Safford, Monika M.

Abstract Aims Post-operative atrial fibrillation (POAF) is associated with stroke and mortality. It is unknown if POAF is associated with subsequent heart failure (HF) hospitalization. This study aims to examine the association between POAF and incident HF hospitalization among patients undergoing cardiac and non-cardiac surgeries. Methods and results A retrospective cohort study was conducted using all-payer administrative claims data that included all non-federal emergency department visits and acute care hospitalizations across 11 states in the USA. The study population included adults aged at least 18 years hospitalized for surgery without a prior diagnosis of HF. Cox proportional hazards regression models were used to examine the association between POAF and incident HF hospitalization after making adjustment for socio-demographics and comorbid conditions. Among 76 536 patients who underwent cardiac surgery, 14 365 (18.8%) developed incident POAF. In an adjusted Cox model, POAF was associated with incident HF hospitalization [hazard ratio (HR) 1.33; 95% confidence interval (CI) 1.25–1.41]. In a sensitivity analysis excluding HF within 1 year of surgery, POAF remained associated with incident HF hospitalization (HR 1.15; 95% CI 1.01–1.31). Among 2 929 854 patients who underwent non-cardiac surgery, 23 763 (0.8%) developed incident POAF. In an adjusted Cox model, POAF was again associated with incident HF hospitalization (HR 2.02; 95% CI 1.94–2.10), including in a sensitivity analysis excluding HF within 1 year of surgery (HR 1.49; 95% CI 1.38–1.61). Conclusions Post-operative atrial fibrillation is associated with incident HF hospitalization among patients without prior history of HF undergoing both cardiac and non-cardiac surgeries. These findings reinforce the adverse prognostic impact of POAF and suggest that POAF may be a marker for identifying patients with subclinical HF and those at elevated risk for HF.

Background: Administrative data such as Medicare data are commonly used for health services research and comparative effectiveness studies. These databases are readily available and a good source of long-term data on healthcare utilization and health outcomes in real-world settings. Outcomes are captured using diagnostic codes, but the evidence on the validity of these codes is scarce in contemporary Medicare data. Methods: We linked the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study data using SSN, date of birth and sex to 2003-2009 Medicare claims. In addition to the events captured by REGARDS phone interviews, medical charts were pursued for Medicare-identified strokes not previously identified in REGRADS. Events were adjudicated by stroke specialists using the retrieved medical charts. Using all the adjudicated strokes as gold standard, we calculated the sensitivity, specificity, PPV and NPV of inpatient stroke algorithms with ICD-9-CM codes [430, 431, 433.x1, 434.x1, 436] in the primary discharge diagnosis. Results: We successfully linked 15,089 REGARDS participants with mean age of 69.3, 52% female and 37% Black. We adjudicated 457 strokes, of which 48 were identified by claims only and not by interviews. The tested algorithms had high specificity (99.8-100%), PPV (88.6-90.5%) and NPV (98.9-99.9%), but low sensitivity (58.6-67.4%) (Table). Conclusions: High specificity and PPV of our algorithms to identify strokes in contemporary Medicare populations support their use in etiological and comparative effectiveness studies. While our inpatient Medicare algorithms identified 12% extra cases of strokes, their usefulness for estimating stroke incidence or related healthcare utilizations is limited by their low sensitivity. Linking cohorts to Medicare data is feasible and should be considered to increase the completeness of follow-up. Further studies are needed to evaluate more sensitive Medicare algorithms.

Background: Stroke symptoms in the general population are common (≈18% of adults 45+) and are associated with future stroke. These symptoms may also identify a broad spectrum of clinically-undetected vascular conditions. Methods: Stroke symptoms (sudden weakness, numbness, unilateral or general loss of vision, and loss of ability to communicate or understand) and time to self-reported hospitalization for any cardiovascular (CVD) reason (heart, stroke, or TIA) or stroke were assessed in the REGARDS Study (a national, population-based, longitudinal study of 30,239 African-American and white adults > 45 years enrolled 2003-2007). The symptom-hospitalization association was assessed by proportional hazards analysis in persons stroke/TIA-free at baseline, with adjustment for demographics (age, race and sex), further adjustment for SES (income and education), CVD risk factors (smoking, hypertension, diabetes, dyslipidemia, atrial fibrillation and heart disease), and “perceived health status.” Results: Over an average follow-up of 5.6 years, presence of any stroke symptom was associated with greater risk of hospitalization for stroke (11% versus 6%; HR = 1.68; 95% CI: 1.52 - 1.85), a risk only modestly attenuated by adjustment for SES (HR = 1.59; 95% CI: 1.44 - 1.76), risk factors (HR = 1.44; 95% CI: 1.29 - 1.60), and perceived health (HR = 1.37; 95% CI: 1.23 - 1.53). However, presence of any stroke symptom was more strongly related to hospitalization for CVD (42% vs. 24%; HR = 1.92; 95 CI: 1.82 - 2.03), only modestly mediated by adjustment for SES (HR = 1.82; 95% CI: 1.73 - 1.93), risk factors (HR = 1.66; 95% CI: 1.57 - 1.76), and perceived health (HR = 1.57; 95% CI: 1.48 - 1.66). Conclusions: Stroke symptoms appear to be a marker not only for stroke risk, but also for general CVD. Simple questions can identify 18% of the general population that have over a 40% chance of hospitalization for CVD over a 5-year horizon. Implications for potential intervention to reduce risk are profound.

