Global Trends in Ischemic Heart Disease Mortality from 1990 to 2021 and 2036 Projections: Insights from GBD 2021 Data

Data sources and definitions

The GBD study, led by the Institute for Health Metrics and Evaluation (IHME) at the University of Washington, Seattle, is the most comprehensive global observational epidemiological study to date. The GBD 2021 employs a consistent methodology to produce standardized health metrics for 204 countries and territories from 1990 to 2021. It examines descriptive epidemiological data on 371 diseases and injuries and 88 risk factors, enabling comparisons both within and between countries (10, 11). Metric and measure definitions can be found in Table S1.

For this study, we focused on IHD, which was defined based on the following International Classification of Diseases (ICD) codes: 410–414 (ICD-9) and I20–I25 (ICD-10). Mortality estimates were derived using vital registration data coded to the ICD system. We obtained cause-specific deaths attributed to IHD from the GBD 2021 database. The epidemiological data of interest includes the absolute death number and age-standardized mortality rates (ASMR) of IHD from 1990 to 2021, categorized by gender, age, region, and country. All estimates from GBD are presented with 95% uncertainty intervals (UIs).

In this study, we utilized two complementary measures—the estimated annual percentage change (EAPC) and the net drift—to describe the trends in ASMR from 1990 to 2021. The EAPC quantifies the average rate of change in ASMR over time by calculating the percentage change using the slope from a logarithmic linear regression model. The net drift value, derived from APC analysis, represents the overall annual percentage change in age-standardized rates over time, adjusted for both period and cohort effects (12).

The analysis was stratified at multiple levels: global, SDI quintiles, GBD regions, and national. The SDI is a composite measure that reflects a country’s development level by combining data on key indicators such as per capita income, education levels, and fertility rates (9, 13). Based on 2021 SDI classification criteria and their SDI values (Tables S2, S3), countries were categorized into five SDI regions: low, low-middle, middle, high-middle, and high (9). Additionally, the 204 countries and territories were grouped into 21 GBD regions according to their geographical locations. This multi-layered analysis provided insights into IHD mortality patterns across various geographical and socioeconomic contexts, allowing for the identification of both broad global trends and specific regional variations in IHD mortality.

We also examined the burden of IHD deaths across different age groups. We divided the death counts into five age categories: 15–29 years, 30–44 years, 45–59 years, 60–74 years, and 75 years and above. We calculated the proportions of deaths for each group to analyze the age distribution of IHD mortality.

Analytical methods and predictive modeling

We employed several analytical methods to examine temporal trends, decompose factors contributing to IHD mortality changes, analyze associated risks, and predict future trends. APC analysis was used to investigate the effects of age, period, and birth cohort on IHD mortality trends from 1992 to 2021 (12, 14). To explore the relationship between socioeconomic development and IHD mortality, we conducted a frontier analysis, identifying the lowest potentially achievable IHD mortality rates at various levels of development (15). A three-factor decomposition method was applied to quantify the contributions of demographic and epidemiological factors to changes in IHD mortality (16, 17). Additionally, we performed a risk factor analysis to examine the contributions of the top eight global risk factors for IHD mortality across different regions and SDI levels in 1990 and 2021 (9). Finally, we utilized a BAPC model to project IHD death cases and mortality rates from 2022 to 2036, accounting for age, period, and cohort effects (18, 19). Detailed methodologies for these analyses are provided in the Supplementary Methods. The GBD 2021 complies with the Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER) statement (20).

Analysis software

Statistical analyses were performed using R version 4.2.3. The BAPC model was implemented using the R packages BAPC (version 0.0.36) and INLA (version 22.05.07).

Global and regional trends

Our analysis revealed significant changes in the global burden of IHD from 1990 to 2021. The total number of IHD deaths globally increased substantially over the past three decades, rising from 5.37 million (95% UI: 5.08–5.56) in 1990 to 8.99 million (95% UI: 8.26–9.53) in 2021, representing a 67.5% increase. However, the global ASMR for IHD showed a declining trend during this period. The EAPC in ASMR was –1.301% per year, with a net drift of –1.1% per year. The trends in IHD mortality varied considerably across different SDI regions, with high SDI regions experiencing the largest decline in ASMR (EAPC: –3.428%, net drift: –2.77%) (Figure 1 A, 1B, Table 1, and Table S4).

Regionally, East Asia, South Asia, and Eastern Europe were the top three regions for IHD deaths in 2021, collectively accounting for 54.6% of global IHD deaths. Central Asia, Eastern Europe, North Africa and Middle East had the highest ASMR, while high-income Asia Pacific, Western Europe, and Australasia had the lowest. From 1990 to 2021, Australasia (EAPC: –4.524%, net drift: –4.55%), Western Europe (EAPC: –3.894%, net drift: –4.12%), and high-income Asia Pacific (EAPC: –3.041%, net drift: –2.74%) showed the most significant decreases in ASMR. However, some regions experienced minimal changes or even increases in ASMR, such as South Asia (EAPC: 0.436%, net drift: –0.03%) and East Asia (EAPC: 0.896%, net drift: –0.02%) (Figure 1C, Table 1, and Table S4).

