Biological Age, Chronological Age, and Survival in Pulmonary Fibrosis: A Causal Mediation Analysis.

Rationale: Accelerated biological aging has been implicated in the development of interstitial lung disease (ILD) and other diseases of aging but remains poorly understood. Objectives: To identify plasma proteins that mediate the relationship between chronological age and survival association in patients with ILD. Methods: Causal mediation analysis was performed to identify plasma proteins that mediated the chronological age-survival relationship in an idiopathic pulmonary fibrosis discovery cohort. Proteins mediating this relationship after adjustment for false discovery were advanced for testing in an independent ILD validation cohort and explored in a chronic obstructive pulmonary disease cohort. A proteomic-based measure of biological age was constructed and survival analysis performed, assessing the impact of biological age and peripheral blood telomere length on the chronological age-survival relationship. Measurements and Main Results: Twenty-two proteins mediated the chronological age-survival relationship after adjustment for false discovery in the idiopathic pulmonary fibrosis discovery cohort (n = 874), with 19 remaining significant mediators of this relationship in the ILD validation cohort (n = 983) and one mediating this relationship in the chronic obstructive pulmonary disease cohort. Latent transforming growth factor-ß binding protein 2 and ectodysplasin A2 receptor showed the strongest mediation across cohorts. A proteomic measure of biological age completely attenuated the chronological age-survival association and better discriminated survival than chronological age. Results were robust to adjustment for peripheral blood telomere length, which did not mediate the chronological age-survival relationship. Conclusions: Molecular measures of aging completely mediate the relationship between chronological age and survival, suggesting that chronological age has no direct effect on ILD survival.

High-Resolution CT Scan Fibrotic Patterns in Stage IV Pulmonary Sarcoidosis: Impact on Pulmonary Function and Survival.

BACKGROUND: Different patterns of fibrosis on high-resolution CT scans (HRCT) have been associated with reduced survival in some interstitial lung diseases. Nothing is known about HRCT scan patterns and survival in sarcoidosis. RESEARCH QUESTION: Will a detailed description of the extent and pattern of HRCT scan fibrosis in patients with stage IV pulmonary sarcoidosis impact pulmonary function and survival? STUDY DESIGN AND METHODS: Two hundred forty patients with stage IV sarcoidosis at two large tertiary institutions were studied. The earliest HRCT scan with fibrosis was reviewed for extent of fibrosis (< 10%, 10%-20%, and > 20%) and presence of bronchiectasis, upper lobe fibrocystic changes, basal subpleural honeycombing, ground-glass opacities (GGOs), large bullae, and mycetomas. Presence of sarcoidosis-associated pulmonary hypertension (SAPH) and pulmonary function testing performed within 1 year of HRCT were recorded. Patients were followed up until last clinic visit, death, or lung transplantation. RESULTS: The mean age was 58.4 years. Seventy-four percent were Black, 63% were female, and mean follow-up was 7.4 years. Death or LT occurred in 53 patients (22%). Thirty-one percent had > 20% fibrosis, 25% had 10%-20% fibrosis, and 44% had < 10% fibrosis. The most common HRCT abnormalities were bronchiectasis (76%), upper lobe fibrocystic changes (36%), and GGOs (28%). Twelve percent had basal subpleural honeycombing, and 32% had SAPH. Patients with > 20% fibrosis had more severe pulmonary impairment, were more likely to have SAPH (53%), and had worse survival (44% mortality; P < .001). Upper lobe fibrocystic changes, basal subpleural honeycombing, and large bullae were associated with worse pulmonary function and worse survival. Patients with basal subpleural honeycombing had the worst pulmonary function and survival (55% mortality; P < .001). GGOs were associated with worse pulmonary function but not worse survival, and mycetomas were associated with worse survival but not worse pulmonary function. A Cox proportional hazards model indicated that basal subpleural honeycombing (hazard ratio, 7.95), diffusion capacity for carbon monoxide < 40% (HR, 5.67) and White race (hazard ratio, 2.61) were independent predictors of reduced survival. INTERPRETATION: HRCT scan features of fibrotic pulmonary sarcoidosis had an impact on pulmonary function and survival. Presence of >20% fibrosis and basal subpleural honeycombing are predictive of worse pulmonary function and worse survival in patients with stage IV pulmonary sarcoidosis.

Application and impact of Lasso regression in gastroenterology: A systematic review.

