Study suggests gastric bypass can reduce cardiovascular disease risk, irrespective of weight loss

In a recent study published in JAMA Surgery, researchers investigated whether Roux-en-Y gastric bypass (RYGB) reduces cardiovascular risk factors independent of calorie restriction and weight loss.

Background

Bariatric surgery is more effective than nonsurgical treatment for reducing body weight and cardiovascular disease risk factors in people with excessive obesity. It is associated with a lower risk of cardiovascular events and overall mortality. However, the precise effects of the surgery, calorie restriction, or weight loss are uncertain.

Roux-en-Y gastric bypass (RYGB) also reduces cardiovascular risk factors, morbidity, and mortality; however, the underlying mechanisms are unclear. While some studies reported no changes between RYGB and diet concerning pancreatic beta-cell function, body composition, insulin sensitivity, or glucose parameters, others showed higher improvements in these aspects, the disposition index, and insulin sensitivity after RYGB.

About the study

In the present non-randomized controlled trial, researchers evaluated the changes in cardiovascular risk variables over six weeks in obese individuals who underwent either a very low-energy diet (VLED, less than 800 kcal/day) or Roux-en-Y gastric bypass surgery along with corresponding caloric restrictions and weight reduction.

The researchers conducted the Impact of Body Weight, Low-Calorie Diet, and Gastric Bypass on Drug Bioavailability, Cardiovascular Risk Factors, and Metabolic Biomarkers (COCKTAIL) study at a clinic providing tertiary care in Norway. The study included severely obese adults planning for VLED or RYGB with stable body weight in the previous three months. Recruitment commenced on February 26, 2015; the initial patient visit was on March 18, 2015, and the final (nine-weeks of follow-up) took place on 9 August 2017. The researchers analyzed data between 30 April 2021 and 29 June 2023.

The study interventions comprised three weeks of LED (less than 1,200 kcal/day) before either a six-week VLED regimen (n=37) or six weeks of VLED following RYGB (n=41). Inter-group comparisons included short-term (within six weeks) changes in cardiovascular risk factors, such as body mass index (BMI), total body fat, waist-hip circumference, insulin sensitivity, fasting glucose, blood lipids, blood pressure, and cardiometabolic biological markers.

The researchers conducted assessments at week 0 (study initiation), week 3 (end of LED), week 5, and week 9 to assess changes in protein/peptide, metabolite, and bile acid in patients undergoing RYGB vs. VLED with matching weight loss. Evaluation parameters included C-peptide, heart rate, low-density lipoprotein (LDL), high-density lipoprotein (HDL), apolipoprotein B, triglycerides, lipoprotein (a), total cholesterol, fat-free mass, and fat mass.

A dietitian provided weekly consultations with participants as part of the trial to enhance dietary adherence. Hospital surgeons conducted standard laparoscopic RYGB and monitored adherence with a four-day diet diary. The Homeostasis Model Assessment estimate of insulin sensitivity (HOMA) evaluates insulin sensitivity.

The researchers performed linear mixed-effects modeling for analysis, adjusting for age, gender, therapy type, and duration. Exploratory objectives were associated with cardiovascular metabolism and the bioavailability and disposal of drugs like midazolam. The researchers intended to include 40 patients per group, with ≥15 patients with type 2 diabetes and ≥15 patients with normal-range glucose tolerance in each group, for exploratory outcomes.

Results

Among 78 patients, the mean age was 48 years; 65% (n=51) were women, and 77 (99%) were white. Except for a slightly higher mean BMI of 44.5 in the RYGB group vs. 41.9 in the VLED group, baseline demographic and clinical characteristics were identical among groups. Primary atherogenic serum lipid molecules such as LDL, non-HDL, apolipoprotein B, and lipoprotein (a) were lowered after RYGB compared to VLED despite comparable fat mass loss. The corresponding inter-group differences (mean) were −18 mg/dL, −17 mg/dL, and −9.9 mg/dL, and the geometric mean ratio was 0.6 U/L, respectively. Changes in glycemic control and blood pressure were similar between groups.

The RYGB group lost more weight than the VLED group, with a mean difference of 2.3 kg. The change in body weight occurred between the third and fifth weeks and remained parallel later. Lipoprotein (a) and apolipoprotein B were reduced after RYGB but not VLED. RYGB led to further lipid and metabolite changes not seen in the VLED group, with lower 21 additional lipids (2%) and the omega-6: omega-3 fatty acid ratio.

Conclusion

The study found that RYGB can reduce cardiovascular risk independently of weight loss, particularly in severely obese individuals. The team observed reduced primary atherogenic lipids six weeks after RYGB but not after VLED despite similar fat mass loss. Both groups improved HbA1c, insulin sensitivity, and blood pressure, with primary metabolic improvements observed during the initial three-week LED period.