Introduction

Non-communicable diseases (NCDs), such as cardiovascular diseases, cancers, chronic respiratory conditions, and diabetes, are the predominant cause of death globally, accounting for approximately 74% of all mortality, as reported by the World Health Organization [1]. This escalating burden, intensifying over recent decades, places significant pressure on health systems worldwide, particularly in low- and middle-income countries (LMICs), where limited resources and infrastructure exacerbate challenges [2]. NCDs disproportionately affect the most vulnerable socioeconomic communities, including those in LMICs, due to factors such as poverty, limited healthcare access, and social inequities, rather than solely rapid urbanization or aging populations [3]. In LMICs, this reflects an epidemiological transition from infectious diseases to chronic conditions, compounding existing health challenges [4,5].

Several interconnected factors fuel the rise of NCDs, including sedentary lifestyles, poor nutrition, tobacco use, excessive alcohol consumption, and environmental exposures such as air pollution [6]. These risk factors are amplified by socioeconomic inequalities, which limit access to prevention, early detection, and treatment, particularly in resource-constrained settings [7]. While high-income countries have made strides in mitigating NCD prevalence through robust public health policies, LMICs continue to grapple with inadequate funding and systemic barriers, resulting in higher morbidity and economic costs [8].

This paper examines the global burden of NCDs by analysing trends in incidence, mortality, and disability-adjusted life years (DALYs) across regions and income levels from 2000 to 2021, with projections extending to 2050. Drawing on data from the Global Burden of Disease (GBD) study and WHO reports, the study employs statistical modelling to assess historical patterns and forecast future trajectories under different policy scenarios. It also investigates the influence of key risk factors such as obesity, smoking, and pollution on NCD outcomes, aiming to identify priorities for intervention. By providing a detailed synthesis of past trends and future projections, this research offers actionable insights for policymakers and health professionals seeking to address the mounting NCD crisis.

Materials and methods

We conducted a secondary analysis of the global burden of non-communicable diseases (NCDs), specifically cardiovascular diseases (CVD), neoplasms, diabetes mellitus (DM), and chronic respiratory diseases (CRDs), from 2000 to 2021, with projections to 2050. These NCDs were classified using the Global Burden of Disease (GBD) 2019 framework, which organizes diseases into three levels: Level 1 includes all NCDs as a broad group, and Level 2 includes major categories such as CVDs, neoplasms, DM, and CRDs [9], S0 Table in S1 File. Our study focused on these Level 2 categories without analysing specific Level 3 subcategories. Data for incidence, mortality, and disability-adjusted life years (DALYs) were sourced from the GBD 2021 estimates provided by the Institute for Health Metrics and Evaluation (IHME), covering 204 countries and territories. The use of the GBD 2019 framework ensures standardized disease classification and methodological consistency, while the updated GBD 2021 dataset provides the most recent estimates, including risk factor contributions and projections to 2050 based on historical trends. [9], covering 204 countries and territories. This comprehensive country selection aligns with the GBD 2019’s standardized framework, which uses consistent data collection and reporting methods across nations to ensure comparability with global health metrics standards. The GBD 2019 provides estimates of incidence, mortality, and disability-adjusted life years (DALYs) [9], a metric combining years of life lost and years lived with disability, derived from integrated health data, along with risk factor contributions and 2050 projections based on historical trends. Ethics approval and consent to participate is not applicable due to the nature of the study.

We reported age-standardized incidence rates (new cases per 100,000 population per year), mortality rates (deaths per 100,000 population per year), and disability-adjusted life years (DALYs; per 100,000 population per year), which combine years of life lost and years lived with disability, for cardiovascular diseases (CVD), neoplasms, diabetes mellitus (DM), and chronic respiratory diseases (CRDs) [9]. Outcomes were evaluated globally, by Socio-Demographic Index (SDI; Low, Low-Middle, Middle, High-Middle, High) [9], WHO region (African, Americas, Eastern Mediterranean, European, South-East Asia, Western Pacific), sex, and country, with highest and lowest rates highlighted where applicable.

The 2021 global NCD burden was aggregated from GBD (rates per 100,000), with proportions calculated as percentages of total deaths or DALYs. Trends from 2000 to 2021 were quantified using the average annual percentage change (AAPC), calculated as [10]:

Where values represent ASR (incidence), deaths (mortality), or DALYs. We note that using counts may partly capture demographic effects such as population growth and aging, rather than solely reflecting changes in disease risk. To address this, country, SDI, and WHO regional comparisons were complemented with age-standardized rates provided by GBD, particularly for the 2050 projections. Risk factor impacts were reported as GBD-provided deaths and DALYs per 100,000 population.

