https://orcid.org/0000-0003-3647-6185
Figures
Abstract
Background
Chronic respiratory diseases (CRDs) and heart failure (HF) impose substantial global burdens. However, the long-term population-level burden of HF impairment under CRD cause categories remains insufficiently characterized within the GBD framework.
Methods
Using GBD 2021 data, we estimated the prevalence and years lived with disability (YLDs) of HF impairment under CRD cause categories among adults aged ≥55 years from 1990 to 2021. CRD cause categories included chronic obstructive pulmonary disease (COPD), interstitial lung disease and pulmonary sarcoidosis (ILD&PS), and pneumoconiosis (PC). Cases, rates, relative changes, and EAPCs were used as primary descriptive measures. Joinpoint regression, age–period–cohort analysis, inequality indices, and BAPC-based projections were used as secondary analyses to describe trend timing, age–cohort patterns, socioeconomic distribution, and historical-trend extensions through 2032.
Results
From 1990 to 2021, the global prevalent cases and YLDs of HF impairment under CRD cause categories increased markedly, while prevalence and YLD rates changed only modestly overall. The burden rose sharply with age, especially after age 75, and was generally higher in males. Temporal trends differed across periods. Patterns varied across SDI strata and differed by CRD subtype. Model-based extensions of historical patterns suggested that this burden pattern may remain substantial through 2032.
Citation: Liu Y, Xu A, Zhang C, Li Z, Li S, Fang H (2026) Global patterns and trends in heart failure burden under chronic respiratory disease cause categories among adults aged 55 years and older: A systematic analysis based on the GBD 2021 Study. PLoS One 21(7): e0353177. https://doi.org/10.1371/journal.pone.0353177
Editor: Harapan Harapan, Universitas Syiah Kuala, INDONESIA
Received: June 6, 2025; Accepted: June 19, 2026; Published: July 21, 2026
Copyright: © 2026 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: AT FTC: follow-up to ensure OSF repository is made public. The data utilized in this study were sourced from the open-access Global Burden of Disease (GBD) database. GBD 2021 data are publicly available online (http://ghdx.healthdata.org/gbd-results-tool). Additionally, the raw data, analytical code, and supplementary materials associated with this study are accessible in Supplementary Material 2 and via the Open Science Framework (OSF) platform (https://osf.io/uv5tm/overview).
Funding: This study was supported by the Wuyingen Shanghai Famous Traditional Chinese Medicine Studio Primary-Level Workstation Project (Grant No. JCGZZ2023076 to Dr. Hong Fang) of the Shanghai Municipal Health Commission, and the Preventive Treatment of Disease in Traditional Chinese Medicine Specialist Alliance Construction Project (Grant No. 2024LM01 to Dr. Hong Fang) of the Shanghai Minhang District Health Commission. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
Abbreviations: CRDs, Chronic respiratory diseases; COPD, Chronic obstructive pulmonary disease; ILD&PS, Interstitial lung disease and pulmonary sarcoidosis; PC, Pneumoconiosis; HF, Heart failure; YLDs, Years lived with disability; GBD, Global Burden of Disease; GHDx, Global Health Data Exchange; SDI, Socio-demographic Index; EAPC, Estimated Annual Percentage Change; APC, Annual Percent Change; AAPC, Average Annual Percent Change; A–P–C, Age–Period–Cohort; SII, Slope Index of Inequality; CI, Concentration Index; BAPC, Bayesian age–period–cohort model; WHO, World Health Organization; ASPR, Age-standardized prevalence rate.
Chronic respiratory diseases (CRDs) are a group of diseases that affect the airways and lungs, including chronic obstructive pulmonary disease (COPD), interstitial lung disease and pulmonary sarcoidosis (ILD&PS), occupational lung diseases (such as pneumoconiosis, PC) and pulmonary hypertension. CRDs are often characterized by long-term persistence, progressive symptoms, and the need for ongoing management. Recurrent exacerbations and inadequate disease control may contribute to functional decline, hospitalizations, and increased mortality risk. According to statistics, CRDs were the third leading cause of death globally in 2019, resulting in approximately 4 million deaths and a global prevalence of 454.6 million cases, placing immense pressure and economic burden on healthcare systems worldwide [1].
Heart failure (HF), a complex syndrome characterized by dyspnea and fluid retention, has seen a global prevalence surge of 106.3% over the past three decades, exceeding 50 million cases by 2019 [2]. This burden is profoundly age-dependent: prevalence and healthcare utilization escalate precipitously with advancing age. For instance, U.S. data (2021–2023) indicate that HF prevalence in octogenarians is nearly double that of the 60–79 age group [3]. Surveillance studies further identify HF as the primary driver of hospitalization and adverse outcomes for individuals aged ≥65 years [4–6]. Ultimately, while age-standardized incidence may be stabilizing in some developed nations [7], the absolute caseload continues to intensify due to demographic aging, solidifying HF as a formidable global public health challenge.
CRDs and HF are prevalent conditions in aging populations, sharing clinical features such as recurrent exacerbations, functional limitation, and high hospitalization rates. In addition to shared risk factors such as smoking and cardiometabolic comorbidities, clinical and epidemiological evidence suggests that chronic respiratory impairment and cardiac dysfunction may intersect through several cardiopulmonary pathways [8,9]. CRD-associated chronic hypoxemia and pulmonary vascular remodeling can increase pulmonary vascular resistance, thereby elevating right ventricular afterload and predisposing susceptible individuals to right-sided cardiac dysfunction and HF decompensation [10,11]. Systemic inflammation and oxidative stress arising from chronic airway inflammation may also extend beyond local pulmonary effects and have been linked to endothelial dysfunction, atherosclerosis progression, and myocardial remodeling [9,12]. In CRDs, particularly COPD, pulmonary hyperinflation and altered intrathoracic pressure can impair venous return and ventricular filling, reduce stroke volume, and exacerbate dyspnea and exercise intolerance, thereby complicating the clinical assessment of HF [13]. Acute respiratory exacerbations, often triggered by infection, may further induce sympathetic activation and increased metabolic demand and have been temporally associated with acute cardiovascular events and HF-related hospitalizations, especially in frail older adults [14]. These overlapping clinical features and cardiopulmonary pathways highlight the relevance of examining the population-level burden of HF impairment under CRD cause categories among older adults.
