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Objectives: This study aimed to define the prognosis for patients with left bundle branch block (LBBB) and a mildly to moderately reduced left ventricular ejection fraction (LVEF) (36% to 50%) as well as to clarify whether LBBB remained a negative prognostic marker in this group., Background: LBBB is associated with worse outcomes in patients with heart failure in the setting of severely reduced LVEF. The level of morbidity and mortality associated with LBBB in the setting of a mildly to moderately reduced LVEF (36% to 50%) has not been clearly characterized. This knowledge is important to clarify the potential benefit of cardiac resynchronization therapy in this group., Methods: All patients identified as having an LBBB from 1994 to 2014 were included in the study if they had a baseline echocardiogram within 1 year and an LVEF between 36% and 50%. A control group without intraventricular conduction abnormality matched on age, sex, baseline LVEF, and date of echocardiogram was created. Outcomes were compared between the 2 groups., Results: Of 1,436 patients meeting inclusion criteria, 54% were male. Mean age was 67 ± 13 years, and mean LVEF at baseline was 44 ± 4%. There was no difference in baseline heart failure diagnosis between groups. There were significantly higher rates of baseline coronary artery disease in the control group and higher rates of aortic stenosis in the LBBB group. LBBB was associated with significantly worse mortality (hazard ratio [HR]: 1.17; 95% confidence interval [CI]: 1.00 to 1.36), an LVEF drop to 35% or less (HR: 1.34; 95% CI: 1.09 to 1.63), and the need for an implantable cardioverter-defibrillator (HR: 1.50; 95% CI: 1.10 to 2.10). Mortality remained significantly higher in the LBBB group when controlled for heart failure, coronary artery disease, and aortic stenosis (p = 0.04)., Conclusions: Patients with a mildly to moderately reduced LVEF and LBBB have poor clinical outcomes that are significantly worse than those for patients without conduction system disease. This group may obtain benefit from cardiac resynchronization therapy and deserves to be studied in prospective trials., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Limited information is available regarding primary care clinicians' response to pharmacogenomic clinical decision support (PGx-CDS) alerts integrated in the electronic health record., Methods: In February 2015, 159 clinicians in the Mayo Clinic primary care practice were sent e-mail surveys to understand their perspectives on the implementation and use of pharmacogenomic testing in their clinical practice. Surveys assessed how the clinicians felt about pharmacogenomics and whether they thought electronic PGx-CDS alerts were useful. Information was abstracted on the number of CDS alerts the clinicians received between October 2013 and the date their survey was returned. CDS alerts were grouped into 2 categories: the alert recommended caution using the prescription, or the alert recommended an alternate prescription. Finally, data were abstracted regarding whether the clinician changed their prescription in response to the alert recommendation., Results: The survey response rate was 57% (n = 90). Overall, 52% of the clinicians did not expect to use or did not know whether they would use pharmacogenomic information in their future prescribing practices. Additionally, 53% of the clinicians felt that the alerts were confusing, irritating, frustrating, or that it was difficult to find additional information. Finally, only 30% of the clinicians that received a CDS alert changed their prescription to an alternative medication., Conclusions: Our results suggest a lack of clinician comfort with integration of pharmacogenomic data into primary care. Further efforts to refine PGx-CDS alerts to make them as useful and user-friendly as possible are needed to improve clinician satisfaction with these new tools., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Heart failure (HF) is associated with excess morbidity and mortality for which noncardiac causes are increasingly recognized. The authors previously described an increased risk of cancer among HF patients compared with community controls., Objectives: This study examined whether HF was associated with an increased risk of subsequent cancer among a homogenous population of first myocardial infarction (MI) survivors., Methods: A prospective cohort study was conducted among Olmsted County, Minnesota, residents with incident MI from 2002 to 2010. Patients with prior cancer or HF diagnoses were excluded., Results: A total of 1,081 participants (mean age 64 ± 15 years; 60% male) were followed for 5,327 person-years (mean 4.9 ± 3.0 years). A total of 228 patients developed HF, and 98 patients developed cancer (excluding nonmelanoma skin cancer). Incidence density rates for cancer diagnosis (per 1,000 person-years) were 33.7 for patients with HF and 15.6 for patients without HF (p = 0.002). The hazard ratio (HR) for cancer associated with HF was 2.16 (95% confidence interval [CI]: 1.39 to 3.35); adjusted for age, sex, and Charlson comorbidity index; HR: 1.71 (95% CI: 1.07 to 2.73). The HRs for mortality associated with cancer were 4.90 (95% CI: 3.10 to 7.74) for HF-free and 3.91 (95% CI: 1.88 to 8.12) for HF patients (p for interaction = 0.76)., Conclusions: Patients who develop HF after MI have an increased risk of cancer. This finding extends our previous report of an elevated cancer risk after HF compared with controls, and calls for a better understanding of shared risk factors and underlying mechanisms., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The prognostic significance of the clinical presentation of atrial fibrillation (AF) is poorly defined., Objective: The purpose of this study was to determine the frequency, associations, and prognostic impact of different clinical presentations of new-onset AF., Methods: One thousand patients with incident AF in Olmsted County, Minnesota, were randomly selected (2000-2010). Patients with AF that was complicated at presentation (heart failure [n = 71], thromboembolism [n = 24]), provoked (n = 346), or unable to determine symptoms (n = 83) were excluded. In the remaining patients, characteristics and prognosis associated with different types of symptoms were examined., Results: Among 476 patients, 193 had typical (palpitations), 122 had atypical (other non-palpitation symptoms), and 161 had asymptomatic AF presentation. Patients with typical presentation had lower CHA2DS2-VASc scores (mean 2.3 ± 2) compared to atypical and asymptomatic presentation (mean 3.2 ± 1.8 and 3.3 ± 1.9, respectively; P <.001). Fifty-nine cerebrovascular events and 149 deaths (n = 49 cardiovascular) were documented over median 5.6 and 6.0 years, respectively. Atypical and asymptomatic AF conferred higher risks of cerebrovascular events compared to typical AF after adjustment for CHA2DS2-VASc score and age (hazard ratio [HR] 3.51, 95% confidence interval [CI] 1.65-7.48, and HR 2.70, 95% CI 1.29-5.66, respectively), and associations remained statistically significant after further adjustments including comorbidities and warfarin use. Asymptomatic AF was associated with an increased risk of cardiovascular (HR 3.12, 95% CI 1.50-6.45) and all-cause mortality (HR 2.96, 95% CI 1.89-4.64) compared to typical AF after adjustment for CHA2DS2-VASc score and age., Conclusion: The type of clinical presentation may have important implications for the prognosis of new-onset AF in the community., (Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Objectives: To investigate the effect of the number and type of comorbid conditions on death and hospitalizations in individuals with incident heart failure (HF)., Design: Population-based cohort study., Setting: Olmsted County, Minnesota., Participants: Olmsted County, Minnesota, residents with incident HF from 2000 to 2010 (mean age 76 ± 14, 56% female) (N = 1,714)., Measurements: The prevalence of 16 chronic conditions obtained at HF diagnosis classified into three groups: cardiovascular (CV) related, other physical, and mental., Results: The mean number of conditions per participant was 2.6 ± 1.5 for CV-related conditions, 1.3 ± 1.1 for other physical conditions, and 0.30 ± 0.61 for mental conditions. After a mean follow-up of 4.2 years, 1,073 deaths and 6,306 hospitalizations had occurred. After adjustment for age, sex, ejection fraction, in- or outpatient status, and number of other conditions, an increase of one other physical condition was associated with a 14% (HR = 1.14, 95% CI = 1.08-1.20) greater risk of death and a 26% (HR = 1.26, 95% CI = 1.20-1.32) greater risk of hospitalization, and an increase of one mental condition was associated with a 31% (HR = 1.31, 95% CI = 1.19-1.44) greater risk of death and an 18% (HR = 1.18, 95% CI = 1.07-1.29) greater risk of hospitalization. In contrast, an increase of one CV-related condition was not associated with greater risk of death and was associated with a 10% (HR = 1.10, 95% CI = 1.06-1.15) greater risk of hospitalization., Conclusion: CV-related conditions are the most common type of comorbid conditions in individuals with HF, but other physical and mental conditions are more strongly associated with death and hospitalizations. This underscores the effect of non-CV conditions on outcomes in HF., (© 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.)

