Obesity and cardiovascular diseases: implications regarding fitness, fatness, and severity in the obesity paradox

Obesity has been increasing in epidemic proportions, with a disproportionately higher increase in morbid or class III obesity, and obesity adversely affects cardiovascular (CV) hemodynamics, structure, and function, as well as increases the prevalence of most CV diseases. Progressive declines in physical activity over 5 decades have occurred and have primarily caused the obesity epidemic. Despite the potential adverse impact of overweight and obesity, recent epidemiological data have demonstrated an association of mild obesity and, particularly, overweight on improved survival. We review in detail the obesity paradox in CV diseases where overweight and at least mildly obese patients with most CV diseases seem to have a better prognosis than do their leaner counterparts. The implications of cardiorespiratory fitness with prognosis are discussed, along with the joint impact of fitness and adiposity on the obesity paradox. Finally, in light of the obesity paradox, the potential value of purposeful weight loss and increased physical activity to affect levels of fitness is reviewed

Developing a framework for the analysis of power through depotentia

Stakeholder participation in tourism policy-making is usually perceived as providing a means of empowerment. However participatory processes drawing upon stakeholders from traditionally empowered backgrounds may provide the means of removing empowerment from stakeholders. Such an outcome would be in contradiction to the claims that participatory processes improve both inclusivity and sustainability. In order to form an understanding of the sources through which empowerment may be removed, an analytical perspective has been developed deriving from Lukes�s views of power dating from 1974. This perspective considers the concept of depotentia as the removal of �power to� without speculating upon the underlying intent and also provides for the multidimensionality of power to be examined within a single study. The application of this analytical perspective has been tested upon findings of the government-commissioned report of the Countryside and Community Research Unit in 2005. The survey and report investigated the progress of Local Access Forums in England created in response to the Countryside and Rights of Way Act 2000. Consideration of the data from this perspective permits the classification of individual sources of depotentia which can each be addressed and potentially enable stakeholder groups to reverse loss of empowerment where it has occurred

Longitudinal algorithms to estimate cardiorespiratory fitness: associations with nonfatal cardiovascular disease and disease-specific mortality

Objectives This study sought to determine the capacity of cardiorespiratory fitness (CRF) algorithms without exercise testing to predict the risk for nonfatal cardiovascular disease (CVD) events and disease-specific mortality. Background Cardiorespiratory fitness (CRF) is not routinely measured, as it requires trained personnel and specialized equipment. Methods Participants were 43,356 adults (21% women) from the Aerobics Center Longitudinal Study, followed up between 1974 and 2003. Estimated CRF was determined on the basis of sex, age, body mass index, waist circumference, resting heart rate, physical activity level, and smoking status. Actual CRF was measured by a maximal treadmill test. Risk reduction per 1-metabolic equivalent increase, discriminative ability (c statistic), and net reclassification improvement were determined. Results During a median follow-up of 14.5 years, 1,934 deaths occurred, 627 due to CVD. In a subsample of 18,095 participants, 1,049 cases of nonfatal CVD events were ascertained. After adjustment for potential confounders, both measured and estimated CRF were inversely associated with risks for all-cause mortality, CVD-related mortality and nonfatal CVD events in men, and all-cause mortality and nonfatal CVD events in women. The risk reduction per 1-metabolic equivalent increase ranged from approximately 10% to 20%. Measured CRF had a slightly better discriminative ability (c statistic) than did estimated CRF, and the net reclassification improvement values in measured CRF versus estimated CRF were 12.3% in men (p < 0.05) and 19.8% in women (p < 0.001). Conclusions These CRF algorithms utilized information routinely collected to obtain an estimate of CRF, which provides a valid indication of health status. In addition to identifying people at risk, this method can provide more appropriate exercise recommendations that reflect initial CRF levels

Multiple functional risk variants in a SMAD7 enhancer implicate a colorectal cancer risk haplotype

