Diabetes, even newly defined by HbA1c testing, is associated with an increased risk of in-hospital death in adults with COVID-19

Abstract Background Diabetes is associated with poor coronavirus disease 2019 (COVID-19) outcomes. However, little is known on the impact of undiagnosed diabetes in the COVID-19 population. We investigated whether diabetes, particularly undiagnosed diabetes, was associated with an increased risk of death from COVID-19. Methods This retrospective study identified adult patients with COVID-19 admitted to Tongji Hospital (Wuhan) from January 28 to April 4, 2020. Diabetes was determined using patients’ past history (diagnosed) or was newly defined if the hemoglobin A1c (HbA1c) level at admission was ≥6.5% (48 mmol/mol) (undiagnosed). The in-hospital mortality rate and survival probability were compared between the non-diabetes and diabetes (overall, diagnosed, and undiagnosed diabetes) groups. Risk factors of mortality were explored using Cox regression analysis. Results Of 373 patients, 233 were included in the final analysis, among whom 80 (34.3%) had diabetes: 44 (55.0%) reported a diabetes history, and 36 (45.0%) were newly defined as having undiagnosed diabetes by HbA1c testing at admission. Compared with the non-diabetes group, the overall diabetes group had a significantly increased mortality rate (22.5% vs. 5.9%, p < 0.001). Moreover, the overall, diagnosed, and undiagnosed diabetes groups displayed lower survival probability in the Kaplan-Meier survival analysis (all p < 0.01). Using multivariate Cox regression, diabetes, age, quick sequential organ failure assessment score, and D-dimer ≥1.0 μg/mL were identified as independent risk factors for in-hospital death in patients with COVID-19. Conclusions The prevalence of undiagnosed pre-existing diabetes among patients with COVID-19 is high in China. Diabetes, even newly defined by HbA1c testing at admission, is associated with increased mortality in patients with COVID-19. Screening for undiagnosed diabetes by HbA1c measurement should be considered in adult Chinese inpatients with COVID-19.

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Diabetes, even newly defined by HbA1c testing, is associated with an increased risk of in-hospital death in adults with COVID-19

10.21203/rs.3.rs-93792/v1 ◽

2020 ◽

Author(s):

Ye Liu ◽

Ran Lu ◽

Junhong Wang ◽

Qin Cheng ◽

Ruitao Zhang ◽

...

Keyword(s):

Risk Factors ◽

Mortality Rate ◽

Survival Probability ◽

Cox Regression ◽

Undiagnosed Diabetes ◽

Hospital Death ◽

Diabetes Group ◽

Risk Of Death ◽

Increased Risk ◽

The Impact

Abstract Aims: Diabetes is associated with poor coronavirus disease 2019 (COVID-19) outcomes. However, little is known on the impact of undiagnosed diabetes in the COVID-19 population. We investigated whether diabetes, particularly undiagnosed diabetes, was associated with an increased risk of death from COVID-19.Methods: This retrospective study identified adult patients with COVID-19 admitted to Tongji Hospital (Wuhan) from January 28 to April 4, 2020. Diabetes was determined using patients’ past history (diagnosed) or was newly defined if the hemoglobin A1c (HbA1c) level at admission was 6.5% (≥ 48 mmol/mol) (undiagnosed). The in-hospital mortality rate and survival probability were compared between the non-diabetes and diabetes (overall, diagnosed, and undiagnosed diabetes) groups. Risk factors of mortality were explored using Cox regression analysis. Results: Of 373 patients, 233 were included in the final analysis, among whom 80 (34.3%) had diabetes: 44 (55.0%) reported a diabetes history, and 36 (45.0%) were newly defined as having undiagnosed diabetes by HbA1c testing at admission. Compared with the non-diabetes group, the overall diabetes group had a significantly increased mortality rate (22.5% vs 5.9%, p <0.001). Moreover, the overall, diagnosed, and undiagnosed diabetes groups displayed lower survival probability in the Kaplan-Meier survival analysis (all p <0.01). Using multivariate Cox regression, diabetes, age, quick sequential organ failure assessment score, and D-dimer ≥ 1.0 mg/mL were identified as independent risk factors for in-hospital death in patients with COVID-19.Conclusions: The prevalence of undiagnosed pre-existing diabetes among patients with COVID-19 is high in China. Diabetes, even newly defined by HbA1c testing at admission, is associated with increased mortality in patients with COVID-19. Screening for undiagnosed diabetes by HbA1c measurement should be considered in adult Chinese inpatients with COVID-19.