Although CRDs and HF have each been widely examined in previous GBD studies, the long-term HF burden under CRD cause categories in older adults remains insufficiently characterized. To address this gap, we used GBD 2021 data to assess the global, regional, and national patterns of this burden among adults aged ≥55 years from 1990 to 2021, focusing on differences by CRD subtype, socioeconomic development level, and model-based trend extensions. These findings may provide a population-level basis for burden monitoring and public health planning in ageing populations.
Methods
Data source and extraction
This study was based on a secondary analysis of the publicly available GBD 2021 database, with data obtained through the Global Health Data Exchange (GHDx) (accessed November 28, 2024). We extracted estimates from 1990 to 2021 at the global, regional, and national levels, including five SDI quintiles and 21 GBD regions. In the GBD framework, heart failure was specified as the impairment of interest, and CRDs and their major subtypes—COPD, ILD&PS, and PC—were specified as causes. The primary outcomes were GBD-reported prevalence and years lived with disability (YLDs), and both number and rate metrics were extracted for each outcome. We restricted the analysis to adults aged ≥55 years to focus on a broad older-adult period, from late midlife to advanced older ages, when cardiopulmonary burden becomes more common [15]. Similar age cutoffs have been used in previous public health and GBD-based studies of older adults [16,17]. With this restriction, cases and YLDs were counted only within this age group, and crude rates were calculated using the corresponding population as the denominator. Because this age group covers a wide age range, crude rates may also be influenced by the age structure within this group. We therefore conducted age-stratified analyses to describe differences across older age groups. Counts and non-age-standardized rates were used for descriptive comparisons, whereas age-standardized rates were used for temporal trend analyses and model-based estimation of future trends to reduce the influence of changes in age structure. No missing values were identified in the extracted analytical dataset, and thus no imputation or complete-case analysis was required. Because this study was based on aggregated GBD estimates rather than original individual-level patient data, a conventional participant recruitment process was not applicable. Institutional review board approval was not required because all data were publicly available and de-identified. Both the raw data and code scripts are available on the Open Science Framework (OSF). For supplementary contextual comparison, corresponding GBD 2023 estimates were also extracted for the same outcomes, age range, CRD cause categories, and selected stratifications.
Definitions
In GBD 2021, causes are organized within a hierarchical cause list. CRDs are classified as a Level 2 cause and comprise three Level 3 causes: COPD, ILD&PS, and PC. PC further includes silicosis, asbestosis, coal workers’ pneumoconiosis, and other pneumoconioses [18]. YLDs quantify non-fatal health loss and are calculated as prevalence multiplied by a disability weight [19]. In the GHDx results interface, HF is available as an impairment category of non-fatal health loss. Accordingly, the present analysis estimated the prevalence and YLDs of HF impairment allocated to CRD cause categories in the GBD framework. Therefore, these estimates should be interpreted as modeled population-level burden estimates within the GBD framework, rather than as clinically confirmed CRD–HF comorbidity or evidence of individual-level causal relationships.
SDI
The Socio-demographic Index (SDI) is a composite measure of population and socioeconomic development, reflecting the link between social development and health outcomes. It combines per capita income, educational attainment for individuals aged 15 + , and fertility rates for women aged 15–24 to rank countries and regions into five SDI quintiles: High, High-middle, Middle, Low-middle, and Low SDI [20].
Statistical analysis
We first summarized GBD-reported prevalent cases, YLDs, and corresponding rates in 1990 and 2021, and calculated relative changes from 1990 to 2021. Long-term changes in prevalence and YLD rates were quantified using the estimated annual percentage change (EAPC), which was derived by fitting a linear regression to the natural logarithm of each annual estimate [21]. This approach provides a concise summary of long-term temporal trends and has been widely used in chronic disease and global burden trend analyses [22]. EAPC estimates were interpreted as increasing, decreasing, or non-significant according to whether the 95% CI was above, below, or crossed zero. The burden measures and EAPC estimates served as the principal descriptive outputs for assessing burden magnitude and long-term direction of change.
Additional analyses were then used to examine specific features of these patterns. Joinpoint regression was applied to the GBD-reported prevalence and YLD rates to describe segment-specific changes in temporal trends. Segment-specific annual percent change (APC) and average annual percent change (AAPC) were estimated using the U.S. National Cancer Institute’s Joinpoint software, with 95% confidence intervals obtained via Monte Carlo permutation tests. Age–period–cohort analysis was used to examine age-, period-, and cohort-related patterns among adults aged ≥55 years [23,24]. Age was divided into nine groups from 55–59 years to ≥95 years, and the study period was divided into six periods from 1992–1996–2017–2021, excluding 1990–1991. The analysis was conducted using the NCI online APC tool, with 55–59 years and 2002–2006 as the reference groups. Sensitivity analyses using alternative reference groups were performed by comparing net drift and local drift estimates [25].
Cross-country inequalities were assessed using the Slope Index of Inequality (SII) and the Concentration Index (CI), with countries ranked by SDI. SII measured absolute rate inequality across the SDI distribution, whereas CI measured the population-weighted concentration of burden. Negative SII or CI values indicated higher rates or burden concentration in lower-SDI settings, while positive values indicated the opposite pattern {Jiang, 2023 #23} [26,27]. The two indices were interpreted as complementary measures of rate-based and population-weighted inequality.
To extend historical age-standardized trends of HF burden under CRD cause categories from 2022 to 2032, we used a Bayesian age–period–cohort (BAPC) model based on historical GBD 2021 estimates, IHME population forecasts, and the WHO 2000–2025 standard population [28,29]. The model generated extrapolated estimates of prevalent cases, YLDs, age-standardized prevalence rates, and age-standardized YLD rates up to 2032. Nordpred was used as a supplementary modelling comparison to examine whether the broad direction of change was consistent across approaches [30]. GBD 2023 estimates were used only for supplementary comparison with the GBD 2021-based results, focusing on whether broad burden patterns and detailed stratified trends differed between the two datasets. Data cleaning, statistical calculations, and visualization were performed using R software version 4.4.1, with graphical visualization generated using the ggplot2 package. Final figure refinement and layout optimization were completed in Adobe Illustrator version 2025 to improve visual clarity.
