Reasons For Geographic And Racial Differences In Stroke Study Research Articles

Rural versus Urban Residence in Adulthood and Incident Cognitive Impairment

Introduction: Rural versus urban living is a social determinant of cognitive health. We estimated the association of rural versus urban residence in the USA with incident cognitive impairment (ICI) and assessed effect heterogeneity by sociodemographic, behavioral, and clinical factors. Methods: The Reasons for Geographic and Racial Differences in Stroke Study (REGARDS) is a population-based prospective observational cohort of 30,239 adults, 57% female, 36% Black, aged 45+ years, sampled from 48 contiguous states in the USA in 2003–2007. We analyzed 20,878 participants who at baseline were cognitively intact with no history of stroke and had ICI assessed on average 9.4 years later. We classified participants’ home addresses at baseline as urban (population ≥50,000), large rural (10,000–49,999), or small rural (≤9,999) by Rural-Urban Commuting Area codes. We defined ICI as ≥1.5 SD below the mean on at least 2 of the following tests: word list learning, word list delayed recall, and animal naming. Results: Participants’ home addresses were 79.8% urban, 11.7% large rural, and 8.5% small rural. ICI occurred in 1,658 participants (7.9%). Small rural residents had higher odds of ICI than urban residents, adjusted for age, sex, race, region, and education (OR = 1.34 [95% CI: 1.10, 1.64]), and after further adjustment for income, health behaviors, and clinical characteristics (OR = 1.24 [95% CI: 1.02, 1.53]). Former smoking versus never, nondrinking versus light alcohol drinking, no exercise versus ≥4 times/week, CES-D depressive symptom score of 2 versus 0, and fair versus excellent self-rated health had stronger associations with ICI in small rural areas than in urban areas. For example, in urban areas, lack of exercise was not associated with ICI (OR = 0.90 [95% CI: 0.77, 1.06]); however, lack of exercise combined with small rural residence was associated with 1.45 times the odds of ICI compared with ≥4 bouts of exercise/week in urban areas (95% CI: 1.03, 2.03). Overall, large rural residence was not associated with ICI; however, black race, hypertension, and depressive symptoms had somewhat weaker associations with ICI, and heavy alcohol drinking a stronger association with ICI, in large rural areas than in urban areas. Conclusion: Small rural residence was associated with ICI among USA adults. Further research to better understand why rural residents are at higher risk for developing ICI and mechanisms to ameliorate that risk will support efforts to advance rural public health.

Plasma Pro-Enkephalin A and Ischemic Stroke Risk: The Reasons for Geographic and Racial Differences in Stroke Cohort

ObjectivesThe opioid neuropeptide pro-enkephalin A (PENK-A) may be a circulating marker of cardiovascular risk, with prior findings relevant to heart failure, kidney disease, and vascular dementia. Despite these findings, the association of PENK-A with ischemic stroke is unknown, so we examined this association in a prospective cohort study and analyzed differences by race and sex. Materials and MethodsThe REasons for Geographic and Racial Differences in Stroke study (REGARDS) is a prospective cohort study of 30,239 Black and White adults. Plasma PENK-A was measured in 473 participants that developed first-time ischemic stroke over 5.9 years and 899 randomly selected participants. Cox models adjusted for demographics and stroke risk factors were used to calculate hazard ratios (HRs) of stroke by baseline PENK-A. ResultsPENK-A was higher with increasing age, female sex, White race, lower body mass index, and antihypertensive medication use. Each SD higher increment of PENK-A was associated with an adjusted HR of 1.20 (95% CI 1.01-1.42) for stroke, with minimal confounding by stroke risk factors. Spline plots suggested a U-shaped relationship, particularly in White men, with an adjusted HR 3.88 (95% CI 1.94-7.77) for the 95th versus 50th percentile of PENK-A in White men. ConclusionsHigher baseline plasma PENK-A was independently associated with future stroke risk in REGARDS. This association was most apparent among White men. There was little confounding by established stroke risk factors, suggesting a possible causal role in stroke etiology. Further research is needed to understand the role of endogenous opioids in stroke pathogenesis.

