The growing trend of vascular intestinal disorder in young individuals: a 20-year analysis

Pojsakorn Danpanichkul^a,b , Yatawee Kanjanakot^c, Siwanart Kongarin^d, Phuuwadith Wattanachayakul^e, Chawin Lopimpisuth^f, Sakditad Saowapa^b, Nattanicha Chaisrimaneepan^b, Priyata Dutta^g, Yanfang Pang^h,i,j, Kwanjit Duangsonk^h

Chiang Mai University, Thailand; Tech University Health Sciences Center, Lubbock, Texas, USA; Mae Fah Luang University, Chiang Rai, Thailand; Chiang Mai University, Thailand; Albert Einstein Healthcare Network, Philadelphia, Pennsylvania, USA; University of Miami/Jackson Memorial Hospital, Miami, Florida, USA; Trinity Health, Ann Arbor, Michigan, USA; Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi China; Key Laboratory of Research on Clinical Molecular Diagnosis for High Incidence Diseases in Western Guangxi, Guangxi, China

^aImmunology Unit, Department of Microbiology, Faculty of Medicine, Chiang Mai University, Thailand (Pojsakorn Danpanichkul); ^bDepartment of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, Texas, USA (Pojsakorn Danpanichkul, Sakditad Saowapa, Nattanicha Chaisrimaneepan); ^cDepartment of Surgery, School of Medicine, Mae Fah Luang University, Chiang Rai, Thailand (Yatawee Kanjanakot); ^dFaculty of Medicine, Chiang Mai University, Thailand (Siwanart Kongarin); ^eDepartment of Medicine, Albert Einstein Healthcare Network, Philadelphia, Pennsylvania, USA (Phuuwadith Wattanachayakul); ^fDepartment of Internal Medicine, University of Miami/Jackson Memorial Hospital, Miami, Florida, USA (Chawin Lopimpisuth); ^gDepartment of Internal Medicine, Trinity Health, Ann Arbor, Michigan, USA (Priyata Dutta); ^hDepartment of Microbiology, Faculty of Medicine, Chiang Mai University, Thailand (Yanfang Pang, Kwanjit Duangsonk); ⁱAffiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi China (Yanfang Pang); ^jKey Laboratory of Research on Clinical Molecular Diagnosis for High Incidence Diseases in Western Guangxi, Guangxi, China (Yanfang Pang)

Correspondence to: Pojsakorn Danpanichkul, MD, Immunology Unit, Department of Microbiology, Faculty of Medicine, Chiang Mai University, Thailand, Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, Texas, USA, e-mail: pojsakorndan@gmail.com

*These are joint first authors

Received 25 November 2023; accepted 8 May 2024; published online 14 June 2024

DOI: https://doi.org/10.20524/aog.2024.0891

Abstract

Background Vascular intestinal disorder (VID) is a condition with a low incidence, but a high mortality risk. The increasing prevalence of substance abuse and metabolic syndrome among young individuals could impact the burden of VID. This study aimed to evaluate the impact of VID on young individuals.

Methods Our study harnessed data from the Global Burden of Disease study, spanning 2000 to 2019. With this extensive dataset, we conducted a comprehensive analysis of the prevalence, mortality rates, and impact on disability-adjusted life years (DALYs) related to VID among young individuals aged 15 to 49 years.

Results Globally, there were an estimated 32,628 cases, 3869 deaths, and 201,099 million DALYs attributed to VID in young individuals. Geographically, the regions of America had the highest burden of VID in young individuals. From 2000-2019, there was an increasing prevalence in all areas, with the most pronounced change observed in Southeast Asia (annual percentage change [APC] +2.17%, P<0.001). Over the study period, there was a more rapid increase in prevalence in males (APC +0.82%, P<0.001) than in females (APC +0.59%, P<0.001). Rates of death and DALYs declined in most regions, except for the Eastern Mediterranean region, where there was a slight increase (APC +0.85%, P<0.001 and 0.88%, P<0.001, respectively).

Conclusion Over the past decade, the burden of VID in young individuals has been increasing, particularly in Southeast Asia and the Eastern Mediterranean region, necessitating immediate and inclusive measures to tackle the rising burden.

Keywords Mesenteric ischemia, vascular disease, epidemiology, gastroenterology

Ann Gastroenterol 2024; 37 (4): 458-465

Introduction

Vascular intestinal disorders (VID), encompassing conditions such as mesenteric ischemia, ischemic colitis and angiodysplasia of the intestine, can present a wide range of clinical symptoms [1]. Traditionally, these disorders were primarily associated with older individuals [2]. However, recent evidence has shown an emergence of these conditions among younger populations [3]. This shift in prevalence may be attributed to the increasing presence of cardiovascular risk factors, including metabolic syndrome, which has increased in recent decades [4-6]. Additionally, there has been a notable increase in the abuse of substances such as cocaine, another risk factor for these conditions in young individuals [7].