Results
Total CRDs
From 1990 to 2021, GBD 2021 estimates showed substantial increases in the global prevalent cases and YLDs of HF impairment under CRD cause categories among adults aged ≥55 years, each rising by approximately 150% (Table 1; Fig 1A; Supplementary Table S1 in S1 File). Based on EAPC, the long-term average change in rates was modest but positive for both the prevalence rate and YLD rate (both EAPC = 0.13). This modest global average masked large between-region contrasts: High-income Asia Pacific had the fastest rate increases (EAPC = 2.75 for prevalence rate; 2.72 for YLD rate), whereas Eastern Europe showed the steepest declines (both EAPCs = −2.27) (Table 1; Fig 1A; Supplementary Table S1 in S1 File). By SDI, the Middle SDI quintile carried the highest burden in 2021, while rate trajectories diverged over time (Middle SDI decreasing: EAPC = −0.68; High SDI increasing most rapidly: EAPC = 1.70) (Table 1; Fig 1A).
(A) CRDs; (B) COPD; (C) ILD&PS; (D) PC.
These average trends occurred against a pronounced age–sex gradient and non-linear development pattern. In 2021, prevalence and YLD rates rose steeply with age—especially from age 75 years onward—and were generally higher in males, with the sex gap widening in the oldest age groups (Fig 2A; S1A Fig). Regionally, rates tended to decline with increasing SDI across low-to-middle SDI settings (SDI ~ 0.4–0.6) but rose again when SDI exceeded ~0.7 and peaked in high-SDI regions (Fig 3; S3A Fig). Country-level patterns were consistent with this heterogeneity: > 90% of countries experienced increases in absolute burden, whereas rate changes were split (52.0% increasing vs 48.0% decreasing) (Fig 4A; S4A Fig; Supplementary Tables S8–S9 in S1 File).
(A) CRDs; (B) COPD; (C) ILD&PS; (D) PC.
(A) CRDs; (B) COPD; (C) ILD&PS; (D) PC.
To further characterize the temporal structure behind the long-term EAPC estimates, Joinpoint regression indicated phase-specific changes in rates. The prevalence rate increased during 1990–2001, then plateaued or declined during 2001–2016, and increased again after 2016 (AAPC = 0.35%, 95% CI: 0.22–0.47) (Fig 5A; Supplementary Table S16 in S1 File). For the YLD rate, the most pronounced recent increase occurred during 2019–2021 (APC = 1.76%) (S5A Fig; Supplementary Table S17 in S1 File). The A–P–C results also highlighted the strong age gradient observed in the descriptive burden estimates. Although the global net drift of prevalence was close to null (−0.06% per year), the age effect increased sharply in the oldest groups, particularly among adults aged ≥80 years, consistent with the cross-sectional pattern in 2021 (Fig 6A; S6A Fig; Supplementary Tables S24–S26 in S1 File). Period effects showed only limited elevation around the late 1990s/early 2000s, whereas cohort effects peaked in earlier birth cohorts and declined in later cohorts (Fig 6B–6C; S6B–S6C Fig; Supplementary Tables S27–S28 in S1 File). SDI-stratified results further indicated sustained increases in high-SDI settings but declines in middle and low SDI quintiles (Supplementary Tables S24–S30 in S1 File).
(A) CRDs; (B) COPD; (C) ILD&PS; (D) PC.
(A) Age effects; (B) Period effects; (C) Cohort effects.
Inequality analyses based on SDI ranking showed that absolute inequality in crude prevalence rates decreased between 1990 and 2021, as indicated by the SII becoming less negative from −120.86 to −46.72 (Fig 7A). In parallel, the concentration curve/CI suggested that prevalent cases in 2021 remained relatively concentrated toward higher-SDI settings (Fig 7B), reflecting differences between rate-based absolute inequality and population-weighted case distribution. When historical age-standardized trends were extended to 2032 using the BAPC model, the corresponding 2032 estimates for ASPR and age-standardized YLD rate were 247.35 and 22.02 per 100,000, respectively. Nordpred showed a broadly consistent direction of change (Fig 8A–8B; Supplementary Tables S31–S33 in S1 File).
(A) Slope index of inequality; (B) Concentration index.
(A) Age-standardized prevalence rate; (B) Age-standardized YLD rate. The black line represents the global estimate, and shaded areas indicate 95% UI.
COPD
Within the COPD cause category, global prevalent cases and YLDs of HF impairment increased substantially among adults aged ≥55 years from 1990 to 2021, each rising by approximately 146% (Fig 1B; Supplementary Tables S2–S3 in S1 File). However, rate-based growth was comparatively modest: EAPC estimates were 0.06 for the prevalence rate and 0.07 for the YLD rate, indicating that the long-term rate increase in the COPD subgroup was weaker than that observed for total CRDs, despite the marked rise in counts. Regional trends remained heterogeneous: High-income Asia Pacific showed the fastest increases (EAPC = 2.28 and 2.26), whereas Eastern Europe showed the clearest declines (EAPC = −2.27 and −2.26) (Fig 1B; Supplementary Tables S2–S3 in S1 File).
In 2021, the COPD subgroup showed a steep age gradient in both prevalence and YLD rates, with higher rates in males and the highest burden observed among adults aged ≥75 years (Fig 2B; S1B Fig). By SDI, the Middle SDI quintile carried the largest burden in 2021, but trajectories diverged: the Middle SDI quintile declined over time (EAPC = −0.71), while the High SDI quintile increased most clearly (EAPC = 1.55) (S2A and S3B Fig; Supplementary Tables S2–S3 in S1 File). At the country level, increases in absolute burden were widespread (93.6% of countries), yet rate increases were less common (observed in 46.6% of countries), indicating that increases in absolute burden were not always accompanied by increases in rates; Luxembourg showed the fastest growth in rates (EAPCs 4.57 and 4.55) (Fig 4B; S4B Fig; Supplementary Tables S10–S11 in S1 File).
Joinpoint regression indicated that the weak long-term rate increase for COPD was not linear. Prevalence rates increased during 1990–2001, plateaued or declined during 2001–2016, and rose again after 2016 (overall AAPC = 0.29%, females 0.32%) (Fig 5B; Supplementary Table S18 in S1 File). YLD rates showed a comparable segmented pattern, with an overall AAPC of 0.33% and the sharpest recent increase during 2019–2021 (APC = 1.87%) (S5B Fig; Supplementary Table S19 in S1 File). A–P–C analysis showed a contrast between the overall rate trajectory and age-specific changes: although the net drift was slightly negative (−0.13% per year), local drift remained positive among adults aged ≥80 years, despite declining among those aged 55–79 years (Fig 6A; S6A Fig; Supplementary Tables S24–S26, S29–S30 in S1 File). Period effects were elevated around 1997–2001, and cohort risks generally declined after 1947, although a rising tendency persisted in more recent female cohorts (Fig 6B–6C; S6B–S6C Fig; Supplementary Tables S27–S28 in S1 File).