Objective: To examine the association between depression and clinical outcomes in heart failure (HF) in a community cohort., Patients and Methods: HF patients in Minnesota, United States completed depression screening using the 9-item Patient Health Questionnaire (PHQ-9) between 1st Oct 2007 and 1st Dec 2011; patients with PHQ-9≥5 were labelled "depressed". We calculated the risk of death and first hospitalization within 2 years using Cox regression. Results were adjusted for 10 commonly used prognostic factors (age, sex, systolic blood pressure, estimated glomerular filtration rate, serum sodium, ejection fraction, blood urea nitrogen, brain natriuretic peptide, presence of diabetes and ischaemic aetiology). Area under the curve (AUC), integrated discrimination improvement (IDI) and net reclassification improvement (NRI) compared depression as a predictor against the aforementioned factors., Results: 425 patients (mean age 74, 57.6% males) were included in the study; 179 (42.1%) had PHQ-9≥5. The adjusted hazard ratio of death was 2.02 (95% CI 1.34-3.04) and of hospitalization was 1.42 (95% CI 1.13-1.80) for those with compared to those without depression. Adding depression to the models did not appreciably change the AUC but led to statistically significant improvements in both the IDI (p = 0.001 and p = 0.005 for death and hospitalization, respectively) and NRI (for death and hospitalization, 35% (p = 0.002) and 27% (p = 0.007) were reclassified correctly, respectively)., Conclusion: Depression is frequent among community patients with HF and associated with increased risk of hospitalizations and death. Risk prediction for death and hospitalizations in HF patients can be improved by considering depression.