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Diabetes, Even Newly Defined by HbA1c Testing, Is Associated With an Increased Risk of in-hospital Death in Adults With COVID-19

10.21203/rs.3.rs-133453/v1 ◽

2020 ◽

Author(s):

Ye Liu ◽

Ran Lu ◽

Junhong Wang ◽

Qin Cheng ◽

Ruitao Zhang ◽

...

Keyword(s):

Risk Factors ◽

Mortality Rate ◽

Survival Probability ◽

Cox Regression ◽

Undiagnosed Diabetes ◽

Hospital Death ◽

Diabetes Group ◽

Risk Of Death ◽

Increased Risk ◽

The Impact

Abstract Background: Diabetes is associated with poor coronavirus disease 2019 (COVID-19) outcomes. However, little is known on the impact of undiagnosed diabetes in the COVID-19 population. We investigated whether diabetes, particularly undiagnosed diabetes, was associated with an increased risk of death from COVID-19.Methods: This retrospective study identified adult patients with COVID-19 admitted to Tongji Hospital (Wuhan) from January 28 to April 4, 2020. Diabetes was determined using patients’ past history (diagnosed) or was newly defined if the hemoglobin A1c (HbA1c) level at admission was 6.5% (≥ 48 mmol/mol) (undiagnosed). The in-hospital mortality rate and survival probability were compared between the non-diabetes and diabetes (overall, diagnosed, and undiagnosed diabetes) groups. Risk factors of mortality were explored using Cox regression analysis. Results: Of 373 patients, 233 were included in the final analysis, among whom 80 (34.3%) had diabetes: 44 (55.0%) reported a diabetes history, and 36 (45.0%) were newly defined as having undiagnosed diabetes by HbA1c testing at admission. Compared with the non-diabetes group, the overall diabetes group had a significantly increased mortality rate (22.5% vs 5.9%, p <0.001). Moreover, the overall, diagnosed, and undiagnosed diabetes groups displayed lower survival probability in the Kaplan-Meier survival analysis (all p <0.01). Using multivariate Cox regression, diabetes, age, quick sequential organ failure assessment score, and D-dimer ≥ 1.0 mg/mL were identified as independent risk factors for in-hospital death in patients with COVID-19.Conclusions: The prevalence of undiagnosed pre-existing diabetes among patients with COVID-19 is high in China. Diabetes, even newly defined by HbA1c testing at admission, is associated with increased mortality in patients with COVID-19. Screening for undiagnosed diabetes by HbA1c measurement should be considered in adult Chinese inpatients with COVID-19.

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Impact of Interstitial Pneumonia on the Survival and Risk Factors Analysis of Patients with Hematological Malignancy

BioMed Research International ◽

10.1155/2013/185362 ◽

2013 ◽

Vol 2013 ◽

pp. 1-9 ◽

Cited By ~ 2

Author(s):

Wei-Liang Chen ◽

Yu-Tzu Tsao ◽

Tsun-Hou Chang ◽

Tsu-Yi Chao ◽

Woei-Yau Kao ◽

...

Keyword(s):

Risk Factors ◽

Overall Survival ◽

Interstitial Pneumonia ◽

Cox Regression ◽

Hematological Malignancy ◽

Prognostic Indicator ◽

Risk Of Death ◽

Increased Risk ◽

Significant Difference ◽

The Impact

Background. The emergence of interstitial pneumonia (IP) in patients with hematological malignancy (HM) is becoming a challenging scenario in current practice. However, detailed characterization and investigation of outcomes and risk factors on survival have not been addressed.Methods. We conducted a retrospective study of 42,584 cancer patients covering the period between 1996 and 2008 using the institutional cancer registry system. Among 816 HM patients, 61 patients with IP were recognized. The clinical features, laboratory results, and histological types were studied to determine the impact of IP on survival and identify the profile of prognostic factors.Results. HM patients with IP showed a significant worse survival than those without IP in the 5-year overall survival (P=0.027). The overall survival showed no significant difference between infectious pneumonia and noninfectious interstitial pneumonia (IIP versus nIIP) (P=0.323). In a multivariate Cox regression model, leukocyte and platelet count were associated with increased risk of death.Conclusions. The occurrence of IP in HM patients is associated with increased mortality. Of interest, nIIP is a prognostic indicator in patients with lymphoma but not in patients with leukemia. However, aggressive management of IP in patients with HM is strongly advised, and further prospective survey is warranted.

