Regional variation in hospitalization for stroke among Asians/Pacific Islanders in the United States: a nationwide retrospective cohort study

Stroke is a disease of major importance in Asia. Reported incidence rates vary dramatically but are generally higher than those of the US [1–3]. For example, reported incidence rates for overall stroke are 39% greater in Japan [4], 23% greater in Taiwan [5], and 81% greater in Northern China[6] compared to the US. It is the second leading cause of death in China, Korea and Taiwan; third in Japan and Singapore; sixth in the Philippines; and tenth in Thailand [3, 7–9].

The incidence of stroke among Asians/Pacific Islanders (APIs) in the US is largely unstudied. The only major epidemiologic study on stroke in a sub-population of APIs was the Honolulu Heart Program [10]. A recent comparison of the 20-year incidence of hospitalized stroke between Japanese-American men in the Honolulu Heart Program and white men in the Framingham Study found a 40% excess of thromboembolic stroke in whites [11]. The incidence of hemorrhagic stroke was similar in the two cohorts. Another study reported a higher mortality rate from hemorrhagic stroke in APIs compared to whites in the US, and that deaths tended to occur at younger ages for some stroke types among APIs [12]. Some small studies have reported differences in the distribution of stroke subtypes between APIs and whites in the US [13, 14]. APIs have constituted only a small proportion of prior population-based cohorts in the US.

Although race-ethnic disparities within the US has been a recent interest [15], the vast majority of studies have focused on African Americans and Hispanics [16, 17], and few studies have described stroke in APIs in the US. API constitutes approximately 4% of the total US population and represents the fastest growing racial-ethnic group in the country. The Bureau of Census estimates that the number of Asians aged 25 years or older will increase 5-fold from 1995 to 2050 and that API will reach 10% of the US population by the year 2050 [18]. In 1998, the Department of Health and Human Services launched the Initiative to Eliminate Racial and Ethnic Disparities in Health with stroke identified as one of the six targeted conditions, and Healthy People 2010 prevention agenda[19] has the same objective.

Examining race-ethnic distributions of stroke incidence and mortality is required to define the burden of disease and to help guide the development of directed prevention programs, and may also be useful in identifying new genetic or environmental risk factors. We sought to characterize the incidence of hospitalized acute ischemic stroke, subarachnoid hemorrhage (SAH), and intracerebral hemorrhage (ICH) in APIs compared to non-Hispanic whites, using data representative of US hospitalizations in 1997. To assess whether stroke rates might differ in API sub-populations in the US, we also characterized regional variation.

We used the Nationwide Inpatient Sample of the 1997 Healthcare Cost Utilization Project (HCUP), release 6, produced by the Agency for Healthcare Research and Quality [20]. The Nationwide Inpatient Sample (NIS) is a sample of US community hospitals, including nonfederal, short-term, general and specialty hospitals. It excludes all long-term hospitals, psychiatric hospitals, and alcoholism/chemical dependency treatment facilities. The NIS is based on a 20% stratified probability sample of hospitals with sampling probabilities proportional to the total number of US community hospitals in each stratum. The five stratification variables are geographic region (Northeast, Midwest, South, and West), ownership (government nonfederal, private not-for-profit, private investor-owned), location (urban vs. rural), teaching status (teaching vs. non-teaching), and size based on number of beds (small, medium and large). The database includes information typically available from discharge abstracts for 7,148,420 inpatient stays in 1,012 hospitals across 22 geographically dispersed states (AZ, CA, CO, CT, FL, GA, HI, IL, IA, KS, MD, MA, MO, NJ, NY, OR, PA, SC, TN, UT, WA, WI). Our study was approved by the Committee on Human Research at the University of California San Francisco.

There were 169,386 hospitalizations for stroke in the 1997 NIS database. Of these, 102,268 (60.4%) were for acute ischemic stroke, 5,172 (3.1%) for SAH and 14,907 (8.8%) for ICH. An additional 47,039 (27.7%) were for non-specific stroke diagnoses, with carotid stenosis or occlusion (ICD-9 433.1) being the most frequent. Using the average discharge weight for each stroke subtype, we calculated the US projections to be 510,113 cases of acute ischemic stroke, 24,893 cases of SAH, and 73,208 cases of ICH. Most patients were admitted through the emergency department (57.9%). The distribution of race-ethnicity was 80.9% white, 1.6% API, 11.4% African American, 4.7% Hispanic, 0.2% Native American, and 1.3% other. The overall average age was 71.7 ± 13.4 years, and 52.7% were female.

