Changes in Lipid Profile of Obese Patients following Contemporary Bariatric Surgery: A Meta-Analysis
Heffron, Sean P; Parikh, Amar; Volodarskiy, Alexandar; Ren-Fielding, Christine; Schwartzbard, Arthur; Nicholson, Joseph; Bangalore, Sripal
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 AND RESULTS: 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, Bilio-Pancreatic Diversion (BPD), or Sleeve Gastrectomy]. The primary outcome was change in lipids from baseline to one-year after surgery. The search yielded 178 studies with 25,189 subjects (pre-operative BMI 45.5+/-4.8kg/m2) and 47,779 patient-years of follow-up. In patients undergoing any bariatric surgery, compared to baseline, there were significant reductions in total cholesterol (TC; -28.5mg/dL), low density lipoprotein cholesterol (LDL-C; -22.0mg/dL), triglycerides (-61.6mg/dL) and a significant increase in high density lipoprotein cholesterol (6.9mg/dL) at one year (P<0.00001 for all). The magnitude of this change was significantly greater than that seen in non-surgical control patients (eg LDL-C; -22.0mg/dL vs -4.3mg/dL). When assessed separately, the magnitude of changes varied greatly by surgical type (Pinteraction<0.00001; eg LDL-C: BPD -42.5mg/dL, RYGBP -24.7mg/dL, Adjustable Gastric Banding -8.8mg/dL, Sleeve Gastrectomy -7.9mg/dL). In the cases of Adjustable Gastric Banding (TC and LDL-C) and Sleeve Gastrectomy (LDL-C), the response at one year following surgery was not significantly different from non-surgical 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.
PMCID:4988934
PMID: 26899751
ISSN: 1555-7162
CID: 1965332
Greater Frequency of Nut Consumption is Associated with Lower Prevalence of Peripheral Arterial Disease
Heffron, Sean P; Rockman, Caron B; Gianos, Eugenia; Guo, Yu; Berger, Jeffrey S
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+/-10.6years 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
PMCID:4518851
PMID: 25532677
ISSN: 0091-7435
CID: 1416232
Laparoscopic gastric banding resolves the metabolic syndrome and improves lipid profile over five years in obese patients with body mass index 30-40 kg/m
Heffron, Sean P; Singh, Amita; Zagzag, Jonathan; Youn, Heekoung A; Underberg, James A; Fielding, George A; Ren-Fielding, Christine J
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.
PMID: 25240114
ISSN: 0021-9150
CID: 1259062
Fitbit-measured physical activity is inversely associated with incident atrial fibrillation among All of Us participants
Barua, Souptik; Upadhyay, Dhairya; Surapaneni, Aditya; Grams, Morgan; Jankelson, Lior; Heffron, Sean
BACKGROUND:Individuals who report meeting weekly moderate to vigorous physical activity (MVPA) guidelines have lower risk of atrial fibrillation (AF). However existing studies have relied on subjective questionnaires or short-duration (<1 week) objective assessments using accelerometry. The objective of this research was to investigate an association between MVPA levels and the incidence of AF, utilizing long-term, free-living accelerometry data. METHODS:1-year Fitbit data, in addition to survey and electronic health record (EHR) data, were extracted from the NIH All of Us (AoU) research database. Cox proportional hazards regression was used to model the association of average MVPA and incident AF over a five-year follow-up period. RESULTS:, 41±12 complete weeks of Fitbit wear). 97 individuals (0.6%) experienced incident AF in the five-year follow-up period. Every additional hour of MVPA was associated with 8% lower AF risk (HR = 0.92 [0.86,0.99], p=0.02). In a subset of 10533 participants with genomic data, this association persisted after adjustment for AF genetic risk score. CONCLUSIONS:Higher amounts of objectively measured MVPA, measured using free-living, long-term accelerometry data, were inversely associated with risk of incident AF, independent of clinical and genetic risk factors.
PMID: 40379038
ISSN: 1097-6744
CID: 5844822
Low functional capacity in peripheral artery disease is associated with increased platelet activity and cardiovascular events
Heffron, Sean P; Muller, Matt; Xia, Yuhe; Luttrell-Williams, Elliot; Rockman, Caron B; Newman, Jonathan D; Rodriguez, Crystalann; Barrett, Tessa J; Berger, Jeffrey S
BACKGROUND AND AIMS/OBJECTIVE:Low functional capacity is an independent risk factor for cardiovascular (CV) events. Regular physical activity may reduce CV risk through suppression of inflammation and reduced platelet activity. We aimed to investigate the association of functional capacity quantified by the validated Duke Activity Status Index (DASI) with platelet activity and incident major adverse CV and limb events (MACLE) in individuals with peripheral artery disease (PAD) undergoing lower extremity revascularization (LER). METHODS:Light transmission aggregometry and platelet RNAseq were performed on specimens isolated from men and women prior to LER. Functional capacity was assessed using DASI. Prospective follow-up occurred at 1, 6, 12, and every 6 months following the LER. Subjects were separated into tertiles of DASI scores and incidence rates for MACLE were calculated using log-rank tests. Mediation analysis using linear regression fit with least squares was performed to test whether DASI exerted its effect on MACLE via platelet aggregation. RESULTS:281 patients completed the DASI questionnaire with scores ranging from 0.0 to 50.2 (bottom tertile: 0.0-9.95). Mean age was 74.4 ± 10.9 years and 32.4 % were female. During a median follow-up of 19 months, 163 (58.0 %) participants experienced a MACLE. After correction for demographics and CV risk factors, individuals in the lowest DASI tertile experienced significantly more MACLE than participants in other tertiles. The association between DASI and MACLE was consistent across multiple subgroups stratified by age, sex, body mass index, antiplatelet therapy, and clinical comorbidities. Mediation analyses suggested higher platelet aggregation to epinephrine in the bottom DASI tertile mediated 24.7 % [5.0 %, 103 %] of increased MACLE risk. Platelet mRNA demonstrated upregulation of inflammation pathways in the most sedentary individuals (lowest DASI tertile). CONCLUSIONS:Patients with PAD and low functional capacity have increased platelet activity and high incidence of MACLE. Our data suggest that elevated platelet aggregation mediates one-quarter of the MACLE risk in persons with low functional capacity undergoing LER. Our findings support a potential platelet-mediated mechanism for improved CV outcomes associated with regular physical activity.