Results

In alignment with the WHO’s Global NCD Monitoring Framework and the Sustainable Development Goal (SDG) 3.4 and WHO report 2024 recommendations of NCDs, aiming to reduce premature mortality from non-communicable diseases by one-third by 2030, this study conducted focused analyses on the four major NCDs: cardiovascular diseases, neoplasms, chronic respiratory diseases, and diabetes mellitus. These diseases were examined in terms of incidence, mortality, and disability-adjusted life years (DALYs), with analyses stratified by time, region, and socio-demographic context. In addition to evaluating historical trends, projections were generated through 2050 to estimate the future burden of NCDs and assess alignment with global health targets.

SDI and WHO region analysis of NCDs (2021)

The burden of NCDs varied widely across SDI groups (S1, S1B in S1 File, Fig 1A). Incidence rates for diabetes, CVDs, and neoplasms were consistently highest in high-SDI regions and lowest in low-SDI regions. CRDs showed a different pattern, with elevated incidence in both high- and low-SDI regions, but lower levels in middle-SDI groups. Mortality also varied: diabetes deaths were greatest in middle and low-middle SDI regions, CVD mortality peaked in the high-middle group, and neoplasm mortality declined steadily from high- to low-SDI regions. CRD mortality was highest in low-middle SDI regions. DALYs followed a mixed pattern: diabetes and neoplasms were most burdensome in high-SDI regions, while CVDs peaked in the high-middle group and CRDs in the low-middle group.

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Fig 1. Global burden of NCDs (A) SDI category and (B) WHO regions in 2021.

https://doi.org/10.1371/journal.pone.0336036.g001

Regional comparisons (S1, S1C, Fig S1B in S1 File) revealed distinct geographic disparities. Incidence was highest in the Americas for diabetes, CRDs, and neoplasms, while Europe led for CVDs. Mortality patterns mirrored these findings, with Europe highest for CVDs and neoplasms, South-East Asia for CRDs, and the Americas for diabetes. DALYs followed similar trends, with Europe highest for CVDs and neoplasms, South-East Asia for CRDs, and Africa generally lowest across all metrics, except for CRD incidence, which remained relatively high.

Country-based analysis (2021)

Across 204 countries, as classified by the United Nations, we evaluated country-level variations in the burden of four major NCDs, cardiovascular diseases (CVDs), neoplasms, chronic respiratory diseases (CRDs), and diabetes mellitus, examining incidence, mortality, and disability-adjusted life years (DALYs). Estimates are illustrated in Fig 2, with additional details provided in S2, S2A–2D in S1 File.

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Fig 2. Country-based Incidence, Mortality, and DALYS rate (per 100,000 population) (2021) CVDs.

(A, B and C), Neoplasm (D, E, and F), CRDs (G, H and I), and DM (J, K and L).

https://doi.org/10.1371/journal.pone.0336036.g002

Risk factors analysis

Globally, metabolic risk factors were the primary drivers of NCDs DALYs, Fi 3A, with high systolic blood pressure contributing 131·49 deaths, Fig 3B, and 2,718·40 DALYs per 100,000 for CVDs. High body-mass index (BMI) and high fasting plasma glucose also had substantial impacts, accounting for 24·13 deaths and 575·65 DALYs (BMI) and 28·04 deaths and 544·28 DALYs (glucose) for CVD, 4·52 deaths and 112·71 DALYs (BMI) and 4·16 deaths and 89·35 DALYs (glucose) for neoplasms, and 9·17 deaths and 498·13 DALYs (BMI) and 20·99 deaths and 1,000·20 DALYs (glucose) for diabetes. Behavioural risk factors amplified the NCD burden, with tobacco use linked to 36·01 deaths and 933·95 DALYs for CVD and 26·74 deaths and 641·25 DALYs for neoplasms, and dietary risks associated with 73·93 deaths and 1,700·34 DALYs for CVD and 8·49 deaths and 207·87 DALYs for neoplasms Fig 3C and 3D)· Environmental risk factors, particularly air pollution, were notable, with 56·80 deaths and 1,262·62 DALYs for CVD and 22·58 deaths and 477·64 DALYs for chronic respiratory diseases, S3 Table S in S1 File.

