Temporal trends in the incidence of heart failure among ...
Temporal trends in the incidence of heart failure among patients with COPD and its impact on mortalityAuthorsEleanor L Axson MPH1*, Varun Sundaram MD1, 2, Chloe I Bloom PhD1, Alex Bottle PhD3, Martin R Cowie MD1, Jennifer K Quint PhD1Affiliations1 National Heart and Lung Institute, Imperial College London, London, UK2 Harrington Heart and Vascular Institute, University Hospitals Cleveland Medical Centre, Case Western Reserve University, Cleveland, USA3 Dr Foster Unit, Department of Primary Care and Public Health, Imperial College London, London, UK*Corresponding AuthorEleanor L Axson MPH AFHEAG05 Emmanuel Kaye BuildingNational Heart and Lung InstituteImperial College LondonManresa RoadLondon, SW3 6LRUnited KingdomE-mail: e.axson@imperial.ac.ukTelephone: +44 (0) 207 594 7987Author ContributionELA conducted the analyses and drafted the manuscript. VS aided in the drafting of the manuscript. CIB, AB, MRC, and JKQ contributed to the design of the study and revision of the manuscript. ELA is the guarantor.FundingThis work was not funded by any particular entity.Conflicts of InterestMiss Axson and Dr Sundaram have nothing to disclose. Dr Bloom reports grants from AstraZeneca, grants from Chiesi, grants from Asthma UK, outside the submitted work. Dr Bottle reports grants from Dr Foster, during the conduct of the study; grants from Medtronic, outside the submitted work. Prof Cowie reports receiving research funding and speaker fees from ResMed, Boston Scientific, Medtronic, and Abbott and consultancy and speaker fees from Servier, Novartis, Vifor, LivaNova, Pfizer, Roche Diagnostics, and Amgen, outside the submitted work. Dr Quint reports grants from MRC, grants from BLF, grants from The Health Foundation, grants and personal fees from AZ, grants and personal fees from BI, grants from Chiesi, grants and personal fees from Bayer, grants and personal fees from GSK, outside the submitted work.DisclaimerThis research was supported by the National Institute for Health Research (NIHR) Imperial Biomedical Research Centre (BRC). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. This study is based in part on data from the Clinical Practice Research Datalink (CPRD) obtained under licence from the UK Medicines and Healthcare products Regulatory Agency. The data is provided by patients and collected by the National Health Service (NHS) as part of their care and support. The Office for National Statistics (ONS) was the provider of the ONS Data contained within the CPRD Data and maintains a Copyright ? 2019, re-used with the permission of The Health & Social Care Information Centre, all rights reserved. The interpretation and conclusions contained in this study are those of the authors alone.Data sharingData are available on request from the Clinical Practice Research Datalink (CPRD). Their provision requires the purchase of a license and our license does not permit us to make them publicly available to all. We used data from the version collected in January 2018 and have clearly specified the data selected in our Methods section. To allow identical data to be obtained by others, via the purchase of a license, we will provide the code lists on request. Licences are available from the CPRD (): The Clinical Practice Research Datalink Group, The Medicines and Healthcare products Regulatory Agency, 10 South Colonnade, Canary Wharf, London E14 4PU.Subject Category9.4 COPD: ComorbiditiesMeSHComorbidity, Epidemiology, Cause of DeathWord Count3,732 wordsThis article has an online supplement, which is accessible from this issue's table of contents online at .AbstractRationaleHeart failure (HF) is a common comorbidity in the chronic obstructive pulmonary disease (COPD) population, but previous research has shown under recognition. ObjectivesTo determine the incidence of HF in a prevalent COPD cohort. To determine the impact of incident HF on short- and long-term mortality of patients with COPD.MethodsCrude incidence of HF in the HF-na?ve primary care COPD population was calculated for each year from 2006-2016 using UK data from the Clinical Practice Research Datalink (CPRD). Patients with COPD were identified using a validated code list and were required to be over 35 years old at COPD diagnosis, have a history of smoking, and have documented airflow obstruction. Office of National Statistics provided mortality data for England. Adjusted mortality rate ratios (aMRR) from Poisson regression were calculated for patients with COPD and incident HF (COPD-iHF) in 2006, 2011, and 2015 compared temporally and with patients with COPD and without incident HF (COPD-no HF) in those years. Regression was adjusted for age, sex, BMI, severity of airflow limitation, smoking status, history of cardiovascular disease, and diabetes.ResultsWe identified 95,987 HF-na?ve patients with COPD. Crude incidence of HF was steady from 2006-2016 (1.18 per 100 person-years (95%CI: 1.09, 1.27)). Patients with COPD-iHF experienced greater than threefold increase in one-year mortality and twofold increase in five-year and 10-year mortality compared with patients with COPD-no HF, with no change based on year of HF diagnosis. Mortality of patients with COPD-iHF did not improve over time, comparing incident HF in 2011 (1-year aMRR 1.26, 95%CI: 0.83, 1.90; 5-year aMRR 1.26, 95%CI: 0.98, 1.61) and 2015 (1-year aMRR 1.63, 95%CI: 0.98, 2.70) with incident HF in 2006.ConclusionsThe incidence of HF in the UK COPD population was stable in the last decade. Survival of patients with COPD and incident HF has not improved over time in England. Bespoke guidelines for the diagnosis and management of HF in the COPD population are needed to improve identification and survival of patients.IntroductionChronic obstructive pulmonary disease (COPD) and heart failure (HF) are both systemic disorders that share risk factors and pathophysiological pathways, with the ability of either condition to exacerbate the other leading to increased healthcare costs PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Db3dpZTwvQXV0aG9yPjxZZWFyPjIwMTQ8L1llYXI+PFJl
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ADDIN EN.CITE.DATA (1-3). Patients with COPD have an increased risk of developing HF, particularly HF with preserved ejection fraction PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5BZ2Fyd2FsPC9BdXRob3I+PFllYXI+MjAxMjwvWWVhcj48
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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5BZ2Fyd2FsPC9BdXRob3I+PFllYXI+MjAxMjwvWWVhcj48