Background: While atrial fibrillation is a recognized risk factor for stroke, contemporary data on trends in stroke incidence after the diagnosis of atrial fibrillation are scarce., Methods and Results: Olmsted County, MN residents with incident atrial fibrillation or atrial flutter (collectively referred to as AF) from 2000 to 2010 were identified. Cox regression determined associations of year of AF diagnosis with ischemic stroke and transient ischemic attack (TIA) occurring through 2013. Among 3247 AF patients, 321 (10%) had an ischemic stroke/TIA over a mean of 4.6 years (incidence rate [95% CI] per 100 person-years: 2.14 [1.91-2.38]). Two hundred thirty-nine (7%) of 3265 AF patients experienced an ischemic stroke (incidence rate: 1.54 [1.35-1.75]). The risk of both outcomes remained unchanged over time after adjusting for demographics and comorbidities (hazard ratio [95% CI] per year of AF diagnosis: 1.00 [0.96-1.04] for ischemic stroke/TIA; 1.01 [0.96-1.06] for ischemic stroke only). In analyses restricted to patients with prescription information, the rates of anticoagulation use did not change over time, reaching 50.8% at 1 year after AF diagnosis. Further adjustment for anticoagulation use did not alter the temporal trends in stroke incidence (hazard ratio [95% CI] per year of AF diagnosis: 1.06 [0.97-1.15] for ischemic stroke/TIA; 1.08 [0.98-1.20] for ischemic stroke only)., Conclusions: Strokes/TIAs are frequent after AF, occurring in 10% of patients after 5 years of follow-up. The occurrence of stroke/TIA did not decline over the last decade, which may be influenced by a leveling off of anticoagulation use. This concerning trend has major public health implications., (© 2016 The Authors and Mayo Foundation for Medical Education and Research. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

The aim of this study was to compare the QRISKII, an electronic health data-based risk score, to the Framingham Risk Score (FRS) and atherosclerotic cardiovascular disease (ASCVD) score. Risk estimates were calculated for a cohort of 8783 patients, and the patients were followed up from November 29, 2012, through June 1, 2015, for a cardiovascular disease (CVD) event. During follow-up, 246 men and 247 women had a CVD event. Cohen's kappa statistic for the comparison of the QRISKII and FRS was 0.22 for men and 0.23 for women, with the QRISKII classifying more patients in the higher-risk groups. The QRISKII and ASCVD were more similar with kappa statistics of 0.49 for men and 0.51 for women. The QRISKII shows increased discrimination with area under the curve (AUC) statistics of 0.65 and 0.71, respectively, compared to the FRS (0.59 and 0.66) and ASCVD (0.63 and 0.69). These results demonstrate that incorporating additional data from the electronic health record (EHR) may improve CVD risk stratification.

Objective: The goal of this study was to identify distinct frailty trajectories (clusters of individuals following a similar progression of frailty over time) in an ageing population and to determine social and behavioural factors associated with frailty trajectories., Design: Population-based cohort study., Setting: Olmsted County, Minnesota., Participants: Olmsted County, Minnesota residents aged 60-89 in 2005., Primary Outcome Measure: Changes in frailty over an 8-year period from 2005 to 2012, measured by constructing a yearly frailty index. Frailty trajectories by decade of age were determined using k-means cluster modelling for longitudinal data., Results: After adjustment for age and sex, all social and behavioural factors (education, marital status, living arrangements, smoking status and alcohol use) were significantly associated with frailty trajectories in those aged 60-69 and 70-79 years. After further adjustment for baseline frailty, the likelihood of being in the high frailty trajectory was greatest among those reporting concerns from relatives/friends about alcohol consumption (OR (95% CI) 2.26 (1.19 to 4.29)) and those with less than a high school education (OR (95% CI) 1.98 (1.32 to 2.96)) in the 60-69 year olds. In the 70-79 year olds, the largest associations were observed among those with concerns from oneself about alcohol consumption (OR (95% CI) 1.92 (1.23 to 3.00)), those with less than a high school education (OR (95% CI) 1.57 (1.12 to 2.22)), and those living with family (vs spouse; OR (95% CI) 1.76 (1.05 to 2.94)). No factors remained associated with frailty trajectories in the 80-89 year olds after adjustment for baseline frailty., Conclusions: Social and behavioural factors are associated with frailty, with stronger associations observed in younger ages. Recognition of social and behavioural factors associated with increasing frailty may inform interventions for individuals at risk of worsening frailty, specifically when targeted at younger individuals., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

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.

