Burden of stroke and risk attributed to smoking in Iran: A Global Burden of Disease Study 2021

Moien AB Khan1, Sohrab Amiri2

1Department of Family Medicine, College of Medicine and Health Sciences, United Arab Emirates University, Al-Ain, United Arab Emirates
2Spiritual Health Research Center, Lifestyle Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran

Keywords: Death, global burden of disease, prevalence, stroke, tobacco smoking.

Abstract

Objectives: This study aimed to provide a report and update on the burden of stroke in Iran and globally and to provide new estimates of disability-adjusted life years (DALYs) and stroke-related deaths attributed to smoking.

Materials and methods: This study was conducted in accordance with the Global Burden of Disease Study 2021. All age and age-standardized estimates of stroke attributed to smoking were calculated for DALYs and death between the years 1990 and 2021. Estimates were based on per 100,000 individuals. The 95% uncertainty interval (UI) was reported for each of the reported estimates.

Results: In 2021, 93 (95% UI 89-99) million stroke cases were detected globally, and 787,178 (95% UI 726,667-855,320) cases were detected in Iran. In 2021, global age-standardized death rate of stroke per 100,000 individuals was 87.45 (95% UI 78.92-94.14), while it was 63.89 (95% UI 56.76-69.69) in Iran. Age-standardized DALYs of stroke per 100,000 individuals in 2021 was 1,886.20 (95% UI 1,738.99-2,017.90) globally and 1,229.18 (95% UI 1,119.52-1,332.60) in Iran. Although the prevalence, incidence, mortality, and disability rates of stroke globally and in Iran decreased between 1990 and 2021, the number of cases increased. In 2021, tobacco use was responsible for over one million deaths worldwide (1,077,804 [95% UI 865,541-1,320,753]), including 4,007 (95% UI 3,159-4,972) in Iran. Compared to 1990, there was an increase in the number of deaths caused by smoking globally (0.52[95% UI 0.31-0.79]) and in Iran (0.20 [95% UI 0.06-0.35]).

Conclusion: The burden caused by stroke on the health system can be significant. Therefore, it is necessary to address the preventable risk factors of stroke, including smoking, which is a major risk factor.

Introduction

Diseases, life expectancy, demographic changes, causes of death, and socioeconomic factors are constantly changing in the world.[1] Globally, stroke is one of the noncommunicable diseases that significantly affects health[2] and is one of the main causes of disability and death worldwide. Stroke remained the second leading cause of death (11.6% of total deaths) and the third cause of death and disability (5.7% of total disability-adjusted life years [DALYs]) in 2019.[3] The costs of poststroke care are high, and 34% of healthcare expenditures are related to stroke.[2,4] The healthcare cost of a patient with stroke in the USA was estimated to be 140,048.[5] The most recently published Global Burden of Disease (GBD) report on stroke shows that stroke as the third most common cause of death at level 3.[6] The global direct and indirect costs of stroke in 2017 were $891 billion, equivalent to 1.12% of global GDP (gross domestic product).[7] Between 1990 and 2019, the incidence of strokes in the world has increased significantly by 70·0% (67·0-73·0), prevalent strokes increased by 85·0% (83·0-88·0), deaths increased by 43·0% (31·0-55·0), and DALYs increased by 32·0% (22·0-42·0).[1] Considering the explosive incidence of stroke, particularly in young groups and in middle-income countries such as Iran, there are concerns in this field.[8,9] According to the GBD report, five main causes of stroke were high systolic blood pressure (79·6 million [67·7-90·8] DALYs), high body mass index (34·9 million [22·3-48·6] DALYs), high fasting plasma glucose (28·9 million [19·8-41·5] DALYs), ambient particulate matter pollution (28·7 million [23·4-33·4] DALYs), and smoking (25·3 million [22·6-28·2] DALYs).[1] Furthermore, based on the GBD Study 2021, substantial increases in DALYs were attributed to high BMI, high ambient temperature, high fasting plasma glucose, sugar-sweetened beverages, low physical activity, high systolic blood pressure, lead exposure, and diet low in omega-6 polyunsaturated fatty acids.[6]