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ADDIN EN.CITE.DATA (12, 13). Studies have found anywhere from 10-46% previously unrecognised left HF with left ventricular dysfunction in COPD populations ADDIN EN.CITE <EndNote><Cite><Author>Rutten</Author><Year>2006</Year><RecNum>261</RecNum><DisplayText>(14)</DisplayText><record><rec-number>261</rec-number><foreign-keys><key app="EN" db-id="9xdxprve7sdt96eerrovwfd3t002fvet0rfe" timestamp="1523436049">261</key><key app="ENWeb" db-id="">0</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Rutten, F. H.</author><author>Cramer, M. J.</author><author>Lammers, J. W.</author><author>Grobbee, D. E.</author><author>Hoes, A. W.</author></authors></contributors><auth-address>Utrecht Heart Failure Organisation (UHFO), Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, PO Box 85060, Stratenum 6.101, 3508 AB Utrecht, the Netherlands. F.H.Rutten@umcutrecht.nl</auth-address><titles><title>Heart failure and chronic obstructive pulmonary disease: An ignored combination?</title><secondary-title>Eur J Heart Fail</secondary-title></titles><periodical><full-title>Eur J Heart Fail</full-title></periodical><pages>706-11</pages><volume>8</volume><number>7</number><edition>2006/03/15</edition><keywords><keyword>Adrenergic beta-Agonists/adverse effects</keyword><keyword>Aged</keyword><keyword>Comorbidity</keyword><keyword>Digitalis/adverse effects</keyword><keyword>Female</keyword><keyword>Heart Failure/*complications/diagnosis/*epidemiology/therapy</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Prevalence</keyword><keyword>Pulmonary Disease, Chronic</keyword><keyword>Obstructive/*complications/diagnosis/*epidemiology/therapy</keyword></keywords><dates><year>2006</year><pub-dates><date>Nov</date></pub-dates></dates><isbn>1388-9842 (Print)
1388-9842 (Linking)</isbn><accession-num>16531114</accession-num><urls><related-urls><url>;(14). Additionally, research is divided as to how incident HF impacts mortality in COPD patients. Newly diagnosed HF was found to significantly increase all-cause mortality in patients with COPD in one study ADDIN EN.CITE <EndNote><Cite><Author>Boudestein</Author><Year>2009</Year><RecNum>214</RecNum><DisplayText>(15)</DisplayText><record><rec-number>214</rec-number><foreign-keys><key app="EN" db-id="9xdxprve7sdt96eerrovwfd3t002fvet0rfe" timestamp="1519135829">214</key><key app="ENWeb" db-id="">0</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Boudestein, L. C.</author><author>Rutten, F. H.</author><author>Cramer, M. J.</author><author>Lammers, J. W.</author><author>Hoes, A. W.</author></authors></contributors><auth-address>Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.</auth-address><titles><title>The impact of concurrent heart failure on prognosis in patients with chronic obstructive pulmonary disease</title><secondary-title>Eur J Heart Fail</secondary-title></titles><periodical><full-title>Eur J Heart Fail</full-title></periodical><pages>1182-8</pages><volume>11</volume><number>12</number><edition>2009/11/06</edition><keywords><keyword>Aged</keyword><keyword>Female</keyword><keyword>Heart Failure/*complications</keyword><keyword>Hospitalization</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Pneumonia/complications</keyword><keyword>Prognosis</keyword><keyword>Pulmonary Disease, Chronic</keyword><keyword>Obstructive/*complications/mortality/physiopathology/therapy</keyword><keyword>Survival Rate</keyword></keywords><dates><year>2009</year><pub-dates><date>Dec</date></pub-dates></dates><isbn>1879-0844 (Electronic)
1388-9842 (Linking)</isbn><accession-num>19887495</accession-num><urls><related-urls><url>;(15); contrastingly, another study found no significant impact of incident HF on all-cause mortality among patients with COPD ADDIN EN.CITE <EndNote><Cite><Author>Plachi</Author><Year>2018</Year><RecNum>259</RecNum><DisplayText>(16)</DisplayText><record><rec-number>259</rec-number><foreign-keys><key app="EN" db-id="9xdxprve7sdt96eerrovwfd3t002fvet0rfe" timestamp="1523434030">259</key><key app="ENWeb" db-id="">0</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Plachi, F.</author><author>Balzan, F. M.</author><author>Sanseverino, R. A.</author><author>Palombini, D. V.</author><author>Marques, R. D.</author><author>Clausell, N. O.</author><author>Knorst, M. M.</author><author>Neder, J. A.</author><author>Berton, D. C.</author></authors></contributors><auth-address>1Hospital de Clinicas de Porto Alegre (HCPA),Universidade Federal do Rio Grande do Sul (UFRGS),Porto Alegre,RS,Brazil.
2Queen's University & Kingston General Hospital,Kingston,ON,Canada.</auth-address><titles><title>Characteristics associated with mortality in patients with chronic obstructive pulmonary disease (COPD)-heart failure coexistence</title><secondary-title>Prim Health Care Res Dev</secondary-title></titles><periodical><full-title>Prim Health Care Res Dev</full-title></periodical><pages>1-5</pages><edition>2018/02/22</edition><keywords><keyword>chronic obstructive pulmonary disease</keyword><keyword>exercise</keyword><keyword>heart failure</keyword><keyword>hospitalization</keyword><keyword>survival</keyword></keywords><dates><year>2018</year><pub-dates><date>Feb 21</date></pub-dates></dates><isbn>1477-1128 (Electronic)
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ADDIN EN.CITE.DATA (18). Patients were required to have acceptable data for research as determined by CPRD. Patients must have had a COPD diagnosis over the age of 35 years, a history of smoking, and documented airflow obstruction (forced expiratory volume in 1 second/forced vital capacity ratio (FEV1/FVC) < 0.70) per UK guidelines ADDIN EN.CITE <EndNote><Cite><Year>2018</Year><RecNum>23153</RecNum><DisplayText>(19)</DisplayText><record><rec-number>23153</rec-number><foreign-keys><key app="EN" db-id="9xdxprve7sdt96eerrovwfd3t002fvet0rfe" timestamp="1552397649">23153</key><key app="ENWeb" db-id="">0</key></foreign-keys><ref-type name="Government Document">46</ref-type><contributors><authors><author>National Institute for Health and Care Excellence (NICE), 2018</author></authors></contributors><titles><title>Chronic obstructive pulmonary disease in over 16s: diagnosis and management</title></titles><dates><year>2018</year></dates><urls><related-urls><url> Institute for Health and Care Excellence (NICE)</custom1></record></Cite></EndNote>(19). HF was identified using a code list created by clinicians (Table E1). All patients with a diagnosis of HF (prevalent HF) prior to the start of follow up were excluded. Patients with incident HF were defined as those for whom the first occurrence of a HF diagnostic code in primary care occurred during the study period, 2006-2016. The start of follow-up was defined as the latest date of the following: 1) the date from which practice data was deemed eligible for research per CPRD, 2) the date from which the patient has continuous data, 3) the patient’s 35th birthdate, 4) the start of the study on 01 January 2006, or 5) the date of COPD diagnosis.CovariatesThe most recent measures for baseline characteristics were obtained at start of follow-up on 01 January 2006. BMI, in kg/m2, was measured continuously. Smoking was categorised as ‘current smoker’ and ‘former smoker’. Severity of airways limitation, within +/- 2 years of start of follow-up, was graded based on the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines and grouped as GOLD1 (mild), GOLD2 (moderate), GOLD3 (severe), and GOLD4 (severe-very severe) ADDIN EN.CITE <EndNote><Cite><Author>GOLD</Author><Year>2017</Year><RecNum>9</RecNum><DisplayText>(20)</DisplayText><record><rec-number>9</rec-number><foreign-keys><key app="EN" db-id="9xdxprve7sdt96eerrovwfd3t002fvet0rfe" timestamp="1515502506">9</key></foreign-keys><ref-type name="Web Page">12</ref-type><contributors><authors><author>GOLD</author></authors></contributors><titles><title>Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017</title></titles><number>10 Jan 2018</number><dates><year>2017</year></dates><work-type>Webpage</work-type><urls><related-urls><url>;(20), validity of spirometry values has been previously assessed as high quality in CPRD PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Sb3RobmllPC9BdXRob3I+PFllYXI+MjAxNzwvWWVhcj48
