Open access Protocol Bariatric surgery and LDL cholesterol (BASALTO) trial study protocol: randomised controlled study evaluating the effect of gastric bypass versus sleeve gastrectomy on high LDL cholesterol David Benaiges ‍ ‍,1,2,3,4 Albert Goday,1,2,3,5 Juana A Flores-­Le Roux,1,2,3 Montserrat Fitó,3,5 Oscar Pozo,6 Jose Rodríguez-­Morató,6 Carme Serra,1 Manuel Pera,7 Gemma Llauradó,1,2,3,4 Elisenda Climent,1,2,3 Olga Castañer,3,5 Jose M Ramon,7 Juan Pedro-­Botet1,2,3 To cite: Benaiges D, Goday A, ABSTRACT Flores-­Le Roux JA, et al. Strengths and limitations of this study Introduction Observational studies have shown gastric Bariatric surgery and LDL bypass to be superior to sleeve gastrectomy in terms of cholesterol (BASALTO) trial ►► This is the first randomised trial focused on bar- low-­density lipoprotein (LDL) cholesterol improvement. If study protocol: randomised iatric surgery and low-­ density lipoprotein (LDL) these results are confirmed in randomised controlled trials, controlled study evaluating the cholesterol. effect of gastric bypass versus presurgical LDL cholesterol status could be a relevant ►► The superiority of gastric bypass on LDL cholester- sleeve gastrectomy on high factor in surgical procedure election. Furthermore, it is ol reduction 1 year after the surgery needs to be LDL cholesterol. BMJ Open also necessary to establish the mechanisms by which LDL confirmed. 2020;10:e037712. doi:10.1136/ cholesterol improves after surgery and whether qualitative ►► Baseline LDL cholesterol could be crucial in the sur- bmjopen-2020-037712 and quantitative changes occur in the different lipoprotein gical technique election between gastric bypass and subclasses. The first objective is to ascertain whether high ►► Prepublication history for sleeve gastrectomy. this paper is available online. LDL cholesterol levels before surgery can be considered ►► Moreover, this study wants to go a step further in- To view these files, please visit an additional factor when selecting the most appropriate vestigating pathophysiologic mechanisms related to the journal online (http://​dx.​doi.​ surgical procedure for each patient (gastric bypass or LDL cholesterol remission. org/​10.​1136/​bmjopen-​2020-​ sleeve gastrectomy). Hence, the 1-­year remission rates ►► Patients with LDL cholesterol >190 mg/dL, familial 037712). of high LDL cholesterol after gastric bypass and sleeve hypercholesterolaemia or are in secondary preven- gastrectomy in patients with morbid obesity will be Received 13 February 2020 tion will not be included in the present trial. compared. Secondary objectives were (1) to compare Revised 16 June 2020 changes in other lipoproteins and LDL composition and (2) Accepted 06 July 2020 to study the pathophysiologic mechanisms related to LDL cholesterol remission. INTRODUCTION Methods and analysis A randomised clinical trial, with Obesity is associated with higher mortality, intention-­to-­treat analysis, will be conducted to compare being related, at least in part, to a higher LDL cholesterol remission between gastric bypass prevalence of cardiovascular risk factors and sleeve gastrectomy, with a 12-­month follow-­up. such as type 2 diabetes, hypertension and Inclusion criteria will be patients between 18 and 60 hypercholesterolaemia.1 2 The characteristic years of age with body mass index ≥40 kg/m2 or ≥35 dyslipidaemia of obesity involves different kg/m2 with significant obesity-­related comorbidity and qualitative and quantitative lipoprotein alter- high LDL cholesterol levels. Patients will be evaluated preoperatively and at 3, 6 and 12 months after bariatric ations and contributes to the high cardiovas- surgery. Examinations will include routine blood chemistry, cular risk in this population.3 © Author(s) (or their Given the lack of effective medical thera- anthropometric measurements, food intake recall, physical employer(s)) 2020. Re-­use activity questionnaires and serum samples for lipidomic peutic strategies, the demand for bariatric permitted under CC BY-­NC. No commercial re-­use. See rights and lipoprotein characterisation. surgery (BS) has been growing worldwide and permissions. Published by Ethics and dissemination Ethics approval has been over the last decade. Laparoscopic sleeve BMJ. granted by the Parc de Salut Mar Ethics Committee gastrectomy (LSG) and laparoscopic Roux-­ For numbered affiliations see (2019/8471/I). The study and its conclusions regarding en-­Y gastric bypass (LRYGB) are two of the end of article. the primary and secondary objectives will be presented most frequent procedures currently used as manuscripts submitted for peer-­reviewed journal for BS.4 In this context, the pros and cons Correspondence to publication. Dr David Benaiges; of both techniques are crucial in clinical Trial registration number NCT03975478. ​96002@​parcdesalutmar.