Incidence tendency and variation in ALL
Globally, new cases of ALL increased from 66 810 in 1990 to 153 320 in 2019, and the ASIR increased by 1.61 per year (95% CI 1.52~1.71) during this period (Table 1). Males had more opportunities to suffer from ALL than females. And the male-to-female ratio was 1.24 in 1990, then 1.22 in 2019 (Additional file 1: Fig. S1A). Although the ASIR of both sexes continued to climb, males’ ASIR increased more quickly than females’ in most age groups (Table 1, Additional file 1: Fig. S2A).
When we compared SDI regions, the middle SDI region had the highest incidence in 1990 (17 450 cases), while the high-middle SDI region had the highest in 2019 (52 070 cases), with the most rapid growth of ASIR (ASIR: 1.51 in 1990 and 3.39 in 2019, EAPC = 3.08, 95% CI 2.79~3.37; Table 1, Additional file 1: Fig. S3A). High SDI region always had the highest ASIR, and had a significant upward trend from 1990 to 2019 (ASIR: 1.02 in 1990 and 3.52 in 2019, EAPC = 1.72, 95% CI 1.44~2). To our delight, the ASIR of ALL decreased in low-middle and low SDI regions, the latter had the lowest incidence burden (Additional file 1: Fig. S1A, Table 1).
Table 1
Incidence and age-standardized incidence rate per 100 000 people for ALL in 1990 and 2019.
|
|
1990
|
2019
|
1990-2019
|
Characteristics
|
Incident cases
No.×103 (95% UI)
|
ASIR per 100 000
No. (95% UI)
|
Incident cases
No.×103 (95% UI)
|
ASIR per 100 000
No. (95% UI)
|
EAPC in ASIR
No. (95% CI)
|
Overall
|
66.81 (52.91 ,88.25)
|
1.23 (0.99 ,1.58)
|
153.32 (128.58 ,170.55)
|
1.96 (1.64 ,2.17)
|
1.61 (1.52 ,1.71)
|
Sex
|
|
|
|
|
|
Males
|
36.94 (28.12 ,50.27)
|
1.36 (1.06 ,1.79)
|
84.12 (66.44 ,96.18)
|
2.18 (1.73 ,2.49)
|
1.71 (1.62 ,1.81)
|
Females
|
29.86 (22.64 ,51.3)
|
1.11 (0.85 ,1.84)
|
69.19 (52.85 ,82.35)
|
1.75 (1.34 ,2.08)
|
1.49 (1.38 ,1.6)
|
SDI region
|
|
|
|
|
|
High SDI
|
16.41 (13.54 ,17.69)
|
2.03 (1.69 ,2.19)
|
40.1 (34.89 ,45.77)
|
3.52 (3.08 ,4.05)
|
1.72 (1.44 ,2)
|
High-middle SDI
|
16.88 (14.91 ,19.38)
|
1.51 (1.33 ,1.74)
|
52.07 (43.22 ,59.67)
|
3.39 (2.8 ,3.89)
|
3.08 (2.79 ,3.37)
|
Middle SDI
|
17.45 (13.04 ,24.02)
|
0.96 (0.74 ,1.31)
|
37.89 (27.19 ,43.65)
|
1.6 (1.16 ,1.83)
|
2.11 (1.71 ,2.52)
|
Low-middle SDI
|
10.23 (6.64 ,17.14)
|
0.76 (0.52 ,1.2)
|
11.66 (9.86 ,13.98)
|
0.66 (0.56 ,0.8)
|
-0.45 (-0.5 ,-0.41)
|
Low SDI
|
5.8 (2.83 ,13.44)
|
0.78 (0.44 ,1.61)
|
8.03 (5.9 ,10.29)
|
0.59 (0.45 ,0.73)
|
-0.85 (-0.92 ,-0.78)
|
GBD region
|
|
|
|
|
|
High-income Asia Pacific
|
4.31 (3.47 ,5.02)
|
2.47 (2.03, 2.88)
|
11.85 (9.57 ,13.75)
|
5.42 (4.56, 6.33)
