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Does bariatric surgery reduce the risk of major cardiovascular events? A retrospective cohort study of morbidly obese surgical patients
Surgery for Obesity and Related Diseases 9 (2013) 32– 41
Original article
Does bariatric surgery reduce the risk of major cardiovascular events? A retrospective cohort study of morbidly obese surgical patients John D. Scott, M.D., F.A.C.S., F.A.S.M.B.S.*, Brent L. Johnson, M.S., Dawn W. Blackhurst, Dr.P.H., Eric S. Bour, M.D., F.A.C.S., F.A.S.M.B.S. Greenville Hospital System University Medical Center, University of South Carolina School of Medicine, Greenville, Greenville, South Carolina Received May 1, 2011; accepted September 5, 2011
Abstract
Background: Morbid obesity is associated with the development of cardiovascular and cerebrovascular disease. Several studies have shown that bariatric surgery results in risk factor reduction; however, studies correlating bariatric surgery to the reduced rates of myocardial infarction, stroke, or death have been limited. Methods: We conducted a large retrospective cohort study of bariatric (BAR) surgical patients (n ⫽ 4747) and morbidly obese orthopedic (n ⫽ 3066) and gastrointestinal (n ⫽ 1327) surgical controls. Data were obtained for all patients aged 40 –79 years, from 1996 to 2008, with a diagnosis code of morbid obesity and a primary surgical procedure of interest. The data sources were the statewide South Carolina Universal Billing Code of 1992 inpatient hospitalization database and death records. The primary study outcome was the time-to-occurrence of the composite outcome of postoperative myocardial infarction, stroke, or death (all-cause). Results: The 5-year Kaplan-Meier life table estimate of the composite index of event-free survival in the BAR, orthopedic, and gastrointestinal cohorts was 84.8%, 72.8%, and 65.8%, respectively. After adjusting for baseline differences and potential confounders, the Cox proportional hazards ratio was .72 (95% confidence interval .58 –.89) for BAR versus orthopedic and .48 (95% confidence interval .39 –.61) for BAR versus gastrointestinal. Conclusion: Bariatric surgery was significantly associated with a 25–50% risk reduction in the composite index of postoperative myocardial infarction, stroke, or death compared with other morbidly obese surgical patients in South Carolina. (Surg Obes Relat Dis 2013;9:32– 41.) © 2013 American Society for Metabolic and Bariatric Surgery. All rights reserved.
Keywords:
Bariatric surgery; Myocardial infarction; Stroke; Cardiovascular events; Mortality
From 1986 to 2005, the prevalence of morbid obesity in the United States quintupled, with recent estimates suggesting nearly 1 in 17 U.S. adults is morbidly obese [1,2]. Bariatric surgery has been established as an efficacious treatment in this population, successfully resulting in reductions in body weight, resolution of type 2 diabetes mellitus and hypertension, and improvements in the lipid profile,
*Correspondence: John D. Scott, M.D., F.A.C.S., F.A.S.M.B.S., Department of Surgery, Greenville Hospital System University Medical Center, University of South Carolina School of Medicine, Greenville Campus, 2104 Woodruff Road, Greenville, SC 29607. E-mail: [email protected]
coronary heart disease risk score, and survival [3,4]. In 2007, two landmark studies explored the effect of bariatric surgery on mortality. The Swedish Obese Subjects study, a prospective controlled study, demonstrated that bariatric surgery is associated with decreased overall mortality [5]. A large retrospective cohort study by Adams et al. [6] also demonstrated that long-term mortality after gastric bypass surgery is significantly reduced. Although gastric bypass and adjustable gastric banding have shown strong evidence of risk factor reduction, evidence correlating the performance of bariatric surgery to a direct reduction in major adverse events, such as myocardial infarction (MI) and cerebrovascular accident, has been limited.
1550-7289/13/$ – see front matter © 2013 American Society for Metabolic and Bariatric Surgery. All rights reserved. doi:10.1016/j.soard.2011.09.002
Bariatric Surgery and Risk of Major Cardiovascular Events / Surgery for Obesity and Related Diseases 9 (2013) 32– 41
To date, we are unaware of any comparative studies examining cardiovascular event rates in patients undergoing bariatric surgery versus similar surgical controls. The purpose of our retrospective cohort study was to compare the incidence of major cardiovascular outcomes (i.e., MI, cerebrovascular accident, death) in bariatric surgical patients versus two surgical control groups.
