Global and national burden of atherosclerosis from 1990 to 2019: trend analysis based on the Global Burden of Disease Study 2019

Abstract

Background:

Atherosclerosis-related diseases represent significant health issues among adults globally. Despite their widespread impact, comprehensive data concerning the global and national burden and trends of these diseases remain sparse. Our objective is to examine the trends in the burden of atherosclerosis among adults from 1990 to 2019 at both global and national levels.

Methods:

We reported the average annual percentage changes (AAPCs) in prevalence, incidence, mortality, and disability-adjusted life years (DALYs) of atherosclerosis-related diseases (ischemic heart disease [IHD], ischemic stroke, and peripheral arterial disease [PAD]) at the global and national levels among individuals based on a trend analysis of the Global Burden of Diseases Study (GBD) 2019. We further analyzed these global trends as a function of age, gender, and the social development index. We also used joinpoint regression analysis to identify the year with the most substantial changes in global trends.

Results:

Globally, the AAPC of IHD incidence rose from 1990 to 2019 (0.20; 95% confidence interval [CI], 0.12–0.28), with substantial surges in 1995, 2001, 2005, 2010, and 2017. Conversely, AAPC of IHD mortality rates exhibited a different trend until a rise in 2014. The AAPC of incidence rates of ischemic stroke and PAD also escalated during the same period, with respective 0.43 (95% CI, 0.39–0.48) and 0.13 (95% CI, 0.06–0.21). For ischemic stroke, both incidence and mortality soared in 2014, while PAD incidence declined in 1994 and 1998, then sharply climbed in 2016. Nationally, the Northern Mariana Islands experienced the steepest increase in IHD and PAD incidence and mortality between 1990 and 2019. China saw a significant rise in ischemic stroke incidence, whereas the highest mortality rate increase occurred in Timor-Leste. By sociodemographic index (SDI) quintile, low-middle-, middle-, and high-middle-SDI countries all showed upward trends in IHD, ischemic stroke, and PAD incidence. Simultaneously, IHD and ischemic stroke mortality rates, as well as DALYs, dropped in the low-, high-middle-, and high-SDI nations. However, PAD mortality rates and DALYs saw an uptick across all SDI quintiles. Regarding age demographics, a global decrease in the AAPC IHD incidence as noted in individuals above 55 years old, in contrast to an increase in the 20–55 age group during this period. AAPC of mortality rates for IHD, ischemic stroke, and PAD decreased across all ages. The AAPC showed an increase in IHD incidence in both genders. Conversely, IHD's DALYs saw a reduction in both males and females. Ischemic stroke patterns mirrored these trends, whereas all measures for PAD exhibited growth for both sexes.

Conclusions:

From 1990 to 2019, there was an overall increasing trend in the global incidence of all three clinical manifestations of atherosclerosis. Between 1990 and 2019, both the mortality rate and DALYs for IHD and ischemic stroke declined across all age groups. Overall, the burden of atherosclerosis-related diseases has not significantly decreased and even shows signs of trending upward. These findings strongly suggest that despite some progress made, efforts to control atherosclerosis diseases globally need to be intensified.

Introduction

Atherosclerosis is a chronic inflammatory disease of medium and large arteries that can cause ischemic heart disease (IHD), ischemic stroke, and peripheral arterial disease (PAD).^[1] During the middle of the 20th century, the mortality rates from IHD and stroke have fallen dramatically in the majority of high-income nations.^[2] Nevertheless, IHD remains the leading cause of premature adult mortality worldwide.^[3] Additionally, most low- and middle-income countries have reported declines in stroke mortality over the past few decades, but trends in IHD mortality have been mixed, with some nations reporting increases and other nations reporting decreases (especially in some Eastern European and Asian nations).^[2,4]

Eating habits and lifestyles in low- and middle-income nations have drastically changed because of globalization. The most prevalent feature of globalization is the gradual substitution of a plant-based diet with the unhealthy diet, which is characterized by meals derived from animals and foods with a lot of added sugars.^[5] The decline in cardiovascular disease (CVD) mortality is also partially attributable to changes in health habits, such as smoking cessation and the application of medications for modifiable risk factors (hypertension and dyslipidemia). ^[6,7,8] However, it is unknown how global changes in pertinent controllable variables in recent years have affected the burden of atherosclerosis.