​cat decision-­making for the most appropriate Benaiges D, et al. BMJ Open 2020;10:e037712. doi:10.1136/bmjopen-2020-037712 1 Open access BS procedure.5 In this respect, different observational 3. Previous successfully instituted and supervised, but studies reported the superiority of LRYGB in terms of failed adequate diet and exercise programme. low-­density lipoprotein (LDL) cholesterol improvement, 4. Elevated LDL cholesterol defined as LDL choles- with no differences in other lipoproteins. Furthermore, terol concentration >130 mg/dL or treatment with a recent meta-­analysis conducted by our group found cholesterol-­lowering drugs. hypercholesterolaemia remission to be more frequent 1 year after LRYGB than LSG (RR: 1.43, 95% CI: 1.27 Exclusion criteria to 1.61), and, the drop in LDL cholesterol levels was 1. BMI>60 kg/m2. greater after LRYGB than after LSG (mean difference: 2. Previous BS. 19.29 mg/dL, 95% CI: 11.93 to 26.64).6 Concurring with 3. Exclusion criteria for BS. these results, the SM-­BOSS and SLEVEPASS trials (two i. Significant psychiatric disorder. randomised trials between LRYGB and LSG with a 5-­year ii. Severe eating disorder, active alcohol or substance follow-­up) reported lower LDL cholesterol levels with abuse. LRYGB but without the net LDL cholesterol decrease or iii. Contraindications for major abdominal surgery. the LDL cholesterol remission rate.7 8 iv. Active gastric ulcer disease. Scientific evidence provided by randomised controlled v. Severe liver disease. trials (RCTs) on the metabolic effects of BS is scant. vi. Pregnancy or breastfeeding. Moreover most RCT comparing LRYGB and LSG focused 4. Cases in which LSG or LRYGB are preferred. mainly on weight loss7 8 or type 2 diabetes remission,9 10 i. Severe symptomatic gastro-­oesophageal reflux dis- obviating the remaining comorbidities. In this respect, ease despite medication. high scientific evidence studies in the field of BS focused ii. Large hiatal hernia. on LDL cholesterol are lacking and could be crucial in iii. Expected presence of dense adhesions at small surgical technique election. bowel level. iv. Need for endoscopic follow-­up of the duodenum, history of inflammatory bowel disease. METHODS AND ANALYSIS v. History of kidney transplantation in which drug Primary objective malabsorption can be caused by a LRYGB. The general aim is to ascertain whether high LDL choles- 5. Cholesterol-­lowering drugs will be withdrawn immedi- terol levels before surgery can be considered an addi- ately after surgery to assess LDL cholesterol remission tional factor when selecting the most appropriate surgical during follow-­up. Cases in which perioperative statin procedure for each patient (LRYGB or LSG). The main cannot be withdrawn will be excluded11: objective is to compare LDL cholesterol remission 1 year i. Established cardiovascular disease or subclinical after LRYGB and LSG. cardiovascular disease (atheromatous plaque de- tection on carotid ultrasonography) in which LDL Secondary objectives cholesterol objectives are more aggressive or stat- The secondary aims are (1) to compare the evolution ins can be prescribed regardless of LDL cholester- of other lipoproteins (high-­density lipoprotein (HDL) ol levels. cholesterol, triglycerides and lipoprotein(a)) and LDL ii. LDL cholesterol >190 mg/dL or history of familial composition and (2) to study the mechanisms involved hypercholesterolaemia. in the different LDL cholesterol remission rates after LRYGB and LSG. Blinding There will be no blinding with regard to the type of Patient and public involvement surgery: patients as well as physicians and dietitians Neither patients nor the public are involved in the assessing follow-­up data will be informed of the proce- conception, design or conduct of the study. dure performed. The researcher responsible for statis- tical analysis will be blinded to group allocation until data Study design analysis is completed. A phase 3, single-­centre, randomised clinical trial with an intention-­to-­treat analysis will be conducted to compare LDL cholesterol remission after