Cerebral infarction remains a major health burden for the US population, with hypertension as its leading risk factor. However, its mortality trends remain understudied. Analyzing these trends helps identify high risk populations and shape future public health strategies. The study aimed to analyze the demographic and regional mortality trends and disparities of hypertension related cerebral infarction in the United States population from 2000 to 2020. CDC Wonder database was utilized to extract death certificate data for hypertension-related cerebral infarction from 2000–2020. Crude mortality rates and Age adjusted mortality rate (AAMR) were calculated per 100,000. Joint point regression determined APC and 95% CI. Data was categorized by gender, sex, age, race/ ethnicity, urbanization, census region and location of death. About 111,398 hypertension related cerebral infarction deaths occurred in the US between 2000–2020. The overall AAMR declined till 2014 followed by a nonsignificant increase in slope from 2014–2017 (APC: 27.9, 95% CI: −4.3 to 70.9) and significant increase from 2017–2020 (APC: 10.7; 95% CI: 0.6 to 21.8). Women initially had higher AAMR, but rates later increased in men. Non-Hispanic (NH) Blacks and the South showed increased AAMR. And compared to urban areas, rural areas had higher mortality trends. Most deaths occurred in medical facilities followed by nursing homes, homes, and hospices. In conclusion, the mortality declined till 2014 then increased later on with significantly higher rates in men, NH Blacks, the South and the rural areas highlighting the need to improve health care system.
Cardiovascular diseases (CVDs) remain the leading cause of mortality worldwide, accounting for approximately 17.9 million deaths globally. Ischemic stroke, which occurs due to a blockage in the blood vessels supplying the brain, represents around 87% of all stroke cases in the United States. Hypertension, often referred to as the “silent killer,” is a well-established risk factor for ischemic stroke, significantly increasing the risk of cerebrovascular events. In the United States, the prevalence of hypertension has steadily increased, with nearly 47.7% of adults affected as of 2023. In 2022, stroke accounted for 17.5% of all cardiovascular-related deaths in the United States, with ischemic stroke being the predominant subtype. Hypertension-related mortality has also been rising with 43,293 deaths reported in 2022. This equates to a death rate of 13.0 per 100,000 population. The burden of complications from hypertension has evolved over the last 20 years due to changes in clinical practice, health policy, and demographics. Significantly, better blood pressure management and stroke care may have changed mortality trends, but these benefits may be offset by growing rates of diabetes, obesity, and health inequities. Disparities persist across racial and socioeconomic groups. African Americans have nearly twice the risk of a first ischemic stroke compared to white Americans, and they experience higher mortality rates from both stroke and hypertension. ,, Another study observed an increase in hypertension-related mortality rates from 5.1 to 6.4 per 100,000 between 2010 and 2020.
This study aims to analyze mortality trends in hypertension-associated cerebral infarction in the United States, using CDC WONDER data. As hypertension is a major modifiable risk factor for stroke therefore understanding these trends is essential to gain insights regarding disparities, epidemiological patterns and evaluate the impact of current prevention and management strategies, identifying at-risk populations, and establishing targeted public health interventions to reduce stroke-related mortality.
Methods
Study setting and population
In this descriptive study, death certificate data were retrieved from the CDC WONDER (Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research) database and examined from 2000 to 2020 for hypertension and cerebral infarction-related mortality in adults. These causes of death were identified using the International Statistical Classification of Diseases and Related Health Problems, 10th Revision (ICD-10), with codes I10–I15 for hypertension and I63.0–I63.6, I63.8, and I63.9 for cerebral infarction. Deaths were included only if both hypertension and cerebral infarction were mentioned on the death certificate, either as contributing or underlying causes. This ensured that the analysis specifically captured cases where both conditions were present at the time of death, thereby strengthening the relevance of co-occurrence to mortality trends.
This dataset includes cause-of-death information from death certificates across all 50 states and the District of Columbia and has been used extensively in previous studies to analyze trends in cardiovascular mortality. We used the Multiple Cause-of-Death Public Use dataset to identify deaths in which hypertension and cerebral infarction were reported on the death certificate, either as contributing or underlying causes.
