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Although healthcare workers may be aware of the risks of physical inactivity, their levels of physical activity (PA) are similar to those of all US adults, with less than half engaging in sufficient PA. The purpose of this health promotion was to encourage daily PA among employees in a large academic healthcare system. We also tested whether individualized progress updates further influenced PA. This 10-week program was available to all employees of NYU Langone Health. Employees could sync their phone or accelerometer via app or web browser to count.it – the vendor chosen to monitor and manage step counts. Participants were asked to voluntarily provide basic information (age, sex, job role, work location) and complete the Physical Activity Vital Sign (minutes/week and intensity of PA) at enrollment and 10 weeks. For 10 weeks, participants were sent a message through their employee ‘MyChart’ portal with a link to information on the benefits of PA, and a reminder of that week’s step-count challenge. Those meeting criteria for weekly challenges were included in gift card raffles. Participants were randomized 1:1 to receive the standard message ± additional emails detailing their progress. 3528 employees registered to participate (8% of all employees) although active users diminished over time (1225 at week 10). Average daily steps remained stable throughout (7319 + 4540 in week 1, 7229 + 5010 in week 10). Although there was no difference in any individual week, receipt of personalized feedback was associated with significantly higher average step counts throughout the 10-wk intervention as a whole (P = 0.01). Age and an urban work location were positively associated with steps, while female sex and a clerical job role were negatively associated with steps counts (all P < 0.005). Our findings provide important insight for workplace interventions to promote PA. They further suggest specific groups that may benefit from targeted efforts. [ABSTRACT FROM AUTHOR]

Aspirin's clinical efficacy may be influenced by body weight and mass. Although inadequate platelet inhibition by aspirin is suggested as responsible, evidence for this in non-diabetic patients is sparse. We investigated the influence of body weight and mass on aspirin's inhibition of platelet aggregation in healthy adults without diabetes. Cohort one (NYU, n = 84) had light transmission aggregometry (LTA) of platelet-rich plasma to submaximal adenosine diphosphate (ADP) and arachidonic acid (AA) before and following 1 week of daily 81 mg non-enteric coated aspirin. Subjects in the validation cohort (Duke, n = 66) were randomized to 81 mg or 325 mg non-enteric coated aspirin for 4 weeks, immediately followed by 4 weeks of the other dose, with LTA to submaximal collagen, ADP, and AA before and after each dosage period. Body mass index (BMI) range was 18.0–57.5 kg/m2 and 25% were obese. Inhibition of platelet aggregation was similar irrespective of BMI, body weight and aspirin dose. There was no correlation between platelet aggregation before or after aspirin with BMI or body weight. Our data demonstrate that aspirin produces potent inhibition of direct and indirect COX1-mediated platelet aggregation in healthy adults without diabetes regardless of body weight or mass – suggesting that other mechanisms explain lower preventive efficacy of low-dose aspirin with increasing body weight/mass. [ABSTRACT FROM AUTHOR]