LRYGB and LSG in Recruitment patients with severe obesity and high LDL cholesterol Participants will be recruited from the BS programme levels. The follow-­up period for the primary end-­point at the Hospital del Mar, Barcelona. Patients who meet will be 12 months, but patients will also be scheduled for the NIH criteria for BS (BMI ≥40 kg/m2 or ≥35 kg/m2 a 5-­year extension study. with significant obesity-­related comorbidities)12 and who express the desire to undergo BS will be referred to the Inclusion criteria BS unit from primary care units. After inclusion in the BS 1. Body mass index (BMI) ≥40 kg/m2 or ≥35 kg/m2 with programmes, patients will follow a standard nutritional significant obesity-­related comorbidities. intervention that includes 6-­ monthly group sessions 2. Age 18–60 years. focused on achieving changes in dietary habits and hence 2 Benaiges D, et al. BMJ Open 2020;10:e037712. doi:10.1136/bmjopen-2020-037712 Open access facilitating adaptation after surgery. After this group the type of operation drawn will be explained again in intervention, patients will be evaluated with routine detail to the subject. blood chemistry by an endocrinologist. If they meet the inclusion criteria for the study and agree to participate, Surgical procedures they will be scheduled for the inclusion visit. The LRYGB technique consists of a 150 cm antecolic Roux limb with a 25 mm circular pouch-­jejunostomy and Inclusion visit the exclusion of 50 cm of the proximal jejunum. In LSG, An endocrinologist who will review the inclusion and longitudinal resection of the stomach from the angle exclusion criteria will evaluate the subjects. An ECG and of His to approximately 5 cm proximal to the pylorus is supra-­aortic trunk ultrasound will be performed. If estab- performed using a 35 French bougie inserted along the lished cardiovascular disease or atheromatous plaques lesser curvature. The same team of surgeons will perform are detected on ultrasonography, patients will not be all operations. included in the study. The proposal to participate in the study will be explained once again, doubts will be resolved Postoperative visits and informed consent for the study will be signed. The Patients will be evaluated by the multidisciplinary team patient will be given time to reconsider whether or not at 3, 6 and 12 months after BS. Anthropometry, blood participate or to return a second time. pressure, smoking status, routine blood chemistry, food intake registry, exercise questionnaire and serum bank Preoperative management will be collected at each visit. Additionally, faecal samples Patients will follow the routine follow-­ up of those for gut microbiota examinations will be collected. included in the Hospital del Mar BS programme from the Statins and other lipid-­lowering drugs will be withdrawn time of study inclusion until the time of surgery. Different during hospital admission for the surgical procedure. examinations will be performed (abdominal ultrasound, Postoperatively, LDL cholesterol status will be evaluated functional respiratory tests and gastroscopy) and results at each visit: evaluated by a multidisciplinary team including dietitian, 1. LDL cholesterol <130 mg/dL: cholesterol-­ lowering surgeon and endocrinologist. Ten days prior to surgery, drugs will not be initiated and patients will be consid- a very low-­calorie diet will be prescribed to achieve addi- ered in remission. tional weight loss. In order to avoid bias that may arise 2. LDL cholesterol 130–190 mg/dL: cholesterol-­lowering due to an open study, a standardised protocol will be drugs will be initiated in patients with persistent es- followed for the two groups regarding dietary recommen- timated cardiovascular risk >10% using REGICOR dations and physical activity as well as the initiation of charts.14 lipid-­lowering medication after the intervention. 