Citations

Background— In patients with heart failure and preserved ejection fraction (HFpEF), atrial fibrillation (AF) may predate, concur with, or develop after HFpEF diagnosis. We sought to define the temporal relationship between AF and HFpEF, to identify factors associated with AF, and to determine the prognostic impact of prevalent and incident AF in HFpEF. Method and Results— From 1983 to 2010, 939 Olmsted County, Minnesota, residents (age, 77±12 years; 61% female) newly diagnosed with HFpEF (EF ≥0.50) were evaluated. Baseline rhythm classification included prior AF (>3 months before HFpEF diagnosis), concurrent AF (±3 months), or sinus rhythm. Incident AF (>3 months after HFpEF diagnosis) and all-cause mortality were ascertained through February 2012. Prior AF (29%) and concurrent AF (23%) were associated with older age, higher brain-type natriuretic peptide, and larger left atrial volume index at HFpEF diagnosis compared with sinus rhythm. Of HFpEF patients in sinus rhythm at diagnosis, 32% developed AF over a median follow-up of 3.7 years (interquartile range, 1.5–6.7 years; 69 events per 1000 person-years). Age and diastolic dysfunction were positively and statin use was inversely associated with incident AF. With no AF used as the referent, prior or concurrent AF (combined hazard ratio, 1.3; 95% confidence interval, 1.0–1.6; P =0.03) and incident AF, modeled as a time-dependent covariate (hazard ratio, 2.1; 95% confidence interval, 1.4–3.0; P <0.001), were independently associated with death after adjustment for pertinent covariates. Conclusions— AF occurs in two thirds of HFpEF patients at some point in the natural history and confers a poor prognosis. Further study is required to determine whether intervention for AF may improve outcomes or if statin use can prevent AF in HFpEF.

Background The prevalence of atrial fibrillation ( AF ) continues to increase; however, there are limited data describing the division of care among practitioners in the community and whether care differs depending on provider specialty. Methods and Results Using the Outcomes Registry for Better Informed Treatment of AF ( ORBIT ‐ AF ) Registry, we described patient characteristics and AF management strategies in ambulatory clinic practice settings, including electrophysiology ( EP ), general cardiology, and primary care. A total of 10 097 patients were included; of these, 1544 (15.3%) were cared for by an EP provider, 6584 (65.2%) by a cardiology provider, and 1969 (19.5%) by an internal medicine/primary care provider. Compared with those patients who were cared for by cardiologists or internal medicine/primary care providers, patients cared for by EP providers were younger (median age, 73 years [interquartile range, IQR , 64, 80 years, Q1, Q3] versus 75 years [ IQR , 67, 82 years] for cardiology and versus 76 years [ IQR , 68, 82 years] for primary care). Compared with cardiology and internal medicine/primary care providers, EP providers used rhythm control (versus rate control) management more often (44.2% versus 29.7% and 28.8%, respectively, P <0.0001; adjusted odds ratio [ OR ] EP versus cardiology, 1.66 [95% confidence interval, CI , 1.05 to 2.61]; adjusted OR for internal medicine/primary care versus cardiology, 0.91 [95% CI , 0.65 to 1.26]). Use of oral anticoagulant therapy was high across all providers, although it was higher for cardiology and EP providers (overall, 76.1%; P =0.02 for difference between groups). Conclusions Our data demonstrate important differences between provider specialties, the demographics of the AF patient population treated, and treatment strategies—particularly for rhythm control and anticoagulation therapy.

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

AbstractTraumatic brain injury (TBI) and post‐traumatic stress disorder (PTSD) are signature injuries of the wars in Iraq and Afghanistan and have been linked to an increased risk of Alzheimer's disease (AD) and other dementias. A meeting hosted by the Alzheimer's Association and the Veterans' Health Research Institute (NCIRE) in May 2012 brought together experts from the U.S. military and academic medical centers around the world to discuss current evidence and hypotheses regarding the pathophysiological mechanisms linking TBI, PTSD, and AD. Studies underway in civilian and military populations were highlighted, along with new research initiatives such as a study to extend the Alzheimer's Disease Neuroimaging Initiative (ADNI) to a population of veterans exposed to TBI and PTSD. Greater collaboration and data sharing among diverse research groups is needed to advance an understanding and appropriate interventions in this continuum of military injuries and neurodegenerative disease in the aging veteran.