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AB0393 PRE-EXISTING MORBIDITY AS A RISK FACTORS FOR MORTALITY IN IgA VASCULITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.2307 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 1224.3-1225

Author(s):

J. Nossent ◽

D. Preen ◽

W. Raymond ◽

H. Keen ◽

C. Inderjeeth

Keyword(s):

Risk Factors ◽

Cohort Study ◽

Mortality Rate ◽

Data Collection ◽

Premature Death ◽

Iga Vasculitis ◽

Risk Of Death ◽

Increased Risk ◽

Serious Infections ◽

Western Australian

Background:IgA vasculitis is generally considered to be a self-limiting condition, but this is at odds with the increased mortality observed in adult patients with IgA vasculitis (1).Objectives:With sparse data on prognostic factors in IgAV, we investigated whether pre-existing conditions are risk factors for mortality in adult IgAV patients.Methods:Observational population-based cohort study using state-wide linked longitudinal health data for adults with IgAV (n=267) and matched controls (n=1080) between 1980-2015. Charlson comorbidity index (CCI) and serious infections (SI) were recorded over an extensive lookback period prior to diagnosis. Date and causes of death were extracted from the WA Death Registry. Mortality rate (deaths/1000 person-years) ratios (MRR) and time dependent survival analysis assessed the risk of death. Age and gender specific mortality rate data were obtained from the Australian Bureau of Statistics.Results:During 9.9 (±9.8) years lookback IgAV patients accrued higher CCI scores (2.60 vs1.50 p<0.001) and had higher risk of SI (OR 8.4, p<0.001), not fully explained by CCI scores. During 19 years follow-up, the risk of death in IgAV patients (n=137) was higher than in controls (n=397) (MRR 2.06, CI 1.70-2.50, p<0.01) and the general population (SMRR 5.64, CI 4.25, 7.53, p<0.001). Survival in IgAV was reduced at five (72.7 vs. 89.7 %) and twenty years (45.2% vs. 65.6 %) (both p<0.05). CCI (HR1.88, CI:1.25 - 2.73, p=0.001), renal failure (HR 1.48, CI: 1.04 - 2.22, p=0.03) and prior SI (HR 1.48, CI:1.01 – 2.16, p=0.04) were independent risk factors. Death from infections (5.8 vs 1.8%, p=0.02) was significantly more frequent in IgAV patients.Conclusion:Premorbid accrual of comorbidity is increased and predicts premature death in IgAV patients. However, comorbidity does not fully explain the increased risk of serious infections prior to diagnosis or the increased mortality due to infections in IgAV.References:[1]Villatoro-Villar M, Crowson CS, Warrington KJ, Makol A, Ytterberg SR, Koster MJ. Clinical Characteristics of Biopsy-Proven IgA Vasculitis in Children and Adults: A Retrospective Cohort Study. Mayo Clin Proc. 2019;94(9):1769-80.Acknowledgements:The authors would like to acknowledge the support of the Arthritis Foundation of WA and acknowledge the Western Australian Data Linkage Branch, the Western Australian Department of Health, and the data custodians of, the Hospital and Morbidity Data Collection, the Emergency Department Data Collection the WA Cancer Register and the WA Death Register for their assistance with the study.Disclosure of Interests:None declared

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The Impact of a Long-Term Rivastigmine and Donepezil Treatment on All-Cause Mortality in Patients With Alzheimer’s Disease

American Journal of Alzheimer s Disease & Other Dementias® ◽

10.1177/1533317518775044 ◽

2018 ◽

Vol 33 (6) ◽

pp. 385-393 ◽

Cited By ~ 3

Author(s):

Jakub Kazmierski ◽

Chaido Messini-Zachou ◽

Mara Gkioka ◽

Magda Tsolaki

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cox Regression ◽

Symptomatic Treatment ◽

Risk Of Death ◽

Increased Risk ◽

Functional Assessments ◽

The Impact

Cholinesterase inhibitors (ChEIs) are the mainstays of symptomatic treatment of Alzheimer’s disease (AD); however, their efficacy is limited, and their use was associated with deaths in some groups of patients. The aim of the current study was to assess the impact of the long-term use of ChEIs on mortality in patients with AD. This observational, longitudinal study included 1171 adult patients with a diagnosis of AD treated with donepezil or rivastigmine. Each patient was observed for 24 months or until death. The cognitive and functional assessments, the use of ChEIs, memantine, antipsychotics, antidepressants, and anxiolytics were recorded. The total number of deaths at the end of the observational period was 99 (8.45%). The patients who had received rivastigmine treatment were at an increased risk of death in the follow-up period. The higher risk of death in the rivastigmine group remained significant in multivariate Cox regression models.

