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Background Heart failure (HF) is a complex disease that contributes to a high number of hospitalizations, deaths, and economic health care costs each year. However, among patients with HF, there is a lack of awareness of their HF diagnosis that has not been fully examined. Methods and Results Residents from 3 counties of southeast Minnesota with a first-ever International Classification of Diseases, Ninth Revision ( ICD-9 ) code 428 or Tenth Revision ( ICD-10 ) code I50 between January 1, 2013 and March 31, 2016 (N=2461) were prospectively surveyed to measure HF self-awareness. A total of 1114 patients returned the survey (response rate, 45%), and 787 had validated HF upon medical record review. Among these 787 patients with HF (mean age, 76 years; 53% men), 37% (n=293) were aware of their HF diagnosis. After adjustment, being a woman (odds ratio [OR], 1.56 [95% CI, 1.10-2.22]), having HF with reduced ejection fraction (OR, 1.58 [95% CI, 1.13-2.22]), attending the HF clinic (OR, 4.07 [95% CI, 2.25-7.36]), and having coronary artery disease (OR, 1.65 [95% CI, 1.16-2.37]) were all associated with increased awareness of an HF diagnosis. Conversely, having diabetes was associated with decreased awareness of an HF diagnosis (adjusted OR, 0.69 [95% CI, 0.50-0.95]). Conclusions Awareness of an HF diagnosis is low in a community population of patients with HF. Strategies to improve patient awareness of their diagnosis should be implemented to improve self-care behaviors and outcomes in patients with HF.

Background and Objectives: Prevention strategies for Alzheimer disease and Alzheimer disease-related dementias (AD/ADRDs) are urgently needed. Lipid variability, or fluctuations in blood lipid levels at different points in time, has not been examined extensively and may contribute to the risk of AD/ADRD. Lipid panels are a part of routine screening in clinical practice and routinely available in electronic health records (EHR). Thus, in a large geographically defined population-based cohort, we investigated the variation of multiple lipid types and their association to the development of AD/ADRD., Methods: All residents living in Olmsted County, Minnesota on the index date January 1, 2006, aged 60 years or older without an AD/ADRD diagnosis were identified. Persons with ≥3 lipid measurements including total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C), or high-density lipoprotein cholesterol (HDL-C) in the 5 years before index date were included. Lipid variation was defined as any change in individual's lipid levels over time regardless of direction and was measured using variability independent of the mean (VIM). Associations between lipid variation quintiles and incident AD/ADRD were assessed using Cox proportional hazards regression. Participants were followed through 2018 for incident AD/ADRD., Results: The final analysis included 11,571 participants (mean age 71 years; 54% female). Median follow-up was 12.9 years with 2,473 incident AD/ADRD cases. After adjustment for confounding variables including sex, race, baseline lipid measurements, education, BMI, and lipid-lowering treatment, participants in the highest quintile of total cholesterol variability had a 19% increased risk of incident AD/ADRD, and those in highest quintile of triglycerides, variability had a 23% increased risk., Discussion: In a large EHR derived cohort, those in the highest quintile of variability for total cholesterol and triglyceride levels had an increased risk of incident AD/ADRD. Further studies to identify the mechanisms behind this association are needed., (Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a “work of the United States Government” for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government.)

Background Among patients with heart failure (HF), social risk factors (SRFs) are associated with poor outcomes. However, less is known about how co-occurrence of SRFs affect all-cause health care utilization for patients with HF. The objective was to address this gap using a novel approach to classify co-occurrence of SRFs. Methods and Results This was a cohort study of residents living in an 11-county region of southeast Minnesota, aged ≥18 years with a first-ever diagnosis for HF between January 2013 and June 2017. SRFs, including education, health literacy, social isolation, and race and ethnicity, were obtained via surveys. Area-deprivation index and rural-urban commuting area codes were determined from patient addresses. Associations between SRFs and outcomes (emergency department visits and hospitalizations) were assessed using Andersen-Gill models. Latent class analysis was used to identify subgroups of SRFs; associations with outcomes were examined. A total of 3142 patients with HF (mean age, 73.4 years; 45% women) had SRF data available. The SRFs with the strongest association with hospitalizations were education, social isolation, and area-deprivation index. We identified 4 groups using latent class analysis, with group 3, characterized by more SRFs, at increased risk of emergency department visits (hazard ratio [HR], 1.33 [95% CI, 1.23-1.45]) and hospitalizations (HR, 1.42 [95% CI, 1.28-1.58]). Conclusions Low educational attainment, high social isolation, and high area-deprivation index had the strongest associations. We identified meaningful subgroups with respect to SRFs, and these subgroups were associated with outcomes. These findings suggest that it is possible to apply latent class analysis to better understand the co-occurrence of SRFs among patients with HF.

Importance: Heart failure (HF) with preserved ejection fraction (HFpEF) is common, is frequently associated with ventricular wall thickening, and has no effective therapy. Transthyretin amyloid cardiomyopathy (ATTR-CM) can cause the HFpEF clinical phenotype, has highly effective therapy, and is believed to be underrecognized., Objective: To examine the prevalence of ATTR-CM without and with systematic screening in patients with HFpEF and ventricular wall thickening., Design, Setting, and Participants: This population-based cohort study assessed ATTR-CM prevalence in 1235 consecutive patients in southeastern Minnesota with HFpEF both without (prospectively identified cohort study) and with (consenting subset of cohort study, n = 286) systematic screening. Key entry criteria included validated HF diagnosis, age of 60 years or older, ejection fraction of 40% or greater, and ventricular wall thickness of 12 mm or greater. In this community cohort of 1235 patients, 884 had no known ATTR-CM, contraindication to technetium Tc 99m pyrophosphate scanning, or other barriers to participation in the screening study. Of these 884 patients, 295 consented and 286 underwent scanning between October 5, 2017, and March 9, 2020 (community screening cohort)., Exposures: Medical record review or technetium Tc 99m pyrophosphate scintigraphy and reflex testing for ATTR-CM diagnosis., Main Outcomes and Measures: The ATTR-CM prevalence by strategy (clinical diagnosis or systematic screening), age, and sex., Results: A total of 1235 patients participated in the study, including a community cohort (median age, 80 years; interquartile range, 72-87 years; 630 [51%] male) and a community screening cohort (n = 286; median age, 78 years; interquartile range, 71-84 years; 149 [52%] male). In the 1235 patients in the community cohort without screening group, 16 patients (1.3%; 95% CI, 0.7%-2.1%) had clinically recognized ATTR-CM. The prevalence was 2.5% (95% CI, 1.4%-4.0%) in men and 0% (95% CI, 0.0%-0.6%) in women. In the 286 patients in the community screening cohort, 18 patients (6.3%; 95% CI, 3.8%-9.8%) had ATTR-CM. Prevalence increased with age from 0% in patients 60 to 69 years of age to 21% in patients 90 years and older (P < .001). Adjusting for age, ATTR-CM prevalence differed by sex, with 15 of 149 men (10.1%; 95% CI, 5.7%-16.1%) and 3 of 137 women (2.2%; 95% CI, 0.4%-6.3%) having ATTR-CM (P = .002)., Conclusions and Relevance: In this cohort study based in a community-based setting, ATTR-CM was present in a substantial number of cases of HFpEF with ventricular wall thickening, particularly in older men. These results suggest that systematic evaluation can increase the diagnosis of ATTR-CM, thereby providing therapeutically relevant phenotyping of HFpEF.

Purpose: The depth and breadth of clinical data within electronic health record (EHR) systems paired with innovative machine learning methods can be leveraged to identify novel risk factors for complex diseases. However, analysing the EHR is challenging due to complexity and quality of the data. Therefore, we developed large electronic population-based cohorts with comprehensive harmonised and processed EHR data., Participants: All individuals 30 years of age or older who resided in Olmsted County, Minnesota on 1 January 2006 were identified for the discovery cohort. Algorithms to define a variety of patient characteristics were developed and validated, thus building a comprehensive risk profile for each patient. Patients are followed for incident diseases and ageing-related outcomes. Using the same methods, an independent validation cohort was assembled by identifying all individuals 30 years of age or older who resided in the largely rural 26-county area of southern Minnesota and western Wisconsin on 1 January 2013., Findings to Date: For the discovery cohort, 76 255 individuals (median age 49; 53% women) were identified from which a total of 9 644 221 laboratory results; 9 513 840 diagnosis codes; 10 924 291 procedure codes; 1 277 231 outpatient drug prescriptions; 966 136 heart rate measurements and 1 159 836 blood pressure (BP) measurements were retrieved during the baseline time period. The most prevalent conditions in this cohort were hyperlipidaemia, hypertension and arthritis. For the validation cohort, 333 460 individuals (median age 54; 52% women) were identified and to date, a total of 19 926 750 diagnosis codes, 10 527 444 heart rate measurements and 7 356 344 BP measurements were retrieved during baseline., Future Plans: Using advanced machine learning approaches, these electronic cohorts will be used to identify novel sex-specific risk factors for complex diseases. These approaches will allow us to address several challenges with the use of EHR., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The rate of decline in cardiovascular disease (CVD) mortality has lessened nationally. How these findings apply to specific states or causes of CVD deaths is not known. Examining these trends at the state level is important to plan local interventions., Methods: We analyzed CVD mortality trends in Minnesota (MN) using the U.S. Centers for Disease Control and Prevention (CDC) Wide-ranging ONline Data for Epidemiologic Research (WONDER). Trends were analyzed by age, sex, type of CVD and location of death., Results: CVD mortality rates in MN declined in 2000-2009 and then leveled off in 2010-2018, paralleling national rates. Age- and sex-adjusted CVD mortality decreased by 3.7% per year in 2000-2009 (average annual percent changes [AAPC]: -3.7; 95% CI: - 4.8, - 2.6) with no change observed in 2010-2018. Those aged 65-84 years had the most rapid early decline in CVD mortality (AAPC: -5.9, 95% CI: - 6.2, - 5.7) and had less improvement in 2010-2018 (AAPC: -1.8, 95% CI: - 2.2, - 1.5), and the younger age group (25-64 years) now experiences the most adverse trends (AAPC: 1.2, 95% CI: 0.7-1.8). Coronary heart disease (CHD) and cerebrovascular disease had the largest relative decreases in mortality in 2000-2009 (CHD AAPC: -5.2; 95% CI: - 6.5,-3.9; cerebrovascular disease AAPC: -4.4, 95% CI: - 5.2, - 3.6) with no change 2010-2018. Heart failure (HF)/cardiomyopathy followed similar trends with a 2.5% decrease (AAPC 95% CI: - 3.5, - 1.5) per year in 2000-2009 and no change in 2010-2018. Deaths from other CVD also decreased in the early time period (AAPC: -1.6, 95% CI: - 2.7, - 0.5) but increased in 2010-2018 (AAPC: 1.9, 95% CI: 0.5, 3.3). In- and out-of-hospital death rates improved in 2000-2009 with a slowing in improvement for in-hospital death and no further improvement for out-of-hospital death in 2010-2018., Conclusion: Concerning CVD mortality trends occurred in MN. In the most recent decade (2010-2018) mortality from all CVD subtypes plateaued or even increased. CVD mortality among the younger age groups increased as well. These data are congruent with adverse national trends supporting their generalizability. These adverse trends underscore the urgent need for CVD prevention and treatment, as well as continued surveillance to assess progress at the state and national level.

