Chamberlain, Alanna M.

Background: Differences in the impact of comorbid conditions on outcomes in atrial fibrillation (AF) patients compared to population controls have not been well documented. Methods: The prevalence of 19 chronic conditions and smoking status was obtained in 1430 patients with incident AF from 2000-2010 and 1430 controls matched 1:1 on sex and age (within 5 years) from Olmsted County, MN. Andersen-Gill models determined associations of each condition with all-cause hospitalizations in AF cases and controls after adjusting for all other conditions and accounting for the matching. Cox regression determined associations of each condition with death. Results: Among 1430 matched pairs (median age 76 years, 48.6% men), the prevalence of chronic conditions was higher in AF cases compared to controls for all conditions except asthma, dementia, depression, hepatitis, and osteoporosis. Over a mean follow-up of 6.3 years, 2678 hospitalizations and 812 deaths occurred. The rates of hospitalization were 59 and 26 per 100 person-years and the rates of death were 10 and 5 per 100 person-years in AF cases and controls, respectively. After adjusting for all other conditions, the risk of hospitalization was lower in AF patients compared to controls for those with coronary artery disease, arthritis, cancer, chronic obstructive pulmonary disease, and osteoporosis (figure). In contrast, the risk of hospitalization was higher in AF cases for those with diabetes and substance abuse. For deaths, the only comorbidity with different associations between AF cases and controls was depression. The hazard ratios (95% CI) for death were 2.02 (1.26-3.24) in AF cases and 0.90 (0.58-1.38) in controls (p-value for interaction=0.008). Conclusions: AF patients have a higher prevalence of chronic conditions compared to population controls. The associations of comorbidities with hospitalizations differed between AF cases and controls, suggesting that management of comorbidities in patients with AF may need to be tailored to this specific patient population.

Objective: To investigate the association between low forced expiratory volume in 1 second (FEV 1 ) and incident atrial fibrillation (AF) in a population-based cohort. Background: Impaired FEV 1 , a complex measure indicating genetic, developmental, obstructive and restrictive airway disease, musculoskeletal function, and motivation, has been inconsistently associated with an increased risk of cardiovascular disease mortality. Also, extant reports do not provide separate estimates for African Americans, who surprisingly have lower AF incidence than Caucasians. Methods: We examined 15,282 middle-aged African Americans (26%) and Caucasians, men (45%) and women from four U.S. communities enrolled in the Atherosclerosis Risk in Communities (ARIC) cohort study. Lung volumes by standardized spirometry and information on covariates were collected on these participants at the baseline visit (1987-1989). Prevalent AF cases were excluded by 12-lead ECG at baseline. Incident AF was defined as the first event identified from the following: ICD codes for AF from hospital discharge records or death certificates, or ECGs performed during three triennial follow-up visits. Results: Over an average follow-up of 17.5 years, a total of 1,733 (11%) participants developed new-onset AF. The rate of incident AF increased monotonically and inversely by tertiles of FEV 1 in each of the 4 gender-race strata. The unadjusted average incidence rates of AF per 100 person years of follow up by tertiles of FEV 1 (from lowest to highest tertile) were 13.6, 8.3, and 5.7 for white men; 8.7, 4.5, and 3.4 for white women; 8.2, 5.5, and 3.8 for black men; 6.9, 4.1, and 2.4 for black women. After multivariable adjustment for traditional cardiovascular disease risk factors and height, hazard ratios (95% CI) of AF comparing the lowest with the highest tertile of FEV 1 were 1.44 (1.16,1.78) among white men, 1.45 (1.12, 1.87) among white women, 1.81 (1.09, 3.02) among black men, and 1.84(1.20, 2.82) among black women. The trend estimate for per 1 Standard-Deviation lower FEV 1 for the corresponding race and gender groups were 1.21 (1.12, 1.32), 1.38 (1.25, 1.54), 1.45 (1.18, 1.76), and 1.35 (1.12, 1.63), respectively. The above associations were observed across all smoking status categories (current, former, and never). The association between low lung function and incidence of AF was similarly unchanged after exclusion of participants with heart failure (n = 689) or CHD (n = 558) at baseline. The hazard of AF was about 50% higher among those with FEV1/FVC ratio below 0.7. Conclusions: In this large population-based cohort study with a long term follow-up, reduced FEV 1 is strongly associated with a higher AF risk, independent of race, gender, smoking, and several other CVD risk factors. These findings suggest the need for research on mechanisms underlying the observed association to seek broader opportunities for prevention of AF.