Least absolute shrinkage and selection operator (Lasso) regression is a statistical technique that can be used to study the effects of clinical variables in outcome prediction. In this study, we aimed at systematically reviewing the application of Lasso regression in gastroenterology for developing predictive models and providing a method of performing Lasso regression. A comprehensive search strategy was conducted in PubMed, Embase and Cochrane CENTRAL databases (Keywords: lasso regression; gastrointestinal tract/diseases) following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies were screened for eligibility based on pre-defined selection criteria and the data was extracted using a standardized form. Total 16 studies were included, comprising a diverse range of gastroenterological disease-related outcomes. Sample sizes ranged from 134 to 8861 subjects. Eleven studies reported liver disease-related prediction models, while five focused on non-hepatic etiology models. Lasso regression was applied for variable selection, risk prediction and model development, with various validation methods and performance metrics used. Model performance metrics included Area Under the Receiver Operating Characteristics (AUROC), C-index and calibration plots. In gastroenterology, Lasso regression has been used in various diseases such as inflammatory bowel disease, liver disease and esophageal cancer. It is valuable for complex scenarios with many predictors. However, its effectiveness depends on high-quality and complete data. While it identifies important variables, it doesn't provide causal interpretations. Therefore, cautious interpretation is necessary considering the study design and data quality.

The prognostic value of gastroesophageal reflux disorder in interstitial lung disease related hospitalizations.

BACKGROUND: Gastroesophageal reflux disease (GERD) is a common comorbidity in patients with interstitial lung disease (ILD). We built and validated a model using the national inpatient sample (NIS) database to assess the contributory role of GERD in ILD-related hospitalizations mortality. METHODS: In this retrospective analysis, we extracted ILD-related hospitalizations data between 2007 and 2019 from the NIS database. Univariable logistic regression was used for predictor selection. Data were split into the training and validation cohorts (0.6 and 0.4, respectively). We used decision tree analysis (classification and regression tree, CART) to create a predictive model to explore the role of GERD in ILD-related hospitalizations mortality. Different metrics were used to evaluate our model. A bootstrap-based technique was implemented to balance our training data outcome to improve our model metrics in the validation cohort. We conducted a variance-based sensitivity analysis to evaluate GERD's importance in our model. FINDINGS: The model had a sensitivity of 73.43%, specificity of 66.15%, precision of 0.27, negative predictive value (NPV) of 93.62%, accuracy of 67.2%, Matthews Correlation Coefficient (MCC) of 0.3, F1 score of 0.4, and area under the curve (AUC) for the receiver operating characteristic (ROC) curve of 0.76. GERD did not predict survival in our cohort. GERD contribution to the model was ranked the eleventh among twenty-nine variables included in this analysis (importance of 0.003, normalized importance of 5%). GERD was the best predictor in ILD-related hospitalizations who didn't receive mechanical ventilation. INTERPRETATIONS: GERD is associated with mild ILD-related hospitalization. Our model-performance measures suggest overall an acceptable discrimination. Our model showed that GERD does not have a prognostic value in ILD-related hospitalization, indicating that GERD per se might not have any impact on mortality in hospitalized ILD patients.

ST-Elevation Myocardial Infarction Among Septic Shock and Coronary Interventions: A National Emergency Database Study.

OBJECTIVE: To study coronary interventions and mortality among patients with ST-elevated myocardial infarction (STEMI) who were admitted with septic shock. METHODS: Data from the national emergency department sample (NEDS) that constitutes 20% sample of hospital-owned emergency departments in the United States was analyzed for the septic shock related visits from 2016 to 2018. Septic shock was defined by the ICD codes. RESULTS: Out of 1 375 507 adult septic shock patients, 521 300 had a primary diagnosis of septic shock (mean age 67.41±15.67 years, 51.1% females) in the national emergency database for the years 2016 to 2018. Of these patients, 2768 (0.53%) had STEMI recorded during the hospitalization. Mortality rates for STEMI patients were higher than patients without STEMI (52.3% vs 23.5%). Mortality rates improved with PCI among STEMI patients (43.8% vs 56.2%). Coronary angiography was performed among 16% of patients of which percutaneous coronary intervention (PCI) rates were 7.7% among patients with STEMI septic shock. PCI numerically improved mortality, however, had no significant difference than patients without PCI on multivariate logistic regression and univariate logistic regression post coarsened exact matching of baseline characteristics among STEMI patients. Among the predictors, STEMI was a significant predictor of mortality in septic shock patients (OR 2.87, 95% CI 2.37-3.49; P<.001). Age, peripheral vascular disease, were predominant predictors of mortality in STEMI with septic shock subgroup (P <.001). Pneumonia was the predominant underlying infection among STEMI (36.4%) and without STEMI group (29.5%). CONCLUSION: STEMI complicating septic shock worsens mortality. PCI and coronary angiography numerically improved mortality, however, had no significant difference from patients without PCI. More research will be needed to improve mortality in such a critically ill subgroup of patients.