In this study, we determined the global trends in the atherosclerosis incidence, disability-adjusted life years (DALYs), prevalence, and mortality by every decade since 1990, then we identified the year with the most substantial changes in trends of these indicators. The global trends were stratified by age group, gender, and sociodemographic index (SDI), and trends at the global and national levels are reported.

Methods

Study population and data collection

For this analysis of the Global Burden of Disease Study (GBD) 2019, we obtained repeated cross-sectional data from the Global Health Data Exchange (GHDx), which includes the global burden of 369 diseases and injuries in 204 countries and territories from 1990 to 2019,^[9] including IHD, ischemic stroke, and PAD.

In accordance with the GBD project definition of atherosclerosis, information on these three clinical manifestations of the disease was gathered from both genders, people of all ages, and regional groupings in 21 countries with similar epidemiologic characteristics and geographic proximity. To describe the burden of different age stages for coronary atherosclerosis in more detail, we used age subgroups by 20–54 years and ≥55 years.

The SDI, a composite indicator of the social and economic factors influencing health outcomes in each locality, was computed by GBD 2019 for each nation. The SDI is the geometric mean of indices ranging from 0 to 1 for total fertility among people <25 years of age, the average years of schooling for people >15 years of age, and the lagged distributed income per capita,^[9] where 0 denotes the combination of the highest fertility, the fewest years of schooling, and the lowest income per capita. Five quintiles (low, medium–low, medium, medium–high, and high) are used to categorize the SDI.

The number of incident and prevalent cases, deaths, DALYs, incidence, and prevalence were obtained from the GBD 2019. Every rate is shown per 100,000 people. The 2.5th and 97.5th values of the ordered 1000 estimates created using the GBD technique served as the 95% uncertainty interval (UI) boundaries. In earlier investigations, specific details of the approach used in GBD 2019 have been described.^[9]

The Institutional Review Board of Beijing Friendship Hospital concluded that the study did not require approval because publicly available data were used. This study followed the Guidelines for Accurate and Transparent Health Assessment Reporting.

Statistical analysis

The initial goal of the study was to determine global trends in the prevalence, mortality, and years of life with a disability-adjusted life expectancy for the three clinical presentations of atherosclerosis. We used linear regression with rates on a logarithmic scale as the dependent variable and each year as the independent variable to determine age-specific rates and the average annual percentage changes (AAPCs). AAPCs are weighted averages of annual percentage changes (APCs), which allow us to use a single number to depict the typical APC across a multi-year period. AAPCs are summary measures of trends within pre-specified fixed intervals. The geometric weighted average of the percentage change values for each year in the regression analysis was used to calculate the APC. The AAPC value represents the percentage change for each year (increase, reduction, or no change). For example, if the AAPC is 0.1, then a 0.1% yearly growth rate is implied. The AAPC value and the 95% confidence interval (CI) show the trend in morbidity. AAPCs were calculated for the periods 1990–1999, 2000–2009, 2010–2019, and 1990–2019.

Finding the year with the biggest shifts in the trends of the aforementioned indicators was the second study goal. We connected multiple different line segments on a logarithmic scale to create the simplest model we could to match the data using joinpoint regression analysis to spot trends in the data over time. The simplest model (i.e., the model with zero joinpoints) is a straight line. These segments are referred to as joinpoints. Each joinpoint is checked using the Monte Carlo permutation approach as additional joinpoints are added. The final model of the joinpoint program was chosen using the authors' expert knowledge and the Weighted Bayesian Information Criterion approaches.

The third goal was to stratify world trends by age group, gender, and SDI. The fourth goal was to report global and national patterns. We followed the same procedure as the AAPC stated earlier for this purpose. The results of statistical tests with effect size and CI, rates, UIs, and precise P-values (estimated at a significance level of 0.05) were given and interpreted.^[10,11] The easyGBD package and the R software (R Core Team, version 4.2.1, Vienna, Austria) were used for all statistical studies.

Results

Global trends

The global IHD incidence decreased between 1990 and 1999 (AAPC, –0.09; 95% CI, –0.16 to –0.02), increased between 2000 and 2009 (AAPC, 0.05; 95% CI, –0.02 to 0.12), and continued to increase, and with the rate of increase even more pronounced between 2010 and 2019 (AAPC, 0.83; 95% CI, 0.71–0.95). Overall, the IHD incidence increased between 1990 and 2019 (AAPC, 0.20; 95% CI, 0.12–0.28). The IHD prevalence and mortality also increased between 2010 and 2019, but the mortality decreased between 1990 and 2019. The DALYs decreased in all periods [Table 1]. Joinpoint regression analysis showed that the years with greater changes in the IHD prevalence, incidence, mortality rate, and DALYs were 1995, 2001, 2005, 2010, and 2017; 1995, 2000, 2005, and 2010; 1994, 2003, and 2014; and 1994, 2003, and 2006, respectively [Figure 1].