Peripheral artery disease (PAD) is a systemic manifestation of atherosclerosis that is associated with a high risk of major adverse cardiovascular events (MACE). LDL aggregation contributes to atherosclerotic plaque progression and may contribute to plaque instability. We aimed to determine if LDL aggregation is associated with MACE in patients with PAD undergoing lower extremity revascularization (LER). Two hundred thirty-nine patients with PAD undergoing LER had blood collected at baseline and were followed prospectively for MACE (myocardial infarction, stroke, cardiovascular death) for one year. Nineteen age, sex and LDL-C-matched control subjects without cardiovascular disease also had blood drawn. Subject LDL was exposed to sphingomyelinase and LDL aggregate size measured via dynamic light scattering. Mean age was 72.3 ± 10.9 years, 32.6% were female, and LDL-cholesterol was 68 ± 25 mg/dL. LDL aggregation was inversely associated with triglycerides, but not associated with demographics, LDL-cholesterol or other risk factors. Maximal LDL aggregation occurred significantly earlier in subjects with PAD than in control subjects. 15.9% of subjects experienced MACE over one year. The 1st tertile (shortest time to maximal aggregation) exhibited significantly higher MACE (25% vs. 12.5% in tertile 2 and 10.1% in tertile 3, p = 0.012). After multivariable adjustment for demographics and CVD risk factors, the hazard ratio for MACE in the 1st tertile was 4.57 (95% CI 1.60–13.01; p = 0.004) compared to tertile 3. Inclusion of LDL aggregation in the Framingham Heart Study risk calculator for recurrent coronary heart disease events improved the c-index from 0.57 to 0.63 (p = 0.01). We show that in the setting of very well controlled LDL-cholesterol, patients with PAD with the most rapid LDL aggregation had a significantly elevated MACE risk following LER even after multivariable adjustment. This measure further improved the classification specificity of an established risk prediction tool. Our findings support broader investigation of this assay for risk stratification in patients with atherosclerotic CVD. Image 1 • Low-density lipoprotein (LDL) aggregation was markedly increased in subjects with peripheral artery disease (PAD) relative to subjects without atherosclerotic cardiovascular disease. • LDL aggregation is associated with major adverse cardiovascular events (MACE) risk over 1 year after lower extremity revascularization. • Incorporation of LDL aggregation improves prediction of events in these patients. [ABSTRACT FROM AUTHOR]

An independent association of body mass index (BMI) with atherosclerotic cardiovascular disease is somewhat controversial and may differ by vascular bed. Sex-specific risk factors for atherosclerosis may further modify these associations. Obesity and peripheral artery disease (PAD) are both more prevalent in women. We sought to determine the association between PAD and BMI using a very large population-based study. Self-referred individuals at >20,000 US sites completed medical questionnaires including height and weight, and were evaluated by screening ankle brachial indices (ABI) for PAD (ABI<0.9). Among 3,250,350 individuals, the mean age was 63.1 ± 10.5 years and 65.5% were women. The mean BMI was 27.7 ± 5.8 kg/m2. 27.8% of participants were obese (BMI ≥30 kg/m2) – 27.6% females, 28.1% males. Overweight individuals (BMI 25–29.9 kg/m2) exhibited the lowest prevalence of PAD. There was a J-shaped association of BMI with prevalent PAD. After adjustment for age and cardiovascular risk factors, underweight was associated with similarly increased odds of PAD (1.72 vs. 1.39, women and men, respectively). The association of obesity with PAD was predominant in women, with only a slight association of increasing BMI with PAD in men (OR = 2.98 vs. 1.37 for BMI ≥40 kg/m2). Our study suggests that increasing BMI is a robust independent risk factor for PAD only in women. This observation requires validation, but highlights the need for further research on sex-specific risk and mechanisms of atherosclerosis. Image 1 • In >3 million persons, there was a J-shaped association of BMI with prevalent PAD. • Overweight individuals (BMI 25–29.9 kg/m2) exhibited the lowest PAD prevalence. • The association of obesity with PAD was markedly stronger in women than men. [ABSTRACT FROM AUTHOR]

Mechanisms explaining the relationship between obesity and cardiovascular disease (CVD) are needed. Despite growing recognition of the importance of the anucleate platelet transcriptome, low levels of RNA in platelets make assessment difficult. We sought to perform unbiased platelet RNA profiling in obesity by performing a prospective study of severe obesity and weight loss via bariatric surgery on platelet characteristics and mRNA profile in 26 pre-menopausal, non-diabetic women (31.6 ± 8.4 years; BMI 43.0 ± 6.5 kg/m2) who underwent sleeve gastrectomy. Totally, 10 women of similar age with normal BMI served as controls. Platelet activation via flow cytometry was assessed before and after surgery. RNA-sequencing (RNAseq) was performed on platelet isolates from a subset of 13 subjects (eight obese women and five normal-BMI subjects). Platelet count, size, and age did not differ between control and obese women. However, platelet surface P-selectin and CD40 were higher in obesity. RNAseq demonstrated 629 differentially abundant transcripts in obesity. Notably, S100A9 and AGER, established markers of cardiovascular risk, were two of the most highly upregulated transcripts (each > 2.5 fold). At 6 months post-operatively, subjects lost 26.1 ± 5.8% body weight and inducible platelet P-selectin expression was reduced. Expression of 170 transcripts was affected by surgery, but only a small fraction (46/629) were genes found altered in obesity. We demonstrate that obesity is associated with an altered platelet transcriptome and increased platelet activation, which is partly attenuated by bariatric surgery. These observations suggest that platelets may contribute to increased cardiovascular risk in obesity through a variety of mechanisms. [ABSTRACT FROM AUTHOR]