Adults were defined as individuals aged 25 years or older at the time of death. This cutoff aligns with previous epidemiological studies utilizing CDC WONDER data and reflects a threshold at which chronic conditions such as hypertension and cerebrovascular diseases typically begin to manifest at higher rates. Choosing age 25 also reduces the potential for misclassification of paediatric and young adult deaths, which often have different etiologies and risk profiles.
This study was exempt from local institutional review board (IRB) approval because it used de-identified, publicly available government data and followed the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guidelines for reporting.
Data extraction
Data on population size, year of death, location of death, demographics, urban-rural classification, region, and state were extracted. Demographic variables included sex, age, and race/ethnicity. Location of death included medical facilities (outpatient, emergency room, inpatient, dead on arrival, or status unknown), home, hospice, and nursing home/long-term care facilities. Race/ethnicity was categorized as non-Hispanic (NH) White, NH Black or African American, Hispanic or Latino, and NH Asian or Pacific Islander. All demographic and cause-of-death classifications were based on information reported on death certificates, a method that has been used in prior analyses of the CDC WONDER database. Urban-rural status was assessed using the National Center for Health Statistics Urban-Rural Classification Scheme, which categorizes counties as urban (large metropolitan area [population ≥1 million], medium/small metropolitan area [population 50,000–999,999]) or rural (population <50,000), according to the 2013 US Census classification. United States regions were classified as Northeast, Midwest, South, or West, following US Census Bureau definitions.
Statistical analysis
To examine national trends in hypertension and cerebral infarction-related mortality, we calculated both crude and age-adjusted mortality rates (AAMRs) per 100,000 population from 2000 to 2020, stratified by year, sex, race/ethnicity, state, and urban-rural status, with 95% confidence intervals (CIs). Crude mortality rates were calculated by dividing the number of relevant deaths by the corresponding United States population for each year. AAMRs were standardized to the year 2000 United States population.
Records with missing or incomplete demographic or cause-of-death data were excluded from subgroup analyses to maintain data integrity. However, they were retained in overall mortality trend analyses where feasible, in line with practices established in prior CDC WONDER-based studies. The completeness of death certificate data was generally high due to standardized reporting protocols across states.
We used the Joinpoint Regression Program (version 4.9.0.0, National Cancer Institute) to analyze trends over time and determine annual percent changes (APCs) with 95% CIs. , A p-value of <0.05 was considered statistically significant. This method applies log-linear regression models to detect significant changes in AAMRs over time. APCs were classified as increasing or decreasing if the slope was significantly different from zero using two-tailed t-tests.
Results
A total of 111,398 hypertension and cerebral infarction related deaths occurred among the adults (aged ≥ 25) between 2000 and 2020. Information for the location of death was available for 107,471 deaths. Of these, 46.6% occurred within medical facilities, 26.4% occurred in nursing homes/ long-term care facilities, 7.2% occurred in hospices, and 19.8% occurred at home.
Overall hypertension and ischemic stroke mortality trends
The AAMR for Cerebral Infarction with Associated Hypertension-Related deaths per 100,000 population was 3.115 and number of deaths was 5,568 in 2000, and in 2020 AAMR was 4.377 with the number of deaths of 11,851. The overall AAMR declined from 2000 to 2003 (APC: −1.2; 95% CI: −13.5 to 12.9), from 2003 to 2007 (APC: −12.8; 95% CI: −24.7 to 1.0), and from 2007 to 2014 (APC: −1.7; 95% CI: −7.1 to 4.0), followed by an increasing slope from 2014 to 2017 (APC: 27.9; 95% CI: −4.3 to 70.9), and from 2017 to 2020 (APC: 10.7; 95% CI: 0.6 to 21.8) ( Figure 1 ) ( Supplemental Table 1 ).
Overall and sex-stratified cerebral infarction with associated hypertension-related AAMRs per 100,000 in adults in the United States, 2000 to 2020. *Indicates that the annual percentage change (APC) is significantly different from zero at α = 0.05. AAMR = age-adjusted mortality rate; CI = Confidence Intervals.