3. LDL cholesterol >190 mg/dL: cholesterol-­ lowering Management of cholesterol-­lowering treatment will be drugs will be initiated. based on the clinical practice guidelines of the Institut Patients will also receive nutritional support in the Català de la Salut.13 Cholesterol-­lowering treatment will immediate postoperative period (at 2, 4 and 8 weeks) with be started in primary prevention in adults with a 10 year the aim of progressing from a liquid to a soft solid diet. estimated cardiovascular risk >10% using REGICOR Thereafter, appointments will be held at 6 and 12 months tables.14 Similarly, cholesterol-­lowering treatment will be to detect and manage possible dietary intolerances. At 1 withdrawn in patients with a 10 year cardiovascular risk year postsurgery, the diet should be solid, varied and low <10% and with no previous LDL cholesterol determina- calorie. tions >190 mg/dL. Two months before BS, a preoperative visit and tests will Outcome definition be carried out in patients included in the study. These Lipid disturbance evaluation will comprise routine blood chemistry, anthropometric 1. LDL cholesterol remission: postoperative LDL choles- measurements (weight, height and abdominal circum- terol <130 mg/dL without cholesterol-­lowering drugs. ference), assessment of current lipid-­lowering treatment, 2. LDL cholesterol improvement: quantification of comorbidities other than high LDL i. Patients without preoperative cholesterol-­lowering cholesterol, food intake measured by 3-­day food registry, drugs: decrease ≥20% in LDL cholesterol concen- physical activity measured by a specific questionnaire, tration without cholesterol-­lowering drugs. serum bank collection for lipidomic determinations and ii. Patients with preoperative cholesterol-­ lowering lipoprotein characterisation, and faecal sample collection drugs: medication withdrawn and LDL cholesterol for gut microbiota examination. >130 mg/dL or decrease ≥20% in LDL cholester- ol concentration without medication withdrawn. Randomisation 3. Hypertriglyceridaemia remission: triglycerides <150 The randomisation list will be electronically generated mg/dL without fibrates. through specific software. Randomisation will be made 4. Low HDL cholesterol remission: HDL cholesterol >50 before the preoperative visit using a sealed envelope, and mg/dL in women or >40 mg/dL in men. Benaiges D, et al. BMJ Open 2020;10:e037712. doi:10.1136/bmjopen-2020-037712 3 Open access Other cardiovascular outcomes (column, mobile phase) and by the acquisition of specific 1. Type 2 diabetes complete remission: glycated haemo- selected reaction monitoring transitions (in LC-­ MS/ globin (HbA1c) value <6.0% and fasting glucose level MS) or using selected ion monitoring (in GC-­MS) for <100 mg/dL without diabetes medications.15 each analyte. Quantification will normally be performed 2. The 10-­ year risk of cardiovascular disease will be either by external calibration or relative response factor estimated using the REGICOR adaptation of the employing the ratio between the analyte and the labelled Framingham Risk Score for the Mediterranean pop- internal standard as a response. In order to assure the ulation.14 Risk factors included in the calculation are between-­batch reproducibility of the measurements, two age, gender, total cholesterol levels, HDL cholesterol quality control samples will be analysed in every batch. levels, diastolic and systolic blood pressures, type 2 dia- Characterisation of the different lipoproteins will be betes and smoking status. made by nuclear magnetic resonance using an advanced lipoprotein test (LIPOSCALE TEST). This determines Anthropometric parameters cholesterol and triglyceride content of the main lipopro- Height will be measured at the inclusion visit with a high tein fractions (Very Low Density Liporpotein (VLDL), precision measuring rod. Weight and blood pressure Intermediate Density Lipoprotein (IDL), LDL and HDL) will be measured at each visit. Patients are measured in in plasma and blood serum. It also analyses the particle lightweight clothing. BMI will be calculated as weight concentration (large, medium and small) of each main in kilograms divided by the square of height in metres. fraction (VLDL, LDL and HDL) and, finally, the size of Weight loss will be measured as the percentage of excess the main lipoprotein fractions (VLDL, LDL and HDL).16 BMI loss (100 × [baseline BMI−follow-­up BMI]/[baseline BMI−25]) and percentage of excess weight loss (initial Microbiota weight—follow-­up weight)/(initial weight—ideal weight Fresh faeces will be collected and immediately frozen and for BMI 25) × 100%. stored at ‒80°C in our centre’s freezers until processed. The microbial composition will be processed using illu- Laboratory methods mina sequencing technique. We will perform microbial Routine blood chemistry performed after a 12 hours DNA genomic and total RNA extraction, sequencing overnight fast will be analysed at our reference labora- of 16S rDNA and 16S rRNA, metagenomic sequencing; tory. Complete lipid