AbstractHigher and lower hemoglobin concentrations are associated with coronary heart disease (CHD), but whether this risk is consistent across age, sex, and race is unclear. The Reasons for Geographic And Racial Differences in Stroke (REGARDS) study is an observational cohort study of 30 239 black, and white, adults aged 45 and older recruited 2003‐7. Participants were included if they had hemoglobin measures, were CHD‐free at baseline, and had all baseline variables. The primary outcome was incident CHD. Multivariable Cox proportional hazards models were used to estimate the hazard ratios (HR) and 95% confidence intervals (CI) for incident CHD by hemoglobin concentration. This was expressed as a continuous variable and divided into age‐, sex‐, and race‐specific quintiles. The 16 332 participants were included, contributing 114 362 person‐years of follow‐up and 915 incident CHD events. The mean age was 63 years, 35% were male, 41% were black, and the mean baseline hemoglobin was 13.6 g/dL (SD 1.4). A significant non‐linear association between hemoglobin and CHD was identified (P < .001). This association differed significantly by race (P = .025) but not by sex or age. In whites, the risk for incident CHD was higher in the lowest (HR 2.28, 95% CI 1.61, 3.33) and highest (HR 1.94, 95% CI 1.35, 2.79) hemoglobin quintiles relative to the third quintile. For blacks, only those in the lowest hemoglobin quintile had an increased risk for incident CHD events (HR 1.70, 95% CI 1.20, 2.41). Hemoglobin is an independent risk factor for CHD in whites and blacks but with different hemoglobin concentrations conferring different risks.

INTRODUCTION: African-Americans (blacks) have higher risk of stroke and coronary heart disease (CHD) - collectively referred to here as cardiovascular disease (CVD), than Caucasian-Americans (whites). Though partly explained by traditional cardiovascular risk factors, half of the excess risk in blacks is not explained by known risk factors. Recent data suggest increased risk of CVD and mortality in individuals with clonal hematopoiesis, which often presents as cytopenia. Using peripheral blood cytopenia as a marker of clonal hematopoiesis, we examined the association between cytopenia and risk of CVD and mortality in blacks and whites. METHODS: The REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort study enrolled 30,239 US black and white adults between 2003 and 2007 (41% black). Socio-demographics and medical history were obtained by telephone interview, and laboratory studies (including complete blood count [CBC]) and physical exam from an in-home visit at baseline. Participants or their proxies were contacted every 6 months to ascertain CVD events, hospitalizations or deaths, and medical records were reviewed to confirm these events. Cytopenia was defined using thresholds in Table 1 as presence of 2 or more of the following: i) hemoglobin in age-, sex-, and race-specific lowest 5th percentile; ii) white cell count in race-specific lowest 5th percentile; iii) platelet count in lowest 5th percentile, and iv) macrocytosis (MCV >98fL). Participants with pre-baseline history of stroke (for analyses including stroke or CVD mortality) or CHD (for analyses including CHD or CVD mortality) and those with missing CBC were excluded. Cox proportional hazards models were used to calculate hazard ratios (HRs) of incident CVD and mortality associated with cytopenia. Models adjusted for socio-demographics (Model 1), Framingham stroke or CHD risk factors (Model 2), and estimated glomerular filtration rate and C-reactive protein (Model 3) were used. Differences in the association of cytopenia with outcomes by race were tested using cross-product interaction terms, using a p of <0.1 for interaction. RESULTS: The study included 19,544 participants who were followed for a median of ~9 years. There were 798 (4.3% of those at risk) incident stroke cases and 727 (4.3%) incident CHD cases; 1033 (5.3%) died of CVD, and 3933 (20.1%) died of all-causes. Cytopenia was present in 378 (1.9%) participants, ranging from 0.9% to 3.5% in blacks, 1.4 to 3.9% in whites, 1.6 to 3.9% in men, and 0.9 to 1.8% in women, with increasing prevalence by age. There was no association between cytopenia and stroke or CHD risk in any model. However, cytopenia was associated with increased risk of all-cause mortality (HR=1.73, 95%CI: 1.34-2.22), and CVD mortality (HR=1.56, 95% CI: 1.11-2.19) in the extended risk factor Model 3 and also in CVD risk factor adjusted model (Model 2), with little evidence of confounding (Table 2). While the race by cytopenia interaction term was not significant in any model for incident CHD or mortality, the interaction for cytopenia by race for stroke was statistically significant (p-interaction=0.08) in Model 2. The HR of stroke for cytopenia in blacks was 0.86 (95%CI: 0.46-1.61), and for whites was 1.96 (95%CI: 1.0-3.82). CONCLUSION: In this large biracial cohort, cytopenia was associated with increased all-cause and CVD mortality. Cytopenia was a race-specific risk factor for stroke affecting white Americans but not black Americans. With growing knowledge on the role of clonal hematopoiesis in CVD risk and mortality, further work is needed to determine if our phenotype of cytopenia is accurate in classifying clonal hematopoiesis and for determining the mortality risk. Given these findings, assessing clonal hematopoiesis and outcomes related to clonal hematopoiesis in diverse populations is critical to understanding the interactions between somatic mutations in hematopoietic cells and CVD/mortality risk. Disclosures Safford: Amgen: Research Funding.

