Global, regional, and national burden of nonrheumatic calcific aortic valve disease based on GBD study 2021

Abstract

Calcific aortic valve disease (CAVD) is among the most prevalent forms of nonrheumatic valvular heart disease, imposing a substantial global health burden. This study examined CAVD trends to provide insights for the development of effective prevention strategies. Using Global Burden of Disease Study 2021 (GBD 2021) data, we analyzed the age-standardized prevalence, incidence, mortality, and disability-adjusted life years (DALYs) of CAVD, along with trends, age- and sex-specific patterns, contributing factors, and projections through 2036. From 1992 to 2021, the number of global CAVD cases rose from 4.97 to 13.32 million and the age-standardized prevalence rate (ASPR) increased from 130.82 to 158.35 per 100,000 people. While both the ASPR and age-standardized incidence rate (ASIR) steadily increased, the age-standardized mortality rate (ASMR) and age-standardized DALYs rate (ASDR) declined. The burden of CAVD progressively worsened with age. Males generally had higher prevalence and incidence rates compared with females. However, in individuals > 85 years, females exhibited significantly higher mortality and DALY burdens. The CAVD burden was positively correlated with the sociodemographic index (SDI); the correlation was stronger in High SDI regions compared with Low SDI regions, and this gap widened over the last three decades. Population growth and aging were the primary contributors to the increasing burden, while epidemiological transitions helped reduce the ASMR and ASDR in regions with a high SDI. By 2036, the ASPR, ASIR, ASMR, and ASDR of CAVD are projected to decline in the High and High-middle SDI regions. In contrast, the ASPR and ASIR are expected to continue to increase, whereas the ASMR and ASDR are anticipated to remain relatively stable in other SDI regions. Although significant progress has been made globally in the prevention and treatment of CAVD, the complex demographic and regional disparities underscore the need for targeted prevention and treatment strategies to further alleviate the burden and enhance patient outcomes.

Supplementary Information

The online version contains supplementary material available at 10.1038/s41598-025-14522-x.

Introduction

Nonrheumatic valvular heart disease has become a significant global cardiovascular health challenge, profoundly affecting physical function, quality of life, and life expectancy¹. Calcific aortic valve disease (CAVD), the most common valvular heart disease in developed countries, is projected to more than double in prevalence in the United States and Europe by 2050². CAVD is characterized by the progressive thickening, fibrosis, and calcification of the aortic valve leaflets, often leading to aortic valve stenosis (AVS)³. Severe AVS, associated with symptoms like angina, exertional dyspnea, and syncope, carries a high mortality risk without effective intervention⁴. Furthermore, even mild or moderate AVS significantly increases the risk of cardiovascular events, including death, independent of left ventricular dysfunction or low-flow status^5,6. A large registry study underscores this risk, reporting a 5-year all-cause mortality rate of 56% for moderate AVS–approaching the 67% rate observed in severe AVS⁷. Consequently, CAVD imposes a substantial healthcare burden and represents a major public health threat.

In recent years, improvements in cardiovascular imaging, surgical techniques, postoperative care, and the expansion of transcatheter interventions have substantially enhanced the outcomes of patients with CAVD⁸. However, these advances are not available worldwide, with stark disparities between high- and low-income countries⁹. Even in high sociodemographic index (SDI) regions, undertreatment and late referral remain prevalent. Despite guideline-recommended interventions, patients still fail to receive timely treatment⁸. The aging of the global population is expected to drive a further increase in CAVD cases, posing significant challenges to public health and healthcare systems. Therefore, understanding the current epidemiological trends, including sex differences, geographic patterns, and temporal changes, is critical for guiding prevention efforts and optimizing resource allocation.

The Global Burden of Disease (GBD) database is essential for studying CAVD epidemiology. However, previous analyses relied primarily on pre-2020 GBD versions, limiting their data to 2019 or earlier^10–12. Crucially, GBD 2021 introduces substantial methodological revisions, leading to a complete re-estimation of key CAVD indicators (prevalence, incidence, mortality, DALYs) even for prior years. These estimates differ significantly from GBD 2019, with CAVD being particularly impacted. Therefore, GBD 2021 represents a major methodological advancement, not merely a data extension. Consequently, reassessing CAVD’s global burden using this updated data is essential to accurately reflect current epidemiological trends and inform public health policy. While recent GBD studies reported aggregated valvular heart disease statistics^13,14, methodological constraints preclude comprehensive epidemiological profiles of CAVD. Furthermore, prior CAVD research lacked depth beyond descriptive analysis.

Our study addresses these gaps by utilizing GBD 2021 data to comprehensively examine the CAVD burden across age, sex, geography, and time. We specifically investigate its relationship with the SDI. Employing advanced methods (decomposition analysis, frontier analysis, health inequality metrics, and BAPC modeling) we identify key drivers of burden trends, reveal global health inequalities, and project future burdens. This represents the first projection of CAVD’s future burden. Collectively, these analyses provide crucial insights for developing targeted strategies against this growing public health challenge.

Materials and methods

Data sources and disease definition

This study used publicly available data from the GBD 2021 dataset (healthdata.org/gbd/2021), which is accessible via the Global Health Data Exchange query tool (https://vizhub.healthdata.org/gbd-results/). The GBD 2021 study provides a comprehensive evaluation of the health impacts of 371 diseases, injuries, and impairments along with 88 risk factors across 204 countries and regions. The data collection methodology of the 2021 GBD dataset is described in the supplementary materials (Supplementary methods 1.1)¹⁵.

In the GBD 2021, CAVD was defined as the clinical diagnosis of stenosis or regurgitation due to progressive calcification of the aortic valve. The definition excludes congenital, rheumatic, or infectious causes but includes stenosis of a bicuspid aortic valve. Cases were identified through echocardiography and met the inclusion criterion of at least moderate severity. Methodological updates specific to CAVD data in GBD 2021 (and their differences from GBD 2019) are documented in the supplementary materials (Supplementary methods 1.2).

For this study, we extracted data spanning 30 years (1992–2021), encompassing information on the CAVD prevalence, incidence, mortality, and DALYs disaggregated by age, sex, and geographic region. The dataset covers 21 GBD-defined regions and includes data from 204 countries and territories, providing a robust foundation for analyzing the temporal trends and geographical disparities in the global burden.

Burden description

We conducted a detailed assessment of the global burden of CAVD until 2021, focusing on its prevalence, incidence, mortality, and DALYs. DALYs, which integrate the years lived with disability (YLDs) and years of life lost (YLLs), provide a comprehensive measure of the disease burden by capturing both premature mortality and reduced quality of life.

To analyze trends in the CAVD burden, we utilized the age-standardized rate (ASR) and estimated annual percentage change (EAPC). Additionally, we examined the distribution of disease burden across various age groups and sexes to identify demographic patterns.

The SDI was used to investigate the impact of socioeconomic development on health outcomes. The SDI is a composite measure that combines the per capita income, total fertility rate, and average educational attainment, with values ranging from 0 to 1¹⁵. Higher SDI values indicate greater socioeconomic development. Based on the SDI quintiles, the 204 countries and regions included in this study were categorized into the following five groups:

• High SDI: 0.8103–1.0000

• High-Middle SDI: 0.7120–0.8103

• Middle SDI: 0.6188–0.7120

• Low-Middle SDI: 0.4658–0.6188

• Low SDI: 0–0.4658

This classification facilitated the systematic analysis of the relationship between socioeconomic development and CAVD burden, enabling a more nuanced understanding of how health outcomes are shaped by varying levels of social and economic progress (Table S1).

Statistical analysis

The ASR was computed per 100,000 individuals utilizing the subsequent formula:

(a_i: age-specific rate in i^th the age group, w: number of people in the corresponding i^th age group among the standard population, and A: number of age groups).

