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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 .

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.

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.

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 ( P trend <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.

Background— Heart failure (HF) can occur in patients with preserved (HFpEF, EF≥50%) or reduced (HFrEF, EF<50%) ejection fraction (EF), but changes in EF after HF diagnosis are not well described. Methods and Results— Among a community cohort of incident HF patients diagnosed from 1984 to 2009 in Olmsted County, Minnesota, we obtained all EFs assessed by echocardiography from initial HF diagnosis until death or last follow-up through March 2010. Mixed effects models fit a unique linear regression line for each person using serial EF data. Compiled results allowed estimates of the change in EF over time in HFpEF and HFrEF. Among 1233 HF patients (48.3% male, mean age 75.0 years, mean follow-up 5.1 years), 559 (45.3%) had HFpEF at diagnosis. In HFpEF, on average, EF decreased by 5.8% over 5 years ( P <0.001) with greater declines in older individuals and those with coronary disease. Conversely, EF increased in HFrEF (average increase 6.9% over 5 years, P <0.001). Greater increases were noted in women, younger patients, individuals without coronary disease, and those treated with evidence-based medications. Overall, 39% of HFpEF patients had an EF<50% and 39% of HFrEF patients had an EF≥50% at some point after diagnosis. Decreases in EF over time were associated with reduced survival whereas increases in EF were associated with improved survival. Conclusions— These data suggest that progressive contractile dysfunction may contribute to the pathophysiology of HFpEF. Prospective longitudinal studies are needed to confirm these observations and establish the mechanism and clinical relevance of decline in EF over time in HFpEF.

Abstract Chronic obstructive pulmonary disease (COPD) is a strong risk factor for lung cancer. Published studies about variations of genes encoding glutathione metabolism, DNA repair, and inflammatory response pathways in susceptibility to COPD were inconclusive. We evaluated 470 single-nucleotide polymorphisms (SNP) from 56 genes of these three pathways in 620 cases and 893 controls to identify susceptibility markers for COPD risk, using existing resources. We assessed SNP- and gene-level effects adjusting for sex, age, and smoking status. Differential genetic effects on disease risk with and without lung cancer were also assessed; cumulative risk models were established. Twenty-one SNPs were found to be significantly associated with risk of COPD (P &lt; 0.01); gene-based analyses confirmed two genes (GCLC and GSS) and identified three additional genes (GSTO2, ERCC1, and RRM1). Carrying 12 high-risk alleles may increase risk by 2.7-fold; eight SNPs altered COPD risk without lung cancer by 3.1-fold and 4 SNPs altered the risk with lung cancer by 2.3-fold. Our findings indicate that multiple genetic variations in the three selected pathways contribute to COPD risk through GCLC, GSS, GSTO2, ERCC1, and RRM1 genes. Functional studies are needed to elucidate the mechanisms of these genes in the development of COPD, lung cancer, or both. Cancer Prev Res; 5(3); 365–73. ©2011 AACR.

Abstract Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-186.

Abstract The contribution of emphysema to lung cancer risk has been recognized, but the effect size needs to be further defined. In this study, 565 primary lung cancer cases were enrolled though a prospective lung cancer cohort at Mayo Clinic, and 450 controls were smokers participating in a lung cancer screening study in the same institution using spiral computed tomography (CT). Cases and controls were frequency matched on age, gender, race, smoking status, and residential region. CT imaging using standard protocol at the time of lung cancer diagnosis (case) or during the study (control) was assessed for emphysema by visual scoring CT analysis as a percentage of lung tissue destroyed. The clinical definition of emphysema was the diagnosis recorded in the medical documentation. Using multiple logistic regression models, emphysema (≥5% on CT) was found to be associated with a 3.8-fold increased lung cancer risk in Caucasians, with higher risk in subgroups of younger (&lt;65 years old, OR = 4.64), heavy smokers (≥40 pack-years, OR = 4.46), and small-cell lung cancer (OR = 5.62). When using &gt;0% or ≥10% emphysema on CT, lung cancer risk was 2.79-fold or 3.33-fold higher than controls. Compared with CT evaluation (using criterion ≥5%), the sensitivity, specificity, positive and negative predictive values, and the accuracy of the clinical diagnosis for emphysema in controls were 19%, 98%, 73%, 84%, and 83%, respectively. These results imply that an accurate evaluation of emphysema could help reliably identify individuals at greater risk of lung cancer among smokers. Cancer Prev Res; 4(1); 43–50. ©2010 AACR.