Table 1.

Global AAPCs in prevalence, incidence, mortality, and DALYs of atherosclerosis-related diseases (IHD, ischemic stroke, and PAD).

Items	Incidence		Prevalence			Mortality			DALYs
	AAPC (95% CI)	P-value	AAPC (95% CI)	P-value		AAPC (95% CI)	P-value		AAPC (95% CI)	P-value
IHD
1990–1999	–0.09 (–0.16 to –0.02)	0.017	0.31 (0.30–0.32)	<0.001		–0.54 (–0.85 to –0.22)	0.001		–0.71 (1.04 to –0.39)	<0.001
2000–2009	0.05 (–0.02 to 0.12)	0.194	0.40 (0.36–0.43)	<0.001		–0.40 (–0.73 to –0.06)	0.019		–0.76 (–1.05 to –0.46)	<0.001
2010–2019	0.83 (0.71–0.95)	<0.001	1.31 (1.26–1.37)	<0.001		0.39 (0.23–0.55)	<0.001		–0.45 (–0.57 to –0.32)	<0.001
1990–2019	0.20 (0.12–0.28)	<0.001	0.67 (0.66–0.69)	<0.001		–0.20 (–0.30 to –0.11)	0.106		–0.71 (–0.76 to –0.67)	<0.001
Ischemic stroke
1990–1999	–0.13 (–0.20 to –0.06)	<0.001	–0.40 (–0.41 to –0.38)	<0.001		–0.17 (–0.58 to 0.25)	0.433		–0.41 (–0.79 to –0.03)	0.033
2000–2009	0.21 (0.15–0.26)	<0.001	0.42 (0.39–0.46)	<0.001		–0.93 (–1.32 to –0.54)	<0.001		–1.07 (–1.42 to –0.72)	<0.001
2010–2019	1.61 (1.57–1.65)	<0.001	1.55 (1.34–1.76)	<0.001		0.49 (0.29–0.68)	<0.001		0.02 (–0.08 to 0.12)	0.701
1990–2019	0.43 (0.39–0.48)	<0.001	0.68 (0.60–0.77)	<0.001		–0.26 (–0.47 to –0.05)	0.015		–0.52 (–0.76 to –0.29)	<0.001
Peripheral artery disease
1990–1999	–0.65 (–0.69 to –0.61)	<0.001	–0.77 (–0.82 to –0.72)	<0.001		1.35 (1.19–1.51)	<0.001		0.09 (–0.02 to 0.21)	0.098
2000–2009	–0.01 (–0.03 to 0.02)	0.584	0.05 (0.02–0.08)	<0.001		0.94 (0.89–0.98)	<0.001		0.09 (0.05–0.13)	0.001
2010–2019	0.91 (0.85–0.97)	<0.001	1.01 (0.96–1.07)	<0.001		1.70 (1.61–1.79)	<0.001		0.86 (0.75–0.98)	<0.001
1990–2019	0.13 (0.06–0.21)	<0.001	0.14 (0.05–0.22)	<0.001		1.25 (1.18–1.32)	0.001		0.31 (0.28–0.33)	0.001

AAPC: Average annual percentage change; CI: Confidence interval; DALYs: Disability-adjusted life-years; IHD: Ischemic heart disease; PAD: Peripheral arterial disease.

Figure 1.

Joinpoint regression analysis of global IHD prevalence (A), incidence (B), mortality rate (C), and DALYs (D) in adults ≥20 years of age from 1990 to 2019. ^*P <0.05. APC: Annual percentage change; DALYs: Disability-adjusted life years; IHD: Ischemic heart disease.