Methods Data sources Administrative inpatient hospitalization data (i.e., Universal Billing Code of 1992) were obtained from the South Carolina Office of Research and Statistics (SCORS) for all patients from 1996 to 2008 who met the study inclusion criteria. The Universal Billing Code of 1992 data have been collected from all hospitals and outpatient surgical facilities by SCORS since 1995. Each patient is assigned a unique registry identification number that allows for linkage and tracking of all reported patient records across multiple hospital admissions and facilities. Death data were obtained from the South Carolina Department of Health and Environmental Control’s Office of Vital Statistics and linked to the SCORS data. Patients The Greenville Hospital System University Medical Center institutional review board approved our study. All patient linkages were performed by SCORS personnel, and all patient identifiers were removed from the final linked data set before the study analyses. The SCORS database was queried for all inpatients aged 40 –79 years who were discharged between January 1, 1996 and December 31, 2008, and who had a diagnosis of morbid obesity and a primary surgical procedure of interest. A detailed flow diagram of patient identification and cohort assignment is provided in Fig. 1. The final linked data set included all hospitalizations and death data available for the 3 cohorts of patients through December 31, 2008. All patients admitted nonemergently and having an “International Classification of Disease, 9th Revision, Clinical Modification” (ICD-9-CM) primary bariatric procedure code of 44.38, 44.39, or 44.95 were identified as the bariatric (BAR) cohort. Any patient not undergoing a bariatric procedure during the study period was then considered for inclusion in one of two surgical control groups. Patients undergoing the orthopedic procedures of joint replacement/ revision or spinal/vertebral/disc surgery were included in the orthopedic (ORT) cohort, and patients undergoing the gastrointestinal procedures of cholecystectomy, hernia repair, or lysis of adhesions were included in the gastrointestinal (GI) cohort. Patients were excluded if they had a documented history of MI or cerebrovascular accident, had
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a primary outcome within 30 days of the index procedure, or had missing or implausible data. Patient characteristics The demographic data were based on the index hospitalization used for cohort assignment. Co-morbid conditions were evaluated for each hospitalization, and a date of the first diagnosis was assigned for each condition. The following co-morbid conditions were assessed and defined using these ICD-9-CM diagnosis codes: morbid obesity (278.01), hypertension (401), diabetes (250), dyslipidemia (272), obstructive coronary artery disease (CAD, 414), sleep apnea (780.5), and a history of transient ischemic attack (TIA, 435). Any of these diagnoses, occurring before or concurrent with the index study procedure admission, were considered positive for that condition. Outcome assessment The primary study outcome was the time-to-occurrence of the composite outcome of MI (ICD-9-CM codes 410 – 413), stroke (434), or death from any cause. Beginning on the date of the index procedure, the patients were assessed for each subsequent hospitalization for a new diagnosis of MI or stroke or a discharge status of death. Patients not experiencing the outcome during the study period were censored on the date of last known hospitalization discharge date. The secondary outcomes were MI, stroke, and death assessed as individual outcomes. Previous definitions of MI and stroke were applied, with the addition of any cause of death consistent with MI (ICD9-CM codes 410 – 413; ICD-10-CM codes I20-I22, I24) or stroke (ICD-9-CM code 434; ICD-10-CM code I63) considered positive for the outcome. Statistical analysis Bivariate analyses were conducted using the Pearson chi-square test for categorical data and analysis of variance and the Kruskal-Wallis test for continuously distributed data. Two-group comparisons of continuous data were completed using the Wilcoxon rank-sum test. Kaplan-Meier life table analyses were used to estimate event-free survival, and the log-rank test was used to identify differences among the groups. Cox proportional hazards regression techniques were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). The models were fit with the type of surgery and adjusted for all demographic characteristics and co-morbid conditions measured. Statistical significance was assessed at ␣ ⫽ .05, except for the post hoc 2-group comparisons, which were assessed at P ⱕ .025. Results From 1996 to 2008, 43,104 patients aged 40 –79 years were hospitalized in South Carolina with a diagnosis of
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J. D. Scott et al. / Surgery for Obesity and Related Diseases 9 (2013) 32– 41
Fig. 1. Patient flow chart.