Background: Although metabolic surgery was originally performed to treat hypercholesterolemia, the effects of contemporary bariatric surgery on serum lipids have not been systematically characterized.Methods: MEDLINE, EMBASE, and Cochrane databases were searched for studies with ≥ 20 obese adults undergoing bariatric surgery (Roux-en-Y gastric bypass [RYGBP], adjustable gastric banding, biliopancreatic diversion [BPD], or sleeve gastrectomy). The primary outcome was change in lipids from baseline to 1 year after surgery. The search yielded 178 studies with 25,189 subjects (preoperative body mass index 45.5 ± 4.8 kg/m(2)) and 47,779 patient-years of follow-up.Results: In patients undergoing any bariatric surgery, compared with baseline, there were significant reductions in total cholesterol (TC; -28.5mg/dL), low-density lipoprotein cholesterol (LDL-C; -22.0 mg/dL), triglycerides (-61.6 mg/dL), and a significant increase in high-density lipoprotein cholesterol (6.9 mg/dL) at 1 year (P < .00001 for all). The magnitude of this change was significantly greater than that seen in nonsurgical control patients (eg LDL-C; -22.0 mg/dL vs -4.3 mg/dL). When assessed separately, the magnitude of changes varied greatly by surgical type (Pinteraction < .00001; eg, LDL-C: BPD -42.5 mg/dL, RYGBP -24.7 mg/dL, adjustable gastric banding -8.8 mg/dL, sleeve gastrectomy -7.9 mg/dL). In the cases of adjustable gastric banding (TC and LDL-C) and sleeve gastrectomy (LDL-C), the response at 1 year following surgery was not significantly different from nonsurgical control patients.Conclusions: Contemporary bariatric surgical techniques produce significant improvements in serum lipids, but changes vary widely, likely due to anatomic alterations unique to each procedure. These differences may be relevant in deciding the most appropriate technique for a given patient. [ABSTRACT FROM AUTHOR]

Nut consumption has been associated with lower risk of coronary heart disease and all-cause mortality. The association between nut intake and peripheral arterial disease (PAD) is uncertain. Objective: We sought to investigate the association between nut consumption and presence of prevalent PAD in a large cross-sectional sample. Methods: Self-referred participants at > 20,000 US sites who completed a medical and lifestyle questionnaire were evaluated by screening ankle brachial indices for PAD. Multivariable logistic regression analysis was used to estimate odds of PAD in different nut consumption categories. Results: Among 3,312,403 individuals, mean age was 63.6 ± 10.6 years and 62.8% were female. There were 219,527 cases of PAD. After multivariable adjustment there was an inverse association of nut intake with PAD. Compared to subjects with consumption of nuts < once/month, daily nut consumption was associated with a 21% (95% CI 20%–23%) lower odds of having PAD. Conclusion: These observations suggest the need for more rigorous testing evaluating the role of nuts in PAD prevention. [ABSTRACT FROM AUTHOR]