Objectives: To estimate the risk of fatal and non-fatal myocardial infarction (MI) and stroke in patients with bipolar I disorder compared to people without bipolar I disorder., Method: Utilizing a records-linkage system spanning 30 years (1966-1996), a population-based cohort of 334 subjects with bipolar I disorder and 334 age and sex-matched referents from Olmsted County, Minnesota, U.S. was identified. Longitudinal follow-up continued until incident MI or stroke (confirmed by board-certified cardiologist/neurologist), death, or study end date (December 31, 2013). Cox proportional hazards models assessed the hazard ratio (HR) for MI or stroke, adjusting for potential confounders., Results: There was an increased risk of fatal or non-fatal MI or stroke (as a composite outcome) in patients with bipolar I disorder [HR 1.54, 95% confidence interval (CI) 1.02, 2.33; p=0.04]. However, after adjusting for baseline cardiovascular risk factors (alcoholism, hypertension, diabetes, and smoking), the risk was no longer significantly increased (HR 1.19, 95% CI 0.76, 1.86; p=0.46)., Limitations: Small sample size for the study design. Findings were not retained after adjustment for cardiovascular disease risk factors. Psychotropic medication use during the follow-up was not ascertained and was not included in the analyses., Conclusion: This study in a geographically defined region in the U.S. demonstrated a significant increased risk of MI or stroke in bipolar I disorder, which was no longer significant after adjustment for cardiovascular risk factors., (Copyright © 2016. Published by Elsevier B.V.)

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.)

Objectives: To identify distinct frailty trajectories (clusters of individuals following a similar progression of frailty over time) in an aging population and to estimate associations between frailty trajectories and emergency department visits, hospitalizations, and all-cause mortality., Design: Population-based cohort study., Setting: Olmsted County, Minnesota., Participants: Olmsted County, Minnesota residents aged 60-89 in 2005., Measurements: Longitudinal changes in frailty between 2005 and 2012 were measured by constructing a yearly Rockwood frailty index incorporating body mass index, 17 comorbidities, and 14 activities of daily living. The frailty index measures variation in health status as the proportion of deficits present of the 32 considered (range 0-1)., Results: Of the 16,443 Olmsted County residents aged 60-89 in 2005, 12,270 (74.6%) had at least 3 years of frailty index measures and were retained for analysis. The median baseline frailty index increased with age (0.11 for 60-69, 0.14 for 70-79, 0.19 for 80-89). Three distinct frailty trajectories were identified in individuals aged 60-69 at baseline and two trajectories in those aged 70-79 and 80-89. Within each decade of age, increasing frailty trajectories were associated with greater risks of emergency department visits, hospitalization, and all-cause mortality, even after adjustment for baseline frailty index., Conclusion: The number of frailty trajectories differed according to age. Within each age group, those in the highest frailty trajectory had greater healthcare use and worse survival. Frailty trajectories may offer a way to target aging individuals at high risk of hospitalization or death for therapeutic or preventive interventions., (© 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.)

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 relationship between central obesity and survival in community-dwelling adults with normal body mass index (BMI) is not well-known., Objective: To examine total and cardiovascular mortality risks associated with central obesity and normal BMI., Design: Stratified multistage probability design., Setting: NHANES III (Third National Health and Nutrition Examination Survey)., Participants: 15,184 adults (52.3% women) aged 18 to 90 years., Measurements: Multivariable Cox proportional hazards models were used to evaluate the relationship of obesity patterns defined by BMI and waist-to-hip ratio (WHR) and total and cardiovascular mortality risk after adjustment for confounding factors., Results: Persons with normal-weight central obesity had the worst long-term survival. For example, a man with a normal BMI (22 kg/m2) and central obesity had greater total mortality risk than one with similar BMI but no central obesity (hazard ratio [HR], 1.87 [95% CI, 1.53 to 2.29]), and this man had twice the mortality risk of participants who were overweight or obese according to BMI only (HR, 2.24 [CI, 1.52 to 3.32] and 2.42 [CI, 1.30 to 4.53], respectively). Women with normal-weight central obesity also had a higher mortality risk than those with similar BMI but no central obesity (HR, 1.48 [CI, 1.35 to 1.62]) and those who were obese according to BMI only (HR, 1.32 [CI, 1.15 to 1.51]). Expected survival estimates were consistently lower for those with central obesity when age and BMI were controlled for., Limitations: Body fat distribution was assessed based on anthropometric indicators alone. Information on comorbidities was collected by self-report., Conclusion: Normal-weight central obesity defined by WHR is associated with higher mortality than BMI-defined obesity, particularly in the absence of central fat distribution., Primary Funding Source: National Institutes of Health, American Heart Association, European Regional Development Fund, and Czech Ministry of Health., Competing Interests: Conflicts of Interest: None declared