PMID: 40315646
ISSN: 1879-1484
CID: 5834552
Suicide and Self-Harm Events With GLP-1 Receptor Agonists in Adults With Diabetes or Obesity: A Systematic Review and Meta-Analysis
Ebrahimi, Pouya; Batlle, Juan Carlos; Ayati, Aryan; Maqsood, M Haisum; Long, Clarine; Tarabanis, Constantine; McGowan, Natalie; Liebers, David T; Laynor, Gregory; Hosseini, Kaveh; Heffron, Sean P
IMPORTANCE/UNASSIGNED:Bariatric surgery, once the criterion standard in obesity treatment, has a small but concerning association with increased suicidality. Glucagon-like peptide 1 receptor agonists (GLP-1 RAs), originally developed to treat diabetes, now provide substantial efficacy in the treatment of obesity. However, concerns of risk of suicidality with these medicines have been raised. OBJECTIVE/UNASSIGNED:To evaluate the risk of suicidality and self-harm in randomized, placebo-controlled trials of GLP-1 RAs in adults with diabetes or obesity. DATA SOURCES/UNASSIGNED:MEDLINE, Embase, ClinicalTrials.gov, and Cochrane databases were systematically searched from inception to August 29, 2023. STUDY SELECTION/UNASSIGNED:Reports of randomized clinical trials (RCTs) lasting 6 or more months comparing GLP-1 RAs with placebo for the treatment of diabetes or obesity published in peer-reviewed journals were identified. Two independent reviewers screened all search-identified studies for inclusion. Records of outcomes were queried from primary papers, ClinicalTrials.gov entries, and corresponding authors. DATA EXTRACTION AND SYNTHESIS/UNASSIGNED:Two independent researchers abstracted data and assessed data quality and validity using PRISMA guidelines. Data were pooled using random-effects models. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Pooled incidence of completed or attempted suicide, occurrences of suicidal ideation, or self-harm. RESULTS/UNASSIGNED:A total of 27 of 144 RCTs meeting inclusion criteria systematically recorded suicide and/or self-harm-related events and included 32 357 individuals receiving GLP-1 RAs and 27 046 treated with placebo, over 74 740 and 68 095 person-years of follow-up, respectively. Event incidence was very low in the GLP-1 RA (0.044 per 100 person-years) and placebo (0.040 per 100 person-years) groups, with no statistically significant difference (rate ratio [RR], 0.76; 95% CI, 0.48-1.21; P = .24). Subgroup analyses did not suggest differences in outcomes based on diabetes status or GLP-1 RA used. Five studies were considered at risk of bias due to the loss of more than 5% of participants to follow-up. Otherwise, studies were not found to be heterogeneous nor at high risk of bias. CONCLUSIONS AND RELEVANCE/UNASSIGNED:There is unlikely to be an increase in the very low incidence of suicide-related adverse events among individuals receiving GLP-1 RAs within the context of RCTs. While these findings may further ease concerns about these adverse effects, continued monitoring is warranted to identify particular patients who may be at risk as extended use of GLP-1 RAs expands.
PMCID:11923776
PMID: 40105856
ISSN: 2168-6238
CID: 5813382
Results of an Organization-wide Physical Activity Promotion Intervention Within a Very Large Academic Health Care System
Heffron, Sean P; O'Neill, Krista; Zhong, Judy; Xia, Yuhe; McCarthy, Margaret
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.
PMID: 40009867
ISSN: 2168-6602
CID: 5801012
Using the EPIS Framework to Implement a Physical Activity Promotion Intervention at a Large: Academic Healthcare System
McCarthy, Margaret M; O'Neill, Krista; Zhong, Judy; Xia, Yuhe; Heffron, Sean P
OBJECTIVES/OBJECTIVE: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. CONCLUSION/CONCLUSIONS:A workplace health promotion focused on employee PA is feasible using EPIS.
