Homocysteine After Laparoscopic Roux-enY Gastric Bypass: a Comprehensive Evalutation in 708 Patients
Conditions: Obesity, Morbid, Homocystine; Metabolic Disorder, Bariatric Surgery Candidate, Folate Deficiency, Vitamin B 12 Deficiency
Sponsor: Medical University of Vienna

 
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Homocysteine in bariatric patients following laparoscopic roux-en-Y 
gastric bypass surgery 
Department of surgery 
Medical university of Vienna 
An exploratory study in 708 consecutive patients. 
 
EK1143/2013 
 
 
 
 
 
 
Marcus Poglitsch, MD 
Associate professor Gerhard Prager, MD 
Department of surgery (head of department: Univ. Prof. Raimund Jakesz, MD), 
Medical University of Vienna 
 
 
 
 
 
 
 
 
 
 
 
 
Translation of the original study protocol document approved by the local ethics 
committee in 2014. 
 

 
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Table of content 
1 
Background ......................................................................................................................... 3 
2 
Outcome .............................................................................................................................. 3 
3 
Patients ................................................................................................................................ 4 
4 
Parameters ........................................................................................................................... 4 
4.1 
Primary outcome .......................................................................................................... 4 
4.2 
Secondary outcomes .................................................................................................... 4 
5 
Methods ............................................................................................................................... 4 
6 
Statistics .............................................................................................................................. 5 
7 
Data privacy protection ....................................................................................................... 5 
8 
Risk-benefit analysis ........................................................................................................... 6 
9 
References ........................................................................................................................... 6 
 

 
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1 
Background 
 
Hyperhomocysteinaemia defined as serum levels above 15 µmol/l is 
associated with numerous risks. There is an elevated risk in suffering from 
cardiovascular events (myocardial infarction, stroke, acute limb ischemia, deep 
veinous thrombosis) who are today’s number one cause of death in the industrialized 
world (1). Furthermore, Homocysteine was found to be a mediator in dementia, 
Alzheimer’s disease (2), osteoporosis induced pathological fractures (3) and diabetic 
retinopathia (4). The role of homocysteine in metabolic diseases is indisputable. 
Obesity is also associated closely with cardiovascular disease events, therefore it is 
necessary to provide a systematically analysis of changes in homocysteine levels 
following weight loss surgery. 
 
Changes 
in homocysteine levels following bariatric surgery remain 
controversially discussed. Where some authors found postoperatively lower values  
(5, 6), others reported elevated values (7-10). Even some found no difference at all 
between preoperative and postoperative values of homocysteine (11-13). Some of 
these studies used outdated bariatric surgery procedures (7, 9, 13). 
 
In literature the postoperative changes of homocysteine after bariatric surgery 
remain unrevealed. Therefore, we designed this survey to assess timeline changes of 
homocysteine with a long-time and high follow-up. This could be of importance to 
postoperative prophylaxis of cardiovascular disease events. 
 
For homocysteine being only a surrogate parameter for cardiovascular events, 
we decided to reveal changes in homocysteine being of clinical relevance via 
assessing the actual cardiovascular disease events (stroke, myocardial infarction, 
deep veinous thrombosis, ...). 
 
 
2 
Outcome 
 
The primary outcome is to assess timeline changes of the peri and 
postoperative values of homocysteine in µmol/l via the CMIA (chemiluminescent 
microparticle immunoassay) through study completion. Secondary outcomes include 

 
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demographic parameters like weight, height, folate, and vitamin B12. Furthermore, 
for determing clinical relevance we assessed the postoperative newly-onset number 
of cardiovascular events. 
 
3 
Patients 
 
All patients received laparoscopic roux-en-Y gastric bypass at the department 
of surgery at the medical university of vienna over a six year period. All patients met 
the criteria for bariatric surgery: BMI of above 40 kg/m2 without comorbidities or BMI 
of above 35 kg/m2 with comorbidities including diabetes mellitus, arterial hypertonia, 
hyperlipidaemia, obstructive sleep apnea syndrome, arthrosis and others. Minimal 
age was 18 years and highest age was 75 years for inclusion. Both female and male 
participants were eligible.  
 
4 
Parameters 
4.1 Primary outcome 
 
Homocysteine in µmol/l assessed by CMIA technique at the timepoints 
peoperatively, 3, 6, 9, 12, 18, 24, 36, 48, 60, 72, 84 and 96 months postoperatively. 
Timeframe: through study completion. 
 
