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Background In participants with concomitant chronic coronary disease and advanced chronic kidney disease (CKD), the effect of treatment strategies on the timing of dialysis initiation is not well characterized. Methods and Results In ISCHEMIA-CKD (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches-Chronic Kidney Disease), 777 participants with advanced CKD and moderate or severe ischemia were randomized to either an initial invasive or conservative management strategy. Herein, we compare the proportion of randomized participants with non-dialysis-requiring CKD at baseline (n=362) who initiated dialysis and compare the time to dialysis initiation between invasive versus conservative management arms. Using multivariable Cox regression analysis, we also sought to identify the effect of invasive versus conservative chronic coronary disease management strategies on dialysis initiation. At a median follow-up of 23 months (25th-75th interquartile range, 14-32 months), dialysis was initiated in 18.9% of participants (36/190) in the invasive strategy and 16.9% of participants (29/172) in the conservative strategy (P=0.22). The median time to dialysis initiation was 6.0 months (interquartile range, 3.0-16.0 months) in the invasive group and 18.2 months (interquartile range, 12.2-25.0 months) in the conservative group (P=0.004), with no difference in procedural acute kidney injury rates between the groups (7.8% versus 5.4%; P=0.26). Baseline clinical factors associated with earlier dialysis initiation were lower baseline estimated glomerular filtration rate (hazard ratio [HR] associated with 5-unit decrease, 2.08 [95% CI, 1.72-2.56]; P

Exercise provides a robust physiological stimulus that evokes cross-talk among multiple tissues that when repeated regularly (i.e., training) improves physiological capacity, benefits numerous organ systems, and decreases the risk for premature mortality. However, a gap remains in identifying the detailed molecular signals induced by exercise that benefits health and prevents disease. The Molecular Transducers of Physical Activity Consortium (MoTrPAC) was established to address this gap and generate a molecular map of exercise. Preclinical and clinical studies will examine the systemic effects of endurance and resistance exercise across a range of ages and fitness levels by molecular probing of multiple tissues before and after acute and chronic exercise. From this multi-omic and bioinformatic analysis, a molecular map of exercise will be established. Altogether, MoTrPAC will provide a public database that is expected to enhance our understanding of the health benefits of exercise and to provide insight into how physical activity mitigates disease.

BackgroundData from a cardiopulmonary exercise (CPX) test are used to determine prognosis in patients with chronic heart failure (HF). However, few published studies have simultaneously compared the relative prognostic strength of multiple CPX variables.ObjectivesThe study sought to describe the strength of the association among variables measured during a CPX test and all-cause mortality in patients with HF with reduced ejection fraction (HFrEF), including the influence of sex and patient effort, as measured by respiratory exchange ratio (RER).MethodsAmong patients (n = 2,100, 29% women) enrolled in the HF-ACTION (HF-A Controlled Trial Investigating Outcomes of exercise traiNing) trial, 10 CPX test variables measured at baseline (e.g., peak oxygen uptake [Vo2], exercise duration, percent predicted peak Vo2 [%ppVo2], ventilatory efficiency) were examined.ResultsOver a median follow-up of 32 months, there were 357 deaths. All CPX variables, except RER, were related to all-cause mortality (all p < 0.0001). Both %ppVo2 and exercise duration were equally able to predict (Wald chi-square: ∼141) and discriminate (c-index: 0.69) mortality. Peak Vo2 (ml·kg(-1)·min(-1)) was the strongest predictor of mortality among men (Wald chi-square: 129) and exercise duration among women (Wald chi-square: 41). Multivariable analyses showed that %ppVo2, exercise duration, and peak Vo2 (ml·kg(-1)·min(-1)) were similarly able to predict and discriminate mortality. In men, a 10% 1-year mortality rate corresponded to a peak Vo2 of 10.9 ml·kg(-1)·min(-1) versus 5.3 ml·kg(-1)·min(-1) in women.ConclusionsPeak Vo2, exercise duration, and % ppVo2 carried the strongest ability to predict and discriminate the likelihood of death in patients with HFrEF. The prognosis associated with a given peak Vo2 differed by sex. (Exercise Training Program to Improve Clinical Outcomes in Individuals With Congestive Heart Failure; NCT00047437).

The article discusses the relationship between inducible ischemia severity, coronary artery disease (CAD) extent, and exercise capacity in patients with chronic coronary disease. The study, called ISCHEMIA, analyzed data from 858 participants who underwent exercise treadmill testing. The results showed that neither ischemia severity nor CAD extent were significant predictors of aerobic exercise capacity beyond demographic and clinical characteristics. These findings are surprising given the expected relationship between exercise limitation and CAD, but recent studies have also questioned this relationship. The study has some limitations, such as the skewed cohort and the lack of follow-up exercise testing. Overall, the article provides valuable insights into the association between ischemia severity, CAD extent, and exercise capacity in patients with chronic coronary disease. [Extracted from the article]

The beneficial effects of physical activity (PA) are well documented, yet the mechanisms by which PA prevents disease and improves health outcomes are poorly understood. To identify major gaps in knowledge and potential strategies for catalyzing progress in the field, the NIH convened a workshop in late October 2014 entitled "Understanding the Cellular and Molecular Mechanisms of Physical Activity-Induced Health Benefits." Presentations and discussions emphasized the challenges imposed by the integrative and intermittent nature of PA, the tremendous discovery potential of applying "-omics" technologies to understand interorgan crosstalk and biological networking systems during PA, and the need to establish an infrastructure of clinical trial sites with sufficient expertise to incorporate mechanistic outcome measures into adequately sized human PA trials. Identification of the mechanisms that underlie the link between PA and improved health holds extraordinary promise for discovery of novel therapeutic targets and development of personalized exercise medicine.