|
2.81 (2.52,3.1)
|
High-income North America
|
3.35 (2.81 ,3.58)
|
1.21 (1.02, 1.31)
|
5.3 (4.44 ,6.3)
|
1.32 (1.11, 1.57)
|
0.3 (0.19,0.41)
|
Western Europe
|
11.75 (9.61 ,12.83)
|
3.18 (2.61, 3.51)
|
29.59 (24.84 ,35.04)
|
6.27 (5.29, 7.42)
|
1.95 (1.47,2.44)
|
Australasia
|
0.37 (0.3 ,0.42)
|
1.85 (1.49, 2.1)
|
0.85 (0.65 ,1.12)
|
2.46 (1.89, 3.24)
|
0.55 (0.29,0.82)
|
Tropical Latin America
|
1.9 (1.72 ,2.19)
|
1.13 (1.02, 1.3)
|
2.18 (1.86 ,2.43)
|
1.06 (0.91, 1.2)
|
0.04 (-0.11,0.19)
|
Andean Latin America
|
0.64 (0.5 ,0.85)
|
1.47 (1.19, 1.95)
|
1.12 (0.76 ,1.44)
|
1.78 (1.21, 2.29)
|
0.83 (0.71,0.96)
|
Central Latin America
|
3.1 (2.85 ,3.49)
|
1.66 (1.55, 1.91)
|
5.65 (4.47 ,6.67)
|
2.3 (1.81, 2.71)
|
1.35 (1.25,1.45)
|
Southern Latin America
|
0.65 (0.6 ,0.73)
|
1.29 (1.19, 1.43)
|
1.15 (0.88 ,1.46)
|
1.72 (1.32, 2.17)
|
1.14 (0.99,1.28)
|
Caribbean
|
0.44 (0.33 ,0.64)
|
1.17 (0.88, 1.67)
|
0.6 (0.45 ,0.77)
|
1.31 (0.98, 1.71)
|
0.53 (0.41,0.65)
|
Eastern Europe
|
4.59 (4.21 ,5.2)
|
2.13 (1.93, 2.41)
|
5.4 (4.73 ,6.15)
|
2.28 (2, 2.58)
|
0.17 (-0.35,0.7)
|
Central Europe
|
1.55 (1.32 ,1.7)
|
1.28 (1.11, 1.41)
|
2.93 (2.48 ,3.5)
|
2.15 (1.83, 2.55)
|
1.97 (1.84,2.11)
|
Central Asia
|
0.97 (0.8 ,1.18)
|
1.31 (1.1, 1.55)
|
0.94 (0.78 ,1.13)
|
1.03 (0.86, 1.23)
|
-0.96 (-1.07,-0.85)
|
North Africa and Middle East
|
4.19 (2.56 ,6.39)
|
1.1 (0.71, 1.61)
|
6.18 (4.31 ,7.53)
|
1.08 (0.76, 1.3)
|
-0.17 (-0.31,-0.02)
|
South Asia
|
9.13 (5.64 ,16.27)
|
0.69 (0.45, 1.17)
|
9.3 (7.66 ,11.39)
|
0.51 (0.42, 0.63)
|
-1.29 (-1.39,-1.19)
|
Southeast Asia
|
4.38 (2.83 ,7.09)
|
0.86 (0.59, 1.37)
|
5.21 (4.27 ,6.54)
|
0.82 (0.67, 1.02)
|
-0.14 (-0.18,-0.11)
|
East Asia
|
10.89 (7.67 ,17.42)
|
0.91 (0.65, 1.47)
|
58.11 (39.98 ,69.92)
|
3.73 (2.52, 4.47)
|
5.86 (4.87,6.86)
|
Oceania
|
0.04 (0.02 ,0.06)
|
0.53 (0.34, 0.82)
|
0.07 (0.04 ,0.11)
|
0.5 (0.33, 0.76)
|
-0.34 (-0.48,-0.2)
|
Western Sub-Saharan Africa
|
1.01 (0.64 ,1.53)
|
0.4 (0.28, 0.56)
|
2.04 (1.5 ,2.7)
|
0.37 (0.28, 0.47)
|
-0.33 (-0.42,-0.24)
|
Eastern Sub-Saharan Africa
|
3.09 (1.26 ,8.38)
|
1.05 (0.51, 2.54)
|
4.15 (2.47 ,5.87)
|
0.79 (0.51, 1.06)
|
-0.89 (-1.01,-0.76)
|
Central Sub-Saharan Africa
|
0.3 (0.12 ,0.67)
|
0.39 (0.18, 0.78)
|
0.5 (0.32 ,0.78)
|
0.31 (0.21, 0.48)
|
-0.54 (-0.67,-0.42)
|
Southern Sub-Saharan Africa
|
0.15 (0.11 ,0.2)
|
0.25 (0.2, 0.33)
|
0.2 (0.15 ,0.25)
|
0.25 (0.19, 0.31)
|
-0.01 (-0.08,0.07)
|
† ASIR, age-standardized incidence rate; CI, confidential interval; EAPC, estimated annual percentage change; No., number; UI, uncertainty interval.