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ADDIN EN.CITE.DATA (21). History of cardiovascular disease included prior diagnosis of ischaemic heart disease, peripheral artery disease, atrial fibrillation, hypertension, and/or stroke.Statistical analysesBaseline characteristics were expressed using mean ± standard deviation for continuous variables and percentages for categorical variables. We calculated sex, age group (35-64, 65-74, 75-84, and 85+ years), smoking status, and GOLD- specific, HF incidence rates per 100 person years at risk for each year (2006-2016) in patients with COPD.To isolate the effect of incident HF on mortality, we calculated crude mortality rate ratios (MRR) by comparing mortality rates at 1, 5 and 10 years of follow-up of patients with COPD with incident HF (COPD-iHF) versus patients with COPD without incident HF (COPD-no HF) for the same time period. For example, patients with COPD with HF diagnosed in 2006 were followed for 1-year, 5-year, and 10-year mortality and compared to patients with COPD without HF diagnosed in 2006. A Kaplan-Meier survivor curve was produced comparing patients with COPD with and without incident HF diagnosis in 2006 over 10 years of follow-up. Furthermore, adjusted mortality rate ratios (1-, 5- and 10-year rates) of patients with COPD with and without incident HF were calculated stratified by GOLD. Censoring was defined as death, transfer from practice, last date for which practice data was available, last date for which linked ONS data was available, or the end of the study (Figure E1).For the analysis of temporal trends in the short term mortality rates of patients with COPD-iHF, crude MRR were calculated comparing 1-year mortality rates of patients with COPD-iHF in 2011 and 2015, with patients with COPD-iHF in 2006 as the reference. Additionally, trends in long-term mortality rates (i.e., 5-year mortality rates) were evaluated by comparing 5-year mortality rates of patients with COPD-iHF in 2011 with the 5-year mortality rate of patients with COPD-iHF in 2006. This analysis was performed to evaluate the changes in the management of incident HF over a decade among patients with COPD. Mortality rate ratios adjusted for age, sex, BMI, GOLD, smoking status, history of cardiovascular disease, and diabetes (aMRR) were estimated using Poisson regression. Robust variance estimates were used in the Poisson regression to account for clustering on general practice (GP).Cause of deathONS mortality data was analysed to assess the trends in the cause of death for COPD-iHF and COPD-no HF over a decade (2006-2010 and 2011-2016). Cause of death by severity of airflow limitation (GOLD1-2 vs GOLD3-4) was also assessed from 2006-2016 for COPD-iHF in 2006. ONS derives the underlying cause of death from death certificates using standardised guidelines and coded using the International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10) ADDIN EN.CITE <EndNote><Cite><Author>Devis</Author><Year>1999</Year><RecNum>66</RecNum><DisplayText>(22)</DisplayText><record><rec-number>66</rec-number><foreign-keys><key app="EN" db-id="9xdxprve7sdt96eerrovwfd3t002fvet0rfe" timestamp="1516028051">66</key><key app="ENWeb" db-id="">0</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Devis, T</author><author>Rooney, C</author></authors></contributors><titles><title>Death certification and the epidemiologist</title><secondary-title>Health Statistics Quarterly</secondary-title></titles><periodical><full-title>Health Statistics Quarterly</full-title></periodical><volume>1</volume><number>21-33</number><dates><year>1999</year></dates><urls></urls></record></Cite></EndNote>(22).Ethics approvalProtocols for this research were approved by the Independent Scientific Advisory Committee (ISAC) for MHRA Database Research (protocol numbers: 18_006R2 and 18_074RARA2) and the approved protocols were made available to the journal and reviewers during peer review. Generic ethical approval for observational research using the CPRD with approval from ISAC has been granted by a Health Research Authority (HRA) Research Ethics Committee (East Midlands – Derby, REC reference number 05/MRE04/87).ResultsBaseline CharacteristicsWe identified 95,987 patients with COPD without a HF diagnosis at the start of follow-up (Figure 1). Patients with COPD-iHF were more likely to be older, male, obese, former smokers and have moderate to severe airflow limitation (Table 1) compared to patients with COPD-no HF. Patients with COPD-iHF were more likely to have traditional risk factors for HF including atrial fibrillation, diabetes, hypertension, and vascular disease (ischaemic heart disease and/or peripheral artery disease) at the start of follow-up. Average length of follow up and the descriptive information regarding the 2006, 2011, and 2015 COPD-iHF cohorts and their comparator COPD-no HF cohorts are outlined in Tables E2-E5.Incidence of HF among patients with COPD The crude incidence of HF in the COPD population was steady from 2006 to 2016 (Figure 2; Supplementary Table 6), averaging 1.18 per 100 person-years (95%CI: 1.09, 1.27). The incidence of HF was higher for males compared with females, at older ages, for former smokers compared with current smokers, and for patients with higher airflow limitation (GOLD3-4 vs GOLD1-2) (Tables E7-E10).MortalityComparison of mortality rates; COPD-iHF vs COPD-no HF The crude 1-year, 5-year, and 10-year mortality rates for patients with COPD-iHF and COPD-no HF in 2006, 2011, and 2015, as appropriate, can be found in Supplementary Tables 11-13. In 2006, patients with COPD-iHF experienced over three times greater 1-year mortality than patients with COPD-no HF (Figure 3a; Table E14). The trends where similar in 2011 and 2015 (Figure 3a; Table E14). Patients with COPD-iHF in 2006 experienced a greater than two-fold increase in 5-year mortality compared with COPD-no HF in 2006, with similar trends observed in 2011 (Figure 3b; Table E14). Similarly, incident HF was associated with a two-fold increase in 10-year mortality among COPD patients compared with those without incident HF (Figure 3c; Table E14). The difference in mortality rates between patients with COPD-iHF diagnosed in 2006 compared to patients with COPD without incident HF in 2006 was consistent over 10 years of follow-up (Figure 4).Comparison of mortality rates COPD-iHF vs COPD-no HF stratified by severity of airflow limitationThere was a non-significant trend towards higher 1-year, 5-year, and 10-year mortality in patients with COPD-iHF with more severe airflow limitation (Figure 5a, 5b, and 5c). The overall 1-year, 5-year and 10-year mortality rates of patients with COPD-iHF were significantly higher than the COPD-no HF patients, regardless of severity of airflow limitation (Figure 5a, 5b and 5c; Table E15).Temporal trends in the mortality rates of patients with COPD-iHF from 2006 to 2016 COPD-iHF patients in 2011 and 2015 experienced 1-year mortality rates that was no different from those patients with COPD-iHF in 2006 (Figure 6a; E16). Similarly, the 5-year mortality rate among patients with COPD-iHF in 2011 was no different than seen in patients with COPD-iHF in 2006 (Figure 6b; Table E16).Causes of deathThere was no difference in the proportion of deaths attributed to cardiovascular causes in patients with COPD-iHF in 2011 vs patients with COPD-iHF in 2006 (42% vs 39%) (Figure 7). Approximately one third of all deaths were attributed to COPD, regardless of whether a patient experienced incident HF or not (Table E17). Among