Background: Contemporary data on survival after incident acute coronary syndrome (ACS), including both myocardial infarction (MI) and unstable angina (UA), are limited. Objective: To describe survival after incident ACS, to determine if it differs by ACS type (MI or UA) and to determine whether it has improved over time. Methods: Olmsted County, MN residents hospitalized between 1/1/2005-12/31/2010 were screened for incident ACS. ACS was defined as either MI validated by standard epidemiological criteria or UA validated by the Braunwald classification. Patients were followed for death from any cause. Cox proportional hazards regression was used to determine whether survival differed by ACS type, while adjusting for year of diagnosis, age, sex and comorbidities. Results: Among 1,160 incident ACS cases (mean±SD age 66.9±14.8, 60% male), 35% were UA and 65% were MI. After a mean (SD) follow up of 3.7 (2.1) years, 274 deaths occurred. The 3-year Kaplan-Meier survival estimate for MI was 79.6% (95% CI: 76.7%-82.6%) and for UA was 84.9% (95% CI: 81.3%-88.6%) (log-rank p=0.011). The association of ACS type with survival differed by age (p=0.056). After adjustment for year of diagnosis, sex and comorbidities, no difference in survival was observed between ACS types among those aged <60 (HR for MI vs. UA: 0.64, 95% 0.29-1.42). By contrast, among patients aged 60-79, those with an MI had 2 times the risk of death compared to those with UA (HR: 2.04, 95% CI: 1.24-3.37). Patients aged 80 or older who had an MI had a 40% increased risk of death compared to patients of the same age who had UA (HR: 1.42, 95% CI: 1.02-1.98). There was no difference in survival over time (HR for 2010 vs. 2005: 0.91, 95% CI: 0.61-1.36). Conclusions: Survival did not differ between UA and MI patients younger than 60, however among patients 60 or older, survival was worse among those with an MI. Survival after ACS did not change over the study period.

Background: Atrial fibrillation (AF) is the most common cardiac arrhythmia in clinical practice, causes substantial morbidity, and is associated with an excess risk of mortality. However, information on contemporary time trends in survival after AF is lacking. Thus, we aimed to determine whether survival after incident AF has changed over the last decade in a community-based cohort of 3413 individuals with incident AF between 2000 and 2010. Methods: Olmsted County, MN residents 18 years of age and older with a first-ever AF or atrial flutter event between 2000 and 2010 were identified using inpatient and outpatient diagnostic codes and electrocardiograms. Deaths from any cause were ascertained through August 31, 2012 and time trends in survival after AF were examined using Kaplan-Meier curves and Cox proportional hazards regression. Results: Among 3413 individuals with incident AF (52% men, age range 18-104) between 2000 and 2010, 1561 deaths were observed over a median follow-up of 3.4 years. Survival did not differ by year of AF diagnosis (figure). In addition, the proportion of cardiovascular disease-related deaths compared to non-cardiovascular deaths did not differ over time. After adjustment for age, sex, and Charlson comorbidity index, the hazard ratios for all-cause mortality were 1.09 (95% CI 0.97-1.23) for those diagnosed with AF in 2004-2007 vs. 2000-2003 and 1.04 (95% CI 0.90-1.12) for 2008-2010 vs. 2000-2003. Furthermore, the risk of death did not differ by sex after adjustment for age and comorbidity (HR 1.00, 95% CI 0.90-1.11 for men vs. women). Conclusions: In the community, survival after AF has remained constant over the last decade despite substantial changes in the recommendations for treatment of AF. This underscores the importance of identification of prognostic factors and continued surveillance of outcomes in AF, as well as a better understanding of how to optimize the management of AF to improve outcomes in these patients.