Genome-wide association studies (GWAS) of colorectal cancer (CRC) have led to the identification of a number of common variants associated with modest risk. Several risk variants map within the vicinity of TGFβ/BMP signaling pathway genes, including rs4939827 within an intron of SMAD7 at 18q21.1. A previous study implicated a novel SNP (novel 1 or rs58920878) as a functional variant within an enhancer element in SMAD7 intron 4. In this study, we show that four SNPs including novel 1 (rs6507874, rs6507875, rs8085824, and rs58920878) in linkage disequilibrium (LD) with the index SNP rs4939827 demonstrate allele-specific enhancer effects in a large, multi-component enhancer of SMAD7. All four SNPs demonstrate allele-specific protein binding to nuclear extracts of CRC cell lines. Furthermore, some of the risk-associated alleles correlate with increased expression of SMAD7 in normal colon tissues. Finally, we show that the enhancer is responsive to BMP4 stimulation. Taken together, we propose that the associated CRC risk at 18q21.1 is due to four functional variants that regulate SMAD7 expression and potentially perturb a BMP negative feedback loop in TGFβ/BMP signaling pathways

Cardiorespiratory Fitness Is Inversely Associated With the Incidence of Metabolic Syndrome: A Prospective Study of Men and Women

Background - Few studies have reported the relationship between cardiorespiratory fitness and metabolic syndrome incidence, particularly in women. Methods and Results - We prospectively studied 9007 men (mean±SD, age, 44±9 years; body mass index, 25±3 kg/m2) and 1491 women (age, 44±9 years; body mass index, 22±2 kg/m2) who were free of metabolic syndrome and for whom measures of waist girth, resting blood pressure, fasting lipids, and glucose were taken during baseline and follow-up examinations. Baseline cardiorespiratory fitness was quantified as duration of a maximal treadmill test. Metabolic syndrome was defined with NCEP ATP-III criteria. During a mean follow-up of 5.7 years, 1346 men and 56 women developed metabolic syndrome. Age-adjusted incidence rates were significantly lower (linear trend P\u3c0.001) across incremental thirds of fitness in men and women. After further adjustment for potential confounders, multivariable hazard ratios for incident metabolic syndrome among men in the low, middle, and upper thirds of fitness, were 1.0 (referent), 0.74 (95% CI, 0.65 to 0.84), and 0.47 (95% CI, 0.40 to 0.54) linear trend (P\u3c0.001); in women, they were 1.0 (referent), 0.80 (95% CI, 0.44 to 1.46), and 0.37 (95% CI, 0.18 to 0.80) (linear trend P=0.01), respectively. Similar patterns of significant inverse association between fitness and metabolic syndrome incidence were seen when men were stratified on categories of body mass index, age, and number of baseline metabolic risk factors, but patterns were variable in women. Conclusions - Low cardiorespiratory fitness is a strong and independent predictor of incident metabolic syndrome in women and men. Clinicians should consider the potential benefits of greater cardiorespiratory fitness in the primary prevention of metabolic syndrome, particularly among patients who have already begun to cluster metabolic syndrome components

The efficacy of vigorous-intensity exercise as an aid to smoking cessation in adults with elevated anxiety sensitivity: study protocol for a randomized controlled trial