morbid obesity. Of these 4747, 3066, and 1327 met the eligibility criteria and were included in the BAR, ORT, and GI cohorts, respectively (Fig. 1). The patients in the BAR cohort were, in general, younger, more frequently women and white, more likely to have been diagnosed with dyslipidemia and sleep apnea, and less likely to have been diagnosed with CAD or TIA than those in each control group (Table 1). The BAR cohort was more likely to have been diagnosed with hypertension than the ORT cohort but was similar to the GI cohort. The BAR group was significantly less likely to require additional hospitalizations during follow-up than were the ORT (P ⬍ .001) and GI (P ⬍ .001) groups, contributing to significant differences in the median follow-up (BAR ⬍1 mo versus ORT 10.4 mo, P ⬍ .001; versus GI 11.4 mo; P ⬍ .001).
Primary outcome Of the BAR cohort, 166 (3.5%) were identified as experiencing the composite index of MI, stroke, or death compared with 364 (11.9%) in the ORT cohort and 215 (16.2%) in the GI cohort. The life-table estimates demonstrated significantly improved event-free survival in the BAR cohort (1-, 3-, and 5-year survival rate 97.5% ⫾ .4%, 92.7% ⫾ .7%, and 84.8% ⫾ 1.4%, respectively) compared with the ORT (96.1% ⫾ .5%, 85.6% ⫾ 1.0%, and 72.8% ⫾ 1.5%, respectively; P ⬍ .001) and GI (93.4% ⫾ .9%, 79.9% ⫾ 1.7%, and 65.8% ⫾ 2.3%, respectively; P ⬍ .001) cohorts (Fig. 2). The adjusted HR estimates further supported a significant independent association of improved composite index event-free survival in the BAR cohort compared with the ORT (HR .72, 95% CI .58 –.89) and GI (HR .48, 95% CI .39 –.61) cohorts (Table 2).
Bariatric Surgery and Risk of Major Cardiovascular Events / Surgery for Obesity and Related Diseases 9 (2013) 32– 41
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Table 1 Patient characteristics by cohort Characteristic
Bariatric
Orthopedic
Gastrointestinal
P value
N Age in Years: N (%) 40–49 50–59 60–69 70–79 Mean ⫾ SD Male Gender: N (%) Race: N (%) Caucasian African-American Other Hypertension: N (%) Dyslipidemia: N (%) Diabetes: N (%) Coronary Artery Disease: N (%) Obstructive Sleep Apnea: N (%) History of TIA: N (%) Subsequent Hospitalization: N (%) Follow-up (Months) Mean ⫾ SD Follow-up (Months) Median (25th, 75th Percentiles)
4747
3066
1327
—
2315 (48.8) 1845 (38.9) 545 (11.5) 42 (0.9) 50.5 ⫾ 7.4 808 (17.0)
619 (20.2) 1095 (35.7) 962 (31.4) 390 (12.7) 58.1 ⫾ 9.3 733 (23.9)
501 (37.8) 498 (37.5) 230 (17.3) 98 (7.4) 53.7 ⫾ 9.3 287 (21.6)
⬍0.001*
3833 (80.8) 860 (18.1) 54 (1.1) 3372 (71.0) 1812 (38.2) 1936 (40.8) 249 (5.3) 1549 (32.6) 19 (0.4)
2060 (67.2) 981 (32.0) 25 (.8) 2372 (77.4) 991 (32.3) 1225 (40.0) 334 (10.9) 597 (19.5) 37 (1.2)
921 (69.4) 392 (29.5) 14 (1.1) 958 (72.2) 318 (24.0) 572 (43.1) 151 (11.4) 297 (22.4) 17 (1.3)
⬍0.001† ⬍0.001* 0.148‡ ⬍0.001* ⬍0.001* ⬍0.001*
2231 (47.0)
2144 (69.9)
847 (63.8)
⬍0.001*
13.7 ⫾ 21.9
25.3 ⫾ 32.5
25.8 ⫾ 32.0
⬍0.001*
0.2 (2 days, 21.7)
10.4 (5 days, 41.0)
11.4 (4 days, 44.5)
⬍0.001*
⬍0.001* ⬍0.001* ⬍0.001*
BAR ⫽ bariatric surgery; ORT ⫽ orthopedic surgery; GI ⫽ gastrointestinal surgery. * BAR vs. ORT P ⬍ 0.001 and BAR vs. GI P ⬍ 0.001. † BAR vs. ORT P ⬍ 0.001 and BAR vs. GI P ⬎ 0.05. ‡ BAR vs. ORT P ⬎ 0.05 and BAR vs. GI P ⬎ 0.05.