profile, glucose, HbA1c, kidney and purification, amplification and sequencing of mRNA; liver function will be determined. Plasma samples will be metagenomic and metatranscriptomic analyses, protein collected and frozen at ‒80°C. Lipoprotein characterisa- extraction together with separation, identification and tion and lipidomic determinations will be carried out in processing of data. all patients when they complete follow-­up. Total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides will be determined using enzymatic Adipose tissue biopsy methods (Roche Cobas 8000 c701, Roche Diagnostics During surgery, 2–5 g visceral adipose tissue and subcu- GmbH, Germany) and lipoprotein(a) by immunoturbi- taneous adipose tissue samples will be removed. Visceral dimetric determination (Roche Cobas 8000 c502, Roche adipose tissue will be obtained from perigastric adipose Diagnostics GmbH, Germany). tissue, and subcutaneous adipose tissue from the site of Targeted lipidomic approaches developed at the Clin- the surgical incision. The adipose tissue samples will be ical Metabolomics Platform at Hospital del Mar Medical processed immediately, cut into small pieces, washed with Research Institute will be applied to provide new insights Phosphate Buffered Saline (PBS) and frozen at ‒80°C into the mechanism(s) responsible for the BS-­induced until further analysis. The subsequent analysis of gene lowering effects on LDL cholesterol. The lipid families/ expression will be performed by quantitative polymerase pathways planned to be targeted are as follows: (1) precur- chain reaction (qPCR) and western blot techniques. sors and metabolites of cholesterol, (2) bile acids, (3) oxys- terols, (4) cholesteryl esters, (5) steroid hormones and Food intake and physical activity metabolites, (6) ceramides, (7) diacylglycerols and (8) All subjects will have to fill in a dietary record for three lysophosphatidylcholines. Based on the Platform’s expe- consecutive days from Sunday to Tuesday. Nutrient rience, methods based on liquid or gas chromatography intakes will be calculated with the DIET ANALYSIS coupled with mass spectrometry (LC-­MS/MS or– GC-­MS) NUTRITIONIST IV software (N Squared Computing, will be applied to detect the targeted lipid molecules. San Bruno, California, USA). Serum/plasma and/or stool samples will be divided Physical activity will be measured using the REGICOR into aliquots for the different lipidomic methods. After Short Physical Questionnaire.17 This questionnaire addition of the appropriate labelled internal standards, covers all four dimensions of physical activity: type, samples will be extracted using solid-­ phase or liquid– frequency, duration and intensity and lists six types of liquid process and/or derivatised. Analytes contained activity: walking, brisk walking, walking on trails/hiking, in the final extract will be determined by LC-­MS/MS or gardening, climbing stairs and sport. To complete the GC-­MS using a specific set-­up for each selected pathway questionnaire, trained personnel will ask participants the 4 Benaiges D, et al. BMJ Open 2020;10:e037712. doi:10.1136/bmjopen-2020-037712 Open access number of days per month and average minutes per day techniques and fewer complications than purely malab- they performed the activity. sorptive surgeries.19 Nevertheless, the use of LSG has increased in the last 10 years, thanks to its technical Sample size simplicity and similar short-­term results than LRYGB in Assuming LDL cholesterol remission rates to be 70% in terms of weight loss and comorbidity remission such as the LRYGB group and 20% in the LSG, a minimum of 18 type 2 diabetes and hypertension.7–9 These advantages patients per arm will provide 80% power to detect a differ- placed LSG for the first time as the most widely used BS ence between groups using a two-­sided α of 0.05. These technique worldwide in 2014, overtaking LRYGB.4 In this estimates were derived from our previous published context, there is intense debate in the scientific commu- data.18 A drop-­out rate of 20% has been anticipated. nity as to whether LSG can replace LRYGB as the new gold standard. Following publication of the SLEEVEPASS and Data analysis SM-­BOSS trials, Arterburn et al5 published an editorial All data will be collected in a central database according in the JAMA where they considered that switching from to a standardised protocol. Data will be expressed as LRYGB to LSG has not been a misadventure and that mean±SD