Development and Validation of Novel Dietary and Lifestyle Inflammation Scores

Chronically higher inflammation, which may partly result from diet and lifestyle, is implicated in risk for multiple chronic diseases. The dietary inflammatory index (DII) and empirical dietary inflammatory pattern (EDIP), developed to characterize dietary contributions to systemic inflammation, have several limitations. There are no scores to characterize contributions of lifestyle to inflammation. To reflect dietary/lifestyle contributions to inflammation, we developed novel, inflammation biomarker panel-weighted, dietary (DIS) and lifestyle (LIS) inflammation scores in a subset (n=639) of the Reasons for Geographic and Racial Differences in Stroke Study (REGARDS) cohort. We selected a priori 19 food groups and 4 lifestyle characteristics to comprise the DIS and LIS, respectively. We calculated the components' weights based on their strengths of association with an inflammation biomarker score [comprising high-sensitivity C-reactive protein (hsCRP), IL-6, IL-8, and IL-10] using multivariable linear regression. The sums of the weighted components constitute the scores, such that higher scores reflect, on balance, more proinflammatory exposures. We calculated the DIS, LIS, DII, and EDIP with cross-sectional data from the remaining REGARDS cohort ( n=14,210 with hsCRP measurements) and 2 other study populations with hsCRP and/or an 8-component inflammation biomarker panel, and investigated their associations with circulating inflammation biomarker concentrations using multivariable logistic regression. In REGARDS, those in the highest relative to the lowest DIS, LIS, DII, and EDIP quintiles had statistically significant 1.66-, 4.29-, 1.56-, and 1.32-fold higher odds of a high hsCRP concentration (>3 mg/dL), respectively (all P-trend<0.001). Those in the highest relative to the lowest joint DIS/LIS quintile had a statistically significant 7.26-fold higher odds of a high hsCRP concentration. Similar findings were noted in the other 2 validation populations. Our results support that dietary and lifestyle exposures collectively contribute substantially to systemic inflammation, and support the use of our novel DIS and LIS.

Abstract 032: Rural Versus Urban Living and Incident Cognitive Impairment in the Reasons for Geographic and Racial Differences in Stroke Study (REGARDS)

Objective: To estimate the association of rural vs urban living in the United States (US) with incident cognitive impairment (ICI), and to assess confounding, mediation, and effect heterogeneity by demographic, social, behavioral, and clinical risk factors. Methods: REGARDS is a cohort of 30,239 adults aged 45+ in the 48 contiguous states. We analyzed 20,592 participants who at baseline (2003-2007) were cognitively intact with no history of stroke and had cognition assessed an average of 7.1 years later. We used Rural-Urban Commuting Area (RUCA) codes to classify participants as urban (n = 16,436), large city/town (n = 2,420), or small/isolated rural (n = 1,736) at baseline. We defined ICI as falling ≥1.5 SD below the mean on at least two of three cognitive tests administered during follow-up: word list learning, word list delayed recall, and animal naming. Using urban as the referent, we estimated odds ratios of ICI for rural and for large city/town. Results: ICI occurred in 1,291 participants (6.3%). Rural residents had 49% higher odds of ICI adjusted for confounding by demographics (Model 2 in Table, OR = 1.49 [95% CI: 1.19, 1.85]). After further adjusting for potential mediators (Models 3-6), odds of ICI remained 25% higher for rural vs urban (Model 6, OR = 1.25 [0.99, 1.56]). In assessing effect heterogeneity, we found synergism of rural dwelling with black race, physical inactivity, and low self-rated health (all P &lt; 0.1; see ORs in Table), but not for other ICI risk factors. We found no difference in ICI for large city/town vs urban (demographics-adjusted OR = 1.08 [0.88, 1.33]; fully adjusted OR = 0.95 [0.77, 1.18]), and no effect heterogeneity of ICI risk factors by large city/town (all P &gt; 0.2). Conclusion: Rural living is an important social determinant of cognitive health in the US. ICI was significantly more frequent among rural dwellers than urban dwellers, partly due to confounding or mediation by ICI risk factors. Odds of ICI were highest for rural dwelling combined with black race, physical inactivity, or low self-rated health.