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Fig 3. Metabolic, Behavioural, and Environmental risk factors DALYs and Mortality 2021.

https://doi.org/10.1371/journal.pone.0336036.g003

Metabolic risk factors by WHO regions and SD categories

WHO regions: CVDs linked to high systolic blood pressure (SBP) is the leading cause of deaths, across WHO regions, with the highest rates in Europe (223·7 deaths and 3,912·2 DALYs per 100,000), S1 Fig and S2 Fig in S1 File, respectively. BMI and elevated FPG also significantly contribute to diabetes and neoplasm burdens, particularly in the Americas and Europe, S3A in S1 File.SDI category: CVDs linked to SBP show the highest death, S3 Fig in S1 File and DALY, S Fig 4, burdens across all SDI levels, peaking in high-middle SDI (215·85 deaths, 3,999·29 DALYs per 100,000). As SDI increases, CVD burdens from LDL, BMI, and FPG rise, with diabetes and neoplasms tied to BMI and FPG also increasing, diabetes + FPG DALYs reach 1,196·51 in high SDI. In contrast, CRD’s linked to BMI show low, variable DALYs, peaking at 70·85 in high SDI despite lower mortality. S3B in S1 File.

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Fig 4. Gender analysis of NCDs burden 2021.

https://doi.org/10.1371/journal.pone.0336036.g004

Analyses of CVD’s, Neoplasms, CRD’s, and DM trends from 2000 to 2021

Between 2000 and 2021, global trends in non-communicable diseases (NCDs) revealed divergent patterns across CVDs, neoplasms, CRDs, and DM, as measured by age-standardized incidence, mortality, and DALY rates per 100,000 population, Fig 5. The figure illustrates that incidence and mortality related to diabetes mellitus (DM) increased steadily, CVDs showed a gradual rise in incidence with relatively stable mortality and slightly declining DALYs, neoplasms demonstrated consistent upward trends across incidence and mortality, while chronic respiratory diseases (CRDs) remained broadly stable or showed slight declines. Quantitative estimates of these changes, expressed as average annual percentage changes (AAPCs), are reported in S5: CVDs (mortality: 0.21%; incidence: 1.01%; DALYs: –0.11%), neoplasms (mortality: 0.53%; incidence: 1.01%; DALYs: 0.07%), CRDs (mortality: –0.02%; incidence: –0.36%; DALYs: –0.34%), and DM (mortality: 1.72%; incidence: 2.41%; DALYs: 2.22%).

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Fig 5. Age-standardized incidence, mortality, and disability-adjusted life year (DALY) trends per 100,000 population for cardiovascular diseases (CVDs), neoplasms, chronic respiratory diseases (CRDs), and diabetes mellitus (DM), 2000–2021.

Incidence values represent rates per 100,000 population. Corresponding absolute case numbers for 2021 (e.g., CVDs = 66.8 million new cases) are reported in the results section.

https://doi.org/10.1371/journal.pone.0336036.g005

Cardiovascular diseases

The highest mortality rates (per 100,000 population) are seen in Eastern Europe and Central Asia (Ukraine 1,203·77; Bulgaria 1,051·62), while the lowest are in sub-Saharan Africa (Uganda 57·89; Mali 63·92). Western Europe and the Americas report moderate rates, such as Germany (400·95) and the U.S. (318·71), Fig 6A. Projected DALY rates from cardiovascular diseases in 2050 show wide global disparities from 1,653 per 100,000 in Uganda to 18,688 in Ukraine, an over 11 fold gap. Eastern Europe and Central Asia have the highest rates (Ukraine 18,688; Bulgaria 16,635), while sub-Saharan Africa reports the lowest (Uganda 1,653; Mali 1,815). High-income countries like the U·S· (5,247) and Germany (5,726) show moderate levels, Fig 6B. S6A in S1 File.

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Fig 6. 2050 Mortality and DALYS rates (per 100,000 population) projection for CVD’s (A and B), Neoplasms (C and D), CRDs (E and F), and DM (G and H), respectively.

https://doi.org/10.1371/journal.pone.0336036.g006

Discussion

The NCD landscape is marked by a striking divergence in disease patterns. Cardiovascular diseases remain the leading cause of NCD mortality, projected to account for 86.1% of deaths by 2050, driven by persistent metabolic risks like hypertension [11]. Neoplasms, fuelled by tobacco use and aging populations, show steady increases in incidence, with high-income regions like the Americas reporting rates as high as 4,877.70 per 100,000 in the U.S. [9]. Diabetes mellitus, however, is the wildcard, with incidence and DALYs surging globally due to the obesity epidemic, projected to disproportionately burden regions like the Pacific islands [12]. Chronic respiratory diseases, while relatively stable, continue to reflect environmental challenges, such as air pollution in South-East Asia [13]. Our estimates for mortality, incidence, and DALYs in 2021 are broadly consistent with those reported by Li J et al [14], reflecting the robustness of Global Burden of Disease (GBD)-based projections.