Cardiac and Obstetric Outcomes Associated With Mitral Valve Prolapse.

Mitral valve prolapse (MVP) is the most common valvular heart disease in women of reproductive age. Whether MVP increases the likelihood of adverse outcomes in pregnancy is unknown. The study objective was to examine the cardiac and obstetric outcomes associated with MVP in pregnant women. This retrospective cohort study, using the Healthcare Cost and Utilization Project National Readmission Sample database between 2010 and 2017, identified all pregnant women with MVP using the International Classification of Disease, Ninth and Tenth Revisions codes. The maternal cardiac and obstetric outcomes in pregnant women diagnosed with MVP were compared with women without MVP using multivariable logistic and Cox proportional hazard regression models adjusted for baseline demographic characteristics. There were 23,000 pregnancy admissions with MVP with an overall incidence of 16.9 cases per 10,000 pregnancy admissions. Pregnant women with MVP were more likely to die during pregnancy (adjusted hazard ratio 5.13, 95% confidence interval [CI] 1.09 to 24.16), develop cardiac arrest (adjusted odds ratio [aOR] 4.44, 95% CI 1.04 to 18.89), arrhythmia (aOR 10.96, 95% CI 9.17 to 13.12), stroke (aOR 6.90, 95% CI 1.26 to 37.58), heart failure (aOR 5.81, 95% CI 3.84 to 8.79), or suffer a coronary artery dissection (aOR 25.22, 95% CI 3.42 to 186.07) compared with women without MVP. Pregnancies with MVP were also associated with increased risks of preterm delivery (aOR 1.21, 95% CI 1.02 to 1.44) and preeclampsia/hemolysis, elevated liver enzymes, and low platelets syndrome (aOR 1.22, 95% CI 1.05 to 1.41). In conclusion, MVP in pregnancy is associated with adverse maternal cardiac outcomes and higher obstetric risks.

National Temporal Trends in Hospitalization and Inpatient Mortality in Patients With Pulmonary Sarcoidosis in the United States Between 2007 and 2018.

BACKGROUND: Sarcoidosis-related hospitalizations have been increasing in the past decade. There is a paucity of data on mortality trends over time in patients with pulmonary sarcoidosis and respiratory failure who are hospitalized. RESEARCH QUESTION: What are the national temporal trends over time in hospitalization and inpatient mortality rates in patients with pulmonary sarcoidosis and respiratory failure hospitalized in the United States between 2007 and 2018? STUDY DESIGN AND METHODS: Hospitalization data between 2007 and 2018 were extracted from the National Inpatient Sample for subjects with pulmonary sarcoidosis. Inpatient mortality was stratified by age, respiratory failure, mechanical ventilation (MV), hospital location, and setting (rural vs urban, academic vs nonacademic). A Cochran-Armitage test for trend was used to assess the linear trend in mortality, respiratory failure, and need for MV. RESULTS: Hospitalizations in patients with pulmonary sarcoidosis increased from 258.5 per 1,000,000 hospitalizations in 2007 to 705.7 per 1,000,000 in 2018. Hospitalizations for respiratory failure increased ninefold from 25.9 to 239.4 per 1,000,000 hospitalizations, and the need for MV increased threefold from 9.4 per 1,000,000 in 2007 to 29.4 per 1,000,000 in 2018. All-cause inpatient mortality was 2.6%; however, mortality was 13 times higher in patients with respiratory failure (10.6% vs 0.8%) and 26 times higher in patients who required MV (31.2% vs 1.2%). Inpatient mortality associated with respiratory failure declined 50% from 17.2% in 2007 to 6.6% in 2018. Independent inpatient mortality predictors were older age (adjusted hazard ratio [aHR], 1.025), respiratory failure (aHR, 3.12), need for MV (aHR, 6.01), pulmonary hypertension (pHTN; aHR, 1.44), pulmonary embolism (aHR, 1.61), and frailty (aHR, 3.10). INTERPRETATION: Hospitalizations for respiratory failure in patients with pulmonary sarcoidosis are increasing; however, inpatient mortality from respiratory failure has declined. Older age, respiratory failure, pHTN, and frailty are important predictors of inpatient mortality in patients with pulmonary sarcoidosis who are hospitalized.