Despite these concerning burdens, there has been a lack of a comprehensive global perspective that outlines the epidemiology of VID in young individuals. Recognizing this knowledge gap, we conducted a study to investigate how the prevalence, mortality, and disability-adjusted life-years (DALYs) associated with VID have changed over time in young individuals, specifically from 2000-2019 [8]. Our analysis considers variations in these trends by region, sociodemographic index (SDI), and sex.

Materials and methods

Data source

This study relied on data from the Global Burden of Disease Study (GBD) 2019, which represents a systematic and comprehensive effort to estimate the burden of 369 diseases and 87 risk factors across 204 countries and territories [8]. Our analysis involved the utilization of annual frequencies and age-standardized rates (ASRs) to assess the prevalence, mortality, and disability-adjusted life-years (DALYs) associated with VID in individuals aged 15-49 years. We conducted this assessment over the years 2000-2019, and we further stratified the data by sex, age, region and country. The data were accessed through the GlobalHealth Data Exchange query tool, an online resource maintained by a collaborative effort involving multiple countries and overseen by the Institute for Health Metrics and Evaluation.

Definitions and measures

VID in young individuals is defined as VID diagnosed in patients aged 15-49 years, based on the relevant International Classification of Diseases Tenth Revision (ICD-10) K52 codes. This includes: K55.0 acute vascular disorders of the intestine, K55.1 chronic vascular disorders of the intestine, K55.2 angiodysplasia of the colon, K55.3 angiodysplasia of the small intestine, K55.8 other vascular disorders of the intestine, and K55.9 vascular disorder of the intestine, unspecified [8,9]. The main aim of this study was to assess the overall disease burden of VID in young individuals on a global scale. We categorized the data into 6 regions defined by the World Health Organization (WHO). These regions include Africa, the Eastern Mediterranean, Europe, the Americas, Southeast Asia, and the Western Pacific. We also categorized countries based on their SDI. The SDI is a composite measure that considers various factors, such as per capita incomes, educational attainment and fertility rates, to provide an overall ranking of countries and territories. This categorization allows us to analyze and compare the disease burden across different regions and varying levels of sociodemographic development (Supplementary Table 1). SDI is measured on a scale from 0-1, where 0 signifies the lowest level of development relevant to health, and 1 signifies the highest theoretical level of development. Using these SDI values, countries are classified into 5 categories: high, high-middle, middle, low-middle, and low SDI categories. A separate research study has provided a detailed explanation of the methodology employed to evaluate the disease burden of VID based on the GBD 2019 data [10]. To ensure the accuracy of the data, the GBD 2019 study assessed the quality of data from each country or territory on a scale ranging from 0 (indicating the lowest quality) to 5 (indicating the highest quality). The ratings for data quality related to the causes of death data from each country can be found in Supplementary Table 2. Various statistical techniques were employed to address data heterogeneity, including correction for misclassification, redistribution of garbage codes, and noise reduction algorithms [8].

The annual prevalence of VID was determined using the formula: Prevalence = Number of diagnosed cases/Population size. Here, “number of cases” refers to the count of confirmed VID diagnoses by the end of the year. The mortality rate linked to VID was calculated by dividing the number of deaths attributed to VID-related causes by the population count at the end of the year. The burden of VID in this age group was assessed in terms of DALYs, which comprise the sum of years of life lost (YLL) and years lived with disability (YLD). YLL is calculated as the number of deaths multiplied by the life expectancy at the time of death. YLD is computed as the prevalence of the disease multiplied by a disability weight, representing the severity of the disease on a scale from 0 (indicating total health) to 1 (indicating death). To ensure consistency between mortality rates and DALYs across various causes, we used DisMod-MR 2.1, a Bayesian meta-regression tool. This helped establish a reliable correlation between these 2 measures. Additionally, we conducted a subgroup analysis to explore potential differences between sexes [8].