To analyze trends in the ASR of the CAVD prevalence, incidence, mortality, and DALYs, we employed the EAPC method. This method uses a regression model expressed as follows¹⁶:

The natural logarithm of the ASR is represented by ln(ASR) in this equation, where X denotes the calendar year under consideration. The y-intercept is denoted by α, while β indicates the slope, which represents the trend over time. Any errors in the model were accounted for using e. The EAPC is expressed as 100 × [exp(β)–1], indicating the yearly percentage change. Trends were evaluated based on the EAPC and its 95% confidence interval (CI). An increasing trend was observed when both the EAPC and lower CI limit were positive, whereas a decreasing trend was observed when both the EAPC and upper CI limit were negative. Trends were considered stable if neither condition was satisfied.

This study also utilized the slope index of inequality (SII) and concentration index, as defined by the World Health Organization (WHO), to measure absolute and relative inequalities in the disease burden¹⁷. Spearman’s correlation was used to assess the association between the SDI and ASR of CAVD.

Frontier analysis, a key quantitative tool in GBD studies, employs data envelopment analysis (DEA) and locally estimated scatterplot smoothing (LOESS) to assess and optimize health system performance. This method is particularly valuable for examining the relationship between disease burden and socio-demographic development. By constructing a “frontier” or best-practice boundary, frontier analysis identifies the minimum achievable age-standardized disease burden at different SDI levels¹⁸.

We also applied decomposition analysis to evaluate the contributions of age structure, population growth, and epidemiological changes to the burden of CAVD. This approach allowed us to calculate the net change in all cases based on the combined effects of the three factors¹⁹.

Finally, to predict future trends in the CAVD burden, we employed the Bayesian age-period-cohort (BAPC) model, incorporating integrated nested Laplace approximations. Previous studies have shown that the BAPC model provides greater accuracy and reliability compared to other predictive methods^20,21. All analyses and visualizations were conducted using R statistical software (version 4.4.1).

Results

Global burden and temporal trends of CAVD from 1992 to 2021

Over the past 30 years, the global prevalence of CAVD has increased significantly by 167.74%, rising from 4,975,351 cases (95% CI 4,125,593–5,863,048) in 1992 to 13,320,896 cases (95% CI 11,422,539–15,249,411) in 2021. The age-standardized prevalence rate (ASPR) also showed an upward trend, rising from 130.82 (95% CI 107.45–153.87) per 100,000 persons in 1992 to 158.35 (95% CI 135.92–181.00) per 100,000 persons in 2021, with an EAPC of 0.89 (95% CI 0.76–1.01) (Table 1, Fig. 1). Similarly, the global incidence of CAVD increased by 150.68%, from 416,615 (95% CI 346,600–485,938) in 1992 to 1,044,370 cases (95% CI 906,615–1,179,672) in 2021. Correspondingly, the age-standardized incidence rate (ASIR) increased from 10.17 (95% CI 8.49–11.85) to 12.03 (95% CI 10.43–13.56) per 100,000 persons, with an EAPC of 0.82 (95% CI 0.71–0.93) (Table 1, Fig. 1). However, despite these increases, the number of global deaths attributed to CAVD in 2021 was 142,205 (95% CI 120,675–155,575), with a declining EAPC of −0.07 (95% CI −0.19–0.05). The age-standardized mortality rate (ASMR) dropped from 1.98 (95% CI 1.78–2.13) per 100,000 persons in 1992 to 1.83 (95% CI 1.54–2.00) per 100,000 persons in 2021 (Table 1, Fig. 1). In terms of DALYs, a total of 2,243,000 DALYs (95% CI 2,004,168–2,459,248) were attributed to CAVD globally in 2021, reflecting a 1.88-fold increase from 1,191,644 DALYs (95% CI 1,104,009–1,292,157) in 1992. Despite this increase, the age-standardized DALYs rate (ASDR) decreased from 32.49 (95% CI 29.8–35.14) per 100,000 persons in 1992 to 27.74 (95% CI 24.67–30.48) per 100,000 persons in 2021, with an EAPC of −0.38 (95% CI −0.49 to −0.26) (Table 1, Fig. 1).

Table 1.

Global and regional trends in calcific aortic valve disease burden: prevalence, incidence, mortality, and disability-adjusted life years (1992–2021).

Location	1992		2021		EAPC (95%CI)
	Number	ASR	Number	ASR
Prevalence	Number	ASPR	Number	ASPR	EAPC
Global	4,975,351 (4,125,593, 5,863,048)	130.82 (107.45, 153.87)	13,320,896 (11,422,539, 15,249,411)	158.35 (135.92, 181.00)	0.89 (0.76, 1.01)
Male	2,641,904 (2,200,549, 3,124,444)	156.40 (129.42, 183.62)	7,302,229 (6,260,247, 8,340,870)	193.24 (166.56, 220.38)	1.00 (0.88, 1.12)
Female	2,333,447 (1,905,552, 2,767,113)	109.59 (89.59, 129.27)	6,018,667 (5,139,856, 6,897,469)	128.88 (110.13, 147.63)	0.75 (0.63, 0.87)
High SDI	3,182,712 (2,640,825, 3,738,916)	270.48 (225.67, 316.87)	7,860,601 (6,819,445, 8,892,889)	349.64 (303.58, 395.77)	1.12 (0.99, 1.25)
High-middle SDI	1,250,621 (1,027,049, 1,494,068)	125.96 (103.51, 150.64)	3,440,879 (2,962,649, 3,931,537)	172.89 (149.52, 197.05)	1.35 (1.22, 1.49)
Middle SDI	350,291 (283,047, 425,960)	34.86 (27.83, 42.08)	1,417,739 (1,134,289, 1,688,924)	54.49 (43.43, 64.98)	1.76 (1.67, 1.84)
Low-middle SDI	152,050 (122,292, 185,391)	25.82 (20.84, 31.35)	496,397 (404,012, 589,829)	36.62 (29.46, 43.57)	1.28 (1.24, 1.32)
Low SDI	31,983 (25,591, 39,792)	14.18 (11.29, 17.32)	85,816 (68,868, 104,074)	17.64 (14.26, 21.19)	0.79 (0.74, 0.84)
Andean Latin America	16,100 (13,444, 19,403)	76.65 (63.88, 92.16)	77,588 (66,210, 89,728)	133.19 (113.31, 154.29)	1.92 (1.87, 1.96)
Australasia	55,746 (46,623, 64,749)	220.45 (185.32, 255.90)	192,488 (165,456, 223,130)	332.99 (286.39, 384.01)	1.62 (1.54, 1.71)
Caribbean	25,483 (21,476, 29,967)	94.61 (79.28, 111.53)	72,781 (62,508, 84,939)	134.62 (115.73, 157.17)	1.41 (1.28, 1.55)
Central Asia	38,926 (31,006, 47,786)	83.75 (66.96, 102.83)	113,426 (93,422, 135,264)	146.37 (119.97, 173.94)	2.28 (2.10, 2.46)
Central Europe	314,922 (260,459, 375,477)	206.08 (170.57, 245.67)	866,860 (755,597, 995,397)	379.57 (330.44, 437.56)	2.52 (2.15, 2.90)
Central Latin America	90,607 (74,254, 108,753)	107.19 (87.00, 129.68)	395,445 (324,616, 470,756)	160.32 (131.28, 191.12)	1.66 (1.45, 1.87)
Central Sub-Saharan Africa	2820 (2236, 3508)	12.49 (9.96, 15.45)	7684 (6109, 9324)	14.67 (11.85, 17.89)	0.57 (0.43, 0.72)
East Asia	151,721 (115,098, 192,579)	18.17 (13.82, 22.74)	719,161 (554,740, 884,832)	33.15 (25.50, 40.55)	2.36 (2.25, 2.46)
Eastern Europe	400,350 (318,821, 492,970)	141.22 (113.10, 173.27)	949,895 (761,766, 1,153,178)	264.72 (213.79, 319.46)	2.57 (2.40, 2.74)
Eastern Sub-Saharan Africa	8888 (7085, 11,040)	11.73 (9.29, 14.38)	22,929 (18,357, 27,771)	13.96 (11.03, 17.01)	0.56 (0.49, 0.64)
High-income Asia Pacific	521,638 (415,514, 639,103)	246.68 (195.85, 299.96)	1,447,553 (1,198,037, 1,699,765)	284.22 (238.29, 333.61)	0.68 (0.56, 0.79)
High-income North America	1,202,216 (951,186, 1,467,434)	316.61 (250.16, 382.51)	2,772,454 (2,360,163, 3,202,756)	403.07 (344.88, 462.72)	1.01 (0.85, 1.17)
North Africa and Middle East	68,549 (56,135, 82,038)	38.60 (31.74, 45.90)	246,280 (205,247, 291,455)	55.12 (46.06, 64.89)	1.29 (1.26, 1.33)
Oceania	556 (434, 694)	21.53 (17.01, 26.18)	1671 (1322, 2032)	27.09 (21.54, 32.45)	0.58 (0.50, 0.65)
South Asia	102,352 (80,194, 128,286)	18.35 (14.38, 23.04)	349,853 (276,806, 429,247)	24.88 (19.64, 30.42)	1.12 (1.07, 1.17)
Southeast Asia	37,098 (28,465, 46,057)	15.50 (11.96, 18.99)	150,953 (115,914, 183,274)	25.31 (19.72, 30.59)	1.76 (1.72, 1.81)
Southern Latin America	79,075 (67,395, 91,442)	166.78 (142.10, 192.67)	234,828 (202,977, 273,602)	262.02 (226.21, 304.68)	1.39 (1.14, 1.64)
Southern Sub-Saharan Africa	5480 (4374, 6736)	18.97 (15.08, 23.21)	13,442 (10,821, 16,420)	23.77 (19.01, 28.8)	0.72 (0.66, 0.78)
Tropical Latin America	102,733 (84,103, 124,857)	108.85 (88.50, 133.47)	355,804 (284,981, 430,930)	139.74 (111.90, 169.21)	1.02 (0.92, 1.12)
Western Europe	1,740,956 (1,503,959, 2,015,719)	280.66 (243.36, 324.70)	4,306,128 (3,789,649, 4,809,887)	425.32 (375.41, 477.97)	1.67 (1.42, 1.93)
Western Sub-Saharan Africa	9137 (7342, 11,240)	9.35 (7.52, 11.39)	23,674 (19,212, 28,589)	11.08 (8.99, 13.41)	0.52 (0.50, 0.55)