Tobacco use is one of the most important health problems that is associated with many health consequences.[10] The tobacco epidemic is one of the biggest health threats in the world, which leads to the death of more than 8 million people every year.[11] Of these, 7 million deaths are directly related to smoking, and 1.3 million are related to exposure to secondhand smoke.[11] The global estimate in 2019 showed that 1.14 billion people in the world were smokers, with 7·41 trillion cigarette-equivalents of tobacco in 2019.[12] Compared to 1990, the prevalence of smoking has decreased for both sexes, but due to population growth, the number of smokers has increased.[12] The role of smoking in mortality and disability is known, with 7·69 million deaths (13·6% of all deaths) and 200 million DALYs (7·89% of all DALYs) attributed to smoking.[12] Smoking has been associated with a wide range of health issues, including risk of cancer,[13,14] tuberculosis,[15] coronary heart disease,[16] stroke,[17-19] sleep-related issues,[20] and physical impairment.[21] The health issues with the highest of deaths attributed to tobacco use were ischemic heart disease (1·68 million), chronic obstructive pulmonary disease (1·59 million), tracheal, bronchial, and lung cancer (1·31 million), and stroke (0·931 million).[12]

In recent decades, Iran has undergone changes in the demographic and health-related structures, including increased life expectancy, decreased fertility rate, and an aging population, and noncommunicable diseases have become a health challenge that requires a multisectoral approach.[22-26] As mentioned, an increasing stroke incidence is observed in Iran,[8,9,27] and smoking is one of the main preventable causes of stroke in the world. The present study followed two main objectives. First, the study aimed to provide a report and an update on the incidence, prevalence, DALYs, and death due to stroke in Iran and globally. The second objective was to report new estimates about DALYs and death due to stroke attributed to smoking.

Material and Methods

Data source

This study was conducted in accordance with the GBD Study 2021.[23,28,29] The GBD Study 2021 reported incidence, prevalence, DALYs, years lived with disability, years of life lost, and death for 371 diseases and injuries, along with estimates of healthy life expectancy.[29] These estimates were provided for sex and age groups in 204 countries and territories, including subnational estimates for 21 countries. Data sources used in the GBD Study 2021 included 100,983 data sources (19,189 new data sources for DALYs), 12 new causes, and other important methodological updates. More details about the data sources and methodology of the GBD Study 2021 were previously reported.[29] This research did not involve human or animal subjects, clinical trials, or sensitive personal data. Therefore, it falls outside the scope of studies requiring ethical clearance according to established guidelines.

Case definitions

Smoking was defined as tobacco smoking, chewing tobacco use, and second-hand smoke exposure.[30] Stroke was defined according to World Health Organization criteria as rapidly developing clinical signs of focal (or less commonly global) disturbance of cerebral function lasting more than 24 h or leading to death with no apparent cause other than that of vascular origin. Cases of transient ischemic attack were not included.[29] Ischemic stroke: (ICD-9 433-435.9, 437.0-437.1, 437.5-437.8) (ICD-10 G45-G46.8, I63-I63.9, I65-I66.9,I67.2-I67.3, I67.5-I67.6, I69.3) “characterized by occlusion of blood flow to part of the brain due to hypoperfusion, most commonly due to a thrombus or embolism. It is defined as an episode of neurological dysfunction caused by focal cerebral, spinal, or retinal infarction”. Intracerebral hemorrhage: (ICD-9 431-432.9, 437.2) (ICD-10 I61-I62, I62.1-I62.9, I68.1-I68.2, I69.1-I69.2) “characterized by the rupture of a blood vessel resulting in bleeding into the intracerebral part of the brain. It is defined as focal collection of blood within the brain parenchyma or ventricular system that is not caused by trauma and results in a clinical stroke”. Subarachnoid hemorrhage: (ICD-9 430-430.9) (ICD-10 I60-I60.9, I62.0, I67.0-I67.1, I69.0) “characterized as bleeding into the subarachnoid space (the space between the arachnoid membrane and the pia mater of the brain or spinal cord) resulting in a clinical stroke”. Refer elsewhere for more details on GBD methodology.[29]

Estimation framework

Years lived with disability were estimated by multiplying prevalence estimates at varying levels of severity by an appropriate disability weight.[29] Years lived with disability were calculated by multiplying cause-specific deaths by the years of life expected to remain at death based on a normative life expectancy.[29] Disability-adjusted life years were calculated as the sum of years lived with disability and years of life lost.[29]

Statistical analysis

Analyses were conducted using Python version 3.10.4 (Python Software Foundation, Wilmington, DE, USA), Stata version 13.1 (StataCorp, College Station, TX, USA), and R version 4.2.1 2 (R Foundation for Statistical Computing, Vienna, Austria). All ages and age-standardized estimates were calculated for prevalence, incidence, DALYs, and death due to stroke between 1990 and 2021.[31] In the GBD Study 2021, the relationship between 88 risk factors with selected health outcomes were estimated.[28] All age and agestandardized estimates of stroke attributed to smoking were calculated for DALYs and death between the years 1990 and 2021.[29] Estimates were based on per 100,000 individuals. A 95% uncertainty interval (UI) was reported for each of the reported estimates. More details about data, data processing, and modeling in the GBD Study 2021 were previously reported.[29] The GBD Study 2021 complied with the GATHER (Guidelines for Accurate and Transparent Health Estimates Reporting).[32]