Objectives: To determine the prevalence and relationship of frailty and health-related quality of life (HRQOL) among residents of long-term care [nursing homes (NH) and assisted living (AL)] facilities. Methods: Residents of NH and AL facilities in La Crosse County, Wisconsin, were recruited 1/2009-6/2010 and assessed for frailty (gait speed, unintended weight loss, grip strength), comorbidity (Charlson index), and HRQOL [Short Form (SF)-36]. Results: Among 137 participants, 85% were frail. Frail residents were older, had more comorbidities (2.0 vs. 0, p < .001) and lower mean SF-36 Physical Component Score (PCS, 32 vs. 48, p < .001). Following adjustments for age, sex, and comorbidities, compared to nonfrail residents, frail residents had lower SF-36 PCS (mean difference −14.7, 95% CI. −19.3,−10.1, p < .001). Frailty, comorbidity, and HRQOL did not differ between NH and AL facilities. Discussion: Frail residents had lower HRQOL, suggesting that preventing frailty may lead to better HRQOL among residents of long-term care facilities.

Abstract Metastasis, the leading cause of cancer death, requires tumor cell intravasation, migration through the bloodstream, arrest within capillaries, and extravasation to invade distant tissues. Few mechanistic details have been reported thus far regarding the extravasation process or re-entry of circulating tumor cells at metastatic sites. Here, we show that neuropilin-2 (NRP-2), a multifunctional nonkinase receptor for semaphorins, vascular endothelial growth factor (VEGF), and other growth factors, expressed on cancer cells interacts with α5 integrin on endothelial cells to mediate vascular extravasation and metastasis in zebrafish and murine xenograft models of clear cell renal cell carcinoma (RCC) and pancreatic adenocarcinoma. In tissue from patients with RCC, NRP-2 expression is positively correlated with tumor grade and is highest in metastatic tumors. In a prospectively acquired cohort of patients with pancreatic cancer, high NRP-2 expression cosegregated with poor prognosis. Through biochemical approaches as well as Atomic Force Microscopy (AFM), we describe a unique mechanism through which NRP-2 expressed on cancer cells interacts with α5 integrin on endothelial cells to mediate vascular adhesion and extravasation. Taken together, our studies reveal a clinically significant role of NRP-2 in cancer cell extravasation and promotion of metastasis. Cancer Res; 73(14); 4579–90. ©2013 AACR.

Background— Physical health status measures have been shown to predict death in heart failure (HF); however, few studies found significant associations after adjustment for confounders, and most were not representative of all HF patients. Methods and Results— HF patients from southeastern MN were prospectively enrolled between 10/2007 and 12/2010, completed a 12-item Short Form Health Survey (SF-12) and a 6-minute walk, and were followed through 2011 for death from any cause. Scores ≤25 on the SF-12 physical component indicated low self-reported physical functioning, and the first question of the SF-12 measured self-rated general health. Low functional exercise capacity was defined as ≤300 m walked during a 6-minute walk. Over a mean follow-up of 2.3 years, 86 deaths occurred among the 352 participants. A 1.6-fold (95% confidence interval, 1.0–2.7) and 1.8-fold (95% confidence interval, 1.1–2.9) increased risk of death was observed among patients with low self-reported physical functioning and low functional exercise capacity, respectively. Poor self-rated general health corresponded to a 2.7-fold (95% confidence interval, 1.5–4.9) increased risk of death compared with good to excellent general health. All measures equally discriminated between who would die and who would survive (C-statistics: 0.729, 0.750, and 0.740 for self-reported physical functioning, self-rated general health, and functional exercise capacity, respectively). Conclusions— Three physical health status measures, captured by the SF-12 and a 6-minute walk, equally predict death among community HF patients. Therefore, the first question of the SF-12, which is the least burdensome to administer, may be sufficient to identify HF patients at greatest risk of death.