Abstract 38: Racial Differences in Intracerebral Hemorrhage Risk: The REasons for Geographic and Racial Differences in Stroke Study (REGARDS)

Introduction: Intracerebral Hemorrhage (ICH) risk is higher in blacks vs whites in the U.S. especially at younger ages. We used the REGARDS study to determine what prospectively assessed factors may underlie black-white differences in ICH risk. Methods: REGARDS recruited black and white individuals aged 45+ in the U.S. to explain regional and racial differences in stroke risk. Cox models with an age*race interaction term estimated the age-dependent hazard ratio (HR) of black versus white individuals for ICH. The 95% confidence interval (CI) of the percent attenuation of the age-dependent hazard ratio (HR) from the baseline to the final model was calculated using bootstrapping. Results: Among 29,694 REGARDS participants (55% women; 41% black), 160 ICH events occurred over 254,440 person-years of follow-up (median 9.5 years). The point estimate for the black-white HR for ICH decreased with increasing age, being 4.8, 2.7, and 1.5 at ages 45y, 55y, and 65y (Table, Baseline Model). In a final model, the point estimate for ages 45, 55, and 65 decreased to 3.9, 2.3, and 1.4, corresponding to a 24% (95% CI 11%. 100%), 24% (95% CI 16%, 100%), and 20% (95% CI 14%, 100%) decrease in the HR at ages 45y, 55y, and 65y. No increased ICH risk was seen in blacks over 65y. When added individually to the baseline model, none of the risk factors except diet (modeled as 6 principle components of dietary patterns) attenuated the association of black race with ICH risk. Conclusions: A quarter of the association of race with ICH may be explained by the risk factors studied here. Diet, particularly salt intake, may play a large role in black-white differences of ICH risk. While the absolute number of ICH events limits our analysis, prospective assessment of risk factors is a huge strength. Future primary and secondary ICH prevention efforts, particularly in younger blacks, should assess efficacy of dietary interventions.

Abstract P181: Contribution of C-Reactive Protein to Racial Disparities in Incident Hypertension: The REasons for Geographic And Racial Differences in Stroke Study (REGARDS)

Introduction: In the US, blacks are at higher risk of hypertension than whites. The single largest contributor to this disparity is the Southern Diet pattern. Inflammation biomarkers are associated with risk of hypertension, and C-reactive protein (CRP) is higher in blacks than whites. We studied whether elevated CRP in blacks relative to whites contributes to the racial disparity in hypertension in blacks. Methods: We included 6,548 black and white men and women age ≥45 years from the REGARDS cohort without hypertension at baseline ('03-'07) and who completed visit 2 in '13-'16. Incident hypertension was defined as BP ≥140/90 mm Hg or hypertension medication use at visit 2. Using logistic regression, the black:white odds ratio (OR) for incident hypertension was calculated adjusting for age, sex, race, and baseline SBP. We assessed the percent change in the black:white OR for incident hypertension after adding CRP. The 95% CI was calculated using 1,000 bootstrapped samples. We determined the impact of known hypertension risk factors and anti-inflammatory medications on the percent mediation by CRP. Results: Hypertension developed in 46% of blacks and 33% of whites. Adjusting for demographics, the black:white OR (95% CI) was 1.51, which was reduced to 1.46, a 9.3% reduction (95% CI 5.4%, 13.2%) by CRP (Table). In models including exercise, waist circumference, BMI, and depressive symptoms, the percent mediation by CRP was 3.7% (1.0%, 6.4%). Similar patterns were seen for models incorporating socioeconomic factors and medication use. After adding Southern diet pattern and dietary Na/K ratio, CRP no longer attenuated the association (1.3% mediation; -1.5, 4.1). Conclusions: CRP significantly attenuated the black-white difference in incident hypertension; however, once dietary factors were accounted for, CRP had no impact on the black:white difference in incident hypertension. Thus, inflammation as measured by CRP, may be part of the reason that dietary factors influence the black:white disparity in incident hypertension.

Abstract 3287: Associations of whole food and lifestyle-based inflammation scores with all-cause, cancer- and cardiovascular disease-specific mortality