Inequality analyses showed a narrowing absolute gap in crude prevalence rates from 1990 to 2021, with the SII changing from approximately −120.73 to −51.15 (S7A Fig). Despite this narrowing, COPD retained a clearly negative SII in 2021, indicating higher crude rates in lower-SDI settings. Meanwhile, the concentration curve/CI suggested that prevalent cases remained relatively concentrated toward higher-SDI settings (S7B Fig). In the BAPC analysis, the 2032 estimates for COPD were 243.91 per 100,000 for ASPR and 21.54 per 100,000 for the age-standardized YLD rate (Fig 8A–8B; Supplementary Tables S31–S32 in S1 File).
ILD&PS
Among the CRD subtypes, the ILD&PS subgroup showed the largest increase in estimated HF impairment burden from 1990 to 2021: global prevalent cases and YLDs rose by more than 500%, and both rates increased rapidly (EAPC = 3.93 for prevalence rate; 3.87 for YLD rate) (Fig 1C; Supplementary Tables S4–S5 in S1 File). Unlike total CRDs and COPD, where the long-term average rate changes were modest, ILD&PS displayed a pronounced and sustained rate escalation. Regional trends varied substantially, with Australasia showing the fastest growth (EAPC = 7.16 and 7.03) and Eastern Europe showing the steepest decline (EAPC = −3.09 for both rates) (Fig 1C; Supplementary Tables S4–S5 in S1 File).
Unlike CRDs overall and COPD, the ILD&PS-specific burden was concentrated in high-development settings. In 2021, both counts and rates peaked in the High SDI quintile, and rates were positively correlated with SDI (S2B Fig; S3C Fig; Supplementary Tables S4–S5 in S1 File). Country-level contrasts were also sharper than those observed for COPD: Montenegro showed the largest increase (and the fastest rate growth; EAPC = 12.48 and 12.47), whereas Mauritania was the only country with a notable decline in absolute burden (Fig 4C; S4C Fig; Supplementary Tables S12–S13 in S1 File). Age–sex patterns followed the expected gradient (higher burden at older ages and generally higher in males); however, at the oldest ages (≥90 years), female burden tended to approach or exceed males in some high-SDI settings (Fig 2C; S1C Fig).
The time pattern for ILD&PS differed from that observed for CRDs overall and COPD. Although the long-term EAPC showed a pronounced increase, Joinpoint analysis indicated that the rise softened in the most recent period, with a decline after 2018 for both prevalence and YLD rates (prevalence AAPC = 3.54%; YLD rate AAPC = 3.49%) (Fig 5C; S5C Fig; Supplementary Tables S20–S21 in S1 File). In the A–P–C analysis, ILD&PS showed continued growth in prevalence, with an overall net drift of 3.49% per year. Period risks increased after 2002, and cohort risks rose among individuals born after 1947, particularly in higher-SDI settings (Fig 6; S6 Fig; Supplementary Tables S24–S30 in S1 File). Inequality analyses showed that ILD&PS differed by SDI in both crude rates and case distribution. For absolute inequality, the SII increased from −0.14 in 1990 to 6.19 in 2021, indicating that crude prevalence rates were higher in higher-SDI settings by 2021 (S7A Fig). For relative, population-weighted inequality, the CI showed that prevalent cases in 2021 were distributed more toward higher-SDI countries (S7B Fig). For ILD&PS, the modelled 2032 values moved in different directions across the two age-standardized indicators, with ASPR declining to 4.80 per 100,000 and the age-standardized YLD rate increasing to 0.46 per 100,000 (Fig 8A-8B; Supplementary Tables S31–S32 in S1 File).
PC
From 1990 to 2021, the PC subgroup showed a distinct count–rate divergence among adults aged ≥55 years: prevalent cases and YLDs increased by 113%, whereas prevalence and YLD rates declined (EAPC = −0.37 and −0.36, respectively) (Fig 1D; Supplementary Tables S6–S7 in S1 File). This pattern contrasted with CRDs overall, COPD, and ILD&PS, where rate changes were more stable or increasing. Regional and country-level results reinforced this PC-specific pattern. Central Europe showed the sharpest rate decline (EAPC = −3.67), whereas Australasia showed the most notable rate increases (EAPC = 4.96 for prevalence; 4.95 for YLDs) (Fig 1D; Supplementary Tables S6–S7 in S1 File). At the country level, the largest rise in absolute burden occurred in the Maldives (+251.9%), while Qatar showed the most substantial decrease (−86%). For rates, declines predominated globally, occurring in 61.8% of countries (Fig 4D; S4D Fig; Supplementary Tables S14–S15 in S1 File).
Joinpoint analysis added temporal detail to the overall declining rate trend. Rates decreased overall (AAPC = −0.17 for prevalence; −0.16 for YLDs), with a brief rise during 1995–2000, a prolonged decline during 2000–2019, and a slight rebound in YLD rates during 2019–2021 (Fig 5D; S5D Fig; Supplementary Tables S22–S23 in S1 File). Sex-specific results showed a different pattern among females, whose prevalence and YLD rates increased throughout the study period (both AAPCs = 0.95%), despite the overall decline (Supplementary Tables S22–S23 in S1 File). The A–P–C results were in line with the overall downward rate tendency for PC. The net drift was −0.35% per year, period risk peaked around 1997–2001, and cohort risks generally declined after 1947 (Fig 6; S6 Fig; Supplementary Tables S24–S30 in S1 File).
Inequality patterns were less pronounced than those observed for the other CRD subtypes. The SII changed only slightly from 0.02 in 1990 to 0.15 in 2021, suggesting limited change in absolute inequality in crude prevalence rates. The CI showed only a mild population-weighted concentration of prevalent cases toward higher-SDI settings (S7A–S7B Fig). In the model-based extension of historical age-standardized trends, the 2032 estimates for PC were 0.73 per 100,000 for ASPR (+10.4%) and 0.06 per 100,000 for the age-standardized YLD rate (−2.2%) (Fig 8A–8B; Supplementary Tables S31–S32 in S1 File).