4.2 Secondary outcomes 
 
Secondary outcome measurements include folate, vitamin B12 being well 
known to have impact on homocysteine metabolism. Furthermore, all standard 
laboratory parameters and demographic data will be assessed also. The 
postoperative incidence of newly-onset cardiovascular disease events will be 
reported. 
 
5 
Methods 
 

 
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Retrospective analysis of existing records of the department of surgery, 
medical university of vienna will be performed. To extract laboratory values out of the 
database the Archimed software will be utilized. 
To reveal clinical relevance of changes in homocysteine values we will perform 
postal screening utilizing a questionnaire in all 708 participants. In the same step the 
informed consent form will be sent to each patient and they will be questioned if they 
have experienced any cardiovascular disease event after surgery (see IC form and 
questionnaire). An encrypted form of these lists is only available to the principal 
investigator and the study nurses. 
Finally, the data will be compared to two state wide databases (AKIM and 
Webokra) to verify cardiovascular events. 
 
6 
Statistics 
 
Descriptives 
 
Case number strategy: the number of participants include all patients 
undergoing roux-en-Y gastric bypass consecutively over a six year period. We expect 
708 cases. For this study being only exploratory we forwent a formal Power analysis. 
 
To reveal statistical relevant postoperative changes of homocysteine we 
performed paired t-tests between preoperatively. Pearson’s or Spearman’s 
Correlations will be performed to reveal the influence of folate and vitamin B12 on the 
homocysteine metabolism. 
 
The results of the postal screening section will be evaluated descriptively and 
compared to general incidences of cardiovascular disease events. 
 
 
7 
Data privacy protection 
 
All patients will be numbered continously and anonymized for further 
evaluation. Only authorized personnel will be able to access original names and data. 

 
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Furthermore, data will be stored and evaluated on personal computers at the medical 
university of Vienna with restricted access. 
 
8 
Risk-benefit analysis 
 
The included participants have no direkt benefit of the survey. The proposed 
study is only a retrospective evaluation of preexistant data, therefore, no risk is 
anticipated. The only relevant risk being emerging of sensitive health data will be 
minimized by anonymous evaluation and restricted access to the data. Results of this 
study can be used as a basis of generating further hypothesis of other surveys. 
 
9 
References 
 
1. 
Boushey CJ, Beresford SA, Omenn GS, Motulsky AG. A quantitative assessment of 
plasma homocysteine as a risk factor for vascular disease. Probable benefits of increasing 
folic acid intakes. JAMA. 1995 Oct 4;274(13):1049-57. 
2. 
Loscalzo J. Homocysteine and dementias. N Engl J Med. 2002 Feb 14;346(7):466-8. 
3. 
Herrmann M, Peter Schmidt J, Umanskaya N, Wagner A, Taban-Shomal O, Widmann 
T, et al. The role of hyperhomocysteinemia as well as folate, vitamin B(6) and B(12) 
deficiencies in osteoporosis: a systematic review. Clin Chem Lab Med. 2007;45(12):1621-32. 
4. 
Agullo-Ortuno MT, Albaladejo MD, Parra S, Rodriguez-Manotas M, Fenollar M, 
Ruiz-Espejo F, et al. Plasmatic homocysteine concentration and its relationship with 
complications associated to diabetes mellitus. Clin Chim Acta. 2002 Dec;326(1-2):105-12. 
5. 
Williams DB, Hagedorn JC, Lawson EH, Galanko JA, Safadi BY, Curet MJ, et al. 
Gastric bypass reduces biochemical cardiac risk factors. Surg Obes Relat Dis. 2007 Jan-
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6. 
Woodard GA, Peraza J, Bravo S, Toplosky L, Hernandez-Boussard T, Morton JM. 
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7. 
Borson-Chazot F, Harthe C, Teboul F, Labrousse F, Gaume C, Guadagnino L, et al. 
Occurrence of hyperhomocysteinemia 1 year after gastroplasty for severe obesity. J Clin 
Endocrinol Metab. 1999 Feb;84(2):541-5. 
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Dixon JB, Dixon ME, O'Brien PE. Elevated homocysteine levels with weight loss 
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Sheu WH, Wu HS, Wang CW, Wan CJ, Lee WJ. Elevated plasma homocysteine 
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10. 
Toh SY, Zarshenas N, Jorgensen J. Prevalence of nutrient deficiencies in bariatric 
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11. 
Gomez-Ambrosi J, Pastor C, Salvador J, Silva C, Rotellar F, Gil MJ, et al. Influence of 
waist circumference on the metabolic risk associated with impaired fasting glucose: effect of 

 
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Sledzinski T, Goyke E, Smolenski RT, Sledzinski Z, Swierczynski J. Decrease in 
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