Background: Although cigarette smoking is a leading cause of death and disability in the United States (US), over 40 million adults in the US currently smoke. Quitting smoking is particularly difficult for smokers with certain types of psychological vulnerability. Researchers have frequently called attention to the relation between smoking and anxiety-related states and disorders, and evidence suggests that panic and related anxiety vulnerability factors, specifically anxiety sensitivity (AS or fear of somatic arousal), negatively impact cessation. Accordingly, there is merit to targeting AS among smokers to improve cessation outcome. Aerobic exercise has emerged as a promising aid for smoking cessation for this high-risk (for relapse) group because exercise can effectively reduce AS and other factors predicting smoking relapse (for example, withdrawal, depressed mood, anxiety), and it has shown initial efficacy for smoking cessation. The current manuscript presents the rationale, study design and procedures, and design considerations of the Smoking Termination Enhancement Project (STEP). Methods: STEP is a randomized clinical trial that compares a vigorous-intensity exercise intervention to a health and wellness education intervention as an aid for smoking cessation in adults with elevated AS. One hundred and fifty eligible participants will receive standard treatment (ST) for smoking cessation that includes cognitive behavioral therapy (CBT) and nicotine replacement therapy (NRT). In addition, participants will be randomly assigned to either an exercise intervention (ST+EX) or a health and wellness education intervention (ST+CTRL). Participants in both arms will meet 3 times a week for 15 weeks, receiving CBT once a week for the first 7 weeks, and 3 supervised exercise or health and wellness education sessions (depending on randomization) per week for the full 15-week intervention. Participants will be asked to set a quit date for 6 weeks after the baseline visit, and smoking cessation outcomes as well as putative mediator variables will be measured up to 6 months following the quit date. Discussion: The primary objective of STEP is to evaluate whether vigorous-intensity exercise can aid smoking cessation in anxiety vulnerable adults. If effective, the use of vigorous-intensity exercise as a component of smoking cessation interventions would have a significant public health impact. Specifically, in addition to improving smoking cessation treatment outcome, exercise is expected to offer benefits to overall health, which may be particularly important for smokers. The study is also designed to test putative mediators of the intervention effects and therefore has the potential to advance the understanding of exercise-anxiety-smoking relations and guide future research on this topic

NMDA Receptor Antibodies and Neuropsychiatric Symptoms in Parkinson's Disease

OBJECTIVE: N-methyl-d-aspartate receptor (NMDAR) encephalitis is an autoantibody-mediated neurological syndrome with prominent cognitive and neuropsychiatric symptoms. The clinical relevance of NMDAR antibodies outside the context of encephalitis was assessed in this study. METHODS: Plasma from patients with Parkinson's disease (PD) (N=108) and healthy control subjects (N=89) was screened at baseline for immunoglobulin A (IgA), IgM, and IgG NMDAR antibodies, phosphorylated tau 181 (p-tau181), and the neuroaxonal injury marker neurofilament light (NfL). Clinical assessment of the patients included measures of cognition (Mini-Mental State Examination [MMSE]) and neuropsychiatric symptoms (Hospital Anxiety and Depression Scale; Non-Motor Symptoms Scale for Parkinson's Disease). A subgroup of patients (N=61) was followed annually for up to 6 years. RESULTS: Ten (9%) patients with PD tested positive for NMDAR antibodies (IgA, N=5; IgM, N=6; IgG, N=0), and three (3%) healthy control subjects had IgM NMDAR antibodies; IgA NMDAR antibodies were detected significantly more commonly among patients with PD than healthy control subjects (χ2=4.23, df=1, p=0.04). Age, gender, and disease duration were not associated with NMDAR antibody positivity. Longitudinally, antibody-positive patients had significantly greater decline in annual MMSE scores when the analyses were adjusted for education, age, disease duration, p-tau181, NfL, and follow-up duration (adjusted R2=0.26, p=0.01). Neuropsychiatric symptoms were not associated with antibody status, and no associations were seen between NMDAR antibodies and p-tau181 or NfL levels. CONCLUSIONS: NMDAR antibodies were associated with greater cognitive impairment over time in patients with PD, independent of other pathological biomarkers, suggesting a potential contribution of these antibodies to cognitive decline in PD

Cardiorespiratory fitness, adiposity and incident asthma in adults

Available large-scale prospective studies on adiposity and asthma used body mass index as an indicator of adiposity. Studies involving more accurate measures of adiposity, such as body fat percentage (BF%), are needed to confirm or contrast body mass index - related results. Cardiorepiratory fitness is a strong predictor of morbidity and mortality, and the available literature suggests that moderate-high cardiorespiratory fitness reduces many of the health hazards associated with obesity. The present study aimed: 1) to examine whether cardiorespiratory fitness and/or BF% are associated with subsequent acquisition of asthma in adults; and 2) to test the hypothesis that a high cardiorespiratory fitness level can reduce the risk of incident asthma in individuals with excess adiposity