|
For GBD regions, East Asia had the highest incidence in 2019, followed by Western Europe, with 58 110 and 29 590 cases, respectively. At the same time, East Asia had the greatest increase in ASIR (EAPC: 5.86, 95% CI: 4.87~6.86), followed by High-income Asia Pacific and Central Europe (Table 1). Notably, South Asia and Central Asia had the most rapid decrease in ASIR of ALL.
At the country or territory level, San Marino had the highest ASIR in 2019 (23.28), 122 times greater than the lowest ASIR (0.19 in Namibia). The ASIR of ALL in four other countries, Italy, Andorra, Monaco, and Spain, was more than 7.0 (Fig. 1A, Additional file 2: Table S2). Further, Taiwan (Province of China) had the fastest growth in ASIR (EAPC = 8.19, 95% CI 7.52~8.88), and Guatemala, South Korea, and Cyprus also presented an obvious increase in ASIR, with all EAPCs above 7.0 (Fig. 1C, Additional file 2: Table S3).
Death tendency and variation in ALL
In general, ALL-related deaths increased slightly from 41 240 in 1990 to 47 650 in 2019, while the ASDR of ALL decreased slightly by 0.57 per year from 0.76 in 1990 to 0.63 in 2019 (Table 2). The number of males died from ALL was 23 950 in 1990 and 28 170 in 2019, higher than females (17 300 in 1990 and 19 480 in 2019). We found the ASDR in both sexes has been decreased, at an annual trend of 0.78/year in females and 0.43/year in males (Table 2, Additional file 1: Fig. S1B).
Table 2
Deaths and age-standardized death rate per 100 000 people for ALL in 1990 and 2019.
|
|
1990
|
2019
|
1990-2019
|
Characteristics
|
Deaths cases
No.×103 (95% UI)
|
ASDR per 100 000
No. (95% UI)
|
Deaths cases
No.×103(95% UI)
|
ASDR per 100 000
No. (95% UI)
|
EAPC in ASDR
No. (95% CI)
|
Overall
|
41.24 (32.02 ,56.59)
|
0.76 (0.61 ,1.02)
|
47.65 (39.37 ,53)
|
0.63 (0.52 ,0.7)
|
-0.57 (-0.65 ,-0.49)
|
Sex
|
|
|
|
|
|
Males
|
23.95 (17.66 ,33.52)
|
0.89 (0.68 ,1.2)
|
28.17 (22.22 ,31.87)
|
0.75 (0.59 ,0.85)
|
-0.43 (-0.53 ,-0.33)
|
Females
|
17.3 (12.07 ,33.43)
|
0.64 (0.46 ,1.2)
|
19.48 (14.98 ,23.25)
|
0.5 (0.39 ,0.61)
|
-0.78 (-0.84 ,-0.72)
|
SDI region
|
|
|
|
|
|
High SDI
|
5.42 (4.48 ,5.72)
|
0.65 (0.54 ,0.69)
|
5.32 (4.72 ,5.8)
|
0.42 (0.38 ,0.46)
|
-1.58 (-1.68 ,-1.49)
|
High-middle SDI
|
10.4 (9.24 ,12.26)
|
0.93 (0.83 ,1.1)
|
10.27 (8.57 ,11.27)
|
0.7 (0.58 ,0.77)
|
-0.9 (-1.01 ,-0.78)
|
Middle SDI
|
13.45 (10.21 ,18.52)
|
0.78 (0.61 ,1.05)
|
17.08 (13.05 ,19.22)
|
0.74 (0.57 ,0.83)
|
0.14 (0 ,0.28)
|
Low-middle SDI
|
7.71 (5.05 ,12.78)
|
0.6 (0.42 ,0.93)
|
8.63 (7.37 ,10.4)
|
0.5 (0.43 ,0.6)
