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Abstract

  1. Top of page
  2. Abstract
  3. Patients and Methods
  4. Results
  5. Discussion
  6. Note Added in Proof
  7. References

Objective:

The aim of this study was to determine acute stroke hospitalization rates for children and young adults and the prevalence of stroke risk factors among children and young adults hospitalized for acute stroke.

Methods:

The study population consisted of 1995–2008 hospitalizations from the Nationwide Inpatient Sample of the Healthcare Cost and Utilization Project. Subarachnoid hemorrhage, intracerebral hemorrhage, and ischemic stroke hospitalizations were identified by the primary International Classification of Diseases, 9th ed, Clinical Modification (ICD-9-CM) code. Seven consecutive 2-year time intervals were selected. Three age groups were utilized: 5 to 14 years, 15 to 34 years, and 35 to 44 years. Stroke risk factors and comorbidities among those hospitalized with acute stroke were identified by secondary ICD-9-CM codes.

Results:

During the period of study, the prevalence of hospitalizations of acute ischemic stroke increased among all age and gender groups except females aged 5 to 14 years. Females aged 15 to 34 years and males and females aged 35 to 44 years showed a decrease in the prevalence of hospitalizations for subarachnoid hemorrhage, whereas females aged 5 to 14 years showed increases for subarachnoid hemorrhage. Hypertension, diabetes, obesity, lipid disorders, and tobacco use were among the most common coexisting conditions, and their prevalence increased from 1995 to 2008 among adolescents and young adults (aged 15–44 years) hospitalized with acute ischemic stroke.

Interpretation:

Increases in the prevalence of ischemic stroke hospitalizations and coexisting traditional stroke risk factors and health risk behaviors were identified among acute ischemic stroke hospitalizations in young adults. Our results from national surveillance data accentuate the need for public health initiatives to reduce risk factors for stroke among adolescents and young adults. ANN NEUROL 2011;

Stroke is the third leading cause of death in the United States and is a major cause of morbidity and years of productive life lost, especially when it occurs in younger persons.1–3 Stroke in children and young adults accounts for 5 to 10% of all stroke and is among the top 10 causes of childhood death.4 Previous reports noted stable rates of stroke incidence5 and decreasing stroke mortality in children and adolescents.6 Recent reports from the Greater Cincinnati Northern Kentucky Stroke Study have suggested a rise in stroke rates in young adults in a limited but generalizable population, but no significant trend in children and adolescents.7, 8 Studies have documented decreasing rates of stroke hospitalizations among adults8, 9 and stroke mortality3 since the late 1990s. Although the incidence of stroke increases greatly with age, there is limited information on recent population-based estimates of trends in acute stroke hospitalization rates by age and gender among children and young adults.6 According to the Agency for Healthcare Quality and Research, 4% of ischemic stroke hospitalizations (16,500 in 2005) and 11% of hemorrhagic stroke hospitalizations (12,200 in 2005) occurred in persons younger than 45 years of age,9 with and an estimated 3,000 strokes occurring among children each year.10 Rising rates of risk factors for stroke, including obesity in youth and adults, hypertension and diabetes in adults, and high rates of tobacco and alcohol use,11–13 have the potential to increase stroke rates in young adults. This report investigates the trends in acute stroke hospitalizations over 14 years from 1995 to 2008 among children and young adults in a large national sample of hospitalizations. It also explores trends in risk factors for stroke in children and young adults admitted with a diagnosis of acute stroke to better understand the relationship between risk factor trends and trends in acute stroke hospitalizations in children and young adults.4, 14–16

Patients and Methods

  1. Top of page
  2. Abstract
  3. Patients and Methods
  4. Results
  5. Discussion
  6. Note Added in Proof
  7. References