Background: Despite improvements in diagnosis and treatment, the prevalence of hyperlipidemia among adults in the United States remains high. Data are limited on treatment patterns and patient perceptions of cardiovascular disease risk since the release of new lipid guidelines., Objectives: The objectives of the PALM registry are to assess contemporary patterns of lipid-lowering therapy use among adults receiving care in a nationally representative cohort of community clinics, determine consistency of treatment with varying lipid guidelines, identify factors affecting use of lipid-lowering therapy including patient-reported statin intolerance, and assess patient and provider knowledge of cardiovascular risk reduction goals., Study Design: The PALM registry will enroll 7,500 patients likely to be considered for lipid-lowering therapy from 175 cardiology, primary care, and endocrinology practices across the United States. In this cross-sectional, observational registry, a novel tablet-based platform will be used to collect patient-reported knowledge, attitudes, and beliefs regarding cardiovascular risk reduction and lipid management. Chart abstraction and core laboratory lipid levels will describe current lipid management. Provider surveys will assess perception of current lipid-lowering goals and barriers to optimal cardiovascular risk reduction., Conclusion: The PALM registry will allow for better understanding of current practice patterns, patient experiences, and patient and provider attitudes toward cholesterol management for cardiovascular disease risk reduction. These data can be used to better understand gaps in care and design targeted interventions to improve uptake of lipid-lowering therapies for cardiovascular risk reduction., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: 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)., Patients and Methods: We performed a retrospective search of electronic medical records of all outpatients seen at Mayo Clinic Rochester from January 1, 2010, through December 31, 2013, to identify residents of Olmsted County, Minnesota, 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 8280 outpatients from Olmsted County who were evaluated at Mayo Clinic Rochester with chest pain, 590 (7.1%) had resting echocardiograms. Ninety-two of these 590 patients (15.6%) had normal resting ECGs. Thirty-three of these 92 patients (35.9%) had other indications for echocardiography. The remaining 59 patients (10.0% of all echocardiograms and 0.7% of all patients) had normal resting ECGs and no other indication for echocardiography. Fifty-seven of these 59 patients (96.6%) had normal echocardiograms. Thirteen of these 59 echocardiograms (22.0%) were "preordered" before the provider (physicians, nurses, physician assistants) visit., Conclusion: The overall rate of echocardiography in Olmsted County outpatients with chest pain seen at Mayo Clinic Rochester is low. Only 1 in 10 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. The rate of unnecessary echocardiograms could be decreased by eliminating preordering., (Copyright © 2015 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Identifying populations of heart failure (HF) patients is paramount to research efforts aimed at developing strategies to effectively reduce the burden of this disease. The use of electronic medical record (EMR) data for this purpose is challenging given the syndromic nature of HF and the need to distinguish HF with preserved or reduced ejection fraction. Using a gold standard cohort of manually abstracted cases, an EMR-driven phenotype algorithm based on structured and unstructured data was developed to identify all the cases. The resulting algorithm was executed in two cohorts from the Electronic Medical Records and Genomics (eMERGE) Network with a positive predictive value of >95 %. The algorithm was expanded to include three hierarchical definitions of HF (i.e., definite, probable, possible) based on the degree of confidence of the classification to capture HF cases in a whole population whereby increasing the algorithm utility for use in e-Epidemiologic research.

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.)

Geoffrey Rose pioneered the concept that, to reduce the burden of disease, improving the population distribution of a risk factor was preferable to interventions that target high-risk individuals. Reflecting on this concept prompted us to ask if temporal trends in the burden of cardiovascular disease support this hypothesis. This perspective article summarizes the Geoffrey Rose lecture given at the European Society of Cardiology meeting in 2014 and examines how cardiovascular diseases have evolved over the past three decades focusing on temporal trends in myocardial infarction and heart failure., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)

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: Healthcare utilization peaks at the end of life (EOL) in patients with heart failure. However, it is unclear what factors affect end of life utilization in patients with heart failure and if utilization has changed over time., Methods and Results: Southeastern Minnesota residents with heart failure were prospectively enrolled into a longitudinal cohort study from 2003 to 2011. Patients who died before December 31, 2012, were included in the analysis. Information on hospitalizations and outpatient visits in the last year of life was obtained using administrative sources. Negative binomial regression was used to assess the association between patient characteristics and utilization. The 698 decedents (47.3% men; 53.4% preserved ejection fraction) experienced 1528 hospitalizations (median 2 per person; range, 0-12; 37.6% because of cardiovascular causes) and 12 927 outpatient visits (median 14 per person; range, 0-119) in their last year of life. Most patients (81.5%) were hospitalized at least once and 28.4% died in the hospital. Patients who were older and those with dementia had lower utilization. Patients who were married, resided in a skilled nursing facility, and had more comorbidities had higher utilization. Patients with preserved ejection fraction had higher rates of noncardiovascular hospitalizations although other utilization was similar. Over time, rates of hospitalizations and outpatient visits decreased, whereas palliative care consults and enrollment in hospice increased., Conclusions: Although patient factors remain associated with differential healthcare utilization at the end of life, utilization declined over time and use of palliative care services increased. These results are encouraging given the high resource use in patients with heart failure., (© 2015 American Heart Association, Inc.)

