As presented in Table 1, the incidence cases of infective endocarditis reached 1,090,530(95% certainty interval [CI]: 913,500-1,296,290) in 2019, while there were 478,000 incidence cases (95% CI: 393,390–572,420) in 1990. The age-standardized incident rate (ASIR) changed from 9.91(95% CI :8.24–11.84) per 100,000 population in 1990 to 13.80(95%CI:11.59–16.34) in 2019 which showed an upward trend worldwide (EAPC, 1.2; 95% CI: 1.16–1.24). In the past thirty years, the incidence of IE in different SDI (Socio-demographic index) regions was rising in a relatively stable trend, whether male or female, and the incidence of male was higher than female (males: EAPC, 1.4; 95% CI: 1.36–1.45; females: EAPC, 0.96; 95% CI, 0.93-1.00) (Fig. 1A, Table 1).
Around the world, due to the imbalance and variety of economy, geography and many other factors, the incidences in different areas are naturally divergent. In 1990, the high-middle SDI region held the most ASIR (11.34 per 100,000 population [95%CI: 9.44–13.59]), though the middle SDI region had the most incidence cases (159,200 [95%CI: 130,200 − 191,000]). And the incidence case or ASIR of low SDI region were the lowest at that time (incidence case:30,590 [95%CI: 24,430 − 38,070] ASIR: 6.29 per 100,000 population [95%CI: 5.23–7.50]) (Table 1). In 2019, although the number of incidence case of IE had almost doubled and ASIR had increased by 1–4 per 100,000 population compared to 1990, the distribution of the SDI regions with the highest case or ASIR remained unchanged. Moreover, the low-SDI region had the lowest number of incident cases and ASIR in both 1990 and 2019. (Table 1). Among the 21 regions divided according to geographical characteristics, the ASIRs of East Asia (13.93 per 100,000 population [95%CI: 11.51–16.57]), North Africa and Middle East (11.47 [95%CI: 9.62–13.59]), Western Europe (11.29 [95%CI: 9.30-13.75]) and Australasia (11.24 [95%CI: 9.32–13.52]) were relatively high, and the ASIR of South Asia (5.02[95%CI: 4.07–6.12]) and Central Asia (5.19 [95%CI: 4.11–6.47]) were relatively low in 1990 (Table 1). In 2019, Tropical Latin America (24.25 per 100,000 population [95%CI: 19.88–29.56]), Southern Latin America (20.55 [95%CI: 17.67–23.68]) and Western Europe (18.06 [95%CI: 15.32–21.34]) maintained high levels of ASIR, while the ASIR of Central Asia (6.35 [95%CI: 5.12–7.83]), South Asia (7.11 [95%CI: 5.79–8.64]) and Sub-Saharan Africa (about 6.8) had low ASIR (Fig. 3A, Table 1). The EAPC of ASIR in our datasets were positive in most regions apart from Western Sub-Saharan Africa and Southern Sub-Saharan Africa, which signifies that the incidence of IE was on the rise in the past 30 years in most regions. And South America and Western Europe had high growth rates, while the growth rates in South Asia, Central Asia and Sub-Saharan Africa were relatively low (Fig. 3D). The top three countries with the highest incidence of IE, Saint Lucia, Grenada, and Barbados are all island nations (Fig. 3A). In Fig. 4A, ASIR and SDI are positively correlated (R = 0.58, P < 0.0001), which seems to just verify our results above. In other words, ASIR seems to be higher in relatively developed regions.
Worldwide, there were 28,750 deaths (95%CI: 24,370 − 35,700) in 1990 and 66,320 deaths (95% CI: 46,210 − 75,860) in 2019 (Table 2). The age-standardized death rate (ASDR) (Fig. 3B) and their changing trends varied among different countries (Fig. 3E). The ASDR (males: EAPC, 0.79; 95% CI, 0.57–1.01; females: EAPC, 0.66; 95% CI, 0.35–0.96) presented an upward trend for both sexes (Table 2). Although the death number in different SDI areas is increasing, their changing trend which means EAPC of ASDR is not all rising. What’s more, female has more deaths from IE than male (males: death,32,630; 95% CI, 22,300 − 37,640; females: death, 33,690; 95% CI, 21,430 − 39,180) in 2019 which probable be due to the more female death number in high SDI region (Fig. 1B, Table 2).