|
-0.61 (-0.66 ,-0.57)
|
Low SDI
|
4.24 (2.11 ,9.66)
|
0.6 (0.35 ,1.21)
|
6.32 (4.7 ,8)
|
0.49 (0.38 ,0.6)
|
-0.74 (-0.79 ,-0.7)
|
GBD region
|
|
|
|
|
|
High-income Asia Pacific
|
1.17 (0.95 ,1.27)
|
0.69 (0.55, 0.75)
|
1.01 (0.78 ,1.1)
|
0.4 (0.34, 0.44)
|
-1.96 (-2.09,-1.83)
|
High-income North America
|
1.88 (1.59 ,1.96)
|
0.65 (0.55, 0.67)
|
2.13 (1.86 ,2.34)
|
0.47 (0.42, 0.52)
|
-1.09 (-1.16,-1.03)
|
Western Europe
|
2.57 (2.07 ,2.74)
|
0.65 (0.53, 0.7)
|
2.36 (2.05 ,2.69)
|
0.41 (0.37, 0.46)
|
-1.83 (-1.93,-1.73)
|
Australasia
|
0.16 (0.13 ,0.17)
|
0.78 (0.64, 0.84)
|
0.14 (0.13 ,0.17)
|
0.42 (0.38, 0.49)
|
-2.61 (-2.87,-2.36)
|
Tropical Latin America
|
1.38 (1.23 ,1.57)
|
0.85 (0.76, 0.97)
|
1.5 (1.27 ,1.65)
|
0.72 (0.61, 0.8)
|
-0.32 (-0.48,-0.16)
|
Andean Latin America
|
0.49 (0.38 ,0.66)
|
1.18 (0.96, 1.56)
|
0.82 (0.55 ,1.05)
|
1.31 (0.88, 1.68)
|
0.55 (0.39,0.7)
|
Central Latin America
|
2.27 (2.1 ,2.55)
|
1.28 (1.2, 1.47)
|
3.66 (2.92 ,4.25)
|
1.49 (1.18, 1.73)
|
0.78 (0.65,0.91)
|
Southern Latin America
|
0.5 (0.46 ,0.55)
|
1 (0.92, 1.11)
|
0.59 (0.52 ,0.64)
|
0.87 (0.77, 0.96)
|
-0.36 (-0.41,-0.32)
|
Caribbean
|
0.32 (0.23 ,0.46)
|
0.87 (0.65, 1.22)
|
0.36 (0.27 ,0.48)
|
0.8 (0.58, 1.09)
|
-0.16 (-0.27,-0.05)
|
Eastern Europe
|
3.26 (3.01 ,3.72)
|
1.48 (1.35, 1.69)
|
2.05 (1.8 ,2.35)
|
0.86 (0.76, 0.98)
|
-2.15 (-2.29,-2.01)
|
Central Europe
|
1.09 (0.94 ,1.19)
|
0.89 (0.77, 0.97)
|
0.7 (0.61 ,0.81)
|
0.51 (0.44, 0.6)
|
-1.87 (-1.94,-1.8)
|
Central Asia
|
0.74 (0.61 ,0.88)
|
1.02 (0.86, 1.2)
|
0.65 (0.55 ,0.78)
|
0.73 (0.61, 0.86)
|
-1.23 (-1.29,-1.18)
|
North Africa & Middle East
|
3.19 (1.96 ,4.85)
|
0.89 (0.58, 1.29)
|
3.61 (2.53 ,4.54)
|
0.64 (0.45, 0.8)
|
-1.12 (-1.16,-1.07)
|
South Asia
|
6.91 (4.34 ,12.22)
|
0.54 (0.36, 0.9)
|
6.9 (5.72 ,8.49)
|
0.39 (0.32, 0.47)
|
-1.45 (-1.57,-1.34)
|
Southeast Asia
|
3.4 (2.24 ,5.5)
|
0.7 (0.49, 1.09)
|
3.93 (3.26 ,4.94)
|
0.63 (0.52, 0.79)
|
-0.34 (-0.38,-0.3)
|
East Asia
|
8.62 (6.08 ,13.97)
|
0.74 (0.53, 1.19)
|
12.14 (8.08 ,14.37)
|
0.82 (0.56, 0.96)
|
0.94 (0.56,1.31)
|
Oceania
|
0.03 (0.02 ,0.05)
|
0.43 (0.29, 0.65)
|
0.05 (0.03 ,0.08)
|
0.41 (0.27, 0.6)
|
-0.36 (-0.48,-0.24)
|
Western Sub-Saharan Africa
|
0.74 (0.48 ,1.1)
|
0.31 (0.22, 0.42)
|
1.5 (1.1 ,2)
|
0.29 (0.22, 0.38)
|
-0.3 (-0.37,-0.22)
|
Eastern Sub-Saharan Africa
|
2.22 (0.93 ,5.84)
|
0.8 (0.41, 1.86)
|
3.01 (1.81 ,4.17)
|
0.61 (0.4, 0.8)
|
-0.85 (-0.97,-0.74)
|
Central Sub-Saharan Africa
|
0.22 (0.09 ,0.49)
|
0.3 (0.15, 0.58)
|
0.37 (0.24 ,0.58)
|
