Gender, Age, and Regional Disparities in the Incidence and Mortality Trends of Infective Endocarditis in the United States Between 1990 and 2019

Abstract

The incidence of infective endocarditis (IE) has increased globally in the past decades, including in the United States. However, little is known about the differences in trends across states, gender, and age groups within the United States. Using the Global Burden of Disease database, we analyzed the incidence and mortality trends of IE in the United States between 1990 and 2019 using Joinpoint regression analyses, and compared between states, gender, and age groups. The age-standardized incidence rate (ASIR) of IE in the United States increased from 10.2/100,000 population in 1990 to 14.4 in 2019. The increase in ASIR was greater among men than women (45.8% vs 34.1%). The incidence increase was driven by 55+ year-olds (112.7% increase), with rapid increases in the 1990s and early 2000s, followed by a plateau around the mid-2000s. In contrast, the incidence among 5-to-19-year-olds decreased by −36.6% over the 30-year period. The incidence increased among all age groups in the last 5 years of observation (2015 to 2019), with the largest increase in 5-to-19-year-olds (3.3% yearly). The 30-year increase in ASIR was greatest in Utah (66.2%) and smallest in California (30.2%). The overall age-standardized mortality attributable to IE increased in the United States by 126% between 1990 and 2019 versus 19.6% globally. In conclusion, although the overall incidence and mortality of IE increased over the past 30 years in the United States, there are significant differences between regions, gender, and age groups. These findings indicate unevenly distributed disease burden of IE across the nation. The incidence of infective endocarditis (IE) has increased globally in the past decades, including in the United States. However, little is known about the differences in trends across states, gender, and age groups within the United States. Using the Global Burden of Disease database, we analyzed the incidence and mortality trends of IE in the United States between 1990 and 2019 using Joinpoint regression analyses, and compared between states, gender, and age groups. The age-standardized incidence rate (ASIR) of IE in the United States increased from 10.2/100,000 population in 1990 to 14.4 in 2019. The increase in ASIR was greater among men than women (45.8% vs 34.1%). The incidence increase was driven by 55+ year-olds (112.7% increase), with rapid increases in the 1990s and early 2000s, followed by a plateau around the mid-2000s. In contrast, the incidence among 5-to-19-year-olds decreased by −36.6% over the 30-year period. The incidence increased among all age groups in the last 5 years of observation (2015 to 2019), with the largest increase in 5-to-19-year-olds (3.3% yearly). The 30-year increase in ASIR was greatest in Utah (66.2%) and smallest in California (30.2%). The overall age-standardized mortality attributable to IE increased in the United States by 126% between 1990 and 2019 versus 19.6% globally. In conclusion, although the overall incidence and mortality of IE increased over the past 30 years in the United States, there are significant differences between regions, gender, and age groups. These findings indicate unevenly distributed disease burden of IE across the nation. Infective endocarditis (IE) is an infection of the endocardium that involves native or prosthetic heart valves.1Rajani R Klein JL Infective endocarditis: a contemporary update.Clin Med (Lond). 2020; 20: 31-35Crossref PubMed Scopus (55) Google Scholar It is a feared life-threatening condition, with in-hospital mortality ranging from 15% to 20% in high-income countries.2Hill EE Herijgers P Claus P Vanderschueren S Herregods MC Peetermans WE Infective endocarditis: changing epidemiology and predictors of 6-month mortality: a prospective cohort study.Eur Heart J. 2007; 28: 196-203Crossref PubMed Scopus (301) Google Scholar,3Hammond-Haley M Hartley A Al-Khayatt BM Delago AJ Ghajar A Ojha U Marshall DC Salciccioli JD Prendergast BD Shalhoub J Trends in the incidence and mortality of infective endocarditis in high-income countries between 1990 and 2019.Int J Cardiol. 