Objectives: To measure the incidence of acute coronary syndrome (ACS), defined as first-ever myocardial infarction (MI) or unstable angina (UA); evaluate recent temporal trends; and determine whether survival after ACS has changed over time and differs by type., Patients and Methods: This was a population surveillance study conducted in Olmsted County, Minnesota (population: 144,248). All persons hospitalized with incident ACS between January 1, 2005, and December 31, 2010, were identified using International Classification of Diseases, Ninth Revision codes, natural language processing of the medical records, and biomarkers. Myocardial infarction was validated by epidemiologic criteria and UA by the Braunwald classification. Patients were followed through June 30, 2013, for death., Results: Of 1244 incident ACS cases, 35% (n=438) were UA and 65% (n=806) were MI. The standardized rates (per 100,000) of ACS were 284 (95% CI, 248-319) in 2005 and 184 (95% CI, 157-210) in 2010 (2010 vs 2005: rate ratio, 0.62; 95% CI, 0.53-0.73), indicating a 38% decline (similar for MI and UA). The 30-day case fatality rates did not differ by year of diagnosis but were worse for MI (8.9%; 95% CI, 6.9%-10.9%) compared with UA (1.9%; 95% CI, 0.6%-3.1%). Among 30-day survivors, the risk of death did not differ by ACS type or diagnosis year., Conclusion: In the community, UA constitutes 35% of ACS. The incidence of ACS has declined in recent years, and trends were similar for UA and MI, reaffirming a substantial decline in all acute manifestations of coronary disease. Survival after ACS did not change over time, but 30-day survival was worse for MI compared with UA., (Copyright © 2015 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

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.)

In 2013, the National Heart, Lung, and Blood Institute assembled a working group on epidemiology and population sciences from its Advisory Council and Board of External Experts. The working group was charged with making recommendations to the National Heart, Lung, and Blood Advisory Council about how the National Heart, Lung, and Blood Institute could take advantage of new scientific opportunities and delineate future directions for the epidemiology of heart, lung, blood, and sleep diseases. Seven actionable recommendations were proposed for consideration. The themes included 1) defining the compelling scientific questions and challenges in population sciences and epidemiology of heart, lung, blood, and sleep diseases; 2) developing methods and training mechanisms to integrate "big data" science into the practice of epidemiology; 3) creating a cohort consortium and inventory of major studies to optimize the efficient use of data and specimens; and 4) fostering a more open, competitive approach to evaluating large-scale longitudinal epidemiology and population studies. By building on the track record of success of the heart, lung, blood, and sleep cohorts to leverage new data science opportunities and encourage broad research and training partnerships, these recommendations lay a strong foundation for the transformation of heart, lung, blood, and sleep epidemiology., (© The Author 2015. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Chronic disease can contribute to functional disability, which can degrade quality of life. However, the prevalence of functional disability and its association with outcomes among patients with heart failure requires further study., Methods and Results: Southeastern Minnesota residents with heart failure were enrolled from September 2003 through January 2012 into a cohort study with follow-up through December 2012. Difficulty with 9 activities of daily living (ADLs) was assessed by a questionnaire. Patients were divided into 3 categories of ADL difficulty (no/minimal, moderate, severe). The associations of ADL difficulty with mortality and hospitalization were assessed using Cox and Andersen-Gill models. Among 1128 patients (mean age, 74.7 years; 49.2% female), a majority (59.4%) reported difficulty with one or more ADLs at enrollment, with 272 (24.1%) and 146 (12.9%) experiencing moderate and severe difficulty, respectively. After a mean (SD) follow-up of 3.2 (2.4) years, 614 patients (54.4%) had died. Mortality increased with increasing ADL difficulty; the hazard ratio (95% confidence interval) for death was 1.49 (1.22-1.82) and 2.26 (1.79-2.86) for those with moderate and severe difficulty, respectively, compared to those with no/minimal difficulty (Ptrend<0.001). Patients with moderate and severe difficulty were at an increased risk for all-cause and noncardiovascular hospitalization. In a second assessment, 17.7% of survivors reported more difficulty with ADLs and patients with persistently severe or worsening difficulty were at an increased risk for death (hazard ratio, 2.10; 95% confidence interval, 1.71-2.58; P<0.001) and hospitalization (hazard ratio, 1.51; 95% confidence interval, 1.31-1.74; P<0.001)., Conclusions: Functional disability is common in patients with heart failure, can progress over time, and is associated with adverse prognosis., (© 2015 American Heart Association, Inc.)