Sex-based hypertension and ischemic stroke mortality trends
Initially, AAMR was higher in women as compared to men, but the later trends show consistently higher AAMR in men (overall AAMR men: 2.477; 95% CI: 2.454 to 2.500; women: 2.329; 95% CI: 2.311 to 2.347). The AAMRs declined in men until 2009 (APC: −7.797; 95% CI: −10.045 to −5.493), with the slight increase in mortality till 2015 (APC: 2.416; 95% CI: −3.933 to 9.185), followed by a significant increase till 2018 (APC: 30.474; 95% CI: 6.023 to 60.565), and then till 2020 (APC: 5.451; 95% CI: −10.546 to 24.308). Similarly, the AAMRs for women constantly declined till 2014, which was then followed by a sudden spike in the mortality to AAMR 3.075 (95% CI: 2.984 to 3.165) in 2017 (APC: 28.537; CI: −1.125 to 67.097), with the constantly increasing slope till 2020 (APC: 10.159; 95% CI: 1.055 to 20.082) ( Figure 1 ) ( Supplemental Table 1 ).
Race/ethnicity-based hypertension and ischemic stroke mortality trends
When stratified by race/ethnicity, AAMRs were highest among NH Black or African American patients followed by Hispanics or Latino, NH White, NH Asian or Pacific Islander, and NH American Indian or Alaska Native populations. The AAMRs for NH Black or African American, NH American Indian or Alaska Native, and NH Asian or Pacific Islander declined till 2016 and AAMRs for Hispanics or Latino, and NH White declined until 2015, followed by the constant increase till 2020 for all races. The AAMR for NH Black or African American showed steady decline from 2000 to 2013 (APC: −8.421; 95% CI: −10.521 to −6.272) followed by a steep increase till 2020 (APC: 18.245; 95% CI: 12.444 to 24.345). For Hispanics or Latino, the AAMR showed decline from 2000 to 2009 (APC: −7.642; 95% CI: −11.457 to −3.663), followed by the slight increase till 2014 (APC: 0.838; 95% CI: −12.059 to 15.627), after which there was a spike in the mortality till 2017 (APC: 35.528; 95% CI: −1.470 to 86.419) and 2020 (APC: 10.068; 95% CI: −0.490 to 21.745). For NH White, AAMR declined from 2000 to 2012 (APC: −6.546; 95% CI: −8.541 to −4.507), followed by an increasing slope till 2020 (APC: 16.124; 95% CI: 12.274 to 20.105). For Asian or Pacific Islander, AAMR declined from 2000 to 2013 (APC: −8.771; 95% CI: −11.744 to −5.698), followed by an increase till 2020 (APC: 18.595; 95% CI: 11.307 to 26.360) ( Figure 2 ) ( Supplemental Table 1 ).
Cerebral infarction with associated hypertension-related AAMRs per 100,000 stratified by race in adults in the United States, 2000 to 2020. *Indicates that the APC is significantly different from zero at α = 0.05. NH = Non-Hispanic; other abbreviations as in Figure 1 .
Regional hypertension and ischemic stroke mortality trends
When stratified by census region, the overall AAMRs were highest in the South, followed by West, Midwest, and Northeast regions (overall AAMR South: 2.646; 95% CI: 2.621–2.671; West: 2.605; 95% CI: 2.573–2.637; Midwest: 2.348; 95% CI: 2.319–2.377; Northeast: 1.883; 95% CI: 1.855–1.911) ( Figure 3 ). For the South, the AAMR showed a decline till 2014, followed by a spike in mortality till 2017 (APC: 30.488; 95% CI: 5.588 to 61.260) and 2020 (APC: 15.013; 95% CI: 7.340 to 23.236). For West, AAMR showed a decline from 2003 till 2014 after an initial rise in 2003, followed by a spike from 2014 till 2018 (APC: 30.030; 95% CI: 20.522 to 40.289), with a stable increase till 2020 (APC: 0.564; 95% CI: −10.005 to 12.374). For Midwest, the AAMR showed the constant decline from 2000 to 2013 (APC: −5.205; 95% CI: −6.806 to −3.576), followed by an increase till 2020 (APC: 14.469; 95% CI: 10.241 to 18.860). For Northeast, the AAMR showed the decline till 2015 from 2000, followed by a rise in mortality till 2018 (APC: 25.197; 95% CI: 5.805 to 48.143), which then showed a slight decrease till 2020 (APC: −2.107; 95% CI: −14.974 to 12.708) ( Figure 4 ) ( Supplemental Table 2 ).