Background Obesity, metabolic syndrome (MS) and dyslipidemia are independent risk factors for cardiovascular disease. Bariatric surgery is increasingly recognized as an effective intervention for improving each of these risk factors. There are sparse data on the long-term durability of metabolic changes associated with bariatric surgery, in particular with laparoscopic gastric banding (LGB). Our objective was to evaluate the durability of metabolic changes associated with LGB in nonmorbid obesity. Methods Fifty obese patients (BMI 30–40) with ≥1 obesity-related comorbidity were prospectively followed for five years. At follow-up, subjects underwent fasting blood measures, including lipid NMR spectroscopy and standard lipid profile. Results Forty-seven patients (45 female, mean age 43.8 years) completed four years follow-up (46 completed five years). Baseline BMI was 35.1 ± 2.6. Subjects exhibited mean weight loss of 22.3 ± 7.9 kg (22.9 ± 7.4%) at year one and maintained this (19.8 ± 10.2%) over five years. At baseline, 43% (20/47) of subjects met criteria for MS. This was reduced to 15% (7/47) at year one and remained reduced over five years (13%, 6/46) ( p < 0.001). There were reductions in triglycerides ( p < 0.001) and increases in HDL cholesterol (HDL-C, p < 0.001) and HDL particle concentration ( p = 0.02), with a trend toward increased HDL particle size ( p = 0.06) at year five. Changes in triglycerides and HDL-C were more prominent in patients with MS at baseline, but unassociated with weight loss or waist circumference. Changes in HDL particle size and concentration were not associated with MS status, weight loss, waist circumference, or statin use. Conclusions LGB produces significant weight loss, resolution of MS and changes in lipid profile suggestive of beneficial HDL remodeling. These changes persist five years following LGB. [ABSTRACT FROM AUTHOR]

Background: Chronic inflammation may contribute to insulin resistance (IR), metabolic syndrome and atherosclerosis although evidence of causality is lacking in humans. We hypothesized that very low-dose experimental endotoxemia would induce adipose tissue inflammation and systemic IR during a low-grade but asymptomatic inflammatory response and thus provide an experimental model for future tests of pharmacologic and genomic modulation of cardio-metabolic traits in humans. Methods: Ten healthy, human volunteers (50% male, 90% Caucasian, mean age 22.7 ± 3.8) were randomized in a double-masked, placebo-controlled, crossover study to separate 36-hour inpatient visits (placebo versus intravenous-LPS 0.6 ng/kg). We measured clinical symptoms via the McGill pain questionnaire and serial vital signs. Plasma and serum were collected for measurement of cytokines, C-reactive protein, insulin and glucose, serial whole blood & subcutaneous adipose tissue mRNA expression were measured by real-time PCR. HOMA-IR, a well-validated measure of IR was calculated to estimate insulin resistance, and frequently sampled intravenous glucose tolerance testing (FSIGTT) was performed to confirm an insulin resistant state. We performed ANOVA and within subject ANOVA to understand the differences in cytokines, adipose tissue inflammation and IR before and after LPS or placebo. Results: There was no significant difference between placebo and LPS in clinical responses of symptom scores, body temperature or heart rate. However, low-dose endotoxemia induced a rapid and transient 25-fold induction of plasma TNF-alpha and 100-fold increase in plasma IL-6 (Figure 1B) (p < 0.001 for both) both peaking at two hours, followed by modest inflammation in adipose tissue with increases in mRNA levels of several inflammatory genes known to modulate adipose and systemic insulin resistance. Adipose tissue mRNA levels of IL-6 (peak 6-fold, ANOVA F = 27.5, p < 0.001) and TNF-alpha (peak 1.8-fold, F = 2.9, p = 0.01) increased with MCP-1 (peak 10-fold, F = 5.6, p < 0.01) and fractalkine (CX3CL1) (peak 15-fold, F = 13.3, p < 0.001). Finally, HOMA-IR was 32% higher following LPS compared to placebo (p < 0.01) and insulin sensitivity declined by 21% following LPS compared to placebo (p < 0.05). Conclusions: We present a low dose human endotoxemia model of inflammation which induces adipose tissue inflammation and systemic insulin resistance in the absence of overt clinical response. Such a model has the potential for broad and safe application in the study of novel therapeutics and genomic influences in cardio-metabolic disease. [ABSTRACT FROM AUTHOR]