Introduction: Idiopathic Dilated (DCM) and hypertrophic cardiomyopathies (HCM) are leading causes of sudden cardiac death. The incidence and prevalence of both DCM and HCM were originally estimated in Olmsted County, MN over 1975-1984. Incidence was 6.0 and prevalence was 36.5 per 100,000 person-years, for DCM; with incidence and prevalence rates of 2.5 and 19.7 per 100,000 person-years for HCM. This study aims to determine the incidence and mortality rates of individuals diagnosed with HCM and DCM in Olmsted County, MN from 1984 to 2016. Methods: The Rochester Epidemiology Project is a validated long term medical record linkage system that collects and links medical information for the approximately 145000 residents of Olmsted County, Minnesota. Using this database and the Electronic Health Record systems at Mayo Clinic and Olmsted Medical Center in Rochester, MN, we manually reviewed and validated the medical records of 4440 patients. This cohort includes all patients with any mention of a cardiomyopathy based on ICD and HICDA codes during the period 1984 to 2016. Data were summarized with mean and standard deviation, frequency and percentage and compared between groups using two sample t-test for continuous data and chi-square for proportions. Survival was computed using Kaplan-Meier methods and compared to expected survival based on age and gender. Incidence was computed using Olmsted County population numbers during the time period and adjusted to the US 1980 white population to allow for comparison with the previous study. Results: The calculated crude incidence rate for DCM and HCM are 10.1 and 7.8 per 100,000 respectively. Incidence rates adjusted for comparison to US 1980 white population (age and sex adjusted) are 10.4 (95% CI: 9.3-11.4) and 8.0 (95% CI: 7.1-8.8) per 100,000 person-years, respectively. The observed number of deaths in this cohort (HCM and DCM) was 420 vs 194 expected. Conclusions: Calculated incidence, both crude and adjusted rates are higher than previously estimated rates. The crude incidence rate for HCM is almost 4-fold higher than that for DCM is 2.4 times higher than the original estimate by Codd et al. Individuals with cardiomyopathies were found to have a higher overall mortality rate than the general population with an observed to expected hazard ratio of 1.73 (95% CI 1.49-2.01, p<0.001) for DCM and 1.44 (95% CI 1.21-1.71, p<0.001) for HCM. Our findings suggest that previous studies may have underestimated the true burden of HCM and DCM in the population which has important implications for healthcare provision and cost.

Introduction: Little is known about the characteristics and resources that enable patients with heart failure (HF) to engage in effective self-management. To address this gap in knowledge, we measured personal and health care resources for self-management and examined associations with mortality among patients with HF. Methods: We surveyed 5543 residents of 11 counties in Southeast Minnesota with a first-ever code for HF [International Classification of Disease, Ninth Revision code 428 or Tenth Revision code I50] between 1/1/2013 and 3/31/2016. Self-management resources were measured with the health care and personal subscales of the Chronic Illness Resources Survey (CIRS), both of which included 3 questions on a 5-point scale. The responses were averaged and participants were categorized as low if the mean score was below the median of the distribution (range from 1 to 5). The survey was returned by 2866 participants (response rate 52%) and those with complete data on the main items of interest were retained for analysis (N=2212). Cox proportional hazards regression was used to determine the association between each subscale and mortality. Results: Among 2212 participants (mean age 72.8 years, 54.1% men) the median health care score was 4, while the personal score was 3. Those with low health care resources were older and less educated than those with a higher score (p<0.05), while those with low personal resources had less comorbidities and lower education attainment compared to those with a higher score (p<0.05). After a mean (SD) follow-up of 1.3 ± 0.6 years, 207 deaths occurred. Low levels of both self-management resources were associated with an increased risk of death compared with patients with high levels (Table). Conclusions: Having limited self-management resources is associated with an increased risk of mortality among patients with HF. Thus, interventions aimed at supporting self-management among patients with HF may improve outcomes.

