Incidence of Cancer and Cardiovascular Disease After Bariatric Surgery in Older Patients

This cohort study evaluates whether bariatric surgery is associated with a decreased risk of obesity-related cancer and cardiovascular disease in patients who underwent surgery at age 60 years or older.


Introduction
More than 1 billion people worldwide have obesity, defined as a body mass index of 30 or greater (calculated as weight in kilograms divided by height in meters squared). 1Obesity increases the risk of several neoplasms, including cancer of the breast, endometrium, esophagus, colon, rectum, and kidney. 2 Furthermore, obesity contributes to cardiovascular disease, including hypertension and coronary artery disease, but also comorbidities such as diabetes, osteoarthritis, sleep disorders, and psychiatric disorders. 3The most well-documented treatment for obesity is bariatric surgery, which induces rapid, profound, and sustained weight loss in contrast to nonoperative treatment, which includes changes in lifestyle, diet, and physical activity. 45][6][7] There is controversy regarding whether patients aged older than 60 years should undergo bariatric surgery, as the benefits of bariatric surgery, including weight loss and resolution of obesity-related comorbidities, seem to attenuate with older age. 8It is therefore possible that bariatric surgery does not prevent obesity-related cancer and cardiovascular disease in older patients, but data in the literature are scarce.Using nationwide data from 3 countries, we aimed to compare the incidence of obesity-related cancer and cardiovascular disease in patients who had undergone bariatric surgery at age 60 years or older with patients who received nonoperative treatment for obesity.
Ethical approvals for the study was granted by the regional ethical review board in Stockholm, and data retrieval permissions came from The National Board of Health and Welfare in Sweden, from The Danish Data Protection Agency in Denmark, and from The National Institute for Health and Welfare and Statistics Finland in Finland.Informed consent was waived due to the registry-based design, which only included deidentified data collected from routine health care.The study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline for cohort studies. 9e study population was identified from the Nordic Obesity Surgery Cohort which contains data from the patient registries, cancer registries, and causes of death registries for the 3 countries. 102][13] The Swedish patient registry has been specifically validated for bariatric surgery with greater than 97% concordance to medical records. 10om the patient registries, we identified all patients who underwent bariatric surgery (including gastric bypass, sleeve gastrectomy, gastric banding, and duodenal shunt with

JAMA Network Open | Surgery
Incidence of Cancer and Cardiovascular Disease After Bariatric Surgery in the Older Patients biliopancreatic diversion; procedure codes are listed in eTable 1 in Supplement 1) at age 60 years or older.For each patient who underwent surgery, exactly 5 patients with an obesity diagnosis who did not undergo surgery (eTable 2 in Supplement 1) of the same country, sex, and age in years at the date of surgery were selected randomly.Patients with a previous diagnosis of cancer or cardiovascular disease were excluded from the study (eTable 3 in Supplement 1).Start of follow-up occurred on the date of bariatric surgery with patients who did not undergo surgery entering on the same date as their matched patient.

End Points
The main outcome was obesity-related cancer, defined as a composite outcome including any cancer of the breast, endometrium, esophagus, colon, rectum, and kidney (eTable 4 in Supplement 1).The cancer diagnoses were identified from the national cancer registries, which collect data regarding all malignant tumors diagnosed in the participating countries.The cancer registries of Denmark, Finland, and Sweden have been validated with high completeness and accuracy. 10,14,15e secondary outcome was cardiovascular disease, defined as a composite outcome of myocardial infarction, ischemic stroke, and cerebral hemorrhage (eTable 4 in Supplement 1), identified from the patient registries.The Danish and Swedish patient registries have been specifically validated for cardiovascular disease with excellent results. 11,16Follow-up ended on the date of diagnosis of obesity-related cancer (for the main outcome only), cardiovascular disease (for the secondary outcome only), bariatric surgery (for patients who did not undergo surgery only), death, or the end of the study period, whichever occurred first.

Confounders
We considered the following variables as confounders: diabetes, hypertension, peripheral vascular disease, chronic obstructive pulmonary disease, and kidney disease (eTable 5 in Supplement 1).
Additionally, we approximated frailty by adjusting for 3 additional variables: deep vein thrombosis or pulmonary embolism, pneumonia, and number of hospital admissions before cohort entry (eTable 5 in Supplement 1).The frailty variables were included to describe and adjust for any apparent selection of more fit candidates for bariatric surgery compared with nonoperative management.Data on all confounders were retrieved from the national patient registries and indexed at study entry.

