Abstract WP482: Early Life Exposure to the Stroke Belt and Later Life Incident Cognitive Impairment: The Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study

Introduction: Incidence of cognitive impairment is higher for residents of the Stroke Belt (SB) compared to those living outside it, but the importance of timing of SB residence is unclear. Methods: Participants were aged 45+ yrs, and enrolled in 2003-2007 in REGARDS. Cognition was assessed annually, by telephone, using the Six-Item Screener (SIS) in 11,488 black or white stroke-free participants currently living in the SB, and 8,949 currently living outside of the SB. Incident cognitive impairment was defined as SIS score of < 4 at last assessment among participants with initial SIS >4. Exposures were defined as SB residence all years, some years, or no years of childhood (ages 0-18) and early adulthood (ages 19-30). Demographic adjusted logistic regression models were stratified by SB residence at enrollment, and were used to estimate the demographic-adjusted odds of incident cognitive impairment. Results: Among those currently residing in the SB, childhood residence outside the SB for some (OR = 0.82; 95% CI: 0.68 - 0.99) or all (OR = 0.76; 95% CI: 0.65 - 0.90) of the time predicted lower odds of incident cognitive impairment. Similarly, early adulthood residence outside the SB for some (OR = 0.86; 95% CI: 0.74 - 0.98) or all (OR = 0.70; 95% CI: 0.58 - 0.84) of the time predicted lower incident cognitive impairment. Conversely, for those currently living outside the SB, the risk of incident cognitive impairment was higher for those who had spent their entire early adulthood in the SB (OR = 1.51; 95% CI: 1.01 - 2.57), with non-significant increased risk for childhood exposure or some early adulthood exposure to the SB (table). Conclusions: These findings suggest that early residence in the SB during childhood or early adulthood increases the risk of cognitive impairment regardless of place of residence in later adulthood. Further research is needed to determine the characteristics of early SB life that are linked to later adult cognitive impairment.

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C-reactive protein and risk of cognitive decline: The REGARDS study

PLoS ONE ◽

10.1371/journal.pone.0244612 ◽

2020 ◽

Vol 15 (12) ◽

pp. e0244612

Author(s):

Miguel Arce Rentería ◽

Sarah R. Gillett ◽

Leslie A. McClure ◽

Virginia G. Wadley ◽

Stephen P. Glasser ◽

...

Keyword(s):

Cognitive Impairment ◽

Cognitive Decline ◽

Racial Differences ◽

Verbal Fluency ◽

Continuous Variable ◽

Latent Growth ◽

Growth Curve Models ◽

Reactive Protein ◽

Increased Risk ◽

Regards Study

Markers of systemic inflammation are associated with increased risk of cognitive impairment, but it is unclear if they are associated with a faster rate of cognitive decline and whether this relationship differs by race. Our objective was to examine the association of baseline C-reaction protein (CRP) with cognitive decline among a large racially diverse cohort of older adults. Participants included 21,782 adults aged 45 and older (36% were Black, Mean age at baseline 64) from the REasons for Geographic And Racial Differences in Stroke (REGARDS) study. CRP was measured at baseline and used as a continuous variable or a dichotomous grouping based on race-specific 90th percentile cutoffs. Cognitive measures of memory and verbal fluency were administered every 2 years for up to 12 years. Latent growth curve models evaluated the association of CRP on cognitive trajectories, adjusting for relevant demographic and health factors. We found that higher CRP was associated with worse memory (B = -.039, 95% CI [-.065,-.014]) and verbal fluency at baseline (B = -.195, 95% CI [-.219,-.170]), but not with rate of cognitive decline. After covariate adjustment, the association of CRP on memory was attenuated (B = -.005, 95% CI [-.031,-.021]). The association with verbal fluency at baseline, but not over time, remained (B = -.042, 95% CI [-.067,-.017]). Race did not modify the association between CRP and cognition. Findings suggest that levels of CRP at age 45+, are a marker of cognitive impairment but may not be suitable for risk prediction for cognitive decline.