2023; 371: 441-451Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar Risk factors for IE include age, injection drug use, valvular disease, cardiac surgery, poor dentition, and an immunocompromised state.2Hill EE Herijgers P Claus P Vanderschueren S Herregods MC Peetermans WE Infective endocarditis: changing epidemiology and predictors of 6-month mortality: a prospective cohort study.Eur Heart J. 2007; 28: 196-203Crossref PubMed Scopus (301) Google Scholar Several studies have shown that the incidence rates and disease burden of IE are increasing worldwide.3Hammond-Haley M Hartley A Al-Khayatt BM Delago AJ Ghajar A Ojha U Marshall DC Salciccioli JD Prendergast BD Shalhoub J Trends in the incidence and mortality of infective endocarditis in high-income countries between 1990 and 2019.Int J Cardiol. 2023; 371: 441-451Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar,4Chen H Zhan Y Zhang K Gao Y Chen L Zhan J Chen Z Zeng Z The global, regional, and national burden and trends of infective endocarditis from 1990 to 2019: results from the global burden of disease Study 2019.Front Med (Lausanne). 2022; 9774224Google Scholar Similar trends have also been reported in the United States.5Pant S Patel NJ Deshmukh A Golwala H Patel N Badheka A Hirsch GA Mehta JL Trends in infective endocarditis incidence, microbiology, and valve replacement in the United States from 2000 to 2011.J Am Coll Cardiol. 2015; 65: 2070-2076Crossref PubMed Scopus (385) Google Scholar,6Alkhouli M Alqahtani F Alhajji M Berzingi CO Sohail MR Clinical and economic burden of hospitalizations for infective endocarditis in the United States.Mayo Clin Proc. 2020; 95: 858-866Abstract Full Text Full Text PDF PubMed Scopus (34) Google Scholar Alkhouli et al6Alkhouli M Alqahtani F Alhajji M Berzingi CO Sohail MR Clinical and economic burden of hospitalizations for infective endocarditis in the United States.Mayo Clin Proc. 2020; 95: 858-866Abstract Full Text Full Text PDF PubMed Scopus (34) Google Scholar reported that the healthcare expenditure related to IE hospitalizations increased from $1.58 billion in 2003 to $2.34 billion in 2016, placing a significant burden on the US healthcare system. In this study, we aimed to explore the incidence and mortality trends of IE between 1990 and 2019 in the United States comparing different gender and age groups across different states, using the Global Burden of Disease database. Data: Our study used data from the Global Burden of Disease study (GBD) 2019. The methods used in GBD 2019 are described in detail by the GBD collaborators.7GBD 2019 Diseases and Injuries CollaboratorsGlobal burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019.Lancet. 2020; 396: 1204-1222Abstract Full Text Full Text PDF PubMed Scopus (4846) Google Scholar In brief, GBD 2019 provides data on incidence, prevalence, mortality, and disability-adjusted life-years for 369 diseases and injuries in 204 countries and territories for the period between 1990 and 2019. The primary data including demographic censuses, vital statistics, and disease registries are gathered through a systematic review of relevant sources. For the United States, primary data sources included the national hospital discharge survey, health insurance claims and encounter databases, statewide inpatient databases, and national vital statistics system mortality data. In GBD 2019, IE is defined as a clinical diagnosis of IE. The International Classification of Diseases (ICD) codes for IE, that is, I33 to I33.9, I38 to I39.9 for ICD-Tenth Revision, and 421 to 421.9 for ICD-Ninth Revision are identified in the primary data sources. In our study, IE cases are defined as cases with diagnoses of IE identified by the previously mentioned diagnostic codes. We extracted data on the incidence and mortality of IE in the 50 US states and Washington, District of Columbia stratified by gender and 3 age groups (5-to-19-year-olds, 20-to-54-year-olds, and 55+ year-olds). Statistical methods: We analyzed trends using Joinpoint regression methods. We