Comparison with GBD 2023 estimates
To contextualize the GBD 2021-based findings, we performed a supplementary comparison using updated GBD 2023 estimates. Broad burden patterns were highly consistent across both datasets, including the longitudinal increase in absolute burden, the steep age-related rise among adults aged ≥55 years, and the persistent heterogeneity across CRD cause categories. Minor variations were noted in some specific estimates, particularly in 2021 rate values and SDI-stratified EAPCs. Overall, the supplementary comparison supported the stability of the broad descriptive findings, while indicating that detailed stratified trend estimates were more sensitive to the dataset used (Supplementary Tables S34–S37 in S1 File).
Discussion
This study examined the global, regional, and national population-level burden of HF impairment under CRD cause categories among adults aged ≥55 years from 1990 to 2021. Evaluated through basic burden metrics and long-term EAPC trends, the findings showed a substantial increase in absolute burden, alongside modest global changes in rates. The data also indicated a strong age gradient concentrated in older age groups, as well as marked heterogeneity across regions, countries, sexes, SDI strata, and CRD subtypes. COPD accounted for the largest share of the burden, whereas ILD&PS and pneumoconiosis showed distinct geographic and temporal patterns. Together, these findings highlight an older-adult burden pattern that differs clearly by age, socioeconomic context, and CRD subtype.
The substantial rise in absolute burden occurred alongside relatively modest long-term changes in rates. This pattern is closely linked to population ageing within the ≥ 55-year group. As the number of older adults increases, especially in the more advanced age groups, prevalent cases and YLDs can rise markedly even when prevalence and YLD rates change only modestly. United Nations projections also indicate that population ageing will continue in the coming decades [31]. As additional background context, longer average life expectancy, a growing proportion of older adults living with multiple chronic diseases, and more comprehensive case reporting systems may further contextualize the increase in case numbers [32–35]. In this setting, counts reflect the absolute volume of health loss, whereas rates describe the burden level within the population being measured. Age-standardized rates provide a more comparable view of temporal and between-population patterns because they reduce the influence of differences in age structure [36,37].
Regional and SDI differences suggest that population ageing alone does not fully account for the heterogeneity observed across settings. In low- and middle-SDI settings, the burden may be viewed alongside continued exposure to tobacco smoke, household and ambient air pollution, and occupational dusts, as well as more limited access to prevention and long-term disease management [1,38]. In high-SDI settings, longer survival with chronic cardiopulmonary disease, residual exposure accumulated earlier in life, and better recognition of chronic cardiopulmonary conditions may be linked to higher recorded burden [39]. Overall, the uneven patterns across SDI levels should be understood in relation to ageing, exposure profiles, and health-system context.
From the perspective of SDI-ranked inequality, the main implication is that a narrowing rate gap should not be interpreted as evidence that the overall burden became lighter or more evenly distributed. In this study, the narrowing of rate-based inequality occurred alongside a continued concentration of prevalent burden toward higher-SDI settings. This pattern is particularly relevant in older populations, where the absolute number of affected individuals is strongly shaped by population ageing, longer survival with chronic disease, and the size of the population at risk. Therefore, lower-SDI settings may still show higher crude rates, while higher-SDI settings account for a larger share of population-weighted prevalent burden. The finding does not indicate inconsistency between inequality measures, but rather shows that rate differences and burden concentration reflect different dimensions of the same SDI-ranked burden pattern. The subtype findings further indicate that this pattern should not be generalized across all CRD categories. ILD&PS showed a clearer shift toward higher-SDI settings, whereas pneumoconiosis displayed a weaker and more mixed inequality pattern. These differences suggest that the overall CRD estimate masks important subtype-specific variation. Interpretation of inequality in GBD-modeled HF impairment under CRD cause categories should therefore consider rate differences, population-weighted burden concentration, absolute case burden, and subtype composition together.
Age- and sex-stratified patterns provide further context for interpreting the burden. The burden increased with age and was highest among adults aged ≥75 years, showing that the burden became more pronounced from age 75 onward. This finding is consistent with previous evidence that chronic disease burden is greater in later life [40]. Rather than reflecting individual clinical diagnoses, this age gradient may be viewed alongside the gradual decline in physiological function and long-term cumulative health loss associated with ageing. Men generally had a higher burden than women, which may be linked to smoking, occupational exposures, and other related risk factors [1,41]. However, this sex difference should be considered together with age structure. In some settings, older women also show a relatively high burden. This pattern may be associated with their longer life expectancy and a larger proportion of women reaching advanced age [42,43]. This heavy concentration of burden at advanced ages highlights why the age-stratified results are so important. Although the overall ≥55-year estimates provide a useful summary of the broad older-adult period, they average out the internal differences within this group. Specifically, the overall rate masks the relatively lower burden among adults aged 55–74 years and the pronounced spike from age 75 onward. Therefore, age-specific results should always be considered together with the overall estimates when interpreting the burden in older adults.
Turning to the temporal dimension, the late-stage patterns differed across CRD subtypes. For CRDs overall and COPD, YLD rates increased during 2019–2021, whereas ILD&PS rates declined from 2018 to 2021. These changes occurred during a period when healthcare access, routine follow-up, diagnosis, and chronic disease management were widely affected [44]. This background may be relevant because COPD often requires continuous management and rehabilitation, while ILD&PS relies more on imaging and specialist assessment [45,46].
The A–P–C results provide a longer-term view of these trends. For CRDs overall, as well as the COPD and PC subgroups, later birth cohorts showed lower risks. This pattern aligns with gradual improvements in disease prevention and routine care, such as the wider use of clinical guidelines [47]. For PC, it may also reflect changes in workplace protection and dust exposure, although earlier occupational exposures remain important because work-related lung damage often develops over many years [41,45,48]. In contrast, ILD&PS showed higher cohort-related estimates in later-born groups. This pattern may be partly related to the slow course of fibrotic lung disease and improved diagnostic recognition over time [49,50]. When the observed historical patterns were extended to 2032, the burden of HF impairment under CRD cause categories among adults aged ≥55 years did not show a clear decline. This was in line with the main finding from 1990 to 2021: the number of cases and YLDs increased substantially, whereas changes in rates were relatively small. As the older population continues to grow, even stable or slowly changing rates may still translate into a considerable care burden. These results suggest that HF impairment under CRD cause categories may remain an important issue for burden monitoring, service planning, and long-term care in older adults. However, the projections should be understood mainly as an extension of past trends, rather than as precise estimates of the future burden.