OBJECTIVE Given temporal changes in diabetes prevalence and stroke incidence, this study investigated age, race, and sex differences in the diabetes–stroke association in a contemporary prospective cohort, the REasons for Geographic and Racial Differences in Stroke (REGARDS) Study. RESEARCH DESIGN AND METHODS We included 23,002 non-Hispanic black and white U.S. adults aged ≥45 years without prevalent stroke at baseline (2003–2007). Diabetes was defined as fasting glucose ≥126 mg/dL, random glucose ≥200 mg/dL, or use of glucose-lowering medication. Incident stroke events were expert adjudicated and available through September 2017. RESULTS The prevalence of diabetes was 19.1% at baseline. During follow-up, 1,018 stroke events occurred. Among adults aged &lt;65 years, comparing those with diabetes to those without diabetes, the risk of stroke was increased for white women (hazard ratio [HR] 3.72 [95% CI 2.10–6.57]), black women (HR 1.88 [95% CI 1.22–2.90]), and white men (HR 2.01 [95% CI 1.27–3.27]) but not black men (HR 1.27 [95% CI 0.77–2.10]) after multivariable adjustment. Among those aged ≥65 years, diabetes increased the risk of stroke for white women and black men, but not black women (HR 1.05 [95% CI 0.74–1.48]) or white men (HR 0.86 [95% CI 0.62–1.21]). CONCLUSIONS In this contemporary cohort, the diabetes–stroke association varied by age, race, and sex together, with a more pronounced effect observed among adults aged &lt;65 years. With the recent increase in the burden of diabetes complications at younger ages in the U.S., additional efforts are needed earlier in life for stroke prevention among adults with diabetes.

Abstract Objective To examine the association of serum inflammatory markers (erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)) and serum lipid measures (low-density lipoprotein (LDL)- and high-density lipoprotein (HDL)-cholesterol) with risk of myocardial infarction (MI) and ischaemic stroke (IS) among rheumatoid arthritis (RA) patients. Methods We conducted a retrospective cohort study using 2005–2010 data from a US commercial health plan. Eligible patients had two or more physician diagnoses of RA during a baseline period of at least 180 days with continuous medical and pharmacy coverage. We computed age-adjusted incidence rates of MI and IS, and used spline regression to assess non-linear associations and Cox-regression to quantify the independent association between the laboratory values and the outcomes. Results We identified 44 418 eligible RA patients (mean age 49 years; 76% women). CRP&gt;10 mg/L compared with &lt;1 mg/L was associated with increased MI risk (HR 2.12; 95% CI 1.02 to 4.38). ESR&gt;42 mm/h compared with &lt;14 mm/h was associated with increased risk of MI (HR 2.53; 95% CI 1.48 to 4.31) and IS (HR 2.51; 95% CI 1.33 to 4.75) risk. HDL-cholesterol ≥60 mg/dL (1.6 mmol/L) compared with &lt;40 mg/dL (1.0 mmol/L) was associated with reduced MI risk (HR 0.37; 0.21 to 0.66). The association between LDL and MI was not linear; the lowest risk was observed among patients with LDL between 70 mg/L (1.8 mmol/L) and 100 mg/L (2.6 mmol/L). We did not observe a significant association between LDL and IS. Conclusions This study provides evidence supporting the hypothesis that RA-related systemic inflammation plays a role in determining cardiovascular risk and a complex relationship between LDL and cardiovascular risk.