Incidence	Number	ASIR	Number	ASIR	EAPC
Global	416,615 (346,600, 485,938)	10.17 (8.49, 11.85)	1,044,370 (906,615, 1,179,672)	12.03 (10.43, 13.56)	0.82 (0.71, 0.93)
Male	221,717 (185,372, 259,260)	11.47 (9.59, 13.30)	570,551 (494,209, 648,141)	13.97 (12.21, 15.85)	0.96 (0.85, 1.07)
Female	194,898 (161,001, 227,598)	8.83 (7.33, 10.33)	473,820 (406,717, 534,180)	10.19 (8.74, 11.47)	0.70 (0.60, 0.80)
High SDI	266,682 (222,137, 310,283)	23.12 (19.55, 26.76)	625,946 (542,702, 701,340)	29.98 (26.09, 33.53)	1.13 (1.02, 1.24)
High-middle SDI	98,796 (81,055, 117,711)	9.28 (7.67, 11.02)	244,578 (208,641, 280,897)	12.13 (10.38, 13.88)	1.18 (1.04, 1.31)
Middle SDI	31,518 (25,702, 37,767)	2.78 (2.27, 3.29)	116,303 (94,896, 139,288)	4.21 (3.43, 5.01)	1.60 (1.54, 1.66)
Low-middle SDI	15,225 (12,580, 18,136)	2.36 (1.96, 2.77)	46,364 (38,524, 54,557)	3.19 (2.68, 3.73)	1.11 (1.07, 1.15)
Low SDI	3817 (3204, 4486)	1.61 (1.37, 1.85)	9847 (8381, 11,323)	1.89 (1.61, 2.16)	0.59 (0.54, 0.63)
Andean Latin America	1295 (1093, 1526)	5.61 (4.65, 6.64)	5711 (4857, 6602)	9.43 (8.03, 10.96)	1.81 (1.77, 1.85)
Australasia	5482 (4615, 6321)	21.53 (18.35, 24.77)	17,028 (14,712, 19,550)	30.99 (26.61, 35.51)	1.47 (1.39, 1.55)
Caribbean	1962 (1646, 2278)	7.07 (5.91, 8.22)	5238 (4478, 6013)	9.70 (8.30, 11.13)	1.27 (1.15, 1.40)
Central Asia	2964 (2381, 3656)	5.89 (4.71, 7.23)	8951 (7346, 10,729)	10.06 (8.23, 11.76)	2.20 (2.03, 2.37)
Central Europe	22,708 (18,763, 27,446)	14.38 (11.93, 17.31)	56,157 (48,783, 64,843)	26.87 (23.56, 30.71)	2.60 (2.21, 2.99)
Central Latin America	7499 (6159, 9005)	8.00 (6.55, 9.64)	30,192 (24,805, 35,812)	11.71 (9.64, 13.86)	1.58 (1.38, 1.78)
Central Sub-Saharan Africa	388 (332, 447)	1.68 (1.47, 1.91)	1031 (886, 1173)	1.88 (1.66, 2.12)	0.41 (0.31, 0.51)
East Asia	13,886 (10,775, 17,127)	1.49 (1.15, 1.81)	57,704 (44,901, 70,370)	2.57 (2.00, 3.12)	2.07 (2.00, 2.14)
Eastern Europe	31,112 (24,048, 38,764)	10.61 (8.3, 13.05)	67,601 (52,991, 83,055)	19.38 (15.36, 23.74)	2.48 (2.31, 2.65)
Eastern Sub-Saharan Africa	1187 (1013, 1357)	1.54 (1.33, 1.74)	2958 (2558, 3360)	1.73 (1.51, 1.95)	0.40 (0.33, 0.46)
High-income Asia Pacific	42,358 (33,705, 51,710)	19.46 (15.64, 23.6)	97,912 (79,649, 115,467)	22.73 (18.8, 26.51)	0.73 (0.60, 0.87)
High-income North America	103,164 (82,346, 124,904)	28.10 (22.67, 33.73)	246,667 (210,369, 283,631)	36.68 (31.54, 41.73)	1.09 (0.94, 1.25)
North Africa and Middle East	6424 (5441, 7459)	3.30 (2.79, 3.83)	21,849 (18,679, 25,206)	4.47 (3.79, 5.14)	1.10 (1.06, 1.14)
Oceania	61 (50, 74)	2.01 (1.65, 2.37)	176 (142, 211)	2.39 (1.95, 2.85)	0.39 (0.31, 0.47)
South Asia	11,464 (9305, 13,882)	1.94 (1.61, 2.29)	36,024 (29,494, 42,470)	2.46 (2.04, 2.91)	0.86 (0.82, 0.91)
Southeast Asia	3766 (2982, 4526)	1.42 (1.13, 1.70)	14,478 (11,611, 17,131)	2.22 (1.8, 2.62)	1.62 (1.57, 1.66)
Southern Latin America	7468 (6409, 8571)	15.54 (13.45, 17.75)	20,017 (17,374, 23,351)	22.85 (19.94, 26.48)	1.20 (0.98, 1.41)
Southern Sub-Saharan Africa	608 (517, 703)	2.05 (1.74, 2.35)	1422 (1194, 1652)	2.48 (2.11, 2.87)	0.60 (0.56, 0.65)
Tropical Latin America	9128 (7486, 10,926)	8.86 (7.21, 10.61)	29,005 (23,277, 34,914)	11.11 (8.97, 13.36)	0.91 (0.81, 1.00)
Western Europe	142,624 (123,122, 161,999)	24.19 (21.14, 27.44)	321,517 (285,402, 354,961)	36.45 (32.41, 40.39)	1.66 (1.43, 1.89)
Western Sub-Saharan Africa	1067 (915, 1231)	1.03 (0.88, 1.17)	2732 (2367, 3117)	1.16 (1.01, 1.32)	0.36 (0.34, 0.38)