Hospital discharge data were obtained from the Nationwide Inpatient Sample (NIS), the largest nationwide all-payer hospital inpatient care database in the United States. The NIS is among a family of databases and software tools developed as part of the Healthcare Cost and Utilization Project (HCUP), sponsored by the Agency for Healthcare Research and Quality (AHRQ) in partnership with state-level data-collection organizations to provide national estimates of inpatient care.17 The NIS is a stratified sample of approximately 20% of all US community hospitals. It includes 100% of discharges from selected hospitals and provides information on 6.7 million discharges in 1995, with yearly increases, and 8.2 million discharges in 2008. Nine hundred thirty-eight hospitals from 19 states participated in the NIS in 1995, increasing to 1,056 hospitals from 42 states and the District of Columbia that participated in 2008. The linear trends were tested using orthogonal polynomial contrasts, and all statistical analyses were conducted using SAS 9.2-callable SUDAAN (Research Triangle Institute, Research Triangle Park, NC) to account for the multistage, disproportionate stratified sampling design.

The study population consisted of all 1995–2008 hospitalizations from the Nationwide Inpatient Sample for those aged 5 to 44 years. The acute subarachnoid hemorrhage (SAH), intracerebral hemorrhage (ICH), and ischemic stroke hospitalizations were identified with a principal discharge diagnosis of stroke using International Classification of Diseases, 9th ed, Clinical Modification (ICD-9-CM) codes (SAH 430; ICH 431; ischemic stroke 433.01, 433.11, 433.21, 433.31, 433.81, 433.91, 434.01, 434.11, 434.91, 436). Seven 2-year time intervals were selected for this study. Three age groups were defined: 5 to 14 years, 15 to 34 years, and 35 to 44 years. Separate stroke hospitalization rates for males and females were estimated for each stroke type and age group. Risk factor prevalence was estimated for the 5- to 14-year age group, and estimated by stroke type and gender for those aged 15 to 34 and 35 to 44 years using secondary ICD-9-CM codes and AHRQ's Clinical Classification Software, taking into account changes in ICD-9-CM coding over time. The following common risk factors for stroke in this population were assessed for linear trends using orthogonal polynomial contrasts: congenital heart disease; valvular heart disease; head trauma; meningitis, encephalitis, or sepsis; sickle cell disease; arteriovenous malformation; coagulation defects; arrhythmia; hypertension; autoimmune disorders; cerebral arteritis; moyamoya disease; brain tumor; leukemia; migraine; cardiac arrest; cardiomyopathy; diabetes; obesity; cerebral aneurysms; lupus; patent foramen ovale; alcohol abuse; tobacco use; carotid and vertebral dissection; ischemic heart disease; lipid disorders; drug abuse (other than alcohol); human immunodeficiency virus; and other malignancies. Linear trends and data were not reported if the data were too sparse to report based on HCUP reporting guidelines.

Results

  1. Top of page
  2. Abstract
  3. Patients and Methods
  4. Results
  5. Discussion
  6. Note Added in Proof
  7. References

During the study period, the prevalence of hospitalizations with a primary diagnosis of ICH decreased significantly among females aged 35 to 44 years, while showing no significant trends among other age groups and gender (Table 1, Fig 1). The prevalence of stroke hospitalizations for SAH increased among females aged 5 to 14 years, and decreased among females aged 15 to 34 years and among males and females aged 35 to 44 years (Table 1, Fig 2). The weighted number of hospitalizations for SAH was greater among females than males aged 35 to 44 years, whereas the weighted number of hospitalizations for ICH was greater among males in all age groups (5–14, 15–34, and 35–44 years).

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Figure 1. Subarachnoid hemorrhage hospitalization rates by age and gender from 1995 to 2008 in 2-year intervals. Diamonds, males aged 5–14 years; squares, females aged 5–14 years; triangles, males aged 15–34 years; crosses, females aged 15–34 years; crosses with vertical lines, males aged 35–44 years; circles, females aged 35–44 years.

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Figure 2. Intracerebral hemorrhage hospitalization rates by age and gender from 1995 to 2008 in 2-year intervals. Diamonds, males aged 5–14 years; squares, females aged 5–14 years; triangles, males aged 15–34 years; crosses, females aged 15–34 years; crosses with vertical lines, males aged 35–44 years; circles, females aged 35–44 years.