computed average annual percentage changes (AAPCs) and years of changing trends (Joinpoints). We allowed a maximum of 4 Joinpoints and a maximum of 5 trend segments. At least 2 observations were required for each segment. We calculated AAPC for the entire period (1990 to 2019) and for the last 5 years of the study period (2015 to 2019). We selected final models using data-driven weighted Bayesian Information Criteria methods. We compared results between states, gender, and age groups. We report results either as a yearly rate (number of cases per 100,000 population) or as a percentage change of rates between 2 time points, that is, (Rt′ − Rt)/Rt*100%. We performed Joinpoint regression analyses using the Joinpoint software (version 4.9.1.0) provided by the United States National Cancer Institute. All other analyses were performed using the statistical software R (version 4.2.1). Incidence: The overall age-standardized incidence rate (ASIR) of IE diagnosed in the United States increased from 10.2/100,000 population in 1990 to 14.4 in 2019 (41.2% increase; Figure 1, Supplementary Table 1A). This was comparable with the global trend (from 9.91/100,000 population in 1990 to 13.8 in 2019, 39.3% increase). The increasing trend of the overall ASIR plateaued around 2004 and started to increase again in 2017 (Table 1).Table 1Joinpoint analysis incidence US-wideTrend 1Trend 2Trend 3Trend 4Trend 5AAPCAgeSexYearAPC (95% CI)YearAPC (95% CI)YearAPC (95% CI)YearAPC (95% CI)YearAPC (95% CI)1990–20192015–2019Age-standardized Both1990–19941.8 (1.7, 1.9)1994–20003.5 (3.4, 3.6)2000–20041.3 (1.1, 1.5)2004–2017-0.2 (−0.2, −0.2)2017–20191.8 (1.4, 2.2)1.2 (1.2, 1.2)0.8 (0.6, 1) Female1990–19941.1 (0.9, 1.3)1994–20003.6 (3.4, 3.7)2000–20031.4 (0.8, 1.9)2003–2017−0.3 (−0.4, −0.3)2017–20192.2 (1.7, 2.8)1 (1, 1.1)0.9 (0.7, 1.2) Male1990–19942.5 (2.4, 2.6)1994–20003.3 (3.2, 3.4)2000–20051.2 (1.1, 1.4)2005–2017−0.1 (−0.1, −0.1)2017–20191.5 (1, 1.9)1.3 (1.3, 1.4)0.7 (0.5, 0.9) 5-19 years Both1990–1994−4.6 (−5.2, −4.1)1994–20002 (1.6, 2.4)2000–2009−5.6 (−5.8, −5.4)2009–2017−0.3 (−0.5, −0.1)2017–20196.8 (5.1, 8.6)−1.6 (−1.7, −1.4)3.3 (2.4, 4.2) Female1990–1994−4.2 (−5.2, −3.3)1994–20001.9 (1.2, 2.6)2000–2008−6.3 (−6.7, −5.9)2008–2016−0.6 (−1, −0.2)2016–20195.6 (4.1, 7.1)−1.5 (−1.8, −1.2)4.1 (2.9, 5.3) Male1990–1994−4.6 (−5, −4.2)1994–20011.4 (1.2, 1.6)2001–2009−5.8 (−5.9, −5.6)2009–2017−0.5 (−0.7, −0.4)2017–20196.1 (4.9, 7.3)−1.6 (−1.7, −1.5)2.8 (2.2, 3.5)20-54 years Both1990–1994−2.2 (−2.4, −1.9)1994–20041.9 (1.8, 1.9)2004–20080.9 (0.5, 1.2)2008–2016−0.2 (−0.3, −0.1)2016–20190.8 (0.4, 1.2)0.5 (0.4, 0.6)0.6 (0.3, 0.8) Female1990–1992−4 (−4.6, −3.4)1992–1995−1.7 (−2.3, −1.1)1995–20051.2 (1.2, 1.3)2005–2017−0.2 (−0.3, −0.2)2017–20191.6 (1.1, 2.2)0 (−0.1, 0.1)0.7 (0.4, 1) Male1990–1994−1.2 (−1.5, −1)1994–20042.4 (2.3, 2.5)2004–20091.1 (0.8, 1.3)2009–2015−0.3 (−0.5, −0.2)2015–20190.5 (0.3, 0.7)0.8 (0.8, 0.9)0.5 (0.2, 0.8)55+ years Both1990–19957.2 (6.9, 7.5)1995–20024.4 (4.1, 4.6)2002–20061.9 (1.2, 2.5)2006–2016−0.2 (−0.3, −0.1)2016–20191 (0.3, 1.6)2.6 (2.5, 2.7)0.7 (0.2, 1.2) Female1990–19976.7 (6.5, 6.8)1997–20034.5 (4.2, 4.7)2003–20061.4 (0.2, 2.5)2006–2016−0.6 (−0.7, −0.5)2016–20191.2 (0.6, 1.7)2.6 (2.5, 2.8)0.7 (0.3, 1.2) Male1990–19938.3 (7.4, 9.1)1993–19975.3 (4.4, 6.1)1997–20033.1 (2.8, 3.5)2003–20071.3 (0.4, 2.1)2007–20190.1 (0, 0.2)2.5 (2.3, 2.7)0.1 (0, 0.2)APC = annual percentage change; AAPC = average annual percentage change; CI = confidence interval. Open table in a new tab APC = annual percentage change; AAPC = average annual percentage change; CI = confidence interval. There was a significant difference in the trends of age-stratified incidence rates (Figure 1, Supplementary Table 1B). There was a substantial increase in the incidence rates among older adults (55+ from in 1990 to in 2019 (112.7% increase). This increase was than the global trend in the age Supplementary Figure the incidence rate in the population 5 to decreased the study period from in 1990 to in 2019 The of was than the global average for the age 20-to-54-year-olds, the change in the incidence rate was increasing from in 1990 to in 2019 