Results

Prevalence and death caused by stroke

The burden caused by stroke globally and in Iran was investigated, and the results are listed in Table 1. Age-standardized prevalence percent of stroke in 2021 was 1.14 (95% UI 1.09-1.21) globally and 0.98 (95% UI 0.90-1.06) in Iran (Supplementary Figure 1). Globally, 93,816,414 (95% UI 89,030,218-99,335,466) strokes were detected in 2021, and 787,178 (95% UI 726,667-855,320) cases of stroke were detected in Iran. The age-standardized prevalence rate of stroke per 100,000 individuals in 2021 was 1,099.31 (95% UI 1,044.17-1,162.11) globally and 934.35 (95% UI 860.27-1,015.71) in Iran. The age-standardized death rate of stroke per 100,000 individuals in 2021 was 87.45 (95% UI 78.92-94.14) globally and 63.89 (95% UI 56.76-69.69) in Iran. Age-standardized DALYs of stroke per 100,000 individuals in 2021 was 1,886.20 (95% UI 1,738.99-2,017.90) globally and 1,229.18 (95% UI 1,119.52-1,332.60) in Iran (Table 1). Although the prevalence, incidence, mortality, and disability rates of stroke globally and in Iran decreased between 1990 and 2021, the number of cases increased (Supplementary Figure 2).

Table 1. Age-standardized and all-age prevalence, incidence, DALY, and death globally and in Iran between 1990 and 2021

Burden of pathological types of stroke in Iran

The highest to lowest prevalence rates were ischemic stroke with 653,015.73 (95% UI 591, 272.44-718,460.97), intracerebral hemorrhage with 81,265.68 (95% UI 72,921.41- 90,120.11), and subarachnoid hemorrhage with 54,855.13 (95% UI 49,044.16-61,208.86). Ischemic stroke had the highest death rate with 34,027.27 (95% 30,355.10-37,131.72), followed by intracerebral hemorrhage (6,875.13 [95% UI 6,192.56-7,539.64]) and subarachnoid hemorrhage (1,005.82 [95% UI 786.71-1,212.57]; Supplementary Figure 3).

Burden of stroke stratified by males and females in Iran

Age-standardized prevalence ratio per 100,000 individuals in 2021 was higher in males (1,011.98 [95% UI 925.92-1,105.32]) than in females (856.98 [95% UI 792.85-928.94]). Age-standardized DALYs per 100,000 individuals in 2021 was higher in males (1,274.02 [95% UI 1,162.97-1,398.27]) than in females (1,190.38 [95% UI 1,058.47-1,307.77]). However, age-standardized death rate per 100,000 in 2021 was higher in females (66.18 [95% UI 56.46-74.20]) than in males (62.37 [95% UI 55.68-68.74]; Table 2, Supplementary Figure 4).

Table 2. Age-standardized prevalence, incidence, DALY, and death in Iran stratified sex between 1990 and 2021

Stroke burden stratified by provinces

The highest age-standardized prevalence rate of stroke per 100,000 individuals was in Bushehr (1,203.06 [95% UI 1,099.39-1,312.52]), and the lowest was in Tehran (809.91 [95% UI 740.53-879.40]). The highest age-standardized DALYs of stroke per 100,000 individuals was in Golestan (1,747.00 [95% UI 1,539.88-1,943.83]), and the lowest was in Tehran (847.70 [95% UI 721.41-985.51]). The highest age-standardized death rate of stroke per 100,000 individuals was in Golestan (85.59 [95% UI 74.89-95.69]), and the lowest was in Tehran (44.67 [95% UI 36.71-52.81]; Table 3 Figure 1).

Table 3. Age-standardized prevalence, incidence, DALY, and death in Iran stratified by provinces between 1990 and 2021

Table 3. Continued

Table 3. Continued

Figure 1. (a) Age-standardized prevalence rate of stroke per 100,000 individuals. (b) Age-standardized DALYs of stroke per 100,000 individuals. (c) Age-standardized death rate of stroke per 100,000 individuals.
DALYs: Disability-adjusted life years.

