Survival Among High-Risk Patients After Bariatric Surgery FREE

Obesity incidence has stabilized after decades of rapid increases,¹ whereas the prevalence of patients with a BMI greater than 35 increased 39% between 2000 and 2005, the prevalence of severe obesity (BMI >40) increased 50%, and the prevalence of superobesity (BMI >50) increased 75%.^2- 3 Obesity is difficult to treat, and bariatric surgery is the most effective means to induce weight loss for the severely obese. Consequently, obesity surgery rates rapidly increased in tandem.⁴ Although bariatric surgery reliably induces weight loss, there are few long-term studies of survival related to surgically induced weight loss.⁵

Previous bariatric surgery survival studies examined outcomes in younger, primarily white and female populations whose obesity-related mortality risk is low⁶ and decreasing.^7- 10 These patients' lower mortality has required studies with large samples to detect any mortality differences.^11- 12 Obesity-related mortality is highest in men and minority patients who have high rates of comorbid diseases,¹³ and these patients would potentially benefit the most from bariatric surgery–induced weight loss.

To date, no study to our knowledge has examined the long-term survival of high-risk patients who underwent bariatric surgery. This study's purpose was to determine whether bariatric surgery is associated with reduced mortality in a multisite cohort of predominantly older male high-risk patients who were older than patients in most previous bariatric outcomes assessments. We compared survival through December 2008 between a cohort of veterans who had bariatric surgery in Veterans Affairs medical centers in 2000-2006 and a cohort of veterans who did not have bariatric surgery. This is the first study that we are aware of to compare survival associated with bariatric surgery in predominantly male cohorts of surgical patients and nonsurgical controls.

This evaluation is a retrospective cohort study of bariatric surgery patients and a cohort of nonsurgical, severely obese controls. As described previously,^14- 15 bariatric patients were identified from a database of major surgical procedures performed in Veterans Affairs medical centers maintained by the VA Surgical Quality Improvement Program (formerly known as the National Surgical Quality Improvement Program). Veterans in the program database were identified as having bariatric surgery in fiscal years 2000-2006, according to an algorithm of Current Procedural Terminology-4 codes (43842, 43843, 43846, 43847, and 43848) and International Classification of Diseases, Ninth Revision (ICD-9) codes (278.01, associated with Current Procedural Terminology-4 codes 43659, 43621, or 43633), with a sensitivity of 99.2% and specificity of 99.9%.¹⁶

We identified 892 patients who had bariatric procedures and excluded revisional procedures for 4 patients (Figure 1). Survival time through December 31, 2008, began with each veteran's first instance of observed BMI greater than or equal to 35 after January 1, 2000. Patients were excluded because of death dates before surgery (n = 4), presurgical BMIs less than 35 (n = 9), or missing presurgical comorbidity scores (n = 25). The final surgical cohort included 850 high-risk veterans who had bariatric surgery. We refer to these surgical patients as high risk according to the high proportion of men, older age, and higher BMI compared with that of cohorts in previous bariatric mortality assessments¹¹ because other work has found that patients with these characteristics have higher rates of postsurgical mortality.^12,17

Nonsurgical controls were identified from a Veterans Affairs registry of 1.8 million veterans whose fiscal year 2000 height and weight data were extracted from Veterans Affairs electronic medical records of outpatient visits from 136 Veterans Affairs medical centers.¹⁸ We identified 98 545 veterans who had recorded BMIs between 29 and 80 and had never undergone bariatric surgery in a Veterans Affairs hospital (Figure 2). Control patients were excluded because of missing patient identifiers needed to link other Veterans Affairs databases (n = 563), deaths before fiscal year 2000 (n = 373), or incomplete data to construct patient covariates (n = 157). We also excluded nonsurgical controls with no BMI values greater than or equal to 35 (n = 4853), with missing baseline comorbidity scores (n = 5836), with age 80 years or older during the study period (n = 8509), or with clinical exclusions related to gastrointestinal cancer requiring surgery or peritoneal effusion/ascites (n = 299). To more closely match the availability of medical care resources between surgical and control groups, we excluded severely obese veterans who lived in Veterans Integrated Service Networks lacking a bariatric surgery center in 2000-2006 (n = 36 711). The final nonsurgical control cohort included 41 244 veterans with an initial eligible BMI in 2000-2006 and complete data on patient characteristics and survival status. This study was approved by the Surgical Quality Data Use Group of the VA Office of Patient Care Services; and the institutional review boards of the Durham, North Texas, and Denver Veterans Affairs Medical Centers and of the Group Health Research Institute.