Statistical analysis

The reported estimates for the frequency of new cases and deaths were accompanied by 95% uncertainty intervals (UIs), representing the range between the 2.5^th and 97.5^th ranked values obtained from,000 draws originating from a posterior distribution. Age-standardized rates were computed using the direct method, employing the GBD 2019 population estimate as a reference [8]. To assess changes in any category between 2000 and 2019, we used the following formula: (Value in 2019 - Value in 2000)/Value in 2000. When examining alterations in age-standardized rates over this timeframe, we computed the annual percentage change (APC) along with its associated 95% confidence interval (CI) using the Joinpoint regression program, version 4.6.1.0, which is maintained by the Statistical Research and Applications Branch at the National Cancer Institute in Bethesda, MD. An increasing trend was identified when both the annualized rate of change and the lower boundary of its 95%CI were positive. Conversely, a decreasing trend was determined when the annualized rate of change and the upper limit were negative.

Results

Global burden of VID in young individuals

Globally in 2019, the numbers of VID-related cases, deaths, and DALYs in patients aged 15-49 years were estimated to be 32,628 (95%UI 22,861-49,024) cases, 3,869 (95%UI 3,482-4,351) deaths, and 201,099 (95%UI 181,017-226,729) DALYs attributable to VID, respectively. In 2019, the estimated VID age-standardized prevalence rate (ASPR), age-standardized death rate (ASDR), and age-standardized DALYs (ASDALYs) in young individuals were 0.83 (95%UI 0.58-1.25), 0.1 (95%UI 0.09-0.11), and 5.11 (95%UI 4.6-5.76), respectively (Table 1). From 2000-2019, ASPR increased, with an APC of 0.71 (95%CI 0.63-0.8, P<0.001). In contrast, ASDR (APC -0.35%, 95%CI -0.45 to -0.26%; P<0.001) and ASDALYs (APC -0.3%, 95%CI -0.38 to -0.23%; P<0.001) decreased (Table 1).

Table 1 Summary of the burden of vascular Intestinal disorder in patients aged 15-49 years and temporal progression from 2000-2019

The burden of VID in young individuals, by sex

In 2019, the number of VID cases in females was estimated at 14,586 (95%UI 10,193-21,879), with 1626 (95%UI 1386-1989) deaths and 85,272 (95%UI 72,406-103,940) DALYs. There were 18,042 (95%UI 12,721-27,102) cases, 2243 (95%UI 2021-2468) deaths, and 115,827 (95%UI 104,489-127,940) DALYs in males aged 15-49 (Table 1). In the given period, ASPR in females increased with an APC of 0.59% (95%CI 0.46-0.72%, P<0.001), whereas in males the increase had an APC of 0.82% (95%CI 0.75-0.89%, P<0.001). In males, ASDR (APC -0.53%, 95%CI -0.62 to -0.44%; P<0.001) and ASDALYs (APC -0.44%, 95%CI -0.52 to -0.37%; P<0.001) decreased. In females, ASDR decreased (APC -0.12%, 95%CI -0.23 to -0.02%; P<0.025), while ASDALYs remained stable.

The burden of VID in young individuals, according to WHO region

The frequency of prevalence, deaths, and DALYs, as well as rates (ASPR, ASDR, and ASDALYs) of VID in young individuals categorized by WHO region, are displayed in Table 1 and Fig. 1A-F. In 2019, the Americas region had the highest VID-related ASR prevalence in young individuals (ASPR 1.22, 95%UI 0.9-1.71) and deaths (ASDR 0.19, 95%UI 0.18-0.2). This region also had the highest VID-related DALYs in young individuals (ASDALYs 9.56, 95%UI 8.91-10.29) (Fig. 1B,1D,1F). Between 2000 and 2019, ASPR increased in all regions, with the highest increase observed in Southeast Asia (APC 2.17%, 95%CI 1.86-2.48%; P<0.001). While ASDRs remained stable in Africa, Southeast Asia and the Western Pacific, they decreased in Europe (APC -0.91%, 95%CI -1.2 to -0.62%; P<0.001) and the region of the Americas (APC -0.27%, 95%CI -0.38 to -0.16%; P<0.001). However, ASDRs increased in the Eastern Mediterranean region (APC 0.85%, 95%CI 0.74-0.96%; P<0.001). Similarly, there was a decrease or stability in ASDALYs attributable to VID in young individuals, except for the Eastern Mediterranean region, where the rates increased (APC 0.88%, 95%CI 0.78-0.99%; P<0.001).