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Table 1. Prevalence of Subarachnoid and Intracerebral Hemorrhage Hospitalization by Age and Gender
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Table 2. Prevalence of Acute Ischemic Stroke Hospitalization by Age and Gender
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The prevalence of hospitalizations with a primary diagnosis of ischemic stroke increased significantly among males and females in all age groups except females aged 5 to 14 years (see Table 2, Fig 3). The largest increases in ischemic stroke hospitalizations occurred in males of all age groups (51.6% from 3.1 to 4.7, aged 5–14 years, p = 0.01; 45.6% from 10.3 to 15.0, aged 15–34 years, p < 0.0001; and 50.4% from 35.7 to 53.7, aged 35–44 years, p < 0.0001). This was followed by slightly smaller relative increases in ischemic stroke hospitalizations among females aged 15 to 34 and 35 to 44 years. Overall, males had higher rates of SAH, ICH, and ischemic stroke hospitalizations than females among those aged 15 to 34 and 35 to 44 years (p < 0.001, data not shown). However, no significant difference was identified for SAH, ICH, or ischemic stroke hospitalization rates between males and females aged 5 to 14 years.

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Figure 3. Ischemic stroke hospitalization rates by age and gender from 1995 to 2008 in 2-year intervals. Diamonds, males aged 5–14 years; squares, females aged 5–14 years; triangles, males aged 15–34 years; crosses females aged 15–34 years; crosses with vertical lines, males aged 35–44 years; circles, females aged 35–44 years.

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For those aged 5 to 14 years, the rate of ischemic stroke hospitalizations with sickle cell disease decreased by more than half from 1995–1996 to 2007–2008 (from 27.8 to 12.6%, p < 0.001, data not shown), whereas the rate of alcohol abuse increased significantly from 2.5% in 1995–1996 to 6.2% in 2007–2008 (p < 0.001, data not shown). The prevalence of ICH stroke hospitalizations associated with congenital heart disease or arteriovenous malformations increased but not significantly over time (20.7 to 28.1%, p = 0.64 and 15.8 to 30.1%, p = 0.19 respectively) among those aged 5 to 14 years (data not shown). Trend estimates for all other stroke risk factors by stroke type among those aged 5 to 14 years were not estimable based on HCUP analytical guidelines.11

Risk factor prevalence among patients with SAH differed by gender and age group. Among patients with SAH, the prevalence of hypertension, arrhythmia, alcohol abuse, tobacco use, and meningitis, encephalitis, or sepsis increased significantly (p ≤ 0.03) over time among males aged 15 to 34 years, whereas hypertension, arrhythmia, tobacco use, and migraine increased significantly among females aged 15 to 34 years (p ≤ 0.03) (Table 3). Among patients aged 35 to 44 years with SAH, the prevalence of hypertension, arrhythmia, alcohol abuse, and tobacco use increased over time among both males and females (p ≤ 0.02), whereas the prevalence of diabetes; obesity; migraine; coagulation defects; meningitis, encephalitis, or sepsis; drug abuse (other than alcohol); and other malignancies increased among females (p ≤ 0.03) (see Table 3). Prevalence rates for risk factors among patients hospitalized for ICH among those aged 15 to 34 and 35 to 44 years were not estimable according to HCUP guidelines.

