta, and Omicron variants of the SARS-CoV-2 virus. The three criteria for enrolling patients were: oropharyngeal swab positivity or fecal findings; moderate symptoms with antibiotic intake; and measurement of blood oxygen saturation during the period of illness. The use of antibiotic combinations, such as amoxicillin with clavulanic acid (875 + 125 mg tablets, every 12 h) plus rifaximin (400 mg tablets every 12 h), as first choice, as suggested from the previous data, or azithromycin (500 mg tablets every 24 h), plus rifaximin as above, allows healthcare professionals to focus on the gut microbiome and its implications in COVID-19 disease during patient care. The primary outcome measured in this study was the estimated average treatment effect, which quantified the difference in mean recovery between patients receiving antibiotics and those not receiving antibiotics at 3 and 9 days after the start of treatment. In the analysis, both vaccinated and unvaccinated groups had a median illness duration of 7 days (interquartile range [IQR] 6-9 days for each; recovery crude hazard ratio [HR] = 0.94, p = 0.700). The median illness duration for the pre-Delta and Delta waves was 8 days (IQR 7-10 days), while it was shorter, 6.5 days, for Omicron (IQR 6-8 days; recovery crude HR = 1.71, p < 0.001). These results were confirmed by multivariate analysis. Patients with comorbidities had a significantly longer disease duration: median 8 days (IQR 7-10 days) compared to 7 days (IQR 6-8 days) for those without comorbidities (crude HR = 0.75, p = 0.038), but this result was not confirmed in multivariate analysis as statistical significance was lost. Early initiation of antibiotic therapy resulted in a significantly shorter recovery time (crude HR = 4.74, p < 0.001). Concomitant use of NSAIDs did not reduce disease duration and in multivariate analysis prolonged the disease (p = 0.041). A subgroup of 42 patients receiving corticosteroids for a median of 3 days (IQR 3-6 days) had a longer recovery time (median 9 days, IQR 8-10 days) compared to others (median 7 days, IQR 6-8 days; crude HR = 0.542, p < 0.001), as confirmed also by the adjusted HR. In this study, a statistically significant reduction in recovery time was observed among patients who received early antibiotic treatment. Early initiation of antibiotics played a crucial role in maintaining higher levels of blood oxygen saturation. In addition, it is worth noting that a significant number of patients who received antibiotics in the first 3 days and for a duration of 7 days, during the acute phase did not develop LC.

CILP-1 Is a Biomarker for Backward Failure and Right Ventricular Dysfunction in HFrEF.

CILP-1 regulates myocardial fibrotic response and remodeling and was reported to indicate right ventricular dysfunction (RVD) in pulmonary hypertension (PH) and heart failure (HF). This study examines CILP-1 as a potential biomarker for RVD and prognosis in heart failure with reduced ejection fraction (HFrEF) patients on guideline-directed medical therapy. CILP-1 levels were measured in 610 HFrEF patients from a prospective registry with biobanking (2016-2022). Correlations with echocardiographic and hemodynamic data and its association with RVD and prognosis were analyzed. The median age was 62 years (Q1-Q3: 52-72), 77.7% of patients were male, and the median NT-proBNP was 1810 pg/mL (Q1-Q3: 712-3962). CILP-1 levels increased with HF severity, as indicated by NT-proBNP and NYHA class (p < 0.0001, for both). CILP-1 showed a weak-moderate direct association with increased left ventricular filling pressures and its sequalae, i.e., backward failure (LA diameter rs = 0.15, p = 0.001; sPAP rs = 0.28, p = 0.010; RVF rs = 0.218, p < 0.0001), but not with cardiac index (CI) and systemic vascular resistance (SVR). CILP-1 trended as a risk factor for all-cause mortality (crude HR for 500 pg/mL increase: 1.03 (95%CI: 1.00-1.06), p = 0.053) but lost significance when it was adjusted for NT-proBNP (adj. HR: 1.00 (95%CI: 1.00-1.00), p = 0.770). No association with cardiovascular hospitalization was observed. CILP-1 correlates with HFrEF severity and may indicate an elevated risk for all-cause mortality, though it is not independent from NT-proBNP. Increased CILP-1 is associated with backward failure and RVD rather than forward failure. Whether CILP-1 release in this context is based on elevated pulmonary pressures or is specific to RVD needs to be further investigated.

