Brittany Butts

The Importance of NLRP3 Inflammasome in Heart Failure

Patients with heart failure continue to suffer adverse health consequences despite advances in therapies over the past 2 decades. Identification of novel therapeutic targets that may attenuate disease progression is therefore needed. The inflammasome may play a central role in modulating chronic inflammation and in turn affecting heart failure progression. The inflammasome is a complex of intracellular interaction proteins that trigger maturation of proinflammatory cytokines interleukin-1β and interleukin-18 to initiate the inflammatory response. This response is amplified through production of tumor necrosis factor α and activation of inducible nitric oxide synthase. The purpose of this review is to discuss recent evidence implicating this inflammatory pathway in the pathophysiology of heart failure.

A pilot test of an integrated self-care intervention for persons with heart failure and concomitant diabetes.

Studies show 30% to 47% of people with heart failure (HF) have concomitant diabetes mellitus (DM). Self-care for persons with both of these chronic conditions is conflicting, complex, and often inadequate. This pilot study tested an integrated self-care program for its effects on HF and DM knowledge, self-care efficacy, self-care behaviors, and quality of life (QOL). Hospitalized HF-DM participants (N = 71) were randomized to usual care or intervention using a 1:2 allocation and followed at 30 and 90 days after intervention. Intervention was an integrated education and counseling program focused on HF-DM self-care. Variables included demographic and clinical data, knowledge about HF and DM, HF- and DM-specific self-efficacy, standard HF and DM QOL scales, and HF and DM self-care behaviors. Analysis included descriptive statistics, multilevel longitudinal models for group and time effects, post hoc testing, and effect size calculations. Sidak adjustments were used to control for type 1 error inflation. The integrated HF-DM self-care intervention conferred effects on improved HF knowledge (30 days, p = .05), HF self-care maintenance (30 and 90 days, p < .001), HF self-care management (90 days, p = .05), DM self-efficacy (30 days, p = .03; 90 days, p = .004), general diet (30 days, p = .05), HF physical QOL (p = .04), and emotional QOL scores (p = .05) at 90 days within the intervention group. The participants in the usual care group also reported increased total and physical QOL. Greater percentages of participants in the intervention group improved self reported exercise between 0 and 30 days (p = .005 and moderate effect size ES = .47) and foot care between 0 and 90 days (p = .03, small ES = .36). No group differences or improvements in DM-specific QOL were observed. An integrated HF-DM self-care intervention was effective in improving essential components of self-care and had sustained (90 day) effects on selected self-care behaviors. Future studies testing HF-DM integrated self-care interventions in larger samples with longer follow-up and on other outcomes such as hospitalization and clinical markers are warranted.

Methylation of Apoptosis-Associated Speck-Like Protein With a Caspase Recruitment Domain and Outcomes in Heart Failure

BACKGROUND Heart failure (HF) is associated with inflammation characterized by the formation of the inflammasome, which triggers maturation of inflammatory cytokines. Apoptosis-associated speck-like protein with a caspase recruitment domain (ASC), a vital component of the inflammasome, is controlled through epigenetic modification, which may be a candidate pathway for worsening HF. This study examined the inflammasome pathway in HF and the relationships between ASC CpG methylation and outcomes in HF. METHODS AND RESULTS Stored samples from 155 HF outpatients (ejection fraction 29.9 ± 14.9%) were analyzed for percentage methylation of 7 CpG sites in the intron region preceding exon 1 of the ASC gene. ASC methylation was inversely related to ASC mRNA (r = -0.33; P < .001) and protein (r = -0.464; P < .001). ASC methylation had a positive linear relationship with ejection fraction (r = 0.85; P < .001), quality of life (r = 0.83; P < .001), and 6-minute walk test (r = 0.59; P = .023) and a negative linear relationship with depression (r = -0.81; P < .001) and anxiety (r = -0.75; P < .001). Higher ASC methylation was associated with a lower risk for clinical events (hazard ratio [HR] 0.16; P = .025), whereas higher protein (HR = 1.78; P = .045) and mRNA expression (HR = 1.18; P = .05) were associated with a greater risk. CONCLUSIONS Increased methylation of CpG sites in the intron region of ASC is associated with improved outcomes in HF. The associated decrease in ASC expression implicates this inflammatory mediator as a possible driver of HF outcomes and may represent a therapeutic target.

