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Stroke. Author manuscript; available in PMC 2015 Aug 1.
Published in final edited form as:
Stroke. 2014 Aug; 45(8): 2318–2323.
Published online 2014 Jul 10. doi:10.1161/STROKEAHA.114.004815
PMCID: PMC4131200
NIHMSID: NIHMS599146
PMID: 25013018
Susan A. Everson-Rose, PhD, MPH,1 Nicholas S. Roetker, BA,2 Pamela L. Lutsey, PhD, MPH,2 Kiarri Kershaw, PhD, MPH,3 WT Longstreth, Jr, MD, MPH,4 Ralph L. Sacco, MD, MS,5 Ana V. Diez Roux, MD, PhD, MPH,6 and Alvaro Alonso, MD, PhD2
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Abstract
Background and Purpose
This study investigated chronic stress, depressive symptoms, anger and hostility in relation to incident stroke and transient ischemic attacks (TIA) in middle-aged and older adults.
Methods
Data were from the Multi-Ethnic Study of Atherosclerosis (MESA), a population-based cohort study of 6,749 adults, ages 45-84 and free of clinical cardiovascular disease at baseline, conducted at 6 U.S. sites. Chronic stress, depressive symptoms, trait anger, and hostility were assessed with standard questionnaires. The primary outcome was clinically adjudicated incident stroke or TIA during a median follow-up of 8.5 years.
Results: 195 incident events (147 strokes; 48 TIA) occurred during follow-up. A gradient of increasing risk was observed for depressive symptoms, chronic stress, and hostility (all p-for-trend ≤0.02) but not for trait anger (p>.10). Hazard ratios (HR) and 95% confidence intervals (CI) indicated significantly elevated risk for the highest-scoring relative to the lowest-scoring group for depressive symptoms [HR=1.86; 95% CI=1.16-2.96], chronic stress [HR=1.59; 95% CI=1.11-2.27], and hostility [HR=2.22; 95% CI=1.29-3.81] adjusting for age, demograhics and site. HR were attenuated but remained significant in risk factor-adjusted models. Associations were similar in models limited to stroke and in secondary analyses utilizing time-varying variables.
Conclusions
Higher levels of stress, hostility and depressive symptoms are associated with significantly increased risk of incident stroke or TIA in middle-aged and older adults. Associations are not explained by known stroke risk factors.
Keywords: stress, emotions, stroke
Stress and negative emotions, including depression, anger, and hostility, adversely affect cardiovascular disease (CVD) morbidity and mortality.1 Less is known about their impact on stroke risk and there are methodological limitations to prior work. Studies limited to men or whites suggest that psychological stress and reactions to stressful experiences may increase stroke risk.2-5 Two recent meta-analyses concluded that stroke risk is elevated in depressed individuals, especially women, though most evidence is from hom*ogenous white populations.6,7 Single-item measures of psychosocial stress and depression were significant stroke risk factors in the INTERSTROKE study, an international multi-center case-control study conducted in 22 predominantly low- and middle-income countries.8 A composite of depressive symptoms, perceived stress, neuroticism, and dissatisfaction with life was related to stroke mortality and incident stroke in community-dwelling blacks and whites.9 Anger, a negative emotion related to hostile personality and aggressive behavior, has been related to excess stroke risk10,11 but was protective in another study;12 two of these studies included only white males and small numbers of strokes.10,12 Many of these prior studies did not use adjudicated stroke events, and most had limited risk factor data and/or limited assessments of psychosocial factors.
We used data from the Multi-Ethnic Study of Atherosclerosis (MESA) to investigate the association of chronic stress and negative emotions with a combined endpoint of incident stroke and transient ischemic attacks (TIA). MESA includes clinically adjudicated outcome data, repeat assessments of stress and negative emotions, and a broad array of risk factor data, allowing us to control for important confounding variables and examine potential underlying mechanisms.