0.25 (0.17, 0.37)
|
-0.48 (-0.6,-0.35)
|
Southern Sub-Saharan Africa
|
0.11 (0.09 ,0.15)
|
0.2 (0.16, 0.26)
|
0.15 (0.12 ,0.19)
|
0.19 (0.15, 0.24)
|
-0.04 (-0.12,0.03)
|
† ASDR, age-standardized death rate; CI, confidential interval; EAPC, estimated annual percentage change; No., number; UI, uncertainty interval.
|
When comparing regions, the most deaths occurred in the middle SDI region (17 080 deaths in 2019), with the highest ASDR (ASDR: 0.74, 95% CI 0.57~0.83) and fastest-growing ASDR (EACP: 0.14, 95% CI 0~0.28). The other four regions showed a decreased tendency. Subgroup analysis of geographical zone indicated that East Asia (8 620 cases) and South Asia (6 910 cases) had the most deaths, with a positive ASDR of 0.94 and a negative ASDR of 1.45, respectively. Also, East Asia had the fastest rise in ASDR (EAPC = 0.94, 95% CI 0.56~1.31), while Australia and Eastern Europe had a remarkable decline trend (EAPC of Australia: -2.61, 95% CI -2·87~-2.36; of Eastern Europe: -2.15, 95% CI -2.29~-2.01; Table 2).
When we compared countries or territories, China and India were the top 2 countries with the most deaths (China: 11 873 in 2019; India: 4 505 in 2019) (Additional file 2: Table S4). Ecuador had the highest ASDR (1.69/100 000) in 2019, while this highest value was 2.22 in Ukraine in 1990 (Fig. 1B, Additional file 2: Table S5, S6). Guatemala had the most rapid increase in ASDR (EAPC: 7.51, 95% CI 6.67~8.35), and it also had a remarkable increase in El Salvador, Lesotho, and Taiwan (Province of China; Fig. 1D, Additional file 2: Table S7).
DALYs tendency and variation in ALL
Globally, compared with 1990, the number of DALYs decreased by about 69 000 in 2019, with 27.3×105 in 1990 and 26.61×105 in 2019. Age-standardized DALYs rate decreased by 0.81 per year (Additional file 2: Table S1). Males were likely the main contributor to ALL DALYs rate. Females not only had a lower age-standardized DALYs rate, but also had a more rapid decrease in this rate (DALYs in 2019, male: 16.07×105, female: 10.54×105; EAPC of age-standardized DALYs rate, male: -0.65, female: -1.06; Table S1, Additional file 1: Fig. S1C).
Subgroup analysis of SDI regions demonstrated that both the highest-burden and lowest decrease of DALYs occurred in the middle SDI region (DALYs: 9.25×105 in 2019, age-standardized DALYs rate: 41.47/100 000 in 2019; EAPC: -0.24, 95% CI: -0.37~-0.11). The ASR of DALYs in the high SDI, high-middle SDI, low-middle SDI, and low SDI regions gradually decreased by 1.75, 1.13, 0.98, and 0.89, respectively.
