Abstract P089: Adiposity and risk of stroke: body shape matters more than body weight

Background: Higher body mass index (BMI) and larger waist circumference (WC), characteristics of increased adiposity, are associated with greater risk of cardiovascular disease (CVD). However, an obesity paradox (improved survival in those with history of stroke) has been observed in some populations. We hypothesized that BMI would be associated with decreased risk of stroke but that this association would be attenuated after accounting for WC. Methods: The REasons for Geographic and Racial Differences in Stroke (REGARDS) study recruited 30,239 black and white participants age 45 years and older from across the United States between 2003 and 2007. WC, height and weight were measured during a baseline in home visit and participants were followed every 6 months. Strokes were adjudicated by physicians after review of medical records. Cox proportional hazards models were used to assess stroke risk. BMI and WC were modeled in quintiles. Results: We observed 1047 incident and recurrent strokes over a mean of 6.3 years. Higher BMI and lower WC were associated with decreased risk of stroke after adjustment for demographic and medical risk factors (Table). Having both BMI and WC in the model dramatically increased the strength of association for the other variable. Collinearity was not present. The observed association was consistent across race, sex, age, WC, and history of stroke (all p for interaction >0.20). Conclusion: Increased BMI, the main measure used to define obesity, was not a stroke risk factor. Increased risk of stroke was observed in WC less than the current recommendations of 88 cm for women and 102 cm for men. Smaller waist sizes and maintenance of lean mass are important targets for stroke prevention.<br

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Electrocardiographic ST-T Abnormities Are Associated With Stroke Risk in the REGARDS Study

Stroke ◽

10.1161/strokeaha.119.028069 ◽

2020 ◽

Vol 51 (4) ◽

pp. 1100-1106

Author(s):

Mitsuaki Sawano ◽

Ya Yuan ◽

Shun Kohsaka ◽

Taku Inohara ◽

Takeki Suzuki ◽

...

Keyword(s):

Ischemic Stroke ◽

Racial Differences ◽

Stroke Risk ◽

Proportional Hazards ◽

The United States ◽

Incidence Rates ◽

Cox Proportional Hazards ◽

Hazard Ratio ◽

Common Finding ◽

Increased Risk

Background and Purpose— In previous studies, isolated nonspecific ST-segment and T-wave abnormalities (NSSTTAs), a common finding on ECGs, were associated with greater risk for incident coronary artery disease. Their association with incident stroke remains unclear. Methods— The REGARDS (Reasons for Geographic and Racial Differences in Stroke) study is a population-based, longitudinal study of 30 239 white and black adults enrolled from 2003 to 2007 in the United States. NSSTTAs were defined from baseline ECG using the standards of Minnesota ECG Classification (Minnesota codes 4-3, 4-4, 5-3, or 5-4). Participants with prior stroke, coronary heart disease, and major and minor ECG abnormalities other than NSSTTAs were excluded from analysis. Multivariable Cox proportional hazards regression was used to examine calculate hazard ratios of incident ischemic stroke by presence of baseline NSSTTAs. Results— Among 14 077 participants, 3111 (22.1%) had NSSTTAs at baseline. With a median of 9.6 years follow-up, 106 (3.4%) with NSSTTAs had ischemic stroke compared with 258 (2.4%) without NSSTTAs. The age-adjusted incidence rates (per 1000 person-years) of stroke were 2.93 in those with NSSTTAs and 2.19 in those without them. Adjusting for baseline age, sex, race, geographic location, and education level, isolated NSSTTAs were associated with a 32% higher risk of ischemic stroke (hazard ratio, 1.32 [95% CI, 1.05–1.67]). With additional adjustment for stroke risk factors, the risk of stroke was increased 27% (hazard ratio, 1.27 [95% CI, 1.00–1.62]) and did not differ by age, race, or sex. Conclusions— Presence of NSSTTAs in persons with an otherwise normal ECG was associated with a 27% increased risk of future ischemic stroke.

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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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Virulence of Marburg Virus Angola Compared to Mt. Elgon (Musoke) in Macaques: A Pooled Survival Analysis

Viruses ◽

10.3390/v10110658 ◽

2018 ◽

Vol 10 (11) ◽

pp. 658 ◽

Cited By ~ 2

Author(s):

Paul Blair ◽

Maryam Keshtkar-Jahromi ◽

Kevin Psoter ◽

Ronald Reisler ◽

Travis Warren ◽

...