Statistical Analysis
Multivariable Cox regression analysis provided hazard ratios (HR) with 95% CIs for both outcomes, adjusted for diabetes (yes or no), hypertension (yes or no), peripheral vascular disease (yes or no), chronic obstructive pulmonary disease (yes or no), kidney disease (yes or no), deep vein thrombosis or pulmonary embolism (yes or no), pneumonia (yes or no), and number of hospital admissions before cohort entry (continuous).SEs were computed using a sandwich estimator clustered on the matching ID variable.The main analysis was conducted with a break-off at exactly 1 year after study entry to allow for latency of the outcomes of bariatric surgery and to avoid biasing the results due to selection of more fit candidates for surgery.Such selection could be declining patients with poor cardiovascular health surgery, optimizing cardiovascular health before surgery, or using diagnostic modalities such as computed tomography or endoscopy to ensure that the patients were free of disease at baseline.All reported HRs were therefore based on person-time and cases occurring after the first year of follow-up unless otherwise stated.Stratified analyses were conducted for the variables country (Denmark, Finland, or Sweden), age (60-65, 66-70, or >70 years), sex (men or women), diabetes (yes or no), and duration of follow-up (<1 year, 1-5 years, 6-10 years, 11-15 years, or Ն16 years).In a sensitivity analysis, subhazard ratios (SHR) of time to main and secondary outcomes were computed considering time to death a competing event.Finally, a subgroup analysis in patients who underwent gastric bypass surgery, which is the bariatric procedure associated with most weight loss and best metabolic control, and corresponding matched controls was conducted.The proportionality assumption of the Cox models was assessed by computing the Schoenfeld residuals  1).Patients who underwent surgery were more frequently diagnosed with diabetes and hypertension, but other comorbidities were comparable between the groups at study entry (Table 1).  1, Figure 2B).The overall risk of cardiovascular disease was similar among patients with bariatric surgery and nonoperative treatments (HR, 0.86; 95% CI, 0.74-1.01)(Table 3).Patients with

Discussion
The main finding of this study was that bariatric surgery in older patients was not associated with a decreased risk of obesity-related cancer or cardiovascular disease.It appeared to be associated with a limited benefit in certain subgroups, however, such as a decreased risk of obesity-related cancer in women and a decreased risk of both obesity-related cancer and cardiovascular disease in patients who underwent gastric bypass.
The long-term risks for obesity-related cancer and cardiovascular disease postbariatric surgery have been studied extensively in adults younger than 60 years.A systematic review and meta-analysis 17 of 33 cohort studies including a total of 25 632 528 patients showed that those who underwent bariatric surgery had a 44% reduced risk of obesity-related cancer (OR, 0.56; 95% CI, 0.46-0.68).Another systematic review and meta-analysis 6 of 39 cohort studies indicated a reduced risk of several cardiovascular diseases, such as myocardial infarction (HR, 0.58; 95% CI, 0.43-0.76),stroke (HR, 0.64; and hypertension (OR, 0.45; 95% CI, 0.37-0.53)compared with those who had gastric bypass before age 60 years.A single-center cohort study in 83 patients with bariatric surgery at age 60 years or older found a similar improvement in obesity-related comorbidities as in younger patients who underwent surgery but was probably underpowered to find smaller differences in comorbidity improvement. 18Another single-center cohort study of 500 patients undergoing bariatric surgery found that patients who underwent surgery at age 60 years or older had less weight loss and lower resolution of comorbidities compared with younger patients who underwent surgery. 19These studies show that bariatric surgery is slightly less efficient with respect to weight loss and comorbidity resolution when performed in older patients.
In this study, older patients with bariatric surgery did not have a decreased risk of obesity-related cancer or cardiovascular disease.These findings may be explained by the poorer weight loss and resolution of comorbidities observed in patients who underwent surgery at an older age. 8,17,18However, we found that women had a lower risk for obesity-related cancer after bariatric surgery.This might be explained by the fact that weight loss reduces the circulating levels of estrogen, which could consequently reduce the risk of estrogen-sensitive cancers such as endometrial and breast cancer. 20The risk of cardiovascular disease was clearly reduced within 1 year of surgery, but the association attenuated to null after this initial period.The initial protective association may be explained by the catabolic state induced by bariatric surgery as a possible protection against cardiovascular diseases. 21Additionally, patients who underwent gastric bypass had a slight but significantly lower risk for both obesity-related cancer and cardiovascular disease.Gastric bypass induces profound weight loss and has a highly effective metabolic impact, which may explain a more powerful association in contrast to all bariatric procedures. 22Similarly, gastric bypass appears to be the most powerful bariatric procedure in the prevention of obesity-related cancer and cardiovascular disease in younger patients. 23