Abstract: Elevated plasma fibrinogen is a prothrombotic risk factor for cardiovascular disease (CVD). Recent small studies report that fibrinogen oxidative modifications, specifically tyrosine residue nitration, can occur in inflammatory states and may modify fibrinogen function. HDL cholesterol is inversely related to CVD and suggested to reduce the oxidation of LDL cholesterol, but whether these antioxidant functions extend to fibrinogen modifications is unknown. We used a recently validated ELISA to quantify nitrated fibrinogen during experimental human endotoxemia (N =23) and in a cohort of healthy adults (N =361) who were characterized for inflammatory and HDL parameters as well as subclinical atherosclerosis measures, carotid artery intima-medial thickness (IMT) and coronary artery calcification (CAC). Fibrinogen nitration increased following endotoxemia and directly correlated with accelerated ex vivo plasma clotting velocity. In the observational cohort, nitrated fibrinogen was associated with levels of CRP and serum amyloid A. Nitrated fibrinogen levels were not lower with increasing HDL cholesterol and did not associate with IMT and CAC. In humans, fibrinogen nitration was induced during inflammation and was correlated with markers of inflammation and clotting function but not HDL cholesterol or subclinical atherosclerosis in our modest sample. Inflammation-induced fibrinogen nitration may be a risk factor for promoting CVD events. [Copyright &y& Elsevier]

The World Health Organization has stated that the workplace is an ideal setting to address common health concerns. A health promotion intervention focusing on improving physical activity levels in diverse employees working in large healthcare system may lead to positive and permanent health behavior changes. Objectives: This study aimed to describe the implementation of a workplace health promotion to address low levels of physical activity (PA). Methods: Using the Exploration, Preparation, Implementation, Sustainment (EPIS) framework, we implemented and evaluated a 10-week workplace step-count challenge to promote PA. All health system employees invited to participate. Data were collected on the exploration, preparation, and implementation phases. Results: During exploration, we recognized inadequate PA among employees. Meetings with key personnel were held to determine details of the health promotion and obtain support. We pursued a step-count PA intervention, capitalizing on employee ownership of smartphones with accelerometers. Vendors to host the intervention were evaluated. All employees were invited to participate. Participants received weekly messages about improving PA and notifications of weekly challenges. Exit interviews provided feedback and suggestions. Conclusions: A workplace health promotion focused on employee PA is feasible using EPIS. [ABSTRACT FROM AUTHOR]

Aim: The Diabetes risk index (DRI) is a composite of NMR-measured lipoproteins and branched chain amino acids predictive of diabetes mellitus development. Bariatric surgery is indicated in patients with severe obesity, many of whom are at high-risk for developing diabetes. Substantial weight loss occurs following bariatric surgery and sustained weight loss likely contributes to reductions in the development of diabetes and cardiovascular disease. However, some evidence suggests that bariatric surgical procedures themselves may contribute to reducing risk of these conditions independent of weight loss. We aimed to investigate DRI and its association with reductions in body weight and adiposity over one year following bariatric surgery. Methods: We examined 51 severely obese premenopausal women without diabetes. DRI, BMI, body weight and waist measurements were made before and at 1, 6 and 12 months after Roux-en-Y Gastric Bypass (RYGB) or Sleeve Gastrectomy. Values were compared to healthy women with normal BMI (18.5–24.9 kg/m2; n = 15). Results: Non-diabetic women with severe obesity (BMI 44.7 ± 6.2 kg/m2) exhibited significantly elevated DRI scores prior to surgery versus controls (35 [26, 39] vs 12 [1, 20]; p < 0.0001). At 1 month after surgery, BMI decreased 5.1 ± 1.1 kg/m2, but DRI decreased so that it no longer differed from that of normal BMI controls (1.9 [1, 17] vs control 12 [1, 20]; p = 0.35). Subjects continued to lose weight, whereas DRI remained similar, throughout follow-up with DRI 1.0 [1, 7] at 12 months. Changes in DRI did not correlate with changes in BMI, body weight or waist circumference at any time during follow-up. There was no difference in change in DRI between surgical procedures or pre-operative metabolic syndrome status. Conclusions: Our analysis of DRI scores supports the capacity of bariatric surgery to reduce risk of developing diabetes in severely obese individuals. Our findings suggest that bariatric surgical techniques may have inherent effects that improve cardiometabolic risk independent of reductions in body weight or adiposity. [ABSTRACT FROM AUTHOR]

