Mortality in a cohort of US firefighters from San Francisco, Chicago and Philadelphia: an update

ObjectivesTo update the mortality experience of a previously studied cohort of 29 992 US urban career firefighters compared with the US general population and examine exposure-response relationships within the cohort.MethodsVital status was updated through 2016 adding 7 years of follow-up. Cohort mortality compared with the US population was evaluated via life table analyses. Full risk-sets, matched on attained age, race, birthdate and fire department were created and analysed using the Cox proportional hazards regression to examine exposure-response associations between select mortality outcomes and exposure surrogates (exposed-days, fire-runs and fire-hours). Models were adjusted for a potential bias from healthy worker survivor effects by including a categorical variable for employment duration.ResultsCompared with the US population, mortality from all cancers, mesothelioma, non-Hodgkin's lymphoma (NHL) and cancers of the oesophagus, intestine, rectum, lung and kidney were modestly elevated. Positive exposure-response relationships were observed for deaths from lung cancer, leukaemia and chronic obstructive pulmonary disease (COPD).ConclusionsThis update confirms previous findings of excess mortality from all cancers and several site-specific cancers as well as positive exposure-response relations for lung cancer and leukaemia. New findings include excess NHL mortality compared with the general population and a positive exposure-response relationship for COPD. However, there was no evidence of an association between any quantitative exposure measure and NHL.

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Relationship Between Urinary 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanol and Lung Cancer Risk in the General Population: A Community-Based Prospective Cohort Study

Frontiers in Oncology ◽

10.3389/fonc.2021.611674 ◽

2021 ◽

Vol 11 ◽

Author(s):

Eun Young Park ◽

Min Kyung Lim ◽

Eunjung Park ◽

Jin-Kyoung Oh ◽

Do-Hoon Lee

Keyword(s):

Lung Cancer ◽

Cohort Study ◽

General Population ◽

Cancer Risk ◽

Prospective Cohort Study ◽

Prospective Cohort ◽

Proportional Hazards ◽

Lung Cancer Risk ◽

Cox Proportional Hazards ◽

Community Based

No published studies have prospectively evaluated the association between urinary 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) levels and lung cancer risk in the general population. Here, we conducted a prospective community-based cohort study in the Republic of Korea to evaluate the relationship between urinary NNAL levels and lung cancer risk using prediagnostic urine samples. This prospective cohort study was based on the Korean National Cancer Center Community Cohort. During the follow-up period, 173 primary lung cancer cases were identified. Total urinary NNAL levels were measured by liquid chromatography-tandem mass spectrometry, and data were analyzed using multivariable Cox proportional hazards regression models. The risk of lung cancer was significantly increased per unit of natural log-transformed urinary NNAL (HR, 1.27; 95% CI, 1.09–1.48), after adjusting for age, region, entry year into the cohort, education achievement, alcohol consumption status, BMI, smoking status, and urinary cotinine levels. Cox proportional-hazards models with NNAL quartiles also showed positive dose-response relationships with risk of lung cancer. A significantly increased risk of lung cancer was found in the fourth quartile of urinary NNAL levels (HR, 3.27; 95% CI, 1.37–7.79, P for trend < 0.01). After stratification with sex, the significant association remained in only men. Urinary NNAL levels are associated with the risk of lung cancer in the general population, and this association is independent from the quantification of cigarette smoking and nicotine uptake.

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Predictors of hospitalizations for heart failure decompensation in patients with comorbid occupational chronic obstructive pulmonary disease

European Heart Journal ◽

10.1093/ehjci/ehaa946.0949 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

L.A Shpagina ◽

O.S Kotova ◽

I.S Shpagin ◽

G.V Kuznetsova ◽

N.V Kamneva ◽

...

Keyword(s):

Heart Failure ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Chronic Obstructive ◽

