Differences in Multiple Risk Factors Between Black and White Individuals With Young-Onset Ischemic Stroke

Abstract

Background and Objectives

Stroke in young adults constitutes 15%–18% of all ischemic stroke cases. Black individuals have an excess risk of ischemic stroke especially in young adults. Although it is known that Black patients have a higher prevalence of hypertension and diabetes, few studies have addressed the association of concurrent multiple vascular risk factors with the excess risk of early-onset stroke among Black individuals.

Methods

A population-based case-control study of early-onset ischemic stroke, ages 15–49 years, was conducted in the Baltimore-Washington DC region between 1992 and 2007. Presence of the risk factors of obesity, hypertension, diabetes, and current smoking were obtained from both cases and controls by an in-person interview. Risk factor groups were defined as (1) 1 risk factor, (2) 2 risk factors, (3) 3 risk factors, and (4) 4 risk factors. Logistic regression analysis adjusting for age and sex was used to evaluate the association between each risk factor group and ischemic stroke compared with the reference group with no risk factors.

Results

The study included 1,034 cases and 1,091 controls. Of the cases, 47% were Black, 54% were men, and the mean (±SD) age was 41.0 (±6.9) years. The odds of having a stroke increased exponentially as the number of risk factors increased, 2.1, 2.6, 7.6, 16.5, all p < 0.001, for groups 1–4, respectively. When stratified by race, Black individuals were approximately 6 times more likely to have all 4 risk factors.

Discussion

The risk of stroke in young adults increased exponentially with the number of risk factors. Young Black patients with ischemic stroke were approximately 6 times more likely to have the co-occurrence of obesity, hypertension, diabetes, and smoking compared with their White counterparts. Targeting public health interventions to identify and improve care to Black young adults with multiple stroke risk factors may have substantial impact on lowering risk of stroke.

Ischemic stroke hospitalizations and the prevalence of traditional vascular risk factors are increasing in young adults.¹ Young adults are also the age group where the excess risk of stroke in Black individuals is most marked.² Multiple risk factors have been associated with stroke in the young, but there is a paucity of race-stratified data on this issue. Although racial disparities in vascular risk factors are driven by broad structural and social determinants of health and do not reflect intrinsic biological differences between racial groups, this does not diminish the importance of studying racial differences in health outcomes. The objective of this report is to compare the number of concurrent risk factors between Black and White young adults with ischemic stroke and determine the association of multiple risk factors with ischemic stroke in each race group.

Methods

The Stroke Prevention in Young Adults Study was designed as a population-based case-control study of early-onset ischemic stroke. During 3 study periods between 1992 and 2008, cases with an incident ischemic stroke ages 15–49 years were identified by discharge surveillance from 59 nonfederal acute care hospitals in the Baltimore/Washington, DC area and by direct referral from regional neurologists. The diagnosis of ischemic stroke and ischemic stroke subtype was determined by 2 neurologists with agreements adjudicated by a third neurologist. Ischemic stroke occurring as complication of trauma, procedures, or subarachnoid hemorrhage were excluded. In the initial study period, only women were recruited, the upper age limit was 44 years, and controls were in a 2:1 ratio to cases and were frequency-matched to cases by age, sex, and region of residence. Women were recruited in the second study period and men in the third study period. In the last 2 study periods, the upper age limit was 49 years, and controls were in a 1:1 ratio to cases and were additionally matched for race. Controls obtained by random digit dialing were frequency-matched to cases by age, sex, and region of residence and except for the initial study phase were additionally matched for race. The most conservatively estimated response rate was 65.6%, while the response rate based on numbers successfully screened was 87.1%.³ Details of the study design and case adjudication have been previously described.^4,5

Age, race, current smoking status, diabetes mellitus, hypertension, and obesity, defined as a body mass index of 30 or greater, were obtained by standardized interview at the study visit from both cases and controls.⁶ For cases, the reference time for risk factor status was the date of the stroke. For controls, the reference time was the date of interview (initial study period) or the day of week that the stroke occurred in the matched case (last 2 study periods).