METHODS
Study Design and Participants
MESA is a longitudinal observational study of risk factors for subclinical and clinical CVD, conducted at 6 field centers (Baltimore, MD; Chicago, IL; St. Paul, MN; Los Angeles, CA; New York City, NY; Forsyth County, NC)13 and adheres to STROBE guidelines (http://www.strobe-statement.org/fileadmin/Strobe/uploads/checklists/STROBE_checklist_v4_combined.pdf). Between July 2000 and August 2002, 6,814 participants (60% of eligible) aged 45 to 84 years and free of clinical CVD were recruited and completed a baseline examination. The cohort is 53% female, 38.5% non-Hispanic white, 27.8% black, 11.8% Chinese, and 21.9% Hispanic. Four additional examinations have been completed (Visit 2: 9/2002 to 2/2004; Visit 3: 3/2004 to 9/2005; Visit 4: 9/2005 to 5/2007; Visit 5: 4/2010 to 2/2012). All visits follow similar study protocols. Institutional review boards at all participating institutions approved the study; each participant provided written informed consent. Persons with missing data on all psychosocial measures or on any demographic variables were excluded; 6,749 participants were eligible for analyses of depressive symptoms, chronic stress burden, and anger, and 6,089 were eligible for analysis of hostility.
Outcome
MESA uses a standard adjudication protocol to classify events, as previously reported.14 Stroke was defined as rapid onset of documented focal neurologic deficits lasting 24 hours or until death and, if <24 hours, with imaging evidence (typically CT or MRI) of a clinically relevant lesion. TIA was defined as a documented focal neurologic deficit lasting 30 sec to 24 hours and without imaging evidence of a clinically relevant lesion or without imaging completed. A combined outcome was used that included 147 strokes (82.3% ischemic; 14.3% hemorrhagic; 3.4% unspecified) and 48 TIA ascertained through 2/22/2012. Prior studies of psychosocial factors and stroke often included TIA as part of the stroke outcome (e.g., defining stroke by ICD-9 codes 430-438) but rarely distinguished TIA from incident stroke events. Detailed outcome data in MESA allows us to make this distinction.
Psychosocial Factors
Standard questionnaires were administered in the respondent's language of choice (English, Spanish, Chinese). Chronic stress was measured at Visits 1 and 3 with the Chronic Burden Scale,15 which assesses presence and severity of ongoing stress in five domains: one's own health problems; health problems of close others; job or ability to work; relationships; finances. Participants were coded as experiencing stress for each domain in which they indicated an ongoing problem as moderately or very stressful. The chronic stress score was the number of domains for which a participant had ongoing difficulties (range, 0-5); 3 stress groups were created based on scores of 0, 1, and ≥2. The 20-item Center for Epidemiologic Studies Depression Scale (CES-D)16 was administered at Visits 1, 3 and 4; higher scores indicate more depressive symptoms (range, 0-60). Five CES-D groups were created based on the score distribution in approximate quartiles, with the top quartile split into two such that the top group represented the 12.9% of persons with a score ≥16, a value commonly used to identify clinically relevant symptoms. The Spielberger Trait Anger scale,17 a 10-item scale that assesses extent and frequency of experiencing anger (range, 10-40), was administered at Visits 1 and 3. Hostility was measured only at Visit 2 using 8 true/false items previously derived from the Cook-Medley Hostility Scale18 that measure individuals’ hostile attitudes and cynical expectations regarding others’ motives.19 All “true” responses were summed to create a hostility score (range, 0-8). For both anger and hostility, 4 groups were created based on approximate quartiles. MESA exam forms are available at http://www.mesa-nhlbi.org/ex1forms.aspx.
Covariates
Sociodemographic variables included age, race/ethnicity, sex, and education. Stroke risk factors included resting systolic blood pressure (SBP) obtained via standard protocol; self-reported smoking and alcohol use; physical activity assessed via the MESA Typical Week Physical Activity Survey,20; measured body mass index (BMI) and height (cm); high density lipoprotein (HDL) cholesterol and triglycerides measured from fasting blood specimens using standard assays; use of anti-hypertensive medications; and diabetes status defined by fasting glucose and ADA criteria.21 Additional covariates were Visit 1 carotid artery intima medial thickness (IMT), assessed by a standard protocol,22 high sensitivity C-reactive protein (CRP), fibrinogen, and interleukin 6 (IL-6), measured from fasting blood specimens using standard assays. Anti-depressant use was coded as a yes/no variable based on self-reported current use of tricyclic anti-depressants, MAO inhibitors, and other non-tricyclic anti-depressants at Visit 1.
Data Analysis
Cox proportional hazards models were used to calculate adjusted hazard ratios (HR) and 95% confidence intervals (CI) for the association of each psychosocial measure with the composite outcome of incident stroke/TIA, and secondarily, with the outcome limited to incident strokes. There was no violation of the proportional hazards assumptions in any model. Person-years accrued from the participant's Visit 1 date (Visit 2 for hostility), to the date of the participant's first stroke or TIA event, loss-to-follow-up, death, or 02/22/2012, whichever occurred first. With the outcome limited to incident strokes, follow-up time accrued until the participant's first stroke, loss-to-follow-up, death, or 02/22/2012.