PMID: 39663962
ISSN: 1536-5948
CID: 5762812
A randomized, double-blind, placebo-controlled trial of weight loss using liraglutide 3.0 mg for weight recurrence after Roux-en-Y gastric bypass
Lofton, Holly F; Maranga, Gabrielle; Hold, Robert; Fielding, George; Youn, Heekoung; Gujral, Akash; Heffron, Sean; Fielding, Christine
BACKGROUND:Bariatric surgery, such as Roux-en-Y gastric bypass (RYGB) remains the gold standard for treating obesity. Most people regain weight from postsurgery nadir. OBJECTIVES/OBJECTIVE:Liraglutide 3.0 mg is approved for weight management. This study will examine the effects on liraglutide 3.0 mg on weight regain post-RYGB. SETTING/METHODS:University Hospital, United States. METHODS:A 56-week, double-blind, placebo-controlled study was conducted in 132 subjects, who achieved ≥25% total body weight loss (TBWL) status-post-RYGB and regained ≥10% TBWL after reaching nadir weight (NW). Subjects 18-120 months post-RYGB were randomized to receive liraglutide 3.0 mg/d (n = 89) or placebo (n = 43) with lifestyle counseling regularly for 56 weeks. The co-primary endpoints were the proportion of subjects losing at least 5%, 10%, and 15% TBWL and achieving weight lower than their NW. RESULTS:53.4% of the placebo group and 65% of the liraglutide group completed the trial due to Severe acute respiratory syndrome coronavirus 2 pandemic. The change in %TBWL from baseline to 56-weeks was -8.8 (8.5, -29.2 to 9.7) and 1.1 (3.5, -7.9 to 5.99) in the liraglutide and placebo groups, respectively. 76% and 17% of subjects achieved ≥5% TBWL at 56 weeks in the liraglutide and placebo groups, respectively; 51% and 26.0% of the liraglutide group achieved ≥10% and ≥15% TBWL, respectively. None of the placebo group lost ≥10% TBWL. Twenty-one percent of subjects receiving liraglutide surpassed postoperative NW. No subjects on placebo met this goal. Nonserious adverse events occurred in 41.6% of subjects on liraglutide. Serious adverse events (SAE) occurred less often on liraglutide. CONCLUSIONS:Liraglutide was significantly more effective than placebo in treating weight regain that occurs post-RYGB without increased SAE.
PMID: 39401933
ISSN: 1878-7533
CID: 5718392
High-Density Lipoprotein Lipid and Protein Cargo and Cholesterol Efflux Capacity Before and After Bariatric Surgery
Zahid, Sohail; Schlamp, Florencia; Gildea, Michael A; Lin, Bing-Xue; Chaloemtoem, Ariya; Falis, Marcin; Parikh, Manish; Fisher, Edward A; Hornemann, Thorsten; Vaisar, Tomas; Heffron, Sean P
BACKGROUND/UNASSIGNED:Cholesterol efflux capacity (CEC) of HDL (high-density lipoprotein) is inversely associated with incident cardiovascular events, independent of HDL cholesterol. Obesity is characterized by low HDL cholesterol and impaired HDL function, such as CEC. Bariatric surgery, including Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG), broadly leads to improved cardiovascular outcomes, but impacts on risk factors differ by procedure, with greater improvements in weight loss, blood pressure, and glycemic control after RYGB, but greater improvements in HDL cholesterol and CEC levels after SG. This study sought to determine effects of RYGB and SG on HDL protein and lipid cargo and investigate associations with CEC changes. METHODS/UNASSIGNED:We prospectively studied nondiabetic, premenopausal Hispanic women with severe obesity not using lipid medications undergoing RYGB (n=31) or SG (n=36). Anthropometric measurements and blood sampling were obtained before and at 6 and 12 months after surgery. HDL was isolated from plasma, and quantitative proteomic and lipidomic assessments were performed with LC-MS/MS (liquid chromatography with tandem mass spectrometry). CEC was assessed ex vivo using apoB-depleted serum. RESULTS/UNASSIGNED:Participants experienced similar, significant weight loss over 12 months following bariatric surgery (38.0±10.4 kg) regardless of the procedure. Relative quantities of 47 proteins (34 increased, 13 decreased) and 150 lipids (71 increased, 79 decreased) carried on HDL were significantly altered following either surgical procedure. Proteins with similar aggregate response patterns were clustered into 15 groups (5 increased, 5 decreased, 5 minimal change) and lipids with similar aggregate responses into 25 groups (7 increased, 11 decreased, 7 minimal change). Network mediation analyses suggested that changes in 4 protein and 2 lipid clusters mediated changes in ABCA1 (ATP-binding cassette transporter A1) CEC and that 1 lipid cluster mediated changes in non-ABCA1 CEC. The protein and lipid clusters that mediated changes in CEC were distinct between SG and RYGB. CONCLUSIONS/UNASSIGNED:Bariatric surgery produces substantial changes in HDL lipid and protein cargo, and specific changes may mediate changes in HDL function in CEC. Further study of these mechanisms may lead to improved interventions to reduce cardiovascular risk in patients with obesity.
PMID: 39744840
ISSN: 1524-4636
CID: 5778262