Acute motor neuropathy with quadriparesis following treatment with triple tyrosine kinase inhibitor, nintedanib.

Idiopathic pulmonary fibrosis (IPF) is a rare progressive interstitial lung disease characterized by declining lung function, worsening dyspnea and poor prognosis with median survival of 3-5 years. IPF predominantly affects people over 60 years, it however has worse prognosis in younger patients with genetic predisposition like short telomere syndrome. Nintedanib, one of two anti-fibrotic therapies approved for IPF treatment has occasional neurological side effects like fatigue, dizziness and headaches. Significant polyneuropathy or motor dysfunction is rarely seen. This case report illustrates a patient who developed quadriparesis following initiation of Nintedanib.

Interstitial Lung Disease in Connective Tissue Disease: A Common Lesion With Heterogeneous Mechanisms and Treatment Considerations.

Connective tissue disease (CTD) related interstitial lung disease (CTD-ILD) is one of the leading causes of morbidity and mortality of CTD. Clinically, CTD-ILD is highly heterogenous and involves rheumatic immunity and multiple manifestations of respiratory complications affecting the airways, vessels, lung parenchyma, pleura, and respiratory muscles. The major pathological features of CTD are chronic inflammation of blood vessels and connective tissues, which can affect any organ leading to multi-system damage. The human lung is particularly vulnerable to such damage because anatomically it is abundant with collagen and blood vessels. The complex etiology of CTD-ILD includes genetic risks, epigenetic changes, and dysregulated immunity, which interact leading to disease under various ill-defined environmental triggers. CTD-ILD exhibits a broad spectra of clinical manifestations: from asymptomatic to severe dyspnea; from single-organ respiratory system involvement to multi-organ involvement. The disease course is also featured by remissions and relapses. It can range from stability or slow progression over several years to rapid deterioration. It can also present clinically as highly progressive from the initial onset of disease. Currently, the diagnosis of CTD-ILD is primarily based on distinct pathology subtype(s), imaging, as well as related CTD and autoantibodies profiles. Meticulous comprehensive clinical and laboratory assessment to improve the diagnostic process and management strategies are much needed. In this review, we focus on examining the pathogenesis of CTD-ILD with respect to genetics, environmental factors, and immunological factors. We also discuss the current state of knowledge and elaborate on the clinical characteristics of CTD-ILD, distinct pathohistological subtypes, imaging features, and related autoantibodies. Furthermore, we comment on the identification of high-risk patients and address how to stratify patients for precision medicine management approaches.

In-hospital mortality trends among patients with idiopathic pulmonary fibrosis in the United States between 2013-2017: a comparison of academic and non-academic programs.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a devastating condition characterized by progressive lung function decline and early mortality. While early accurate diagnosis is essential for IPF treatment, data evaluating the impact of hospital academic status on IPF-related mortality remains limited. Here we examined in-hospital mortality trends for patients with IPF from 2013 to 2017. We hypothesized that in-hospital IPF mortality would be influenced by hospital academic setting. METHODS: Hospitalization data was extracted from the National Inpatient Sample (NIS) for subjects with an international classification of disease code for IPF. In-hospital mortality stratified by hospital setting (academic versus non-academic) was the primary outcome of interest, with secondary analyses performed for subgroups with and without respiratory failure and requiring mechanical ventilation. Predictors of mortality were then assessed. RESULTS: Among 93,680 patients with IPF requiring hospitalization, 58,450 (62.4%) were admitted to academic institutions. In-hospital mortality decreased significantly in those admitted to an academic hospital (p < 0.001) but remained unchanged in patients admitted to a non-academic hospital. A plateau in-hospital mortality was observed among all hospitalized patients (p = 0.12), with a significant decrease observed for patients with admitted respiratory failure (p < 0.001) and those placed on mechanic ventilation (p < 0.001). CONCLUSION: In-hospital mortality decreased significantly for patients with IPF admitted to an academic hospital, suggesting that management strategies may differ by hospital setting. Mortality among those with respiratory failure and those requiring mechanical ventilation has dropped significantly. Our findings may underscore the importance of promoting early referral to an academic institution and adherence to international treatment guidelines.