Abstract Chronically higher levels of inflammation have been implicated in the etiology of cancer and other major chronic diseases. Contributors to chronic inflammation likely include diet, physical activity, obesity, and smoking. We developed dietary (DIS), lifestyle (LIS), and overall (OIS) inflammation scores to characterize the aggregate of pro- and anti-inflammatory exposures, and investigated associations of the scores with all-cause, cancer- and cardiovascular disease (CVD)-specific mortality in the prospective Reasons for Geographic and Racial Differences in Stroke Study (REGARDS) (n=21,426). The components of the scores were selected based on biological plausibility and previous literature. The dietary components included processed meats, red meat, white meat, fish, nuts, legumes, coffee, tea, dairy products, refined and whole grains, and nine other botanical categories. The lifestyle components included body mass index, smoking status, alcohol intake, and exercise level. Associations of each score component with a panel of biomarkers of inflammation in a subset of 577 male and female, black and white, chronic disease-free participants in REGARDS were assessed using multivariable linear regression, and the resulting beta coefficients were used to weight each score component. For each study participant, the weighted score components were summed to produce the scores such that a higher score was more pro-inflammatory. The scores were categorized according to quintiles of their distributions among all REGARDS participants at baseline, and their associations with mortality were assessed using multivariable Cox proportional hazards regression. Over an average of 7.89 years follow-up, 2,964 individuals died, including 854 from cancer. With increasing levels of each score, there was increasing risk for all-cause, cancer- and CVD-specific mortalities. For those in the highest relative to the lowest quintiles of the OIS, DIS, and LIS, the multivariable-adjusted hazard ratios (95% confidence intervals) for all-cause mortality were: 2.16 (1.87, 2.49; Ptrend&amp;lt;0.0001), 1.25 (1.10, 1.41; Ptrend&amp;lt;0.0001), and 1.94 (1.69, 2.24; Ptrend&amp;lt;0.0001), respectively. The corresponding findings for cancer mortality were 1.79 (1.38, 2.32; Ptrend&amp;lt;0.0001), 1.20 (0.95, 1.50; Ptrend=0.10), and 1.83 (1.42, 2.37; Ptrend&amp;lt;0.0001), respectively, and for CVD mortality 2.38 (1.83, 3.09; Ptrend&amp;lt;0.0001), 1.28 (1.02, 1.61; Ptrend=0.03), and 1.90 (1.49, 2.42; Ptrend&amp;lt;0.0001). These results suggest that pro-inflammatory diets and lifestyles may be associated with higher risk for all-cause, cancer- and CVD-specific mortality. Citation Format: Doratha Byrd, Ashley Holmes, Suzanne Judd, W Dana Flanders, Roberd M. Bostick. Associations of whole food and lifestyle-based inflammation scores with all-cause, cancer- and cardiovascular disease-specific mortality [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3287. doi:10.1158/1538-7445.AM2017-3287

Haemostasis biomarkers and risk of intracerebral haemorrhage in the REasons for Geographic and Racial Differences in Stroke Study.

Pathologic alterations in haemostasis cause bleeding disorders, but it is unknown if variation within the normal range relates to intracerebral haemorrhage (ICH) risk. It was our objective to assess the prospective associations of haemostasis biomarkers with ICH risk. The REasons for Geographic and Racial Differences in Stroke study (REGARDS) recruited 30,239 U. S. individuals aged ≥45 years. ICH was ascertained through biannual telephone contact and review of deaths followed by medical record evaluation. Haemostasis biomarkers (factor VIII (FVIII), factor IX (FIX), factor XI (FXI), fibrinogen, protein C, and D-dimer) were measured in a case cohort study consisting of ICH and a 1,104 person cohort random sample. The hazard ratio (HR) and 95 % confidence interval (CI) by biomarker were estimated using Cox models and adjusted for ICH risk factors. Individuals with a prior history of stroke, ICH or on warfarin were excluded. Over a median 5.8 years 66 ICH occurred. Fibrinogen, FVIII, FXI, and protein C were not associated with ICH risk in any analysis. Lower FIX increased risk of ICH with the bottom versus the top tertile of FIX associated with an HR of 5.68 (95 % CI 2.30, 14.05). D-dimer demonstrated a non-linear relationship with a potential threshold effect with increased risk only in the top 5th percentile (HR 3.22; 95 % CI 1.01, 10.31; pnon-linear = 0.04).In conclusion, low FIX levels within the normal range were associated with increased ICH risk. These data suggest non-pathologic alterations in haemostasis impact intracranial bleeding risk.

Dietary Flavonoid Intake and Incident Coronary Heart Disease in the Reasons for Geographic and Racial Differences in Stroke Study (REGARDS)

Dietary Flavonoid Intake and Incident Coronary Heart Disease in the Reasons for Geographic and Racial Differences in Stroke Study (REGARDS)

PCSK9 variation and association with blood pressure in African Americans: preliminary findings from the HyperGEN and REGARDS studies.