Background Prior reports indicate that living in a rural area may be associated with worse health outcomes. However, data on rurality and heart failure (HF) outcomes are scarce. Methods and Results Residents from 6 southeastern Minnesota counties with a first-ever code for HF ( International Classification of Diseases, Ninth Revision [ ICD-9 ], code 428, and International Classification of Diseases, Tenth Revision [ ICD-10 ] code I50) between January 1, 2013 and December 31, 2016, were identified. Resident address was classified according to the rural-urban commuting area codes. Rurality was defined as living in a nonmetropolitan area. Cox regression was used to analyze the association between living in a rural versus urban area and death; Andersen-Gill models were used for hospitalization and emergency department visits. Among 6003 patients with HF (mean age 74 years, 48% women), 43% lived in a rural area. Rural patients were older and had a lower educational attainment and less comorbidity compared with patients living in urban areas ( P <0.001). After a mean (SD) follow-up of 2.8 (1.7) years, 2440 deaths, 20 506 emergency department visits, and 11 311 hospitalizations occurred. After adjustment, rurality was independently associated with an increased risk of death (hazard ratio [HR], 1.18; 95% CI, 1.09-1.29) and a reduced risk of emergency department visits (HR, 0.89; 95% CI, 0.82-0.97) and hospitalizations (HR, 0.78; 95% CI, 0.73-0.84). Conclusions Among patients with HF, living in a rural area is associated with an increased risk of death and fewer emergency department visits and hospitalizations. Further study to identify and address the mechanisms through which rural residence influences mortality and healthcare utilization in HF is needed in order to reduce disparities in rural health.

Purpose: Prior studies observed that women experienced worse outcomes than men after myocardial infarction but did not convincingly establish an independent effect of female sex on outcomes, thus failing to impact clinical practice. Current data remain sparse and information on long-term nonfatal outcomes is lacking. To address these gaps in knowledge, we examined outcomes after incident myocardial infarction for women compared with men., Methods: We studied a population-based myocardial infarction incidence cohort in Olmsted County, Minnesota, between 2000 and 2012. Patients were followed for recurrent myocardial infarction, heart failure, and death. A propensity score was constructed to balance the clinical characteristics between men and women; Cox models were weighted using inverse probabilities of the propensity scores., Results: Among 1959 patients with incident myocardial infarction (39% women; mean age 73.8 and 64.2 for women and men, respectively), 347 recurrent myocardial infarctions, 464 heart failure episodes, 836 deaths, and 367 cardiovascular deaths occurred over a mean follow-up of 6.5 years. Women experienced a higher occurrence of each adverse event (all P <0.01). After propensity score weighting, women had a 28% increased risk of recurrent myocardial infarction (hazard ratio: 1.28, 95% confidence interval: 1.03-1.59), and there was no difference in risk for any other outcomes (all P >0.05)., Conclusion: After myocardial infarction, women experience a large excess risk of recurrent myocardial infarction but not of heart failure or death independently of clinical characteristics. Future studies are needed to understand the mechanisms driving this association., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: The best management strategy for patients with atrial fibrillation (AF) with heart failure (HF) and preserved left ventricular ejection fraction (LVEF) is unknown., Methods and Results: This cohort study was conducted in Olmsted County, Minnesota, with resources of the Rochester Epidemiology Project. Patients with incident AF occurring between 2000 and 2014 with a prior or concurrent HF were included. Patients with LVEF ≥ 50% were designated as HF and preserved ejection fraction (HFpEF) and those with LVEF < 50% were designated as HF and reduced ejection fraction (HFrEF). Rhythm control in the first year after AF diagnosis was defined as prescriptions for an antiarrhythmic drug, catheter ablation, or maze procedure. The primary endpoint was all-cause mortality. The secondary endpoints were cardiovascular death, cardiovascular hospitalization, and stroke or transient ischemic attack. Of 859 patients (age, 77.2 ± 12.1 years; 49.2%, female), 447 had HFpEF-AF, and 412 had HFrEF-AF. There was no difference in all-cause mortality (10-year mortality, 83% vs 79%; p = .54) or secondary endpoints between the HFpEF-AF and HFrEF-AF, respectively. Compared with the rate control strategy, rhythm control in HFpEF-AF patients (n = 40, 15.9%) offered no survival benefits (adjusted HR, 0.70; 95% CI, 0.42-1.16; p = .16), whereas rhythm control in HFrEF-AF patients (n = 52, 22.5%) decrease cardiovascular mortality (HR, 0.38; 95% CI, 0.17-0.86; p = .02)., Conclusions: Patients with HFpEF-AF and HFrEF-AF had similar poor prognoses. Rhythm control strategy was seldom adopted in community care in patients with HF and AF. A rhythm control strategy may provide survival benefit for patients with HFrEF-AF and the benefit of rhythm control in patients with HFpEF-AF warrants further study., (© 2020 Wiley Periodicals LLC.)

Background: Differences in comorbid conditions in patients with heart failure compared with population controls, and whether differences exist by type of heart failure or age, have not been well documented., Methods: The prevalence of 17 chronic conditions were obtained in 2643 patients with incident heart failure from 2000 to 2013 and controls matched 1:1 on sex and age from Olmsted County, Minnesota. Logistic regression determined associations of each condition with heart failure., Results: Among 2643 matched pairs (mean age 76.2 years, 45.6% men), the comorbidities with the largest attributable risk of heart failure were arrhythmia (48.7%), hypertension (28.4%), and coronary artery disease (33.9%); together these explained 73.0% of heart failure. Similar associations were observed for patients with reduced and preserved ejection fraction, with the exception of hypertension. The risk of heart failure attributable to hypertension was 2-fold higher in patients with heart failure with preserved ejection fraction (38.7%) than in patients with heart failure with reduced ejection fraction (17.8%). Hypertension, coronary artery disease, arrhythmia, and diabetes were more strongly associated with heart failure in younger (≤75 years) compared to older (>75 years) persons., Conclusions: Patients with heart failure have a higher prevalence of many chronic conditions than controls. Similar associations were observed in patients with reduced and preserved ejection fraction, with the exception of hypertension, which was more strongly associated with heart failure with preserved ejection fraction. Finally, some cardiometabolic risk factors were more strongly associated with heart failure in younger persons, highlighting the importance of optimizing prevention and treatment of risk factors and, in particular, cardiometabolic risk factors., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: To identify differences between participants and nonparticipants in a survey of physical and psychosocial aspects of health among a population-based sample of patients with heart failure (HF)., Patients and Methods: Residents from 11 Minnesota counties with a first-ever code for HF (International Classification of Diseases, Ninth Revision 428 and Tenth Revision I50) between January 1, 2013, and December 31, 2016, were identified. Participants completed a questionnaire by mail or telephone. Characteristics and outcomes were extracted from medical records and compared between participants and nonparticipants. Response rate was calculated using guidelines of the American Association for Public Opinion Research. The association between nonparticipation and outcomes was examined using Cox proportional hazards regression for death and Andersen-Gill modeling for hospitalizations., Results: Among 7911 patients, 3438 responded to the survey (American Association for Public Opinion Research response rate calculated using formula 2 = 43%). Clinical and demographic differences between participants and nonparticipants were noted, particularly for education, marital status, and neuropsychiatric conditions. After a mean ± SD of 1.5±1.0 years after survey administration, 1575 deaths and 5857 hospitalizations occurred. Nonparticipation was associated with a 2-fold increased risk for death (hazard ratio, 2.29; 95% CI, 2.05-2.56) and 11% increased risk for hospitalization (hazard ratio, 1.11; 95% CI, 1.02-1.22) after adjusting for age, sex, time from HF diagnosis to index date, marital status, coronary disease, arrhythmia, hyperlipidemia, diabetes, cancer, chronic kidney disease, arthritis, osteoporosis, depression, and anxiety., Conclusion: In a large survey of patients with HF, participation was associated with notable differences in clinical and demographic characteristics and outcomes. Examining the impact of participation is critical to draw inference from studies of patient-reported measures., (Copyright © 2019 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Background Temporal declines in cardiac stress tests results, coronary revascularization, and cardiovascular mortality have suggested a decline in the population burden of coronary disease until the 2000s. However, recent data indicate these favorable trends could be ending. We aimed to assess the evolution of the population burden of coronary disease in the community by examining trends in angiography and revascularization. Methods and Results We analyzed age- and sex-adjusted trends from all coronary angiographic diagnostic procedures and revascularizations performed in Olmsted County, MN from 2000 to 2018. A total of 12 981 invasive angiograms were performed among 9049 individuals (64% men; 55% aged ≥65 years). Adjusted angiography rates decreased by 30% (95% CI, 25%-34%) between 2000 and 2009 and leveled off thereafter. Including computed tomography, angiography uncovered an increase in angiography use in recent years (risk ratio=1.15 [95% CI, 1.07-1.23] for 2018 versus 2014) and a decline in the prevalence of anatomic CAD from 2000 to 2018. CAD severity declined substantially from 2000 to 2009, followed by a plateau. Among 6570 revascularizations (72% men; 57% aged ≥65 years), 77% were percutaneous coronary interventions and 23% coronary artery bypass graft surgeries. The adjusted revascularization rates declined by 34% (95% CI, 27%-39%) from 2000 to 2009, followed by a plateau (risk ratio=1.10 [95% CI, 1.00-1.22]). Conclusions Between 2000 and 2018 in the community, coronary angiography use declined initially, leveled off, and then increased. Trends in CAD severity and revascularization use decreased then plateaued. The most recent trends are concerning as they suggest the burden of coronary disease is no longer declining. This warrants reinvigorated primary prevention and population surveillance.