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.)

Background: With the goal of reducing exposure to secondhand smoke, the state of Minnesota (MN), enacted a smoke-free law (i.e., Freedom to Breathe Act) in all workplaces, restaurants, and bars in 2007. This retrospective cohort study analyzes emergency department (ED) visits in Olmsted County, MN, for chronic obstructive pulmonary disease (COPD) and asthma over a five-year period to assess changes after enactment of the smoke-free law., Methods: We calculated the rates of ED visits in Olmsted County, MN, with a primary diagnosis of COPD and asthma in the five-year period from January 1, 2005 to December 31, 2009. Analyses were performed using segmented Poisson regression to assess whether ED visit rates declined following enactment of the smoke free law after adjusting for potential underlying temporal trends in ED visit rates during this time period., Results: Using segmented Poisson regression analyses, a significant reduction was detected in asthma-related ED visits (RR 0.814, p < 0.001) but not for COPD-related ED visits following the enactment of the smoke-free law. The reduction in asthma related ED visits was observed in both adults (RR 0.840, p = 0.015) and children (RR 0.751, p = 0.015)., Conclusions: In Olmsted County, MN, asthma-related ED visits declined significantly after enactment of a smoke-free law. These results add to the body of literature supporting community health benefits of smoke-free policies in public environments and their potential to reduce health care costs.

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.)

Background: The prevalence and clinical significance of right ventricular (RV) systolic dysfunction (RVD) in patients with heart failure and preserved ejection fraction (HFpEF) are not well characterized., Methods and Results: Consecutive, prospectively identified HFpEF (Framingham HF criteria, ejection fraction ≥50%) patients (n=562) from Olmsted County, Minnesota, underwent echocardiography at HF diagnosis and follow-up for cause-specific mortality and HF hospitalization. RV function was categorized by tertiles of tricuspid annular plane systolic excursion and by semiquantitative (normal, mild RVD, or moderate to severe RVD) 2-dimensional assessment. Whether RVD was defined by semiquantitative assessment or tricuspid annular plane systolic excursion ≤15 mm, HFpEF patients with RVD were more likely to have atrial fibrillation, pacemakers, and chronic diuretic therapy. At echocardiography, patients with RVD had slightly lower left ventricular ejection fraction, worse diastolic dysfunction, lower blood pressure and cardiac output, higher pulmonary artery systolic pressure, and more severe RV enlargement and tricuspid valve regurgitation. After adjustment for age, sex, pulmonary artery systolic pressure, and comorbidities, the presence of any RVD by semiquantitative assessment was associated with higher all-cause (hazard ratio=1.35; 95% confidence interval, 1.03-1.77; P=0.03) and cardiovascular (hazard ratio=1.85; 95% confidence interval, 1.20-2.80; P=0.006) mortality and higher first (hazard ratio=1.99; 95% confidence interval, 1.35-2.90; P=0.0006) and multiple (hazard ratio=1.81; 95% confidence interval, 1.18-2.78; P=0.007) HF hospitalization rates. RVD defined by tricuspid annular plane systolic excursion values showed similar but weaker associations with mortality and HF hospitalizations., Conclusions: In the community, RVD is common in HFpEF patients, is associated with clinical and echocardiographic evidence of more advanced HF, and is predictive of poorer outcomes., (© 2014 American Heart Association, Inc.)

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.)

Heart failure (HF) is a major public health problem affecting more than five million Americans and more than 23 million patients worldwide. The epidemiology of HF is evolving. Data suggests that the incidence of HF peaked in the mid-1990s and has since declined. Survival after HF diagnosis has improved, leading to an increase in prevalence. The case mix is also changing, as a rising proportion of patients with HF have preserved ejection fraction and multimorbidity is increasingly common. After diagnosis, HF can have a profound associated morbidity. Hospitalizations in HF remain both frequent and costly, though they may be declining as a result of preventive efforts. The need for skilled nursing facility care in HF has risen. The role of palliative medicine in the care of patients with advanced HF is evolving as we learn how to best care for this population with a large symptom burden.

Objective: To evaluate the long-term prognostic effect of resting heart rate (HR) at index myocardial infarction (MI) and during the first year after MI among 1-year survivors., Patients and Methods: The community-based cohort consisted of 1571 patients hospitalized with an incident MI from January 1, 1983, through December 31, 2007, in Olmsted County, Minnesota, who were in sinus rhythm at index MI and had HR measurements on electrocardiography at index and during the first year after MI. Outcomes were all-cause and cardiovascular deaths., Results: During a median follow-up of 7.0 years, 627 deaths and 311 cardiovascular deaths occurred. Using patients with HRs of 60/min or less as the referent, this study found that long-term all-cause mortality risk increased progressively with increasing HR at index (hazard ratio, 1.62; 95% CI, 1.25-2.09) and even more with increasing HR during the first year after MI (hazard ratio, 2.16; 95% CI, 1.64-2.84) for patients with HRs greater than 90/min, adjusting for clinical characteristics and β-blocker use. Similar results were observed for cardiovascular mortality (adjusted hazard ratio, 1.66; 95% CI, 1.14-2.42; and adjusted hazard ratio, 1.93; 95% CI, 1.27-2.94; for HR at index and within 1 year after MI, respectively)., Conclusion: These data from a large MI community cohort indicate that HR is a strong predictor of long-term all-cause and cardiovascular mortality not only at initial presentation of MI but also during the first year of follow-up., (Copyright © 2014 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

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.