Background: Current guidelines recommend oral anticoagulation for the prevention of stroke in most patients with atrial fibrillation (AF). Direct oral anticoagulants (DOACs) are associated with lower risk of ischemic stroke and intracranial bleeding than warfarin and, therefore, may reduce risk of dementia among patients with AF. Hypothesis: AF patients initiating DOACs for stroke prevention will have lower risk of dementia than patients initiating warfarin. Methods: We used data from two US healthcare claim databases, MarketScan (2007-2015) and Optum Clinformatics (2009-2015). Using validated algorithms, we identified patients with AF who initiated oral anticoagulation. Dementia was defined as having an International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code of 290.xx, 294.xx, or 331.0. Comorbidities and use of other medications were defined based on inpatient, outpatient, and pharmacy claims. We performed a series of head-to-head comparisons of different oral anticoagulants (warfarin, dabigatran, rivaroxaban, and apixaban) in propensity score-matched cohorts. In each database, multivariable-adjusted Cox regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for incident dementia for each comparison of propensity score-matched cohorts, adjusting for age, sex, comorbidities, use of other medications, and markers of socioeconomic status (in the Optum database only). We meta-analyzed database-specific results using a random-effects model. Results: The analysis included 307,099 AF patients from the MarketScan database and 161,346 from the Optum database, of which 6,572 and 4,391 respectively had a diagnosis of incident dementia. Mean follow up ranged between 0.7 to 2.3 years and incident of diagnosed dementia between 7 to 14 cases per 1000 person-years across different oral anticoagulant initiator groups. Patients initiating DOACs had a lower risk of incident dementia than those initiating warfarin (dabigatran: HR 0.85, 95%CI 0.71, 1.01; rivaroxaban: HR 0.85, 95%CI 0.76, 0.94; apixaban: HR 0.80, 95%CI 0.65, 0.97). There were no differences in risk of incident dementia comparing DOAC user groups (dabigatran vs. rivaroxaban: HR 1.02, 95%CI 0.79, 1.32; dabigatran vs. apixaban: HR 0.92, 95%CI 0.63, 1.36; apixaban vs. rivaroxaban: HR 1.01, 95%CI 0.86, 1.19). Conclusions: Patients with AF initiating DOACs experienced lower rates of incident dementia than warfarin users. No obvious benefit was observed for any particular DOAC in relation to dementia rates.

Background: Oral anticoagulants (OACs) are recommended for AF patients for the prevention of thromboembolic events, including stroke. Stroke risk stratification scores (e.g., CHA 2 DS 2 -VASc) are used to tailor therapeutic recommendations for patients in different risk groups. However, these were derived before the advent of direct OACs. At present, there is no tool that estimates a patient’s stroke risk, given their individual characteristics, by type of OAC. Methods: We used healthcare utilization data from two independent US databases (MarketScan and Optum) to construct and validate a predictive model of ischemic stroke in patients with AF initiating OACs. Patients with non-valvular AF initiating OACs were identified from the MarketScan data for years 2007-2015. Using bootstrapping methods and backward selection of 44 candidate variables, we developed a model which selected variables predicting stroke. The final model was validated in patients with non-valvular AF in the Optum Clinformatics database in the period 2009-2015. Results: Among 135,523 patients with AF initiating OAC in the MarketScan dataset, 2,028 experienced an ischemic stroke after anticoagulant initiation. The stepwise model identified 15 variables (including type of OAC) associated with ischemic stroke (Table). The discrimination (c-statistic) of the model was adequate [0.68, 95% confidence interval (CI) 0.66-0.70], showing excellent calibration (χ 2 = 7.7 p=0.57). The model was then applied to the 84,549 AF patients in the Optum data set (1408 stroke events). The model showed similar discrimination (c-statistic 0.67, 95%CI 0.65-0.70) and calibration (χ 2 = 12.8 p=0.17). However, previously-developed predicted models had similar discriminative ability (CHA 2 DS 2 -VASc 0.67, 95%CI 0.65-0.68; ATRIA 0.67, 95%CI 0.65-0.68) Conclusion: A novel model using extensive administrative healthcare data for the identification of patients at higher risk of ischemic stroke by type of anticoagulant did not perform better than established simple models.