Initial models adjusted for race, sex, age, education, and MESA field center site. Subsequent models adjusted for SBP, alcohol use, smoking status, physical activity, BMI, height, antihypertensive medication use, diabetes, HDL cholesterol, and triglycerides. Similar models were run with the psychosocial measures modeled continuously and then categorically according to the groupings described. Interactions between psychosocial measures and age, sex, and race/ethnicity were evaluated by including cross-product terms in each model. Additional Cox models adjusted for IMT and inflammatory markers (CRP, fibrinogen, and IL-6), or anti-depressant use (CES-D models only).
Primary analyses estimated the association of the psychosocial measures with the outcome ascertained over follow-up, and included covariates from Visit 1 (Visit 2 for hostility except alcohol use, assessed at Visit 1 only). The psychosocial measures were evaluated in separate models. Secondary analyses were conducted with psychosocial measures modeled simultaneously, with CES-D, chronic stress and anger, obtained at Visit 1, in one model, together with baseline covariates and risk factors, and hostility from Visit 2 added in a second model.
Additional analyses utilized repeat assessments of psychosocial factors and stroke risk factors through Visit 4. Initial time-dependent models updated just the covariates across study visits to determine if changes in behaviors and risk factors accounted for any observed associations; subsequent models updated data on both psychosocial measures and covariates to determine whether more recent experiences of these psychosocial characteristics were more strongly related to the outcome than prior assessments.
RESULTS
Table 1 presents baseline characteristics of all participants and by the primary outcome. Persons who experienced an incident event had more vascular risk factors than those who did not. Correlations among psychosocial measures ranged from r=.05 (stress and hostility) to r=.39 (CES-D and stress). Median follow-up was 8.5 years (range, 0.02-10.9 years).
Table 1
Participant Characteristics, Visit 1: MESA, 2000-2002
| All participants | Incident stroke or TIA | |||
|---|---|---|---|---|
| Yes | No | |||
| (N=6,749) | (N=195) | (N=6,554) | P-value* | |
| N (%) | N (%) | N (%) | ||
| Men | 3181 (47.1) | 96 (49.2) | 3085 (47.1) | 0.55 |
| Women | 3568 (52.9) | 99 (50.8) | 3469 (52.9) | -- |
| Race | 0.02 | |||
| Non-Hispanic White | 2602 (38.6) | 79 (40.5) | 2523 (38.5) | |
| Black | 1863 (27.6) | 58 (29.7) | 1805 (27.5) | |
| Hispanic | 1485 (22.0) | 49 (25.1) | 1436 (21.9) | |
| Chinese | 799 (11.8) | 9 (4.6) | 790 (12.0) | |
| Education | 0.03 | |||
| Less than high school diploma | 1214 (18.0) | 43 (22.0) | 1171 (17.9) | |
| High school diploma or some college | 3150 (46.7) | 100 (51.3) | 3050 (46.5) | |
| College degree or higher | 2385 (35.3) | 52 (26.7) | 2333 (35.6) | |
| Smoking status | 0.36 | |||
| Never | 3395 (50.3) | 96 (49.2) | 3299 (50.3) | |
| Former | 2472 (36.6) | 67 (34.4) | 2405 (36.7) | |
| Current | 882 (13.1) | 32 (16.4) | 850 (13.0) | |
| Alcohol use | 0.69 | |||
| Non-drinker | 3217 (48.1) | 91 (47.4) | 3126 (48.1) | |