Introduction: Myocardial infarction (MI) is associated with an increase in subsequent heart failure (HF), recurrent ischemic events, sudden cardiac arrest, and ventricular arrhythmias (SCA-VA). The primary objective of the study to determine the role of intercurrent HF and ischemic events on the development of SCA-VA following first type I MI., Methods and Results: A retrospective cohort study of patients experiencing first type 1 MI in Olmsted County, Minnesota (2002-2012) was conducted by identifying patients using the medical records linkage system (Rochester epidemiology project). Patients aged ≥18 years were followed from the time of MI till death or 31 July, 2017. Intercurrent HF and ischemic events were the primary exposures following MI and their association with outcome SCA-VA was assessed. Eight hundred and sixty-seven patients (mean age was 63 ± 14.5 years; 69% male; 49.8% ST-elevation myocardial infarction) who had their first type I MI during the study period were included. Majority of acute MI patients were revascularized using percutaneous coronary intervention and bypass surgery (628 [72.43%] and 87 [10.03%] respectively). During a mean follow-up of 7.69 ± 4.17 years, HF, recurrent ischemic events and SCA-VA occurred in 155 (17.9%), 245 (28.3%), and 40 (4.61%) patients respectively. Low ejection fraction (adjusted hazard ratio [HR] 0.95; 95% confidence interval [CI], 0.93-0.98; P < .001), intercurrent HF (adjusted HR 3.11; 95% CI, 1.39-6.95; P = .006) and recurrent ischemic events (adjusted HR 3.47; 95% CI, 1.68-7.18; P < .001) were associated with subsequent SCA-VA., Conclusion: SCA-VA occurred in a small proportion of patients after MI and is associated with intercurrent HF and recurrent ischemic events., (© 2019 Wiley Periodicals, Inc.)

Objective: The nonaortic cardiovascular morbidity and mortality of patients with aortic dissection (AD), intramural hematoma (IMH), and penetrating aortic ulcer (PAU) is unknown. We aimed to define the rates of cardiovascular (CV) events in a cohort of patients with newly diagnosed AD, IMH, and PAU., Methods: We performed a retrospective review of all Olmsted County, Minnesota, residents diagnosed with AD, IMH, and PAU from 1995 to 2015. The primary outcome was nonaortic CV death. The secondary outcome was a first-time nonfatal CV event (myocardial infarction, heart failure [HF], or stroke). The outcomes were compared with age- and sex-matched population referents using Cox proportional hazards regression, with adjustment for comorbidities., Results: A total of 133 patients (77 with AD, 21 with IMH, 35 with PAU; 57% male) with a mean age of 71.8 ± 14.1 years were identified. The median follow-up was 10 years. Compared with the population referents, the patients with AD/IMH/PAU had an increased risk of CV death (adjusted hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.4-4.2; P = .003) and an increased risk of any first-time nonfatal CV event (adjusted HR, 3.0; 95% CI, 1.9-4.8; P < .001), mainly resulting from an increased risk of first-time HF (adjusted HR, 2.7; 95% CI, 1.7-4.3; P < .001). When excluding events within 14 days of the diagnosis, the patients with AD/IMH/PAU remained at increased risk of CV death (adjusted HR, 2.6; 95% CI, 1.4-4.7; P = .002), any first-time nonfatal CV event (adjusted HR, 2.6; 95% CI, 1.5-4.4, P <.001), and first-time HF (adjusted HR 2.5, 95% CI 1.5-4.3; P < .001)., Conclusions: Compared with the population referents, the patients with AD/IMH/PAU had a two- to threefold risk of nonaortic CV death, any first-time nonfatal CV event, and first-time HF. These data implicate the need for long-term cardiovascular management for patients with AD/IMH/PAU., (Copyright © 2019 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Galectin-3 (Gal-3) is implicated in cardiac fibrosis, but its association with adverse outcomes after myocardial infarction (MI) is unknown., Objectives: The purpose of this study was to examine the prognostic value of Gal-3 in a community cohort of incident MI., Methods: A population-based incidence MI cohort was prospectively assembled in Olmsted County, Minnesota, between 2002 and 2012. Gal-3 levels were measured at the time of MI. Patients were followed for heart failure (HF) and death., Results: A total of 1,342 patients were enrolled (mean age 67.1 years; 61.3% male; 78.8% non-ST-segment elevation MI). Patients with elevated Gal-3 were older and had more comorbidities. Over a mean follow-up of 5.4 years, 484 patients (36.1%) died and 368 (27.4%) developed HF. After adjustment for age, sex, comorbidities, and troponin, patients with Gal-3 values in tertiles 2 and 3 had a 1.3-fold (95% confidence interval [CI]: 0.9-fold to 1.7-fold) and a 2.4-fold (95% CI: 1.8-fold to 3.2-fold) increased risk of death, respectively (p trend  < 0.001) compared with patients with Gal-3 values in tertile 1. Patients with Gal-3 values in tertiles 2 and 3 had a higher risk of HF with hazard ratios of 1.4 (95% CI: 1.0 to 2.0) and 2.3 (95% CI: 1.6 to 3.2), respectively (p trend  < 0.001). With further adjustment for soluble suppression of tumorigenicity-2, elevated Gal-3 remained associated with increased risk of death and HF. The increased risk of HF did not differ by HF type and was independent of the occurrence of recurrent MI., Conclusions: Gal-3 is an independent predictor of mortality and HF post-MI. These findings suggest a role for measuring Gal-3 levels for risk stratification post-MI., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background As the population with cardiovascular disease ages, geriatric conditions are of increasing relevance. A possible geriatric prognostic indicator may be a fall risk score, which is mandated by The Joint Commission to be measured on all hospitalized patients. The prognostic value of a fall risk score on outcomes after dismissal is not well known. Thus, we aimed to determine whether a fall risk score is associated with death and hospital readmissions in patients with a recent incident cardiovascular disease event. Methods and Results In this retrospective cohort study, Olmsted County, MN patients with incident heart failure, myocardial infarction, or atrial fibrillation between August 1, 2005, and December 31, 2011, who were hospitalized within 180 days after the event were studied. Fall risk was measured by the Hendrich II fall risk model. Patients were followed for death or readmission within 30 days or 1 year. Among 2456 hospitalized patients with recent incident cardiovascular disease (549 heart failure, 784 myocardial infarction, 1123 atrial fibrillation; mean [SD] age, 71 [15] years; 55% men), the fall risk score was high in 22% of patients and moderate in 38%. The risk of death was increased if the fall risk score was increased, independent of age and comorbidities (moderate hazard ratio, 1.51; 95% CI, 1.09-2.08; high hazard ratio, 3.49; 95% CI, 2.52-4.85). Similarly, the risk of 30-day readmissions was substantially increased with a greater fall risk score (moderate hazard ratio, 1.29; 95% CI, 1.03-1.62; high hazard ratio, 1.63; 95% CI, 1.23-2.15). Results were similar for readmissions within 1 year. Conclusions More than half of hospitalized patients with recent incident cardiovascular disease have an elevated fall risk score, which is associated with an increased risk in readmissions and death. These results delineate an approach for risk stratification and management that may prevent readmissions and improve survival.

Objectives: To characterize the individual and combined effects of multimorbidity and functional limitation on healthcare use and mortality in a large, community cohort of individuals with heart failure (HF)., Design: Prospective cohort study., Setting: Eleven southeastern Minnesota counties., Participants: Individuals (mean age 74, 54% male) with a first-ever HF code (International Classification of Diseases, Ninth Revision code 428 or Tenth Revision code I50) between January 1, 2013 and March 31, 2016 (N=2,692)., Measurements: Eight activities of daily living measured using a survey on a Likert scale (1=without any difficulty, 5=unable to do; median=8). Participants with a score greater than 8 were categorized as having functional limitation. Multimorbidity was defined as having 2 or more noncardiac comorbidities., Results: Twenty-five percent of participants had neither multimorbidity nor functional limitation, 35% had multimorbidity, 9% had functional limitation, and 31% had both. After adjustment, participants with multimorbidity and functional limitation had greater risks of all outcomes (death: hazard ratio (HR)=4.92, 95% confidence interval (CI)=3.03-8.00; emergency department (ED) visit: HR=3.67, 95% CI=2.94-4.59; hospitalization: HR=3.66, 95% CI=2.85-4.70; outpatient visit: HR=1.73, 95% CI=1.52-1.96) than those with neither. Participants with functional limitation alone had greater risks of death (HR=4.84, 95% CI=2.78-8.43), ED visits (HR=2.35, 95% CI=1.75-3.16), and hospitalizations (HR=2.10, 95% CI=1.52-2.88) but not outpatient visits. Those with multimorbidity alone had similar risks of ED visits and hospitalizations as those with functional limitation alone but were more likely to have outpatient visits (HR=1.50, 95% CI=1.34-1.67)., Conclusion: Individuals with both multimorbidity and functional limitation have the highest risk of death and healthcare use. Individuals with only functional limitation have similar rates of hospitalizations and ED visits as those with only multimorbidity, underscoring the need to consider both when managing individuals with HF., (© 2018, Copyright the Authors Journal compilation © 2018, The American Geriatrics Society.)