Length Of Service ◽

Obstructive Pulmonary Disease ◽

Copd Patients ◽

Patients With Heart Failure ◽

Occupational Copd ◽

Heart Failure Decompensation

Abstract Background Heart failure decompensation requiring hospitalization is an important event, associated with mortality and investigating its predictors is topical problem. Chronic obstructive pulmonary disease (COPD) is a common comorbidity for heart failure. Both conditions share common molecular mechanisms such as systemic inflammation. COPD is heterogeneous and subpopulations with different inflammation patterns may interact with heart failure in different manner. Airway inflammation in occupational COPD may differs from COPD in tobacco smokers. Additionally cardiotoxicity of industrial chemicals influence heart failure features. Despite this biological plausibility, heart failure and occupational COPD comorbidity is not studied enough. Purpose To reveal predictors of hospitalizations for heart failure decompensation in patients with heart failure and occupational COPD comorbidity. Methods Occupational COPD patients (n=115) were investigated in a prospective cohort observational study. Comparison group – 115 tobacco smokers with COPD. Control group – 115 healthy persons. Controls were selected by propensity score matching, covariates were COPD duration, age and gender. Then COPD groups were stratified according to heart failure. Working conditions, echocardiography, spirometry, pulsoxymetry, 6-mitute walking test were done. Molecular markers of tissue damage – chemokine ligand 18 (CCL 18), lactate dehydrogenase, cardiac troponin T, N-terminal pro-B-type natriuretic peptide (NT pro-BNP), protein S100 beta, von Willebrand factor were measured in serum by ELISA. Follow up after initial assessment was 12 month. Predictors were determined by Cox proportional hazards regression with ROC analysis. Results Heart failure rate in occupational COPD patients were higher – 54.8% versus 36.5% in tobacco smokers with COPD, p<0.05. Heart failure with preserved ejection fraction was predominant – 40.9%. Prevalence of biventricular heart failure was 38.3%, isolated right heart failure – 13%, left heart failure – 2.6%. Cumulative hospitalization rate in occupational COPD with heart failure group was higher than in comparison group, 17.5% and 9.5% respectively, p=0.01. In Cox proportional hazards regression model predictors of hospitalizations for heart failure decompensation during 12 months in this group were length of service (HR 1.22, 95% CI: 1.03–2.5), aromatic hydrocarbons concentration at workplaces air (HR 1.4, 95% CI: 1.15–1.96), serum protein S100 beta (HR 1.10, 95% CI: 1.02–1.87), SaO2 (HR 1.2, 95% CI: 1.06–2.13). Area under the ROC curve was 0.82. Conclusion Length of service, aromatic hydrocarbons concentration at workplaces air, serum protein S100 beta, SaO2 are considered to be independent risk factors of heart failure decompensation required hospitalization in patients with heart failure and occupational COPD comorbidity. Funding Acknowledgement Type of funding source: None

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Pre-diagnosis neutrophil-to-lymphocyte ratio and mortality in individuals who develop lung cancer

Cancer Causes & Control ◽

10.1007/s10552-021-01469-3 ◽

2021 ◽

Author(s):

Laurie Grieshober ◽

Stefan Graw ◽

Matt J. Barnett ◽

Gary E. Goodman ◽

Chu Chen ◽

...

Keyword(s):

Lung Cancer ◽

Proportional Hazards ◽

Smoking Status ◽

Cox Proportional Hazards ◽

Neutrophil To Lymphocyte Ratio ◽

Blood Draw ◽

Lymphocyte Ratio ◽

Cox Proportional Hazards Models ◽

Inflammatory Profile ◽

Heavy Smokers

Abstract Purpose The neutrophil-to-lymphocyte ratio (NLR) is a marker of systemic inflammation that has been reported to be associated with survival after chronic disease diagnoses, including lung cancer. We hypothesized that the inflammatory profile reflected by pre-diagnosis NLR, rather than the well-studied pre-treatment NLR at diagnosis, may be associated with increased mortality after lung cancer is diagnosed in high-risk heavy smokers. Methods We examined associations between pre-diagnosis methylation-derived NLR (mdNLR) and lung cancer-specific and all-cause mortality in 279 non-small lung cancer (NSCLC) and 81 small cell lung cancer (SCLC) cases from the β-Carotene and Retinol Efficacy Trial (CARET). Cox proportional hazards models were adjusted for age, sex, smoking status, pack years, and time between blood draw and diagnosis, and stratified by stage of disease. Models were run separately by histotype. Results Among SCLC cases, those with pre-diagnosis mdNLR in the highest quartile had 2.5-fold increased mortality compared to those in the lowest quartile. For each unit increase in pre-diagnosis mdNLR, we observed 22–23% increased mortality (SCLC-specific hazard ratio [HR] = 1.23, 95% confidence interval [CI]: 1.02, 1.48; all-cause HR = 1.22, 95% CI 1.01, 1.46). SCLC associations were strongest for current smokers at blood draw (Interaction Ps = 0.03). Increasing mdNLR was not associated with mortality among NSCLC overall, nor within adenocarcinoma (N = 148) or squamous cell carcinoma (N = 115) case groups. Conclusion Our findings suggest that increased mdNLR, representing a systemic inflammatory profile on average 4.5 years before a SCLC diagnosis, may be associated with mortality in heavy smokers who go on to develop SCLC but not NSCLC.