Deaths	Number	ASMR	Number	ASMR	EAPC
Global	62,911 (57,386, 67,303)	1.98 (1.78, 2.13)	142,205 (120,675, 155,575)	1.83 (1.54, 2.00)	-0.07 (-0.19, 0.05)
Male	27,217 (25,414, 29,077)	2.01 (1.86, 2.13)	59,649 (53,125, 63,372)	1.89 (1.66, 2.02)	0.05 (-0.10, 0.21)
Female	35,694 (31,371, 38,993)	1.90 (1.65, 2.07)	82,556 (66,341, 92,743)	1.73 (1.40, 1.95)	-0.12 (-0.24, -0.01)
High SDI	44,528 (39,779, 46,960)	3.88 (3.45, 4.11)	92,579 (74,404, 102,071)	3.43 (2.81, 3.76)	-0.16 (-0.33, 0.01)
High-middle SDI	8600 (7932, 9125)	1.03 (0.93, 1.10)	23,646 (20,186, 25,781)	1.27 (1.08, 1.39)	0.84 (0.61, 1.07)
Middle SDI	4543 (4016, 5187)	0.50 (0.44, 0.59)	11,640 (10,228, 13,303)	0.49 (0.43, 0.57)	0.02 (-0.09, 0.12)
Low-middle SDI	3588 (2565, 4730)	0.68 (0.48, 0.90)	10,223 (8152, 12,209)	0.84 (0.67, 1.01)	0.79 (0.7, 0.88)
Low SDI	1599 (948, 2238)	0.87 (0.50, 1.20)	3951 (2656, 5097)	0.98 (0.64, 1.31)	0.58 (0.4, 0.77)
Andean Latin America	139 (113, 160)	0.64 (0.53, 0.73)	356 (293, 436)	0.61 (0.50, 0.74)	-0.15 (-0.42, 0.12)
Australasia	870 (782, 929)	3.66 (3.26, 3.91)	2002 (1662, 2221)	3.09 (2.59, 3.42)	-0.46 (-0.77, -0.15)
Caribbean	260 (232, 283)	0.98 (0.88, 1.06)	545 (476, 614)	1.01 (0.88, 1.14)	0.20 (-0.08, 0.47)
Central Asia	38 (34, 43)	0.08 (0.07, 0.09)	205 (179, 231)	0.30 (0.26, 0.34)	6.01 (5.14, 6.90)
Central Europe	1167 (1076, 1305)	0.83 (0.76, 0.94)	6366 (5693, 6900)	2.68 (2.40, 2.91)	4.76 (4.34, 5.18)
Central Latin America	818 (791, 837)	0.94 (0.91, 0.97)	2226 (1985, 2480)	0.91 (0.82, 1.02)	0.09 (-0.3, 0.48)
Central Sub-Saharan Africa	221 (139, 318)	1.27 (0.77, 1.81)	569 (352, 857)	1.45 (0.88, 2.27)	0.45 (0.31, 0.59)
East Asia	876 (624, 1243)	0.13 (0.10, 0.18)	1757 (1422, 2248)	0.10 (0.08, 0.12)	-1.53 (-2.14, -0.92)
Eastern Europe	433 (417, 446)	0.17 (0.16, 0.17)	2230 (2063, 2391)	0.64 (0.59, 0.69)	5.24 (4.82, 5.67)
Eastern Sub-Saharan Africa	606 (377, 849)	0.99 (0.57, 1.34)	1379 (899, 1885)	1.02 (0.66, 1.44)	0.09 (-0.01, 0.19)
High-income Asia Pacific	7066 (6254, 7509)	3.81 (3.33, 4.08)	19,320 (13,988, 22,319)	2.46 (1.84, 2.80)	-0.17 (-0.8, 0.46)
High-income North America	15,707 (13,717, 16,712)	4.06 (3.55, 4.32)	27,282 (22,212, 29,883)	3.60 (2.97, 3.93)	-0.49 (-0.76, -0.23)
North Africa and Middle East	1483 (1004, 1920)	0.90 (0.59, 1.16)	3276 (2414, 4032)	0.81 (0.61, 0.99)	-0.26 (-0.37, -0.15)
Oceania	26 (19, 38)	1.07 (0.82, 1.46)	54 (40, 77)	0.84 (0.64, 1.20)	-0.83 (-0.99, -0.67)
South Asia	3469 (2357, 4789)	0.74 (0.49, 1.04)	11,192 (8668, 13,804)	0.92 (0.70, 1.13)	0.84 (0.68, 0.99)
Southeast Asia	392 (257, 713)	0.19 (0.12, 0.36)	1243 (942, 1951)	0.25 (0.19, 0.39)	0.79 (0.50, 1.08)
Southern Latin America	1745 (1604, 1881)	3.99 (3.64, 4.30)	2765 (2449, 3011)	3.01 (2.67, 3.27)	-0.55 (-0.80, -0.31)
Southern Sub-Saharan Africa	252 (202, 306)	1.03 (0.81, 1.25)	525 (426, 626)	1.23 (0.98, 1.45)	0.56 (0.36, 0.76)
Tropical Latin America	1658 (1579, 1709)	1.83 (1.71, 1.90)	3837 (3444, 4097)	1.55 (1.39, 1.66)	-0.33 (-0.49, -0.18)
Western Europe	24,919 (22,637, 26,247)	4.04 (3.67, 4.26)	53,518 (43,825, 58,592)	4.23 (3.53, 4.60)	0.34 (0.25, 0.44)
Western Sub-Saharan Africa	766 (466, 1048)	1.07 (0.63, 1.54)	1557 (966, 2404)	1.04 (0.65, 1.63)	-0.25 (-0.34, -0.16)