The global incidence of ischemic stroke decreased between 1990 and 1999 (AAPC, –0.13; 95% CI, –0.20 to –0.06), increased between 2000 and 2009 (AAPC, 0.21; 95% CI, 0.15–0.26), and increased at a greater rate between 2010 and 2019 (AAPC, 1.61; 95% CI, 1.57–1.65). Overall, the ischemic stroke incidence increased between 1990 and 2019 (AAPC, 0.43; 95% CI, 0.39–0.48). The prevalence of ischemic stroke followed the same pattern, but the mortality rate and DALYs due to ischemic stroke decreased in all periods except 2010–2019 [Table 1]. Joinpoint regression analysis identified a substantial increase in the global prevalence and incidence of ischemic stroke in 2006 and 2005, respectively. The years with a greater ischemic stroke mortality rate and DALYs were 1994, 1998, 2003, 2007 and 2014, and 1994, 1998, 2003, 2007, and 2014, respectively [Figure 2].

Figure 2.

Joinpoint regression analysis of global ischemic stroke prevalence (A), incidence (B), mortality rate (C), and DALYs (D) in adults ≥20 years of age from 1990 to 2019. ^*P <0.05. APC: Annual percentage change; DALYs: Disability-adjusted life years.

The global incidence of PAD decreased between 1990 and 1999 (AAPC, –0.65; 95% CI, –0.69 to –0.61), albeit at a slower rate, decreased between 2000 and 2009 (AAPC, –0.01; 95% CI, –0.03 to 0.02), and increased rapidly between 2010 and 2019 (AAPC, 0.91; 95% CI, 0.85–0.97). Overall, the PAD incidence increased between 1990 and 2019 (AAPC, 0.13; 95% CI, 0.06–0.21). The PAD prevalence, mortality rate, and DALYs increased in all periods except the PAD prevalence between 1990 and 1999 [Table 1]. Joinpoint regression analysis identified a substantial increase in the global prevalence and incidence of PAD in 2004 and 2009, respectively. However, both the mortality rate and DALYs were on a progressive upward trend [Figure 3].

Figure 3.

Joinpoint regression analysis of global PAD prevalence (A), incidence (B), mortality rate (C), and DALYs (D) in adults ≥20 years of age from 1990 to 2019. ^*P <0.05. APC: Annual percentage change; DALYs: Disability-adjusted life years; PAD: Peripheral arterial disease.

Global trends by gender

There were global increases in IHD incidence from 1990 to 2019 in both males and females, with an AAPC of 0.26 (95% CI, 0.15–0.38) in males and 0.18 (95% CI, 0.09–0.26) in females. There were decreases in the IHD DALYs in both males (AAPC, –0.55; 95% CI, –0.69 to –0.41) and females (AAPC, –0.70; 95% CI, –0.86 to –0.55) [Table 2]. The ischemic stroke measures nearly followed the same pattern, but the PAD incidence, prevalence, mortality rate, and DALYs were all increased in both genders.

Table 2.

Prevalence, incidence, mortality, and DALYs of atherosclerosis-related diseases and their AAPCs from 1990 to 2019 at different levels.