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Risk factors for myocardial injury and death in patients with COVID-19: insights from a cohort study with chest computed tomography

Cardiovascular Research ◽

10.1093/cvr/cvaa193 ◽

2020 ◽

Vol 116 (14) ◽

pp. 2239-2246 ◽

Cited By ~ 3

Author(s):

Giuseppe Ferrante ◽

Fabio Fazzari ◽

Ottavia Cozzi ◽

Matteo Maurina ◽

Renato Bragato ◽

...

Keyword(s):

Risk Factors ◽

Computed Tomography ◽

Cohort Study ◽

Myocardial Injury ◽

Troponin I ◽

Cox Regression ◽

Chest Ct ◽

Chest Computed Tomography ◽

Risk Of Death ◽

Increased Risk

Abstract Aims Whether pulmonary artery (PA) dimension and coronary artery calcium (CAC) score, as assessed by chest computed tomography (CT), are associated with myocardial injury in patients with coronavirus disease 2019 (COVID-19) is not known. The aim of this study was to explore the risk factors for myocardial injury and death and to investigate whether myocardial injury has an independent association with all-cause mortality in patients with COVID-19. Methods and Results This is a single-centre cohort study including consecutive patients with laboratory-confirmed COVID-19 undergoing chest CT on admission. Myocardial injury was defined as high-sensitivity troponin I >20 ng/L on admission. A total of 332 patients with a median follow-up of 12 days were included. There were 68 (20.5%) deaths; 123 (37%) patients had myocardial injury. PA diameter was higher in patients with myocardial injury compared with patients without myocardial injury [29.0 (25th–75th percentile, 27–32) mm vs. 27.7 (25–30) mm, P < 0.001). PA diameter was independently associated with an increased risk of myocardial injury [adjusted odds ratio 1.10, 95% confidence interval (CI) 1.02–1.19, P = 0.01] and death [adjusted hazard ratio (HR) 1.09, 95% CI 1.02–1.17, P = 0.01]. Compared with patients without myocardial injury, patients with myocardial injury had a lower prevalence of a CAC score of zero (25% vs. 55%, P < 0.001); however, the CAC score did not emerge as a predictor of myocardial injury by multivariable logistic regression. Myocardial injury was independently associated with an increased risk of death by multivariable Cox regression (adjusted HR 2.25, 95% CI 1.27–3.96, P = 0.005). Older age, lower estimated glomerular filtration rate, and lower PaO2/FiO2 ratio on admission were other independent predictors for both myocardial injury and death. Conclusions An increased PA diameter, as assessed by chest CT, is an independent risk factor for myocardial injury and mortality in patients with COVID-19. Myocardial injury is independently associated with an approximately two-fold increased risk of death.

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Altered Lipid Profile is a Risk Factor for the Progression Andrecurrenceof COVID-19: From Two Retrospective Cohorts

10.21203/rs.3.rs-60159/v1 ◽

2020 ◽

Author(s):

Hui Jin ◽

Junji He ◽

Chuan Dong ◽

Luhong Cao ◽

Xing Qi ◽

...

Keyword(s):