Circulating Plasma Biomarkers of Survival in Antifibrotic-Treated Patients With Idiopathic Pulmonary Fibrosis.

BACKGROUND: A number of circulating plasma biomarkers have been shown to predict survival in patients with idiopathic pulmonary fibrosis (IPF), but most were identified before the use of antifibrotic (AF) therapy in this population. Because pirfenidone and nintedanib have been shown to slow IPF progression and may prolong survival, the role of such biomarkers in AF-treated patients is unclear. RESEARCH QUESTION: To determine whether plasma concentration of cancer antigen 125 (CA-125), C-X-C motif chemokine 13 (CXCL13), matrix metalloproteinase 7 (MMP7), surfactant protein D (SP-D), chitinase-3-like protein-1 (YKL-40), vascular cell adhesion protein-1 (VCAM-1), and osteopontin (OPN) is associated with differential transplant-free survival (TFS) in AF-exposed and nonexposed patients with IPF. STUDY DESIGN AND METHODS: A pooled, multicenter, propensity-matched analysis of IPF patients with and without AF exposure was performed. Optimal thresholds for biomarker dichotomization were identified in each group using iterative Cox regression. Longitudinal biomarker change was assessed in a subset of patients using linear mixed regression modeling. A clinical-molecular signature of IPF TFS was then derived and validated in an independent IPF cohort. RESULTS: Three hundred twenty-five patients were assessed, of which 68 AF-exposed and 172 nonexposed patients were included after propensity matching. CA-125, CXCL13, MMP7, YKL-40, and OPN predicted differential TFS in AF-exposed patients but at higher thresholds than in AF-nonexposed individuals. Plasma biomarker level generally increased over time in nonexposed patients but remained unchanged in AF-exposed patients. A clinical-molecular signature predicted decreased TFS in AF-exposed patients (hazard ratio [HR], 5.91; 95% CI, 2.25-15.5; P < .001) and maintained this association in an independent AF-exposed cohort (HR, 3.97; 95% CI, 1.62-9.72; P = .003). INTERPRETATION: Most plasma biomarkers assessed predicted differential TFS in AF-exposed patients with IPF, but at higher thresholds than in nonexposed patients. A clinical-molecular signature of IPF TFS may provide a reliable predictor of outcome risk in AF-treated patients but requires additional research for optimization and validation.

Derivation and Validation of a Diagnostic Prediction Tool for Interstitial Lung Disease.

BACKGROUND: Interstitial lung disease (ILD) results in high morbidity and health-care utilization. Diagnostic delays remain common and often occur in nonpulmonology settings. Screening for ILD in these settings has the potential to reduce diagnostic delays and improve patient outcomes. RESEARCH QUESTION: This study sought to determine whether a pulmonary function test (PFT)-derived diagnostic prediction tool (ILD-Screen) could accurately identify incident ILD cases in patients undergoing PFT in nonpulmonology settings. STUDY DESIGN AND METHODS: Clinical and physiologic PFT variables predictive of ILD were identified by using iterative multivariable logistic regression models. ILD status was determined by using a multi-reader approach. An ILD-Screen score was generated by using final regression model coefficients, with a score ≥ 8 considered positive. ILD-Screen test performance was validated in an independent external cohort and applied prospectively to PFTs over 1 year to identify incident ILD cases at our institution. RESULTS: Variables comprising the ILD-Screen were age, height, total lung capacity, FEV1, diffusion capacity, and PFT indication. The ILD-Screen showed consistent test performance across cohorts, with a sensitivity of 0.79 and a specificity of 0.83 when applied prospectively. A positive ILD-Screen strongly predicted ILD (OR, 18.6; 95% CI, 9.4-36.9) and outperformed common ILD clinical features, including cough, dyspnea, lung crackles, and restrictive lung physiology. Prospective ILD-Screen application resulted in a higher proportion of patients undergoing chest CT imaging compared with a historical control cohort (74% vs 56%, respectively; P = .003), with a significantly shorter median time to chest CT imaging (5.6 vs 21.1 months; P < .001). INTERPRETATION: The ILD-Screen showed good test performance in predicting ILD across diverse geographic settings and when applied prospectively. Systematic ILD-Screen application has the potential to reduce diagnostic delays and facilitate earlier intervention in patients with ILD.

Therapeutic hypothermia and mortality in the intensive care unit: systematic review and meta-analysis.