Abstract 14990: A Propensity Score Analysis of Five-Year Outcomes After Coronary Thrombus Aspiration in Acute Myocardial Infarction: Insights From the FAST-MI Real-Life Registry

Introduction: Though previous trials and registries have shown no short-term benefit of thrombectomy in acute myocardial infarction (AMI), data on long-term outcomes are lacking. Hypothesis: Use of coronary thrombectomy in real-life conditions does not affect 5-year outcome. Methods: FAST-MI program consists of 3 nationwide French surveys (2005, 2010, 2015), including consecutive AMI patients over a 1-month period. This analysis focused on patients undergoing percutaneous coronary intervention (PCI, N=9,731). Five-year follow-up is &gt;96%. Results: Thrombectomy was used in 1,781 patients (18%; 2005: 7%, 2010: 27%, 2015: 18%), 87% of them had STEMI. They were younger (61±13 vs 65±14 yo), mostly men (81% vs 74%, p&lt;0.001), with less multivessel coronary artery disease (47% vs 55%, P&lt;0.001) and a culprit lesion mostly on the right coronary artery (40% vs 31%, P&lt;0.001). Crude in-hospital death was higher with thrombectomy (3.1% vs 2.0%, P=0.005) but 5-year death lower (13% vs 17%, P&lt;0.001; crude HR 0.74 [95%CI 0.66-0.82]). After adjustment on the propensity score (PS) for getting thrombectomy, OR for in-hospital death was 1.24[95%CI 0.82-1.87] and HR for 5-year death: 0.95 [95%CI 0.79-1.14], P=0.58. In hospital survivors, Cox multivariate adjustment including discharge medications yielded similar results (HR 0.96, 95%CI 0.76-1.21, P=0.73). After PS matching, the two cohorts (N=1,430 each) had even distributions for all baseline characteristics and medications. In-hospital death was similar (2.7% vs 2.6%, P=0.91) but stroke was numerically higher (0.8% vs 0.3%, P=0.13) with thrombectomy. Five-year survival was similar in the 2 cohorts: HR 0.93, 95%CI 0.75-1.14, P=0.46. (Figure) Conclusions: These real-world data show that the use of thrombectomy has increased until 2010 and declined thereafter, in keeping with international guidelines, and suggest that thrombectomy has no beneficial nor detrimental effect on long-term survival compared to PCI alone.

Development of a plasma-free amino acid-based risk score for the incidence of cardiovascular diseases in a general population: The Nagahama study

Levels of circulating amino acids (AAs) have been suggested to be associated with cardiovascular diseases (CVDs). This study aimed to develop a plasma-free amino acid (PFAA)-based CVD risk-prediction model in a general population. The study participants consisted of 9220 community residents (mean age, 53.2 years; standard deviation, 13.3 years). Circulating levels of 19 PFAAs were measured via high-performance liquid chromatography/electrospray ionization mass spectrometry. The incidence of CVDs was determined by reviewing participants' clinical records. The prediction model was developed using the Cox proportional hazards model with the brute force variable selection and then cross-validated. During the 8.5-year follow-up, 220 CVD events were observed. Six AAs (alanine, citrulline, glycine, histidine, serine, and tyrosine) were identified as components of the prediction model, of which the C-index was 0.72. The association between the fourth quartile of the risk score calculated using the prediction model and the CVD events was independent of conventional risk factors (adjusted hazard ratio [HR], 1.9; 95% confidence interval, 1.1-3.3). When examining crude relationships between conventional risk factors and the PFAA-based risk score by subgroup analyses, the association was significant for most subpopulations, men [crude HR=6.4 (2.0-20.2)] and women [crude HR=4.9 (2.6-9.3)], and individuals with [crude HR=4.7 (2.5-8.9)] and without [crude HR=7.2 (2.7-18.9)] lifestyle-related diseases, but not for older (≥70 years) participants [crude HR=3.3 (0.8-13.5)]. The risk score successfully identified at-risk individuals [HR=2.1 (1.2-3.5)] from participants who were classified as low risk by a conventional CVD risk score. The PFAA-based risk score predicted CVD events independently of conventional risk factors.