Figure 1

National trends

Figure 2 and Table S5 reveal significant global disparities and dynamic patterns of change in ASMR for IHD across countries from 1990 to 2021. In 2021, San Marino, Japan, South Korea, and France reported the lowest ASMR. EAPC and net drift data demonstrate significant changes and consistent improvement trends in these developed countries: San Marino (EAPC: –3.28%, net drift: –3.18%), Japan (EAPC: –2.95%, net drift: –2.25%), South Korea (EAPC: –3.03%, net drift: –4.15%), and France (EAPC: –3.48%, net drift: –3.44%). These countries are depicted in deep blue or dark blue in Figures 2C and 2D, indicating substantial downward trends.

Figure 2

In contrast, some countries in Eastern Europe, Central Asia, the Middle East, and North Africa generally show higher ASMR, such as Ukraine, Belarus, Egypt, and Syria. However, most of these countries demonstrate positive trends, as seen in Ukraine (EAPC: –0.30%, net drift: –0.96%) and Syria (EAPC: –0.47%, net drift: –1.34%). Notably, Sub-Saharan African countries face severe challenges, with many showing rising IHD mortality rates. Kenya (EAPC: 1.71%, net drift: 1.39%), Lesotho (EAPC: 2.84%, net drift: 3.49%), and Zimbabwe (EAPC: 1.75%, net drift: 2.24%) all demonstrate significant upward trends. These countries are colored orange in Figures 2C and 2D, reflecting concerning trends.

Age and sex disparities

The age distribution of IHD deaths exhibited a clear shift towards older age groups from 1990 to 2021 (Figure S1 and Table S6). Globally, the proportion of IHD deaths in the 75+ age group rose from 47.9% in 1990 to 52.0% in 2021. This shift was evident in both high SDI regions (61.4% to 68.5%) and low SDI regions (25.7% to 32.9%). Australasia, high-income Asia Pacific, and Western Europe had the highest proportions of IHD deaths in the 75+ age group in 2021 (75.5%, 76.5%, and 77.0% respectively). In contrast, Oceania, Central Sub-Saharan Africa, and Eastern Sub-Saharan Africa had much lower proportions in this age group (22.6%, 28.8%, and 32.4% respectively), with a higher proportion of deaths in younger age groups. Although ASMR decreased for both sexes, the decline was more pronounced in females. The gender disparity was most notable in high SDI regions, where the ratio of male to female ASMR increased from 1.79 in 1990 to 1.97 in 2021 (Figure S2 and Table S7).

Age-period-cohort effects

Figure 3 and Tables S8–S11 present estimates for age, period, cohort effects, and local drift on IHD mortality by SDI quintile. Local drift analysis revealed an overall downward trend in mortality rates across all age groups globally, with significant variations between SDI regions. High SDI regions showed the most pronounced changes, with substantial decreases across all age groups, particularly for those aged 60 and above. The most significant annual percentage decrease of 4.10% was observed in the 72.5 years age group. In contrast, low SDI and low-middle SDI regions exhibit an upward trend among individuals aged 75 and above, with the increase being more pronounced among males.

Figure 3

Age effects analysis demonstrated that IHD mortality rates increased exponentially with age across all SDI regions. Low SDI regions showed the steepest increase, particularly for females aged 60 and above. In contrast, high SDI regions exhibited the lowest IHD mortality rates across all age groups, with rapid increases primarily concentrated after age 75. The age curves showed that the inflection point occurred at 62.5 years in low SDI regions, while it was observed at 77.5 years in high SDI regions.

Period effects analysis indicated an overall declining trend globally, but with significant variations across different SDI regions. High and high-middle SDI regions demonstrated the most pronounced changes, with substantial decreases in IHD mortality risk. In high SDI regions, the relative risk decreased from 1.38 in 1994 to 0.70 in 2019, compared to the reference year 2004. In contrast, middle-low and low SDI regions showed more modest changes. Notably, these regions experienced an upward trend among males during the 2009 and 2014 periods.

Cohort effects analysis also revealed an overall declining trend globally. High and high-middle SDI regions exhibited the most significant downward trends. In high SDI regions, the relative risk decreased dramatically from 5.31 for the 1902 birth cohort to 0.30 for the 2002 cohort, compared to the reference 1952 birth cohort. In comparison, middle, low-middle, and low SDI regions showed more modest changes. Gender disparities were particularly evident in these regions: females showed a slow downward trend, while males exhibited an upward trend. In low SDI regions, the relative risk for female cohorts decreased from 1.17 for the 1902 cohort to 0.50 for the 2002 cohort, while for males, it increased from 0.70 to 0.82 over the same period.