ASC Methylation and Interleukin-1β Are Associated with Aerobic Capacity in Heart Failure.

Background Aerobic capacity, as measured by peak oxygen uptake (V˙O2), is one of the most powerful predictors of prognosis in heart failure (HF). Inflammation is a key factor contributing to alterations in aerobic capacity, and interleukin (IL)-1 cytokines are implicated in this process. The adaptor protein ASC is necessary for inflammasome activation of IL-1&bgr; and IL-18. ASC expression is controlled through epigenetic modification; lower ASC methylation is associated with worse outcomes in HF. The purpose of this study is to examine the relationships between ASC methylation, IL-1&bgr;, and IL-18 with V˙O2peak in persons with HF. Methods This study examined the relationship between ASC methylation, IL-1&bgr;, and IL-18 with V˙O2peak in 54 stable outpatients with HF. All participants were NYHA class II or III, not engaged in an exercise program, and physically able to complete an exercise treadmill test. Results Mean V˙O2peak was 16.68 ± 4.7 mL·kg−1·min−1. V˙O2peak was positively associated with mean percent ASC methylation (r = 0.47, P = 0.001) and negatively associated with IL-1&bgr; (r = −0.38, P = 0.007). Multiple linear regression models demonstrated that V˙O2peak increased by 2.30 mL·kg−1·min−1 for every 1% increase in ASC methylation and decreased by 1.91 mL·kg−1·min−1 for every 1 pg·mL−1 increase in plasma IL-1&bgr;. Conclusions Mean percent ASC methylation and plasma IL-1&bgr; levels are associated with clinically meaningful differences in V˙O2peak in persons with HF. Inflammasome activation may play a mechanistic role in determining aerobic capacity. ASC methylation is a potentially modifiable mechanism for reducing the inflammatory response, thereby improving aerobic capacity in HF.

Increased Inflammation in Pericardial Fluid Persists 48 Hours after Cardiac Surgery

Cardiac surgery causes direct trauma to cardiac tissue, breaches the pericardium, and disrupts the normal composition of the fluid largely produced from the myocardial interstitium and epicardial and visceral pericardium. This leaves the heart exposed to pericardial fluid (PCF) and mediastinal contents comprising inflammatory cells and their products that now bathe the heart. This can potentially have adverse effects on the thin-walled atria leading to postoperative atrial fibrillation (AF).1 After cardiac surgery, the pericardium remains open, and chest drains are routinely placed to prevent fluid accumulation around the heart. Here, we describe the concentration and trajectory of blood proinflammatory factors in the PCF after cardiac surgery over time. The study protocol was approved by the University of Alabama at Birmingham. Institutional Review Board approval and informed consent were obtained from all patients. PCF (n=19) was collected immediately after pericardiotomy (time 0) and from the pericardial drains at times 4, 12, 24, and 48 hours after surgery. The patient population (mean age, 60±3 years) included 26.3% women and 26.3% blacks undergoing cardiac surgery (coronary artery bypass graft, n=14; coronary artery bypass graft+valve procedure, n=3; valve procedure alone, n=2). Patients with ventricular assist devices, AF surgery, thoracic aorta surgery, and AF within 6 months prior were excluded. All participants who had valve replacement (with or without coronary artery bypass graft) underwent on-pump surgeries. Of the patients undergoing coronary artery bypass …

20 Things You Didn't Know About Exercise.

1. Exercise for your health is ancient history! Ancient physicians, including Hippocrates (460Y370 BCE) and Galen (129Y200 CE) prescribed exercise to promote health and cure disease. 2. What’s in a name? The President’s Council on Fitness, Sports and Nutrition (2010), formerly thePresident’s Council onPhysical Fitness andSports (1968), formerly thePresident’sCouncil on Physical Fitness (1963), was first created in 1956 by Dwight D. Eisenhower as the President’s Council on Youth Fitness in reaction to the poor state of youth fitness in theUnited States. This council began a pilot study of a national testing programwith 8500 children, known today as the President’s Challenge. 3. A way to stimulate your cellular appetite? Aerobic exercise promotes autophagy, which can lead to increased plasticity in the brain and removal of deranged proteins and other cellular debris implicated in neurodegenerative diseases, such as Alzheimer’s. (What was that last part again?)