The supplementary comparison with GBD 2023 provides important context for interpreting the GBD 2021-based findings. Differences between GBD versions are expected because GBD updates may include new data sources, revised modelling strategies, and changes in disease classification. In this study, the main burden patterns were relatively stable between the two GBD versions, whereas small rate changes and narrowly stratified estimates were more likely to vary after database updates. Therefore, the main value of this study lies in identifying large-scale burden patterns, SDI-related differences, and subgroup heterogeneity, rather than in providing exact numerical estimates. Detailed stratified trends should consequently be interpreted with caution.
Ultimately, these findings suggest that the burden of HF impairment within CRD cause categories in older adults should be understood as a population-level disability burden within the GBD framework. When monitoring this burden, it is more practical to look at the number of cases, prevalence rates, and disability as a whole, as each paints a different part of the clinical picture. For planning services, the rising absolute number of patients underscores the need for ongoing support—including chronic care, rehabilitation, and disability management—as our populations age. Practically, these results suggest that resource allocation should be focused on the specific groups or settings bearing the heaviest load, rather than just the global average.We hope this evidence provides a clearer map for health systems to prioritize services and meet these evolving clinical needs.
Limitations
This study has several limitations. First, GBD estimates depend on the availability and quality of source data and on modelling assumptions across countries and regions. In settings with sparse data or incomplete surveillance systems, estimates may have greater uncertainty, and updates to GBD data inputs or modelling methods may affect some stratified results. Second, differences in diagnostic capacity, healthcare access, and reporting standards may lead to under-ascertainment or misclassification of HF and CRDs, thereby influencing prevalence and YLD estimates. Third, the analysis was restricted to adults aged ≥55 years. Although this restriction allowed us to focus on older adults, the estimates are not directly comparable with all-age studies, and crude rates may still be affected by the age structure within the ≥ 55-year population. Fourth, this study used aggregated population-level estimates and could not account for individual-level factors. Therefore, the findings should be interpreted as population-level epidemiological patterns rather than individual-level clinical relationships or causal effects. Finally, the BAPC projections were extensions of historical age-period-cohort patterns rather than deterministic forecasts. Their precision may decrease over a ten-year horizon, and future changes in population structure, diagnostic access, healthcare practice, environmental exposures, or GBD modelling strategies may lead to trends that differ from the projected estimates.
Conclusion
In summary, using GBD 2021 data, this study described the burden of HF impairment under CRD cause categories among adults aged ≥55 years from 1990 to 2021. The burden varied across regions, SDI strata, age groups, sex, and CRD subtypes. Within the GBD framework, these findings may help inform burden monitoring, public health planning, resource allocation, and long-term service planning for older adults.
Supporting information
S1 Fig. Sex- and age-specific YLD rates of HF impairment under CRD cause categories overall and for COPD, ILD&PS, and PC in 2021 among adults aged ≥55 years.
(A) CRDs; (B) COPD; (C) ILD&PS; (D) PC.
https://doi.org/10.1371/journal.pone.0353177.s001
(TIF)
S2 Fig. Associations between SDI and prevalence rates of HF impairment under the COPD, ILD&PS, and PC cause categories across 21 GBD regions, and temporal trends in prevalence rates from 1990 to 2021 among adults aged ≥55 years.
(A) COPD; (B) ILD&PS; (C) PC.
https://doi.org/10.1371/journal.pone.0353177.s002
(TIF)
S3 Fig. Associations between SDI and YLD rates of HF impairment under CRD cause categories overall and for COPD, ILD&PS, and PC across 21 GBD regions, and temporal trends in YLD rates from 1990 to 2021 among adults aged ≥55 years.
(A) CRDs; (B) COPD; (C) ILD&PS; (D) PC.
https://doi.org/10.1371/journal.pone.0353177.s003
(TIF)
S4 Fig. Percentage change in prevalent cases of HF impairment under CRD cause categories overall and for COPD, ILD&PS, and PC across 204 countries and territories from 1990 to 2021 among adults aged ≥55 years.
(A) CRDs; (B) COPD; (C) ILD&PS; (D) PC.
https://doi.org/10.1371/journal.pone.0353177.s004
(TIF)
S5 Fig. Joinpoint regression analysis of temporal trends in YLD rates for HF impairment under CRD cause categories overall and for COPD, ILD&PS, and PC from 1990 to 2021 among adults aged ≥55 years.
(A) CRDs; (B) COPD; (C) ILD&PS; (D) PC.
https://doi.org/10.1371/journal.pone.0353177.s005
(TIF)
S6 Fig. Age, period, and cohort effects on YLD rates of HF impairment under CRD cause categories overall and for COPD, ILD&PS, and PC among adults aged ≥55 years.
(A) Age effects; (B) Period effects; (C) Cohort effects.
https://doi.org/10.1371/journal.pone.0353177.s006
(TIF)
S7 Fig. Health inequality in the prevalence burden of HF impairment under the COPD, ILD&PS, and PC cause categories worldwide from 1990 to 2021 among adults aged ≥55 years.
(A) Slope index of inequality; (B) Concentration index.
https://doi.org/10.1371/journal.pone.0353177.s007
(TIF)
S1 File. This file contains all supplementary tables, including Tables S1–S37.
https://doi.org/10.1371/journal.pone.0353177.s008
(DOCX)
Acknowledgments
The authors appreciate the work by the GBD 2021 and GBD 2023 collaborators and all who helped with this study.
References
- 1. Momtazmanesh S, Moghaddam SS, Ghamari S-H, Rad EM, Rezaei N, Shobeiri P. Global burden of chronic respiratory diseases and risk factors, 1990–2019: an update from the Global Burden of Disease Study 2019. eClinicalMedicine. 2023;59:101936.