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Risk factors for ‘microsize’ vs. usual myocardial infarctions in the REasons for Geographic and Racial Differences in Stroke (REGARDS) study

European Heart Journal - Quality of Care and Clinical Outcomes ◽

10.1093/ehjqcco/qcz007 ◽

2019 ◽

Vol 5 (4) ◽

pp. 343-351

Author(s):

Zaid I Almarzooq ◽

Lisandro D Colantonio ◽

Peter M Okin ◽

Joshua S Richman ◽

Todd M Brown ◽

...

Keyword(s):

Risk Factors ◽

Racial Differences ◽

Myocardial Infarctions ◽

Baseline Risk ◽

Current Smoking ◽

Increased Risk ◽

All Cause Mortality ◽

Regards Study ◽

Stroke Belt ◽

Future Management

Abstract Aims A recently described phenomenon is that of myocardial infarction (MI) events that meet criteria for MI, but that have very low peak troponin elevations, so-called ‘microsize MI’. These events are very common and associated with increased risk of all-cause mortality. Our aim is to compare risk factors for microsize MI vs. usual MI events. Methods and results Among 24 470 participants of the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort free of coronary heart disease at baseline, heart-related hospitalizations were expert adjudicated for MI using published guidelines. Myocardial infarctions were classified as microsize MI (peak troponin <0.5 ng/mL) or usual MI (peak troponin ≥0.5 ng/mL). Competing risk analyses assessed associations between baseline risk factors and incident microsize vs. usual MI. Between 2003 and 2013 there were 891 MIs; 279 were microsize MI and 612 were usual MI. Risk factors for both usual MI and microsize MI include age, gender, diabetes, and urinary albumin to creatinine ratio. Risk factors for only usual MI include Residence in the Stroke Belt and Buckle regions and current smoking. Black race was associated with a uniquely lower risk of usual MI. Conclusion The similarities in risk profiles suggest a possible common aetiology and should encourage clinicians to both treat reversible risk factors for microsize MI and to initiate secondary prevention strategies following these events until this emerging clinical entity is better understood. Future studies should further assess the clinical outcomes of these two entities and their effect on future management.

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Abstract P281: Medication Adherence and Stroke/TIA Risk in Treated Hypertensives: Results from the REasons for Geographic and Racial Differences in Stroke (REGARDS) Study

Circulation ◽

10.1161/circ.125.suppl_10.ap281 ◽

2012 ◽

Vol 125 (suppl_10) ◽

Author(s):

Doyle M Cummings ◽

Abraham J Letter ◽

George Howard ◽

Virginia J Howard ◽

Monika Safford ◽

...

Keyword(s):

Medication Adherence ◽

Racial Differences ◽

Population Based ◽

Hazard Ratio ◽

Logistic Regression Models ◽

Adherence Score ◽

Increased Risk ◽

Regards Study ◽

Ischemic Attack ◽

Perfect Adherence

Background: Low medication adherence in treated hypertensives is an important modifiable barrier to achieving blood pressure (BP) control. The contribution of poor medication adherence to adverse cardiovascular outcomes such as stroke and transient ischemic attack (TIA) relative to other cerebrovascular risk factors is less well understood. We therefore examined the relationship between medication adherence and both adequate BP control (< 140/90 mmHg) and stroke/TIA incidence in treated hypertensive subjects (n = 15,071 subjects free of stroke/TIA at baseline; 51% black; 57% living in the Stroke Belt) in REGARDS, a population-based cohort study. Methods: BP was measured in the subject’s home by a trained health professional following a standardized protocol. Medication adherence was measured at baseline (4-item validated Morisky scale: 0 = perfect adherence, 4 = lowest adherence). Participants were contacted bi-annually by telephone for a median follow-up time of 5 years and self-reported stroke or TIA events were adjudicated by medical record review. We used logistic regression models to examine the association between medication adherence and BP control and Cox modeling to evaluate the effect of adherence on stroke/TIA risk, examining the mediating effects of systolic BP. Results: Perfect medication adherence (score = 0) was reported by 69% of subjects, 23% a score of 1, 5% a score of 2, and 3% a score of 3 or 4. Mean systolic BP varied from 130.8 ± 16.2 in those reporting perfect adherence (Morisky score of 0) to 137.8 ± 19.5 in those reporting low medication adherence (score of 3 or 4) (p for trend< 0.0001). Compared to a Morisky score of 0, each level of worsening medication adherence was associated with significant and increasing odds of inadequately controlled BP (≥ 140/90 mmHg) in fully adjusted models: score = 1, odds ratio (95% CI) = 1.19 (1.09 – 1.30); score = 2, 1.27 (1.08–1.49); score = 3 or 4, 2.21 (1.75 – 2.78). Compared to perfect adherence, low medication adherence was not independently associated with stroke [hazard ratio = 1.04 (95% CI: 0.51 – 2.12)] or stroke and/or TIA [hazard ratio = 0.81 (95% CI: 0.38 – 1.73)] after multivariable adjustment. However, in analyses with systolic BP as the mediating variable, low medication adherence was associated with an increased risk for stroke (hazard ratio = 1.08 (95% CI: 1.04 – 1.14) and for stroke and/or TIA [hazard ratio = 1.08 (95% CI: 1.03 – 1.12)] in fully adjusted models. Conclusion: These findings add further evidence that low medication adherence is strongly associated with poor BP control; and through BP, low adherence is also associated with an increased risk of stroke or TIA.