The primary outcome was all-cause mortality, defined as survival time from first BMI greater than or equal to 35 until death date or the end of the observation period (December 31, 2008). The maximum possible survival time was 9 years (January 1, 2000, to December 31, 2008). Trained VA Surgical Quality Improvement Program nurses tracked operative death and perioperative death up to 30 days after the operation with a standardized abstraction form by following the patient by chart review during hospitalization. The nurse then contacted the patient or family 30 days after the operation to identify any subsequent adverse events and validated and updated mortality by checking against a Veterans Affairs vital status database.¹⁹ Veterans Affairs death dates beyond 30 days for case patients and for all controls were obtained from 4 administrative data sets (Beneficiary Identification and Record Locator Subsystem Death File, Veterans Affairs Inpatient utilization files, Medicare Vital Status file, and Social Security Administration Death Master File).²⁰

Unadjusted differences between patients undergoing or not undergoing bariatric surgery were compared with χ² tests for categorical variables and 2-tailed unpaired t tests for continuous variables in the unmatched cohorts, McNemar tests and paired t tests in the matched cohorts, and standardized differences to enable comparison of covariate imbalance between the matched and unmatched cohorts.²¹ The association between bariatric surgery and all-cause mortality was examined in the unmatched cohorts with crude mortality rate comparisons and unadjusted and multivariable Cox proportional hazards regression models.

Operations occurred at different points for the surgical cohort, with considerable delay (median duration = 539 days) between the “zero time” of first reported BMI greater than 35 and day of surgery; therefore, surgery was modeled as a time-dependent treatment to account for survivor treatment bias. Failure to account for this bias would generate biased hazard ratios (HRs) (<1) if the true treatment effect were null.^22- 23 The proportional hazards assumption was confirmed by inspection of log (−log[survival]) curves.

In a multivariable Cox model, we controlled for baseline age, sex, self-reported race, marital status, BMI, comorbidity burden measured by the diagnostic cost group score, and Veterans Integrated Service Network of residence. Baseline BMI was constructed from data contained in the corporate data warehouse vital status files, the registry file, and VA Surgical Quality Improvement Program files on the surgical cases but relied primarily on corporate data warehouse values after exclusion of weight values 3 SDs above or below the presurgical or postsurgical mean for each patient. The diagnostic cost group score aggregates inpatient and outpatient diagnoses in the year before baseline, with scores greater than 1.0 implying above-average expected expenditures and scores less than 1.0 implying below-average expected expenditures. Diagnostic cost group scores were as predictive of veterans' 1-year mortality as other comorbidity scores^24- 26 and were highly predictive of mortality,¹⁴ use, and expenditures¹⁵ in bariatric surgery.

In a third analysis, we accounted for the nonequivalence (eg, selection bias) of the nonsurgical control cohort via propensity score matching with logistic regression, which has been shown to be less biased than propensity adjustment or weighting in survival analysis.²⁷ A propensity score represents the predicted probability that a given patient will undergo bariatric surgery, and patients who had bariatric surgery procedures were matched to controls with a greedy algorithm.²⁸ The propensity score model included interaction of age, age squared, diagnostic cost group, BMI, BMI squared, BMI cubed, sex, race, marital status, and Veterans Integrated Service Networks, as well as numerous 2-way interactions,²⁹ and had a concordance index of 0.85.