- 2. Liu Z, Li Z, Li X, Yan Y, Liu J, Wang J, et al. Global trends in heart failure from 1990 to 2019: an age-period-cohort analysis from the Global Burden of Disease study. ESC Heart Fail. 2024;11(5):3264–78. pmid:38937863
- 3. Palaniappan LP, Allen NB, Almarzooq ZI, Anderson CAM, Arora P, Avery CL, et al. 2026 heart disease and stroke statistics: a report of US and global data from the American Heart Association. Circulation. 2026. pmid:41562125
- 4. Chang PP, Wruck LM, Shahar E, Rossi JS, Loehr LR, Russell SD, et al. Trends in hospitalizations and survival of acute decompensated heart failure in four US Communities (2005-2014): ARIC study community surveillance. Circulation. 2018;138(1):12–24. pmid:29519849
- 5. Voors AA, Angermann CE, Teerlink JR, Collins SP, Kosiborod M, Biegus J, et al. The SGLT2 inhibitor empagliflozin in patients hospitalized for acute heart failure: a multinational randomized trial. Nat Med. 2022;28(3):568–74. pmid:35228754
- 6. Immanuel SS, Yonatan ER, Tandecxi G, Anthony CP, Chan JZ, Sunardi AE, et al. Redefining treatment paradigms: Early use of dapagliflozin and empagliflozin in acute heart failure - a systematic review and meta-analysis of randomized controlled trials. Narra J. 2025;5(1):e1833. pmid:40352167
- 7. Conrad N, Judge A, Tran J, Mohseni H, Hedgecott D, Crespillo AP, et al. Temporal trends and patterns in heart failure incidence: a population-based study of 4 million individuals. Lancet. 2018;391(10120):572–80. pmid:29174292
- 8. Ragnoli B, Chiazza F, Tarsi G, Malerba M. Biological pathways and mechanisms linking COPD and cardiovascular disease. Ther Adv Chronic Dis. 2025;16:20406223251314286. pmid:40161556
- 9. Ahmad S, Isbatan A, Chen S, Dudek SM, Minshall RD, Chen J. The interplay of heart failure and lung disease: clinical correlations, mechanisms, and therapeutic implications. J Respir Biol Transl Med. 2024;1(4). pmid:39916950
- 10. Rosenkranz S, Howard LS, Gomberg-Maitland M, Hoeper MM. Systemic consequences of pulmonary hypertension and right-sided heart failure. Circulation. 2020;141(8):678–93. pmid:32091921
- 11. Kent BD, Mitchell PD, McNicholas WT. Hypoxemia in patients with COPD: cause, effects, and disease progression. Int J Chron Obstruct Pulmon Dis. 2011;6:199–208. pmid:21660297
- 12. Corneanu LE, Sîngeap MS, Mutruc V, Petriș OR, Toma TP, Șorodoc V, et al. The complex relationship between heart failure and chronic obstructive pulmonary disease: a comprehensive review. J Clin Med. 2025;14(13):4774. pmid:40649150
- 13. Xu Y, Yamashiro T, Moriya H, Tsubakimoto M, Tsuchiya N, Nagatani Y, et al. Hyperinflated lungs compress the heart during expiration in COPD patients: a new finding on dynamic-ventilation computed tomography. Int J Chron Obstruct Pulmon Dis. 2017;12:3123–31. pmid:29123390
- 14. de Miguel-Diez J, Nunez Villota J, Santos Perez S, Manito Lorite N, Alcazar Navarrete B, Delgado Jimenez JF. Multidisciplinary management of patients with chronic obstructive pulmonary disease and cardiovascular disease. Arch Bronconeumol. 2024;60(4):226–37. pmid:38383272
- 15. Schoenborn CA, Vickerie JL, Powell-Griner E, Centers for Disease Control and Prevention NC for HS. Health characteristics of adults 55 years of age and over: United States, 2000-2003. Adv Data. 2006;(370):1–31. pmid:16617926
- 16. Bleumink GS, Knetsch AM, Sturkenboom MCJM, Straus SMJM, Hofman A, Deckers JW, et al. Quantifying the heart failure epidemic: prevalence, incidence rate, lifetime risk and prognosis of heart failure The Rotterdam Study. Eur Heart J. 2004;25(18):1614–9. pmid:15351160
- 17. Wang M-S, Deng J-W, Geng W-Y, Zheng R, Xu H-L, Dong Y, et al. Temporal trend and attributable risk factors of cardiovascular disease burden for adults 55 years and older in 204 countries/territories from 1990 to 2021: an analysis for the Global Burden of Disease Study 2021. Eur J Prev Cardiol. 2025;32(7):539–52. pmid:39591503
- 18. Diseases GBD, Injuries C. Global incidence, prevalence, years lived with disability (YLDs), disability-adjusted life-years (DALYs), and healthy life expectancy (HALE) for 371 diseases and injuries in 204 countries and territories and 811 subnational locations, 1990-2021: a systematic analysis for the Global Burden of Disease Study 2021. Lancet. 2024;403(10440):2133–61. pmid:38642570
- 19. Vos T, Flaxman AD, Naghavi M, Lozano R, Michaud C, Ezzati M, et al. Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380(9859):2163–96. pmid:23245607
- 20. Collaborators G B D D. Global age-sex-specific fertility, mortality, healthy life expectancy (HALE), and population estimates in 204 countries and territories, 1950-2019: a comprehensive demographic analysis for the Global Burden of Disease Study 2019. Lancet. 2020;396(10258):1160–203. pmid:33069325
- 21. Yang X, Chen H, Zhang T, Yin X, Man J, He Q, et al. Global, regional, and national burden of blindness and vision loss due to common eye diseases along with its attributable risk factors from 1990 to 2019: a systematic analysis from the global burden of disease study 2019. Aging (Albany NY). 2021;13(15):19614–42. pmid:34371482
- 22. Zhang D, Liu S, Li Z, Wang R. Global, regional and national burden of gastroesophageal reflux disease, 1990-2019: update from the GBD 2019 study. Ann Med. 2022;54(1):1372–84. pmid:35579516
- 23. Tang K, Zhu L, Shan S, Luo Z, Zhou J, Ying J, et al. Global, regional and national trends in the epidemiology of rheumatoid arthritis from 1990 to 2021: an age-period-cohort effect analysis of the global burden of disease study 2021. RMD Open. 2025;11(2):e005383. pmid:40221149
- 24. Cao F, Li D-P, Wu G-C, He Y-S, Liu Y-C, Hou J-J, et al. Global, regional and national temporal trends in prevalence for musculoskeletal disorders in women of childbearing age, 1990-2019: an age-period-cohort analysis based on the Global Burden of Disease Study 2019. Ann Rheum Dis. 2024;83(1):121–32. pmid:37666645
- 25. Masters R, Powers D. Clarifying assumptions in age-period-cohort analyses and validating results. PLoS One. 2020;15(10):e0238871. pmid:33021978
- 26. Jiang C-Y, Han K, Yang F, Yin S-Y, Zhang L, Liang B-Y, et al. Global, regional, and national prevalence of hearing loss from 1990 to 2019: A trend and health inequality analyses based on the Global Burden of Disease Study 2019. Ageing Res Rev. 2023;92:102124. pmid:37972859
- 27. Cao F, He Y-S, Wang Y, Zha C-K, Lu J-M, Tao L-M, et al. Global burden and cross-country inequalities in autoimmune diseases from 1990 to 2019. Autoimmun Rev. 2023;22(6):103326. pmid:36958621
- 28. Liu Z, Xu K, Jiang Y, Cai N, Fan J, Mao X, et al. Global trend of aetiology-based primary liver cancer incidence from 1990 to 2030: a modelling study. Int J Epidemiol. 2021;50(1):128–42. pmid:33349860
- 29. Yuan M, Zhu Y, Ren Y, Chen L, Dai X, Wang Y, et al. Global burden and attributable risk factors of breast cancer in young women: historical trends from 1990 to 2019 and forecasts to 2030 by sociodemographic index regions and countries. J Glob Health. 2024;14:04142. pmid:39026460
- 30. Gao Y, Wang X, Wang Q, Jiang L, Wu C, Guo Y, et al. Rising global burden of common gynecological diseases in women of childbearing age from 1990 to 2021: an update from the Global Burden of Disease Study 2021. Reprod Health. 2025;22(1):57. pmid:40259342
- 31.