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Clinical outcomes of pediatric macular edema associated with non-infectious uveitis

Journal of Ophthalmic Inflammation and Infection ◽

10.1186/s12348-021-00236-4 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Anh Hong Nguyen ◽

Bethlehem Mekonnen ◽

Eric Kim ◽

Nisha R. Acharya

Keyword(s):

Visual Acuity ◽

Macular Edema ◽

San Francisco ◽

Pediatric Patients ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Study Cohort ◽

Common Diagnosis ◽

Corticosteroid Injections

Abstract Background Macular edema (ME) is the most frequent cause of irreversible visual impairment in patients with uveitis. To date, little data exists about the clinical course of ME in pediatric patients. A retrospective, observational study was performed to examine the visual and macular thickness outcomes of ME associated with chronic, noninfectious uveitis in pediatric patients. Methods Pediatric patients with noninfectious uveitis complicated by ME seen in the University of California San Francisco Health System from 2012 to 2018 were identified using ICD-9 and ICD-10 codes. Data were collected from medical records including demographics, diagnoses, ocular history, OCT imaging findings, complications, and treatments at first encounter and at 3, 6, 9, and 12-month follow-up visits. Cox proportional hazards regression was used to investigate the association between different classes of treatment (steroid drops, steroid injections, oral steroids and other immunosuppressive therapies) and resolution of macular edema. Results The cohort comprised of 21 children (26 eyes) with a mean age of 10.5 years (SD 3.3). Undifferentiated uveitis was the most common diagnosis, affecting 19 eyes (73.1%). The majority of observed macular edema was unilateral (16 patients, 76.2%) and 5 patients had bilateral macular edema. The mean duration of follow-up at UCSF was 35.3 months (SD 25.7). By 12 months, 18 eyes (69.2%) had achieved resolution of ME. The median time to resolution was 3 months (IQR 3–6 months). Median best-corrected visual acuity (BCVA) at baseline was 0.54 logMAR (Snellen 20/69, IQR 20/40 to 20/200). Median BCVA at 12 months was 0.1 logMAR (Snellen 20/25, IQR 20/20 to 20/50) Corticosteroid injections were associated with a 4.0-fold higher rate of macular edema resolution (95% CI 1.3–12.2, P = 0.01). Conclusions Although only 15% of the pediatric patients with uveitis in the study cohort had ME, it is clinically important to conduct OCTs to detect ME in this population. Treatment resulted in 69% of eyes achieving resolution of ME by 12 months, accompanied with improvement in visual acuity. Corticosteroid injections were significantly associated with resolution of macular edema.

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Reproduction Rates After Cancer Treatment: Experience From the Norwegian Radium Hospital

Journal of Clinical Oncology ◽

10.1200/jco.2007.15.3130 ◽

2009 ◽

Vol 27 (3) ◽

pp. 334-343 ◽

Cited By ~ 67

Author(s):

Milada Cvancarova ◽

Sven Ove Samuelsen ◽

Henriette Magelssen ◽

Sophie Dorothea Fosså

Keyword(s):

General Population ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Control Group ◽

Birth Registry ◽

Hazard Ratios ◽

Norwegian Radium Hospital ◽

Before And After ◽

Primary Focus ◽

After Cancer

Purpose Most studies on postcancer reproduction are limited in patient numbers and lack of control group. We have computed 10-year first postdiagnosis cumulative reproduction rates (10-PDRs) and hazard ratios (HRs) avoiding these limitations. Patients and Methods Six thousand seventy-one patients with cancer age 15 to 45 years at diagnosis, treated from 1971 to 1997, and 30,355 controls from the general population, all born after 1950, were observed from the true (patients) or assigned (controls) date of diagnosis for a median of 10 years (range, 0 to 35). The primary focus of the study was the 10-PDR before and after 1988+ based on data from the Medical Birth Registry of Norway. Cox proportional hazards regression models were adjusted for age and calendar year at diagnosis, stratified by sex and prediagnosis parenthood. Results Across all cancer types, HRs of females were approximately 50% lower than those of the controls, the comparable percentage for male patients being approximately 30%, with some improvement after 1988+ for selected diagnoses. The highest 10-PDRs were observed in childless patients, with more favorable HRs in male than in female patients. In survivors with at least one child at diagnosis, the post-1988+ HRs improved significantly in patients with testicular and localized cervical cancer compared to pre-1988+ reproduction, with borderline improvement in localized ovarian cancer. Conclusion Postcancer reproduction is lower than that of the general population and influenced by sex, age at diagnosis, prediagnosis parenthood, and diagnostic period with more favorable rates in males than in females. Post-1988+ fertility-saving strategies may have improved the reproduction rates for select genital cancers.