Secondary outcomes The BAR cohort experienced 81 MIs, 18 strokes, and 82 deaths during the follow-up period. The corresponding 5-year event-free survival estimates for MI, stroke, and
death were 92.4% ⫾ 1.0%, 98.1% ⫾ .5%, and 92.7% ⫾ 1.0%, respectively. The ORT cohort experienced 186 MIs, 48 strokes, and 215 deaths, with associated 5-year eventfree survival estimates of 85.6% ⫾ 1.2% (P ⬍ .001 versus BAR), 96.1% ⫾ .7% (P ⫽ .013), and 84.2% ⫾ 1.3% (P ⬍ .001). The GI cohort experienced 95 MIs, 21 strokes, and 143 deaths, with associated 5-year event-free survival estimates of 83.9% ⫾ 1.8% (P ⬍ .001 versus BAR), 96.1% ⫾ 1.0% (P ⫽ .022), and 77.8% ⫾ 2.0% (P ⬍ .001). Bariatric surgery remained significantly associated with improved MI-free survival on multivariate analysis compared with each control group (versus ORT, HR .59, 95% CI .44 –.79; and versus GI, HR .49, 95% CI .36 –.68). Associations with improved stroke-free survival and improved overall survival were seen among the BAR cohort versus the GI cohort (stroke, HR .49, 95% CI .24 –.98, death, HR .45, 95% CI .33–.60) but not the ORT cohort (stroke, HR .69, 95% CI .37–1.30; death, HR .81, 95% CI .60 –1.10). However, a general tendency toward improved event-free survival was noted in the BAR cohort (Fig. 3).
Discussion Fig. 2. Kaplan-Meier life table for cardiovascular outcomes in morbidly obese surgical patients undergoing bariatric surgery (BAR), orthopedic surgery (ORT), or gastrointestinal surgery (GI).
The results of the present study are consistent with a 25–50% relative risk reduction for a first MI, stroke, or
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J. D. Scott et al. / Surgery for Obesity and Related Diseases 9 (2013) 32– 41
Table 2 Cox proportional hazard ratios and 95% confidence intervals for primary and secondary outcomes stratified by cohort (full models) Factor BAR versus ORT Orthopedic surgery Bariatric surgery Age group 40–49 50–59 60–69 70–79 Race White Black Other Gender Female Male Hypertension Dyslipidemia Diabetes CAD OSA History of TIA BAR versus GI Orthopedic surgery Bariatric surgery Age group (yr) 40–49 50–59 60–69 70–79 Race White Black Other Gender Female Male Hypertension Dyslipidemia Diabetes CAD OSA History of TIA
Composite outcome
MI
Stroke
Death
Referent .72 (.6–.9)
Referent .59 (.4–.8)
Referent .69 (.4–1.3)
Referent .81 (.6–1.1)
Referent 1.30 (1.0–1.6) 1.62 (1.2–2.1) 1.94 (1.4–2.7)
Referent 1.05 (.8–1.5) 1.20 (.8–1.7) 1.10 (.7–1.7)
Referent 1.48 (.7–3.0) 2.00 (.9–4.4) 2.66 (1.1–6.5)
Referent 1.47 (1.0–2.1) 2.41 (1.7–3.5) 3.43 (2.3–5.2)
Referent .95 (.8–1.2) .98 (.2–3.9)
Referent .82 (.6–1.1) —
Referent 1.46 (.9–2.5) 10.3 (2.4–43.9)
Referent 1.07 (.8–1.4) 1.57 (.4–6.4)
Referent 1.57 (1.3–1.9) 1.08 (.9–1.4) 1.13 (.9–1.4) 1.41 (1.2–1.7) 1.52 (1.2–1.9) 1.01 (.8–1.2) .89 (.4–2.0)
Referent 1.55 (1.2–2.1) 1.19 (.9–1.7) 1.27 (1.0–1.7) 1.70 (1.3–2.2) 1.95 (1.4–2.7) .86 (.7–1.1) .49 (.1–2.0)