Background: Perceived social isolation has been shown to have a negative impact on health outcomes, particularly among older adults. However, these relationships have not been fully examined among patients with heart failure., Methods and Results: Residents from 11 southeast Minnesota counties with a first-ever International Classification of Diseases, Ninth Revision ( ICD-9 ) code 428 for heart failure between January 1, 2013, and March 31, 2015 (N=3867), were prospectively surveyed to measure perceived social isolation. A total of 2003 patients returned the survey (response rate, 52%); 1681 patients completed all questions and were retained for analysis. Among these patients (53% men; mean age, 73 years), ≈19% (n=312) had moderate perceived social isolation and 6% (n=108) had high perceived social isolation. After adjustment, patients reporting moderate perceived social isolation did not have an increased risk of death, hospitalizations, or emergency department visits compared with patients reporting low perceived social isolation; however, patients reporting high perceived social isolation had >3.5 times increased risk of death (hazard ratio, 3.74; 95% confidence interval [CI], 1.82-7.70), 68% increased risk of hospitalization (hazard ratio, 1.68; 95% CI, 1.18-2.39), and 57% increased risk of emergency department visits (hazard ratio, 1.57; 95% CI, 1.09-2.27). Compared with patients who self-reported low perceived social isolation, patients reporting moderate perceived social isolation had a 16% increased risk of outpatient visits (rate ratio, 1.16; 95% CI, 1.03-1.31), whereas those reporting high perceived social isolation had a 26% increased risk (rate ratio, 1.26; 95% CI, 1.04-1.53)., Conclusions: In patients with heart failure, greater perceived social isolation is associated with an increased risk of death and healthcare use. Assessing perceived social isolation during the clinical encounter with a brief screening tool may help identify patients with heart failure at greater risk of poor outcomes., (© 2018 The Authors, Mayo Clinic and Olmsted County Public Health Services. Published on behalf of the American Heart Association, Inc., by Wiley.)

Introduction: The goal of this project was to develop an interactive, web-based tool to explore patterns of prevalence and co-occurrence of diseases using data from the expanded Rochester Epidemiology Project (E-REP) medical records-linkage system., Methods: We designed the REP Data Exploration Portal (REP DEP) to include summary information for people who lived in a 27-county region of southern Minnesota and western Wisconsin on January 1, 2014 (n = 694,506; 61% of the entire population). We obtained diagnostic codes of the International Classification of Diseases, 9th edition, from the medical records-linkage system in 2009 through 2013 (5 years) and grouped them into 717 disease categories. For each condition or combination of 2 conditions (dyad), we calculated prevalence by dividing the number of persons with a specified condition (numerator) by the total number of persons in the population (denominator). We calculated observed-to-expected ratios (OERs) to test whether 2 conditions co-occur more frequently than would co-occur as a result of chance alone., Results: We launched the first version of the REP DEP in May 2017. The REP DEP can be accessed at http://rochesterproject.org/portal/. Users can select 2 conditions of interest, and the REP DEP displays the overall prevalence, age-specific prevalence, and sex-specific prevalence for each condition and dyad. Also displayed are OERs overall and by age and sex and maps of county-specific prevalence of each condition and OER., Conclusion: The REP DEP draws upon a medical records-linkage system to provide an innovative, rapid, interactive, free-of-charge method to examine the prevalence and co-occurrence of 717 diseases and conditions in a geographically defined population.

Objectives: To determine how often unnecessary resting echocardiograms that are "not recommended" by clinical practice guidelines are performed in patients with stable chest pain and normal resting electrocardiograms (ECGs)., Background: There are scant data to indicate how often Class III recommendations are ignored in clinical practice., Patients and Methods: We searched electronically all medical records of referral outpatients seen at Mayo Clinic Rochester from January 1, 2010, through December 31, 2013, to identify patients with stable chest pain and known or suspected coronary artery disease who underwent resting echocardiography and had normal resting ECGs and no other indication for echocardiography., Results: Of the 15,529 referral outpatients who were evaluated at Mayo Clinic Rochester with chest pain, 3976 (25.6%) had resting echocardiograms. Eight hundred seventy of these 3976 patients (21.9%) had normal resting ECGs. Six hundred nineteen of these 870 patients (71.1%) had other indications for echocardiography. The remaining 251 patients (6.3% of all echocardiograms and 1.6% of all patients) had normal resting ECGs and no other indication for echocardiography. Two hundred thirty-nine of these 251 patients (95.2%) had normal echocardiograms. Of the 12 abnormal echocardiograms, only 4 led to any change in clinical management. Sixty-one of these 251 echocardiograms (24.3%) were "preordered" before the provider (physicians, nurses, physician assistants) visit., Conclusion: Echocardiograms were performed in 1 in 4 referral outpatients with chest pain seen at Mayo Clinic Rochester. However, only 1 in 16 of these echocardiograms was performed in violation of the class III recommendation in the American College of Cardiology Foundation/American Heart Association guidelines for the management of stable angina. These unnecessary echocardiograms were almost always normal, and had little impact on clinical management. The rate of unnecessary echocardiograms could be decreased by eliminating preordering., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: To study the association between time in therapeutic range (TTR) during warfarin therapy and risk of dementia in a population-based cohort of incident atrial fibrillation (AF)., Patients and Methods: We conducted an observational population-based study of 2800 nondemented patients with incident AF from January 1, 2000, through December 31, 2010. The association of incident dementia with warfarin therapy and TTR was examined using Cox proportional hazards regression models., Results: Mean patient age was 71.2 years; 53% were men (n=1495), and warfarin was prescribed to 50.5% (n=1414) within 90 days of AF diagnosis. Incident dementia diagnosis occurred in 357 patients (12.8%) over a mean ± SD follow-up of 5.0±3.7 years. After adjusting for confounders, warfarin therapy was associated with a reduced incidence of dementia (hazard ratio [HR], 0.80; 95% CI, 0.64-0.99). However, only those in the 2 highest quartiles of TTR were associated with lower risk of dementia. A 10% increase in TTR with a 10% reduction in time spent in the subtherapeutic (HR, 0.71; 95% CI, 0.64-0.79) and supratherapeutic (HR, 0.67; 95% CI, 0.57-0.79) ranges were associated with decreased risk of dementia., Conclusion: In the community, warfarin therapy for AF is associated with a 20% reduction in risk of dementia. Increasing TTR on warfarin is associated with reduced risk of dementia. The risk of dementia was reduced with a reduction in time spent in subtherapeutic and supratherapeutic international normalized ratio range. Effective anticoagulation may prevent cognitive impairment in patients with AF., (Copyright © 2017 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Objective: To examine the impact of health literacy on hospitalizations and death in a population of patients with heart failure (HF)., Patients and Methods: Residents from the 11-county region in southeast Minnesota with a first-ever International Classification of Diseases, Ninth Revision code 428 or Tenth Revision code 150 (n=5121) from January 1, 2013, through December 31, 2015, were identified and prospectively surveyed to measure health literacy using established screening questions. A total of 2647 patients returned the survey (response rate, 52%); 2487 patients with complete health literacy data were retained for analysis. Health literacy, measured as a composite score on three 5-point scales, was categorized as adequate (≥8) or low (<8). Cox proportional hazards regression and Andersen-Gill models were used to examine the association of health literacy with mortality and hospitalization., Results: Of 2487 patients (mean age, 73.5 years; 53.6% male [n=1333]), 10.5% (n= 261) had low health literacy. After mean ± SD follow-up of 15.5±7.2 months, 250 deaths and 1584 hospitalizations occurred. Low health literacy was associated with increased mortality and hospitalizations. After adjusting for age, sex, comorbidity, education, and marital status, the hazard ratios for death and hospitalizations in patients with low health literacy were 1.91 (95% CI, 1.38-2.65; P<.001) and 1.30 (95% CI, 1.02-1.66; P=.03), respectively, compared with patients with adequate health literacy., Conclusion: Low health literacy is associated with increased risks of hospitalization and death in patients with HF. The clinical evaluation of health literacy could help design interventions individualized for patients with low health literacy., (Copyright © 2017 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Background: Recent data suggest that patient activation, or having the knowledge, skills, and confidence to engage and manage one's own health, favorably impacts patient behaviors and health outcomes. However, the role of activation in patients with heart failure is unknown., Objectives: The aims of this study are to measure the level of activation of patients hospitalized with acute decompensated heart failure (ADHF) and to determine whether activation is associated with in-hospital and early postdischarge outcomes., Methods: We prospectively recruited Southeastern Minnesota residents hospitalized at Mayo Clinic hospitals with ADHF from January 2014 to July 2015. Activation was measured using the Patient Activation Measure questionnaire., Results: Among the 302 patients enrolled, the mean age was 77.3 years, 57.3% were men, and 46.8% had preserved ejection fraction. The median (25th-75th percentile) length of stay was 4 (3-7) days. In total, 7 (2.3%) patients died before discharge. Most survivors were discharged to home (73.6%) or skilled nursing facilities (23.7%). The number of patients in each activation level from highest to lowest was 9 (3.0%), 121 (40.1%), 122 (40.4%), and 50 (16.6%). Patients with lower activation were older, were less educated, had lower patient satisfaction, and had worse health literacy. They were more often discharged to skilled nursing facilities and had higher 30-day mortality, although 30-day readmission did not differ by activation., Conclusions: Patients hospitalized with ADHF with lower activation are less satisfied, have worse health literacy, more often require skilled care, and are at increased risk for early postdischarge mortality. Activation can be easily measured and may help clinicians identify high-risk patients.