Proprotein convertase subtilisin/kexin type 9 (encoded by PCSK9) plays a well-known role in the regulation of low-density lipoprotein (LDL) receptors, and an inhibitor of this enzyme is a promising new therapeutic for hyperlipidemia. Recently, animal and human studies also implicate PCSK9 genetic variation in the regulation of blood pressure. The goal of this study was to examine if common and rare polymorphisms in PCSK9 are associated with blood pressure in an African-American population at high risk for cardiovascular disease. Using genomic data assayed on the Affymetrix 6.0 array (n = 1199) and the Illumina HumanExome Beadchip (n = 1966) from the Hypertension Genetic Epidemiology Network (HyperGEN), we tested the association of PCSK9 polymorphisms with blood pressure. We used linear mixed models and the sequence kernel association test (SKAT) to assess the association of 31 common and 19 rare variants with blood pressure. The models were adjusted for age, sex, center, smoking status, principal components for ancestry and diabetes as fixed effects and family as a random effect. The results showed a marginally significant effect of two genome-wide association study (GWAS) single-nucleotide polymorphisms (SNPs) (rs12048828: β = 1.8, P = 0.05 and rs9730100: β = 1.0, P = 0.05) with diastolic blood pressure (DBP); however these results were not significant after correction for multiple testing. Rare variants were cumulatively associated with DBP (P = 0.04), an effect that was strengthened by restriction to non-synonymous or stop-gain SNPs (P = 0.02). While gene-based results for DBP did not replicate (P = 0.36), we found an association with SBP (P = 0.04) in the Reasons for Geographic And Racial Differences in Stroke study (REGARDS). The findings here suggest rare variants in PCSK9 may influence blood pressure among African Americans, laying the ground work for further validation studies.

Left Ventricular Hypertrophy and Incidence of Acute Coronary Heart Disease and Mortality in the Reasons for Geographic and Racial Differences in Stroke Study (REGARDS)

1 Division of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC, USA. 2 Department of Biostatistics, University of Alabama at Birmingham School of Public Health, Birmingham, Alabama, USA. 3 Division of Preventive Medicine, University of Alabama at Birmingham School of Medicine, Birmingham, AL, USA. 4 Division of Cardiovascular Disease, University of Alabama at Birmingham School of Medicine, Birmingham, AL, USA. 5 Department of Epidemiology, Rollins School of Public health, Emory University, Atlanta, AL, USA.

Adoption of Outpatient Treatment of Deep Vein Thrombosis in the U.S.: The Reasons for Geographic and Racial Differences in Stroke Study (REGARDS)

▪Introduction: Outpatient treatment of deep vein thrombosis (DVT) has been shown equivalent to inpatient treatment in clinical trials and results in cost savings and increased patient-convenience. Despite the advantages, there are few studies on the national uptake of outpatient care of DVT in the U.S. and there are no national surveillance studies of DVT. Through understanding the current treatment patterns of DVT, we can design interventions to reduce health care costs and increase patient convenience.Methods: Between 2003-07, 30,239 participants ≥45 years old were enrolled in REGARDS, a nationally representative cohort recruited from the contiguous U.S. By design, 55% were female, 41% were black, and 56% lived in the southeast. Venous thrombosis (VTE) events were ascertained through 2011, with identification by telephone interview, review of reported hospitalizations, and review of deaths and validated by physician review of hospital and outpatient records. Using all available information, characteristics of the VTE event and treatment were systematically recorded. Location of residence was defined by geocoding of the address with urbanicity defined by census tract, and other risk factors were obtained through surveys, telephone interviews, or an in-home visit. We used logistic regression to determine the predictors of outpatient treatment of DVT among those with DVT.Results: Over 5 years of follow-up 379 VTE events occurred (incident and recurrent); 185 were diagnosed with a pulmonary embolism and 53 occurred as a complication of hospitalization (and not eligible for outpatient treatment) leaving 141 DVT events potentially eligible for outpatient treatment. Only 28% of DVT events (39 of 141) were treated as an outpatient. Factors significantly associated with being treated as an outpatient include younger age, female sex, white race, later year of DVT diagnosis, and living in an urban area (Table). Other risk factors with high odds ratios that were not statistically significant were living outside the southeast of the U.S. and being a high school graduate (Table).Conclusions: In a contemporary, nationally representative cohort, only 28% of DVT events were treated as an outpatient. Adverse socioeconomic status, residence in a rural area, advancing age, race, and male sex were independently associated with lower likelihood of outpatient treatment. These data highlight the low proportion of DVTs currently treated on an outpatient basis, as well as disparities in the outpatient treatment of DVT. Outpatient DVT treatment has the potential to reduce the cost of medical care for DVT in the U.S.Table:Predictors of Outpatient treatment of DVTs in the REGARDS StudyVariablePrevalence of Factor(%, n)Odds ofOutpatient Treatment*Age (per 10 years younger)69 years (Median)1.90 (1.19, 3.02)Year of VTE (per 1 year later)2008 (Median, range 2003-11)1.35 (1.03, 1.77)Sex (female vs male)46.8% (66)2.41 (1.06, 5.47)Race (white vs black)66.0% (93)3.29 (1.30, 8.30)Region (elsewhere vs southeast)50.4% (71)2.00 (0.87, 4.63)High School Graduate (yes vs no)90.8% (128)4.51 (0.52, 38.82)Income >$20,000 (yes vs no)63.8% (90)2.63 (0.87, 7.94)Living in a Urban Area (yes vs no)75.2% (106)4.16 (1.25, 13.79)Adjusted for age, sex, race, VTE event year and region* DisclosuresNo relevant conflicts of interest to declare.