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Lobectomy Versus Segmentectomy in Patients with Stage T (>2 cm and ≤3 cm) N0M0 Non-small Cell Lung Cancer: A Propensity Score Matching Study

10.21203/rs.3.rs-97312/v1 ◽

2020 ◽

Author(s):

Linlin Wang ◽

Lihui Ge ◽

Guofeng Zhang ◽

Yi Ren ◽

Yongyu Liu

Keyword(s):

Lung Cancer ◽

Propensity Score ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Small Cell ◽

Seer Database ◽

Regression Analyses ◽

Small Cell Lung

Abstract Background: Whether lung segmentectomy is a safe and effective surgical treatment in patients with early non-small cell lung cancer (NSCLC) remains controversial. We have therefore reviewed the clinicopathologic characteristics and survival outcomes of patients receiving a lobectomy vs. segmentectomy to treat early T (>2 cm and ≤3 cm) N0M0 NSCLC.Methods: We obtained data from the Surveillance, Epidemiology, and End Results (SEER) database for patients who underwent lobectomy or segmentectomy between 2004 and 2015. To reduce bias and imbalance between the treatment groups, propensity score matching (PSM) analysis was performed. We used Kaplan-Meier curves to estimate overall survival (OS) and lung cancer-speciﬁc survival (LCSS), performed univariate and multivariate Cox proportional hazards regression analyses to identify independent prognostic factors for OS and CSS, and applied the Cox proportional hazards model to create forest plots. Results: A total of 5783 patients from the SEER database were included. Of these, 5531 patients underwent lobectomy, and 252 patients underwent segmentectomy. Before matching, both univariate and multivariate Cox regression analyses showed that patients who underwent lobectomy had better OS (hazard ratio [HR]: 1.561; 95% confidence interval [CI] 1.292-1.885; P <0.001) and LCSS (HR: 1.551; 95% CI 1.198-2.009; P=0.001) than patients who underwent segmentectomy. However, survival differences between the groups were not significant; OS (P=0.160) and LCSS (P=0.097) after matching. Regression analyses revealed that age, sex, lymph node dissection, and grade were independent predictors of OS and LCSS (P <0.05).Conclusions: For patients with stage T (>2 cm and ≤3 cm) N0M0 non-small cell lung cancer, segmentectomy can achieve the same OS and LCSS compared with lobectomy. A large number of patients require further long-term follow-up analyses.

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The incidence and predictors of new brain metastases in patients with non–small cell lung cancer following discontinuation of systemic therapy

Journal of Neurosurgery ◽

10.3171/2021.9.jns212150 ◽

2021 ◽

pp. 1-11

Author(s):

Dennis London ◽

Dev N. Patel ◽

Bernadine Donahue ◽

Ralph E. Navarro ◽

Jason Gurewitz ◽

...

Keyword(s):

Lung Cancer ◽

Brain Metastases ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Systemic Therapy ◽

Recurrent Events ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Small Cell ◽

Small Cell Lung

OBJECTIVE Patients with non–small cell lung cancer (NSCLC) metastatic to the brain are living longer. The risk of new brain metastases when these patients stop systemic therapy is unknown. The authors hypothesized that the risk of new brain metastases remains constant for as long as patients are off systemic therapy. METHODS A prospectively collected registry of patients undergoing radiosurgery for brain metastases was analyzed. Of 606 patients with NSCLC, 63 met the inclusion criteria of discontinuing systemic therapy for at least 90 days and undergoing active surveillance. The risk factors for the development of new tumors were determined using Cox proportional hazards and recurrent events models. RESULTS The median duration to new brain metastases off systemic therapy was 16.0 months. The probability of developing an additional new tumor at 6, 12, and 18 months was 26%, 40%, and 53%, respectively. There were no additional new tumors 22 months after stopping therapy. Patients who discontinued therapy due to intolerance or progression of the disease and those with mutations in RAS or receptor tyrosine kinase (RTK) pathways (e.g., KRAS, EGFR) were more likely to develop new tumors (hazard ratio [HR] 2.25, 95% confidence interval [CI] 1.33–3.81, p = 2.5 × 10−3; HR 2.51, 95% CI 1.45–4.34, p = 9.8 × 10−4, respectively). CONCLUSIONS The rate of new brain metastases from NSCLC in patients off systemic therapy decreases over time and is uncommon 2 years after cessation of cancer therapy. Patients who stop therapy due to toxicity or who have RAS or RTK pathway mutations have a higher rate of new metastases and should be followed more closely.