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Disparities in cognitive impairment with anticholinergic drug use: A population-based study

Neurology Clinical Practice ◽

10.1212/cpj.0000000000000952 ◽

2020 ◽

pp. 10.1212/CPJ.0000000000000952

Author(s):

Md Motiur Rahman ◽

George Howard ◽

Jingjing Qian ◽

Kimberly Garza ◽

Ash Abebe ◽

...

Keyword(s):

Cognitive Impairment ◽

Racial Differences ◽

Urban Areas ◽

Anticholinergic Drug ◽

Population Based ◽

Beers Criteria ◽

Logistic Regression Models ◽

Interaction Terms ◽

Regards Study ◽

Adjusted Model

Objectives:We aim to evaluate the association between anticholinergic drug (ACH) use and cognitive impairment and the effect of disparity parameters (sex, race, income, education, and rural or urban areas) on this relationship.Methods:The analyses included 13,623 adults aged ≥65 years from the REasons for Geographic And Racial Differences in Stroke (REGARDS) study (recruited 2003-2007). The ACH use was defined by the 2015 Beers Criteria and cognitive impairment was measured by the Six-Item Cognitive Screener. Multivariable logistic regression models assessed disparities in cognitive impairment with ACH use, iteratively adjusting for disparity parameters and other covariates. The full models included interaction terms between ACH use and other covariates. A similar approach was used for class-specific ACH exposure and cognitive impairment analyses.Results:Approximately 14% of the participants used at least one ACH listed in the Beers criteria. Antidepressants were the most frequently prescribed ACH class. A significant sex-race interaction illustrated that females compared with males (in blacks: odds ratio [OR]=1.28, 95% CI 1.10–1.49 and in whites: OR=1.96, 95% CI 1.74–2.20), and especially white females (black vs. white: OR=0.71, 95% CI 0.64–0.80) were more likely to receive ACHs. Higher odds of cognitive impairment were observed among ACH users compared with the non-users (OR=1.26, 95% CI 1.01–1.58). In our class level analyses, only antidepressant users (OR=1.60, 95% CI 1.14–2.25) showed a significant association with cognitive impairment in the fully adjusted model.Conclusion:We observed demographic and socioeconomic differences in ACH use and in cognitive impairment, individually.

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Abstract T P146: Vitamin D Deficiency is Associated With Stroke in Black and White Participants of the REGARDS Study

Stroke ◽

10.1161/str.45.suppl_1.tp146 ◽

2014 ◽

Vol 45 (suppl_1) ◽

Author(s):

Suzanne E Judd ◽

Virginia J Howard ◽

Paul Muntner ◽

Brett M Kissela ◽

Bhupesh Panwar ◽

...