Figure 1 (A) The number of cases of vascular intestinal disorder (VID) in patients aged 15-49 years: cases in 2000 and 2019, stratified by World Health Organization (WHO) region. (B) Age-standardized prevalence rates attributable to VID in patients aged 15-49 in 2000 and 2019, stratified by WHO region. (C) The number of VID-related deaths in patients aged 15-49 in 2000 and 2019, stratified by the WHO region. (D) Age-standardized death rates attributable to VID in patients aged 15-49 in 2000 and 2019, stratified by WHO region. (E) The number of VID-related disabilities in patients aged 15-49 in 2000 and 2019, stratified by WHO region. (F) Age-standardized disability-adjusted life-years attributable to VID in patients aged 15-49 in 2000 and 2019, stratified by WHO region

ASPR, age standardized prevalence rate; ASDR, age standardized death rate; ASDALYs, age standardized disability adjusted life years; DALYs, disability adjusted life years

The burden of VID in young individuals, by SDI

The data related to VID in young individuals, including cases, deaths, and DALYs, as well as ASPR, ASDR and ASDALYs stratified by SDI, are shown in Table 1. In 2019, the highest ASRs of VID cases (ASPR 2.11, 95%UI 1.52-2.99) were observed in high SDI strata, whereas the highest rates of death (ASDR 0.13, 95%UI 0.12-0.14) and DALYs (ASDALYs 6.36, 95%UI 5.86-6.91) in young individuals were observed in high-middle SDI countries (Fig. 2A-C). From 2000-2019, ASPR increased in all SDI strata. Low-middle SDI countries experienced the highest increase in ASPR (APC 1.86%, 95%CI 1.64-2.07%; P<0.001). ASDR decreased in low (APC -0.27%, 95%CI -0.34 to -0.2%; P<0.001), high-middle (APC -0.97%, 95%CI -1.19 to -0.74%; P<0.001), and high (APC -0.81, 95%Cl -0.93 to -0.69%; P<0.001) SDI strata, but increased in low-middle SDI countries (APC 0.31%, 95%CI 0.03-0.59%; P=0.033) and middle SDI countries (APC 0.31%, 95%CI 0.15-0.46%; P<0.001). ASDALYs decreased in low (APC -0.24%, 95%CI -0.32 to -0.16%; P<0.001), high-middle (APC -0.94%, 95%CI -1.14 to -0.74%; P<0.001), and high (APC -0.67%, 95%CI -0.78 to -0.57%; P<0.001) SDI, but increased in low-middle SDI countries (APC 0.3%, 95%CI 0.08-0.53%; P=0.008), and middle SDI strata (APC 0.27%, 95%CI 0.12-0.42%; P<0.001; Table 1).

Figure 2 (A) Age-standardized prevalence rates attributable to vascular intestinal disorder (VID) in patients aged 15-49 in 2000 and 2019, stratified by Sociodemographic Index (SDI). (B) Age-standardized death rates attributable to VID in patients aged 15-49 in 2000 and 2019, stratified by SDI. (C) Age-standardized disability-adjusted life years attributable to VID in patients aged 15-49 in 2000 and 2019, stratified by SDI

ASPR, age standardized prevalence rate; ASDR, age standardized death rate; ASDALYs, age standardized disability adjusted life years; SDI, sociodemographic index

Discussion

The present study is the first that comprehensively assesses the epidemiology of VID among young individuals over the past decades. In 2019, the global incidence of VID cases in young individuals exceeded 30,000. Our findings indicate a notably higher burden of this condition among males. Over 2 decades, we observed an upward trend in the prevalence rates of VID, coupled with an increase in mortality and disability rates, particularly prominent in the Eastern Mediterranean region.

Consistent with earlier investigations, our study uncovered a comparatively lower disease burden associated with VID in young individuals, compared to the broader population and the elderly demographic [9]. Nonetheless, it is imperative not to underestimate the significance of VID in young individuals. Given its high mortality rate, prompt and accurate diagnosis and timely therapeutic interventions stand as critical cornerstones in addressing this condition [11]. Moreover, it is worth noting that, while some risk factors for VID overlap with those observed in older individuals, such as atherosclerotic risk factors, there are unique contributors in the younger demographic [6]. For instance, autoimmune diseases such as systemic lupus erythematosus heighten the risk of mesenteric ischemia, a subtype of VID [12,13]. In terms of sex, our study found that the burden of VID in males was lower than in females, which was consistent with previous study conducted in the older population using the same database [9,14]. However, previous cohort studies reported that the burden was higher in females compared to males; this could be due to differences in the methodologies used in the 2 studies [15,17]. Importantly, these studies were conducted in the general population, which patients with VID tend to be middle-aged or older individuals, rather than young individuals [16]. Therefore, it is plausible to consider VID in young individuals as a potentially distinct entity, albeit sharing some etiological factors with older individuals. This area remains relatively unexplored, warranting further research to elucidate the precise distinctions and commonalities between these populations.