Statistical analysis was performed using SAS 9.4 (SAS Institute, Cary, NC). The study included participants who identified themselves White, White Hispanic background, Black, and Black Hispanic background, and everyone else was excluded. The number of Hispanic persons in our catchment area is small, and only 3% of White and 2.2% Black participants identified themselves to be of Hispanic origin. We defined 4 different risk factor groups based on the presence or absence of current smoking, diabetes mellitus, hypertension, and obesity: group 1—1 risk factor, group 2—2 risk factors, group 3—3 risk factors, and group 4—4 risk factors. Logistic regression analysis was used to evaluate the association between each multiple risk factor group and ischemic stroke as compared with those with no risk factors after adjusting for age and sex. Primary analyses were stratified by race, but analyses were also performed stratified by race and sex and by age groups 15–34 and 35–49 years. To test the association between risk factor groupings and race and sex, a log-linear model was fit using the SAS CATMOD procedure. The study was reported in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guideline for case-control studies; the STROBE checklist can be found in the supplemental materials.

Standard Protocol Approvals, Registrations, and Patient Consents

The study was approved by the Institutional Review Board of the University of Maryland, Baltimore, and all participants or their legally authorized representative gave written informed consent.

Data Availability

Anonymized phenotype data that support the findings of this study are available from dbGaP (https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000292.v1.p).

Results

After exclusion of 10 cases and 8 controls lacking complete data on all 4 risk factors, there were a total of 1,034 young adults with stroke and 1,091 nonstroke controls. Participant characteristics stratified by case-control status is shown in Table 1. The cases and controls were similar in age, sex, and race distribution, but there were a higher proportion of hypertension, diabetes mellitus, obesity, and low education among the cases. The Trial of ORG 10172 in Acute Stroke Treatment (TOAST) subtype classification among Black cases and White cases, respectively, were cardioembolism, 20.4% and 20.8%; large artery, 5.5% and 7.7%; small vessel, 17.4% and 11.6%; other, 6.9% NS 10.1%; and undetermined, 49.8% and 49.8%. Atrial fibrillation was diagnosed in less than 1% of patients in each race group. Participant characteristics stratified by race is shown in Table 2. Black participants had a higher proportion of each vascular risk factor and a higher proportion of low educational status.

Table 1.

Participant Characteristics Stratified by Case-Control Status

Table 2.

Participant Characteristics Stratified by Race

The distribution of risk factor groups among cases, stratified by race and sex, is shown in Table 3. Log-linear analysis was performed to determine the association of race and sex on the risk factor group distribution. Black race (p < 0.0001) and male sex (p < 0.0118) were highly associated with the groups with higher numbers of risk factors.

Table 3.

Distribution of Risk Factor Groups Among Cases Stratified by Race and Sex

The association of risk factor groups with stroke risk, stratified by race, is shown in Table 4. For both Black and White adults, there was an exponential increase in stroke risk with increasing number of risk factors.

Table 4.

Association of Risk Factor Groups With Stroke Risk, Stratified by Race^a

We further stratified the cases and controls by age. In the age group 35–49 years, 26.1% patients had 3 or 4 risk factors as compared with 1.9% in the age group 15–34 years. An exponential increase in stroke risk with increasing number of risk factors was preserved in the age group 35–49 years. A similar pattern by age was seen after stratification by race.

Discussion

Black stroke cases were 6 times more likely than White cases to have all 4 risk factors. We found an exponential increase in ischemic stroke risk as the number of risk factors increased. This risk gradient was similar among Black and White adults. There was also a marked difference in multiple risk factor burden by age. Cases ages 35–49 years were 14 times more likely to have 3 or 4 risk factors than cases ages 15–34.