Referent 1.29 (.7–2.3) 1.20 (.6–2.4) 1.27 (.8–2.2) 1.41 (.9–2.3) 1.38 (.7–2.7) 1.41 (.8–2.4) 1.06 (.1–7.9)
Referent 1.45 (1.1–1.9) 1.02 (.8–1.4) .96 (.7–1.3) 1.14 (.9–1.5) 1.08 (.8–1.5) 1.15 (.9–1.5) 1.11 (.4–3.0)
Referent .48 (.4–.6)
Referent .49 (.4–.7)
Referent .49 (.2–.9)
Referent .45 (.3–.6)
Referent 1.21 (.9–1.5) 1.83 (1.4–2.5) 2.86 (1.9–4.4)
Referent .84 (.6–1.2) 1.19 (.8–1.8) 1.29 (.6–2.7)
Referent 2.29 (1.0–5.2) 4.64 (1.9–11.2) —
Referent 1.49 (1.1–2.1) 2.37 (1.6–3.5) 5.10 (3.1–8.5)
Referent 1.07 (.8–1.4) .91 (.2–3.7)
Referent 1.04 (.7–1.5) 1.96 (.5–8.0)
Referent 1.46 (.7–2.9) —
Referent 1.19 (.9–1.6) 1.13 (.3–4.6)
Referent 1.33 (1.0–1.7) 1.00 (.8–1.3) 1.28 (1.0–1.6) 1.54 (1.2–1.9) 1.37 (1.0–1.8) 1.16 (.9–1.5) .85 (.3–2.1)
Referent 1.40 (1.0–2.0) 1.05 (.7–1.5) 1.67 (1.2–2.3) 1.85 (1.3–2.6) 1.91 (1.3–2.8) 1.08 (.8–1.5) 1.60 (.6–4.5)
Referent .82 (.3–2.0) 3.08 (1.1–9.0) 1.24 (.6–2.5) 1.14 (.6–2.2) .56 (.2–1.9) 1.31 (.7–2.6) —
Referent 1.27 (.9–1.8) .79 (.6–1.1) 1.07 (.8–1.5) 1.49 (1.1–2.0) 1.17 (.8–1.7) 1.22 (.9–1.6) .84 (.3–2.7)
BAR ⫽ bariatric surgery; ORT ⫽ orthopedic surgery; GI ⫽ gastrointestinal surgery; CAD ⫽ coronary artery disease; OSA ⫽ obstructive sleep apnea; TIA ⫽ transient ischemic attack.
death associated with bariatric surgery and a 20 –50% relative risk reduction for each component considered individually. Although the risks of stroke and death were not statistically significantly reduced in the BAR cohort compared with the ORT cohort, other factors might have influenced this result. We used the last discharge date from a South Carolina hospital as the censor date for patients not experiencing the primary outcome. This practice, although statistically conservative, might have artificially influenced our results because patients not requiring subsequent hospitalizations (i.e., the healthiest patients after surgery) were censored at the discharge date of the index procedure hospitalization. If one is willing to assume that patients not
included in the death index and not requiring hospital readmission remained event free to the end of the study period, our results are more marked (Fig. 3). Most likely, the true estimate lies somewhere in the middle of these two approaches. Several previous studies have evaluated changes in the Framingham risk score after bariatric surgery, with most estimates proposing a relative Framingham risk score reduction of 20 – 60% achieved at 1 year [7–10]. The 40 –50% relative risk reduction for a first MI we have reported appears consistent with these prediction models. In the only known controlled study reporting on incident stroke and MI, Adams et al. [11] reported exceedingly low rates of MI and
Bariatric Surgery and Risk of Major Cardiovascular Events / Surgery for Obesity and Related Diseases 9 (2013) 32– 41
Fig. 3. Estimated HRs and 95% CIs for cardiovascular outcomes in morbidly obese surgical patients undergoing bariatric surgery, orthopedic surgery, or gastrointestinal surgery.