those with COPD-iHF, over 10 years of follow-up, the proportion of deaths attributed to cardiovascular causes was not affected by severity of airflow limitation (33% GOLD1-2 vs 33% GOLD3-4; Figure 7).DiscussionThis study of a large, nationally representative population in the UK over one decade provides vital insights into trends in the incidence of HF within the primary care COPD population. We also investigate the impact of incident HF on mortality among patients with COPD and how this has changed over time and with the severity of airflow limitation.The major findings of the study could be summarised as follows: 1) in the UK, the crude incidence of HF in the COPD population was 1.18 per 100 persons years and this has remained steady over the past decade; 2) in patients with COPD, the incidence of HF was much higher among men, the elderly, and those with severe airflow limitation (GOLD3-4); 3) in patients with COPD, incident HF was associated with a greater than three-fold increase in 1-year mortality and a two-fold increase in 5- and 10-year mortality compared with those who did not develop HF; and 4) the effect of incident HF on the short- and long-term mortality of patients with COPD did not improve over time, nor was it different in relation to severity of airflow limitation.COPD and the risk of incident HF: mechanistic explanationPrevious studies have demonstrated an association between COPD and incident HF. A large population-based study of patients in the community revealed a linear relationship between severity of airflow obstruction and impaired left ventricular filling without significant changes in left ventricular ejection fraction ADDIN EN.CITE <EndNote><Cite><Author>Graham Barr</Author><Year>2010</Year><RecNum>23236</RecNum><DisplayText>(23)</DisplayText><record><rec-number>23236</rec-number><foreign-keys><key app="EN" db-id="9xdxprve7sdt96eerrovwfd3t002fvet0rfe" timestamp="1563867105">23236</key><key app="ENWeb" db-id="">0</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Graham Barr, R.</author><author>Bluemke, D. A.</author><author>Ahmed, F. S.</author><author>Jeffery Carr, J.</author><author>Enright, P.</author><author>Hoffman, E.</author><author>Jiang, R.</author><author>Kawut, S. M.</author><author>Kronmal, R.</author><author>Lima, J.A.C.</author><author>Shahar, E.</author><author>Smith, L.</author><author>Watson, K.</author></authors></contributors><titles><title>Percent emphysema, airflow obstruction, and impair left ventricular filling</title><secondary-title>The New England Journal of Medicine</secondary-title></titles><periodical><full-title>The New England Journal of Medicine</full-title></periodical><pages>217-227</pages><volume>362</volume><dates><year>2010</year></dates><urls></urls></record></Cite></EndNote>(23). Our results are similar to those of large community cohorts and registries where the incidence of HF was 1-1.5 per 100 person years at risk in patients with severe airflow limitation PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5BZ2Fyd2FsPC9BdXRob3I+PFllYXI+MjAxMjwvWWVhcj48
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ADDIN EN.CITE.DATA (4). There have been several potential explanations for the increased risk of HF in patients with COPD. Firstly, multiple traditional risk factors are associated with both COPD and HF; for instance, smoking, the most common cause of COPD ADDIN EN.CITE <EndNote><Cite><Author>Mannino</Author><Year>2006</Year><RecNum>23243</RecNum><DisplayText>(24)</DisplayText><record><rec-number>23243</rec-number><foreign-keys><key app="EN" db-id="9xdxprve7sdt96eerrovwfd3t002fvet0rfe" timestamp="1563874540">23243</key><key app="ENWeb" db-id="">0</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Mannino, D. M.</author><author>Watt, G.</author><author>Hole, D.</author><author>Gillis, C.</author><author>Hart, C.</author><author>McConnachie, A.</author><author>Davey Smith, G.</author><author>Upton, M.</author><author>Hawthorne, V.</author><author>Sin, D. D.</author><author>Man, S. F.</author><author>Van Eeden, S.</author><author>Mapel, D. W.</author><author>Vestbo, J.</author></authors></contributors><auth-address>Division of Pulmonary and Critical Care Medicine, University of Kentucky Medical Center, 800 Rose Street, MN 614 Lexington, KY 40536, USA. dmannino@uky.edu</auth-address><titles><title>The natural history of chronic obstructive pulmonary disease</title><secondary-title>Eur Respir J</secondary-title></titles><periodical><full-title>Eur Respir J</full-title></periodical><pages>627-43</pages><volume>27</volume><number>3</number><edition>2006/03/02</edition><keywords><keyword>Cardiovascular Diseases/etiology</keyword><keyword>Humans</keyword><keyword>*Pulmonary Disease, Chronic</keyword><keyword>Obstructive/complications/epidemiology/physiopathology</keyword></keywords><dates><year>2006</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>0903-1936 (Print)
0903-1936 (Linking)</isbn><accession-num>16507865</accession-num><urls><related-urls><url>;(24), has been associated with a 50% increased risk of HF ADDIN EN.CITE <EndNote><Cite><Author>Suskin</Author><Year>2001</Year><RecNum>23241</RecNum><DisplayText>(25)</DisplayText><record><rec-number>23241</rec-number><foreign-keys><key app="EN" db-id="9xdxprve7sdt96eerrovwfd3t002fvet0rfe" timestamp="1563874153">23241</key><key app="ENWeb" db-id="">0</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Suskin, Neville</author><author>Sheth, Tej</author><author>Negassa, Abdissa</author><author>Yusuf, Salim</author></authors></contributors><titles><title>Relationship of current and past smoking to mortality and morbidity in patients with left ventricular dysfunction</title><secondary-title>Journal of the American College of Cardiology</secondary-title></titles><periodical><full-title>Journal of the American College of Cardiology</full-title></periodical><pages>1677-1682</pages><volume>37</volume><number>6</number><section>1677</section><dates><year>2001</year></dates><isbn>07351097</isbn><urls></urls><electronic-resource-num>10.1016/s0735-1097(01)01195-0</electronic-resource-num></record></Cite></EndNote>(25). Secondly, there is a high prevalence of subclinical cardiac dysfunction PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5HcmFoYW0gQmFycjwvQXV0aG9yPjxZZWFyPjIwMTA8L1ll
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ADDIN EN.CITE.DATA (23, 26) and HF precursors (e.g., diabetes mellitus, atrial fibrillation, hypertension etc.) in patients with COPD ADDIN EN.CITE <EndNote><Cite><Author>Morgan</Author><Year>2018</Year><RecNum>10957</RecNum><DisplayText>(27)</DisplayText><record><rec-number>10957</rec-number><foreign-keys><key app="EN" db-id="9xdxprve7sdt96eerrovwfd3t002fvet0rfe" timestamp="1537870387">10957</key><key app="ENWeb" db-id="">0</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Morgan, A. D.</author><author>Rothnie, K. J.</author><author>Bhaskaran, K.</author><author>Smeeth, L.</author><author>Quint, J.</author></authors></contributors><titles><title>Chronic obstructive pulmonary disease and the risk of 12 cardiovascular diseases: a population-based study using UK primary care data</title><secondary-title>Thorax</secondary-title></titles><periodical><full-title>Thorax</full-title></periodical><pages>877–879</pages><volume>73</volume><dates><year>2018</year></dates><urls></urls></record></Cite></EndNote>(27). Furthermore, patients with COPD and cardiovascular disease (e.g., ischemic heart disease, atrial fibrillation etc.) are systemically under-prescribed cardiovascular medications including beta-blockers, statins, and aspirin ADDIN EN.CITE <EndNote><Cite><Author>Rasmussen</Author><Year>2018</Year><RecNum>10959</RecNum><DisplayText>(28)</DisplayText><record><rec-number>10959</rec-number><foreign-keys><key app="EN" db-id="9xdxprve7sdt96eerrovwfd3t002fvet0rfe" timestamp="1537872299">10959</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Rasmussen, D.