Comparing GBD region levels, similar to deaths, East Asia had the highest DALYs both in 1990 and 2019 (5.61×105 in 1990 and 5.88×105 in 2019), followed by South Asia. Almost all regions had a negative EAPC except Andean Latin America, Central Latin America, and East Asia. Thereinto, Australasia had the most notable decrease in ASR of DALYs (EAPC: -2.78, 95% CI: -3.02~-2.54; Additional file 2: Table S1). Promisingly, there were five countries’ age-standardized DALYs rate more than 100 (Ukraine: 145.937, Ethiopia, Belarus, Honduras, and Moldova) in 1990, but the highest age-standardized DALYs rate in 2019 was under 100 (Mexico, 98.25, followed by Ecuador, 97.7; Additional file 1: Fig. S4A, Additional file 2: Table S8 and S9). Guatemala's age-standardized DALYs rate grew fastest over the past 30 years (EAPC = 7.33, 95% CI 6.5~8.18; Additional file 1: Fig. S5B, Additional file 2: Table S10).
Influential factors for EAPCs of ALL burden
We found a significant positive correlation between the EAPC of ASIR and baseline ASIR in 1990 (ρ= 0.167, P =0.017) and SDI in 2019 (ρ= 0.357, P =1.7e-07) at the national level (Fig. 2A-2B). However, the reverse relationship between EAPC of ASDR and baseline ASDR in 1990 (ρ= -0.401, P =2.6e-09) and SDI in 2019 (ρ= -0.596, P <2.2e-16) were observed (Fig. 2C-2D). Albeit the ASIR increased significantly in most countries and territories with SDI more than 0.7 in 2019, the corresponding ASDR dropped obviously, which indicated the treatment protocol in high SDI region would be worth learning and promoting in other areas. For EAPC of DALYs, a similar characteristic to ASDR is shown in Additional file (Figure S3).
We then investigated the correlation between SDI and ASIR, ASDR, and age-standardized DALYs rate in 21 GBD regions. Results showed that annual ASIR had remained relatively stable with SDI progressing in most low-burden GBD regions; however, the ASIR presented a steep increase in most high-burden GBD regions, especially East Asia, Western Europe, and High-income Asia Pacific (Fig. 3A). Inversely, the ASDR and age-standardized DALYs rate markedly dropped with SDI development in most GBD regions, especially in high SDI region. Notably, the ASDR and age-standardized DALYs rate rose beforehand and decreased afterward in Central Latin America and Andean Latin America (Fig. 3B, Additional file 1: Fig. S6).
Age characters of ALL
We divided the population into 20 groups according to ages in the global and SDI regional areas: patients aged 0~90 years old were divided into 19 groups, with a component gap of 5-years, and the final group was above 95 years old. Globally, children aged 0~9 years old and the elderly were the most vulnerable populations according to incidence and death rates (Additional file 1: Fig. S7A-S7C), but which presented an obvious disparity referring to SDI regions (Fig. 4A-4B, Additional file 1: Fig. S8). In low-middle and low SDI regions, the ALL burden focused on the population under 25 years old. Conversely, the proportion of patients aged 25 years and older increased gradually from 1990 to 2019 among both sexes in the remained three SDI regions (Fig. 4A, Additional file 1: Fig. S8). In addition, the incidence rate of ALL in young people usually decreased, but increased among the elderly, whose ASIR had almost twice as many as children in 2019 (Fig. 5A, Additional file 1: Fig. S9A). Death rate and DALYs rate in children remained high, but the older patients’ death rate became much higher, even exceeding children, showing a positive correlation with age (Fig. 5B, Additional file 1: Fig. S9B-S9C, S10). The rate of increase in adults was also the fastest; EAPCs of 25-69 years old patients were around 2.5 from Additional file (Figure S2A). Particularly, middle SDI region patients (both sexes) over 60 years old had a higher EAPC in age-standardized death/DALYs rate, while EAPC in children was under 0, presenting hopeful treatment strategies (Additional file 1: Fig. S3B-S3C, S2).
Risk factors contributing to ALL-related deaths or DALYs
Smoking was the predominant contributor to ALL-related DALYs for males across the world, while high body mass index was the main cause of ALL-related DALYs for females in 2019 (Fig. 6A-6C). In high SDI region, the role of smoking in females ALL-related DALYs was greater than the role of high body mass index (Fig. 6B-6C). Occupational exposure to formaldehyde gradually became an important factor from 1990 to 2019, especially in middle, low-middle, and low SDI regions (Fig. 6). Subgroup analysis of the GBD geographic zone suggested that the ratio of high body mass index accounted for an increasing proportion of all risk factors from 1990 to 2019 (Additional file 1: Fig. S11).