Although the low SDI region had the lowest number of deaths (2,960 [95%CI: 1,830-4,070]) in 1990, the mortality rate (ASDR, 0.9 per 100,000 population [95%CI: 0.55–1.38]) was the highest, and it continues to be the region with the lowest number of deaths (5,070 [95%CI: 3,720-6,610]) in 2019. High SDI region had the highest number of deaths (24,680 [95%CI: 11,730 − 30,810]) and ASDR (1.16 per 100,000 population [95%CI: 0.58–1.43]) at the same time in 2019 (Table 2). The EAPC data of ASDR from 1990 to 2019 showed that there were significant differences in the changes of ASDR in each SDI region in the past 20 years. The ASDR of high SDI region grew fastest (EAPC, 2.01 [95%CI: 1.51–2.51]) while the ASDR of middle (EAPC, -0.62 [95%CI: -0.76- -0.48]) and low SDI regions (EAPC, -0.56 [95%CI: -0.64- -0.48]) is decreasing (Table 2), which is different from the continuous increase of death number in each SDI region in the past 30 years shown in Fig. 1B. Between the 21 regions, Oceania had the lowest number of death in 1990 (40 [95%CI: 20–60]) and 2019 (120 [95%CI: 80–160]), while the region with the highest number of deaths changed from East Asia in 1990 (4,360 [95%CI: 2,730-5,340]) to Western Europe in 2019 (13,790 [95%CI: 6,580 − 17,120]) (Table 2). Furthermore, Southern Latin America and Oceania hold the highest and the second ASDR both in 1990 and 2019 respectively (Fig. 3B, Table 2). Fascinatingly, East Asia which had the most death number in 1990 (4,360 [95%CI: 2,730-5,340]) held the lowest ASDR in 2019 (0.29 per 100,000 population [95%CI: 0.21–0.34]) and became the fastest decline region in ASDR from 1990 to 2019 (EAPC, -2.4 [95%CI: -2.78- -2.02]). The EAPC of ASDR of different regions is also quite heterogeneous, High-income North America (3.26 [95%CI: 2.43–4.09]), Western Europe (2.59 [95%CI: 2.15–3.03]) and Eastern Europe (2.44 [95%CI: 2.05–2.83]) had a relatively high growth rate, while East Asia (-2.4 [95%CI: -2.78- -2.02]) and Western Sub-Saharan Africa (-1.77 [95%CI: -1.99- -1.55]) had a relatively high decline rate (Fig. 3E, Table 2). The ASDR was not correlated with SDI (R = − 0.06, P = 0.10) which means there is no specific relationship between ASDR and SDI even if the high SDI region had the most death number and ASDR in 2019 (Fig. 4B, Table 2).
The number of DALY attributable to IE was on the rise globally from 1990 (1,118,120 [95%CI: 836,790 ~ 1,318,660]) to 2019 (1,723,590 [95%CI: 1,355,670 ~ 1,935,250]) with preference to males (Table 3, Fig. 1C). However, the age-standardized disability-adjusted life years (DALYs) changed from 22.78 (95%CI: 17.98–26.97) per 100,000 population in 1990 to 21.93 (95༅CI: 17.17–24.60) in 2019 around the world and the EAPC of age-standardized DALYs rate was negative whether male or female while the drop was even greater among female (overall: EAPC, -0.21; 95༅CI, -0.35- -0.08; males: EAPC, -0.05; 95% CI, -0.18-0.07; females: EAPC, -0.41; 95% CI, -0.56- -0.25) (Table 3). The middle SDI region got the highest number of DALY both in 1990 and 2019 as the low SDI region had the lowest. What's more, the low SDI region retained the highest at the aspect of age-standardized DALYs rate in 1990 and 2019. The global trend is on the decline, DALY in the high SDI region (1.32 [95༅CI: 0.95–1.7]) only increased significantly though, while the other four SDI regions all decreased, which may be associated with the lowest age-standardized DALYs rate in 1990 of high SDI region (16.27 per 100,000 population [95༅CI: 13.51-24]) (Table 3).