Objective: To study the temporal distribution and causes of hospitalizations after heart failure (HF) diagnosis., Patients and Methods: Hospitalizations were studied in 1972 Olmsted County, Minnesota, residents with incident HF from January 1, 2000, to December 31, 2011. All hospitalizations were examined for the 2 years following incident HF, and each was categorized as due to HF, other cardiovascular causes, or noncardiovascular causes. Negative binomial regression examined associations between time periods (0-30, 31-182, 183-365, and 366-730 days after diagnosis) and hospitalizations., Results: During the 2 years after diagnosis, 3495 hospitalizations were observed among 1336 of the 1972 patients with HF. The age- and sex-adjusted rates of hospitalizations were highest in the first 30 days after diagnosis (3.33 per person-year vs 1.33, 1.07, and 1.00 per person-year for 31-182 days, 183-365 days, and 366-730 days, respectively). The rates of hospitalizations were similar across sex, presentation of HF (inpatient or outpatient), and type of HF (preserved or reduced ejection fraction). Patients diagnosed as inpatients who had long hospital stays (>5 days) experienced more than a 30% increased risk of rehospitalization within 30 days of dismissal. Importantly, most hospitalizations (2222 of 3495 [63.6%]) were due to noncardiovascular causes, and a minority (440 of 3495 [12.6%]) were due to HF. The rates of noncardiovascular hospitalizations were higher than those for HF or other cardiovascular hospitalizations across all follow-up for all time periods after HF., Conclusion: Patients with HF experience high rates of hospitalizations, particularly within the first 30 days, and mostly for noncardiovascular causes. To reduce hospitalizations in patients with HF, an integrated approach focusing on comorbidities is required., (Copyright © 2016 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Importance: Whether the extent of coronary artery disease (CAD) is associated with the occurrence of heart failure (HF) after myocardial infarction (MI) is not known. Furthermore, whether this association might differ by HF type according to preserved or reduced ejection fraction (EF) has yet to be determined., Objectives: To evaluate in a community cohort of patients with incident (first-ever) MI the association of angiographic CAD with subsequent HF and to examine the prognostic role of CAD according to HF subtypes: HF with reduced EF and HF with preserved EF., Design, Setting, and Participants: A population-based cohort study was conducted in 1922 residents of Olmsted County, Minnesota, with incident MI diagnosed between January 1, 1990, and December 31, 2010, and no prior HF; study participants were followed up through March 31, 2013. The extent of angiographic CAD was determined at baseline and categorized according to the number of major epicardial coronary arteries with 50% or more lumen diameter obstruction., Main Outcomes and Measures: The primary end point was time to incident HF. The primary exposure variable was the extent of CAD as expressed by the number of major coronary arteries with significant obstruction (0-, 1-, 2-, or 3-vessel disease) obtained from coronary angiograms performed no more than 1 day after the MI. Heart failure was ascertained by the Framingham criteria and classified by type according to EF (50% cutoff)., Results: Of the 1922 participants, 1258 (65.4%) were men (mean [SD] age, 64 [13] years). During a mean follow-up period of 6.7 (5.9) years, 588 patients (30.6%) developed HF. With death and recurrent MI modeled as competing risks, the cumulative incidence rates of post-MI HF among patients with 0 or 1, 2, and 3 diseased vessels were 10.7%, 14.6%, and 23.0% at 30 days; and 14.7%, 20.6%, and 29.8% at 5 years, respectively (P < .001 for trend). After adjustment for clinical characteristics in a Cox proportional hazards regression model, the hazard ratios (95% CIs) for HF were 1.25 (0.99-1.59) and 1.75 (1.40-2.20) in patients with 2 and 3 vessels vs 0 or 1 occluded vessel, respectively (P < .001 for trend). The increased risk with a greater number of occluded vessels was independent of the occurrence of a recurrent MI and did not differ appreciably by HF type., Conclusions and Relevance: The extent of angiographic CAD is an indicator of post-MI HF regardless of HF type and independent of recurrent MI. These data underscore the need to further investigate the processes taking place in the transition from myocardial injury to HF.

Background: We previously investigated trends in subclinical coronary artery disease and associated risk factors among autopsied non-elderly adults who died from nonnatural causes. Although grade of atherosclerosis declined from 1981 through 2009, the trend was nonlinear, ending in 1995, concurrent with increasing obesity/diabetes in this population. The previous study used linear regression and examined trends for all 4 major epicardial coronary arteries combined. The present investigation of coronary artery disease trends for the period 1995 through 2012 was prompted by a desire for more detailed examination of more recent coronary artery disease trends in light of reports that the epidemics of obesity and diabetes have slowed and are perhaps ending., Methods: This population-based series of cross-sectional investigations identified all Olmsted County, Minnesota residents aged 16-64 years who died 1995 through 2012 (N = 2931). For decedents with nonnatural manner of death, pathology reports were reviewed for grade of atherosclerosis assigned each major epicardial coronary artery. Using logistic regression, we estimated calendar-year trends in grade (unadjusted and age- and sex-adjusted) for each artery, initially as an ordinal measure (range, 0-4); then, based on evidence of nonproportional odds, as a dichotomous variable (any atherosclerosis, yes/no) and as an ordinal measure for persons with atherosclerosis (range, 1-4)., Results: Of 474 nonnatural deaths, 453 (96%) were autopsied; 426 (90%) had coronary stenosis graded. In the ordinal-logistic model for trends in coronary artery disease grade (range, 0-4), the proportional odds assumption did not hold. In subsequent analysis as a dichotomous outcome (grades 0 vs 1-4), each artery exhibited a significant temporal decline in the proportion with any atherosclerosis. Conversely, for subjects with coronary artery disease grade 1-4, age- and sex-adjusted ordinal regression revealed no change over time in 2 arteries and statistically significant temporal increases in severity in 2 arteries., Conclusions: Findings suggest that efforts to prevent coronary artery disease onset have been relatively successful. However, statistically significant increases in the grade of atherosclerosis in 2 arteries among persons with coronary artery disease may be indicative of a major public health challenge., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Contemporary data are lacking on the prognostic importance of heart failure (HF) after myocardial infarction (MI). We evaluated the prognostic impact of HF post MI according to preserved/reduced ejection fraction and the timing of its occurrence., Methods and Results: All Olmsted County, Minnesota, residents (n=2596) with incident MI diagnosed in 1990 to 2010 and no prior HF were followed through March 2013. Cox models were used to examine (1) the hazard ratios for death associated with HF type and timing and (2) secular trends in survival by HF status. During a mean follow-up of 7.6 years, there were 1116 deaths, 634 in the 902 patients who developed HF (70%) and 482 in the 1694 patients who did not develop HF (28%). After adjustment for age and sex, HF as a time-dependent variable was strongly associated with mortality (hazard ratio =3.31, 95% confidence interval: 2.93-3.75), particularly from cardiovascular causes (hazard ratio =4.20, 95% confidence interval: 3.50-5.03). Further adjustment for MI severity and comorbidity, acute treatment, and recurrent MI moderately attenuated these associations (hazard ratio =2.49 and 2.94 for all-cause and cardiovascular mortality, respectively). Mortality did not differ by ejection fraction, but was higher for delayed- versus early-onset HF (P for heterogeneity =0.002). The age- and sex-adjusted 5-year survival estimates in 2001 to 2010 versus 1990 to 2000 were 82% and 81% among HF-free and 61% and 54% among HF patients, respectively (P for heterogeneity of trends =0.05)., Conclusions: HF markedly increases the risk of death after MI. This excess risk is similar regardless of ejection fraction but greater for delayed- versus early-onset HF. Mortality after MI declined over time, primarily as a result of improved HF survival., (© 2015 American Heart Association, Inc.)

Background: The authors sought to estimate incremental economic impact of atrial fibrillation (AF) and the timing of its onset in myocardial infarction (MI) patients., Hypothesis: Concurrent AF and its timing are associated with higher costs in MI patients., Methods: This retrospective cohort study included incident MI patients from Olmsted County, Minnesota, treated between November 1, 2002, and December 31, 2010. We compared inflation-adjusted standardized costs accumulated between incident MI and end of follow-up among 3 groups by AF status and timing: no AF, new-onset AF (within 30 days after index MI), and prior AF. Multivariate adjustment of median costs accounted for right-censoring in costs., Results: The final study cohort had 1389 patients, with 989 in no AF, 163 in new-onset AF, and 237 in prior AF categories. Median follow-up times were 3.98, 3.23, and 2.55 years, respectively. Mean age at index was 67 years, with significantly younger patients in the no AF group (64 years vs 76 and 77 years, respectively; P < 0.001). New-onset and prior AF patients had more comorbid conditions (hypertension, heart failure, and chronic obstructive pulmonary disease). After accounting for differences in baseline characteristics, we found adjusted median (95% confidence interval) costs of $73 000 ($69 000-$76 000) for no AF; $85 000 ($81 000-$89 000) for new-onset AF; and $97 000 ($94 000-$100 000) for prior AF. Inpatient costs composed the largest share of total median costs (no AF, 82%; new-onset AF, 84%; prior AF, 83%)., Conclusions: Atrial fibrillation frequently coexists with MI and imposes incremental costs, mainly attributable to inpatient care. Timing of AF matters, as prior AF was found to be associated with higher costs than new-onset AF., (© 2015 Wiley Periodicals, Inc.)

Importance: Heart failure (HF) is commonly referred to as an epidemic, posing major clinical and public health challenges. Yet, contemporary data on its magnitude and implications are scarce., Objective: To evaluate recent trends in HF incidence and outcomes overall and by preserved ejection fraction (HFpEF) or reduced ejection fraction (HFrEF)., Design, Setting, and Participants: Incidence rates of HF in Olmsted County, Minnesota (population, approximately 144,248), between January 1, 2000, and December 31, 2010, were assessed., Main Outcomes and Measures: Patients identified with incident HF (n = 2762) (mean age, 76.4 years; 43.1% male) were followed up for all-cause and cause-specific hospitalizations (through December 2012) and death (through March 2014)., Results: The age- and sex-adjusted incidence of HF declined substantially from 315.8 per 100,000 in 2000 to 219.3 per 100,000 in 2010 (annual percentage change, -4.6), equating to a rate reduction of 37.5% (95% CI, -29.6% to -44.4%) over the last decade. The incidence declined for both HF types but was greater (interaction P = .08) for HFrEF (-45.1%; 95% CI, -33.0% to -55.0%) than for HFpEF (-27.9%; 95% CI, -12.9% to -40.3%). Mortality was high (24.4% for age 60 years and 54.4% for age 80 years at 5 years of follow-up), frequently ascribed to noncardiovascular causes (54.3%), and did not decline over time. The risk of cardiovascular death was lower for HFpEF than for HFrEF (multivariable-adjusted hazard ratio, 0.79; 95% CI, 0.67-0.93), whereas the risk of noncardiovascular death was similar (1.07; 95% CI, 0.89-1.29). Hospitalizations were common (mean, 1.34; 95% CI, 1.25-1.44 per person-year), particularly among men, and did not differ between HFpEF and HFrEF. Most hospitalizations (63.0%) were due to noncardiovascular causes. Hospitalization rates for cardiovascular causes did not change over time, whereas those for noncardiovascular causes increased., Conclusions and Relevance: Over the last decade, the incidence of HF declined substantially, particularly for HFrEF, contrasting with no apparent change in mortality. Noncardiovascular conditions have an increasing role in hospitalizations and remain the most frequent cause of death. These results underscore the need to augment disease-centric management approaches with holistic strategies to reduce the population burden of HF.