This heterogeneity demands a shift from a one-size-fits-all approach to precision-targeted prevention. For CVDs, sustained efforts in hypertension management and lipid control are critical, with high systolic blood pressure linked to 131.49 deaths per 100,000 globally [15]. Diabetes requires aggressive action on diet and physical activity, addressing the “global syndemic” of obesity and metabolic dysregulation [16]. Neoplasms call for enhanced screening and risk factor reduction [17], while CRDs necessitate clean air policies alongside smoking cessation. The WHO’s “best buys” (cost-effective interventions like tobacco taxation and salt reduction) provide a foundation, but their adaptation must reflect each NCD’s unique trajectory [18].

The NCD burden is deeply inequitable, shaped by socioeconomic and geographic fault lines. High Socio-Demographic Index (SDI) regions face elevated DM and neoplasm rates due to aging populations and lifestyle risks, while low SDI settings suffer higher CRD mortality from environmental exposures [19]. Middle SDI countries, in epidemiological transition, struggle with rising DM amid underfunded health systems. Regionally, Europe leads in CVD mortality (e.g., Bulgaria’s 1,114.15 per 100,000), the Americas in neoplasm incidence, and South-East Asia in CRD deaths [2].

Country-level disparities are stark: Qatar’s CVD mortality (35.19 per 100,000) contrasts sharply with Bulgaria’s, while Somalia’s neoplasm incidence (130.93) pales beside the U.S.’s. Gender further complicates the picture: males globally exhibit higher CVD and neoplasm mortality, yet females in Europe show an unexpected rise in CVD deaths, possibly tied to underrecognized risks like postmenopausal hypertension [20]. These patterns reflect systemic inequities in healthcare access, prevention, and social determinants such as urbanization, education, and income, underscoring the need for an equity-driven response.

NCD risk factors are not just drivers of disease but opportunities for policy innovation. Metabolic risks, particularly hypertension, dominate CVDs, while behavioural risks, tobacco, poor diet, and physical inactivity, fuel neoplasms and DM [21]. Air pollution, a growing concern, exacerbates CRDs, contributing to 7 million deaths annually [13]. These risks are actionable: salt reduction campaigns could avert millions of CVD deaths, tobacco taxes could curb neoplasms, and clean air initiatives could reduce CRD burdens [16].

The Pacific islands, facing a DM crisis, could pioneer community-based prevention, blending traditional diets with modern health education [12]. Europe’s female CVD anomaly highlights the need for sex-specific interventions, challenging the male-centric focus of past efforts [22]. Multisectoral action, spanning health, environment, and economic policy, is essential to turn risk factors into levers for equity.

The variation we observed in the burden of major NCDs can be explained by differences in demographics, exposures, and health system performance, each carrying clear policy implications. For instance, the very high cardiovascular mortality seen in Eastern Europe is closely linked to poor blood pressure control, high alcohol consumption, and weaker health systems [23]. In contrast, the sharp rise in diabetes, particularly in Pacific Island nations, reflects the global obesity epidemic and rapid shifts toward unhealthy diets [24]. The steady increase in cancer incidence is largely driven by aging populations and continued exposure to risk factors such as tobacco and alcohol [25], while the ongoing burden of chronic respiratory diseases in Asia highlights the role of air pollution and smoking [26]. These findings point to the need for context-specific prevention strategies: stronger hypertension and lipid management programs, sugar and salt reduction policies, tobacco and alcohol taxation, clean air initiatives, and more robust primary care.

Additionally, an important and novel aspect of our findings is the variation in NCD burden by sex. Overall, men experienced higher mortality and DALY rates for CVDs and neoplasms, consistent with previous evidence linking male behavioural risk patterns, such as higher tobacco and alcohol use, to excess burden [27]. However, our analysis also showed an unexpected rise in CVD mortality among women in Europe, which may be related to postmenopausal hypertension and under-recognition of female-specific cardiovascular risk factors [27]. In contrast, neoplasm incidence was consistently higher among women across SDI categories, reflecting both biological differences and greater utilization of screening services [25]. These disparities underscore the need for sex-specific prevention and management strategies, aligning with recent calls to integrate gender-sensitive approaches into NCD policy and research [28].

The 2050 projections are a clarion call: without action, NCDs will overwhelm health systems, deepened by post-COVID-19 vulnerabilities like delayed care and increased metabolic risks [14]. Scaling up primary care, integrating NCD services, and leveraging digital health are critical to bridge access gaps. The WHO’s 2023–2030 NCD Roadmap offers a blueprint, but its success depends on political commitment and investment in the most vulnerable, rural populations, low-income regions, and women facing unique risks.