Comparison between interventional versus medical therapy in patients with rheumatic mitral valve stenosis in Tanzania.

Rheumatic heart disease remains the most common cardiovascular disease in children and young adults. The outcome of interventional versus medical therapy on the long term is not fully elucidated yet. This study provides contemporary data on the clinical profile, treatment and follow up of patients with rheumatic mitral stenosis (MS) in Tanzania. Patients' medical information, investigations and treatment data were recorded in this prospective cohort study. They were followed up for 6-24 months to determine the long-term outcome. Interventional therapy was defined as a combination of surgery and percutaneous balloon mitral valvuloplasty. Kaplan-Meier curves and Cox proportional hazards model were used in analyses. p-Value < 0.05 was considered statistically significant. We enrolled 290 consecutive patients. Interventions were done in half of the patients. Median follow up was 23.5 months. Mortality was higher in the medical than interventional treatment (10.4% vs. 4%, log-rank p = 0.001). Median age was 36 years, females (68.3%) and low income (55.5%). Multivalvular disease was found in 116 (40%) patients, atrial fibrillation (31.4%), stroke/transient ischaemic attack (18.9%) and heart failure class III-IV (44.1%). Median (IQR) duration of disease was 3 (4) years, secondary prophylaxis (27.7%) and oral anticoagulants use (62.3%). In multivariable analysis, the risk of death among patients on medical was 3.07 times higher than those on interventional treatment (crude HR 3.07, 95% CI 1.43-6.56, p = 0.004), 2.44 times higher among patients with arrhythmias versus without arrhythmias (crude HR 2.44, 95% CI 1.19-4.49, p = 0.015) and 2.13 times higher among patients with multivalvular than single valve disease (crude HR 2.13, 95% CI 1.09-4.16, p = 0.026). Intervention is carrying low mortality compared to medical treatment. Arrhythmias and multivalvular disease are associated with a high mortality. Rheumatic MS is more prevalent in young people, females and individuals with low income. There is a late hospital presentation and a low use of both secondary prophylactic antibiotics and anticoagulants.

Association between Red Cell Distribution Width and Outcomes of Nonagenarians Admitted to the Intensive Care Unit-A Retrospective Cohort Study.