</author><author>Bodtger, U.</author><author>Lamberts, M.</author><author>Lange, P.</author><author>Jensen, M. </author></authors></contributors><titles><title>Beta-blocker, aspirin and statin usage after myocardial infarction in patients with and without COPD. A nationwide analysis from 1995 to 2015 in Denmark</title><secondary-title>European Respiratory Journal</secondary-title></titles><periodical><full-title>European Respiratory Journal</full-title></periodical><pages>1933</pages><volume>52</volume><number>Suppl 62</number><dates><year>2018</year></dates><urls></urls></record></Cite></EndNote>(28), which may hasten development of HF, especially in patients with antecedent subclinical cardiac dysfunction. Thirdly, while COPD has been associated with an increased risk of both HF reduced ejection fraction and HF preserved ejection fraction, there appears to be a differential predilection to HF preserved ejection fraction PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5BZ2Fyd2FsPC9BdXRob3I+PFllYXI+MjAxMjwvWWVhcj48
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ADDIN EN.CITE.DATA (32). Finally, cor pulmonale and the effect of pulmonary hyperinflation on ventricular hemodynamics could be other plausible explanations for this association ADDIN EN.CITE <EndNote><Cite><Author>Shujaat</Author><Year>2007</Year><RecNum>23246</RecNum><DisplayText>(33)</DisplayText><record><rec-number>23246</rec-number><foreign-keys><key app="EN" db-id="9xdxprve7sdt96eerrovwfd3t002fvet0rfe" timestamp="1563889407">23246</key><key app="ENWeb" db-id="">0</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Shujaat, A.</author><author>Minkin, R.</author><author>Eden, E.</author></authors></contributors><titles><title>Pulmonary hypertension and chronic cor pulmonale in COPD</title><secondary-title>International Journal of COPD</secondary-title></titles><periodical><full-title>International Journal of COPD</full-title></periodical><pages>273-282</pages><volume>2</volume><number>3</number><dates><year>2007</year></dates><urls></urls></record></Cite></EndNote>(33).Temporal trends in the incidence of HF in patients with COPD in the UK: stable incidence or continued under recognition?The crude incidence of HF in the COPD population was steady over time; meanwhile, the crude incidence of HF in the general UK population is increasing ADDIN EN.CITE <EndNote><Cite><Author>Conrad</Author><Year>2017</Year><RecNum>225</RecNum><DisplayText>(10)</DisplayText><record><rec-number>225</rec-number><foreign-keys><key app="EN" db-id="9xdxprve7sdt96eerrovwfd3t002fvet0rfe" timestamp="1520603542">225</key><key app="ENWeb" db-id="">0</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Conrad, Nathalie</author><author>Judge, Andrew</author><author>Tran, Jenny</author><author>Mohseni, Hamid</author><author>Hedgecott, Deborah</author><author>Crespillo, Abel Perez</author><author>Allison, Moira</author><author>Hemingway, Harry</author><author>Cleland, John G.</author><author>McMurray, John J. V.</author><author>Rahimi, Kazem</author></authors></contributors><titles><title>Temporal trends and patterns in heart failure incidence: a population-based study of 4 million individuals</title><secondary-title>The Lancet</secondary-title></titles><periodical><full-title>The Lancet</full-title></periodical><pages>572-580</pages><volume>391</volume><number>10120</number><section>572</section><dates><year>2017</year></dates><isbn>01406736</isbn><urls></urls><electronic-resource-num>10.1016/s0140-6736(17)32520-5</electronic-resource-num></record></Cite></EndNote>(10). Crude incidence was higher in males, at older ages, in former smokers, and in those with more severe airflow limitation (GOLD3-4). Higher crude incidence in former smokers and in those with more severe airflow limitation may, at least in part, be attributed to age as older persons are more likely to be former smokers than current smokers and have more severe disease than younger persons. The stable incidence of HF in the past decade observed in our study could be a consequence of under recognition and lack of improvement in the diagnosis of HF in patients with COPD. It has previously been demonstrated that HF is often underdiagnosed in the COPD population PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Cb3VkZXN0ZWluPC9BdXRob3I+PFllYXI+MjAwOTwvWWVh
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ADDIN EN.CITE.DATA (14, 15, 34, 35), despite patients with COPD being at greater risk for developing HF and HF precursors, such as angina and myocardial infarction, than people without COPD ADDIN EN.CITE <EndNote><Cite><Author>Morgan</Author><Year>2018</Year><RecNum>10957</RecNum><DisplayText>(27)</DisplayText><record><rec-number>10957</rec-number><foreign-keys><key app="EN" db-id="9xdxprve7sdt96eerrovwfd3t002fvet0rfe" timestamp="1537870387">10957</key><key app="ENWeb" db-id="">0</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Morgan, A. D.</author><author>Rothnie, K. J.</author><author>Bhaskaran, K.</author><author>Smeeth, L.</author><author>Quint, J.</author></authors></contributors><titles><title>Chronic obstructive pulmonary disease and the risk of 12 cardiovascular diseases: a population-based study using UK primary care data</title><secondary-title>Thorax</secondary-title></titles><periodical><full-title>Thorax</full-title></periodical><pages>877–879</pages><volume>73</volume><dates><year>2018</year></dates><urls></urls></record></Cite></EndNote>(27). There are a number of possible explanations for this under-recognition. Firstly, HF and COPD share dyspnoea as a primary complaint, and determining the exact mechanism for dyspnoea is difficult ADDIN EN.CITE <EndNote><Cite><Author>Beghe</Author><Year>2013</Year><RecNum>23250</RecNum><DisplayText>(36)</DisplayText><record><rec-number>23250</rec-number><foreign-keys><key app="EN" db-id="9xdxprve7sdt96eerrovwfd3t002fvet0rfe" timestamp="1564134491">23250</key><key app="ENWeb" db-id="">0</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Beghe, B.</author><author>Verduri, A.</author><author>Roca, M.</author><author>Fabbri, L.</author></authors></contributors><titles><title>Exacerbation of respiratory symptoms in COPD patients may not be exacerbations of COPD</title><secondary-title>Eur Respir J</secondary-title></titles><periodical><full-title>Eur Respir J</full-title></periodical><pages>993-995</pages><volume>41</volume><number>4</number><edition>2013/04/02</edition><dates><year>2013</year><pub-dates><date>Apr</date></pub-dates></dates><urls></urls></record></Cite></EndNote>(36). Secondly, there is no single diagnostic test for HF PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Qb25pa293c2tpPC9BdXRob3I+PFllYXI+MjAxNjwvWWVh
