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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.
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
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

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
Purpose: Roux-en-Y gastric bypass (RYGB) leads to the improvement of many obesity-associated conditions. The degree to which post-operative macronutrient composition contributes to metabolic improvement after RYGB is understudied. Methods: A mouse model of RYGB was used to examine the effects of diet on the post-operative outcomes of RYGB. Obese mice underwent either Sham or RYGB surgery and were administered either chow or HFD and then monitored for an additional 8 weeks. Results: After RYGB, reductions to body weight, fat mass, and lean mass were similar regardless of diet. RYGB and HFD were independently detrimental to bone mineral density and plasma vitamin D levels. Independent of surgery, HFD accelerated hematopoietic stem and progenitor cell proliferation and differentiation and exhibited greater myeloid lineage commitment. Independent of diet, systemic iron deficiency was present after RYGB. In both Sham and RYGB groups, HFD increased energy expenditure. RYGB increased fecal energy loss, and HFD after RYGB increased fecal lipid content. RYGB lowered fasting glucose and liver glycogen levels but HFD had an opposing effect. Indices of insulin sensitivity improved independent of diet. HFD impaired improvements to dyslipidemia, NAFLD, and fibrosis. Conclusion: Post-operative diet plays a significant role in determining the degree to which RYGB reverses obesity-induced metabolic abnormalities such as hyperglycemia, dyslipidemia, and NAFLD. Diet composition may be targeted in order to assist in the treatment of post-RYGB bone mineral density loss and vitamin D deficiency as well as to reverse myeloid lineage commitment. HFD after RYGB continues to pose a significant multidimensional health risk. Graphical Abstract: [Figure not available: see fulltext.].
ISSN: 0960-8923
CID: 5630102

Correction: The Effect of Diet Composition on the Post-operative Outcomes of Roux-en-Y Gastric Bypass in Mice (Obesity Surgery, (2024), 10.1007/s11695-023-07052-w)

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
The original article has been corrected to replace the Electronic Supplemental Material.
ISSN: 0960-8923
CID: 5629732

Reviewing the cardiovascular and other health effects of olive oil: Limitations and future directions of current supplement formulations

Tarabanis, Constantine; Long, Clarine; Scolaro, Bianca; Heffron, Sean P
AIMS/OBJECTIVE:We reviewed the literature to date for high-level evidence on the cardiovascular and other health effects of olive oil with a focus on the amount, frequency of use and type of olive oil consumed in prior studies. A total of twelve prospective cohort studies with sample sizes of at least 4000 individuals and one meta-analysis were identified. DATA SYNTHESIS/RESULTS:The majority of cohorts followed individuals aged ≥55 years old, free of cardiovascular disease (CVD) at baseline but at high risk, over periods of 4-10 years and with daily consumption amounts of 10-35 g/day. With the exception of the PREDIMED cohort that employed extra virgin olive oil, most remaining studies did not differentiate between different types of olive oil. Taken together, the data suggests an association between greater olive oil consumption and a lower CVD incidence/mortality and stroke risk. We use this information to evaluate the use of commercially available, capsule-based olive oil dietary supplements and suggest future directions. Notably, achieving minimum total daily doses described in the aforementioned studies would be challenging with current market formulations of olive oil supplements dosed at 1-1.25 g/capsule. CONCLUSIONS:Outside of mechanistic studies, little progress has been made in determining the olive oil component(s) underlying the observed health effects given the lack of compositional reporting and consistency across large scale human studies. We propose the use of supplements of varying composition, such as varying total phenolic content, in pragmatic trial designs focused on low-cost methodologies to address this question.
PMID: 37788953
ISSN: 1590-3729
CID: 5611542