Despite the large (n = 41 244) sample of controls, we conducted one-to-one matching to avoid the possible bias of many-to-one matching.³⁰ Each surgical case patient was matched to a single nonsurgical control if their predicted propensity scores were identical to 8 digits. If such a match was not found, the case patient was matched to a control on the basis of a 7-, 6-, 5-, 4-, 3-, 2-, or 1-digit match. This process matched 847 surgical case patients (of 850 possible; 99.6%) to 847 nonsurgical controls, and covariate balance between matched surgical case patients and nonsurgical controls was assessed via McNemar tests, 2-tailed paired t tests, and standardized differences. We then conducted an unadjusted Cox regression stratified on the matched pairs to account for the lack of independence between cohorts induced by matching and a Cox regression adjusted for differences in the year indicating zero time. Alternative propensity score analyses from many-to-one matching generated similar results, so we present the 1:1 matching results here.

The a priori level of statistical significance was set at P < .05 for all analyses, which were 2-tailed and performed with SAS, version 9.2 (SAS Institute Inc, Cary, North Carolina).

The unmatched cohort of 850 veterans who underwent bariatric surgery in 2000-2006 was significantly younger (49.5 vs 54.7 years; P < .001), had higher BMIs (47.4 vs 42.0; P < .001), and had greater comorbidity burden as measured by diagnostic cost group score (0.60 vs 0.47; P < .001) than the 41 244 veterans in the nonsurgical control cohort (Table 1). The surgical patients were more likely to be superobese (BMI ≥50; 31.3% vs 7.0%; P < .001) and white (77.9% vs 67.8%; P < .001) but less likely to be aged 65 years or older (2.1% vs 20.7%; P < .001), men (73.9% vs 91.7%; P < .001), or married (52.1% vs 57.7%; P = .001). The first observation of a BMI greater than or equal to 35 that defined the start time for tracking survival was earlier for nonsurgical controls than case patients (P < .001). As a result, the surgical case patients were observed 1 year less (6.69 years vs 7.62 years; P < .001) than the nonsurgical controls; nearly 85% of the controls had their first recorded BMI greater than 35 in 2000 compared with only 40% of surgical case patients. The mean follow-up time was 6.7 years.

Eleven of 850 surgical case patients (1.29%) died within 30 days of surgery. The surgical case patients had lower crude mortality rates than the nonsurgical controls (1 year, 1.5% vs 2.2%, P = .17; 2 year, 2.2% vs 4.6%, P < .001; 6 year, 6.8% vs 15.2%, P < .001). In an unadjusted Cox regression, bariatric surgery was associated with reduced mortality (HR, 0.64; 95% confidence interval [CI], 0.51-0.80; P < .001). Given the significant differences between surgical case patients and nonsurgical controls, these crude and unadjusted results cannot represent the unbiased association of treatment and survival. After adjustment for baseline covariates (eTable), bariatric surgery remained associated with reduced mortality but to a lesser extent (adjusted HR, 0.80; 95% CI, 0.63-0.995; P = .045).

Propensity score matching resulted in well-balanced cohorts of surgical case patients (n = 847) and nonsurgical controls (n = 847), which were similar in all observed characteristics except year of study entry (Table 2), improving covariate balance from the unmatched cohorts (Table 1). Eleven of the 847 surgical case patients (1.30%) died within 30 days of surgery. Crude mortality differed between matched case patients and controls only at 6 years (1 year, 1.5% vs 2.0%, P = .58; 2 year, 2.2% vs 3.5%, P = .14; 6 year, 6.7% vs 12.8%, P < .001). In Cox regressions using the 1694 propensity-matched patients, bariatric surgery was no longer associated with reduced mortality in unadjusted analysis (HR, 0.83; 95% CI, 0.61-1.14) and in analysis adjusting for differences in start times (HR, 0.94; 95% CI, 0.64-1.39) (Table 3).

Older predominantly male patients with obesity-related comorbid conditions have high mortality and could benefit the most from aggressive obesity treatment. In a propensity-matched cohort of obese high-risk primarily male patients, bariatric surgery was not significantly associated with survival during a mean of 6.7 years of follow-up. These results are in contrast to those of several previous observational studies, which can be explained by important differences in the populations examined, the duration of follow-up, and the extent of covariate adjustment.