Keyword(s):

Proportional Hazards ◽

Clinical Laboratory ◽

Cynomolgus Macaque ◽

The United States ◽

Cox Proportional Hazards ◽

Marburg Virus ◽

Time To Death ◽

Risk Of Death ◽

Published Evidence ◽

Increased Risk

Angola variant (MARV/Ang) has replaced Mt. Elgon variant Musoke isolate (MARV/MtE-Mus) as the consensus standard variant for Marburg virus research and is regarded as causing a more aggressive phenotype of disease in animal models; however, there is a dearth of published evidence supporting the higher virulence of MARV/Ang. In this retrospective study, we used data pooled from eight separate studies in nonhuman primates experimentally exposed with either 1000 pfu intramuscular (IM) MARV/Ang or MARV/MtE-Mus between 2012 and 2017 at the United States Army Medical Research Institute of Infectious Diseases (USAMRIID). Multivariable Cox proportional hazards regression was used to evaluate the association of variant type with time to death, the development of anorexia, rash, viremia, and 10 select clinical laboratory values. A total of 47 cynomolgus monkeys were included, of which 18 were exposed to MARV/Ang in three separate studies and 29 to MARV/MtE-Mus in five studies. Following universally fatal Marburg virus exposure, compared to MARV/MtE-Mus, MARV/Ang was associated with an increased risk of death (HR = 22.10; 95% CI: 7.08, 68.93), rash (HR = 5.87; 95% CI: 2.76, 12.51) and loss of appetite (HR = 35.10; 95% CI: 7.60, 162.18). Our data demonstrate an increased virulence of MARV/Ang compared to MARV/MtE-Mus variant in the 1000 pfu IM cynomolgus macaque model.

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Pain in Patients With Type 2 Diabetes-Related Polyneuropathy Is Associated With Vascular Events and Mortality

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgaa394 ◽

2020 ◽

Vol 105 (9) ◽

pp. 3005-3014

Author(s):

Brittany R Lapin ◽

Kevin M Pantalone ◽

Alex Milinovich ◽

Shannon Morrison ◽

Andrew Schuster ◽

...

Keyword(s):

Type 2 Diabetes ◽

Proportional Hazards ◽

Negative Binomial ◽

Cox Proportional Hazards ◽

Vascular Events ◽

Proportional Hazards Regression ◽

Increased Risk ◽

History Of ◽

Mortality Hazard Ratio

Abstract Purpose Type 2 diabetes–related polyneuropathy (DPN) is associated with increased vascular events and mortality, but determinants and outcomes of pain in DPN are poorly understood. We sought to examine the effect of neuropathic pain on vascular events and mortality in patients without DPN, DPN with pain (DPN + P), and DPN without pain (DPN-P). Methods A retrospective cohort study was conducted within a large health system of adult patients with type 2 diabetes from January 1, 2009 through December 31, 2016. Using an electronic algorithm, patients were classified as no DPN, DPN + P, or DPN-P. Primary outcomes included number of vascular events and time to mortality. Independent associations with DPN + P were evaluated using multivariable negative binomial and Cox proportional hazards regression models, adjusting for demographics, socioeconomic characteristics, and comorbidities. Results Of 43 945 patients with type 2 diabetes (age 64.6 ± 14.0 years; 52.1% female), 13 910 (31.7%) had DPN: 9104 DPN + P (65.4%) vs 4806 DPN-P (34.6%). Vascular events occurred in 4538 (15.1%) of no DPN patients, 2401 (26.4%) DPN + P, and 1006 (20.9%) DPN-P. After adjustment, DPN + P remained a significant predictor of number of vascular events (incidence rate ratio [IRR] = 1.55, 95% CI, 1.29-1.85), whereas no DPN was protective (IRR = 0.70, 95% CI, 0.60-0.82), as compared to DPN-P. Compared to DPN-P, DPN + P was also a significant predictor of mortality (hazard ratio = 1.42, 95% CI, 1.25-1.61). Conclusions Our study found a significant association between pain in DPN and an increased risk of vascular events and mortality. This observation warrants longitudinal study of the risk factors and natural history of pain in DPN.

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Increased risk of prostate cancer following sexually transmitted infection in an Asian population

Epidemiology and Infection ◽

10.1017/s0950268813000459 ◽

2013 ◽

Vol 141 (12) ◽

pp. 2663-2670 ◽

Cited By ~ 6

Author(s):

S. D. CHUNG ◽

Y. K. LIN ◽

C. C. HUANG ◽

H. C. LIN

Keyword(s):