OBJECTIVE Stroke symptoms among individuals reporting no physician diagnosis of stroke are associated with an increased risk of future stroke. Few studies have assessed whether individuals with diabetes or prediabetes, but no physician diagnosis of stroke, have an increased prevalence of stroke symptoms. RESEARCH DESIGN AND METHODS This study included 25,696 individuals aged ≥45 years from the REasons for Geographic And Racial Differences in Stroke (REGARDS) study who reported no history of stroke or transient ischemic attack at baseline (2003–2007). Glucose measurements, medication use, and self-reported physician diagnosis were used to categorize participants into diabetes, prediabetes, or normal glycemia groups. The presence of six stroke symptoms was assessed using a validated questionnaire. RESULTS The prevalence of any stroke symptom was higher among participants with diabetes (22.7%) compared with those with prediabetes (15.6%) or normal glycemia (14.9%). In multivariable models, diabetes was associated with any stroke symptom (prevalence odds ratio [POR] 1.28 [95% CI 1.18–1.39]) and two or more stroke symptoms (1.26 [1.12–1.43]) compared with normal glycemia. In analyses of individual stroke symptoms, diabetes was associated with numbness (1.15 [1.03–1.29]), vision loss (1.52 [1.31–1.76]), half-vision loss (1.54 [1.30–1.84]), and lost ability to understand people (1.34 [1.12–1.61]) after multivariable adjustment. No association was present between prediabetes and stroke symptoms. CONCLUSIONS In this population-based study, almost one in four individuals with diabetes reported stroke symptoms, which suggests that screening for stroke symptoms in diabetes may be warranted.

OBJECTIVE To examine elevated depressive symptoms and antidepressant use in relation to diabetes incidence in the Women’s Health Initiative. RESEARCH DESIGN AND METHODS A total of 161,808 postmenopausal women were followed for over an average of 7.6 years. Hazard ratios (HRs) estimating the effects of elevated depressive symptoms and antidepressant use on newly diagnosed incident diabetes were obtained using Cox proportional hazards models adjusted for known diabetes risk factors. RESULTS Multivariable-adjusted HRs indicated an increased risk of incident diabetes with elevated baseline depressive symptoms (HR 1.13 [95% CI 1.07–1.20]) and antidepressant use (1.18 [1.10–1.28]). These associations persisted through year 3 data, in which respective adjusted HRs were 1.23 (1.09–1.39) and 1.31 (1.14–1.50). CONCLUSIONS Postmenopausal women with elevated depressive symptoms who also use antidepressants have a greater risk of developing incident diabetes. In addition, longstanding elevated depressive symptoms and recent antidepressant medication use increase the risk of incident diabetes.

Background and Purpose— Warfarin reduces stroke risk by approximately 60% in patients with atrial fibrillation (AF). Differences in awareness and treatment of AF may contribute to racial and geographic disparities in stroke mortality. The objective was to examine predictors of awareness of the diagnosis of AF and treatment with warfarin. Methods— RE asons for G eographic a nd R acial D ifferences in S troke (REGARDS) is a national, population-based, longitudinal study of 30 239 blacks and whites ≥45 years old with oversampling from blacks and the southeastern stroke belt states. Participants were enrolled January 2003 to October 2007. Data were collected using telephone interview, in-home evaluation, and self-administered questionnaires. The main variable of awareness of AF was defined by a positive answer to “Has a doctor or other health professional ever told you that you had atrial fibrillation?” and whether there was evidence of treatment on the basis of an in-home medications inventory. Results— From baseline electrocardiograms, 432 individuals (88 black and 344 white) had AF. Of these, 88% (360 of 409) had at least 1 additional CHADS 2 stroke risk factor and 60% (258 of 432) were aware of their AF. The odds of blacks being aware of their AF were one third that of whites (OR=0.32; 95% CI: 0.20 to 0.52). Among those aware, the odds of blacks being treated with warfarin were only one fourth as great as whites (OR=0.28; 0.13 to 0.60). Conclusion— Blacks were less likely than whites to be aware of having AF or to be treated with warfarin. Potential reasons for the racial disparity in warfarin treatment warrant further investigation.