At the regional level, the DALY was found to be highest in East Asia in 1990 (225,160 [95%CI: 123,240–291,150]) and South Asia in 2019 (287,100 [95༅CI: 225,890 − 360,890]) (Table 3). The age-standardized DALYs rates of Southern Latin America (1.38 per 100,000 population [95%CI: 0.94–1.77] in 1990; 1.84 [95༅CI: 1.42–2.16] in 2019), Oceania (1.25 [95%CI: 0.78–2.25] in 1990; 1.64 [95༅CI: 1.13–2.26] in 2019) and Southeast Asia (1.22 [95%CI: 0.97–1.69] in 1990; 1.29 [95%CI: 1.04–1.76] in 2019) were relatively high both in 1990 and 2019, as the age-standardized DALYs rates of East Asia (0.48 [95%CI: 0.31–0.58] in 1990; 0.29 [95༅CI: 0.21–0.34] in 2019), Central Asia (0.21 [95%CI: 0.16–0.27] in 1990; 0.33 [95%CI: 0.28–0.44] in 2019) and Central Europe (0.34 [95%CI: 0.30–0.50] in 1990; 0.48 [95%CI: 0.28–0.59] in 2019) were relatively low (Table 3, Fig. 3C). Eastern Europe (2.81 [95༅CI: 2.35–3.27]) and High-income North America (2.66 [95༅CI: 2.01–3.32]) held the highest number of the EAPC of age-standardized DALYs rate which is congruous with the conclusion above that the high SDI region increased the fastest (Table 3, Fig. 3F).
As showed in Fig. 3B and Fig. 3C, the distribution of countries with the age-standardized DALYs rate and ASDR in 2019 is similar. Kiribati, Fiji and American Samoa are the top 3 countries both in the ranking of ASDR and the age-standardized DALYs rate in 2019. In addition, the countries which held the lowest ASDR like China, Azerbaijan and Armenia had the lowest age-standardized DALYs rate simultaneously. Thailand and Grenada, the country with the first and second place of EAPC of ASIR, is also the second and third place in EAPC of age-standardized DALYs rate. And the country with the biggest change in DALY is Kiribati (Fig. 3F). In Fig. 4C, the SDI negatively correlated with age-standardized DALYs rate (R=-0.40, P < 0.0001) which means that the more developed region is more likely to have low DALY.
Age distribution is likewise a vital parameter of IE epidemiology. Globally, patients aged 50 years or older presented nearly 63% of IE incidence (Fig. 2A) and 79% of IE mortality (Fig. 2B) in 2019, significantly outnumbering the incidence and mortality in 1990 (respectively 35% and 60%). That signified the great disease burden in aged IE patients, especially in relatively developed regions. In contrast, patients aged under 14 years had an evident decline on IE incidence and mortality in 2019 than in 1990 (incidence from 31–12% and mortality from 15–3%), which demonstrated the obviously improved IE affection to young individuals as society progresses. However, the morbidity and mortality of the youngers remained to maintain in relatively high levels in low SDI regions. As for DALYs, although there exhibited an upward trend in the globe (Fig. 2C), the age-standardized DALYs and EAPC were both decreased (Table 3). Interestingly, the IE patients aged under 5 years had a major number of DALY in 1990, but almost decreased to the lowest in 2019, and meanwhile the same changes in this age group were observed in all SDI regions. Generally, despite of varying greatly in different age groups in different regions, the IE burden predominately affected the elders and showed an alleviation in the youngers.
A significant positive association was found between the SDI and EAPC in 2019, regardless of the EAPC of ASIR (r = 0.47, p < 0.001), ASDR (r = 0.35, p < 0.001), or age-standardized DALYs rate (r = 0.32, p < 0.001) (Figs. 5A, Fig. 5B and Fig. 5C). These scatter plots indicate that the more developed region it is, the more changes of disease burden it possibly makes. Furthermore, we analyzed the association between ASIR in 1990 and EAPC of ASRs, all presenting no distinctiveness (Fig. 5D, Fig. 5E, Fig. 5F), which demonstrated the baseline of IE incidence in 1990 produced no significant impact on annual changes of IE burden.