Weston, Susan A.

BACKGROUND Epidemiological cohorts can assist with post-marketing surveillance as they provide community-based outcomes data. Concern was raised about the adverse impact of sulfonylureas (SU) drugs on the outcome of diabetes after myocardial infarction (MI). We evaluated the outcome of MI according to treatment among diabetic persons compared to non-diabetic counterparts in a community-based cohort. METHODS All MIs that occurred in Olmsted County, MN between 1979 and 2002 were validated by standardized epidemiological including cardiac pain, biomarkers and ECG Minnesota coding. Diabetes mellitus (DM) was defined by the National Diabetes Data Group criteria. RESULTS Among 2732 persons with MI (mean age 70 ± 12 years, 44% men), 486 (18%) had DM. Subjects with DM were treated with second generation SU (SU2) (24%), insulin (47%) or diet alone (22%) Diabetic subjects were more likely to be overweight, hyperlipidemic and to receive reperfusion therapy during hospitalization than non-diabetic subjects. One year after the MI, 518 subjects died. Diabetic subjects taking SU2 experienced better survival than subjects without diabetes, while subjects treated with diet alone or insulin experienced worse survival. (Figure ). After adjusting for age, sex, reperfusion and duration of DM, an excess risk of death was detected among persons with insulin-treated DM, particularly those with long-standing DM. No association was found for DM patients treated with SU2 or diet. CONCLUSION These data do not support the concern for an adverse impact of SU2 on survival and underscore the potential role of community studies for population surveillance.

Introduction: Mortality among patients with heart failure (HF) is high. Though individual biomarkers have been studied to determine their value in risk prediction, the role of a multimarker strategy in predicting mortality above established risk indicators requires evaluation in a relevant cohort using robust analytical methods. Objective: To determine whether adding C-reactive protein (CRP), B-type natriuretic peptide (BNP), and troponin T (TnT) to established risk indicators improved HF mortality risk prediction. Methods: Olmsted County residents presenting with HF from July 2004 to September 2007 were prospectively recruited to undergo biomarker measurement. We investigated whether addition of CRP, BNP, and TnT to a model including established risk indicators improved 6-month mortality risk prediction using multiple methods ( c statistic, net reclassification index, integrated discrimination improvement). Results: Of 566 participants (mean age 77±13 years, 48% male), 87(15%) patients died after 6 months follow-up. Patients with CRP (<12.1mg/L), BNP (<341pg/mL), and TnT (≥0.01ng/mL) below the median (n=112) had the lowest mortality (3%), those with one or two biomarkers above the median had intermediate mortality, and those with all biomarkers above the median (n=105) had markedly increased 6-month mortality (33%). After adjustment for other predictors, higher CRP, BNP, and TnT were each associated with increased mortality, with odds ratios (95% confidence intervals) of 1.66(1.24 –2.24), 2.06(1.42–3.07), and 1.45(1.12–1.87), respectively. While adding CRP, BNP, and TnT individually to the model improved mortality risk prediction, the combination of two or more biomarkers offered greater incremental benefit. Using all biomarkers resulted in an increase in the c statistic from 0.747 to 0.832 (p<0.001), a net reclassification index of 0.33 (p<0.001), and a 100% relative improvement in risk discrimination (integrated discrimination improvement 0.097, p<0.001). Conclusions: The combined use of CRP, BNP, and TnT markedly improved the prediction of 6-month mortality in HF beyond established risk indicators. Implementation of a multimarker strategy including CRP, BNP, and TnT for risk prediction in HF should be considered. This research has received full or partial funding support from the American Heart Association, AHA Midwest Affiliate (Illinois, Indiana, Iowa, Kansas, Michigan, Minnesota, Missouri, Nebraska, North Dakota, South Dakota & Wisconsin).