| Light drinker (1-7 drinks/week) | 2440 (36.5) | 67 (34.9) | 2373 (36.5) | |
| Moderate drinker (8-14 drinks/week) | 574 (8.6) | 21 (10.9) | 553 (8.5) | |
| Heavy drinker (>14 drinks/week) | 458 (6.8) | 13 (6.8) | 445 (6.8) | |
| Use of anti-hypertensives | 2514 (37.3) | 104 (53.3) | 2410 (36.8) | <0.0001 |
| Fasting glucose/diabetes status | <0.0001 | |||
| Normal | 4949 (73.6) | 121 (62.4) | 4828 (73.9) | |
| Impaired fasting glucose | 928 (13.8) | 26 (13.4) | 902 (13.8) | |
| Untreated diabetes | 179 (2.7) | 7 (3.6) | 172 (2.6) | |
| Treated diabetes | 669 (9.9) | 40 (20.6) | 629 (9.6) | |
| Anti-depressant use | 496 (7.3) | 17 (8.7) | 479 (7.3) | 0.46 |
| Mean (SD) | Mean (SD) | Mean (SD) | ||
| Age, years | 62.1 (10.2) | 68.3 (9.4) | 62.0 (10.2) | <0.0001 |
| SBP, mmHg | 126.6 (21.5) | 140.7 (23.4) | 126.2 (21.3) | <0.0001 |
| BMI, kg/m2 | 28.3 (5.5) | 28.6 (4.9) | 28.3 (5.5) | 0.40 |
| Height, cm | 166.3 (10.0) | 165.3 (9.9) | 166.4 (10.0) | 0.13 |
| Moderate/vigorous physical activity (MET- min/wk) | 5753 (5896) | 4948 (5116) | 5777 (5917) | 0.03 |
| HDL cholesterol, mg/dL | 51.0 (14.8) | 47.6 (12.0) | 51.1 (14.9) | 0.0001 |
| Triglycerides, mg/dL | 131.7 (88.9) | 144.4 (78.0) | 131.3 (89.2) | 0.02 |
| Psychosocial Measures | ||||
| CES-D (range, 0-60) | 7.6 (7.6) | 8.6 (8.2) | 7.5 (7.6) | 0.06 |
| Chronic Stress (range 1-5) | 1.22 (1.21) | 1.27 (1.21) | 1.22 (1.21) | 0.31 |
| Trait Anger (range, 10-40) | 14.8 (3.7) | 14.5 (3.4) | 14.8 (3.7) | 0.43 |
| Hostility (range, 0-8)† | 2.7 (2.3) | 3.0 (2.3) | 2.7 (2.3) | 0.08 |
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*P-values from Chi-square tests or t-tests, as appropriate, are for comparisons of those who did or did not experience a stroke or TIA during follow-up.
†Hostility was measured at Visit 2 only (N=6,089; 137 with and 5,952 without an event).
Controlling for race, sex, age, education, and site, each 1-point higher score for CES-D (HR, 1.03; 95% CI, 1.01-1.04), chronic stress (HR, 1.19; 95% CI, 1.05-1.34) and hostility (HR, 1.10; 95% CI, 1.01-1.19) was related to increased risk of stroke/TIA in separate models. Associations remained significant with further risk factor adjustment [CES-D: HR, 1.02 (95% CI, 1.01-1.04); chronic stress: HR, 1.16 (95% CI, 1.02-1.31); hostility: HR, 1.08 (95% CI, 1.00-1.17)]. Anger was not significantly related to risk of stroke or TIA (p-values >0.10). As shown in Table 2, with the psychosocial measures modeled categorically, statistically significant gradients of increasing risk were observed for depressive symptoms, chronic stress, and hostility; the trend for anger was non-significant but associations were in the expected direction. Persons in the top groups (those with the highest scores) for CES-D, chronic stress and hostility were at 1.5 to more than two-fold increased risk of stroke/TIA during follow-up, relative to the lowest scoring group on each measure (Model 1). HR were diminished but remained significant with further risk factor adjustment (Model 2). Adjusting for anti-depressant use had no effect on observed associations (not shown).
Table 2
Categorical Psychosocial Measures and Risk of Stroke or TIA: MESA, 2000-2012.