The red cell distribution width (RDW) measures the heterogeneity of the erythrocyte volume. Different clinical conditions are associated with increased RDW, and high levels (>14.5%) have been described as a predictive marker for unfavorable outcomes and mortality in critically ill patients. However, there is a lack of data on very elderly critically ill patients. Therefore, we aimed to investigate the association of RDW with outcomes in critically ill patients ≥ 90 years. A retrospective analysis was conducted for all consecutive critically ill patients ≥ 90 years who were admitted to the Department of Intensive Care Medicine of the Medical University Centre Hamburg-Eppendorf (Hamburg, Germany) with available RDW on admission. Clinical course and laboratory were analyzed for all patients with eligible RDW. High RDW was defined as (>14.5%). We clinically assessed factors associated with mortality. Univariable and multivariable Cox regression analysis was performed to determine the prognostic impact of RDW on 28-day mortality. During a 12-year period, we identified 863 critically ill patients ≥ 90 years old with valid RDW values and complete clinical data. In total, 32% (n = 275) died within 28 days, and 68% (n = 579) survived for 28 days. Median RDW levels on ICU admission were significantly higher in non-survivors compared with survivors (15.6% vs. 14.8%, p < 0.001). Overall, 38% (n = 327) had low, and 62% (n = 536) had high RDW. The proportion of high RDW (>14.5%) was significantly higher in non-survivors (73% vs. 57%, p < 0.001). Patients with low RDW presented with a lower Charlson Comorbidity Index (p = 0.014), and their severity of illness on admission was lower (SAPS II: 35 vs. 38 points, p < 0.001). In total, 32% (n = 104) in the low and 35% (n = 190) in the high RDW group were mechanically ventilated (p = 0.273). The use of vasopressors (35% vs. 49%, p < 0.001) and renal replacement therapy (1% vs. 5%, p = 0.007) was significantly higher in the high RDW group. Cox regression analysis demonstrated that high RDW was significantly associated with 28-day mortality [crude HR 1.768, 95% CI (1.355-2.305); p < 0.001]. This association remained significant after adjusting for multiple confounders [adjusted HR 1.372, 95% CI (1.045-1.802); p = 0.023]. High RDW was significantly associated with mortality in critically ill patients ≥ 90 years. RDW is a useful simple parameter for risk stratification and may aid guidance for the therapy in very elderly critically ill patients.

Increased risk of osteoporosis and femoral neck fractures in patients with familial Mediterranean fever-a large retrospective cohort study.

The direct impact of inflammatory conditions and their therapy with corticosteroids contribute to an increased risk of osteoporosis with associated fractures. Familial Mediterranean fever (FMF) is an autoinflammatory disorder not commonly treated with corticosteroids. Evidence regarding FMF association with osteoporosis and femur fractures is anecdotal. We aimed to evaluate the incidence and risk of osteoporosis and femoral neck fracture in FMF patients compared with the general population. A retrospective cohort study using the electronic database of Clalit Health Services of all FMF patients first diagnosed between 2000 and 2016 and controls was conducted including age- and sex-matched controls in a 1:1 ratio. Follow-up continued until the first diagnosis of osteoporosis or fracture. Risk for these conditions was compared using univariate and multivariate Cox regression models. A total of 9769 FMF patients were followed for a median period of 12.5 years. Of these, 304 FMF patients were diagnosed with osteoporosis compared with 191 controls, resulting in an incidence rate (per 10 000 persons-years) of 28.8 and 17.8, respectively, and a crude hazard ratio of 1.62 (95% CI 1.35, 1.93; P < 0.001). Patients were diagnosed with osteoporosis at a considerably younger age than controls [60.1 (s.d. 12.4) vs 62.5 (s.d. 11.0) years; P = 0.028]. A total of 56 FMF patients were diagnosed with femoral neck fracture compared with 35 controls, resulting in an incidence rate of 5.3 and 3.3, respectively, and a crude HR of 1.60 (95% CI 1.05, 2.44; P < 0.05). FMF patients are at increased risk for osteoporosis and consequently femur fracture. Our findings emphasize the importance of considering bone health in the management of FMF patients.

Sex/Gender-Based Disparities in Early Transplant Access by Attributed Cause of Kidney Disease–Evidence from a Multiregional Cohort in the Southeast United States