BackgroundIn the main Digitalis Investigation Group (DIG) trial, digoxin reduced the risk of 30-day all-cause hospitalization in older systolic heart failure patients. However, this effect has not been studied in older diastolic heart failure patients.MethodsIn the ancillary DIG trial, of the 988 patients with chronic heart failure and preserved (> 45%) ejection fraction, 631 were age ≥ 65 years (mean age 73 years, 45% women, 12% non-whites), of whom 311 received digoxin.ResultsAll-cause hospitalization 30-day post randomization occurred in 4% of patients in the placebo group and 9% each among those in the digoxin group receiving 0.125 mg and ≥ 0.25 mg a day dosage (P = .026). Hazard ratios (HR) and 95% confidence intervals (CI) for digoxin use overall for 30-day, 3-month, and 12-month all-cause hospitalizations were 2.46 (1.25-4.83), 1.45 (0.96-2.20) and 1.14 (0.89-1.46), respectively. There was one 30-day death in the placebo group. Digoxin-associated HRs (95% CIs) for 30-day hospitalizations due to cardiovascular, heart failure, and unstable angina causes were 2.82 (1.18-6.69), 0.51 (0.09-2.79), and 6.21 (0.75-51.62), respectively. Digoxin had no significant association with 30-day all-cause hospitalization among younger patients (6% vs 7% for placebo; HR 0.80; 95% CI, 0.36-1.79).ConclusionsIn older patients with chronic diastolic heart failure, digoxin increased the risk of 30-day all-cause hospital admission, but not during longer follow-up. Although chance finding due to small sample size is possible, these data suggest that unlike in systolic heart failure, digoxin may not reduce 30-day all-cause hospitalization in older diastolic heart failure patients.

BackgroundHeart failure is the leading cause for hospital readmission, the reduction of which is a priority under the Affordable Care Act. Digoxin reduces 30-day all-cause hospital admission in chronic systolic heart failure. Whether digoxin is effective in reducing readmission after hospitalization for acute decompensation remains unknown.MethodsOf the 5153 Medicare beneficiaries hospitalized for acute heart failure and not receiving digoxin, 1054 (20%) received new discharge prescriptions for digoxin. Propensity scores for digoxin use, estimated for each of the 5153 patients, were used to assemble a matched cohort of 1842 (921 pairs) patients (mean age, 76 years; 56% women; 25% African American) receiving and not receiving digoxin, who were balanced on 55 baseline characteristics.ResultsThirty-day all-cause readmission occurred in 17% and 22% of matched patients receiving and not receiving digoxin, respectively (hazard ratio [HR] for digoxin, 0.77; 95% confidence interval [CI], 0.63-0.95). This beneficial association was observed only in those with ejection fraction

ObjectivesThis study sought to examine the relationship between niacin treatment, lipoproteins, and cardiovascular (CV) outcomes in this secondary analysis of the AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides and Impact on Global Health Outcomes) trial.BackgroundDuring a 3-year follow-up in 3,414 patients with established CV disease and low high-density lipoprotein cholesterol (HDL-C) levels, combined niacin + low-density lipoprotein cholesterol (LDL-C)-lowering therapy did not reduce CV events compared with LDL-C-lowering therapy alone.MethodsSubjects taking simvastatin and/or ezetimibe were randomized to receive extended-release (ER) niacin 1,500 to 2,000 mg or minimal immediate-release niacin (≤ 150 mg) as placebo at bedtime. LDL-C levels in both groups were maintained from 40 to 80 mg/dl. Hazard ratios were estimated by using Cox proportional hazards models for relationships between lipoproteins and the composite endpoint of CV death, myocardial infarction, acute coronary syndrome, ischemic stroke, or symptom-driven revascularization.ResultsCV outcomes were not associated with ER niacin in any baseline lipoprotein tertile. In a subset of patients in both the highest triglyceride (≥ 198 mg/dl) and lowest HDL-C (

BackgroundAnemia is associated with decreased functional capacity, reduced quality of life, and worsened outcomes among patients with heart failure (HF) due to reduced left ventricular ejection fraction (HFREF). We sought to evaluate the independent effect of anemia on clinical outcomes among those with HFREF.HypothesisAnemia is associated with cardiovascular events in patients with heart failure.MethodsThe HF-ACTION trial was a prospective, randomized trial of exercise therapy vs usual care in 2331 patients with HFREF. Patients with New York Heart Association class II to IV HF and left ventricular ejection fractions of ≤ 35% were recruited. Hemoglobin (Hb) was measured up to 1 year prior to entry and was stratified by quintile. Anemia was defined as baseline Hb

Although physical activity (PA) is an important determinant of exercise capacity, the association between these constructs is modest. The authors investigated the associations of self-reported and objectively measured PA with maximal and submaximal tests of exercise capacity. Participants aged ≥40 years (N = 413; 49.6% female) completed a PA questionnaire, wore a uniaxial accelerometer (5.2 ± 1.1 days), and performed maximal (cardiopulmonary exercise test [CPET]) and submaximal (long-distance corridor walk) tests with indirect calorimetry (oxygen consumption, VO2). Linear regression models were fitted to assess the variation in exercise capacity explained (partial eta squared, η²) by PA variables. Accelerometer-measured vigorous (η² = 22% female; η² = 16% male) and total PA (η² = 17% female; η² = 13% male) explained the most variance in CPET VO2 (p < .001). All η² values were lower for long-distance corridor walk VO2 (η² ≤ 11%). Age contributed more to CPET VO2 than any PA variable in males (η² = 32%), but not in females (η² = 19%). Vigorous and total PA play important roles in CPET VO2 in mid to late life. [ABSTRACT FROM AUTHOR]