vs the incidence rates in the last 5 years of the study period increased in all age with the largest increase in the population confidence to The increase in ASIR over the study period was greater among men to than women to increase). The 30-year percentage changes in ASIR stratified by gender and states are in Figure In all states for and District of and Washington, the increase in ASIR was greater in men than in There were significant differences in the incidence rates and trends (Figure Supplementary Figure 1, Supplementary Table In the 2019, the overall ASIR per 100,000 population was in and in The incidence rate in 2019 among 55+ year-olds was in Supplementary Figure and in For this was in and in California and for 20-to-54-year-olds, in and in The incidence rate among 5-to-19-year-olds decreased in all states over the 30-year that among 55+ year-olds an increasing trend with a plateau around the in All states an increase in the ASIR over the study period. The ASIR increase was in Utah and in California (30.2%). stratified by age and the incidence rate among 5-to-19-year-olds decreased in all states over the study with the percentage ranging from in to in The incidence rate among 55+ year-olds increased in all states over 30 years with the percentage increase ranging from in to in For 20-to-54-year-olds, the 30-year percentage increase from in to in The overall age-standardized mortality rate attributable to IE increased from in 1990 to in 2019 in the United States increase; Figure 1, Supplementary Table This increase was than the global average the period increase). There was a increase in the in the 1990s between and with the AAPC of and per in and (Table The overall has plateaued analysis mortality US-wideTrend 1Trend 2Trend 3Trend 4Trend 5AAPCAgeSexYearAPC (95% CI)YearAPC (95% CI)YearAPC (95% CI)YearAPC (95% CI)YearAPC (95% (3.4, (2.5, (4.1, (2.8, (2.2, (1.1, years (0.2, (2.5, (0.4, (0.5, (0.5, (0.4, (4.1, (1.6, (0.4, (0.5, (0.4, years (0.5, (0, (1.7, 0.8) (3.4, (1.1, (0.2, (2.3, 1) (1.6, (1.7, years (2.8, (3.4, (0.2, (2.5, = annual percentage change; AAPC = average annual percentage change; CI = confidence interval. Open table in a new tab APC = annual percentage change; AAPC = average annual percentage change; CI = confidence interval. The increase in the overall to driven by older adults (55+ with a percentage increase in mortality over the study period of (Figure 1, Supplementary Table This increase was 3 as as the global trend in the age increase). The difference in the trends between the United States and the global average was substantial among 20-to-54-year-olds, with a 30-year percentage change in the United States of the global average vs The mortality rate among 5-to-19-year-olds decreased over the study period by this increased by in the United States. The mortality increase was among women to increase vs than men to increase vs In all states, with the increase in mortality over 30 years was in women than in men (Figure this gender difference was in the with incidence there were differences in mortality rates of IE across states (Figure Supplementary Table The in 2019 was in Utah and in The trends of mortality rates across states in different age groups followed the trends of incidence rates Figure 1, Supplementary Table However, states as and mortality rates among older adults than incidence states a plateau or a in the mortality rates among older adults the mid-2000s. The mortality rates among increased in states among 5-to-19-year-olds in all The age-stratified mortality is in Supplementary Figure The increasing incidence and disease burden of IE are of reported we that the overall incidence of IE is also increasing in the United States. In our study significant age, gender, and differences in the incidence and mortality trends of IE within the United States. Our findings that the disease burden of IE is unevenly distributed across the and factors are to the changes in trends of the US population in different of the findings of our study is that the incidence trends between age groups. For 55+ the incidence increased by than the of the overall In the the