Background: Cardiovascular disease (CVD) remains the leading cause of death for African-American (AA) adults. There is a low prevalence of ideal cardiovascular health (CVH) (as defined by the American Heart Association’s Life’s Simple 7 TM (LS7)), especially diet, physical activity and obesity among AAs placing them at a disproportionately high risk for CVD. The identification of psychosocial stress that may influence ideal CVH could assist in the development of more effective behavior change interventions among AAs. Objectives: The aim of this study is to examine the associations of multidimensional stressors (chronic stress, minor stressors, and major life events - MLEs) with the LS7 components (classified as poor, intermediate and ideal) in AAs. We hypothesize that stress is negatively associated with the likelihood of achievement of intermediate/ideal levels of the LS7 components and LS7 composite score after adjusting for traditional socio-demographic factors. Methods: Using the Jackson Heart Study (JHS), a cohort of AAs based in Jackson, Mississippi (n=4383), we conducted a cross-sectional analysis of the association of stress measures with LS7 components (smoking, diet, physical activity, body mass index, blood pressure, total cholesterol and glucose). This association was measured using logistic regression which assessed the odds ratios (OR, 95% confidence interval (CI)) of the achievement of intermediate/ideal levels of CVH with progressive adjustment for demographic, socioeconomic, behavioral and biomedical factors. A composite LS7 score was calculated [range 0-14; categorized as 0 to 6 (poor), 7 to 8 (intermediate) and 9 to 14 (ideal)]. We also constructed a cumulative stress score as a summation of tertiles of each stress measure (range 3-9). Results: Fewer participants achieved intermediate or ideal CVH for the LS7 components including diet (39%), physical activity (51%) and BMI (47%). Higher chronic stress and minor stressors scores were associated a decreased likelihood of achievement of ideal/intermediate levels for smoking [OR 0.80; 95% CI 0.73-0.88 and OR 0.84; 95% CI 0.75-0.94, respectively). Higher MLE scores were associated decreased likelihood of achievement of ideal/intermediate levels for smoking (OR 0.84; 95% CI 0.76-0.92) and glucose (OR 0.90; 95% CI 0.82-0.98). Those with higher minor stressors and MLE scores were less likely to achieve intermediate or ideal LS7 composite score categories (OR 0.89; 95% CI 0.81-0.97 and OR 0.91; 95% CI 0.84-0.98, respectively). There was no statistically significant association between LS7 composite scores and cumulative stress scores. Conclusions: Our results suggest that key stress measures may contribute adversely to CVH among AAs. These findings provide support for future lifestyle interventions which integrate a focus on alleviating stressors in this high risk population to improve CVH.

Background: Multimorbidity is common in patients with atrial fibrillation (AF), yet comorbidity patterns are not well documented. Methods: The prevalence of 18 chronic conditions was obtained in patients with AF from 2013-2017 from a 27-county region in the Midwest. All patients had AF documented on an electrocardiogram or Holter monitor. To compare comorbidity patterns between patients with and without AF, controls were matched 1:1 on age (± 5 years) and sex. For AF patients and controls separately, the Somers’ D statistic was used to quantify the non-random concordance of each pair of chronic conditions beyond chance (ranging from -1 [perfect disagreement] to 1 [perfect agreement]; 0 indicating coincidental agreement by chance alone). Significance of the Somers’ D statistic was evaluated using a permutation approach with the Benjamini-Hochberg procedure for controlling the false discovery rate at 0.1%. Results: Among the 16,543 patients with AF (median age 76 years, 57% men), the most common conditions were hypertension (70%), hyperlipidemia (61%), arthritis (41%), and diabetes (40%). Many pairs of chronic conditions co-occurred more frequently than expected. However, no material differences were observed in the co-occurrence of conditions in patients with AF compared to controls (data not shown). Among patients with AF, the co-occurrence of conditions differed by age (Figure). In those ≤65 years, the strongest co-occurrence of conditions was depression/anxiety, although several condition pairs had Somers’ D statistics of >0.4. In those aged 65-74 years, hypertension/hyperlipidemia and depression/anxiety had the strongest co-occurrence, whereas hypertension/hyperlipidemia was strongest for those aged ≥75 years. Conclusion: Although differences in the co-occurrence of conditions did not exist between AF and community controls, among the patients with AF, the patterns of co-existing conditions differed by age. A better understanding of the clinical consequences of multimorbidity in AF patients is needed.