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Abstract P073: Co-morbidities and Cardiac Associated Mortality in Smokers

Circulation ◽

10.1161/circ.135.suppl_1.p073 ◽

2017 ◽

Vol 135 (suppl_1) ◽

Author(s):

Gregory L Kinney ◽

Kendra A Young ◽

Katherine Pratte ◽

Elizabeth A Regan ◽

Lindsey Duca ◽

...

Keyword(s):

Pulmonary Disease ◽

Latent Class ◽

Proportional Hazards ◽

Airway Disease ◽

Cox Proportional Hazards ◽

Chronic Obstructive ◽

Longitudinal Assessment ◽

Vascular Effects ◽

Obstructive Pulmonary Disease ◽

Cvd Mortality

Background: Chronic Obstructive Pulmonary Disease (COPD) is a complex syndrome involving all aspects of the lungs which is strongly associated with cigarette smoking. Parenchymal destruction and remodeling are disease processes involving inflammatory pathways likely to have systemic vascular effects outside of the lungs. Indeed cardiovascular disease (CVD) is a leading cause of mortality in people affected by COPD and many co-morbid conditions are also associated with the disease. We explored CVD mortality in smokers considering aspects of COPD as well as co-morbidities in the longitudinal follow-up of the COPDGene study. Methods: The COPDGene study includes baseline and longitudinal assessment of mortality for 8,157 participants with (3,604) and without COPD (4,553) all of whom reported >10 pack-years smoking exposure. Aspects of COPD including CT phenotyping and pulmonary function were combined using Principal Components Analysis (PCA), co-morbidities were combined using Latent Class Analysis (LCA) and cause specific mortality was assessed using study center reports, SSRI searches and single clinician adjudication. Cox Proportional Hazards models accounting for the effects of competing risks were used to assess the association between PCA factors and CVD mortality and PCA factors plus LCA classes and CVD mortality. Results: PCA analysis resulted in 5 factors describing emphysema, airway disease, gas trapping, BMI and its effect on CT measurement and hyperinflation and LCA analysis identified 7 classes of co-morbidities. CVD associated mortality occurred in 128 participants and competing causes of mortality occurred in 605. The PCA factor describing airway disease predicted CVD mortality in the PCA only model (HR 1.8, 95%C.I. 1.4-2.3,p<0.0001), as well as in the LCA model (HR 1.7, 95% C.I. 1.3-2.2, p<0.0001). LCA classes associated with CVD mortality include a class describing diabetes, high BP and high Cholesterol (HR 3.5, 95% C.I. 1.8-6.8, p=0.0003) and a class describing known CVD (HR 2.9, 95% C.I. 1.3-6.7, p=0.01). Conclusions: Co-morbidities of COPD represent independent predictors of CVD associated mortality in smokers accounting for pulmonary disease and competing mortality risks. Clustering of comorbidities using LCA is an approach that may be informative in complex diseases.

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Abstract P005: Comparative Effectiveness of Rivaroxaban versus Warfarin for the Treatment of Patients with Non-valvular Atrial Fibrillation

Circulation ◽

10.1161/circ.133.suppl_1.p005 ◽

2016 ◽

Vol 133 (suppl_1) ◽

Author(s):

Faye L Norby ◽

Lindsay G Bengtson ◽

Lin Y Chen ◽

Richard F MacLehose ◽

Pamela L Lutsey ◽

...