Background: Our previous study of nonelderly adult decedents with nonnatural (accident, suicide, or homicide) cause of death (96% autopsy rate) between 1981 and 2004 revealed that the decline in subclinical coronary artery disease (CAD) ended in the mid-1990s. The present study investigated the contributions of trends in obesity and diabetes mellitus to patterns of subclinical CAD and explored whether the end of the decline in CAD persisted., Methods and Results: We reviewed provider-linked medical records for all residents of Olmsted County, Minnesota, who died from nonnatural causes within the age range of 16 to 64 years between 1981 and 2009 and who had CAD graded at autopsy. We estimated trends in CAD risk factors including age, sex, systolic blood pressure, diabetes (qualifying fasting glucose or medication), body mass index, smoking, and diagnosed hyperlipidemia. Using multiple regression, we tested for significant associations between trends in CAD risk factors and CAD grade and assessed the contribution of trends in diabetes and obesity to CAD trends. The 545 autopsied decedents with recorded CAD grade exhibited significant declines between 1981 and 2009 in systolic blood pressure and smoking and significant increases in blood pressure medication, diabetes, and body mass index ≥30 kg/m(2). An overall decline in CAD grade between 1981 and 2009 was nonlinear and ended in 1994. Trends in obesity and diabetes contributed to the end of CAD decline., Conclusions: Despite continued reductions in smoking and blood pressure values, the previously observed end to the decline in subclinical CAD among nonelderly adult decedents was apparent through 2009, corresponding with increasing obesity and diabetes in that population., (© 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Atrial fibrillation (AF) frequently occurs with acute coronary syndromes (ACS) and adds complexity to the selection of an appropriate antithrombotic strategy. We determined whether associations of antithrombotic treatment with bleeding, stroke, and death differ between patients with ACS with and without AF. Residents of Olmsted County, Minnesota, hospitalized with incident ACS during 2005 to 2010 were classified according to the presence or absence of AF either before or during the index ACS hospitalization. Antithrombotic strategy at discharge was categorized as double/triple agents versus no/single agent. Patients were followed through 2012, and propensity scores were used to estimate associations of treatment with bleeding, ischemic stroke, and mortality. Of 1,159 patients with incident ACS, 252 (21.7%) had concomitant AF (ACS + AF). Over a median follow-up of 4.3 years, 312 bleeds, 67 ischemic strokes, and 268 deaths occurred. The overall risks of bleeding, stroke, and death were similar between treatment strategies. Although limited by the small number of events, a suggestion of a lower risk of ischemic stroke for patients with ACS + AF on double/triple therapy was observed; the hazard ratios for stroke with double/triple versus no/single therapy were 0.30 (0.07 to 1.26) and 1.10 (0.52 to 2.33) in those with and without AF, respectively (p value for interaction = 0.10). In conclusion, the choice of antithrombotic strategy is not associated with the risk of ischemic stroke, bleeding, or death in patients with ACS overall. Patients with ACS + AF on double/triple therapy may experience reduced risks of stroke, although future studies are needed to confirm this finding., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Contemporary data on temporal trends in incidence and survival after atrial fibrillation are scarce., Methods: Residents of Olmsted County, Minn., with a first-ever atrial fibrillation or atrial flutter event between 2000 and 2010 were identified. Age- and sex-adjusted incidence rates were standardized to the 2010 US population, and the relative risk of atrial fibrillation in 2010 versus 2000 was calculated using Poisson regression. Standardized mortality ratios of observed versus expected survival were calculated, and time trends in survival were examined using Cox regression., Results: We identified 3344 patients with incident atrial fibrillation/atrial flutter events (52% were male, mean age 72.6 years, 95.7% were white). Incidence did not change over time (age- and sex-adjusted rate ratio, 1.01; 95% confidence interval [CI], 0.91-1.13 for 2010 vs 2000). Within the first 90 days, the risk of all-cause mortality was greatly elevated compared with individuals of a similar age and sex distribution in the general population (standardized mortality ratios 19.4 [95% CI, 17.3-21.7] and 4.2 [95% CI, 3.5-5.0] for the first 30 days and 31 to 90 days after diagnosis, respectively). Survival within the first 90 days did not improve over the study period (adjusted hazard ratio, 0.96; 95% CI, 0.71-1.32 for 2010 vs 2000); likewise, no difference in mortality between 2010 and 2000 was observed among 90-day survivors (hazard ratio, 1.05; 95% CI, 0.85-1.31)., Conclusions: In the community, atrial fibrillation incidence and survival have remained constant over the last decade. A dramatic and persistent excess risk of death was observed in the 90 days after atrial fibrillation diagnosis, underscoring the importance of early risk stratification., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: To study the incidence of de novo multimorbidity across all ages in a geographically defined population with an emphasis on sex and ethnic differences., Design: Historical cohort study., Setting: All persons residing in Olmsted County, Minnesota, USA on 1 January 2000 who had granted permission for their records to be used for research (n=123 716)., Participants: We used the Rochester Epidemiology Project medical records-linkage system to identify all of the county residents. We identified and removed from the cohort all persons who had developed multimorbidity before 1 January 2000 (baseline date), and we followed the cohort over 14 years (1 January 2000 through 31 December 2013)., Main Outcome Measures: Incident multimorbidity was defined as the development of the second of 2 conditions (dyads) from among the 20 chronic conditions selected by the US Department of Health and Human Services. We also studied the incidence of the third of 3 conditions (triads) from among the 20 chronic conditions., Results: The incidence of multimorbidity increased steeply with older age; however, the number of people with incident multimorbidity was substantially greater in people younger than 65 years compared to people age 65 years or older (28 378 vs 6214). The overall risk was similar in men and women; however, the combinations of conditions (dyads and triads) differed extensively by age and by sex. Compared to Whites, the incidence of multimorbidity was higher in Blacks and lower in Asians., Conclusions: The risk of developing de novo multimorbidity increases steeply with older age, varies by ethnicity and is similar in men and women overall. However, as expected, the combinations of conditions vary extensively by age and sex. These data represent an important first step toward identifying the causes and the consequences of multimorbidity., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: Contemporary data on the epidemiology of myocardial infarction in the population are limited and derived primarily from cohorts of hospitalized myocardial infarction patients. We assessed temporal trends in incident and recurrent myocardial infarction, with further partitioning of the rates into prehospital deaths and hospitalized events, in a geographically defined community., Methods: All myocardial infarction events recorded among Olmsted County, Minnesota residents aged 25 years and older from 1995-2012, including prehospital deaths, were classified into incident and recurrent. Standardized rates were calculated and temporal trends compared., Results: Altogether, 5258 myocardial infarctions occurred, including 1448 (27.5%) recurrences; 430 (8.2%) prehospital deaths were recorded. Among hospitalized events, recurrent myocardial infarction was associated with greater mortality risk than incident myocardial infarction (age-, sex-, and year-adjusted hazard ratio, 1.49; 95% confidence interval, 1.37-1.61). Although the overall rate of myocardial infarction declined over time (average annual percent change, -3.3), the magnitude of the decline varied widely. Incident hospitalized myocardial infarction rate fell 2.7%/y, compared with decreases of 1.5%/y in recurrent hospitalized myocardial infarction, 14.1%/y in prehospital fatal incident myocardial infarction, and 12.3%/y in prehospital fatal recurrent myocardial infarction (all P for diverging trends < .05). These trends resulted in an increasing proportion of recurrences among hospitalized myocardial infarctions (25.3% in 1995-2000, 26.8% in 2001-2006, and 29.0% in 2007-2012, Ptrend = .02)., Conclusions: Over the past 18 years, a heterogeneous decline in myocardial infarction rates occurred in Olmsted County, resulting in transitions from incident to recurrent events and from prehospital deaths to hospitalized myocardial infarctions. Recurrent myocardial infarction confers a worse prognosis, thereby stressing the need to optimize prevention strategies in the population., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: To investigate the incidence of atrial fibrillation (AF) among patients with rheumatoid arthritis (RA) compared to the general population., Methods: A population-based inception cohort of Olmsted County, Minnesota, residents with incident RA in 1980-2007 and a cohort of non-RA subjects from the same population base were assembled and followed until 12/31/2008. The occurrence of AF was ascertained by medical record review., Results: The study included 813 patients with RA and 813 non-RA subjects (mean age 55.9 (SD:15.7) years, 68% women in both cohorts). The prevalence of AF was similar in the RA and non-RA cohorts at RA incidence/index date (4% versus 3%; P = 0.51). The cumulative incidence of AF during follow-up was higher among patients with RA compared to non-RA subjects (18.3% versus 16.3% at 20 years; P = 0.048). This difference persisted after adjustment for age, sex, calendar year, smoking, and hypertension (hazard ratio: 1.46; 95% CI: 1.07, 2.00). There was no evidence of a differential impact of AF on mortality in patients with RA compared to non-RA subjects (hazard ratio 2.5 versus 2.8; interaction P = 0.31)., Conclusion: The incidence of AF is increased in patients with RA, even after adjustment for AF risk factors. AF related mortality risk did not differ between patients with and without RA.