for continuous variables after a normal distribu- either technique is a great decision. Moreover, they high- tion, as median with IQR for continuous variables with a lighted that five different points need to be considered in non-­normal distribution and as percentages and frequen- the difficult choice between the two: (1) the election has to cies for categorical variables. Normality of the models be decided jointly between the patient and medical team, will be evaluated visually and by the Kolmogorov-­Smirnov (2) there are no differences in weight loss, (3) the pres- test. For skewed variables, a logarithmic transformation ence of type 2 diabetes does not render LRYGB preferable will be used to achieve normality. Student’s t-­test will be to LSG, (4) LRYGB is preferred in patients with gastro-­ performed to assess differences between two means. χ2 oesophageal reflux disease and (5) there are no differ- or Fisher’s exact tests will be used to assess the degree ences in the rate of postsurgical reoperation for different of association among categorical variables (including the reasons (gastro-­oesophageal reflux with LSG and small primary outcome: LDL cholesterol remission at 1 year). bowel obstruction or internal hernia with LRYGB). Never- Analysis of variance models will be used to study the evolu- theless, if the BASALTO trial confirms the superiority of tion of continuous variables in each group and analyse LRYGB over LSG in terms of LDL cholesterol remission, differences between groups at each time point from base- we believe this should be the sixth point to be taken into line. The effect of BS on lipidome will be analysed with account in the surgical procedure decision. mixed generalised linear models for repeated measure- This trial will attempt to go one step further to study ments, adjusting for covariates such as weight, BMI and the pathophysiologic mechanism(s) involved in LDL physical activity, among others. A two-­sided p value <0.05 changes after both techniques. As reported by our group will be considered statistically significant. in previous studies, LDL cholesterol improvement is greater in patients with higher baseline LDL cholesterol levels and is not related to postoperative weight loss. ETHICS AND DISSEMINATION The predominant mechanism involved in LDL choles- The study will be conducted in accordance with the terol after LRYGB appears to be malabsorption. In this basic principles of protection of rights and dignity of respect, Pihlajamäki et al20 found a reduction in choles- the human being, as stated in the Helsinki Declaration terol absorption markers only after LRYGB, an effect and with current regulations. Law 14/2007 of Biomed- not previously reported following a restrictive technique ical Research (LIB) will be adhered to the studies with (gastric banding). Moreover, other authors suggest that biologic samples. All the information obtained will be the LDL cholesterol decrease could be related to bile treated confidentially in compliance with the personal acid metabolism.21 Nevertheless, if the only mechanism data protection legislation (Ley Orgánica 3/2018, de is malabsorption, we cannot explain why approximately 5 de diciembre, de Protección de Datos Personales y one in every five patients operated on with LSG can garantía de los derechos digitales). Participants will sign achieve LDL cholesterol remission. Analysis of the lipi- their informed consent to participate in the study. Ethics dome in BASALTO study subjects will permit us to iden- approval has been granted by the Parc de Salut Mar Ethics tify the changes in plasma concentrations of different Committee (2019/8471/I). The study and its conclusions lipid compounds due to surgical interventions and deter- regarding the primary and secondary objectives will be mine which metabolic pathways would be modulated presented as manuscripts submitted for peer-­ reviewed with each technique to later correlate this information journal publication. with the alterations observed in LDL cholesterol. Thus, the targeted lipidomic analysis of the present study will be essential to obtain an overall view that affords under- DISCUSSION standing of the changes in LDL cholesterol with each LRYGB has been considered the gold standard and most technique. used BS technique for several years owing to its supe- On the other hand, that the atherogenic profile of rior risk–benefit balance, better results than restrictive LDL particles may vary