Keyword(s):

Vitamin D ◽

Vitamin D Deficiency ◽

Racial Differences ◽

Sex Education ◽

The United States ◽

Dietary Vitamin ◽

Equal Distribution ◽

Black And White ◽

Increased Risk ◽

Regards Study

Objective: Black Americans are at greater risk of both stroke and vitamin D deficiency than white Americans. We have previously shown that both higher dietary vitamin D and sunlight exposure are associated with decreased risk of stroke; however, serum 25(OH) is thought to be a better marker of vitamin D status. Methods: Using a case cohort design, we examined the association of plasma 25(OH)D with incident stroke in the REasons for Geographic and Racial Differences in Stroke (REGARDS) study, a cohort of black and white participants from across the United States enrolled between 2003 and 2007. Medical records were reviewed by physicians and strokes were classified on the basis of symptoms and neuroimaging. Strokes through July 1, 2011 were included. A stratified cohort sample was selected to ensure approximately equal numbers of black and white participants and an equal distribution across ages. We used Cox proportional hazards models weighted back to the original 30,239 participants, excluding those with history of stroke. Serum 25(OH)D was measured by Immunodetection Systems ELISA. Results: Over mean follow-up of 4.4 years, there were 539 ischemic and 71 hemorrhagic strokes. The stroke-free sub-cohort included 939 participants. After adjustment for age, race, sex, education, diabetes, hypertension, smoking, atrial fibrillation, heart disease, physical activity, kidney function, calcium and phosphorous, 25(OH)D level 30 ng/mL. The direction of association was similar for hemorrhagic stroke though not statistically significant (HR=1.59; 95%CI=0.78, 3.24). Vitamin D deficiency was associated with an increased risk of all stroke (HR=1.54; 95%CI=1.05, 2.23). This effect was greater in blacks (HR=2.09; 95%CI=1.09, 3.99) than whites (HR=1.38; 95%CI=0.78, 2.42). Results were not as strong when we modeled 25(OH)D as a continuous variable (HR=0.99 per 1 ng/ml change in 25(OH)D; 95%CI=0.98, 1.01). Discussion: Similar to low vitamin D intake, vitamin D deficiency is a risk factor for incident stroke. These findings support evidence from cardiovascular and cancer epidemiology that treating low 25(OH)D may prevent strokes.

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Abstract 187: Electrocardiographic Heart Rate-corrected Qt Interval And Risk Of Stroke In The REasons For Geographic And Racial Differences In Stroke (REGARDS) Study

Stroke ◽

10.1161/str.43.suppl_1.a187 ◽

2012 ◽

Vol 43 (suppl_1) ◽

Author(s):

Elsayed Z Soliman ◽

George Howard ◽

Mary Cushman ◽

Brett Kissela ◽

...

Keyword(s):

Heart Rate ◽

Racial Differences ◽

Qt Interval ◽

Proportional Hazards ◽

Left Ventricular ◽

Cox Proportional Hazards ◽

Corrected Qt Interval ◽

Cardiovascular Morbidity And Mortality ◽

Increased Risk ◽

Regards Study

Background: Prolongation of heart rate-corrected QT interval (QTc) is a well established predictor of cardiovascular morbidity and mortality. Little is known, however, about the relationship between this simple electrocardiographic (ECG) marker and risk of stroke. Methods: A total of 27,411 participants aged > 45 years without prior stroke from the REasons for Geographic and Racial Differences in Stroke (REGARDS) study were included in this analysis. QTc was calculated using Framingham formula (QTcFram). Stroke cases were identified and adjudicated during an up to 7 years of follow-up (median 2.7 years). Cox proportional hazards analysis was used to estimate the hazard ratios for incident stroke associated with prolonged QTcFram interval (vs. normal) and per 1 standard deviation (SD) increase, separately, in a series of incremental models. Results: The risk of incident stroke in the study participants with baseline prolonged QTcFram was almost 3 times the risk in those with normal QTcFram [HR (95% CI): 2.88 (2.12, 3.92), p<0.0001]. After adjustment for age, race, sex, antihypertensive medication use, systolic blood pressure, current smoking, diabetes, left ventricular hypertrophy, atrial fibrillation, prior cardiovascular disease, QRS duration, warfarin use, and QT-prolonging drugs (full model), the risk of stroke remained significantly high [HR (95% CI): 1.67 (1.16, 2.41), p=0.0060)], and was consistent across several subgroups of REGARDS participants. When the risk of stroke was estimated per 1 SD increase in QTcFram, a 24% increased risk was observed [HR (95% CI): 1.24 (1.16, 1.33), p<0.0001)]. This risk remained significant in the fully adjusted model [HR (95% CI): 1.12 (1.03, 1.21), p=0.0055]. Similar results were obtained when other QTc correction formulas including Hodge’s, Bazett’s and Fridericia’s were used. Conclusions: QTc prolongation is associated with a significantly increased risk of incident stroke independently from known stroke risk factors. In light of our results, examining the risk of stroke associated with QT-prolonging drugs may be warranted.