The objective of the present study was to investigate the relation of ventricular premature complex (VPC) burden, origin, and electrocardiographic characteristics with left ventricular function and survival. Of 1,589 study patients, 388 (25%), 610 (38%), and 591 (37%) had low (<1,000/24 hours), moderate (1,000 to 10,000/24 hours), and high (>10,000/24 hours) VPC burden, respectively. Twenty-three percent of study patients had a left ventricular (LV) ejection fraction <50% (8% in low-, 20% in moderate-, and 36% in high-VPC-burden groups, p <0.001). High VPC burden was associated with lower LV ejection fraction in the presence (r = -0.17, p <0.001) and absence (r = -0.20, p <0.001) of heart diseases. The Kaplan-Meier survival estimates showed a significant difference among the 3 VPC burden groups (p = 0.046). The survival rates were significantly lower for patients with a VPC coupling interval of ≥480 ms than those with a VPC coupling interval of <480 ms (p = 0.002) and lower for those with a VPC QRS duration of ≥150 ms than those with a VPC QRS duration of <150 ms (p <0.001). In conclusion, high VPC burden is detrimental to LV systolic function. Broader VPC QRS duration and longer VPC coupling interval adversely impact on long-term survival., (Published by Elsevier Inc.)

Objective: To review the evidence on and estimate the risk of myocardial infarction and stroke in bipolar disorder., Method: A systematic search using MEDLINE, EMBASE, PsycINFO, Web of Science, Scopus, Cochrane Database of Systematic Reviews, and bibliographies (1946 - May, 2013) was conducted. Case-control and cohort studies of bipolar disorder patients age 15 or older with myocardial infarction or stroke as outcomes were included. Two independent reviewers extracted data and assessed quality. Estimates of effect were summarized using random-effects meta-analysis., Results: Five cohort studies including 13 115 911 participants (27 092 bipolar) were included. Due to the use of registers, different statistical methods, and inconsistent adjustment for confounders, there was significant methodological heterogeneity among studies. The exploratory meta-analysis yielded no evidence for a significant increase in the risk of myocardial infarction: [relative risk (RR): 1.09, 95% CI 0.96-1.24, P = 0.20; I(2)  = 6%]. While there was evidence of significant study heterogeneity, the risk of stroke in bipolar disorder was significantly increased (RR 1.74, 95% CI 1.29-2.35; P = 0.0003; I(2)  = 83%)., Conclusion: There may be a differential risk of myocardial infarction and stroke in patients with bipolar disorder. Confidence in these pooled estimates was limited by the small number of studies, significant heterogeneity and dissimilar methodological features., Competing Interests: Declaration of interestThis project was partially supported by Grant Number UL1 TR000135 from the National Center for Advancing Translational Sciences (NCATS). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. It was also partially supported by Mayo Foundation for Medical Education and Research. Dr. Prieto has received honoraria for speaker activities and development of educational presentations from GlaxoSmithKline, has received travel support from GlaxoSmithKline, Lilly, Lundbeck, Pharmavita, and has received scholarship support from the Government of Chile. Dr. Bellivier has received honoraria for speaker activities from AstraZeneca, Bristol-Myers Squibb, Euthérapie, Lundbeck, Otsuka, European Space Agency, and for consulting from Bristol-Myers Squibb, Lundbeck, Otsuka, European Space Agency. Dr. Frye has been a consultant (unpaid) for Allergan, Merck, Myriad, Sanofi-Aventis, Sunovion, Takeda Global Research, Teva Pharmaceuticals, United Biosource Corporation, has received grant support from Myriad, Pfizer, National Alliance for Schizophrenia and Depression (NARSAD), National Institute of Mental Health (NIMH), National Institute of Alcohol Abuse and Alcoholism (NIAAA), Mayo Foundation, and has received travel support from Chilean Society of Neurology, Psychiatry and Neurosurgery (Sociedad de Neurologia, Psiquiatria y Neurocirugia), Advanced Health Media, GlaxoSmithKline, Colombian Society of Neuropsychopharmacology, AstraZeneca, Bristol-Myers-Squib, Otsuka, Sanofi-Aventis. For the remaining authors, no further conflict of interests were declared., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)