Table 3. Prevalence (%) of Risk Factors among Patients Hospitalized with Subarachnoid Hemorrhage by Age and Gender
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Among patients with ischemic stroke, the trend over time in the prevalence of hypertension, diabetes, obesity, lipid disorders, congenital heart disease, arrhythmia, migraine, coagulation defects, tobacco use, and patent foramen ovale increased significantly (p < 0.01) among males and females aged 15 to 34 and 35 to 44 years (Table 4). In males aged 15 to 34 years with ischemic stroke, additional increases were identified in the prevalence of cardiomyopathy, alcohol abuse, drug abuse (other than alcohol), and meningitis, encephalitis, or sepsis (p ≤ 0.05). Among males aged 15 to 34 years with ischemic stroke, the prevalence of human immunodeficiency virus (HIV) decreased from 5.8 to 2.4% (p < 0.001); among females aged 15 to 34 years with ischemic stroke, the prevalence of valvular heart disease decreased (p = 0.03). In addition, among males and females aged 35 to 44 years with ischemic stroke, increasing trends were identified in the prevalence of alcohol abuse and drug abuse (other than alcohol) (p < 0.001), whereas males also had an increase in the prevalence of cardiomyopathy (p < 0.001). Females and males aged 35 to 44 years were found to have a decrease in the prevalence of valvular heart disease associated with ischemic stroke (p ≤ 0.02) (see Table 4).

Table 4. Prevalence (%) of Risk Factors among Patients Hospitalized with Ischemic Stroke by Age and Gender
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Discussion

  1. Top of page
  2. Abstract
  3. Patients and Methods
  4. Results
  5. Discussion
  6. Note Added in Proof
  7. References

The key findings reported in this study are: (1) there is an increasing trend in the prevalence of hospitalization rates for ischemic stroke among male and female children and young adults; (2) just less than half of all children aged 5 to 14 years hospitalized for stroke experienced an ischemic stroke, approximately ¼ experienced SAH, and ¼ experienced ICH; (3) the prevalence of sickle cell disease has decreased among children with ischemic stroke, whereas the prevalence of alcohol abuse has increased among children with ischemic stroke; (4) hypertension, diabetes, obesity, lipid disorders, and tobacco use were among the most common coexisting conditions, and their prevalence increased from 1995 to 2008 among adolescents and young adults (aged 15–44 years) hospitalized with acute ischemic stroke; and (5) the prevalence of traditional cardiovascular risk factors (hypertension, diabetes, obesity, lipid disorders, tobacco use, and alcohol abuse), congenital heart disease, coagulation defects, arrhythmias, patent foramen ovale, drug abuse, and migraines increased among adolescents and young adults experiencing ischemic stroke.

Whereas rates of ischemic stroke hospitalizations and mortality have decreased among older adults during the past 15 years,3, 8, 9, 18 we have identified significant increasing trends in ischemic stroke hospitalizations as well as decreasing hospitalizations for SAH among adolescents and young adults during the same years, with the increases in ischemic stroke the most significant. Rates of traditional risk factors for stroke among children and young adults are increasing, and smoking rates have failed to decline.11–13 We identified increases in ischemic stroke hospitalizations associated with increases in these traditional risk factors among adolescents and young adults. Nearly ⅓ of those aged 15 to 34 years and >½ of those aged 35 to 44 years with ischemic stroke also had a diagnosis of hypertension. More than ¼ of those with ischemic stroke aged 35 to 44 years had diabetes. One in three males aged 15 to 34 and 35 to 44 years and females aged 35 to 44 years with ischemic stroke are tobacco users, as are ¼ of females aged 15 to 34 years admitted for acute ischemic stroke. Tobacco use has been shown to have a dose–response relationship with ischemic stroke in young women.19

Although not all of the increases in risk factor prevalence are easily explained, some may be explained by improved ability to diagnose these conditions over time, such as coagulation defects and patent foramen ovale. Increases in ischemic stroke associated with congenital heart disease may reflect that more people with congenital heart disease are living into adulthood than in the past. Increases in ischemic stroke associated with arrhythmia may also be due to atrial fibrillation being a common complication in adults with congenital heart disease.20 The higher prevalence of migraine in females is consistent with other reports.21, 22 Encouraging trends were seen in reduction in the prevalence of sickle cell disease in children with ischemic stroke and in the prevalence of HIV among males aged 15 to 34 years with ischemic stroke, likely reflecting improved care for those populations.