DALYs	Number	ASMR	Number	ASMR	EAPC
Global	1,191,644 (1,104,009, 1,292,157)	32.49 (29.80, 35.14)	2,243,000 (2,004,168, 2,459,248)	27.74 (24.67, 30.48)	-0.38 (-0.49, -0.26)
Male	608,594 (564,588, 658,888)	36.09 (33.73, 38.85)	1,101,322 (1,006,118, 1,205,565)	31.09 (28.38, 33.93)	-0.32 (-0.47, -0.17)
Female	583,050 (518,859, 651,286)	28.61 (25.53, 31.68)	1,141,678 (966,439, 1,281,684)	24.41 (20.72, 27.45)	-0.39 (-0.49, -0.3)
High SDI	736,914 (679,640, 777,890)	64.22 (59.17, 67.75)	1,222,299 (1,042,435, 1,341,836)	50.38 (44.16, 54.83)	-0.6 (-0.79, -0.41)
High-middle SDI	185,210 (170,893, 201,553)	19.50 (17.97, 21.24)	394,694 (352,937, 434,424)	21.00 (18.75, 23.06)	0.33 (0.18, 0.48)
Middle SDI	130,200 (117,072, 147,896)	11.26 (10.10, 12.82)	276,278 (242,967, 316,116)	10.76 (9.48, 12.35)	-0.13 (-0.24, -0.02)
Low-middle SDI	95,444 (71,058, 126,187)	14.43 (10.56, 18.92)	245,090 (199,020, 292,247)	17.20 (13.85, 20.50)	0.63 (0.58, 0.68)
Low SDI	42,690 (26,683, 60,833)	17.69 (10.61, 24.78)	101,674 (68,878, 130,980)	19.33 (13.08, 24.89)	0.36 (0.22, 0.50)
Andean Latin America	4202 (3404, 4894)	16.82 (13.81, 19.26)	9992 (8267, 12,214)	16.44 (13.57, 19.98)	-0.13 (-0.38, 0.12)
Australasia	14,646 (13,523, 15,730)	60.09 (55.21, 64.49)	27,116 (23,306, 29,987)	45.22 (39.49, 49.74)	-0.83 (-1.13, -0.52)
Caribbean	7035 (6273, 7756)	24.32 (21.77, 26.73)	13,275 (11,395, 15,250)	24.98 (21.44, 28.74)	0.15 (-0.13, 0.42)
Central Asia	1554 (1271, 1978)	3.18 (2.56, 4.19)	5878 (5034, 6995)	7.85 (6.66, 9.47)	4.21 (3.54, 4.88)
Central Europe	29,136 (26,562, 33,122)	19.70 (17.96, 22.45)	112,642 (102,498, 123,896)	50.10 (45.80, 54.99)	3.75 (3.37, 4.14)
Central Latin America	24,009 (23,176, 25,089)	24.02 (23.06, 25.32)	58,212 (52,221, 65,462)	23.08 (20.68, 26.05)	0.04 (-0.32, 0.39)
Central Sub-Saharan Africa	5967 (3844, 8618)	25.44 (15.88, 36.61)	14,883 (9600, 21,789)	27.84 (17.20, 41.81)	0.30 (0.15, 0.44)
East Asia	26,060 (18,504, 36,332)	2.90 (2.11, 4.01)	43,823 (35,366, 55,392)	2.25 (1.83, 2.82)	-1.26 (-1.66, -0.86)
Eastern Europe	15,777 (13,287, 20,043)	5.90 (4.97, 7.47)	60,663 (53,910, 70,346)	18.23 (16.32, 20.87)	4.10 (3.80, 4.41)
Eastern Sub-Saharan Africa	17,104 (11,212, 24,511)	20.09 (12.55, 28.08)	37,760 (24,921, 50,626)	20.20 (13.21, 27.55)	-0.06 (-0.15, 0.04)
High-income Asia Pacific	119,175 (109,260, 126,686)	60.16 (54.71, 64.14)	220,492 (172,646, 252,863)	32.75 (27.02, 37.01)	-0.89 (-1.49, -0.28)
High-income North America	260,235 (239,122, 276,649)	69.51 (64.16, 73.74)	382,828 (333,801, 419,029)	54.41 (48.14, 59.30)	-0.92 (-1.26, -0.58)
North Africa and Middle East	47,969 (33,047, 62,354)	22.16 (15.28, 28.78)	93,596 (68,114, 115,367)	19.01 (14.14, 23.21)	-0.52 (-0.59, -0.45)
Oceania	928 (613, 1428)	23.76 (17.48, 34.56)	2016 (1395, 2977)	20.77 (15.34, 29.45)	-0.49 (-0.65, -0.33)
South Asia	87,510 (60,274, 122,331)	14.79 (10.19, 20.34)	251,747 (197,292, 310,183)	17.69 (13.81, 21.73)	0.65 (0.56, 0.74)
Southeast Asia	10,207 (6895, 16,826)	3.81 (2.57, 6.58)	27,996 (21,601, 41,440)	4.73 (3.64, 7.14)	0.62 (0.38, 0.87)
Southern Latin America	33,292 (31,297, 35,592)	71.82 (67.34, 76.86)	46,480 (42,450, 50,689)	52.09 (47.68, 56.73)	-0.79 (-1.01, -0.58)
Southern Sub-Saharan Africa	6672 (5587, 8414)	20.39 (16.69, 24.75)	12,228 (10,014, 14,946)	21.98 (17.85, 26.40)	0.24 (0.02, 0.47)
Tropical Latin America	47,451 (45,878, 48,720)	44.08 (42.19, 45.48)	83,552 (77,538, 88,493)	33.00 (30.52, 35.02)	-0.83 (-1.01, -0.65)
Western Europe	414,818 (385,594, 436,922)	69.08 (64.40, 72.42)	700,284 (600,116, 766,678)	62.44 (54.95, 67.78)	-0.21 (-0.30, -0.11)
Western Sub-Saharan Africa	17,899 (11,186, 24,351)	19.90 (12.16, 27.15)	37,536 (23,078, 57,538)	19.11 (11.83, 29.47)	-0.31 (-0.41, -0.21)

Fig. 1.

Trends in CAVD prevalence, incidence, deathes and disability-adjusted life-years from 1992 to 2021.

Regional Burden of CAVD from 1992 to 2021

Age-standardized prevalence rate

From 1992 to 2021, the highest ASPR of CAVD was consistently observed in the High SDI region, starting at 270.48 (95% CI 225.67–316.87) per 100,000 persons in 1992 and rising to 349.64 (95% CI 303.58–395.77) per 100,000 persons in 2021 (Table 1). In contrast, the Low SDI region had the lowest ASPR in 2021, at 14.18 (95% CI 11.28–17.32) per 100,000 persons. All SDI regions experienced a significant increase in ASPR over this period, particularly in the Middle, High-middle, Low-middle, and High SDI regions (all EAPC > 1.12) (Table 1, Fig. 1). In 2021, the highest ASPR for CAVD was observed in Western Europe, High-income North America, and Central Europe, ranging from 379.57 to 425.32 per 100,000 persons. In contrast, Western, Eastern, and Central Sub-Saharan Africa had the lowest ASPRs, ranging from 11.08 to 14.67 per 100,000 people (Table 1, Fig. 2A). From 1992 to 2021, the ASPR of CAVD increased across all GBD regions, particularly in high-burden areas such as Eastern Europe (EAPC = 2.57).

Fig. 2.

Global burden of CAVD across 204 countries and territories in 2021. (A) Age-standardized prevalence rate; (B) Age-standardized incidence rate; (C) Age-standardized mortality rate; (D) Age-standardized disability-adjusted life years.

Age-standardized incidence rate

In terms of ASIR in 2021, the High SDI region again had the highest rate, at 29.98 (95% CI 26.09–33.53) per 100,000 persons, while the Low SDI region recorded the lowest, at 1.89 (95% CI 1.61–2.16) per 100,000 persons (Table 1). The ASIR also rose significantly across all SDI regions from 1992 to 2021, with a sharp increase in the Middle, High-middle, High, and Low-middle SDI regions (all EAPC > 1.11) (Table 1, Fig. 1). In 2021, High-income North America, Western Europe, and Australasia had the highest ASIRs, with rates ranging from 30.99 to 36.68 per 100,000 persons, while Western Sub-Saharan Africa had the lowest ASIR (EAPC = 1.16) (Table 1, Fig. 2B).

Age-standardized mortality rate

For the ASMR in 2021, the High SDI region had the highest rate at 3.43 (95% CI 2.81–3.76) per 100,000 persons, and the Middle SDI region had the lowest, at 0.49 (95% CI 0.43–0.57) per 100,000 persons (Table 1). The High SDI region showed a decline in ASMR (EAPC −0.16), whereas the Middle SDI region remained relatively stable (EAPC 0.02). In contrast, the ASMR increased in the other three regions over the past 30 years (Table 1, Fig. 1). Despite the overall increase in the ASPR and ASIR, the ASMR declined in several regions over the past three decades, including East Asia, Oceania, Southern Latin America, and High-income North America. In 2021, the ASMR remained highest in Western Europe, High-income North America, and Australasia, with rates of 4.23, 3.60, and 3.09 per 100,000 persons, respectively. Conversely, Central Asia, Eastern Europe, and Central Europe showed significant increases in the ASMR, with all EAPC values exceeding 4.76. East Asia had the lowest ASMR, at 0.25 (95% CI 0.19–0.39) per 100,000 persons, followed by Southeast Asia and Central Asia (Table 1, Fig. 2C).

Age-standardized disability-adjusted life years rate

Similarly, the ASDR in 2021 was highest in the High SDI region, at 27.74 (95% CI 44.16–54.83) per 100,000 persons (Table 1). While the ASDR decreased in the High (EAPC -0.60) and Middle (EAPC −0.13) SDI regions, it increased in the High-middle, Low-middle, and Low SDI regions over the past three decades, particularly in the Low-middle SDI region (EAPC 0.63) (Table 1, Fig. 1). The ASDR mirrored the trend observed for ASMR, although with a more pronounced downward trend. In 2021, the highest ASDR were recorded in Western Europe (62.44), High-income North America (54.41), and Southern Latin America (52.09) per 100,000 persons. Despite these high rates, these regions exhibited a declining trend in ASDR over the past decades, with all showing EAPC values below -0.21. In contrast, East Asia recorded the lowest ASDR, at 2.25 (95% CI 1.83–2.82) per 100,000 persons, showing a significant decline with an EAPC of -1.26 (Table 1, Fig. 2D). Central Asia, Eastern Europe, and Central Europe experienced substantial increases in the ASDR, with EAPC values exceeding 3.75, indicating a notable upward trend.