Items	Incidence		Prevalence		Mortality		DALYs
	AAPC (95% CI)	P-value	AAPC (95% CI)	P-value	AAPC (95% CI)	P-value	AAPC (95% CI)	P-value
IHD
Sex
Male	0.26 (0.15–0.38)	<0.001	0.70 (0.68–0.72)	<0.001	–0.07 (–0.23 to 0.08)	0.357	–0.55 (–0.69 to –0.41)	<0.001
Female	0.18 (0.09–0.26)	<0.001	0.64 (0.62–0.65)	<0.001	–0.26 (–0.44 to –0.09)	0.003	–0.70 (–0.86 to –0.55)	<0.001
Age groups
20–54 years	0.36 (0.27–0.45)	<0.001	0.65 (0.62–0.68)	<0.001	–0.25 (–0.37 to –0.12)	<0.001	–0.27 (–0.39 to –0.15)	<0.001
≥55 years	–0.51 (–0.59 to –0.44)	<0.001	–0.05 (–0.06 to –0.03)	<0.001	–0.87 (–1.01 to –0.72)	<0.001	–1.22 (–1.37 to –1.07)	<0.001
SDI
Low	–0.03 (–0.12 to 0.05)	0.421	0.07 (0.05–0.09)	<0.001	–0.38 (–0.40 to –0.35)	<0.001	–0.50 (–0.67 to –0.34)	<0.001
Low-middle	0.73 (0.64–0.83)	<0.001	0.95 (0.94–0.96)	<0.001	0.75 (0.66–0.83)	<0.001	0.17 (–0.11 to 0.46)	0.226
Middle	1.33 (1.20–1.45)	<0.001	1.39 (1.35–1.44)	<0.001	1.18 (1.11–1.24)	<0.001	0.34 (0.28–0.40)	<0.001
High-middle	0.24 (0.10–0.38)	0.001	0.70 (0.65–0.74)	<0.001	–0.12 (–0.39 to 0.15)	0.385	–0.83 (–1.14 to –0.52)	<0.001
High	–0.93 (–1.04 to –0.82)	<0.001	–0.03 (–0.07 to 0.01)	0.101	–1.58 (–1.72 to –1.43)	<0.001	–2.31 (–2.46 to –2.16)	<0.001
Ischemic stroke
Sex
Male	0.70 (0.66–0.74)	<0.001	0.78 (0.69–0.88)	<0.001	0.24 (0.05–0.43)	0.015	–0.13 (–0.30 to 0.05)	0.152
Female	0.30 (0.27–0.32)	<0.001	0.49 (0.44–0.53)	<0.001	–0.44 (–0.67 to –0.20)	<0.001	–0.67 (–0.84 to –0.51)	<0.001
Age groups
20–54 years	0.49 (0.43–0.55)	<0.001	0.45 (0.17–0.74)	0.002	–0.25 (–0.51 to 0.01)	0.055	–0.07 (–0.24 to 0.10)	0.394
≥55 years	–0.24 (–0.26 to –0.21)	<0.001	0.01 (–0.02 to 0.04)	0.583	–0.88 (–1.11 to –0.65)	<0.001	–1.07 (–1.24 to –0.91)	<0.001
SDI
Low	–0.20 (–0.27 to –0.13)	<0.001	–0.10 (–0.16 to –0.04)	0.002	–0.09 (–0.20 to 0.01)	0.088	–0.21 (–0.26 to –0.17)	<0.001
Low-middle	0.88 (0.81–0.95)	<0.001	0.78 (0.73–0.83)	<0.001	0.91 (0.75–1.07)	<0.001	0.48 (0.35–0.60)	<0.001
Middle	1.61 (1.55–1.67)	<0.001	1.39 (1.33–1.45)	<0.001	1.23 (1.08–1.38)	<0.001	0.61 (0.51–0.72)	<0.001
High-middle	0.44 (0.38–0.51)	<0.001	0.57 (0.54–0.60)	<0.001	–0.33 (–0.65 to –0.01)	0.044	–0.80 (–1.10 to –0.50)	<0.001
High	–0.63 (–0.71 to –0.55)	<0.001	0.33 (0.22–0.45)	<0.001	–1.42 (–1.58 to –1.25)	<0.001	–1.74 (–1.86 to –1.63)	<0.001
Peripheral artery disease
Sex
Male	0.18 (0.15–0.20)	<0.001	0.23 (0.21–0.25)	<0.001	1.38 (1.31–1.45)	<0.001	0.52 (0.46–0.57)	<0.001
Female	0.02 (0–0.03)	0.033	0.03 (0.01–0.05)	0.003	1.27 (1.18–1.36)	<0.001	0.19 (0.13–0.25)	<0.001
Age groups
20–54 years	0.30 (0.24–0.36)	<0.001	0.26 (0.19–0.33)	<0.001	0.54 (0.42–0.66)	<0.001	0.47 (0.38–0.56)	<0.001
≥55 years	–0.68 (–0.70 to –0.66)	<0.001	–0.65 (–0.68 to –0.63)	<0.001	0.59 (0.53–0.65)	<0.001	–0.31 (–0.35 to –0.27)	<0.001
SDI
Low	–0.07 (–0.08 to –0.05)	<0.001	–0.03 (–0.05 to –0.02)	<0.001	0.78 (0.66–0.9)	<0.001	0.27 (0.17–0.36)	<0.001
Low-middle	0.64 (0.63–0.66)	<0.001	0.78 (0.76–0.80)	<0.001	2.83 (2.74–2.93)	<0.001	1.15 (1.13–1.18)	<0.001
Middle	1.22 (1.21–1.23)	<0.001	1.39 (1.38–1.41)	<0.001	2.66 (2.63–2.69)	<0.001	1.10 (1.07–1.14)	<0.001
High-middle	0.37 (0.35–0.39)	<0.001	0.49 (0.45–0.54)	<0.001	1.32 (1.24–1.40)	<0.001	0.38 (0.30–0.45)	<0.001
High	–0.46 (–0.51 to –0.41)	<0.001	–0.40 (–0.46 to –0.33)	<0.001	2.00 (1.90–2.10)	<0.001	0.64 (0.59–0.69)	<0.001

AAPC: Average annual percentage change; CI: Confidence interval; DALYs: Disability-adjusted life-years; IHD: Ischemic heart disease; SDI: Sociodemographic index.