Background: Comorbidities are a major concern in heart failure, leading to adverse outcomes, increased health care utilization, and excess mortality. Nevertheless, the epidemiology of comorbid conditions and differences in their occurrence by type of heart failure and sex are not well documented., Methods: The prevalence of 16 chronic conditions defined by the US Department of Health and Human Services was obtained among 1382 patients from Olmsted County, Minn. diagnosed with first-ever heart failure between 2000 and 2010. Heat maps displayed the pairwise prevalences of the comorbidities and the observed-to-expected ratios for occurrence of morbidity pairs by type of heart failure (preserved or reduced ejection fraction) and sex., Results: Most heart failure patients had 2 or more additional chronic conditions (86%); the most prevalent were hypertension, hyperlipidemia, and arrhythmias. The co-occurrence of other cardiovascular diseases was common, with higher prevalences of co-occurring cardiovascular diseases in men compared with women. Patients with preserved ejection fraction had one additional condition compared with those with reduced ejection fraction (mean 4.5 vs 3.7). The patterns of co-occurring conditions were similar between preserved and reduced ejection fraction; however, differences in the ratios of observed-to-expected co-occurrence were apparent by type of heart failure and sex. In addition, some psychological and neurological conditions co-occurred more frequently than expected., Conclusion: Multimorbidity is common in heart failure, and differences in co-occurrence of conditions exist by type of heart failure and sex, highlighting the need for a better understanding of the clinical consequences of multiple chronic conditions in heart failure patients., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: We assessed changes in adherence to screening mammography recommendations with the introduction of the new U.S. Preventive Services Task Force (USPSTF) recommendations in 2009., Methods: Using the Rochester Epidemiology Project data linkage system, we examined mammography screening from 2004 to 2013 in 31,377 women 40years of age and older residing in Olmsted County, MN before and after the 2009 change in recommendations. Chi-square was used to compare screening rates before and after changes in recommendations overall, by age group, and by baseline adherence., Results: Among women 40 years and older, declines in screening were observed: 69% of the population was adherent in 2004-2005, 61% in 2006-2009 and 53% in 2010-2013. Absolute decreases in screening were observed from pre- to post-change for those ages 40-49 (4%), 50-74 (9%), and those 75+ (19%, all p<0.0001). Relative declines in screening rates were observed among women aged 70-74 years who were non-adherent at baseline and among women who were adherent at baseline, overall, and in each age group (all p<.001)., Conclusions: Declines in screening, both absolute and relative, were most pronounced among women who were adherent at baseline. Research is needed to assess factors that influence screening in the context of evolving recommendations., (Copyright © 2014. Published by Elsevier Inc.)

Background: To assess whether the individual housing-based socioeconomic status (SES) measure termed HOUSES was associated with post-myocardial infarction (MI) mortality., Methods: The study was designed as a population-based cohort study, which compared post-MI mortality among Olmsted County, Minnesota, USA, residents with different SES as measured by HOUSES using Cox proportional hazards models. Subjects' addresses at index date of MI were geocoded to real property data to formulate HOUSES (a z-score for housing value, square footage, and numbers of bedrooms and bathrooms). Educational levels were used as a comparison for the HOUSES index., Results: 637 of the 696 eligible patients with MI (92%) were successfully geocoded to real property data. Post-MI survival rates were 60% (50-72), 78% (71-85), 72% (60-87), and 87% (81-93) at 2 years for patients in the first (the lowest SES), second, third, and fourth quartiles of HOUSES, respectively (p < 0.001). HOUSES was associated with post-MI all-cause mortality, controlling for all variables except age and comorbidity (p = 0.036) but was not significant after adjusting for age and comorbidity (p = 0.24)., Conclusions: Although HOUSES is associated with post-MI mortality, the differential mortality rates by HOUSES were primarily accounted for by age and comorbid conditions. HOUSES may be useful for health disparities research concerning cardiovascular outcomes, especially in overcoming the paucity of conventional SES measures in commonly used datasets.

Objective: To describe the prevalence of multimorbidity involving 20 selected chronic conditions in a geographically defined US population, emphasizing age, sex, and racial/ethnic differences., Patients and Methods: Using the Rochester Epidemiology Project records linkage system, we identified all residents of Olmsted County, Minnesota, on April 1, 2010, and electronically extracted the International Classification of Diseases, Ninth Revision codes associated with all health care visits made between April 1, 2005, and March 31, 2010 (5-year capture frame). Using these codes, we defined the 20 common chronic conditions recommended by the US Department of Health and Human Services. We counted only persons who received at least 2 codes for a given condition separated by more than 30 days, and we calculated the age-, sex-, and race/ethnicity-specific prevalence of multimorbidity., Results: Of the 138,858 study participants, 52.4% were women (n=72,732) and 38.9% had 1 or more conditions (n=54,012), 22.6% had 2 or more conditions (n=31,444), and 4.9% had 5 or more conditions (n=6853). The prevalence of multimorbidity (≥2 conditions) increased steeply with older age and reached 77.3% at 65 years and older. However, the absolute number of people affected by multimorbidity was higher in those younger than 65 years. Although the prevalence of multimorbidity was similar in men and women overall, the most common dyads and triads of conditions varied by sex. Compared with white persons, the prevalence of multimorbidity was slightly higher in black persons and slightly lower in Asian persons., Conclusion: Multimorbidity is common in the general population; it increases steeply with older age, has different patterns in men and women, and varies by race/ethnicity., (Copyright © 2014 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Introduction: Because the association of myocardial infarction (MI) and venous thromboembolism (VTE) is uncertain, we tested MI as a VTE risk factor and VTE as a predictor of MI., Materials and Methods: Using Rochester Epidemiology Project resources, we identified all Olmsted County, MN residents with objectively-diagnosed incident VTE over the 13-year period, 1988-2000 (n=1311), one to two resident controls per VTE case (n=1511), and all residents with incident MI over the 31-year period, 1979-2010. For VTE cases and controls, we reviewed their complete medical records in the community for VTE and MI risk factors. Using conditional logistic regression we tested MI as a potential VTE risk factor, both unadjusted and after adjusting for VTE risk factors. We also followed VTE cases and controls without prior MI forward in time for incident MI through 12/31/2010, and using Cox proportional hazards modeling, tested VTE as a predictor of MI, both unadjusted and after adjusting for MI risk factors., Results: The number (%) of MI prior to VTE among cases and controls were 75 (5.7) and 51 (3.4), respectively, and the number (%) of MI after VTE among cases and controls were 58 (4.4) and 77 (5.1), respectively. In univariate analyses, MI was significantly associated with VTE but not after adjusting for VTE risk factors. In both univariate and multivariate analyses, VTE (overall or idiopathic) was not a predictor of MI., Conclusions: MI is not an independent risk factor for VTE, and VTE is not a predictor of MI., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: Participation in cardiac rehabilitation has been shown to decrease mortality after acute myocardial infarction, but its impact on readmissions requires examination., Methods: We conducted a population-based surveillance study of residents discharged from the hospital after their first-ever myocardial infarction in Olmsted County, Minnesota, from January 1, 1987, to September 30, 2010. Patients were followed up through December 31, 2010. Participation in cardiac rehabilitation after myocardial infarction was determined using billing data. We used a landmark analysis approach (cardiac rehabilitation participant vs not determined by attendance in at least 1 session of cardiac rehabilitation at 90 days post-myocardial infarction discharge) to compare readmission and mortality risk between cardiac rehabilitation participants and nonparticipants accounting for propensity to participate using inverse probability treatment weighting., Results: Of 2991 patients with incident myocardial infarction, 1569 (52.5%) participated in cardiac rehabilitation after hospital discharge. The cardiac rehabilitation participation rate did not change during the study period, but increased in the elderly and decreased in men and younger patients. After adjustment, cardiac rehabilitation participants had lower all-cause readmission (hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.65-0.87; P < .001), cardiovascular readmission (HR, 0.80; 95% CI, 0.65-0.99; P = .037), noncardiovascular readmission (HR, 0.72; 95% CI, 0.61-0.85; P < .001), and mortality (HR, 0.58; 95% CI, 0.49-0.68; P < .001) risk., Conclusions: Cardiac rehabilitation participation is associated with a markedly reduced risk of readmission and death after incident myocardial infarction. Improving cardiac rehabilitation participation rates may have a large impact on post-myocardial infarction healthcare resource use and outcomes., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The full-service US hospital has been described organizationally as a "solution shop," in which medical problems are assumed to be unstructured and to require expert physicians to determine each course of care. If universally applied, this model contributes to unwarranted variation in care, which leads to lower quality and higher costs. We purposely disrupted the adult cardiac surgical practice that we led at Mayo Clinic, in Rochester, Minnesota, by creating a "focused factory" model (characterized by a uniform approach to delivering a limited set of high-quality products) within the practice's solution shop. Key elements of implementing the new model were mapping the care process, segmenting the patient population, using information technology to communicate clearly defined expectations, and empowering nonphysician providers at the bedside. Using a set of criteria, we determined that the focused-factory model was appropriate for 67 percent of cardiac surgical patients. We found that implementation of the model reduced resource use, length-of-stay, and cost. Variation was markedly reduced, and outcomes were improved. Assigning patients to different care models increases care value and the predictability of care process, outcomes, and costs while preserving (in a lesser clinical footprint) the strengths of the solution shop. We conclude that creating a focused-factory model within a solution shop, by applying industrial engineering principles and health information technology tools and changing the model of work, is very effective in both improving quality and reducing costs.