The racial differences in multiple risk factor prevalence needs to be interpreted within the context of the social factors that drive these racial disparities. The importance of social factors as a determinant of vascular risk factors and vascular disease has been known at least since the prospective Whitehall study of British civil servants.⁸ More recently, a prospective study in Kaiser Permanente Northern California reported that education level and concentrated neighborhood poverty were each associated with the risk of developing hypertension and diabetes, and furthermore, there was a graded response between the risk of developing these 2 important vascular risk factors and the number of social and behavioral risk factors⁹. The Reasons for Geographical And Racial Differences in Stroke (REGARDS) study also found a graded association between the risk of developing hypertension and the count of social vulnerabilities defined across multiple domains including education, income, health insurance, residence in a health professional shortage area, and concentrated neighborhood poverty.¹⁰

The appreciation that stroke risk increases exponentially with the number of risk factors has been seen in other studies. The Framingham Heart Study⁶ evaluated adults aged 55–84 years and found that each additional risk factor over and above hypertension significantly and exponentially increased the risk for stroke. This study did not include young adults or address race disparities but suggested a synergistic pathophysiologic effect of coexistent risk factors on overall vascular health.

The importance of multiple risk factors for ischemic stroke in young adults is supported by a study of the National Inpatient Sample that found the prevalence of multiple risk factors in young adults, ages 18–63 years, with acute ischemic stroke had nearly doubled from 2003–2004 to 2011–2012 concurrent with a marked increase in hospitalization rates.¹ This report did not compare the prevalence of multiple vascular risk factors between Black and White patients and, because there was no control group, could not assess the stroke risk gradient associated with multiple risk factors. Both these limitations are addressed by this study.

A European study⁷ of a cohort of 4,467 patients aged 18–55 years previously described a marked increase in the proportion of ischemic stroke patients with 3 or more risk factors when patients were grouped by decade from 18–24 to 45–55. Although we could not stratify our patients as finely by age because our sample size was smaller, our findings by age were similar.

In the sifap1 study, multiple risk factors were not stratified by race. In addition, because there was no control group, the stroke risk gradient associated with multiple risk factors could not be addressed. The relative lack of multiple vascular risk factors among ischemic strokes in the age group 15–34 years suggests that stroke risk in this age group may be driven by other rare inherited or acquired causes.

Our study has several limitations. Our sample size precluded further stratification by age and by a larger number of risk factor groups. We only included analysis of 4 major risk factors—hypertension, diabetes, smoking, and obesity. It is highly probable that our analyses underestimated the importance of these risk factors because we did not measure blood pressure or duration of hypertension; similarly, we did not include amount and duration of smoking in our analyses. We could not include cholesterol or obstructive sleep apnea because we did not have complete information on our population of cases and controls. Our study was conducted in the Baltimore-Washington region, and our results may not generalize to Black and White individuals throughout the United States, but if anything, the differences might be more dramatic in other states, particularly in the stroke belt. Because our study was conducted between 1992 and 2007, our findings may not be indicative of contemporary risks. However, we believe that our findings remain relevant because the prevalence of multiple risk factors is increasing in young-onset ischemic stroke¹ and Black stroke patients continue to have markedly higher prevalence of hypertension, diabetes and, to a lesser extent, current smoking. In addition, the number of patients in our 4-risk factor subgroup was small, thus leading to very wide confidence intervals for the magnitude of effect of odds of having a stroke. Finally, because this was a retrospective case-control study, selection bias in recruitment of case and control participants, differential recall, and unrecognized confounding are possible.

Our study has several strengths. In contrast to studies based on hospitalization data that could include recurrent stroke and studies restricted to tertiary care medical centers, our study included first-ever strokes collected from all hospitals in a defined geographic region. Unlike previous studies of stroke in young adults, we were able to examine the prevalence of multiple vascular risk factors and the risk gradient associated with increasing numbers of traditional vascular risk factors in Black and White patients separately.

Our study highlights the disproportionate presence of multiple stroke risk factors in young Black ischemic stroke patients. This finding underscores not only the need for risk factor screening and intervention in this group but also the need for interventions addressing the social determinants of these vascular risk factors. Because the risk for stroke rises exponentially with each additional risk factor, prevention or treatment of even 1 risk factor, such as hypertension, could markedly reduce overall risk of stroke.

Appendix. Authors

Study Funding

This material is the result of work supported with resources and the use of facilities at the VA Maryland Health Care System, Baltimore, Maryland, and was also supported in part by the NIH (R01NS45012, R01NS105150, R01NS100178). The contents do not represent the views of the U.S. Department of Veterans Affairs or the United States Government.

Disclosure

The authors report no disclosures relevant to the manuscript. Go to Neurology.org/N for full disclosures.