Abstract: The primary purpose of this study was to examine the effect of energy restriction on antioxidant capacity in trained athletes. Secondly, our study determined whether dietary protein source influenced the antioxidant response, performance, and immunity. Twenty male cyclists consumed either whey or casein supplement (40 g/day) in addition to their diet for 17 days. All subjects subsequently underwent 4 days of energy restriction using a formula diet (20 kcal/kg) while continuing protein supplementation. Energy restriction caused 2.7 ± 0.3 kg weight loss, increased lymphocyte total glutathione (tGSH) 37%, red blood cell glutathione peroxidase 48%, plasma cysteine 12%, and decreased whole blood reduced to oxidized GSH (rGSH/GSSG) ratio by 52%. The only immunity factor altered by energy restriction was an increase in stimulated phagocytosis (65%). Acute submaximal exercise reduced blood tGSH but increased glutathione peroxidase. Performance of a high intensity cycle test following 45 min of moderate exercise tended to be reduced by energy restriction (P = 0.06) but was unaffected by protein source. Energy restriction caused a negative nitrogen balance with no difference from dietary protein source. In conclusion, acute energy restriction increased plasma cysteine and several markers of the glutathione antioxidant system in trained athletes. A high cysteine dietary protein source did not influence these responses. [Copyright &y& Elsevier]

Atherosclerosis is a disease of chronic inflammation. We investigated the roles of the cytokines IL-4 and IL-13, the classical activators of STAT6, in the resolution of atherosclerosis inflammation. Using Il4-/-Il13-/- mice, resolution was impaired, and in control mice, in both progressing and resolving plaques, levels of IL-4 were stably low and IL-13 was undetectable. This suggested that IL-4 is required for atherosclerosis resolution, but collaborates with other factors. We had observed increased Wnt signaling in macrophages in resolving plaques, and human genetic data from others showed that a loss-of-function Wnt mutation was associated with premature atherosclerosis. We now find an inverse association between activation of Wnt signaling and disease severity in mice and humans. Wnt enhanced the expression of inflammation resolving factors after treatment with plaque-relevant low concentrations of IL-4. Mechanistically, activation of the Wnt pathway following lipid lowering potentiates IL-4 responsiveness in macrophages via a PGE2/STAT3 axis. [ABSTRACT FROM AUTHOR]

Chronic inflammation drives many obesity‐associated conditions including atherosclerosis. GlycA, a marker of systemic inflammation with lower intra‐individual variability than high sensitivity C‐reactive protein, is independently associated with incident cardiovascular events and mortality. Although GlycA is elevated in obesity, correlations with anthropometric measures are modest and the effect of body weight loss on GlycA is untested. Obese (body mass index [BMI] 44.6 ± 6.6 kg/m2), non‐diabetic women (33.7 ± 8.2 years) undergoing Roux‐en‐Y gastric bypass (n = 23) or sleeve gastrectomy (n = 31) were prospectively studied at baseline, 6 and 12 months postprocedure. Women with normal BMI (n = 14) served as controls. Bariatric surgery significantly reduced GlycA by 6 months (451 ± 47 μmol/L vs. 383 ± 50 μmol/L; P < 0.001) with further reduction at 12 months (348 ± 41 μmol/L; P < 0.001) and no difference between procedures. At 12 months, despite 41% of surgical subjects maintaining BMI >30 kg/m2, GlycA levels did not differ between surgical and control subjects (P = 0.13). Increased high density lipoprotein particle size was strongly associated with reduced GlycA (r = −0.49; P < 0.001) and was found to mediate up to 43% of its body weight‐loss‐associated fall. This is the first study to demonstrate that surgical body weight loss markedly reduces levels of GlycA. [ABSTRACT FROM AUTHOR]