United Nations Department of Economic and Social Affairs, Population Division. World Population Ageing 2023: Challenges and opportunities of population ageing in the least developed countries. United Nations; 2023.
- 32. Rizzuto D, Melis RJF, Angleman S, Qiu C, Marengoni A. Effect of chronic diseases and multimorbidity on survival and functioning in elderly adults. J Am Geriatr Soc. 2017;65(5):1056–60. pmid:28306158
- 33. Yang H-M, Ryu MH, Carey VJ, Kinney GL, Hokanson JE, Dransfield MT, et al. Chronic obstructive pulmonary disease exacerbations increase the risk of subsequent cardiovascular events: a longitudinal analysis of the COPDGene Study. J Am Heart Assoc. 2024;13(11):e033882. pmid:38818936
- 34. Krishnan JA. The case for case-finding in asthma and chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2025;211(11):1982–3. pmid:41086412
- 35. Haroon S, Adab P, Griffin C, Jordan R. Case finding for chronic obstructive pulmonary disease in primary care: a pilot randomised controlled trial. Br J Gen Pract. 2013;63(606):e55-62. pmid:23336474
- 36. Tian N, Kobau R, Zack MM, Greenlund KJ. Barriers to and disparities in access to health care among adults aged ≥18 years with epilepsy - United States, 2015 and 2017. MMWR Morb Mortal Wkly Rep. 2022;71(21):697–702. pmid:35617131
- 37. Klein RJ, Schoenborn CA. Age adjustment using the 2000 projected U.S. population. Healthy People 2010 Stat Notes. 2001;(20):1–10. pmid:11676466
- 38.
World Health Organization. WHO report on the global tobacco epidemic, 2025: warning about the dangers of tobacco. World Health Organization; 2025.
- 39. Heidenreich PA, Bozkurt B, Aguilar D, Allen LA, Byun JJ, Colvin MM, et al. 2022 AHA/ACC/HFSA guideline for the management of heart failure: executive summary: a report of the American College of Cardiology/American heart association joint committee on clinical practice guidelines. Circulation. 2022;145(18):e876–94. pmid:35363500
- 40. Coats AJS. Ageing, demographics, and heart failure. Eur Heart J Suppl. 2019;21(Suppl L):L4–7. pmid:31885504
- 41. Cullinan P, Muñoz X, Suojalehto H, Agius R, Jindal S, Sigsgaard T, et al. Occupational lung diseases: from old and novel exposures to effective preventive strategies. Lancet Respir Med. 2017;5(5):445–55. pmid:28089118
- 42. Chowdhury SR, Chandra Das D, Sunna TC, Beyene J, Hossain A. Global and regional prevalence of multimorbidity in the adult population in community settings: a systematic review and meta-analysis. EClinicalMedicine. 2023;57:101860. pmid:36864977
- 43. Pepine CJ, Merz CNB, El Hajj S, Ferdinand KC, Hamilton MA, Lindley KJ, et al. Heart failure with preserved ejection fraction: similarities and differences between women and men. Int J Cardiol. 2020;304:101–8. pmid:31959407
- 44. Tsutsui M, Gerayeli F, Sin DD. Pulmonary rehabilitation in a post-COVID-19 world: telerehabilitation as a new standard in patients with COPD. Int J Chron Obstruct Pulmon Dis. 2021;16:379–91. pmid:33642858
- 45. Tomášková H, Šplíchalová A, Šlachtová H, Urban P, Hajduková Z, Landecká I, et al. Mortality in miners with coal-workers’ pneumoconiosis in the czech republic in the period 1992-2013. Int J Environ Res Public Health. 2017;14(3):269. pmid:28272360
- 46. Durhan G, Ardalı Düzgün S, Baytar Y, Gülsün Akpınar M, Başaran Demirkazık F, Arıyürek OM. Two in one: Overlapping CT findings of COVID-19 and underlying lung diseases. Clin Imaging. 2023;93:60–9. pmid:36395576
- 47.
GOLD. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease (2025 report). 2024.
- 48. Gbondo D, Zhao Y, Pham M, Rumchev K. Trends in exposure to respirable dust and respirable crystalline silica among lithium mine workers in Western Australia. Saf Health Work. 2024;15(4):481–90. pmid:39697313
- 49. Snyder LD, Mosher C, Holtze CH, Lancaster LH, Flaherty KR, Noth I, et al. Time to diagnosis of idiopathic pulmonary fibrosis in the IPF-PRO Registry. BMJ Open Respir Res. 2020;7(1):e000567. pmid:32624493
- 50. Zangiabadi A, De Pasquale CG, Sajkov D. Pulmonary hypertension and right heart dysfunction in chronic lung disease. Biomed Res Int. 2014;2014:739674. pmid:25165714