One reason bariatric surgery was not associated with survival in this study might be the higher perioperative mortality observed for Roux-en-Y gastric bypass in veteran cohorts.^16,31 The 30-day mortality rates of 1.3% observed in this study is 4-fold higher than that reported in the recent multisite Longitudinal Assessment of Bariatric Surgery study, which included a younger, predominantly female cohort.⁹ Roux-en-Y operations are inherently more difficult in large male patients and are known to be associated with higher mortality rates than for female patients, who have anatomy more favorable for performing complex gastric surgery.¹⁷ Our previous research on this cohort demonstrated less than expected benefit in other outcomes as well. We observed less medication discontinuation³² than that in studies of lower-risk, mostly female diabetic patients³³ and found that health care expenditures were not improved by bariatric surgery¹⁵ within 3 years after surgery. Operations with lower perioperative event rates, such as laparoscopic adjustable banding procedures or gastric sleeve resections, could prove more beneficial. There are no reliable long-term studies of these operations in high-risk cohorts that would suggest that these operations result in lower mortality than gastric bypass procedures.

Our conclusion of no association of bariatric surgery with survival in this high-risk predominantly male cohort contrasts with that of several previous studies, which have differed in cohort characteristics, control identification, and comorbidity adjustment. In a comparison in a cohort of 154 patients with diabetes who underwent Roux-en-Y and 78 obese diabetic patients evaluated for bariatric surgery at the same center,³⁴ unadjusted survival was greater (91%) after a mean follow-up of 9 years in the surgical group compared with the nonsurgical group (72%) at 6 years. The higher mortality observed in the nonsurgical group may be explained by the larger number of minority patients (50% vs 23%), who are known to have greater obesity-related mortality than whites,¹³ and by the lack of comorbidity adjustment. Our unadjusted cohort resembles these patients, but in our rigorous propensity matching analysis, the significant association of bariatric surgery observed in our unmatched analyses was eliminated.

Christou et al³⁵ examined survival for a cohort of 1035 bariatric surgery patients compared with 5746 control patients identified as obese by having an ICD-9 entry of obesity (278.00) or morbid obesity (278.01) in their medical record and no codes for obesity surgery. This analysis yielded lower mortality (0.68% vs 6.17%) for the bariatric surgery cohort compared with the controls during a 5-year follow-up period. The control group was matched 6:1 on patient age, sex, and duration of follow-up, but no clinical information was available for comorbidity adjustment. Flum and Dellinger³⁶ performed an observational study of bariatric patients and controls identified from diagnostic codes in hospital discharge data from Washington State. Bariatric surgery was associated with improved survival (HR, 1.59; 95% CI, 1.49-1.72) after adjustment by age, sex, and Charlson comorbidity score. Both of these studies relied on ICD-9 codes to identify severely obese control patients, which likely identified a more chronically ill and superobese population and likely failed to identify many less severely obese patients who would also have been eligible for bariatric surgery and have served as a valid contrast to the bariatric patients.

Adams et al¹¹ compared survival outcomes for 7925 patients who underwent gastric bypass surgery in Utah with that of 7925 individuals identified as obese from self-reported height and weight information in driver's license applications. Patients were matched on BMI, age, and sex but lacked clinical information for comorbidity adjustment. A modest difference in unadjusted mortality was observed: After 7.1 years of follow-up, the surgical group experienced 2.7% mortality compared with 4.1% in the controls (adjusted HR, 0.60; 95% CI, 0.45-0.67). The average age was much younger¹¹ than in this Veterans Affairs surgical cohort (39.5 vs 49.5) and the proportion of women was much higher¹¹ (84% vs 26%). Demographic differences and lack of comorbidity adjustment may be important factors explaining discrepancies between the results obtained by Adams et al¹¹ and by us.