| Group 1 | Group 2 | Group 3 | Group 4 | Group 5 | p-for-trend | |
|---|---|---|---|---|---|---|
| CES-D score | 0-2 | 3-5 | 6-10 | 11-15 | ≥16 | |
| Model 1 | referent | 1.14 (0.75-1.73) | 1.17 (0.78-1.77) | 1.31 (0.80-2.15) | 1.86 (1.16-2.96) | 0.02 |
| Events/N | 46/1821 | 42/1539 | 48/1699 | 25/810 | 33/869 | |
| Model 2 | referent | 1.09 (0.71-1.67) | 1.15 (0.76-1.74) | 1.26 (0.77-2.08) | 1.73 (1.08-2.77) | 0.03 |
| Events/N | 46/1805 | 40/1515 | 47/1674 | 25/796 | 32/853 | |
| Chronic Stress score | 0 | 1 | ≥2 | --- | --- | |
| Model 1 | referent | 1.22 (0.85-1.74) | 1.59 (1.11-2.27) | 0.01 | ||
| Events/N | 57/2292 | 64/2098 | 72/2324 | |||
| Model 2 | referent | 1.13 (0.79-1.63) | 1.48 (1.03-2.13) | 0.03 | ||
| Events/N | 57/2263 | 62/2073 | 70/2283 | |||
| Hostility score | 0 | 1-2 | 3-4 | ≥5 | --- | |
| Model 1 | referent | 1.47 (0.88-2.46) | 1.49 (0.86-2.57) | 2.22 (1.29-3.81) | 0.006 | |
| Events/N | 24/1426 | 39/1723 | 31/1522 | 43/1418 | ||
| Model 2 | referent | 1.36 (0.81-2.28) | 1.37 (0.79-2.38) | 2.00 (1.15-3.47) | 0.02 | |
| Events/N | 24/1412 | 38/1706 | 31/1511 | 42/1400 | ||
| Trait Anger score | 10-12 | 13-14 | 15-16 | ≥17 | --- | |
| Model 1 | referent | 1.23 (0.85-1.79) | 1.17 (0.76-1.78) | 1.45 (0.98-2.14) | 0.09 | |
| Events/N | 60/1991 | 52/1697 | 34/1308 | 48/1746 | ||
| Model 2 | referent | 1.27 (0.87-1.87) | 1.21 (0.78-1.89) | 1.41 (0.95-2.10) | 0.11 | |
| Events/N | 59/1965 | 51/1678 | 32/1282 | 48/1721 |
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Note. Ns varied based on availability of data on psychosocial measures and covariates. Ns for Hostility analyses are lower because it was assessed at MESA Visit 2; all other psychosocial measures were assessed at Visit 1. Psychosocial measures were analyzed in separate models. Model 1 adjusted for age, race, sex, education and study site. Model 2 further adjusted for systolic blood pressure, alcohol use, smoking status, moderate and vigorous physical activity, body mass index, height, use of anti-hypertensives, diabetes/fasting blood glucose status, high density lipoprotein cholesterol, and triglycerides. Values shown are HR (95% CI) unless otherwise noted.
With CES-D scores, chronic stress and anger modeled simultaneously with Visit 1 covariates, each measure showed a non-significant gradient of increasing risk across categories (all p-for-trend>.10). HR and 95% CI for the highest relative to the lowest scoring category were 1.41 (0.84-2.35) for the CES-D, 1.35 (0.92-1.98) for chronic stress, and 1.27 (0.84-1.92) for anger. This analysis included 188 events among 6,607 participants. With hostility included there were 133 events among 5,962 participants. The HR (95% CI) for the most versus least hostile group was 1.74 (0.99-3.06) but the risk gradient across groups was non-significant (p-for-trend=.08).
No interactions between psychosocial measures and age, sex, or race/ethnicity were observed (all p>.10; not shown) but power to detect differences by race/ethnicity in particular was limited by small numbers. Adjusted models that also included IMT, CRP, or IL-6 were unchanged from those shown in Table 2, Model 2 (not shown).
Patterns of association with the outcome limited to total incident strokes or incident ischemic strokes were similar to analyses with the combined endpoint (Supplemental Table I). Analyses with time-varying variables also showed results similar to the primary analyses (Supplemental Table II), with the highest-scoring groups for depressive symptoms and chronic stress having slightly larger HR when those measures were time-varying rather than baseline measures. Further controlling for marital status as a proxy for social support did not alter results (Supplemental Table III).
DISCUSSION
This study found higher levels of depressive symptoms, greater chronic stress, and higher levels of hostility predicted increased risk of stroke and TIA. There was a similar albeit non-signficant trend for trait anger. Associations were relatively unchanged after adjusting for known stroke risk factors in our primary analyses using risk factors assessed at baseline and in the time-dependent models with time-varying covariates. Results were similar when limiting analyses to incident strokes. Findings highlight the importance of considering non-traditional factors when assessing risk of stroke/TIA.
Assuming a causal association, the pathways by which stress and negative emotions contribute to increased risk of stroke and TIA need to be elucidated. Common biologic mechanisms may link these individual psychosocial characteristics with adverse cardiovascular outcomes, including stroke. Stress and negative emotions activate the hypothalamic-pituitary-adrenal axis, leading to changes in glucocorticoids and increases in circulating catecholamines, influence endothelial dysfunction and platelet activation, and have documented metabolic, neuroendocrine, and immunologic effects.23,24 Therefore, persons who experience higher levels of stress, depressive symptoms or hostility could experience autonomic or neuroendocrine changes that exacerbate risk for stroke and TIA. However, the present study did not evaluate specific mechanisms related to such pathways. Inflammatory pathways also are plausible; the psychosocial factors measured here are associated with increased CRP, fibrinogen and IL-6,25,26 which are related to stroke risk.27-28 Yet, adjusting for these variables did not alter observed relationships. We only had baseline measures of these inflammatory markers but this study provides little evidence for an inflammatory pathway. Including baseline IMT as a covariate did not alter observed associations, suggesting that non-atherosclerotic mechanisms could be involved.