African Americans and Mexican Americans have a higher incidence of ischemic stroke,1 and Mexican Americans have been noted to have higher rates of SAH compared to non-Hispanic whites.23 Both African Americans and Hispanics experience stroke at younger ages than non-Hispanic whites.1 The proportion of Hispanics in the United States has risen from 8.9% in 1990 to 15.8% in 2009, but we are unable to discern how these changes in demographics over time may have influenced our findings. States do not consistently report data on race and ethnicity to the NIS. Previous reports have documented approximately 20% missing data on race and ethnicity, and not all states are required to report this information, leading to nonrandom missing data.24, 25 Consistent reporting of race/ethnicity data would allow further investigation into the influence of changing demographics on stroke hospitalization rates in adolescents and young adults.

A major strength of this study is that it represents a large cohort across multiple states; however, this report has limitations. Coding practices for comorbidities may have changed over time and may be prone to coding bias. Changes in diagnostic practices may have changed over time, such as the increased use of magnetic resonance imaging for ischemic stroke, and this could lead to an increase in the diagnosis of ischemic stroke and/or comorbidities, while having less effect on hemorrhagic stroke diagnoses. Over time, the number of states contributing data to the NIS has increased, which could lead to bias based on the changing sample frame over time. The unit of analysis is a hospitalization, so we do not know the impact of repeated events for the same individual. Due to relatively small numbers of younger patients, we were unable to identify trends over time for many important risk factors for stroke in this data set, especially among children aged 5 to 14 years. This analysis is not able to identify the cause of stroke, but rather identifies prevalence of associated risk factors for stroke. It is possible that the identified increasing trends in hospitalizations could reflect secular trends in hospital admitting practices leading to fewer admissions for less serious diseases or trends in payment practices, but decreasing stroke hospitalizations have been reported among older adults during this time period.9 Although pregnancy is associated with stroke,26 strokes occurring in pregnancy are typically a secondary diagnosis, whereas our methodology identified stroke as the primary diagnosis; therefore this study may have underestimated stroke associated with pregnancy. Also, the rate of stroke hospitalizations in females aged 15 to 34 and 35 to 44 years appears to be low due to the large number of pregnancy-related hospitalizations in these age groups. Lastly, although oral contraceptive use is an important risk factor for stroke,26 we were unable to identify prior history of use in this data set.

Conclusions

This report has identified increasing trends in ischemic stroke hospitalizations among adolescents and young adults, and decreasing trends in SAH hospitalizations among adolescents and young adults, but the increase in ischemic stroke far outweighs the decreases in SAH. Significant increases in traditional cardiovascular risk factors, health risk behaviors, and other common risk factors for stroke among adolescents and young adults who experience stroke (that may reflect secular trends among all young adults) were also identified. The trends in hemorrhagic stroke are not explained by this study and deserve further investigation such as changes in population demographics over time. The costs and lifelong morbidity associated with stroke are great when stroke occurs in the young.10, 27 Urgent public health initiatives are needed to reverse the rising trends in modifiable risk factors and unhealthy behaviors associated with stroke in adolescents and young adults.

Note Added in Proof

  1. Top of page
  2. Abstract
  3. Patients and Methods
  4. Results
  5. Discussion
  6. Note Added in Proof
  7. References

Authorship

M.G.G. was responsible for study concept and design, analysis, and interpretation of the data, drafting of the manuscript, critical revision of the manuscript for important intellectual content, and administrative support. X.T. was responsible for study concept and design, analysis and interpretation of the data, drafting of the manuscript, critical revision of the manuscript for important intellectual content, and statistical analysis. E.V.K. was responsible for study concept and design, analysis and interpretation of the data, drafting of the manuscript, and statistical analysis. D.R.L. was responsible for analysis and interpretation of the data, drafting of the manuscript, critical revision of the manuscript for important intellectual content, and supervision.

Potential Conflicts of Interest

The findings and conclusions in this article are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.

References

  1. Top of page
  2. Abstract
  3. Patients and Methods
  4. Results
  5. Discussion
  6. Note Added in Proof
  7. References
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