incidence among the population decreased by The increase in incidence among 55+ year-olds was than the global the in incidence among the population was also than the global increases in the incidence are in all age groups in the last 5 years of the study with the largest AAPC in the population in the study period. The increasing incidence among older adults to the increased of valve and or among older early study reported a increase in cardiac and among between 1990 and rates of cardiac among Heart J. PubMed Scopus Google Scholar cardiac within this period increased by rates of cardiac among Heart J. PubMed Scopus Google Scholar study that the incidence of cardiac increased by from to AJ Patel JD Trends in in the United States from to increasing of and Am Coll Cardiol. PubMed Scopus Google Scholar a trend of increasing in the the incidence of plateaued around the to the study, with the plateau of the increasing incidence of IE in older adults in our the of valve among increased by in the to the of valve replacement M A Y AJ S A Trends in and valve replacement among older adults in the United Am Coll Cardiol. PubMed Scopus Google Scholar is to a the of IE is reported to to that with valve K Infective endocarditis and valve a of the Am Heart 2020; Scholar This are of IE. IE in the population is and reported to with heart disease, cardiac including valve and heart K S of with infective PubMed Scopus Google Scholar to our the largest in the incidence of IE in the population in the 2000s, with a yearly percentage of for with heart disease are among with IE, that in the of heart diseases have to this overall K S of with infective PubMed Scopus Google Scholar In are reported to in the although there to and in JD Trends of in 2022; PubMed Scopus Google Scholar the overall incidence of heart disease, for to 15% of IE S A microbiology, and of infective endocarditis in in the United Heart PubMed Scopus Google Scholar is in GA L A M Trends and of in mortality among US PubMed Scopus Google Scholar studies and in the incidence and mortality trends of heart L N S S Klein J R S A Marshall J L M K A S H M S M N A heart disease in the United results of a Am Heart PubMed Scopus Google Scholar In our the percentage of IE incidence among 5-to-19-year-olds between 1990 and 2019 among states, ranging from in to in California Table 1B). Our results the of the incidence of IE in years is increasing among all age groups in the United States. is the increased of injection J J H J L M H A trends in hospitalizations to injection drug to 2020; PubMed Scopus Google J R J S and of infective endocarditis with drug in the United States from to Am Heart PubMed Scopus Google GA in the of infective endocarditis with mortality in Cardiol. PubMed Scopus Google Scholar of all IE cases are with drug J R J S and of infective endocarditis with drug in the United States from to Am Heart PubMed Scopus Google GA in the of infective endocarditis with mortality in Cardiol. PubMed Scopus Google Scholar study in reported an increase in the of hospitalizations to or by drug between and J J H J L M H A trends in hospitalizations to injection drug to 2020; PubMed Scopus Google Scholar et GA in the of infective endocarditis with mortality in Cardiol. PubMed Scopus Google Scholar reported that the incidence of IE with drug is and are by this increasing In study, than years for in compared with in In are with the greatest incidence increase of IE in the J R J S and of infective endocarditis with drug in the United States from to Am Heart PubMed Scopus Google Scholar the changes in a in the increasing trend of IE is In the Heart and that IE for to with cardiac M M A M M P Heart and Disease Heart on Disease in the Heart on Clinical Heart on and of and of infective endocarditis: from the Heart a from the Heart and Disease on Disease in the and the on Clinical on and and the of and 2007; PubMed Scopus Google Scholar significant difference in the incidence trend and the change of R Y of change on incidence of infective endocarditis in and Heart J. PubMed Scopus Google Scholar However, among the the incidence of IE by was to have increased and the change of R Y of change on incidence of infective endocarditis in and Heart J. PubMed Scopus Google Scholar the incidence of IE among adults increased the change of S Patel NJ Deshmukh A Golwala H Patel N Badheka A Hirsch GA Mehta JL Trends in infective endocarditis incidence, microbiology, and valve replacement in the United States from 2000 to 2011.J Am Coll Cardiol. 