Strengths and Limitations
This was the first study we know of to examine the risk of obesity-related cancer and cardiovascular disease in older patients undergoing bariatric surgery.Methodological strengths of the study included the nationwide coverage of patients from 3 Nordic countries, which allowed for a large sample size of patients followed up for a long period of time.The data sources used in the study have been extensively validated specifically cancer diagnoses and cardiovascular disease with excellent results.The large sample size allowed for stratified analyses, which identified subgroups that could benefit from bariatric surgery.Due to the nationwide design with mandatory participation among all permanent residents of the 3 participating countries, follow-up was complete and there were no missing data.The long follow-up time allowed for a long latency between surgery and outcomes and the avoidance of selection bias due to losses to follow-up.Finally, the populationbased design facilitated the generalization of the results to countries with similar health care structures and demographics as the participating countries (eg, the other Nordic countries).
This study had limitations.One limitation was potential residual confounding, including missing data on body mass index and smoking, which were not available from the national health registries.
We took steps to control confounding by matching and adjustments for comorbidities associated with both obesity-related cancer and cardiovascular disease, thereby indirectly adjusting for any residual confounding as well.After the matching process, we found the group who underwent surgery and the group who did not to be similar with respect to most comorbidities and frailty, indicating no clear differences between the groups.The exceptions were diabetes and hypertension, which was expected, as the presence of these comorbidities increases the indication for having bariatric surgery.Similarly, unobserved selection cannot be excluded, as patients accepted for and accepting to undergo bariatric surgery may be different from those refraining from or being declined surgery (eg, regarding fitness, cardiopulmonary health, or psychiatric stability).Some of these more nuanced differences may represent a systematic difference between patients who undergo surgery and those who do not, which may not be possible to measure using registry data but may only be observable in the clinical setting and may therefore not have been corrected in the matching and adjustment process.Thus, the observational design and possibilities for residual confounding and selection prohibits a causal interpretation of the results.
It should also be acknowledged that the null association between bariatric surgery and outcomes observed in this study may be due to imprecision (ie, limited power).While the sample size of the study was comparably large, both main and subanalyses consistently yielded results with point estimates below 1 but with CIs encompassing 1.It is therefore possible that future studies with larger sample sizes and lower risk of random error will provide statistically significant results supporting bariatric surgery as a method to reduce incidence of obesity-related cancer and cardiovascular disease in older patients.This uncertainty will likely be answered when more data from other study settings are available.Additionally, the results should be generalized to patients currently receiving bariatric surgery and not necessarily to patients receiving bariatric surgery in the future (eg, in the circumstance where the eligibility criteria for bariatric surgery is expanded beyond the age of 60 years).

Table 2 .
Risk of Obesity-Related Cancer in Older Patients Treated With Bariatric Surgery vs Nonoperative Treatment for ObesityIncidence of Cancer and Cardiovascular Disease After Bariatric Surgery in the Older Patients 95% CI, 0.53-0.77),and cardiovascular mortality (HR, 0.59; 95% CI, 0.47-0.73)following bariatric surgery compared with conservative nonoperative treatment.However, these studies were conducted in younger patients and the association between bariatric surgery and obesity-related cancer or cardiovascular disease specifically in patients older than 60 years was not investigated.Some previous studies have examined the resolution of comorbidities in older patients undergoing bariatric surgery.A large Swedish cohort study 8 of 2687 patients undergoing gastric bypass at age 60 years or older found inferior resolution of diabetes (OR, 0.70; 95% CI, 0.57-0.86) Abbreviation: HR, hazard ratio.a Patients who did not undergo surgery served as the reference group.b Excluding the first year of follow-up.JAMA Network Open | Surgery JAMA Network Open.2024;7(8):e2427457.doi:10.1001/jamanetworkopen.2024.27457(Reprinted) August 13, 2024 6/10 Downloaded from jamanetwork.comby guest on 09/05/2024

Table 3 .
Risk of Cardiovascular Disease in Older Patients Treated With Bariatric Surgery vs Nonoperative Treatment for Obesity Incidence of Cancer and Cardiovascular Disease After Bariatric Surgery in the Older Patients a Patients who did not undergo surgery served as the reference group.bExcluding the first year of follow-up.
Procedural Codes for Bariatric Surgery eTable 2. Diagnosis Codes for Obesity eTable 3. Diagnosis Codes for Exclusion Criteria eTable 4. Diagnosis Codes for Main and Secondary Outcomes eTable 5. Diagnosis Codes for Confounders eTable 6. P-values for the Null Hypothesis that the Proportionality Assumption of the Cox Regression is Valid (Analysis of the Schoenfeld Residuals on Time) eTable 7. Characteristics Among Older Patients With Gastric Bypass and Matched Controls With Nonoperative Treatment For Obesity eTable 8. Risk of Obesity-Related Cancer and Cardiovascular Disease in Older Patients With Gastric Bypass Versus Nonoperative Treatment for Obesity eAppendix.Study Protocol eReferences.