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ADDIN EN.CITE.DATA (37, 38). In contrast to HFrEF, where the diagnosis is reasonably straightforward, the diagnosis of HF preserved ejection fraction is cumbersome, especially in patients presenting with dyspnoea and multiple co-morbidities. For diagnosing HF preserved ejection fraction, dyspnoea and a normal left ventricular ejection fraction need to be coupled with additional measures of left ventricular diastolic dysfunction (e.g. left ventricular hypertrophy, increased left atrial diameter, tissue Doppler studies etc.), and plasma levels of natriuretic peptides PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Qb25pa293c2tpPC9BdXRob3I+PFllYXI+MjAxNjwvWWVh
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ADDIN EN.CITE.DATA (41). As previous research has shown that HF is often under-diagnosed in the COPD population and that patients with COPD experience higher risk for HF than the general population, the lack of a similar trend in HF incidence in the COPD population as seen in the general population suggests that HF may still be under-recognised.Impact of incident HF on mortality in COPD patientsIn patients with COPD, incident HF was associated with a greater than three-fold increase in 1-year mortality rate and a two-fold increase in 5-year and 10-year mortality rates. While the incidence of HF was higher in patients with severe airflow limitation, the impact of incident HF on mortality was not modified by the degree of airflow limitation. The effect of incident HF on the mortality of patients with COPD did not improve over time, contrary to improved survival following incident HF in the general population PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5UYXlsb3I8L0F1dGhvcj48WWVhcj4yMDE5PC9ZZWFyPjxS
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ADDIN EN.CITE.DATA (44, 45). When it is recognised, diagnosis of HF in the COPD population is often delayed, which may mean HF is more severe and the provision of treatment delayed ADDIN EN.CITE <EndNote><Cite><Author>Hayhoe</Author><Year>2019</Year><RecNum>23203</RecNum><DisplayText>(46)</DisplayText><record><rec-number>23203</rec-number><foreign-keys><key app="EN" db-id="9xdxprve7sdt96eerrovwfd3t002fvet0rfe" timestamp="1558358217">23203</key><key app="ENWeb" db-id="">0</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Hayhoe, B.</author><author>Kim, D.</author><author>Aylin, P. P.</author><author>Majeed, F. A.</author><author>Cowie, M. R.</author><author>Bottle, A.</author></authors></contributors><auth-address>Department of Primary Care and Public Health, Imperial College London, London, UK.
Dr Foster Unit, Department of Primary Care and Public Health, Imperial College London, London, UK.
National Heart & Lung Institute, Imperial College London, London, UK.</auth-address><titles><title>Adherence to guidelines in management of symptoms suggestive of heart failure in primary care</title><secondary-title>Heart</secondary-title></titles><periodical><full-title>Heart</full-title></periodical><pages>678-685</pages><volume>105</volume><number>9</number><edition>2018/12/06</edition><keywords><keyword>heart disease</keyword><keyword>quality And Outcomes Of Care</keyword><keyword>consultant cardiologist, working in the NHS.</keyword></keywords><dates><year>2019</year><pub-dates><date>May</date></pub-dates></dates><isbn>1468-201X (Electronic)
1355-6037 (Linking)</isbn><accession-num>30514731</accession-num><urls><related-urls><url>;(46), negatively impacting survival. Additionally, it is well known that HF and other cardiovascular conditions are under-treated in the COPD population, with patients with COPD less likely to be prescribed survival-modifying cardiovascular medication than the general population ADDIN EN.CITE <EndNote><Cite><Author>Rasmussen</Author><Year>2018</Year><RecNum>10959</RecNum><DisplayText>(28)</DisplayText><record><rec-number>10959</rec-number><foreign-keys><key app="EN" db-id="9xdxprve7sdt96eerrovwfd3t002fvet0rfe" timestamp="1537872299">10959</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Rasmussen, D.</author><author>Bodtger, U.</author><author>Lamberts, M.</author><author>Lange, P.</author><author>Jensen, M. </author></authors></contributors><titles><title>Beta-blocker, aspirin and statin usage after myocardial infarction in patients with and without COPD. A nationwide analysis from 1995 to 2015 in Denmark</title><secondary-title>European Respiratory Journal</secondary-title></titles><periodical><full-title>European Respiratory Journal</full-title></periodical><pages>1933</pages><volume>52</volume><number>Suppl 62</number><dates><year>2018</year></dates><urls></urls></record></Cite></EndNote>(28). Our findings underscore the importance of identification of HF in patients with COPD early in the course of the disease where initiation of disease-modifying HF therapy, especially in HF reduced ejection fraction, may improve long term outcomes.Causes of death and temporal trends in cardiovascular mortality among COPD-iHF There no difference in cardiovascular mortality in patients with COPD-iHF over the study period. This contrasts the trend seen in the wider COPD population towards decreasing cardiovascular deaths PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5HYXlsZTwvQXV0aG9yPjxZZWFyPjIwMTk8L1llYXI+PFJl
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ADDIN EN.CITE.DATA (47). Taylor et al. looked at the causes of death in patients with HF from the general UK primary care population from 2000-2017 but did not look at changes over time ADDIN EN.CITE <EndNote><Cite><Author>Taylor</Author><Year>2019</Year><RecNum>23134</RecNum><DisplayText>(42)</DisplayText><record><rec-number>23134</rec-number><foreign-keys><key app="EN" db-id="9xdxprve7sdt96eerrovwfd3t002fvet0rfe" timestamp="1551693258">23134</key><key app="ENWeb" db-id="">0</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Taylor, C. J.</author><author>Ordonez-Mena, J. M.</author><author>Roalfe, A. K.</author><author>Lay-Flurrie, S.</author><author>Jones, N. R.</author><author>Marshall, T.</author><author>Hobbs, F. D. R.</author></authors></contributors><auth-address>Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford OX2 6GG, UK clare.taylor@phc.ox.ac.uk.
Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford OX2 6GG, UK.
Institute of Applied Health Research, University of Birmingham, Birmingham, UK.</auth-address><titles><title>Trends in survival after a diagnosis of heart failure in the United Kingdom 2000-2017: population based cohort study</title><secondary-title>BMJ</secondary-title></titles><periodical><full-title>BMJ</full-title></periodical><pages>l223</pages><volume>364</volume><edition>2019/02/15</edition><dates><year>2019</year><pub-dates><date>Feb 13</date></pub-dates></dates><isbn>1756-1833 (Electronic)
0959-8138 (Linking)</isbn><accession-num>30760447</accession-num><urls><related-urls><url>;(42). Taylor et al. found that 55.7% of deaths of patients with HF were attributed to cardiovascular causes ADDIN EN.CITE <EndNote><Cite><Author>Taylor</Author><Year>2019</Year><RecNum>23134</RecNum><DisplayText>(42)</DisplayText><record><rec-number>23134</rec-number><foreign-keys><key app="EN" db-id="9xdxprve7sdt96eerrovwfd3t002fvet0rfe" timestamp="1551693258">23134</key><key app="ENWeb" db-id="">0</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Taylor, C. J.</author><author>Ordonez-Mena, J. M.</author><author>Roalfe, A. K.</author><author>Lay-Flurrie, S.</author><author>Jones, N. R.</author><author>Marshall, T.</author><author>Hobbs, F. D. R.</author></authors></contributors><auth-address>Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford OX2 6GG, UK clare.taylor@phc.ox.ac.uk.
Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford OX2 6GG, UK.
Institute of Applied Health Research, University of Birmingham, Birmingham, UK.</auth-address><titles><title>Trends in survival after a diagnosis of heart failure in the United Kingdom 2000-2017: population based cohort study</title><secondary-title>BMJ</secondary-title></titles><periodical><full-title>BMJ</full-title></periodical><pages>l223</pages><volume>364</volume><edition>2019/02/15</edition><dates><year>2019</year><pub-dates><date>Feb 13</date></pub-dates></dates><isbn>1756-1833 (Electronic)
0959-8138 (Linking)</isbn><accession-num>30760447</accession-num><urls><related-urls><url>;(42), which is much more than the 36% of deaths attributed to cardiovascular causes in the COPD-iHF population from 2011-2016 seen here. The difference does appear to be made up by a greater proportion of deaths attributed to respiratory causes in the COPD-iHF population than in the wider HF population (COPD-iHF [presented here] vs wider HF population ADDIN EN.CITE <EndNote><Cite><Author>Taylor</Author><Year>2019</Year><RecNum>23134</RecNum><DisplayText>(42)</DisplayText><record><rec-number>23134</rec-number><foreign-keys><key app="EN" db-id="9xdxprve7sdt96eerrovwfd3t002fvet0rfe" timestamp="1551693258">23134</key><key app="ENWeb" db-id="">0</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Taylor, C. J.</author><author>Ordonez-Mena, J. M.</author><author>Roalfe, A. K.</author><author>Lay-Flurrie, S.</author><author>Jones, N. R.</author><author>Marshall, T.</author><author>Hobbs, F. D. R.</author></authors></contributors><auth-address>Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford OX2 6GG, UK clare.taylor@phc.ox.ac.uk.
Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford OX2 6GG, UK.
Institute of Applied Health Research, University of Birmingham, Birmingham, UK.</auth-address><titles><title>Trends in survival after a diagnosis of heart failure in the United Kingdom 2000-2017: population based cohort study</title><secondary-title>BMJ</secondary-title></titles><periodical><full-title>BMJ</full-title></periodical><pages>l223</pages><volume>364</volume><edition>2019/02/15</edition><dates><year>2019</year><pub-dates><date>Feb 13</date></pub-dates></dates><isbn>1756-1833 (Electronic)
0959-8138 (Linking)</isbn><accession-num>30760447</accession-num><urls><related-urls><url>;(42): 39% vs 16%) as proportions of death attributed to all other causes were similar in the two populations.Increasing airflow limitation saw no change in the proportion of deaths attributed to cardiovascular causes in patients with COPD-iHF. These trends are different to those seen in the wider COPD population, where deaths due to respiratory causes increase and deaths due to cardiovascular causes decrease with increasing airflow limitation PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5BbGZhZ2VtZTwvQXV0aG9yPjxZZWFyPjIwMTA8L1llYXI+
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ADDIN EN.CITE.DATA (49). When looking only at patients with incident HF with COPD, Lawson et al. found significantly greater adjusted odds of mortality for patients with more severe airflow limitation (GOLD3-4) compared with those with milder airflow limitation (GOLD1-2) PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5MYXdzb248L0F1dGhvcj48WWVhcj4yMDE4PC9ZZWFyPjxS
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ADDIN EN.CITE.DATA (49). Here, we found increased effect of HF on the mortality rate of patients with COPD with more severe airflow limitation in the short-term (1-year), but the difference was not significant and attenuated when looking at longer-term mortality rates. The cohort from Lawson et al. had a higher proportion of patients with severe-to-very-severe airflow limitation than our cohort, which may also contribute to the differences PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5MYXdzb248L0F1dGhvcj48WWVhcj4yMDE4PC9ZZWFyPjxS
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ADDIN EN.CITE.DATA (18); however, although no validation of a case definition for HF has been undertaken in CPRD we used Read codes reviewed by two cardiologists and two respiratory physicians. Another limitation is that measurements of ejection fraction and biomarkers used to determine the severity or type of HF are not available in CPRD data. As we cannot determine type of HF reliably, we are unable to determine if patients with HF reduced ejection fraction are being managed according to guidelines.ConclusionsThe incidence of HF in the UK primary care COPD population in the last decade was steady, contrary to increasing incidence of HF seen in the general population of the UK ADDIN EN.CITE <EndNote><Cite><Author>Conrad</Author><Year>2017</Year><RecNum>225</RecNum><DisplayText>(10)</DisplayText><record><rec-number>225</rec-number><foreign-keys><key app="EN" db-id="9xdxprve7sdt96eerrovwfd3t002fvet0rfe" timestamp="1520603542">225</key><key app="ENWeb" db-id="">0</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Conrad, Nathalie</author><author>Judge, Andrew</author><author>Tran, Jenny</author><author>Mohseni, Hamid</author><author>Hedgecott, Deborah</author><author>Crespillo, Abel Perez</author><author>Allison, Moira</author><author>Hemingway, Harry</author><author>Cleland, John G.</author><author>McMurray, John J. V.</author><author>Rahimi, Kazem</author></authors></contributors><titles><title>Temporal trends and patterns in heart failure incidence: a population-based study of 4 million individuals</title><secondary-title>The Lancet</secondary-title></titles><periodical><full-title>The Lancet</full-title></periodical><pages>572-580</pages><volume>391</volume><number>10120</number><section>572</section><dates><year>2017</year></dates><isbn>01406736</isbn><urls></urls><electronic-resource-num>10.1016/s0140-6736(17)32520-5</electronic-resource-num></record></Cite></EndNote>(10). Patients with COPD-iHF experienced a significantly higher mortality than patients with COPD-no HF. The mortality rates in England of patients with COPD-iHF have not improved over the last decade, indicating that patients with COPD-iHF have not seen the same increases in survival previously seen in the general population with incident HF PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5UYXlsb3I8L0F1dGhvcj48WWVhcj4yMDE5PC9ZZWFyPjxS