Keyword(s):

Atrial Fibrillation ◽

Ischemic Stroke ◽

Real World ◽

Proportional Hazards ◽

Large Population ◽

Population Based ◽

Cox Proportional Hazards ◽

Gi Bleeding ◽

Cox Proportional Hazards Models ◽

The Us

Background: Rivaroxaban is a novel oral anticoagulant approved in the US in 2011 for prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (NVAF). Information on risks and benefits among rivaroxaban users in real-world populations is limited. Methods: We used data from the US MarketScan Commercial and Medicare Supplemental databases between 2010 and 2013. We selected patients with a history of NVAF and initiating rivaroxaban or warfarin. Rivaroxaban users were matched with up to 5 warfarin users by age, sex, database enrollment date and drug initiation date. Ischemic stroke, intracranial bleeding (ICB), myocardial infarction (MI), and gastrointestinal (GI) bleeding outcomes were defined by ICD-9-CM codes in an inpatient claim after drug initiation date. Cox proportional hazards models were used to assess the association between rivaroxaban vs. warfarin use and outcomes adjusting for age, sex, and CHA2DS2-VASc score. Separate models were used to compare a) new rivaroxaban users with new warfarin users, and b) switchers from warfarin to rivaroxaban to continuous warfarin users. Results: Our analysis included 34,998 rivaroxaban users matched to 102,480 warfarin users with NVAF (39% female, mean age 71), in which 487 ischemic strokes, 179 ICB, 647 MI, and 1353 GI bleeds were identified during a mean follow-up of 9 months. Associations of rivaroxaban vs warfarin were similar in new users and switchers; therefore we pooled both analyses. Rivaroxaban users had lower rates of ICB (hazard ratio (HR) (95% confidence interval (CI)) = 0.72 (0.46, 1.12))) and ischemic stroke (HR (95% CI) = 0.88 (0.68, 1.13)), but higher rates of GI bleeding (HR (95% CI) = 1.15 (1.01, 1.33)) when compared to warfarin users (table). Conclusion: In this large population-based study of NVAF patients, rivaroxaban users had a non-significant lower risk of ICB and ischemic stroke than warfarin users, but a higher risk of GI bleeding. These real-world findings are comparable to results reported in published clinical trials.

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P1666Do beta-blockers increase the risk for hospitalizations in heart failure with preserved ejection fraction? A secondary analysis of beta-blocker use in the TOPCAT trial

European Heart Journal ◽

10.1093/eurheartj/ehz748.0424 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

D N Silverman ◽

T B Plante ◽

M I Infeld ◽

S P Juraschek ◽

G Dougherty ◽

...

Keyword(s):

Heart Failure ◽

Ejection Fraction ◽

Beta Blocker ◽

Proportional Hazards ◽

Beta Blockers ◽

Secondary Analysis ◽

Cox Proportional Hazards ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Reduced Ejection Fraction

Abstract Background The use of beta-blockers for treatment of heart failure (HF) with a reduced ejection fraction (EF) is unequivocally beneficial, but their role in the treatment of preserved EF (HFpEF) remains unclear. Purpose In a contemporary HFpEF cohort, we sought to assess the association of HF hospitalizations and the use of beta-blockers in patients with an EF above and below 50%. Methods The TOPCAT trial tested spironolactone vs. placebo among patients with HFpEF, including some with mild reductions in EF between 45–50%. The primary outcome was a composite of cardiovascular (CV) mortality, aborted cardiac arrest, or HF hospitalizations. Medication use, including beta-blockers, was reported at each visit and hospitalization. In the 1,761 participants from the Americas, we compared the association of beta-blocker use (vs. no use) and HF hospitalization or CV mortality using Cox proportional hazards models adjusted for baseline demographics, history of myocardial infarction, atrial fibrillation, chronic obstructive pulmonary disease, asthma, and hypertension. The analyses were repeated in the EF strata ≥50% and <50%. Results Among patients included in the current analysis (mean age 72 years, 50% female, 78% white), 1,496/1,761 (85%) received beta-blockers and 1,566/1,761 (89%) had an EF ≥50%. HF hospitalizations and CV mortality occurred in 399/1,761 (23%) and 223/1,761 (13%) of participants, respectively. Beta-blocker use was associated with an increase in risk of HF hospitalization among patients with preserved EF ≥50% [HR 1.56, (95% CI 1.09–2.24), p=0.01] and was associated with a reduction in risk of hospitalization in patients with an EF <50% [HR 0.42, (95% CI 0.18- 0.99), p<0.05]. We found a significant interaction for EF threshold and beta-blocker use on incident HF hospitalizations (p=0.01). There were no differences in CV mortality. Figure 1. Kaplan Meier incidence plots Conclusions Beta-blocker use was associated with an increase in HF hospitalizations in patients with HFpEF (EF≥50%) but did not affect CV mortality. Further research is needed to confirm these findings and elucidate causality.

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