Prostate Cancer ◽

Proportional Hazards ◽

Asian Population ◽

Population Based ◽

Cox Proportional Hazards ◽

Study Cohort ◽

Transmitted Infection ◽

Sexually Transmitted ◽

Increased Risk ◽

History Of

SUMMARYThe relationship between sexually transmitted infections (STIs) and prostate cancer (PC) remains inconclusive. Moreover, all such studies to date have been conducted in Western populations. This study aimed to investigate the risk of PC following STI using a population-based matched-cohort design in Taiwan. The study cohort comprised 1055 patients with STIs, and 10 550 randomly selected subjects were used as a comparison cohort. Cox proportional hazards regression analysis revealed that the hazard ratio for PC during the 5-year follow-up period for patients with a STI was 1·95 (95% confidence interval 1·18–3·23), that of comparison subjects after adjusting for urbanization level, geographical region, monthly income, hypertension, diabetes, hyperlipidaemia, obesity, chronic prostatitis, history of vasectomy, tobacco use disorder, and alcohol abuse. We concluded that the risk of PC was higher for men who were diagnosed with a STI in an Asian population.

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Peripheral Blood Cytopenia and Risk of Cardiovascular Disease and Mortality

Journal of the American Heart Association ◽

10.1161/jaha.121.020809 ◽

2021 ◽

Vol 10 (18) ◽

Author(s):

Radhika Gangaraju ◽

Insu Koh ◽

Marguerite R. Irvin ◽

Leslie Lange ◽

Damon E. Houghton ◽

...

Keyword(s):

Cardiovascular Disease ◽

Racial Differences ◽

Mortality Risk ◽

Peripheral Blood ◽

Stroke Risk ◽

Complete Blood Count ◽

Disease Risk ◽

Cox Proportional Hazards ◽

Increased Risk ◽

Study Participants

Background Individual blood cell count abnormalities have been associated with cardiovascular disease and increased mortality. In this study, we defined a “cytopenia phenotype,” reflecting bone marrow hypoproliferation, to determine if peripheral blood cytopenia is associated with increased cardiovascular disease and mortality risk. Methods and Results Study participants were derived from a biracial observational cohort study, REGARDS (Reasons for Geographic and Racial Differences in Stroke), that enrolled 30 239 Black and White participants aged ≥45 years between 2003 and 2007. Median follow up was ≈9 years. The current study included 19 864 participants from REGARDS study (37.9% men, 40% Black participants) who have complete blood count available at study enrollment. We defined a cytopenia phenotype based on age‐, sex‐, and race‐adjusted lowest fifth percentile of blood counts. Multivariable Cox proportional hazards models estimated the hazard ratios (HR) and 95% CI of cytopenia for mortality and incident cardiovascular disease in adjusted models. Mean age of the study participants was 64 years (SD:9.7). The prevalence of cytopenia was 1.9% (n=378). Cytopenia was associated with increased risk of all‐cause mortality (HR, 1.73; 95% CI, 1.34–2.22) and cardiovascular disease mortality (HR, 1.56; 95% CI, 1.11–2.29). Cytopenia was associated with stroke risk in Black but not White participants (HR, 1.96 versus 0.86; P ‐interaction for race=0.08) and was not associated with coronary heart disease risk. Conclusions We defined a cytopenia phenotype with clinical implications for mortality and stroke risk in a large biracial and geographically diverse population. Whether generated through somatic mutations or decreased organ function, cytopenia was associated with mortality risk and was a race‐specific risk factor for stroke.

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Depressive symptoms and risk of stroke in a national cohort of blacks and whites from REGARDS

Neurology Clinical Practice ◽

10.1212/cpj.0000000000000983 ◽

2020 ◽

pp. 10.1212/CPJ.0000000000000983

Author(s):

Cassandra D. Ford ◽

Marquita S. Gray ◽

Martha R. Crowther ◽

Virginia G. Wadley ◽

Audrey L. Austin ◽

...

Keyword(s):