Background: Little is known about the resuscitation preferences of patients with heart failure, how they may change over the course of the disease, and their association with mortality., Methods and Results: We enrolled consecutive Southeastern Minnesota residents with heart failure from October 2007 through September 2011 into a longitudinal study. Information on resuscitation preferences (Full Code or do-not-resuscitate [DNR]) was obtained from medical records through April 1, 2013. Of 608 patients enrolled, 237 died during follow-up. At enrollment, most patients (73.4%) were Full Code, whereas at death, most (78.5%) were DNR. The independent predictors of DNR status at enrollment were advanced age, chronic obstructive pulmonary disease, previous malignancy, and decreased mobility. Patients who were DNR were at increased risk of death (unadjusted hazard ratio, 2.03; 95% confidence interval, 1.48-2.73; P<0.001), but this risk did not persist after adjusting for age, comorbidity, and self-perceived general health (hazard ratio, 0.97; 95% confidence interval, 0.74-1.30; P=0.83). Of 481 patients who were Full Code during follow-up, 22 (4.6%) received cardiopulmonary resuscitation for an in-hospital cardiac arrest. Eight patients survived to hospital discharge; only 2 (9.1% of those receiving cardiopulmonary resuscitation) made a complete recovery and returned home. The median time from a final decision to be DNR until death was only 37 (7,70) days., Conclusions: The resuscitation preferences of patients with heart failure seem to be driven by the decline in clinical status that often accompanies advanced age and multimorbidity. Furthermore, these data suggest that electing DNR status does not independently affect a patient's risk of death., Competing Interests: Disclosures. None., (© 2014 American Heart Association, Inc.)

Background: Frailty is recognized as a major prognostic indicator in heart failure. There has been interest in understanding whether pre-operative frailty is associated with worse outcomes after implantation of a left ventricular assist device (LVAD) as destination therapy., Methods: Patients undergoing LVAD implantation as destination therapy at the Mayo Clinic, Rochester, Minnesota, from February 2007 to June 2012, were included in this study. Frailty was assessed using the deficit index (31 impairments, disabilities and comorbidities) and defined as the proportion of deficits present. We divided patients based on tertiles of the deficit index (>0.32 = frail, 0.23 to 0.32 = intermediate frail, <0.23 = not frail). Cox proportional hazard regression models were used to examine the association between frailty and death. Patients were censored at death or last follow-up through October 2013., Results: Among 99 patients (mean age 65 years, 18% female, 55% with ischemic heart failure), the deficit index ranged from 0.10 to 0.65 (mean 0.29). After a mean follow-up of 1.9 ± 1.6 years, 79% of the patients had been rehospitalized (range 0 to 17 hospitalizations, median 1 per person) and 45% had died. Compared with those who were not frail, patients who were intermediate frail (adjusted HR 1.70, 95% CI 0.71 to 4.31) and frail (HR 3.08, 95% CI 1.40 to 7.48) were at increased risk for death (p for trend = 0.004). The mean (SD) number of days alive out of hospital the first year after LVAD was 293 (107) for not frail, 266 (134) for intermediate frail and 250 (132) for frail patients., Conclusions: Frailty before destination LVAD implantation is associated with increased risk of death and may represent a significant patient selection consideration., (Copyright © 2014 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Frailty, an important prognostic indicator in heart failure (HF), may be defined as a biological phenotype or an accumulation of deficits. Each method has strengths and limitations, but their utility has never been evaluated in the same community HF cohort., Methods: Southeastern Minnesota residents with HF were recruited from 2007 to 2011. Frailty according to the biological phenotype was defined as 3 or more of: weak grip strength, physical exhaustion, slowness, low activity and unintentional weight loss >10 lb in 1 year. Intermediate frailty was defined as 1 to 2. The deficit index was defined as the proportion of deficits present out of 32 deficits., Results: Among 223 patients (mean age 71 ± 14, 61% male), 21% were frail and 48% intermediate frail according to the biological phenotype. The deficit index ranged from 0.02-0.75, with a mean (SD) of 0.25 (0.13). Over a mean follow-up of 2.4 years, 63 patients died. After adjustment for age, sex and ejection fraction, patients categorized as frail by the biological phenotype had a 2-fold increased risk of death compared to those with no frailty, whereas a 0.1 unit increase in the deficit index was associated with a 44% increased risk of death. Both measures predicted death equally (C-statistics: 0.687 for biological phenotype and 0.700 for deficit index)., Conclusion: The deficit index and the biological phenotype equally predict mortality. As the biological phenotype is not routinely assessed clinically, the deficit index, which can be ascertained from medical records, is a feasible alternative to ascertain frailty., (© 2013.)

Objective: To determine whether the impact of aging on cardiovascular disease (CVD) risk in patients with rheumatoid arthritis (RA) differs from that in the general population (as estimated by the Framingham Risk Score [FRS])., Methods: A population-based inception cohort of Olmsted County, Minnesota residents ages≥30 years who fulfilled the American College of Rheumatology 1987 criteria for RA in 1988-2008 was assembled and followed up until death, migration, or July 1, 2012. Data on CVD events were collected by medical records review. The 10-year FRS for CVD was calculated. Cox models adjusted for FRS were used to examine the influence of age on CVD risk., Results: The study included 563 patients with RA without prior CVD (mean age 55 years, 72% women, and 69% seropositive [i.e., rheumatoid factor and/or anti-citrullinated protein antibody positive]). During a mean followup of 8.2 years, 98 patients developed CVD (74 seropositive and 24 seronegative), but the FRS predicted only 59.7 events (35.4 seropositive and 24.3 seronegative). The gap between observed and predicted CVD risk increased exponentially across age, and the effect of age on CVD risk in seropositive RA was nearly double its effect in the general population, with additional log(age) coefficients of 2.91 for women (P=0.002) and 2.06 for men (P=0.027)., Conclusion: Our findings indicate that age exerts an exponentially increasing effect on CVD risk in seropositive RA, but no increased effect among seronegative patients. The causes of accelerated aging in patients with seropositive RA deserve further investigation., (Copyright © 2013 by the American College of Rheumatology.)

Background: Atrial fibrillation (AF) often complicates myocardial infarction (MI). While AF adversely impacts survival in MI patients, the impact of AF on health care utilization has not been studied., Methods: The risk of hospitalizations, emergency department (ED) visits, and outpatient visits associated with prior, new-onset (<30 days post-MI), and late-onset (≥30 days post-MI) AF was assessed among incident MI patients from the Olmsted County, Minnesota, community., Results: Of 1,502 MI patients, 237 had prior AF, 163 developed new-onset AF, 113 developed late-onset AF, and 989 had no AF. Over a mean follow-up of 3.9 years, 3,661 hospitalizations, 5,559 ED visits, and 80,240 outpatient visits occurred. After adjustment, compared with patients without AF, those with prior and new-onset AF exhibited a 1.6-fold and 1.3-fold increased risk of hospitalization, respectively. In contrast, late-onset AF carried a 2.2-fold increased risk of hospitalization. The hazard ratios were 1.4, 1.2, and 1.8 for ED visits and 1.4, 1.2, and 1.7 for outpatient visits for prior, new-onset, and late-onset AF. Additional adjustment for time-dependent recurrent MI and heart failure attenuated the results slightly for hospitalizations and ED visits; however, patients with late-onset AF still exhibited a >50% increased risk for both utilization measures., Conclusions: In MI patients, the risk of hospitalizations, ED visits, and outpatient visits differed by the timing of AF onset, with the greatest risk conferred by late-onset AF. Atrial fibrillation imparts an adverse prognosis after MI, underscoring the importance of its management in MI patients., (© 2013.)

Objectives: This study sought to evaluate the risk of cancer in patients with heart failure (HF) compared with community controls and to determine the impact of cancer post-HF on outcomes., Background: HF is associated with excess morbidity and mortality. Noncardiac causes of adverse outcomes in HF are increasingly recognized, but not fully characterized., Methods: In a case-control study, we compared the history of cancer among community subjects newly diagnosed with HF from 1979 to 2002 to age-, sex-, and date-matched community controls without HF (961 pairs). Individuals without cancer at the index date (596 pairs) were followed for cancer in a cohort design, and the survival of HF patients who developed cancer was assessed., Results: Before the index date, 22% of HF cases and 23% of controls had a history of cancer (odds ratio [OR]: 0.94; 95% confidence interval [CI]: 0.75 to 1.17). During 9,203 person-years of follow-up (7.7 ± 6.4 years), 244 new cancer cases were identified; HF patients had a 68% higher risk of developing cancer (hazard ratio [HR]: 1.68; 95% CI: 1.13 to 2.50) adjusted for body mass index, smoking, and comorbidities. The HRs were similar for men and women, with a trend toward a stronger association among subjects ≤75 years of age (p = 0.22) and during the most recent time period (p = 0.075). Among HF cases, incident cancer increased the risk of death (HR: 1.56; 95% CI: 1.22 to 1.99) adjusted for age, sex, index year, and comorbidities., Conclusions: HF patients are at increased risk of cancer, which appears to have increased over time. Cancer increases mortality in HF, underscoring the importance of noncardiac morbidity and of cancer surveillance in the management of HF patients., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate the risk profiles, treatment, and outcomes of patients with rheumatoid arthritis (RA) with myocardial infarction (MI) and matched MI patients without RA., Methods: We used a population-based cohort of Olmsted County, Minnesota, residents with MI from the period 1979-2009. We identified 77 patients who fulfilled the American College of Rheumatology 1987 criteria for RA and 154 MI patients without RA matched for age, sex, and calendar year. Data collection from medical records included RA and MI characteristics, antirheumatic and cardioprotective medications, reperfusion therapy, and outcomes (mortality, heart failure, and recurrent ischemia)., Results: The mean age at MI was 72.4 years and 55% of patients were female in both cohorts. Cardiovascular risk factor profiles, MI characteristics, and treatment with reperfusion therapy or cardioprotective medications were similar in MI patients with and those without RA. Patients with RA experienced poorer longterm outcomes compared to patients without RA--for mortality: hazard ratio (HR) 1.47; 95% CI 1.04, 2.08; and for recurrent ischemia: HR 1.51; 95% CI 1.04, 2.18., Conclusion: MI patients with RA received similar treatment with reperfusion therapy and cardioprotective medications and had similar short-term outcomes compared to patients without RA. Patients with RA had poorer longterm outcomes. Despite similar treatment, MI patients with RA had worse longterm outcomes than MI patients without RA.