The only published study examining survival after bariatric surgery that compared groups with high-quality clinical data was the Swedish Obese Subjects (SOS) Study.¹² Clinical information was available for 2027 patients who had bariatric surgery compared with 2037 who elected not to pursue bariatric surgery. These cohorts were followed up for a mean of 11 years and matched according to 18 clinical variables. Bariatric surgery was associated with better survival (adjusted HR, 0.76; 95% CI, 0.59-0.99), according to a 1.3% absolute mortality difference. The Swedish analysis is not comparable to ours because of the different mortality risk in the control groups. The 11-year mortality in the control group was 6.3% in the SOS Study, whereas the 7-year unadjusted mortality rate in the control group was 22.4% in our study. Additionally, two-thirds of the SOS cohort underwent vertical banded gastroplasty, an operation no longer performed in the United States, limiting the generalizability of that study to modern bariatric practice.

Our results highlight the importance of statistical adjustment and careful selection of surgical and nonsurgical cohorts, particularly during evaluation of bariatric surgery according to administrative data.³⁷ Previous studies claiming a survival benefit for bariatric surgery had limited clinical information to conduct detailed risk adjustment or matching.^{10- 11,35- 36} The survival differences between the bariatric surgery and control groups were modest in most previous studies, so the beneficial effects of surgery may have been attenuated if adjustment for confounders had been possible. We demonstrated that risk adjustment with regression analysis resulted in a significant association of surgery and survival that was reduced when equivalence in baseline characteristics improved via propensity matching in this high-risk patient group.

These results suggest that bariatric surgery is not associated with reduced mortality at 6.7 years for older men with higher than average baseline risk for obesity-related complications and mortality compared with bariatric cohorts considered in previous evaluations.¹⁷ This analysis was based on a multisite sample, with data abstracted in a standardized process to ensure high-quality data and minimal measurement error. Additionally, comprehensive claims data enabled us to adjust for patient factors (race, BMI, comorbidity burden, marital status) related to receipt of bariatric surgery and mortality that are unavailable in many health systems. The well-validated diagnostic cost group risk score is used by the Centers for Medicare & Medicaid Services to risk-adjust payments made to Medicare managed care plans³⁸ and has been shown to predict 1-year mortality¹⁴ and presurgical and postsurgical expenditures of this surgical cohort.¹⁵ Careful adjustment for risk differences is a critical need in bariatric evaluations,³⁹ and the use of this risk adjustment measure represents a significant advance in reducing confounding in the mortality association of bariatric surgery.

Our study is subject to several limitations. First, we focused on a cohort of older, predominantly male, sicker patients, so results may not generalize to nonveteran, younger, female, or healthier populations. It is possible that bariatric surgery reduces mortality for younger patients and not for older male patients, but we did not have sufficient sample size to examine whether the association varied across subgroups. Second, our study does not include patients who underwent laparoscopic banding procedures; thus, we cannot generalize our results to such patients. Third, the sample size was restricted in the 1:1 propensity-matched analysis such that large CIs were generated, which cannot rule out that bariatric surgery provides clinically significant benefit or harm to some patients. However, 4:1 propensity-matched analysis yielded similar results. Future studies with larger samples should also consider stratification across clinically relevant patient factors to fully understand which subgroups benefit most from bariatric surgery. Fourth, these results do not account for unobserved confounding that may persist even after propensity score matching because this analysis was based on a quasi-experimental design from administrative data, not a randomized trial.³⁷ The estimated treatment represents an association and not necessarily the causal effect of bariatric surgery on survival. We were able to effectively reduce imbalance in observed covariates via one-to-one propensity score matching, without a significant loss in surgical sample size. This finding was also robust to alternative propensity score approaches, which suggests we strengthened the internal validity of our results without sacrificing generalizability.

These results suggest that bariatric surgery is not associated with reduced mortality among older men within a few years after surgery, which is not entirely surprising; the survival benefit in the SOS Study was not observed until a median of 13 years of follow-up. Therefore, it is possible that we would also observe a protective benefit 10 or more years after surgery, and additional observation time may be required in this older predominantly male cohort. Even though bariatric surgery is not associated with reduced mortality among older male patients, many patients may still choose to undergo bariatric surgery, given the strong evidence for significant reductions in body weight and comorbidities and improved quality of life.

According to propensity score–adjusted analyses of a cohort of predominantly older men, bariatric surgery does not appear to be associated with survival during a mean of 6.7 years of follow-up.