Abstract P217: Coagulation Factor IX Levels and Risk of Stroke and Coronary Heart Disease: The REasons for Geographic And Racial Differences in Stroke Study (REGARDS)

Introduction: The role of coagulation in coronary heart disease (CHD) and stroke remains controversial. We examined the association of levels of coagulation factor IX (FIX) with incident CHD and ischemic stroke in REGARDS. Methods: REGARDS recruited 30,239 participants in their homes across the contiguous U.S. between 2003-07; by design 41% were black, 55% female, and 56% lived in the southeast. Levels of FIX were measured in participants with incident CHD (n=654), incident stroke (n=646), and in a cohort random sample (n=1,104). Cox models were used to calculate the hazard ratio (HR) per standard deviation (SD) higher FIX level for incident CHD and stroke adjusting for traditional cardiovascular disease (CVD) risk factors, and testing a race by FIX interaction term. Participants with hemorrhagic stroke were excluded from the stroke analyses (n=73). Results: Levels of FIX were higher with increasing age, black race, female gender, diabetes, hypertension, dyslipidemia, and among those living in the southeastern U.S. (all p&lt;0.0001). As shown in the table, FIX levels (per 1 SD higher) were associated with CHD, but not stroke, after adjustment for CVD risk factors. When stratified by race, the association with CHD was stronger in blacks than whites (p-interaction = 0.08) with no association for stroke in either blacks or whites (p-interaction 0.71). Analyses of FIX by quintiles did not alter the results. Discussion: Levels of coagulation factor IX were significantly associated with incident CHD, but not stroke in blacks but not whites, after adjustment for CVD risk factors. These data suggest that higher levels of FIX are a risk factor for CHD in blacks but not whites, and may indicate different roles for hemostasis in vascular disease risk by race and by vascular disease type.

Racial and Regional Differences in Venous Thromboembolism in the United States in 3 Cohorts

Blacks are thought to have a higher risk of venous thromboembolism (VTE) than whites. However, prior studies are limited to administrative databases that lack specific information on VTE risk factors or have limited geographic scope. We ascertained VTE from 3 prospective studies: the Atherosclerosis Risk in Communities Study (ARIC), the Cardiovascular Health Study (CHS), and the Reasons for Geographic and Racial Differences in Stroke study (REGARDS). We tested the association of race with VTE using Cox proportional hazard models adjusted for VTE risk factors. Over 438 090 person-years, 916 incident VTE events (302 in blacks) occurred in 51 149 individuals (17 318 blacks) who were followed up. In risk factor-adjusted models, blacks had a higher rate of VTE than whites in the CHS (hazard ratio, 1.81; 95% confidence interval, 1.20-2.73) but not ARIC (hazard ratio, 1.21; 95% confidence interval, 0.96-1.54). In REGARDS, there was a significant region-by-race interaction (P=0.01): Blacks in the Southeast had a significantly higher rate of VTE than blacks in the rest of the United States (hazard ratio, 1.63; 95% confidence interval, 1.08-2.48) that was not seen in whites (hazard ratio, 0.83; 95% confidence interval, 0.61-1.14). The association of race with VTE differed in each cohort, which may reflect the different time periods of the studies or different regional rates of VTE. Further studies of environmental and genetic risk factors for VTE are needed to determine which underlie racial and perhaps regional differences in VTE.