Global trends by age group

The global decrease in IHD incidence between 1990 and 2019 was observed in individuals aged ≥55 years (AAPC, –0.51; 95% CI, –0.59 to –0.44). However, the incidence of IHD increased in individuals aged 20–54 years during this period (AAPC, 0.36; 95% CI, 0.27–0.45). The IHD mortality rate and DALYs decreased in both age groups. The ischemic stroke and PAD results were similar to IHD, except the PAD DALYs, which increased in individuals aged 20–54 years (AAPC, 0.47 [0.38–0.56]) and decreased in individuals aged ≥55 years (AAPC, –0.31; 95% CI, –0.35 to –0.27) [Table 2].

Global trends by SDI

The largest decrease in IHD incidence by SDI quintile was observed in the high-SDI quintile (AAPC, –0.93; 95% CI, –1.04 to –0.82). The low-middle-, middle-, and high-middle-SDI countries all exhibited increasing trends in IHD incidence during this period. The decrease in ischemic stroke incidence by SDI quintile was observed in the high- and low-SDI countries (high-SDI [AAPC, –0.63; 95% CI, –0.71 to –0.55]; low-SDI [AAPC, –0.20; 95% CI, –0.27 to –0.13]). The other SDI quintiles all exhibited increasing trends in the ischemic stroke incidence; the PAD measures were similar. The IHD and ischemic stroke mortality rate and DALYs decreased in the low-, high-middle-, and high-SDI countries, but increased in the low-middle- and middle-SDI countries. The PAD mortality rate and DALYs increased in all SDI quintiles, especially in the low-middle- and middle-SDI countries [Table 2].

National trends

At the national level, the most pronounced increase in the incidence of IHD between 1990 and 2019 occurred in the Northern Mariana Islands (AAPC, 3.37; 95% CI, 3.21–3.53) and the most pronounced increase in the IHD mortality rate between 1990 and 2019 was also in the Northern Mariana Islands (AAPC, 4.13; 95% CI, 3.91–4.35). China also increases fast during this period (incidence rate [AAPC, 2.09; 95% CI, 1.98–2.19]; mortality rate [AAPC, 2.44; 95% CI, 2.29–2.59]). The country with the highest IHD incidence in 2019, however, was Estonia (1539.99/100,000 population; 95% UI, 1332.31–1756.65) and the highest IHD mortality rate in 2019 was Ukraine (928.76/100,000 population; 95% UI, 812.00–1059.06) [Appendix A, http://links.lww.com/CM9/B707]. Notably, the most pronounced increase in the incidence of ischemic stroke between 1990 and 2019 occurred in China (AAPC, 2.84; 95% CI, 2.79–2.89) and its mortality rate also increase (AAPC, 1.99; 95% CI, 1.72–2.26). And, the greatest increase in the ischemic stroke mortality rate occurred in Timor-Leste (AAPC, 2.84; 95% CI, 2.79–2.89). The country with the highest ischemic stroke incidence and mortality rate in 2019 was Bulgaria (incidence [427.44/100,000 population; 95% UI, 369.32–485.93]; mortality rate [359.30/100,000 population; 95% UI, 298.56–425.96]) [Appendix B, http://links.lww.com/CM9/B707]. Between 1990 and 2019, the largest increase in PAD incidence and mortality rate was observed in Northern Mariana Islands (incidence rate [AAPC, 4.19; 95% CI, 4.02–4.35]; mortality rate [AAPC, 6.36; 95% CI, 4.61–8.14]) and the highest incidence and mortality rate in 2019 was in Denmark and Barbados, respectively (incidence [543.25/100,000 population; 95% UI, 465.01–4626.08]; mortality rate [15.13/100,000 population; 95% UI, 7.21–28.00]) Appendix C,http://links.lww.com/CM9/B707]. A moderately elevated trend of PAD incidence and mortality rate was observed in China between 1990 and 2019 (incidence rate [AAPC, 1.77; 95% CI, 1.75–1.80]; mortality rate [AAPC, 3.01; 95%CI, 2.78–3.24]).