2015; 65: 2070-2076Crossref PubMed Scopus (385) Google Scholar that heart disease years the of K K and heart incidence and in the of to PubMed Scopus Google Scholar the of the changes on the incidence of IE is to Our study differences between men and women in the incidence and mortality trends of IE. The incidence increase was among men in states, the was for mortality Similar trends were in other high-income M Hartley A Al-Khayatt BM Delago AJ Ghajar A Ojha U Marshall DC Salciccioli JD Prendergast BD Shalhoub J Trends in the incidence and mortality of infective endocarditis in high-income countries between 1990 and 2019.Int J Cardiol. 2023; 371: 441-451Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar The incidence increase among men men are to cardiac K N S L P S A differences in selected cardiac A statewide Am Heart 2022; PubMed Scopus Google Scholar and J R J S and of infective endocarditis with drug in the United States from to Am Heart PubMed Scopus Google L S J R L Z N J J S for Disease and States, Google Scholar The mortality rates among women incidence rates are It is that the increase in incidence among men cardiac increase the mortality, are to for cardiac and and In are and have studies that women with IE are to have of the valve than the and heart the time of F L L et between early valve and mortality in with infective endocarditis in a cohort PubMed Scopus Google Scholar A study gender to an of in-hospital mortality a to JL L The of infective endocarditis in a study to Am Coll Cardiol. PubMed Scopus Google Scholar with IE were also to valve replacement surgery, and than F L L et between early valve and mortality in with infective endocarditis in a cohort PubMed Scopus Google A P differences in the and of cardiac valve replacement for infective endocarditis: from the National Am Heart Scopus Google Scholar It is the of valve replacement among women is to or to gender in the of the difference in the mortality increase between men and women was as globally as in all US studies are to explore of the gender in the United States and to of diagnostic also to the increasing diagnoses of A in infective endocarditis: a 2020; PubMed Scopus Google Scholar The of cardiac and other cardiac A in infective endocarditis: a 2020; PubMed Scopus Google Scholar of have A diagnosis of of the 2015; Full Text Full Text PDF PubMed Scopus Google Scholar At the diagnosis of IE on has decreased to the significant in the of The changing of in the United States, Google Scholar We states as and mortality rates to IE, incidence and mortality rates incidence The rates of IE between to differences in the of clinical the incidence and mortality trends of IE. Our study has the GBD codes for or between native versus prosthetic or versus we were to analyses of trends by there substantial differences in trends between The National or used to the trends by different of IE to the changing epidemiology of IE in on the or of cardiac was in this database. used in studies to the that the increased incidence of cardiac to the increasing incidence of IE. We study to the the of factors as insurance or to data of trends of IE by factors using data the of in our In of the changes in the trends to changes in the diagnostic of IE over defined by different diagnostic in our the trend analyses were on the reported and there are to cases included in the Our results the rates of IE among or of the US In conclusion, the overall incidence and mortality of IE increased over the past 30 years in the United States. There are significant differences between regions, gender, and age groups. These findings indicate the unevenly distributed disease burden of IE across the nation. The have of to with

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