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ADDIN EN.CITE.DATA (42, 43). This survival differential may be explained by previous research showing that patients with COPD and cardiovascular conditions are often under-managed compared to the general population ADDIN EN.CITE <EndNote><Cite><Author>Rasmussen</Author><Year>2018</Year><RecNum>10959</RecNum><DisplayText>(28)</DisplayText><record><rec-number>10959</rec-number><foreign-keys><key app="EN" db-id="9xdxprve7sdt96eerrovwfd3t002fvet0rfe" timestamp="1537872299">10959</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Rasmussen, D.</author><author>Bodtger, U.</author><author>Lamberts, M.</author><author>Lange, P.</author><author>Jensen, M. </author></authors></contributors><titles><title>Beta-blocker, aspirin and statin usage after myocardial infarction in patients with and without COPD. A nationwide analysis from 1995 to 2015 in Denmark</title><secondary-title>European Respiratory Journal</secondary-title></titles><periodical><full-title>European Respiratory Journal</full-title></periodical><pages>1933</pages><volume>52</volume><number>Suppl 62</number><dates><year>2018</year></dates><urls></urls></record></Cite></EndNote>(28). Our results, coupled with previous research, suggest that HF remains under-diagnosed in the COPD population and that, when recognised, may be under-treated resulting in poorer survival. Bespoke clinical guidelines for the diagnosis and management of HF in the presence of COPD, and implementation tools with audit to support quality improvement, are needed in order to improve diagnosis and outcome.References ADDIN EN.REFLIST 1.Cowie MR, Anker SD, Cleland JGF, Felker GM, Filippatos G, Jaarsma T, et al. Improving care for patients with acute heart failure: before, during and after hospitalization. ESC Heart Fail. 2014;1(2):110-45. 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Office of National Statistics (ONS); 2014.51.Death Certification Reform: A Case Study on the Potential Impact on Mortality Statistics, England and Wales. In: (ONS) OoNS, editor. 2012.Figure LegendsFigure SEQ Figure \* ARABIC 1. Defining the study population from the Clinical Practice Research Datalink (CPRD). Chronic obstructive pulmonary disease (COPD). Heart failure (HF).Figure SEQ Figure \* ARABIC 2. Crude incidence of heart failure (HF) in the chronic obstructive pulmonary disease (COPD) population, 2006-2016. Incidence per 100 person-years. 95% confidence intervals shown.Figure SEQ Figure \* ARABIC 3. Adjusted mortality rate ratios (aMRR) with 95% confidence intervals comparing the a) 1-year, b) 5-year, and c) 10-year mortality of patients with chronic obstructive pulmonary disease (COPD) and incident heart failure (HF) in 2006, 2011, and 2015 with the 1-year, 5-year, and 10-year mortality of patients with COPD without incident HF in 2006, 2011, and 2015, respectively. Estimates from Poisson regression adjusted for age, sex, body mass index, severity of airflow limitation, smoking status, history of cardiovascular disease, and diabetes.Figure SEQ Figure \* ARABIC 4. Kaplan-Meier survivor curve with 95% confidence intervals (CI) comparing patients with chronic obstructive pulmonary disease (COPD) with (hf_2006 = 1) and without (hf_2006 = 0) incident heart failure (HF) in 2006 over 10 years of follow-up.Figure SEQ Figure \* ARABIC 5. Adjusted mortality rate ratios (aMRR) with 95% confidence intervals comparing the 1-year, 5-year, and 10-year mortality of patients with COPD and incident HF in 2006 with the mortality of patients with COPD without incident HF in 2006 stratified by severity of airflow limitation. Global Initiative for Chronic Obstructive Lung Diseases (GOLD) staging of COPD severity (20) where GOLD1-2 is mild-to-moderate airflow limitation and GOLD3-4 is severe-to-very severe airflow limitation. Estimates from Poisson regression adjusted for age, sex, body mass index, smoking status, history of cardiovascular disease, and diabetes.Figure SEQ Figure \* ARABIC 6. Adjusted mortality rate ratios (aMRR) with 95% confidence intervals comparing the 1-year and 5-year mortality of patients with chronic obstructive pulmonary disease (COPD) with incident heart failure (HF) in 2011 and 2015 with the mortality of patients with COPD with incident HF in 2006. Estimates from Poisson regression adjusted for age, sex, body mass index, severity of airflow limitation, smoking status, history of cardiovascular disease, and diabetes.Figure 7. The proportion of deaths attributed to respiratory (J), circulatory (I), neoplasm (C, D00-D49), and all other causes for patients with chronic obstructive pulmonary disease (COPD) with incident heart failure (HF) in (A) 2006 and (B) 2011 over five years of follow-up and for patients with COPD with incident HF in 2006 over ten years of follow-up stratified by severity of airflow limitation (C) mild-to-moderate airflow limitation (GOLD1-2) and (D) severe-to-very severe airflow limitation (GOLD3-4). Chapters defined according to the International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10). Global Initiative for Chronic Obstructive Lung Diseases (GOLD) staging of COPD severity (20).Tables?Incident HF n (%)No Incident HF n (%)?Number of Patients (N)4,86291,125 % of patients with COPD5.194.9?Female1,733 (35.6)40,606 (44.6)?Age at COPD Diagnosis, yearsMedian (interquartile range)68.8 (61.2, 75.9)64.5 (56.9, 72.3)Age at HF Diagnosis, yearsMedian (interquartile range)75.9 (69.0, 81.8)~?Smoking Status Current Smoker1,660 (34.1)41,325 (45.4) Former Smoker3,202 (65.9)49,800 (54.6)?Body Mass Index Underweight (< 18.5)166 (3.4)4,923 (5.4) Healthy Weight (18.5-24.9)1,461 (30.1)33,728 (37.0) Overweight (25.0-29.9)1,655 (34.0)29,454 (32.3) Obese (>= 30)1,512 (31.1)21,518 (23.6) Missing Data68 (1.40)1,502 (1.7)GOLD Stage 1: Mild1,527 (31.4)32,761 (36.0) 2: Moderate1,819 (37.4)36,241 (39.8) 3: Severe1,231 (25.3)18,108 (19.8) 4: Very Severe285 (5.9)4,015 (4.4)HF Risk Factors* Atrial Fibrillation659 (13.6)4,201 (4.6) Diabetes769 (15.8)9,030 (9.9) Hypertension2,345 (48.2)43,463 (47.7) Ischaemic Heart Disease1,499 (30.8)13,162 (14.4) Peripheral Artery Disease493 (10.1)5,371 (5.9) Stroke411 (8.5)5,089 (5.6)Table SEQ Table \* ARABIC 1. Descriptive statistics.Presented for patients with chronic obstructive pulmonary disease (COPD) with incident heart failure (HF) during the study period and those without incident HF during the study period. Interquartile range (IQR). Global Initiative for Chronic Obstructive Lung Diseases (GOLD) staging of COPD severity ADDIN EN.CITE <EndNote><Cite><Author>GOLD</Author><Year>2017</Year><RecNum>9</RecNum><DisplayText>(20)</DisplayText><record><rec-number>9</rec-number><foreign-keys><key app="EN" db-id="9xdxprve7sdt96eerrovwfd3t002fvet0rfe" timestamp="1515502506">9</key></foreign-keys><ref-type name="Web Page">12</ref-type><contributors><authors><author>GOLD</author></authors></contributors><titles><title>Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017</title></titles><number>10 Jan 2018</number><dates><year>2017</year></dates><work-type>Webpage</work-type><urls><related-urls><url>;(20). *Recorded at start of follow-up; patients could have multiple risk factors. ................
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