Risk Factor ◽

Lipid Profile ◽

Cox Regression ◽

Lipid Lowering ◽

Hospital Death ◽

Lipid Lowering Therapy ◽

Clinical Endpoints ◽

Increased Risk ◽

The Impact ◽

The Relationship

Abstract Background The COVID-19 pandemic has spread worldwide. However, the impact of lipid profile and lipid-lowering treatment on clinical endpoints in COVID-19 have not previously been investigated. Methods In this retrospective, multicenter cohort study, we consecutively enrolled 430 adult COVID-19 patients from two Chinese hospitals (one each in Chengdu and Wuhan) admitted during February 2020 and followed-up until April 30. Demographic, metabolic profile, laboratory, treatment and clinical endpoint data including in-hospital death and recurrence of COVID-19, were collected. Results In Chengdu patients, univariable and multivariable Cox regression showed that the low-density lipoprotein cholesterol (LDL-C) dyslipidemia on admission was associated with the recurrence of COVID-19 during the follow-up period. In Wuhan cohort, the patients with triglycerides hyperlipemia had an increased risk of in-hospital death. However, in both cohorts, statin therapy during COVID-19 course did not affect these clinical endpoints. Compared to the Chengdu cohort, the Wuhan patients tended to have more severe COVID-19 but, unexpectedly, had lower levels of serum lipid. It is of interesting to notice that the relationship between the observed biomarkers of inflammation and lipid do not match the relationship between the organ function measures and this lipid. Conclusions The baseline dyslipidemia should be considered as a risk factor for poor prognosis and recurrence of COVID-19. The lipid level may be altered during COVID-19 course, since lipidology may be distinctly affected by both inflammation and organic damage for SARS-CoV-2. Further investigation is needed on the role of use of lipid-lowering therapy among patients with COVID-19 infections.

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The impact of extrahepatic disease among patients undergoing liver-directed therapy for neuroendocrine liver metastasis: A multi-institutional analysis.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.4_suppl.277 ◽

2017 ◽

Vol 35 (4_suppl) ◽

pp. 277-277

Author(s):

Aslam Ejaz ◽

Timothy M. Pawlik ◽

Bradley Reames ◽

Shishir Kumar Maithel ◽

George A. Poultsides ◽

...

Keyword(s):

Liver Metastasis ◽

Cox Regression ◽

Wedge Resection ◽

Extrahepatic Disease ◽

Primary Tumors ◽

Entire Cohort ◽

Risk Of Death ◽

Increased Risk ◽

Neuroendocrine Liver Metastasis ◽

The Impact

277 Background: Management of neuroendocrine liver metastasis (NELM) in the presence of synchronous extrahepatic disease (EHD) is controversial. We sought to examine the outcomes of patients undergoing liver-directed therapy for NELM in the presence of EHD using a large multicenter international cohort of patients. Methods: 612 patients who underwent liver-directed therapy were identified from 8 participating institutions. Postoperative outcomes, as well as overall (OS) and progression-free survival (PFS) were compared between patients with (N = 70, 11.4%) and without (N = 542, 88.6%) EHD. Results: Median age of the cohort was 57 years (IQR: 48, 65) with a slight majority of patients being male (N = 326, 53.3%). The majority of primary tumors were located in the pancreas (N = 254, 41.8%) followed by the small bowel (N = 188, 30.9%). At the time of liver-directed surgery, patients underwent surgery alone (N = 471, 77.0%), ablation alone (N = 15, 2.5%), or a combined approach (N = 126, 20.6%). Most patients underwent a non-anatomic wedge resection (N = 404, 66.0%). Patients with EHD had more aggressive high-grade tumors (EHD: 44.4% vs. no EHD: 16.1%; P < 0.001). EHD was most commonly located in the peritoneum (N = 29, 41.4%) and lung (N = 19, 27.1%). Among the 70 patients with EHD, 20.0% (N = 14) underwent concurrent resection for the EHD. After a median follow-up of 51 months, 174 (28.4%) patients died with a median OS of 140.4 months among the entire cohort. Patients with EHD had a shorter median OS versus patients who did not have EHD (EHD: 87 months vs. no EHD: not reached; P = 0.002). Similarly, PFS was shorter among patients with EHD compared with patients without EHD (EHD: 46.8 months vs. no EHD: 68.6 months; P = 0.005). In the cox regression model, the presence of EHD was independently associated with an increased risk of death (HR: 2.56, 95%CI 1.16-5.62; P = 0.02). Conclusions: Patients with NELM and EHD had more aggressive tumors, which conferred over a 2-fold increased risk of death compared with patients who did not have EHD. Surgical treatment of NELM among patients with EHD should be individualized.