OBJECTIVE: Therapeutic hypothermia (TH) is defined as the designed reduction of the human body's core temperature to 32°C-35°C for a period of 24-48 hours. TH has been studied extensively in many diseases related to critical care illness. This meta-analysis assesses the effect of TH on mortality across different indications in medical, neurological and cardiothoracic care. DATA SOURCES: The online databases Embase, Ovid MEDLINE, TRIP and CINAHL were searched for eligible studies published between 1940 and October 2018. STUDY SELECTION: Randomised clinical trials of induced TH in adults for any indication. DATA EXTRACTION: Information about baseline characteristics of patients, mortality outcomes, cooling strategy and target temperature achieved in hypothermia and normothermia groups was collected. DATA SYNTHESIS: Eighty studies, with a total of 13 418 patients, were included in this meta-analysis: 22 studies for traumatic brain injury, six studies for stroke, five studies for out-of-hospital cardiac arrest (OHCA), 34 studies for intraoperative cardiopulmonary bypass, and 13 studies for other diseases. A total of 6901 patients (51.4%) were randomly allocated to the TH group and 6517 patients (48.6%) were randomised to the normothermia control group. The unadjusted analysis showed no significant difference in mortality across different critical care illnesses. However, after adjusting for population, gender, age and temperature, only the OHCA group showed a small statistically significant difference favouring TH, but this had a questionable clinical significance. CONCLUSIONS: This meta-analysis suggests that after decades of extensive research, TH has yet to show a beneficial effect on mortality across different critical care diseases.

Interstitial lung abnormality is prevalent and associated with worse outcome in patients undergoing transcatheter aortic valve replacement.

BACKGROUND: Interstitial lung abnormality (ILA) is found in 5-10% of the general population and is associated with increased mortality risk. Risk factors for ILA, including advanced age and smoking history also increase the risk for aortic stenosis (AS). Transcatheter aortic valve replacement (TAVR) has become an increasingly utilized intervention for patients with severe AS, and requires a high-resolution computed tomography (HRCT) of the chest to assess aortic valve dimensions. OBJECTIVES: To determine the prevalence and clinical significance of ILA on HRCT performed in patients referred for TAVR. METHODS: Consecutive pre-TAVR HRCTs performed over a 5-year period were reviewed. ILA was defined as bilateral, nondependent reticular opacities. All-cause mortality among TAVR recipients was compared between ILA cases and non-ILA controls matched 2:1 by age and gender using Cox proportional hazards regression and the Kaplan Meier estimator. RESULTS: Of 623 HRCTs screened, ILA was detected in 92 (14.7%), including 62 patients that underwent TAVR. Among ILA cases, 17 (27.4%) had a typical or probable usual interstitial pneumonia pattern, suggesting a diagnosis of idiopathic pulmonary fibrosis. Survival was worse in ILA cases compared to non-ILA controls (p = 0.008) and ILA was an independent predictor of mortality after multivariable adjustment (HR 3.29, 95% CI 1.34-8.08; p = 0.009). CONCLUSIONS: ILA is a common finding among patients with severe AS and is associated with increased mortality in those undergoing TAVR. Further research is needed to elucidate the biology underpinning this observation and determine whether ILA evaluation and risk stratification modulates this mortality risk.

Meta-Analysis of Continuous Positive Airway Pressure as a Therapy of Atrial Fibrillation in Obstructive Sleep Apnea.

Atrial fibrillation (AF) is a significant health care problem for patients with obstructive sleep apnea (OSA). Continuous positive airway pressure (CPAP) as a therapy for OSA is underused, and it is unknown if CPAP might reduce rates of AF. We systematically reviewed the published reports on CPAP use and risk of AF. MEDLINE, EMBASE, CINAHL, Web of Science, meeting abstracts, and Cochrane databases were searched from inception to June 2015. Studies needed to report the rates of AF in participants who were and were not on CPAP. Data were extracted by 2 authors. A total of 8 studies on OSA were identified (1 randomized controlled trial) with 698 CPAP users and 549 non-CPAP users. In a random effects model, patients treated with CPAP had a 42% decreased risk of AF (pooled risk ratio, 0.58; 95% confidence interval, 0.47 to 0.70; p <0.001). There was low heterogeneity in the results (I(2) = 30%). In metaregression analysis, benefits of CPAP were stronger for younger, obese, and male patients (p <0.05). An inverse relationship between CPAP therapy and AF recurrence was observed. Results suggest that more patients with AF also should be tested for OSA.