Stroke burden stratified by age in Iran

The highest age-standardized prevalence rate of stroke per 100,000 individuals was detected in those aged 55 years or older (3,171.30 [95% UI 2,824.99-3,512.51]), and the lowest was detected in those aged 15 to 19 years (228.55 [95% UI 197.74-265.27]). The highest age-standardized DALYs rate of stroke per 100,000 individuals was in those aged 55 years or older (5,268.44 [95% UI 4,798.71-5,719.31]), and the lowest was in those aged 15 to 19 years (134.79 [95% UI 117.79-150.88]). More than 90% of all stroke deaths occured in those aged 55 years or older (38,308.07 [95% UI 34,084.10-41,826.74]; Table 4).

Table 4. Age-standardized prevalence, incidence, DALY, and death in Iran stratified by age between 1990 and 2021

Stroke attributed to smoking

Age-standardized DALYs of stroke attributed to smoking per 100,000 individuals was 328.94 [95% UI 270.32-393.11] globally and 141.75 [95% UI 112.46-173.37] in Iran. The global age-standardized death from stroke attributed to smoking per 100,000 individuals was 12.65 [95% UI 10.09-15.55], with 5.40 [95% UI 4.18-6.81] in Iran. More than one million cases of death have been attributed to tobacco use in the world (1,077,804 [95% UI 865,541-1,320,753]), with 4,007 [95% UI 3,159-4,972] in Iran. Compared to 1990, there was an increase in the number of deaths caused by tobacco use (0.20 [95% UI 0.06-0.35]), and this growth was higher in Iran (0.52 [95% UI 0.31-0.79]; Table 5; Figure 2).

Table 5. Stroke (death and DALYs per 100,000 individuals) attributed to smoking globally and in Iran between 1990 and 2021

Table 5. Continued

Table 5. Continued

Figure 2. (a) Global age-standardized DALYs of stroke attributed to smoking per 100,000 individuals. (b) Global age-standardized deaths from stroke attributed to smoking per 100,000 individuals.
DALYs: Disability-adjusted life years.

Stroke attributed to smoking stratified by sex

Age-standardized DALYs of stroke attributed to smoking per 100,000 individuals was 218.97 [95% UI 176.33-265.12] in males and 64.77 [95% UI 45.87-84.77] in females. Number of DALYs of stroke attributed to smoking was 93,526 [95% UI 75,896-112,357] in males and 26,886 [95% UI 19,240-34,988] in females.

Age-standardized death from stroke attributed to smoking per 100,000 individuals was 8.18 [95% UI 6.42-10.23] in males and 2.63 [95% UI 1.77-3.55] in females. Almost a quarter of deaths attributed to tobacco use in Iran were in males (3,084 [95% UI 2,469-3,784]) compared with females (922 [95% UI 636-1,223]). This finding suggests that the burden of stroke attributable to smoking was much higher in males than in females (Table 6; Supplementary Figure 5).

Table 6. Stroke (death and DALYs per 100,000 individuals) attributed to smoking stratified by sex between 1990 and 2021

Table 6. Continued

Table 6. Continued

Stroke attributed to smoking stratified by provinces

The highest age-standardized DALYs attributed to smoking per 100,000 individuals was in Golestan (207.43 [95% UI 162.20-264.40]), and the lowest was in Tehran (99.95 [95% UI 75.87-131.30]). The highest age-standardized death rate attributed to smoking per 100,000 individuals was in Golestan (7.53 [95% UI 5.79-9.79]), and the lowest was in South Khorasan (3.75 [95% UI 2.67-5.04]; Table 7, Figure 3).

Table 7. Death and DALYs attributed to smoking stratified by provinces between 1990 and 2021

Table 7. Continued

Table 7. Continued

Figure 3. (a) Age-standardized DALYs of stroke attributed to smoking per 100,000 individuals stratified by provinces. (b) Age-standardized deaths from stroke attributed to tobacco smoking per 100,000 individuals stratified by provinces.
DALYs: Disability-adjusted life years.

Stroke attributed to smoking stratified by age in Iran

The highest DALYs attributed to smoking per 100,000 individuals was in those aged 55 years or older (542.17 [95% UI 423.69-675.10]), and the lowest was in Tehran (99.95 [95% UI 75.87-131.30]). More than a third of stroke-related deaths attributed to smoking occurred in those aged 55 years or older (3,124 [95% UI 2,391-3,981]; Table 8; Supplementary Figure 6).

Discussion

Stroke is one of the important health challenges in the international classification of diseases.[33] This research was based on the most comprehensive epidemiological estimate of the global burden of diseases in 2021. In the first section, incidence, prevalence, DALYs, and death due to stroke in Iran and globally were estimated. In the second section, new estimates on DALYs and stroke-related deaths attributed to smoking were reported.