depending on their size and Benaiges D, et al. BMJ Open 2020;10:e037712. doi:10.1136/bmjopen-2020-037712 5 Open access composition is well known. Thus, the presence of small Acknowledgements We thank Miss Christine O’Hara for review of the English and dense LDL particles has been associated with obesity, version of the manuscript. diabetes and increased cardiovascular risk. Evidence of Contributors DB performed the study conceptualisation, data curation, funding the effects of BS on the size and composition of LDL acquisition, methodology, investigation, project administration, supervision and creating the original draft. AG helped in conceptualisation, project administration, is limited. In this regard, Kjellmo et al reported that supervision, review and editing of draft. JF-­LR performed the project biliopancreatic diversion and LRYGB reduce the number administration and supervision. MF helped in funding acquisition, methodology, of large LDL particles but have no effect on small and project administration and supervision. OP helped in conceptualisation, data dense LDL.22 To our knowledge, no studies have been curation, funding acquisition, methodology and investigation. JR-­M performed study conceptualisation, data curation, funding acquisition, methodology conducted on the effects of LSG on the size and compo- and investigation. CS helped in investigation. GL helped in data curation and sition of LDL. methodology. EC helped in Investigation. OC performed funding acquisition, data This study has certain limitations. Since patients with curation, methodology and project administration. JMR helped in conceptualisation, LDL cholesterol >190 mg/dL, familial hypercholes- methodology, investigation, project administration and supervision. JP-­B performed conceptualisation, methodology, funding acquisition, project administration, terolaemia or those on secondary prevention will not supervision, review and editing of draft. be included in the present trial, the results will not be Funding This work was supported by (Spanish National Health System Grant) able to be extrapolated to the overall population with grant number [PI19/00006]. severe obesity and high LDL cholesterol concentra- Competing interests None declared. tions. However, it must be highlighted that the number Patient and public involvement Patients and/or the public were not involved in of patients on secondary prevention who undergo BS is the design, or conduct, or reporting, or dissemination plans of this research. low. In this respect, only 2.2% patients included in the Patient consent for publication Not required. Swedish Obese Subjects study presented myocardial Provenance and peer review Not commissioned; externally peer reviewed. infarction or stroke previous to surgery.23 Moreover, in patients receiving treatment with cholesterol-­ lowering Open access This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-­NC 4.0) license, which drugs before surgery, it will not be possible to assess the permits others to distribute, remix, adapt, build upon this work non-­commercially, absolute changes in LDL cholesterol concentration, and and license their derivative works on different terms, provided the original work is changes in lipoprotein size and composition should be properly cited, appropriate credit is given, any changes made indicated, and the use interpreted with caution. is non-­commercial. See: http://​creativecommons.​org/​licenses/​by-​nc/​4.​0/. ORCID iD David Benaiges http://​orcid.​org/​0000-​0001-​5411-​364X TRIAL STATUS This study obtained the Ethics Committee approval in March 2019 and was registered at ​clinicaltrials.​gov in June REFERENCES 1 Allison DB, Fontaine KR, Manson JE, et al. Annual deaths attributable 2019. Enrolment in the trial began in July 2019 and 11 of to obesity in the United States. JAMA 1999;282:1530–8. the 36 required subjects have been recruited to date. A 2 Must A, Spadano J, Coakley EH, et al. The disease burden Spanish National health System Grant was recently adju- associated with overweight and obesity. JAMA 1999;282:1523–9. 3 Grundy SM. Obesity, metabolic syndrome, and cardiovascular dicated (PI19/00006). This study is sponsored by a Public disease. J Clin Endocrinol Metab 2004;89:2595–600. Health Hospital (Parc de Salut Mar). 4 Angrisani L, Santonicola A, Iovino P, et al. Bariatric surgery and endoluminal procedures: IFSO worldwide survey 2014. 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