Discussion

This is a trend analysis study that explores the global and national burden of atherosclerosis from 1990 to 2019. Our study aim is to provide a comprehensive overview and comparison of the prevalence, incidence, mortality rates, and DALYs of atherosclerosis across the globe and in various nations over the period from 1990 to 2019. From 1990 to 2019, there was an overall increasing trend in the global incidence of all three clinical manifestations of atherosclerosis (ischemic stroke, IHD, and PAD). Between 1990 and 2019, the mortality rate and DALYs for ischemic stroke and IHD declined in all age groups, whereas adults aged 20–54 years were the main driver for the rising incidence of atherosclerosis. Europe countries had the highest overall incidence and mortality rate in 2019, and East Asia countries had the highest increase in atherosclerosis incidence and DALYs between 1990 and 2019. The middle-SDI countries had the largest increase in atherosclerosis incidence and DALYs between 1990 and 2019.

IHD remains a significant threat to public health. Despite the advances in healthcare coverage, medical technology, and early treatment of IHD, our study revealed that the incidence of IHD continued to increase and the decline in mortality rate and DALYs gradually slowed between 1999 and 2019. One of the major factors contributing to the rise in the incidence of IHD is the aging population worldwide. As a result, it is imperative to implement early prevention strategies, which may differ by geographic region. High-SDI countries may need to focus on controlling systolic blood pressure, dietary risk factors, high LDL-cholesterol, high body mass index, and tobacco use,^[12] whereas, in middle-SDI countries, the emphasis may be more on the control of tobacco and ambient particulate matter pollution.^[13] It is important to note that the changes in incidence and mortality rate vary by gender, age, and geographic region. For example, females exhibited a lower rate of increase in the IHD incidence, along with a greater decline in the mortality rate and DALYs, which could be attributed to different CVD risk exposures, such as tobacco smoking.^[14,15] In the past 30 years, both the IHD incidence and mortality rate have declined for the population of ≥55 years of age, highlighting the significance of prevention and early treatment of high-risk individuals. It is concerning, however, that the younger population between 20 and 54 years of age exhibited a constant, rapid increase in the IHD incidence. This trend is consistent with the rise in CVD risk factors, such as hypertension in young adults,^[16] and requires immediate global attention. Central and Eastern Europe, and North and Central Asia were the geographic regions with the highest IHD incidence and mortality rate in 2019, indicating the need for multisectoral interventions that address social and economic factors.^[17]

Ischemic strokes constituted 62.4% of all new strokes in 2019 according to recent data.^[18] Earlier studies reported that ischemic strokes comprise 85% of all stroke cases.^[19] From 1990 to 2019, the total number of incident ischemic stroke cases increased by 87.55% globally.^[20] Our research demonstrated that the ischemic stroke incidence and prevalence climbed steadily over the past three decades, with the mortality rate and DALYs decreasing gradually, following the same pattern as IHD. It is important to note, however, that the burden of ischemic stroke has increased over the past decade, as reflected by a sustained rise in the incidence, prevalence, mortality rate, and DALYs. To address this mounting concern, primary prevention measures must focus on controlling and avoiding the five main risk factors for stroke: high systolic blood pressure, high body mass index, high fasting glucose level, environmental particulate matter pollution, and smoking.^[18] Sustained global efforts in these directions will be crucial in the fight against CVD.

With respect to PAD, our findings revealed a significant increase in the global prevalence, incidence, mortality rate, and DALYs from 1990 to 2019. Interestingly, we also found that the global change in PAD prevalence and incidence initially decreased, then increased after 2004 and 2009. In fact, there were no standardized criteria for PAD diagnosis across different countries^{[21,22,23,24]} until the American Heart Association and American College of Cardiology guidelines recommended that an ankle-brachial index value <0.90 was a reliable diagnostic cut-off value for PAD in 2005. Since then, this cut-off value has been widely adopted in subsequent research for diagnosing PAD.^[25] An insufficient understanding of the PAD diagnosis may have resulted in a large number of undetected cases. Clearly, further investigation into the underlying reasons may require additional comprehensive data support.

The incidence of PAD is declining in high-income Asia Pacific, Australasia, Western Europe, and high-income North America. It is plausible to expect a decline in the incidence of PAD in these areas because there are some similarities in the pathogenesis of PAD and coronary heart disease.^[26] Previous findings showed that the age-adjusted incidence of coronary heart disease was declining over time in developed countries.^[27] In contrast, the incidence of PAD was increasing in some regions, particularly Oceania, East Asia, and Southeast Asia, with China being one of the countries experiencing the most dramatic change in disease incidence worldwide. The health systems in these countries are unable to cope with the increasing burden of PAD, underscoring the importance of primary prevention programs, including multilevel prevention methods at both the population and individual levels, as a key part of mitigating the burden of rising PAD.