National Burden of CAVD from 1992 to 2021

In 2021, the global disparity in the ASPR of CAVD was striking, with a 115-fold difference between regions. Slovenia had the highest ASPR (993.08/100,000), while Niger had the lowest (8.64/100,000) (Table S2, Fig. 2A). The geographical distribution of ASIR in 2021 closely followed the trends of ASPR, with Slovenia having the highest rate (78.56/100,000), Mali having the lowest (0.93/100,000) (Table S2, Fig. 2B). The ASMR in 2021 was the highest in Slovenia (10.25/1000,000), followed by Cyprus, Norway, Uruguay, the Netherlands, Luxembourg, Germany, and Belgium. Tajikistan had the lowest ASMR (0.007/100,000), followed by Azerbaijan, China, North Korea, and Cambodia (Table S2, Fig. 2C). The ASDR mirrored the ASPR pattern in 2021, with Slovenia having the highest (154.36/1000,000) and Tajikistan having the lowest (1.36/100,000) rate (Table S2, Fig. 2D). These significant regional disparities underscore the need for targeted interventions and policies to address the global CAVD burden.

From 1992 to 2021, the ASPR increased in 200 of 204 countries. The country with the largest annualized growth in ASPR was Croatia, with an EAPC of 4.52 (95% CI 4.29–4.75), while the fastest decline occurred in Somalia, with an EAPC of −0.27 (95% CI −0.3, −0.23) (Table S2). Similarly, the ASIR rose in 200 out of 204 countries, with the largest increase in Croatia (EAPC = 4.78; 95% CI 4.52–5.04) and the largest decrease in Burundi (EAPC = -0.37; 95% CI −0.42, −0.31) (Table S2). Encouragingly, the ASMR decreased in 92 countries and the ASDR dropped in 99 countries from 1992 to 2021. The highest EAPCs for both ASMR and ASDR were observed in Georgia (EAPC = 13.04 and 10.02, respectively). The lowest EAPC for ASMR was found in Guam (EAPC = −3.12), while the lowest EAPC for ASDR was in Lebanon (EAPC = −2.62). Additionally, an EAPC of ASMR exceeding 5.00 was observed in 14 other countries, including Poland, the Czech Republic, and Turkmenistan. Meanwhile, countries including Lebanon, Qatar, Sri Lanka, Jordan, and Cyprus exhibited EAPC values of ASMR < −2.12 (Table S2). The trends in the ASDR followed a pattern very similar to that of the ASMR. An EAPC of ASDR exceeding 4.00 was noted in 10 additional countries, including Poland, the Czech Republic, Bulgaria, Lithuania, Croatia, Uzbekistan, Turkmenistan, Russia, Latvia, and Estonia (Table S2). These findings highlight significant regional variations in the CAVD burden and suggest that targeted interventions may be needed in countries experiencing the fastest increase or decline in the disease burden.

Sex and age patterns

In 2021, the global ASPR for CAVD was higher in males compared with females. The ASPR for males was 193.24 (95% CI 166.56–220.38) per 100,000, whereas for females it was 128.88 (95% CI 110.13–147.68) per 100,000. Similarly, the ASIR was also higher in males than females (13.97 vs. 10.19) (Table 1). From 1992 to 2021, both the ASPR and ASIR increased in both sexes, but the increase was more pronounced in males. Over the past 30 years, the ASMR for males showed minimal change (EAPC = 0.05), whereas that for females declined (EAPC = −0.12) (Table 1). In 2021, the ASDR for males was 31.09 (95% CI 28.38–33.93) per 100,000, while for females it was 24.41 (95% CI 20.72–27.45) per 100,000. Despite these sex differences, both males and females exhibited a significant decrease in ASDR over time (EAPC = −0.32, −0.39, respectively), indicating improvements in survival and overall health outcomes for both sexes (Table 1).

In 2021, the global prevalence of CAVD increased with age, reaching its peak among individuals aged 90–94 years. The prevalence was consistently higher in males than in females across all age groups. The peak prevalence in males occurred at ages 70–74 years, with a total of 1,367,389 cases, while for females, the peak occurred at ages 80–84 years, with 1,108,104 cases (Fig. 3A). The incidence of CAVD also increased with age, and similar to the prevalence, males generally had a higher incidence rate than females. In 2021, the incidence peaked in the 70–84 age group, with the absolute number of new cases being the highest in the 65–74 age group, after which it gradually declined with increasing age (Fig. 3B). Regarding mortality and DALYs, the burden of CAVD increased with age. There was no significant sex difference before the age of 85 years, with males having slightly higher rates than females; however, after the age of 85 years, the mortality rate in females rose rapidly and surpassed that in males (Fig. 3C and D). Additionally, from 1992 to 2021, the overall ASPR, ASIR, and ASDR burdens for males were higher than those for females, and in recent years, the ASMR showed a similar trend (Figure S1).

Fig. 3.

Sex- and age-structured analysis of CAVD burden in 2021. (A) Prevalence numbers and rates; (B) Incidence numbers and rates; (C) Mortality numbers and rates; (D) DALYs numbers and rates.

The relationship between the burden of CAVD and the SDI

There was a positive correlation between the ASPR (r = 0.88, p < 0.001), ASIR (r = 0.89, p < 0.001), and SDI, indicating that prevalence and incidence rates increased concurrently with increasing SDI values (Fig. 4A and B). In regions with an SDI > 0.5, economic development was significantly correlated with higher prevalence and incidence rates. This positive correlation was particularly prominent in areas such as High-income North America, Western Europe, and Australasia. ASMR and ASDR also showed upward trends (ASMR r = 0.41, p < 0.001; ASDR r = 0.45, p < 0.001) (Fig. 4C and D). When the SDI was below 0.6, the ASMR and ASDR remained relatively stable; however, both gradually increased as the SDI increased above 0.6, reaching their peak at an SDI of approximately 0.8.

Fig. 4.

Relationship between SDI levels and the ASR for CAVD in Global and 21 GBD region. (A) Age-standardized prevalence rate; (B) Age-standardized incidence rate; (C) Age-standardized mortality rate; (D) Age-standardized disability-adjusted life years.

Frontier analysis of the CAVD Burden

The frontier line represents the countries or regions with the lowest disease burden per unit of SDI. The effective difference refers to the gap between the actual disease burden and the expected burden based on the SDI, highlighting the potential for unrealized health improvement. This significant gap suggests opportunities for reducing the number of CAVD-related DALYs during development. In 2021, the top five countries and regions with the largest effective differences were Slovenia, Cyprus, Uruguay, Hungary, and Luxembourg, with values ranging from 83.22 to 153.24 (Figure S2, Table S3). The countries and regions with the smallest effective differences among the regions with lower levels of economic development (SDI < 0.5) included Somalia, Timor-Leste, Niger, Cambodia, and Laos. (Figure S2). Among the economically developed countries and regions (SDI > 0.8), those with the largest effective differences were Slovenia, Cyprus, Luxembourg, Bermuda, Germany, Norway, the Netherlands, Belgium, Greenland, and Finland, with values ranging from 71.90 to 153.24. (Figure S2, Table S3). Economically developed countries and regions with the smallest effective differences included Singapore, Kuwait, Taiwan (China), South Korea, Qatar, Bahamas, San Marino, Russia, and Monaco, with a range of 9.37 to 20.96 (Figure S2, Table S3). The frontier analysis results for the ASPR, ASIR, and ASMR of CAVD are presented in Figure S3 and Table S3.