Risk Factor ◽

Depressive Symptoms ◽

Stroke Risk ◽

Proportional Hazards ◽

Depressive Symptomatology ◽

National Sample ◽

Epidemiological Studies ◽

Cox Proportional Hazards ◽

Stroke Risk Factor ◽

Blacks And Whites

AbstractObjective.The purpose of this study was to examine depressive symptoms as a risk factor for incident stroke and determine whether depressive symptomatology was differentially predictive of stroke among blacks and whites.Methods.The study was comprised of 9,529 black and 14,516 white stroke-free participants, aged 45 and older, enrolled in REGARDS (2003-2007). Incident stroke was first occurrence of stroke. Association between baseline depressive symptoms (assessed via the 4-item Center for Epidemiological Studies Depression (CES-D-4) scale: 0, 1-3, or >4) and incident stroke was analyzed with Cox proportional hazards models adjusted for demographics, stroke risk factors, and social factors.Results.There were 1,262 strokes over an average follow-up of 9.21 (SD 4.0) years. Compared to participants with no depressive symptoms, after demographic adjustment, participants with CES-D-4 scores of 1-3 had 39% increased stroke risk (HR = 1.39, 95% CI = 1.23-1.57), with slight attenuation after full adjustment (HR = 1.27, 95% CI = 1.11-1.43). Participants with CES-D-4 scores of > 4 experienced 54% higher risk of stroke after demographic adjustment (HR = 1.54, 95% CI = 1.27-1.85), with risk attenuated in the full model similar to risk with 1-3 symptoms (HR = 1.25, 95% CI = 1.03-1.51). There was no evidence of a differential effect by race (p = 0.53).Conclusions.The association of depressive symptoms with increased stroke risk factor was similar among a national sample of blacks and whites. These findings suggest assessment of depressive symptoms should be considered in primary stroke prevention for both blacks and whites.

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Extended Mortality Follow-up of a Cohort of 25,460 Workers Exposed to Acrylonitrile

American Journal of Epidemiology ◽

10.1093/aje/kwz086 ◽

2019 ◽

Vol 188 (8) ◽

pp. 1484-1492 ◽

Cited By ~ 2

Author(s):

Stella Koutros ◽

Jay H Lubin ◽

Barry I Graubard ◽

Aaron Blair ◽

Patricia A Stewart ◽

...

Keyword(s):

Bladder Cancer ◽

Proportional Hazards ◽

Cox Regression ◽

The United States ◽

Cox Proportional Hazards ◽

Sensitivity Analyses ◽

Increased Risk ◽

Total Cancer ◽

Standardized Mortality Ratios

Abstract We extended the mortality follow-up of a cohort of 25,460 workers employed at 8 acrylonitrile (AN)-producing facilities in the United States by 21 years. Using 8,124 deaths and 1,023,922 person-years of follow-up, we evaluated the relationship between occupational AN exposure and death. Standardized mortality ratios (SMRs) based on deaths through December 31, 2011, were calculated. Work histories and monitoring data were used to develop quantitative estimates of AN exposure. Hazard ratios were estimated by Cox proportional hazards regression. All-cause mortality and death from total cancer were less than expected compared with the US population. We observed an excess of death due to mesothelioma (SMR = 2.24, 95% confidence interval (CI): 1.39, 3.42); no other SMRs were elevated overall. Cox regression analyses revealed an elevated risk of lung and bronchial cancer (n = 808 deaths; for >12.1 ppm-year vs. unexposed, hazard ratio (HR) = 1.43, 95% CI: 1.13, 1.81; P for trend = 0.05), lagged 10 years, that was robust in sensitivity analyses adjusted for smoking and co-exposures including asbestos. Death resulting from bladder cancer (for >2.56 ppm vs. unexposed, lagged 10-year HR = 2.96, 95% CI: 1.38, 6.34; P for trend = 0.02) and pneumonitis (for >3.12 ppm-year vs. unexposed, HR = 4.73, 95% CI: 1.42, 15.76; P for trend = 0.007) was also associated with AN exposure. We provide additional evidence of an association between AN exposure and lung cancer, as well as possible increased risk for death due to bladder cancer and pneumonitis.

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History of premorbid depression is a risk factor for COVID-related mortality: Analysis of a retrospective cohort of 1,387 COVID+ patients

10.1101/2020.12.17.20248362 ◽

2020 ◽

Author(s):

Sean Clouston ◽

Benjamin J Luft ◽

Edward Sun

Keyword(s):

Risk Factors ◽

Risk Factor ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Models ◽

Risk Of Mortality ◽

Increased Risk ◽

History Of ◽

History Of Depression ◽

Related Mortality

Background: The goal of the present work was to examine risk factors for mortality in a 1,387 COVID+ patients admitted to a hospital in Suffolk County, NY. Methods: Data were collated by the hospital epidemiological service for patients admitted from 3/7/2020-9/1/2020. Time until final discharge or death was the outcome. Cox proportional hazards models were used to estimate time until death among admitted patients. Findings: In total, 99.06% of cases had resolved leading to 1,179 discharges and 211 deaths. Length of stay was significantly longer in those who died as compared to those who did not p=0.007). Of patients who had been discharged (n=1,179), 54 were readmitted and 9 subsequently died. Multivariable-adjusted Cox proportional hazards regression revealed that in addition to older age, male sex, and heart failure, a history of premorbid depression was a risk factor for COVI-19 mortality. Interpretation: While an increasing number of studies have shown effects linking cardiovascular risk factors with increased risk of mortality in COVID+ patients, this study reports that history of depression is a risk factor for COVID mortality.

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