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
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
Targeted deletion of Fibroblast Growth Factor-23 rescues metabolic dysregulation of diet-induced obesity in female mice
Park, Min Young; Tu, Chia-Ling; Perie, Luce; Verma, Narendra; Serdan, Tamires Duarte Afonso; Shamsi, Farnaz; Shapses, Sue; Heffron, Sean; Gamallo-Lana, Begona; Mar, Adam C; Alemán, José O; Mueller, Elisabetta; Chang, Wenhan; Sitara, Despina
Fibroblast Growth Factor-23 (FGF23) is a bone secreted protein widely recognized as a critical regulator of skeletal and mineral metabolism. However, little is known about non-skeletal production of FGF23 and its role in tissues other than bone. Growing evidence indicates that circulating FGF23 levels rise with high fat diet (HFD) and they are positively correlated with body mass index (BMI) in humans. In the present study, we show for the first time that increased circulating FGF23 levels in obese humans correlate with increased expression of adipose Fgf23 and both positively correlate with BMI. To understand the role of adipose-derived Fgf23, we generated adipocyte-specific Fgf23 knockout mice (AdipoqFgf23Δfl/Δfl) using the Adiponectin (Adipoq)-Cre driver, which targets mature white, beige, and brown adipocytes. Our data show that targeted ablation of Fgf23 in adipocytes prevents HFD-fed female mice from gaining body weight and fat mass while preserving lean mass, but has no effect on male mice, indicating the presence of sexual dimorphism. These effects are observed in the absence of changes in food and energy intake. Adipose Fgf23 inactivation also prevents dyslipidemia, hyperglycemia, and hepatic steatosis in female mice. Moreover, these changes are associated with decreased respiratory exchange ratio (RER) and increased brown fat Ucp1 expression in KO mice compared to HFD-fed control mice (Fgf23fl/fl). In conclusion, this is the first study highlighting that targeted inactivation of Fgf23 is a promising therapeutic strategy for weight loss and lean mass preservation in humans.
PMID: 39446375
ISSN: 1945-7170
CID: 5740092
Cohort profile: study design and baseline characteristics of an observational longitudinal weight loss cohort and biorepository of patients undergoing sleeve gastrectomy in the USA
Vanegas, Sally M; Curado, Silvia; Gujral, Akash; Valverde, Gabriela; Parraga, Susan; Aleman, Jose O; Reid, Migdalia; Elbel, Brian; Schmidt, Ann Marie; Heffron, Sean P; Segal, Eran; Li, Huilin; Abrams, Courtney; Sevick, Mary A; Popp, Collin; Armijos, Evelyn; Merriwether, Ericka N; Ivezaj, Valentina; Ren-Fielding, Christine; Parikh, Manish; Jay, Melanie
PURPOSE/OBJECTIVE:We developed a comprehensive sleeve gastrectomy (SG) weight loss study cohort and biorepository to uncover mechanisms, biomarkers and predictive factors of weight loss, weight maintenance and amelioration of obesity-related comorbidities. For this purpose, we collected psychosocial, anthropometric, clinical data and a variety of samples pre-surgery, intraoperatively and 1.5, 3, 12 and 24 months post-surgery. For longer-term assessment, the collection of psychosocial and anthropometric data was extended to 10 years. Here, we present in-depth characterisation of the cohort and detailed overview of study procedures as a foundation for future analyses. PARTICIPANTS/METHODS:We consented 647 participants between June 2017 and March 2020 from two bariatric surgery clinics in New York City-one major urban hospital and one private hospital. Of 355 participants who provided baseline data, 300 underwent SG. Of these, 79% are females with an average age of 38 years, 68% are Hispanic, 20% are non-Hispanic Black and 11% are non-Hispanic White. FINDINGS TO DATE/RESULTS:We collected intraoperative adipose and stomach tissues from 282 patients and biosamples (blood, urine, saliva, stool) from 245 patients at 1.5 months, 238 at 3 month, 218 at 12 months and 180 at 24 months post-surgery. We are currently collecting anthropometric and psychosocial data annually until 10 years post-surgery. Data analysis is currently underway. FUTURE PLANS/UNASSIGNED:Our future research will explore the variability in weight loss outcomes observed in our cohort, particularly among Black and Hispanic patients in comparison to their White counterparts. We will identify social determinants of health, metabolic factors and other variables that may predict weight loss success, weight maintenance and remission of obesity-related comorbidities. Additionally, we plan to leverage our biorepository for collaborative research studies. We will complete long-term follow-up data by December 2031. We plan to apply for funding to expand biosample collection through year 10 to provide insights into the mechanisms of long-term weight maintenance.
PMCID:11344502
PMID: 39181563
ISSN: 2044-6055
CID: 5697372
Early administration of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors in patients with acute coronary syndrome: a systematic review and meta-analysis
Hosseini, Kaveh; Soleimani, Hamidreza; Maleki, Saba; Nasrollahizadeh, Amir; Tayebi, Sima; Nelson, John; Heffron, Sean P
BACKGROUND:High-intensity statin therapy is currently recommended initial guideline therapy in ACS treatment. However, only a minority of patients are achieving LDL-C attainment goal at 6 months. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are on recommended guideline therapy post-ACS if LDL-C goal attainment is not achieved after high-intensity statin (4-6 weeks) and after the addition of ezetimibe if guideline goal attainment is not achieved after an additional 4-6 weeks. Thus, it has been recommended that PCSK9 inhibitors be considered earlier post-ACS. However, the efficacy of early PCSK9 inhibitors initiation in ACS patients remains uncertain. METHODS:This systematic review and meta-analysis was conducted following PRISMA guidelines. Randomized controlled trials (RCTs) and observational studies involving ACS patients who received PCSK9 inhibitors within 48 h of hospitalization were included. Common and random effects models were used to evaluate the pooled effect of early PCSK9 inhibitor administration. Nine RCTs and three cohort studies were included. RESULTS:Early PCSK9 inhibitor administration reduced the incidence of MI, ACS hospitalization, and revascularization at 6-18 months post-ACS. Although there was a drift towards reduced stroke, all-cause mortality, and cardiovascular death, no statistically significant reduction was observed. Additionally, PCSK9 inhibitors significantly enhanced lipid control at 4-12 weeks after index hospitalization. CONCLUSION/CONCLUSIONS:Early PCSK9 inhibitors initiation in ACS patients reduces MACE and improves lipid profiles. While the results propose promising benefits in terms of stroke and mortality, further research with longer follow-up is required for more decisive evidence.
PMCID:11287928
PMID: 39080549
ISSN: 1471-2261
CID: 5696412
Correction: The Effect of Diet Composition on the Post-operative Outcomes of Roux-en-Y Gastric Bypass in Mice
Stevenson, Matthew; Srivastava, Ankita; Nacher, Maria; Hall, Christopher; Palaia, Thomas; Lee, Jenny; Zhao, Chaohui Lisa; Lau, Raymond; Ali, Mohamed A E; Park, Christopher Y; Schlamp, Florencia; Heffron, Sean P; Fisher, Edward A; Brathwaite, Collin; Ragolia, Louis
PMID: 38236349
ISSN: 1708-0428
CID: 5737482