Cross-national CAVD health inequality

In 1992 and 2021, the SII for DALYs (per 100,000 people) were 27.9 and 55.6, respectively (Figure S4). This indicates a positive correlation between the crude DALY rate and SDI, which became stronger by 2021. The rise in the SII suggests that inequities in the burden of CAVD between high- and low-income countries intensified over this period. Both the SII and CI indicate that despite reductions in the burden of CAVD in certain regions, the global wealth gap continues to exert a substantial influence on health outcomes (Figure S4). The global health inequality results for the ASPR, ASIR, and ASMR of CAVD are presented in Figure S5.

Decomposition analysis of the CAVD burden

Decomposition analysis was conducted using data from 1992 to 2021 to evaluate the impact of aging, population growth, and epidemiological changes on the CAVD burden. The global increase in prevalence was primarily driven by population growth (45.94%) and aging (35.31%) (Fig. 5A, Table S4). Aging was the dominant driver in the High, High-middle, and Middle SDI regions, accounting for 40.47%, 41.84%, and 35.74% of the burden increase, respectively. In contrast, population growth was the leading driver in the Low-middle and Low SDI regions, contributing 51.61% and 83.55% of the burden, respectively. Decomposition analysis of the incidence mirrored the prevalence findings (Fig. 5B, Table S4). Aging and population growth were the primary contributors to global mortality, accounting for 60.28% and 55.83% of the increase, respectively. However, epidemiological changes had a negative effect on mortality growth (−16.11%) (Fig. 5C, Table S4). Regarding DALYs, population growth was the main global driver of the increased burden (72.29%), whereas epidemiological changes had a negative impact (−31%). In the High SDI regions, aging was the most significant factor (88.91%), with epidemiological changes exerting the most pronounced negative influence (−41.47%) (Fig. 5D, Table S4).

Fig. 5.

Population-level determinant changes in aging, population growth, and epidemiological changes for CAVD burden worldwide and in various SDI regions from 1992 to 2021. (A) Prevalence; (B) Incidence; (C) Mortality; (D) Disability-adjusted life years.

Future forecasts of the global burden of CAVD

The forecast analysis indicated that the global ASPR for CAVD is expected to decrease from approximately 158 cases per 100,000 in 2021 to 144 cases per 100,000 by 2036, whereas the ASIR is projected to decrease from 12 cases per 100,000 to 10.5 cases per 100,000 (Figure S6, Table S5). By 2036, approximately 1,383,495 new cases of CAVD will occur globally and approximately 19,407,938 people will live with CAVD. In the High and High-middle SDI regions, the CAVD incidence and prevalence are also expected to follow a similar trend, with projections decreasing to approximately 311 cases per 100,000 and 163 cases per 100,000, respectively (Figure S6, Table S5). However, in other SDI regions, the incidence and prevalence are expected to continue to increase. Regarding mortality and DALYs, by 2036, the ASMR and ASDR for CAVD are expected to decrease to 1.47 cases per 100,000 and 24 cases per 100,000, respectively. High and High-middle SDI regions will also show a significant downward trend (Figure S6), with the ASDR in High SDI regions decreasing from 50.4 cases per 100,000 to 39.7 cases per 100,000 (Table S6). For the Middle, Low-middle, and Low SDI regions, these two indicators are expected to remain relatively stable. The projected ASR for the global burden of CAVD from 2022 to 2036 are shown in Table S5.

Discussion

Using the latest GBD 2021 data, we systematically assessed the global trends and regional variations in CAVD, covering key indicators such as the prevalence, incidence, mortality, and DALYs, providing valuable insights for global public health policies and resource allocation. In 2021, the global prevalence of CAVD was 158.3 cases per 100,000, and with an aging population, the number of CAVD cases increased more than two-fold from 4.97 million in 1992 to 13.32 million in 2021. Additionally, in 2021, there were 1.04 million new cases, with an incidence rate of 12 cases per 100,000 people. The number of deaths attributed to CAVD was 140,000, and the DALYs was 2.24 million. The ASDR decreased from 32.5 per 100,000 in 1992 to 27.7 in 2021. Over the past 30 years, the global prevalence and incidence of CAVD have shown consistent upward trends. Although the mortality and DALY rates have declined, reflecting advances in disease prevention and treatment, the burden of CAVD remains substantial. Overall, the increasing number of deaths, hospitalizations, complications, life-years lost, and associated healthcare costs pose a significant threat to public health and healthcare systems, highlighting the urgent need for sustained interventions and optimized resource allocation.

Over the past three decades, the ASPR and ASIR of CAVD have been higher in High- and High-middle SDI regions but lower in Low SDI regions. The incidence of CAVD increased progressively with an increasing SDI. This trend was driven by multiple factors, including population aging, an increased burden of metabolic diseases, lifestyle changes, and improved healthcare services. First, regions with a High SDI typically have longer life expectancies and more pronounced population aging, and the risk of CAVD increases significantly with age. Aging and congenital bicuspid aortic valve morphology are important and unmodifiable risk factors for CAVD²². Second, modifiable risk factors such as hypertension, elevated plasma lipoprotein (a) levels, obesity, and diabetes are more prevalent in aging societies, further exacerbating the risk of CAVD^23–26. Additionally, marked differences in lifestyle and psychosocial factors are observed across SDI regions. A recent study of 30,561 participants in China investigated the association between Life’s Essential 8 (LE8) and aortic valve calcification (AVC) ²⁷. It found a higher LE8 score was associated with a lower AVC risk. Analysis of individual LE8 components showed diet, physical activity, body mass index, blood lipids, blood glucose, and blood pressure were each associated with reduced AVC risk; however, sleep and smoking showed no significant impact. In High SDI regions, factors like Western diets, physical inactivity, chronic stress, anxiety, and depression likely contribute to higher CAVD incidence. Finally, advanced medical standards and diagnostic technologies, comprehensive health coverage, and high screening rates in High SDI regions facilitate the early detection of valvular diseases, including asymptomatic cases²⁸. In contrast, the lower incidence of CAVD in regions with a low SDI can be attributed to factors such as a higher prevalence of other diseases (e.g., infectious diseases, malnutrition, or acute cardiovascular events) that result in higher early mortality rates²⁹ as well as a lack of comprehensive data collection and reporting systems, which may lead to underestimation of the incidence and prevalence of CAVD. The lowest ASMR for CAVD was observed in the Middle SDI regions, likely due to the combination of relatively low incidence rates and moderately advanced medical care. Although the incidence of CAVD is low in regions with a low SDI, the ASMR and ASDR remain higher. This is primarily due to insufficient diagnosis, delayed referrals, and inadequate treatment, all of which contribute to higher mortality rates⁸.

In 2021, High SDI regions had the highest ASMR and ASDR for CAVD. This phenomenon is related to the high incidence of CAVD in High SDI regions, but undertreatment and delayed referrals may be the primary contributors to the high mortality and disability rates^30,31. The IMPULSE registry, a large multicenter prospective registry from 23 centers across 9 European countries, showed that patients were still referred late in the course of the disease with severe symptoms and/or left ventricular dysfunction, and that despite the availability of transcatheter aortic valve replacement (TAVR), more than 20% of the symptomatic patients were denied an intervention³². However, these metrics showed declining trends over the past three decades. This is primarily attributed to the robust healthcare systems and advanced diagnostic technologies in High SDI regions³³, as well as significant advancements in medical technologies and treatment options, which have markedly improved patient prognosis^34,35. For example, progress in the field of surgical valve replacement, such as rapid deployment and sutureless valves, totally endoscopic surgery, robotic surgical platforms, hemisternotomy or right anterior minithoracotomy has continuously enhanced treatment efficacy^36,37. In addition, the development of TAVR has provided more feasible treatment options for high-risk patients³⁸.