Atherosclerosis commonly leading to severe CVDs and strokes, has seen a rising incidence from 1990 to 2019. This rise can be attributed to a variety of factors. Firstly, global aging trends have led to a higher prevalence of the disease, given that age is a significant risk factor for atherosclerosis.^[28] Secondly, modern lifestyle habits, including high-fat diets, lack of exercise, smoking, and excessive alcohol consumption, have increased atherosclerosis risk.^[29] Lastly, there has been a rise in chronic diseases such as diabetes and hypertension, which are significant risk factors for atherosclerosis.^[30] Conversely, the mortality rate of atherosclerosis has been gradually declining. This decline can be connected to advancements in medical technology that allow earlier detection and treatment of the disease.^[28] Moreover, the implementation of public health policies, such as smoking bans, promotion of healthy diets, and regular health check-ups, have increased public awareness and effectively prevented the onset of the disease, further contributing to the decreasing mortality rate.^[29] Simultaneously, the escalating disease burden in regions with low-middle and middle-SDI— China being a prime example— is a significant factor contributing to this outcome. China holds the grim distinction of having the world's largest number of deaths from CVD. Compounding this issue, the incidence and mortality of atherosclerotic CVD saw an upward trend between 1999 and 2019.^[31] Moreover, we also observed that the overall burden of atherosclerosis within China escalated during this period, underscored by a concurrent increase in its AAPC. Several factors contribute to this persistent challenge. Primarily, the rapid urbanization and lifestyle changes accompanying economic development have led to an increased prevalence of risk factors such as obesity, hypertension, and diabetes, all of which contribute to atherosclerosis.^[32] Additionally, the management of these conditions remains suboptimal.^[33] While treatment options have improved, access to healthcare varies widely across regions and socioeconomic groups, potentially leading to disparities in disease management.^[34] Public awareness of cardiovascular health is also relatively low, leading to late-stage diagnoses and poorer health outcomes.^[35] As China's population ages, the burden of atherosclerosis could increase unless targeted measures are taken to address the issue. Addressing the burden of atherosclerosis in China necessitates a multi-faceted approach that acknowledges the complex interplay of lifestyle, healthcare access, and socioeconomic factors. Primarily, public health interventions could aim to reduce the prevalence of risk factors. This could include programs promoting physical activity, healthy eating, and smoking cessation, as well as early detection and management of conditions like hypertension and diabetes.^[36] Secondly, strategies to improve healthcare access are crucial. Telemedicine could be one solution, leveraging digital technology to provide remote patient monitoring and consultations, particularly in rural or under-resourced areas.^[37] Policies should also aim to reduce health disparities, which could include insurance reforms or investments in local healthcare infrastructure to ensure equitable access to care.^[34] Finally, public health education campaigns can help raise awareness about atherosclerosis, encouraging early screening and treatment.^[35] Such comprehensive efforts may help lessen the burden of atherosclerosis across various socioeconomic groups in China.

Our study had several limitations. First, particularly from low- and middle-income countries, the varying quality of GBD data and missing data constrained our analysis. Second, the lack of data on gender minorities in GBD 2019 limited the representativeness of our findings. Third, we solely took into account the year as an independent variable. Finally, the GBD database was the sole source of data for this investigation. Other global databases that compile information from many sources include the Global Health Estimates of the World Health Organization.

In conclusion, the IHD and ischemic stroke mortality rates and DALYs declined in adults globally between 1990 and 2019, consistent with the implementation of advanced public health tools. The continued increase in mortality and DALYs for PAD is associated with a surge in new cases, while treatment guidelines remain incompletely implemented and treatment options are inferior to those for coronary artery disease. Overall, the burden of atherosclerosis-related disease is still not significantly decreasing and is even trending upward, especially in low- and middle-income countries and in younger populations. There is an urgent need for more targeted treatment and management in younger populations and in low-middle and middle-income countries.

Acknowledgements

The authors thank the participants and staff of the GBD database for their valuable contributions.

Funding

This study was supported by grants from the Summit Talent Plan, Beijing Hospital Management Center (No. DFL20190101; Beijing, China).

Conflicts of interest

None.

Supplementary Material

cm9-136-2442-s001.docx ^{(271.3KB, docx)}