In 2021, stroke remained the second leading cause of death and the third leading cause of disability among noncommunicable diseases. Although the prevalence, incidence, mortality, and disability rates of stroke globally and in Iran decreased between 1990 and 2021, the number of cases increased. Among stroke pathologies, ischemic stroke was the highest in the world and Iran. In the USA, 87% of strokes were reported as ischemic strokes.[34] More than 90% of all stroke-related deaths occurred in those aged 55 years or older. In similar studies, it was shown that the highest rate of stroke occurred in older ages,[35] and almost three-quarters of strokes occurred in those aged 65 years or older.[35] Age remains the largest risk factor for stroke.[36] Mechanisms of aging and stroke were based on changes in brain activity.[36] Since stroke is a vascular disease, it is necessary to pay attention to the effects of aging on vascular diseases and based on the study showed that “Aging was also associated with decreased expression of endothelial nitric oxide synthase (eNOS) and increased production of inducible nitric oxide synthase (iNOS), factors that alter vascular function”.[37]

Smoking was a major factor in stroke globally and in Iran. The 2019 global estimate of stroke-related factors showed that smoking was the fifth leading cause of stroke, with 25.3 million DALYs attributed to smoking.[1] Ten stroke risk factors were identified, and 88% of stroke risk factors were attributed to these; researchers stated that stroke could be prevented to a large extent.[38] The evidence for the relationship between tobacco use and stroke is well established.[39,40] Some studies reported up to six times the risk of stroke caused by smoking.[41] The effects of exposure to secondhand smoke and the risk of stroke were shown in the current study, as well as in previous studies.[41-45] The mechanisms listed for how the relationship between smoking and the risk of stroke are extensive include carboxyhemoglobinemia, increased platelet aggregability, increased fibrinogen levels, reduced high-density lipoprotein cholesterol, and direct toxic effects of compounds, such as 1,3-butadiene, a vapor phase constituent of environmental tobacco smoke that accelerated atherosclerosis in animal models.[46] Furthermore, secondhand smoking was related to atherosclerosis as measured by B-mode ultrasound of the carotid wall,[47,48] as well as to early arterial damage as assessed by endothelium-dependent brachial artery dilatation.[49]

This study shared certain limitations with the GBD Study 2021, which were previously addressed.[28,29] While smoking was a major focus, future studies could expand to include other emerging risk factors for stroke, such as dietary habits and physical inactivity, to provide a more comprehensive picture of the disease's burden.

In conclusion, this was a comprehensive study on the burden of stroke and its burden attributable to tobacco use globally and in Iran. The evidence obtained from this study, representing the most up-to-date estimates, is insightful. The findings obtained from the current study show that stroke remains a noncommunicable disease with a major burden, and although its prevalence has decreased compared to previous decades, due to the increase in the population, the case of stroke has also increased. Considering the decrease in the fertility rate in the world, particularly in Iran, and the increase in the elderly population in the coming decades, the burden caused by stroke on the health system can be significant. Therefore, it is necessary to address the preventable risk factors of stroke, including tobacco use, which is a major risk factor, helping to reduce the burden of stroke.

Supplementary Figure 1. Global age-standardized prevalence of stroke in 2021.

Supplementary Figure 2. Prevalence, death, and DALYs of stroke per 100,000 individuals globally and in Iran.
DALYs: Disability-adjusted life years.

Supplementary Figure 3. Count estimates of pathological types of stroke in Iran.

Supplementary Figure 4. Age-standardized prevalence, death, and DALYs of stroke stratified by sex.
DALYs: Disability-adjusted life years.

Supplementary Figure 5. All-age DALYs and death of stroke attributed to smoking stratified by sex.
DALYs: Disability-adjusted life years.

Supplementary Figure 6. All-age deaths from stroke attributed to smoking stratified by ages.

Cite this article as: Khan MAB, Amiri S. Burden of stroke and risk attributed to smoking in Iran: A Global Burden of Disease Study 2021. Turk J Neurol 2025;31(2):159-185. doi: 10.55697/tnd.2025.292.

Data Sharing Statement

The data sources of this study were taken from GBD 2021, which is publicly available. The data can be accessed through the links below. https://vizhub.healthdata.org/gbd-results/, https://vizhub.healthdata.org/gbd-compare/

Author Contributions

Conceptualization, extraction, analysis, writing and revision: S.A.; Conceptualization, writing and revision: M.A.K

Conflict of Interest

The authors declared no conflicts of interest with respect to the authorship and/ or publication of this article.

Financial Disclosure

The authors received no financial support for the research and/or authorship of this article.

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