Frontier analysis

Figure 4 and Table S12 present the results of the frontier analysis, revealing that many countries demonstrated a general decrease in ASMR from 1990 to 2021. However, some countries, particularly those with lower SDI values, exhibited an increase in ASMR. As SDI values increased, ASMR tended to converge toward lower levels. However, significant variations were observed even among countries with similar SDI levels. The countries with the highest effective differences included Nauru, Ukraine, the Syrian Arab Republic, Egypt, Turkmenistan, Belarus, Uzbekistan, Vanuatu, Azerbaijan, and Afghanistan. These countries exhibit the greatest potential for reducing IHD mortality given their current levels of development. Notably, some higher SDI countries, such as Lithuania, Saudi Arabia, Slovakia, the United Arab Emirates, and Latvia, also displayed substantial distances from the frontier. Conversely, low SDI regions such as Somalia, Niger, Mozambique, Ethiopia, and Rwanda were found to be closest to the frontier, showcasing relatively good performance in IHD mortality control despite socioeconomic constraints.

Figure 4

Decomposition and risk factor analysis

Decomposition analysis provides crucial insights into the driving factors behind the changes in IHD mortality across different SDI regions and GBD regions (Figure 5 A and Table S13). Globally, population growth emerged as the most significant factor contributing to the increase in IHD mortality. High SDI regions demonstrated the most notable epidemiological improvements, with advancements in prevention, treatment, and healthcare systems outweighing the effects of population aging and growth, resulting in a net decrease in deaths. In contrast, middle SDI regions experienced the largest increase in death numbers, primarily due to population aging coupled with less substantial improvements in epidemiological factors.

Regionally, South Asia and East Asia emerged as the two areas with the largest increases in IHD deaths. South Asia’s growth was primarily driven by population increase, while East Asia’s was mainly attributed to population aging. These two regions exhibited a unique pattern where epidemiological changes did not reduce deaths but instead contributed to an increase in IHD mortality. In contrast, high-income North America and Western Europe experienced a decline in IHD deaths, primarily due to substantial epidemiological improvements that surpassed the effects of aging and population growth.

Figure 5

Figure 5B and Table S14 demonstrate that in 2021, high systolic blood pressure was the primary risk factor for IHD mortality both globally and across all SDI regions. From 1990 to 2021, the contribution of high systolic blood pressure to IHD mortality increased in all SDI regions except for the high SDI region. Dietary risks (20.4% to 19.0%) and high low-density lipoprotein (LDL) cholesterol (13.7% to 13.1%) remained the second and third leading factors contributing to IHD mortality globally. However, in low, low-middle, and middle SDI regions, although the contribution of air pollution decreased, it remained the third highest risk factor in these areas. Notably, the contribution of high fasting plasma glucose and high body-mass index increased across all SDI regions. The high SDI region showed the most significant growth, with high fasting plasma glucose increasing from 5.1% to 8.5%, and high body-mass index from 4.9% to 7.2%.

Regionally, except for high-income North America and high-income Asia Pacific, the proportion of high systolic blood pressure risk increased in other GBD regions. Additionally, high fasting plasma glucose and high body-mass index increased in all GBD regions, with high-income North America showing the most significant increase. Regarding air pollution, high-income North America’s air pollution decreased to the lowest level of 2.3%, while in regions like Asia and Africa, air pollution still accounted for over 10% of the risk, ranking third among risk factors. In Eastern Sub-Saharan Africa and Western Sub-Saharan Africa, it exceeded 20%.

Projection from 2022 to 2036

The global ASMR of IHD is projected to decrease by 8.5%, from 146.7 per 100,000 in 2021 to 134.3 per 100,000 by 2036, despite a gradual increase in the number of deaths, as shown in Figure 6 and Tables S15-S16. However, trends vary significantly across regions, Western Europe and Southern Latin America are projected to experience continued declines in both death numbers and ASMR. High-income North America, High-income Asia Pacific, North Africa and Middle East, Central Europe, Australasia, and most Asian regions are also expected to see decreases in ASMR, but the number of deaths in these regions will still increase, primarily due to deaths in the 75+ age group. In contrast, over the next 15 years, most regions in Africa are projected to experience increasing trends in both death numbers and ASMR. Southern Sub-Saharan Africa is projected to see a notable increase in ASMR, increasing from 113.3 to 160.0 per 100,000, a 41.2% increase. Notably, Eastern Europe is expected to see the most dramatic increase, with ASMR rising from 340.9 to 1,406.0 per 100,000, a 312.4% increase.

Figure 6