Overall cerebral infarction with associated hypertension-related AAMRs per 100,000 stratified by census region in adults in the United States, 2000 to 2020.
Cerebral infarction with associated hypertension-related AAMRs per 100,000 stratified by census region in adults in the United States, 2000 to 2020. *Indicates that the APC is significantly different from zero at α = 0.05. Abbreviations as in Figure 1 .
Urban-rural disparities in hypertension and ischemic stroke-related mortality
When stratified by 2013 Urbanization, the AAMRs were higher in the rural population than the urban (overall AAMR rural: 2.52; 95% CI: 2.486–2.554; and urban: 2.303; 95% CI: 2.288–2.318). For urban population, the AAMR declined from 2000 to 2014 (APC: −6.005; 95% CI: −7.586 to −4.397), followed by a spike in mortality till 2017 (APC: 34.140; 95% CI: −5.303 to 90.040), with a constant increase till 2020 (APC: 9.577; 95% CI: −2.341 to 22.950). For rural population, there was an initial rise in mortality from 2000 to 2003 (APC: 2.452; 95% CI: −12.342 to 2.086), which then decreased till 2007 (APC: −14.028; 95% CI: −27.599 to 2.086), followed by a slight increase till 2014 (APC: 1.026; 95% CI: −5.410 to 7.899), with a spike from 2014 till 2020 (APC: 18.686; 95% CI: 13.134 to 24.510) ( Figure 5 and Supplemental Figure 1 ) ( Supplemental Table 3 ).
Cerebral infarction with associated hypertension-related AAMRs per 100,000 stratified by urban-rural status in adults in the United States, 2000 to 2020. *Indicates that the APC is significantly different from zero at α = 0.05. Abbreviations as in Figure 1 .
Discussion
It has been strongly established according to several studies that hypertension is a major preventable risk factor for all types of strokes, contributing to high morbidity and mortality worldwide. ,, Developing successful public health interventions requires an understanding of the trends in the prevalence of hypertension and cerebral infarction related mortality. Recent studies have highlighted that substantial geographical differences exist in these trends mainly due to socioeconomic disparities, modifications in lifestyle, and access to healthcare facilities. ,
In this nationwide retrospective analysis, of death certificates data collected from CDC WONDER database examining hypertension and cerebral infarction-related mortality from 2000 to 2020, we observed distinct and evolving trends over time. In this section we report several noteworthy findings of our study. Firstly, we noticed in the study that, there was a period of consistent decline in mortality rates from 2000 to 2014. However, this period of progress was not sustained. We saw a reversal of trends midway through the study period, with mortality rates showing a gradual then more pronounced increase, particularly from 2014 onwards. This upward trend was consistent across sex, racial and ethnic groups, geographic regions, and urban-rural classifications, suggesting that the burden of hypertension-related stroke mortality became more widespread and pervasive. Secondly, women had higher mortality rates at the start of study period but over time, men began to show consistently higher rates, indicating a significant shift in health outcomes between the genders. Thirdly, the study revealed significant racial disparities in health outcomes, with Black or African American individuals experiencing the highest mortality rates, followed by Hispanics or Latinos. Non-Hispanic White populations had lower mortality, suggesting the need to address the systemic issues behind these inequalities. Moreover, the study shows noticeable regional disparity in mortality rates, with the South consistently recording the highest rates and the Northeast the lowest. Lastly, nonmetropolitan areas experienced greater challenges in terms of mortality rates compared to metropolitan areas, highlighting the need to address health disparities between urban and rural communities. The setting of death also highlighted important aspects of healthcare delivery and access, with a substantial proportion of deaths occurring outside hospital settings, including in nursing homes, hospices, and homes ( Central Illustration ).