Persons experiencing stress and negative emotions typically have more adverse behavioral risk profiles and experience difficulty maintaining healthy lifestyles and adhering to treatment recommendations. When controlling for baseline measures of smoking, physical activity, alcohol consumption, BMI and blood pressure, or allowing these risk factors to vary across time, the effects of stress, depressive symptoms and hostility on risk for stroke/TIA remained robust. Our data suggest that these lifestyle factors are not a primary pathway through which stress and negative emotions contribute to subsequent stroke.
Several study limitations should be noted. We had relatively small numbers of events; only 195 participants experienced either a stroke or TIA during follow-up, which is unsurprising given the initial age of MESA participants (mean, 62.1 years). This limitation impacted our ability to examine potential racial/ethnic differences in the observed associations. Also, psychosocial factors are challenging to measure. We used standard self-report questionnaires with good reliability and validity, yet measurement error may be present if participants did not feel comfortable endorsing certain statements or chose not to respond in a forthright manner. Such error would be expected to weaken associations. The robustness and consistency of our findings across analytic models suggest that measurement error did not unduly influence our results. Only selected psychosocial characteristics were included in this study; other important psychosocial constructs not evaluated here could either exacerbate or protect against stroke risk. We did not evaluate coping strategies, which could mitigate adverse effects of stress and negative emotions. Finally, we cannot rule out the possibility that covert vascular disease such as white matter changes or brain infarcts (defined by imaging) could be present in our participants and influencing their levels of depressive symptoms, stress, hostility and anger.
These limitations are offset by several strengths. MESA uses clinically adjudicated outcomes for event data, including incident stroke and TIA, which distinguishes this study from many prior reports. Our findings are consistent with previous studies that have linked measures of stress and depression with stroke outcomes, ascertained by self-report, administrative databases, or registry data2,3,9,10,29 and add to the literature by showing higher levels of hostility increase risk for stroke and TIA. We had assessments of stress, depressive symptoms, and anger from more than one study visit. The consistency of findings across models suggests these psychosocial characteristics may be relatively stable attributes. With a broad array of risk factor data we were able to evaluate the impact of many important stroke risk factors on our observed associations. Finally, MESA is a population-based study conducted at 6 U.S. sites and includes participants from four racial/ethnic groups, thereby enhancing generalizability of the findings.
Conclusion
Our study demonstrates associations between excess stroke/TIA risk and depressive symptoms, chronic stress, and hostility, which were not explained by traditional stroke risk factors, inflammatory markers or subclinical atherosclerosis. Better understanding of important potentially modifiable stroke risk factors, including stress and negative emotions, is needed given the aging population and increasing burden of stroke.
Supplementary Material
Chronic Stress_ Depressive Symptoms_ Anger_ Hostility and Risk of Stroke and Transient Ischemic Attack in the MESA Study
Click here to view.(116K, pdf)
ACKNOWLEDGMENTS
Dr. Everson-Rose and Mr. Roetker had full access to all data and take responsibility for the integrity and accuracy of the data and analyses.
The authors thank investigators, staff, and participants of the MESA study for their valuable contributions. A full list of participating MESA investigators and institutions is at http://www.mesa-nhlbi.org.
SOURCES OF FUNDING
Supported by contracts N01-HC-95159 through N01-HC-95169 from the National Heart, Lung, and Blood Institute (NHLBI) and by grants UL1-RR-024156 and UL1-RR-025005 from National Center for Research Resources (NCRR). Dr. Everson-Rose received support from N01 HC95163, the Applied Clinical Research Program and Program in Health Disparities Research at the University of Minnesota. Dr. Diez Roux was supported in part by the Michigan Center for Integrative Approaches to Health Disparities (2P60MD002249, Diez Roux PI). Contents of this paper are solely the responsibility of the authors and do not necessarily represent views of the NIH, NHLBI, or NCRR.
Footnotes
DISCLOSURES
None.
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