Background: Referral to a skilled nursing facility (SNF) should contribute to reducing hospital readmissions; however, a “revolving door” phenomenon after admission to SNF has been hypothesized to drive readmissions. The urgent need to study the impact of SNF on readmissions in heart failure (HF) was recently emphasized, yet this has never been studied in the community. Objectives: To evaluate the association between discharge to SNF and 30-day readmissions in a community cohort of hospitalized incident HF patients. Methods: Olmsted County, MN residents hospitalized with first ever (incident) HF (International Classification of Diseases-9 th Revision code 428) from 1995 through 2010 were identified. HF was validated by Framingham criteria. Patients residing in a SNF prior to hospitalization were excluded from the analysis. Logistic regression was used to examine the association between discharge to SNF and 30-day readmissions. Results: Among 1360 HF patients (mean age 74±14, 47% male), 241(18%) were referred to a SNF. Overall, 296 (22%) patients were readmitted within 30-days after index hospitalization. The proportion of 30-day readmissions was greater among patients discharged to a SNF compared to patients discharged home (27% vs 21%, p=0.031). After adjustment for age and sex, patients discharged to a SNF had a 40% increase in the odds of having a hospital readmission within 30 days post HF compared to those discharged home (OR: 1.42, 95% CI 1.01-1.99). Further adjustment for year of HF diagnosis, ejection fraction, anemia, renal function, dementia and cancer did not alter the strength of the association (OR: 1.43, 95% CI: 0.99-2.09). Conclusion: Among community patients with HF, 30-day readmissions remain frequent and are more likely to occur among patients discharged to a SNF compared to those discharged home. These data provide new insight into the drivers of HF readmissions and suggest that interventions targeted to HF patients in SNFs may be warranted.

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

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

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

P46 While heart failure (HF), an emerging epidemic, complicates myocardial infarction (MI), little is known on the predictors of HF post-MI, in particular the impact of reperfusion therapy. This population-based study was undertaken to examine the association between clinical characteristics and post-MI HF between 1979 and 1994. Hospitalized incident MIs were validated using enzymes, chest pain, and Minnesota coding of the ECG. Framingham criteria were used to ascertain both in- and outpatient HF. Proportional hazard regression was used to identify predictors of CHF. In the study period, 1657 patients (pts.) (mean age 67.2 ± 13.9 years, 43% women) had an incident MI. History of diabetes, hypertension and prior HF was found in 19%, 54% and 11% of pts respectively. After 5 years, 43% of pts had experienced HF. Factors independently associated with HF were (see table). There was a 2% decline per year in occurrence of HF. Adding reperfusion therapy in the model attenuated the association between year and HF (adjusted RR for reperfusion 0.67, 95% CI 0.53, 0.84, p=0.006; adjusted for year 0.99; 95% CI 0.97, 1.01, p=0.37). Thus, while remaining frequent post-MI CHF has declined over time. Reperfusion therapy accounted for most of the effect of year. Table 1.

Background: A decline in all forms of coronary revascularization has been previously reported. Whether the decline has continued after the turn of the century is unknown as well as whether it is influenced by trends in the use and results of coronary angiography. Methods: All diagnostic and therapeutic coronary procedures performed among Olmsted County, MN residents from 2000-2015 were analyzed. Standardized rates (per 100,000 population) were calculated applying the direct method and temporal trends compared using Poisson regression models. Trends in disease severity, defined as 3-vessel and/or left main coronary artery disease (CAD), were assessed using logistic regression models. Results: Between 2000 and 2015, 11,691 coronary angiographies were performed (63% men; 54% ≥ 65 years of age). The age- and sex-standardized rates of angiography decreased over time (p trend < 0.001; Figure). Overall, 30% of the subjects had 3-vessel and/or left main CAD, and this proportion decreased over time (age- and sex-adjusted odds ratios (95% CI) for severe CAD: 0.68 (0.62-0.76) in 2005-2009 and 0.69 (0.63-0.77) in 2010-2015 compared with 2000-2004). Among 5,222 coronary revascularization procedures performed, 78% were PCI and 22% CABG. The age- and sex-standardized rates of any revascularization declined during the study period, reflecting temporal decreases in both PCI and CABG (all p trend < 0.001; Figure). The declines in angiography rates, CAD severity, and revascularization utilization were consistently greater in women than men (all P for interactions < 0.01). Conclusions: Declines in all forms of coronary revascularization, which were greater in women than men, have occurred in Olmsted County, MN, from 2000-2015. The declines occurred in the context of fewer angiograms performed in the population and reduced severity of anatomic CAD.

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

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