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Abstract P316: Multiple Vulnerabilities to Health Disparities and Incident Coronary Heart Disease in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study

Circulation ◽

10.1161/circ.137.suppl_1.p316 ◽

2018 ◽

Vol 137 (suppl_1) ◽

Author(s):

Monika M Safford ◽

Laura Pinheiro ◽

Madeline Sterling ◽

Joshua Richman ◽

Paul Muntner ◽

...

Keyword(s):

Health Disparities ◽

Racial Differences ◽

Low Income ◽

Proportional Hazards ◽

Health Management ◽

Cox Proportional Hazards ◽

Southeastern Us ◽

Cox Proportional Hazards Models ◽

Increased Risk ◽

Regards Study

Social determinants contribute to disparities in incident CHD but it is not known if they have an additive effect. We hypothesized that having more socially determined vulnerabilities to health disparities is associated with increased risk of incident CHD in the REGARDS study, a large biracial prospective cohort with physiological and survey measures. Experts adjudicated incident fatal and nonfatal CHD over 10 years of follow-up. Vulnerabilities included black race, low education, low income, and Southeastern US residence. The risks for CHD outcomes associated with 1, 2, and 3+ vs 0 vulnerabilities were calculated with Cox proportional hazards models adjusted for medical conditions, functional status, health behaviors, and physiologic variables. Of the 19,645 participants free of CHD at baseline (mean age 64 years, 57% women), 16% had 0 vulnerabilities, 36% had 1, 29% had 2, and 18% had 3+. Increasing numbers of vulnerabilities were associated with higher incidence (Figure) and risk of CHD that attenuated somewhat after multivariable adjustment (Table). These findings may provide a method of risk stratification useful for population health management.

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Dementia associated with alcohol and other drug use

International Psychogeriatrics ◽

10.1017/s1041610205001985 ◽

2005 ◽

Vol 17 (s1) ◽

pp. S109-S127 ◽

Cited By ~ 50

Author(s):

Gary K. Hulse ◽

Nicola T. Lautenschlager ◽

Robert J. Tait ◽

Osvaldo P. Almeida

Keyword(s):

Cognitive Impairment ◽

Cognitive Function ◽

Drug Use ◽

Negative Impact ◽

Diagnostic Category ◽

Later Life ◽

Increased Risk ◽

Causal Pathway ◽

Chronic Use

The acute use of alcohol and several other licit and illicit drugs can affect mental state and cognitive function. The chronic use of certain drugs may also increase the risk of cognitive impairment and perhaps dementia in later life. This paper focuses on the long-term cognitive consequences of using alcohol, benzodiazepines, tobacco and cannabis. Currently available evidence indicates that mild to moderate alcohol consumption is not associated with increased risk of cognitive decline and may in fact have a protective effect against dementia, although heavy, long-term consumption is likely to have a negative impact on cognitive function. The degree that alcohol-related cognitive impairment must reach to be classified as dementia is currently obscure. Longer-term smoking is associated with increased risk of cognitive impairment and possibly dementia. The chronic use of benzodiazepines has been associated with increased risk of cognitive impairment but information relating to dementia remains inconclusive. The chronic use of cannabis may impair intellectual abilities but data on this topic remain sparse and difficult to interpret. In conclusion, there is evidence that some drugs contribute to the causal pathway that leads to the development of cognitive impairment but currently available data do not support the introduction of a separate diagnostic category of drug-induced dementia (such as alcohol-related dementia). Health promotion programs designed to decrease tobacco smoking and “harmful” alcohol use (and possibly other drug use) may decrease the burden of cognitive impairment and perhaps dementia in later life.

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