We examined sex/gender disparities across the continuum of transplant care by attributed cause of end-stage kidney disease (ESKD). All adults (18-79 years; N= 43,548) with new-onset ESKD in Georgia, North Carolina, or South Carolina between 2015 and 2019 were identified from the United States Renal Data System (USRDS). Individuals were linked to the Early Steps to Transplant Access Registry (E-STAR) to obtain data on referral and evaluation. Waitlisting data was ascertained from USRDS. Using a Cox-proportional hazards model, with follow-up through 2020, we assessed the association between sex/gender and referral within 12 months (among all incident dialysis patients), evaluation start within 6 months (among referred patients), and waitlisting (among all evaluated patients) by attributed cause of ESKD (type 1 diabetes mellitus, type 2 diabetes mellitus, hypertension, glomerulonephritis, cystic disease, and other). Overall, women (vs. men) with type 2 diabetes-attributed ESKD were 13% (crude hazard ratio [HR]: 0.87 [0.83-0.91]), 14% (crude HR: 0.86 [0.81-0.91]), and 14% (crude HR: 0.86 [0.78-0.94]) less likely to be referred, evaluated, and waitlisted, respectively. Women (vs. men) with hypertension-attributed ESKD were 14% (crude HR: 0.86 [0.82-0.90]) and 8% (crude HR: 0.92 [0.87-0.98]) less likely to be referred and evaluated, respectively, but similarly likely to be waitlisted once evaluated (crude HR: 1.06 [0.97-1.15]). For all other attributed causes of ESKD, there was no sex/gender disparity in referral, evaluation, or waitlisting rates. In the Southeast United States, sex/gender disparities in early access to kidney transplantation are specific to people with ESKD attributed to type 2 diabetes and hypertension.

Very long-term outcomes after acute myocardial infarction in young men and women: Insights from the FAST-MI program

AimsConflicting data exists about long-term outcomes in young women and men experiencing acute myocardial infarction (AMI). MethodsThe FAST-MI program consists of three nationwide French surveys carried out 5years apart from 2005 to 2015, including consecutive patients with AMI over a 1-month period with up to 10-year follow-up. The present analysis focused on adults≤50 yo according to their gender. ResultsWomen accounted for 17.5% (335) of the 1912 patients under 50 yo and had a similar age as men (43.9±5.1 vs. 43.9±5.5years, P=0.92). They received less percutaneous coronary interventions (PCI) than men (85.9% vs. 91.3%, P=0.005), even in ST-elevation myocardial infarction (83.6% vs. 93.5%, P<0.001). Recommended secondary prevention medications were less frequently prescribed at discharge in women (40.6% vs. 52.8%, P<0.001), a trend that persisted in 2015 (59.1% vs. 72.8% in 2015, P<0.001). Still, ten-year survival was similar in men (90.5%) and women (92.3%) (crude HR: 0.86 [95% CI: 0.55–1.35], P=0.52, adjusted HR: 0.63 [95% CI: 0.38–1.07], P=0.09); similar results were found for ten-year survival among hospital survivors (91.2% in men vs. 93.7% in women, adjusted HR: 0.87 [95% CI: 0.45–1.66], P=0.66). Of the 1684 patients alive at hospital discharge with morbidity follow-up≥6months available, death, AMI or stroke at 8years occurred in 12.9% men and 11.2% in women (adjusted HR: 0.90 [95% CI: 0.60–1.33], P=0.59). ConclusionsYoung women with AMI undergo less cardiac interventions and are less often prescribed secondary prevention treatment than men, even when significant coronary artery disease is present, but keep a similar long-term prognosis after AMI. Optimal management of these young patients, regardless of gender, is necessary to ensure best outcomes after this major cardiovascular event.

Expression molecular subtype as a predictor of outcomes of chemoradiotherapy for esophageal cancer.