At the national level, since 1992, several European countries, including Poland, the Czech Republic, Bulgaria, Lithuania, Croatia, and Russia, have experienced significant increases in mortality and DALY rates, which are particularly concerning. The prevalence of CAVD has remained persistently high owing to widespread aging in European countries. If attention and healthcare resources for CAVD remain insufficient, mortality and disability rates will continue to increase. Our study reveals that, in addition to significant disparities between high and low SDI countries, there are also substantial differences in the epidemiological features of CAVD within High SDI countries. These variations are likely influenced by factors such as differences in healthcare systems, health policies, and the degree of population aging in each country. A survey of European countries showed significant differences in the number of patients undergoing aortic valve replacement per million people (PPM) across countries. In 2020, Germany led with 508 PPM (60% of which were TAVR), whereas Poland had only 174 PPM (25% of which were TAVR), ranking lowest among the surveyed countries³⁹. Additionally, the study revealed that the adoption of TAVR in Poland has been slow, and there are significant regional disparities in the experience levels of TAVR centers, reflecting that the pace of CAVD treatment advancements lags behind the increase in prevalence⁴⁰. This imbalance led to a rapid rise in the ASMR and ASDR, as well as the highest recorded EAPC. In 2021, Germany performed 32.0 TAVR procedures per 100,000 people; the rates in Switzerland and the US were 23.9 and 22.2, respectively (2019 data) ⁴¹. Despite its ample surgical supply, Germany still faces a high mortality and DALYs related to CAVD. Germany, one of the countries with the highest level of aging, is projected to see an increase of 8,748 diagnosed cases of aortic stenosis (a 13% rise) by 2035 compared to 2021, while the number of TAVR procedures is expected to rise by 4,673 (an 18% increase)⁴². Therefore, even developed countries should continue to strengthen or maintain TAVR-related healthcare services and implement policy measures, such as improving compensation and benefits for elderly care staff⁴³, to address this growing health challenge. The frontier analysis further examined the potential of different countries to reduce the burden of CAVD. The points form an inverted triangle shape, with lower values on the left and higher values on the right. As SDI increases, the range of point distribution expands, suggesting that countries with higher SDI levels may have greater potential for reducing the disease burden. The analysis highlighted that European countries, such as Slovenia, Cyprus, Luxembourg, Norway, the Netherlands, Belgium, Finland, and Hungary, need to fully utilize existing socioeconomic resources, optimize policies, and provide healthcare services to narrow the gap between different countries and regions, effectively addressing the disease burden of CAVD caused by aging.

This study revealed significant sex- and age-related differences among patients with CAVD. First, the prevalence and incidence rates were slightly higher in men than in women. Research shows that men are more prone to significant valve calcification, a key factor in the progression of aortic stenosis (AS)^44,45. In contrast, women tend to exhibit fibrotic valve remodeling with a lighter calcification burden and slower calcification progression⁴⁶. Additionally, our study found that in women aged > 85 years, mortality and DALYs rose sharply, with CAVD-related deaths and DALYs significantly exceeding those in men. Several factors might have contributed to this observation. In response to AS, men typically show left ventricular (LV) dilatation remodeling associated with the characteristics of heart failure with a reduced ejection fraction, whereas women are more likely to develop hypertrophic LV remodeling, often associated with heart failure with a preserved ejection fraction⁴⁷. Furthermore, levels of the male hormone dihydrotestosterone are associated with myocardial maladaptive remodeling in patients with aortic stenosis⁴⁸. Differences in the calcification severity and LV remodeling may explain the differences in the frequency and timing of AS diagnoses between men and women. Data show that women tend to receive longer periods of conservative treatment, are diagnosed at older ages, and have lower rates of surgical referral^49–51. Additionally, female patients bear a higher symptom burden and have a higher prevalence of mitral and tricuspid regurgitation^52,53. Surveys have also found that women are less likely to undergo AVR than men and face higher surgical risks^39,54. To address the challenges posed by sex differences, future initiatives should place greater emphasis on the undertreatment of female patients. Preventive strategies should include increasing the screening frequency for older women, optimizing referral pathways to ensure timely specialist evaluation and treatment, and conducting careful preoperative risk assessments. When appropriate, minimally invasive procedures such as TAVR should be prioritized to reduce surgical risks and improve outcomes⁵⁵.

Our study is the first to conduct a projection analysis of the global burden of CAVD, which helps to accurately quantify the burden of CAVD, improve decision-making, plan resource allocation, and provide scientific evidence for policy development. The results indicate that the prevalence and incidence of CAVD are expected to decrease in the future, which may reflect the positive impact of global efforts related to CAVD prevention and treatment. In recent years, the rapid development of TAVR and other percutaneous treatment options has dramatically changed the treatment approach for patients with valvular heart disease (VHD), attracting widespread attention from clinicians, researchers, engineers, device manufacturers, and investors. This is a highly innovative and rapidly evolving field. Recent reviews have summarized the latest progress in the field of valvular heart disease, as well as four key areas of ongoing development: utilization of artificial intelligence and digital methods to strengthen screening, diagnosis, and planning procedures; integrating imaging and clinical data to improve the classification of VHD severity and risk stratification; developing new medical therapies, molecular targets, and pharmacological strategies to halt VHD progression; and advances in cardiac valve engineering and tissue engineering^38,56. Despite these positive advances, it is important to recognize that the burden of CAVD remains substantial. It is estimated that by 2036, approximately 19,407,938 people will develop CAVD, approximately 199,795 people will die from CAVD, and approximately 3,140,755 DALYs will be attributed to CAVD, highlighting the ongoing importance of attention and intervention. Furthermore, the BAPC projection analysis highlighted disparities in the burden of CAVD across different SDI regions. Except for the High and High-middle SDI regions, the CAVD incidence and prevalence are expected to continue rising in other SDI regions that are in the process of economic development. Particularly, in the context of accelerated population aging, there is an urgent need to increase societal resource investment, strengthen CAVD screening, and improve treatment and care levels in these regions.

This study has some limitations. First, the data came primarily from the GBD database, which relies on health records from various countries. However, the quality and accuracy of the data may vary across regions, particularly in low-income and resource-poor countries, where incomplete reporting or misclassification may occur. Consequently, the integrity and accuracy of the data may have been compromised, potentially affecting the reliability of the findings. Secondly, this study focused on global and regional-level data analysis rather than a detailed exploration of the specific burden of CAVD in individual countries or regions. In reality, even within the same region, the disease burden may vary significantly, potentially affecting the overall understanding of the CAVD burden. Additionally, although the study made projections of the future burden of CAVD based on historical trends, these forecasts rely heavily on past data and assumptions without fully considering potential changes in healthcare policies, the emergence of innovative treatments, or new risk factors. Consequently, the future burden of CAVD may be either overestimated or underestimated, particularly in the context of advancing technology and the increasing prevalence of early diagnosis. Therefore, future research should focus on the accuracy of the data, regional differences, and factors that could influence the future burden of CAVD to provide more precise and targeted intervention strategies.

Conclusion

In summary, this study is the first to use GBD 2021 data to describe the global, regional, and national burdens of CAVD and analyze trends in CAVD from 1992 to 2021. The results show that, globally, the ASPR and ASIR of CAVD are increasing, whereas the ASMR and ASDR have significantly decreased. Population aging and growth are the main drivers behind the increase in the prevalence and incidence, whereas epidemiological changes have contributed to a reduction in mortality and the DALYs burden. Significant disparities exist in the CAVD burden across countries and regions. High SDI regions currently bear a larger CAVD burden. Although this burden may decrease in the future, it remains substantial. In contrast, regions with lower SDI levels have a lighter current burden, but the number of patients with CAVD is expected to increase. Therefore, it remains crucial to develop targeted prevention and treatment strategies at both the global and national levels.

Supplementary Information

Below is the link to the electronic supplementary material.

Author contributions

BW and ZM: Conceptualization, software, and visualization. BW, HY, WG, LM: Data interpretation and writing—original draft. BW, LM, GA: Writing—review & editing, supervision, and validation. All authors reviewed the drafted manuscript and approved the final version.

Funding

This work was supported by the National Natural Science Foundation of China (81800382).

Data availability

All data downloaded from GBD database (https://www.healthdata.org/research-analysis/gbd). Further inquiries can be directed to the corresponding author.

Declarations

Competing interests

The authors declare no competing interests.

Ethical approval

Not applicable.