Obesity Duration and Cardiometabolic Disease

Sidhu, Sharnendra K; Aleman, Jose O; Heffron, Sean P
Cardiovascular disease risk is known to be influenced by both the severity of a risk factor and the duration of exposure (eg, LDL [low-density lipoprotein] cholesterol, tobacco smoke). However, this concept has been largely neglected within the obesity literature. While obesity severity has been closely linked with cardiometabolic diseases, the risk of developing these conditions among those with obesity may be augmented by greater obesity duration over the life span. Few longitudinal or contemporary studies have investigated the influence of both factors in combination-cumulative obesity exposure-instead generally focusing on obesity severity, often at a single time point, given ease of use and lack of established methods to encapsulate duration. Our review focuses on what is known about the influence of the duration of exposure to excess adiposity within the obesity-associated cardiometabolic disease risk equation by means of summarizing the hypothesized mechanisms for and evidence surrounding the relationships of obesity duration with diverse cardiovascular and metabolic disease. Through the synthesis of the currently available data, we aim to highlight the importance of a better understanding of the influence of obesity duration in cardiovascular and metabolic disease pathogenesis. We underscore the clinical importance of aggressive early attention to obesity identification and intervention to prevent the development of chronic diseases that arise from exposure to excess body weight.
PMID: 37650325
ISSN: 1524-4636
CID: 5618352

Bariatric surgery normalizes diabetes risk index by one month post-operation

Sinatra, Vincent J; Lin, BingXue; Parikh, Manish; Berger, Jeffrey S; Fisher, Edward A; Heffron, Sean P
AIM/OBJECTIVE: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:; n = 15). RESULTS:, 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.
PMID: 36350383
ISSN: 1432-5233
CID: 5357342

Eicosapentaenoic Acid for Cardiovascular Events Reduction- Systematic Review and Network Meta-Analysis of Randomized Controlled Trials

Yokoyama, Yujiro; Kuno, Toshiki; Morita, Sae X; Slipczuk, Leandro; Takagi, Hisato; Briasoulis, Alexandros; Latib, Azeem; Bangalore, Sripal; Heffron, Sean P
BACKGROUND:Randomized clinical trials (RCTs) investigating the impact of omega-3-fatty acid supplementation on cardiovascular events have largely shown no benefit. However, there is debate about the benign nature of the placebo in these trials. We aimed to conduct a network meta-analysis of RCTs to compare the outcomes of omega-3 fatty acid supplementation to various placebo oils. METHODS:MEDLINE and EMBASE were searched through May, 2021 to identify RCTs investigating cardiovascular outcomes with omega-3-fatty acid formulations [eicosapentaenoic acid (EPA), decosahexanoic acid (DHA), or the combination] versus placebo or standard of care controls. RESULTS:Our analysis included 17 RCTs that enrolled a total of 141,009 patients randomized to EPA (n=13,655), EPA+DHA (n=56,908), mineral oil placebo (n=5,338), corn oil placebo (n =8,876), olive oil placebo (n=41,009), and controls (no placebo oil; n=15,223). Rates of cardiovascular death [hazard ratio (HR) (95% confidence interval, CI) =0.80 (0.65-0.98); p =0.033], myocardial infarction [HR (95% CI) =0.73 (0.55-0.97); p=0.029] and stroke [HR (95% CI) =0.74 (0.58-0.94); p=0.014] were significantly lower in those receiving EPA compared to those receiving mineral oil, but were not different from rates in those receiving other oils or controls. Rates of coronary revascularization were significantly lower in those receiving EPA than in those receiving either EPA+DHA, mineral oil, corn oil, or olive oil placebo, but not controls. All-cause death was similar among all groups, but combined EPA+DHA was associated with reduced risk of cardiovascular death compared to controls [HR (95%CI): 0.83 (0.71-0.98)]. CONCLUSIONS:Our analyses demonstrate that although EPA supplementation lowers risk of coronary revascularization more than other oils, there may not be a benefit relative to standard of care. Further, EPA reduces the risk of cardiovascular events only in comparison to mineral oil and not when compared with other placebo oils or controls. In contrast, combined EPA+DHA was associated with reduced risk of cardiovascular death compared to controls.
PMID: 35914996
ISSN: 1876-4738
CID: 5287882

Platelet inhibition by low-dose aspirin is not influenced by body mass or weight

Heffron, Sean P; Windheim, Joseph; Barrett, Tessa J; Voora, Deepak; Berger, Jeffrey S
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.
PMID: 35768902
ISSN: 1369-1635
CID: 5281232