Few studies have examined stroke in APIs in the US and no population-based study on stroke in API is available. Thus, the incidence of stroke in API in the US is not known. Using a 1997 national database to overcome problems with small sample size, we found that the overall US incidence rates for SAH and ICH were higher for APIs than for non-Hispanic whites. Our age-adjusted and gender-specific incidence rates for total stroke and for each stroke subtype for non-Hispanic whites are similar to those reported elsewhere[31, 32]. The age and gender-adjusted incidence of first-ever strokes among whites in Rochester was 179 per 100,000[31]. A recent population-based study of the greater Cincinnati metropolitan area reported the age and gender-adjusted incidence rates for non-Hispanic whites to be 212 per 100,000 for first and recurrent strokes, 137 per 100,000 for first ischemic stroke, 6 per 100,000 for first SAH, and 18 per 100,000 for first ICH[32].

We found a significant interaction between race-ethnicity and geographic region. The stroke incidence rates varied over 3-fold in APIs among different US regions. Geographic variation was less dramatic in non-Hispanic whites. It is not likely that the heterogeneity in rates was due to small numbers given that the incidence rates were statistically heterogeneous among the regions for all stroke types. This dramatic regional variation might reflect the different distributions of subgroups of APIs (such as Chinese, Japanese, Filipinos, etc.) in the US, as suggested by the significant differences in patient characteristics across regions (Table 2). Striking regional differences in stroke incidence between northern and southern China [3], and between countries in Asia[7] have been reported. These reports and our current findings suggest that combining these distinct subpopulations into one race-ethnic category may be inappropriate.

Our finding of a higher incidence of ICH in APIs is consistent with prior reports from Asia of high rates of hemorrhagic strokes in Asians [3, 5, 33]. Studies from Asia also reveal a high prevalence of hypertension in these populations [33]. It is not known how much uncontrolled hypertension contributes to the differential burden of hemorrhage in APIs in the US. Other differences in diet (such as a higher salt intake), prevalence of smoking, or genetic factors might also contribute to this difference in ICH incidences.

On average, APIs had longer hospital stays for ischemic stroke and ICH, had higher total hospital charges, and were more likely to be discharged to another facility rather than home. These findings were not explained by differences in stroke subtypes. One possible explanation of these findings is that APIs are hospitalized with more severe strokes, as has been suggested by one prior study showing higher case fatality rates for APIs with ICH [12]. However, we found no significant difference in all-cause in-hospital mortality between API and non-Hispanic white after adjusting for important potential confounders. Whether cultural differences in preferences for end-of-life care could mask an impact of greater stroke severity on case fatality cannot be answered in our study.

There are several limitations to our study. We only included in our analyses patients who were hospitalized for stroke. Thus, non-hospitalized strokes, which account for approximately 10% of all strokes in the US [34], were not included. Furthermore, incidence-rate calculations were based on all stroke hospitalizations including recurrent cases. The accuracy of our incidence estimates depends on the accuracy of ICD-9 coding in the database. Although we used only ICD-9 codes that were previously identified as more accurate in order to enhance the precision of our estimates, reliability of coding is still imperfect [21–23]. In addition, by using only ICD-9 codes in the primary position, we recognize that we increase specificity but decrease the sensitivity of case ascertainment [35]. Another limitation is the lack of reliable coding for comorbidities. Consequently, we were unable to fully adjust for severity of disease or to evaluate risk factors. We also did not have data on do-not-resuscitate status of the patients, which could influence the in-hospital mortality rate. Furthermore, API was not broken down into distinct ethnic subgroups in the database. This is a problem encountered by all similar studies. Despite the limitations, the study reveals several important and interesting findings that deserve further exploration.

In summary, analyses from a large nationwide database revealed that APIs appear to have a higher risk than non-Hispanic whites for ICH and SAH. However, differences between APIs and whites vary dramatically between regions, with the highest rates among APIs in the West. Which sub-populations of APIs are at greater risk, and the factors that predict this elevated risk remain to be determined. APIs come from nearly 50 distinct countries and ethnic groups, each with its own set of cultures and traditions, and potentially very different genetic and/or environmental risk factors for stroke. Our findings suggest the need for further studies to examine the differences in stroke incidence and risk factors among the subpopulations of APIs. Furthermore, understanding of the racial-ethnic differences in stroke should lead to the development of more efficient and effective stroke prevention strategies.