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Symptom burden of patients with advanced pancreas cancer (APC): A provincial cancer institute observational study.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.4_suppl.384 ◽

2019 ◽

Vol 37 (4_suppl) ◽

pp. 384-384

Author(s):

Julie Ward ◽

Christina Kim ◽

Pascal J Lambert

Keyword(s):

Metastatic Disease ◽

Cox Regression ◽

Advanced Pancreatic Cancer ◽

Symptom Burden ◽

Joint Model ◽

Assessment System ◽

Risk Of Death ◽

Model Average ◽

Increased Risk ◽

The Impact

384 Background: Patients (pts) with advanced pancreatic cancer (APC) experience many disease-related symptoms. The Edmonton Symptom Assessment System (ESAS) measures the severity of 9 separate domains, and is completed by pts at each visit at our provincial cancer institute. The aim of this study was to describe symptom burden at baseline and over time for chemotherapy (CT) treated pts with APC, using ESAS. Methods: Pts diagnosed with APC between 2012-2016 and treated with at least 1 cycle of CT were identified. ESAS scores were extracted from the electronic medical record. Descriptive statistics were used to report the most common symptoms of pts with APC. A joint model was used to describe the trajectory of ESAS during follow-up while controlling for death. Multivariable Cox regression was used to identify independent predictors of death. Results: Of 123 pts identified, 61% had metastatic disease, 82.1% had a baseline ECOG of 0-1, with an average age of 64.8. 1608 clinic visits had an ESAS score documented and 87% of pts completed ≥ 2 ESAS assessments. Median overall survival was 10.2 months. Median progression free survival was 6.7 months. At baseline, the 10th percentile, median and 90th percentile for total symptom distress (TSD) score were 6.2, 24 and 53 respectively. 86% of pts had at least one ESAS score of ≥ 4 at baseline, with the most common being: fatigue, nausea, anxiety, and shortness of breath. Using a joint model, average TSD scores for the cohort improved for the first 4 to 5 months after starting CT and started to rise after 6 months. Average TSD scores at 15 to 18 months were similar to scores at baseline. Controlling for metastatic disease and CT type, for every increase of 10 in baseline TSD score, there was a 5% increased risk of death. Conclusions: The ESAS tool reflects the heavy burden of cancer-associated symptoms in APC. Symptoms improve months after starting CT and eventually worsen. The impact of early intervention to address symptom management is an important area of investigation in APC.

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P2746Survival of people with valvular heart disease in the community (OxValve-Survive)

European Heart Journal ◽

10.1093/eurheartj/ehz748.1063 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

C Taylor ◽

J M Ordonez-Mena ◽

A K Roalfe ◽

J Wilson ◽

S Myerson ◽

...

Keyword(s):

Heart Disease ◽

Cause Of Death ◽

Valvular Heart Disease ◽

Cox Regression ◽

Severe Disease ◽

Research Centre ◽

Mortality Data ◽

Risk Of Death ◽

Increased Risk ◽

The Impact

Abstract Background Valvular heart disease (VHD) occurs commonly in older patients (>65 years) but the majority is mild disease, which is of uncertain importance. Understanding the impact of VHD on mortality in this older group of patients would help determine its relevance and aid the appropriate use of healthcare resources. OxValve is a cohort study in Oxfordshire screening people aged 65 and over for VHD. Over 4,009 participants were recruited between August 2009 and May 2016 and screened using echocardiography to establish the presence and severity of VHD. AIMS To report survival in the OxValve cohort, and to investigate whether people with VHD are at increased risk of death. Methods The OxValve cohort was linked to Office for National Statistics mortality data to obtain date and cause of death. Cox regression was used to investigate the association of any VHD, VHD of significant severity, and VHD subtypes with all-cause and cause-specific mortality, adjusting for potential confounders including age, sex, socioeconomic status, smoking, and comorbidities. Results Linked mortality data was available for 3,511 OxValve participants up to September 2018 (median 5.85 years follow-up). VHD was present in 2,645 (75.3%) participants and of these 288 (8.2%) had significant VHD. In total, 311 (8.9%) participants had died. Cancer was the commonest cause of death (n=135), followed by cardiovascular disease (n=75) and respiratory disease (n=35). After adjustment for age and other covariates, mild to moderate VHD was not associated with increased all-cause mortality (HR 1.16, 95% CI: 0.89 to 1.50). However, VHD of significant severity (moderate or severe disease) was associated with a nearly two-fold higher risk of death overall (HR 1.92, 95% CI: 1:38 to 2.67) including increased CVD mortality (HR 2.25, 95% CI: 1.21 to 4.18). DISCUSSION Mild to moderate VHD was very common, but was not associated with increased mortality. Significant VHD was however associated with a two-fold reduction in survival. Further research is required to understand the natural history of VHD, how to identify those with progressive disease and when to intervene. Acknowledgement/Funding NIHR Biomedical Research Centre, Oxford

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