In addition to the noted increase in the age-adjusted prevalence rate of VID in young individuals, a simultaneous decrease in age-adjusted death and DALY rates was observed. This trend held true across most regions, except for the Eastern Mediterranean region, where rising mortality and DALYs rates were observed. Regarding pathophysiology, regardless of etiology, VID arises from an imbalance between the oxygenation supply and demand of the intestine, and the etiology includes blood loss, thromboembolism, hypercoagulable state, substance use (such as cocaine-induced vasoconstriction), and atherosclerotic risk factors [1,18,19]. Therefore, the upsurge in prevalence can be partially attributed to shifts in the landscape of metabolic risk factors and changing demographics, such as the increasing prevalence of obesity among young populations over the past few decades [19,20]. Nevertheless, the heterogeneity of the ICD-10 code in this umbrella term makes it difficult to quantify the exact root cause. However, it is important to note that the pathophysiology of VID is heterogeneous, varying between conditions such as mesenteric ischemia and angiodysplasia of the colon. Despite some shared pathophysiological aspects, there are also non-overlapping features. A notable limitation is that GBD 2019 combines these conditions into a single category, potentially masking crucial distinctions between them. To address this knowledge gap, there is a clear need for more extensive cohort studies that can provide more accurate and granular epidemiological and pathophysiological data. Such research endeavors are crucial to unravelling the complexities of VID in young individuals and developing targeted interventions for specific subtypes.

Our study has illuminated significant regional disparities in the burden of VID among young individuals. The Americas have emerged as the region with the highest burden of this condition, while Southeast Asia has experienced the most substantial increase in its prevalence. Notably, mortality and DALY rates have generally declined across regions, except for an observed increase in the Eastern Mediterranean region. These variations may be attributed to differences in healthcare infrastructure and detection systems for this condition, and an increased prevalence of metabolic syndrome in these regions [21]. However, it is essential to underscore the heterogeneous nature of the etiology of VID, even when classified under the same ICD-10 code. The underlying pathophysiology can vary significantly and may include factors such as vasculitis, hypercoagulable states, trauma, atherosclerosis and aneurysms. Further comprehensive research is needed to better understand these distinct entities and their respective contributions to the overall burden. Further studies, including the next cycle of GBD that provided more granularity of the individual cause under the umbrella term of VID, could be highly beneficial and help strategize further trajectories in the field. Moreover, while the increasing burden of VID in the Americas deserves attention, we must not let it overshadow the declining trends observed in other regions. It is crucial to acknowledge the methodological approach of the GBD study, which estimates mortality and morbidity due to a single cause of disease. In the case of VID, it is often a consequence of other underlying diseases rather than a primary cause.

Therefore, there is an immediate and critical need for the development of policies and strategies to mitigate the burden of VID among young individuals, especially in regions where the burden is high and increasing. These efforts should consider the multifaceted nature of the condition and the specific risk factors contributing to its occurrence.

There are a few limitations in our research that need to be mentioned. Firstly, our study critically relies on estimates sourced from the GBD study, and consequently, it inherits any inherent constraints associated with these estimates. The precision of GBD estimates is intrinsically tied to the quality and comprehensiveness of each country’s vital registration systems. In regions with deficient data sources, GBD estimates predominantly hinge on modeling methodologies, predictive variables, historical trends or extrapolations from neighboring geographic areas. Secondly, the elusive nature of VID, characterized by diagnostic challenges, may introduce an element of underestimation in portraying its genuine burden. Thirdly, it is essential to acknowledge that the GBD estimation methods, predominantly grounded in ICD-10, can potentially introduce an inherent underestimation of the actual disease burden. Lastly, our descriptive study possesses limitations regarding granularity. Specifically, it lacks detailed insights into various risk factors that could differentiate conditions like angiodysplasia from mesenteric ischemia. Such differentiations are pivotal for comprehensively understanding the burden associated with these distinct disorders [22].

In summary, the prevalence of VID amongst young individuals witnessed a significant surge from 2000 to 2019, with a more pronounced burden in males. Nearly every nation had a marked increase in VID prevalence over 2 decades. This rise should trigger significant alarm, and the development of strategies to deal with the possible risk factors.

Summary Box

What is already known:

Vascular intestinal disorder (VID) is a condition with high mortality and morbidity
VID commonly occurs in older individuals, but little is known about the epidemiology of this condition in young individuals

What the new findings are:

Prevalence rates of young individuals living with VID are increasing globally
Mortality rates declined globally over the period 2000-2019, but increased in people living in the Eastern Mediterranean region
Young males have a higher prevalence compared to young females

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Notes

Conflict of Interest: None