The NCD crisis tests our commitment to global health equity. It exposes fractures between rich and poor, urban and rural, male and female and demands a future where health is a universal right. From Bulgaria’s CVD burden to Fiji’s DM challenge, the stakes are clear: without bold action, NCDs will derail SDG 3.4 and widen disparities. This is a scientific, economic, and moral imperative, calling for innovation, solidarity, and a relentless focus on those left behind.

The NCD landscape is marked by a striking divergence in disease patterns. Cardiovascular diseases remain the leading cause of NCD mortality, projected to account for 86.1% of deaths by 2050, driven by persistent metabolic risks like hypertension [11]. Neoplasms, fuelled by tobacco use and aging populations, show steady increases in incidence, with high-income regions like the Americas reporting rates as high as 4,877.70 per 100,000 in the U.S. [9]. Diabetes mellitus, however, is the wildcard, with incidence and DALYs surging globally due to the obesity epidemic, projected to disproportionately burden regions like the Pacific islands [12]. Chronic respiratory diseases, while relatively stable, continue to reflect environmental challenges, such as air pollution in South-East Asia [13].

This heterogeneity demands a shift from a one-size-fits-all approach to precision-targeted prevention. For CVDs, sustained efforts in hypertension management and lipid control are critical, with high systolic blood pressure linked to 131.49 deaths per 100,000 globally [15]. Diabetes requires aggressive action on diet and physical activity, addressing the “global syndemic” of obesity and metabolic dysregulation [16]. Neoplasms call for enhanced screening and risk factor reduction, while CRDs necessitate clean air policies alongside smoking cessation. The WHO’s “best buys” (cost-effective interventions like tobacco taxation and salt reduction) provide a foundation, but their adaptation must reflect each NCD’s unique trajectory [18].

The NCD burden is deeply inequitable, shaped by socioeconomic and geographic fault lines. High Socio-Demographic Index (SDI) regions face elevated DM and neoplasm rates due to aging populations and lifestyle risks, while low SDI settings suffer higher CRD mortality from environmental exposures [19]. Middle SDI countries, in epidemiological transition, struggle with rising DM amid underfunded health systems. Regionally, Europe leads in CVD mortality (e.g., Bulgaria’s 1,114.15 per 100,000), the Americas in neoplasm incidence, and South-East Asia in CRD deaths [2].

Country-level disparities are stark: Qatar’s CVD mortality (35.19 per 100,000) contrasts sharply with Bulgaria’s, while Somalia’s neoplasm incidence (130.93) pales beside the U.S.’s. Gender further complicates the picture: males globally exhibit higher CVD and neoplasm mortality, yet females in Europe show an unexpected rise in CVD deaths, possibly tied to underrecognized risks like postmenopausal hypertension [20]. These patterns reflect systemic inequities in healthcare access, prevention, and social determinants such as urbanization, education, and income, underscoring the need for an equity-driven response.

NCD risk factors are not just drivers of disease but opportunities for policy innovation. Metabolic risks, particularly hypertension, dominate CVDs, while behavioural risks, tobacco, poor diet, and physical inactivity, fuel neoplasms and DM [21]. Air pollution, a growing concern, exacerbates CRDs, contributing to 7 million deaths annually [13]. These risks are actionable: salt reduction campaigns could avert millions of CVD deaths, tobacco taxes could curb neoplasms, and clean air initiatives could reduce CRD burdens [16].

A key consideration in interpreting our findings is the nature of the GBD data. Estimates are generated from multiple sources, including civil registration systems, disease registries, surveys, hospital records, and verbal autopsies, and are harmonized through statistical modelling. While this allows for global comparability, it also introduces uncertainty, particularly in countries with limited data. Misclassification of causes of death, uneven data quality, and reliance on modelling make independent validation difficult.

Our data ended in 2021, so the full impact of the COVID-19 pandemic is not captured. Projections to 2050 are based on current trends and may not reflect future advances in prevention, treatment, or policy. The use of individual risk factors such as hypertension and tobacco may oversimplify the overlap of multiple risks, and subgroup disparities beyond sex (such as age or geography) were not examined. Finally, average annual percentage change (AAPC) was calculated using aggregated counts, which may reflect population growth and aging rather than true shifts in disease risk, though age-standardized rates were included to mitigate this.

Conclusion

The rising global burden of NCDs, especially cardiovascular diseases and diabetes, calls for urgent, equity-focused prevention and stronger health systems. Regional, gender, and socioeconomic disparities highlight the need to tackle systemic inequities to meet Sustainable Development Goal 3.4. Despite data and projection challenges, this study offers a vital foundation for advancing WHO’s NCD Roadmap and fostering a healthier future by 2050.

Supporting information