4030 Background: The standard treatment for advanced esophageal cancer is preoperative chemoradiotherapy (CRT) followed by surgery or definitive CRT (NCCN Guideline 2022 ver5). CRT has the advantage of preserving organs and functions and the prognosis for patients achieved complete response by CRT is good. However, it is currently impossible to predict the outcomes of CRT before treatment. We have performed RNA expression analysis of pre-treatment biopsy specimens of esophageal cancer and identified several intrinsic molecular subtypes, as well as E-type (high expression of squamous markers) with good prognosis for CRT and M2-type (high expression of stromal markers) with poor prognosis for CRT (US patent No 10,969,390 B2). Herein, we performed an integrated analysis to confirm the relationship between intrinsic expression molecular subtype classification and prognosis in the pooled population from two prospective cohort studies (UMIN000043637). Methods: Two cohort studies were as follows; 1) single institute prospective cohort study conducted at National Cancer Center Hospital East (n=157, UMIN-C000000459), 2) multicenter prospective cohort study conducted at 10 institutions (n=226, UMIN000016141). A total 383 cases met inclusion criteria and the Affymetrix U331Plus 2 panel (47,104 transcripts, 38,572 genes) was used to identify E-type and M2-type. The clinical course and outcome were blinded for subtype classification. Treatment was performed as usual at each institution, and treatment details and outcomes were examined by subtype. Results: Among 383 patients, 181 and 164 patients were treated by CRT and surgery, respectively. Ninety-nine percent (n=342) were squamous cell carcinoma. Stage I/II/III/IV were 13/61/86/21 and 17/63/81/3 in CRT group and surgery group, respectively. Among them, 76 (22%), 100 (29%), 169 (49%) patients were classified as E, M2 and others, respectively. Among the patients treated by CRT, CR rate of E-type and M2-type were 62.8% (95% CI, 47.8-75.7) and 33.3% (95% CI, 21.9-47.1) (p=0.006). The 5-year progression free survival (PFS) and overall survival (OS) rates of CRT group was 50.5% (95% CI, 34.7-64.4) and 59.8% (95% CI, 42.6-73.3) for E-type vs. 23.0% (95% CI, 12.0-36.2) and 29.0% (95%CI, 16.8-42.4) for M2-type, with statistically significant difference (p=0.011, p=0.003). Cox regression analysis showed that crude HR for PFS and OS of E vs M2 were 0.50 (95% CI, 0.296-0.859, p=0.012) and 0.41 (95% CI, 0.226-0750, p=0.004), respectively. In contrast, E and M2-type did not show the survival difference in surgery group. Conclusions: For the first time in the world, we confirmed that expression molecular subtype of esophageal cancer has the potential to predict the outcomes of CRT. The results may provide precision medicine in the selection of treatment for esophageal cancer.

Dental Caries a Risk Factor for Intracerebral Hemorrhage

Introduction: Streptococcus mutans is a known cause of dental caries that contains a collagen-binding protein, Cnm, and exhibits inhibition of platelet aggregation and matrix metalloproteinase-9 activation. This strain has been linked to aggravation of experimental intracerebral hemorrhage (ICH) and may be a risk factor for ICH. The purpose of this study was to test the association between dental caries and incident ICH. Methods: The presence of dental caries and periodontal disease was assessed in subjects from the Dental Atherosclerosis Risk in Communities (DARIC) study without prior stroke or ICH. This cohort was followed for incident ICH over a period of 10 years. Cox regression was used to compute crude and adjusted hazards ratio from the dental assessment. Results: Among 6,315 subjects, dental surface caries and/or root caries were recorded in 1,338 (27%) subjects. Of those, 7 (0.5%) had incident ICH over a period of 10 years following the visit 4 assessment. Of the remaining 4,977 subjects, 10 (0.2%) had incident ICH. Those with dental caries versus those without dental caries were slightly younger (mean age 62.0 ± 5.7 vs. 62.4 ± 5.6, p = 0.012), had a greater proportion of males (51 vs. 44%, p < 0.001), African Americans (44 vs. 10%, p < 0.001), and were hypertensive (42 vs. 31%, p < 0.001). The association between caries and ICH was significant (crude HR 2.69, 95% CI 1.02–7.06) and strengthened after adjustment for age, gender, race, education level, hypertension, and periodontal disease (adjusted HR 3.88, 95% CI 1.34–11.24). Conclusion: Dental caries is a potential risk for incident ICH after caries detection. Future studies are needed to determine if treatment of dental caries can reduce the risk of ICH.