stroke within two years across bariatric and nonsurgical control groups and, thus, was severely underpowered to adequately address this question. Mortality data are both more readily available and have been more rigorously studied than the Framingham risk score and cardiovascular event data. The Swedish Obesity Subjects study, a prospective, controlled observational study of 4047 obese subjects (mean follow-up 10.9 yr) reported a significant relative mortality risk reduction of 29% among patients undergoing bariatric surgery compared with matched nonsurgical controls [5]. In a similar study of statewide administrative data, Flum et al. [12] reported a 33% risk reduction among bariatric patients versus nonsurgical controls when examining those patients who had survived ⱖ1 year. A recent meta-analysis of 8 controlled clinical trials, including 44,022 patients, reported a 45% relative risk reduction for mortality in patients undergoing bariatric surgery; the effect was stronger for cardiovascular causes (HR .58) than for noncardiovascular causes (HR .70) [13]. Again, our results (19 –55% relative risk reduction) are consistent with those from previous reports. We selected a composite primary outcome measure because it is an accepted and frequently used outcome in epidemiologic cohort studies. All-cause mortality, instead of cardiovascular mortality, was selected, because it is an accepted outcome measure and the data are more reliable. The cause-of-death information on death certificates is often inconsistent and subjective. Thus, because we had no ability to review the medical records and verify the cause of death, we chose the more reliable measure.
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The results of our study must be considered in the context of several strengths and limitations of our study design. The limitations of administrative billing data are well-documented [14 –16]. These data are subject to significant misclassification and omission, identify only the 15 leading ICD-9 diagnoses at each hospitalization, and might be highly variable from coder to coder. This limited our ability to successfully adjust for key risk factors, such as smoking, and could not rule out significant residual confounding due to misclassification for those risk factors we were able to assess. Furthermore, the placement of the morbid obesity diagnosis code in the diagnostic hierarchy is predominantly attributable to reimbursement directives, resulting in a primary diagnosis of morbid obesity in nearly 100% of the BAR cohort and a secondary diagnosis in the ORT and GI cohorts. Thus, we could not compare the ranking of this code across groups as an assessment of the baseline health status. In reviewing our own institutional data for placement of the morbid obesity code in patients undergoing ORT or GI procedures, 65% of patients had code 278.01 located within the top five diagnoses and 84% and 94% had this code in the top 10 and 15 codes, respectively. Patients with morbid obesity codes outside the top 15 codes are likely very ill patients, and the exclusion of these patients from the control groups prevented inclusion of the sickest ORT and GI patients. Additionally, administrative data often lack key diagnostic and empirical data. In our study, the lack of body mass index or weight data are a valid criticism. The absence of data supporting the proposed mechanism of risk reduction limits any assessment of a causal relationship. The SCORS registry passively follows patients, recording events only if they occur within the confines of a South Carolina healthcare institution. If an index procedure was performed in South Carolina, but the patient relocated to another state and had a composite outcome event, this would not be reflected in our data. We believe that the rate of relocation of bariatric patients is at least similar, if not lower, than that of orthopedic or general surgical patients. Additionally, if a patient assumes a normal healthy life after surgery and requires no additional hospitalizations, this patient would have been censored at the date of discharge of the index hospitalization, limiting the contribution of this healthiest group of patients to the overall results. Our results reflect that the BAR cohort was significantly less likely to require subsequent hospitalizations than the ORT and GI cohorts This might indicate differences in the baseline health status. It could also be a direct result of bariatric surgery, because the myriad health benefits of surgically induced weight loss have been shown to be significantly associated with fewer hospitalizations. A number of specific diseases or conditions, including cardiovascular and circulatory diseases, cancers, endocrine conditions, infections, and musculoskeletal conditions, have been shown to decrease during the first five years after surgery [17]. Most
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importantly, despite a median follow-up among the BAR cohort consistent with the discharge date of the index procedure hospitalization, statistically significant differences were still present. Long-term outcomes were not captured well in our study and would likely require active follow-up and a longer study duration. Bariatric surgical patients are a truly unique population. The lower prevalence of diagnosed CAD and history of TIA at baseline were likely consistent with the younger age of the BAR cohort compared with the two control groups. We made our best attempt at choosing two separate control groups with a reasonably comparable baseline health status. Although these two groups were a perfect match the BAR group, it is unlikely that such a group exists outside of randomization. One might propose matching patients for CAD and a history of TIA as an alternative approach. However, given the longitudinal nature of the study with substantial known losses to follow-up occurring in each patient cohort, it is unlikely that matching would offer any benefit because the composition of the cohorts was altered substantially within a short period after the index procedure. Thus, one would still need to rely on the use of regression techniques to account for differences in CAD, a history of TIA, age, and any other confounding variables, just as we have done. Furthermore, the penalties for such a design strategy would include the loss of data and preclude any analysis of matched variables. Although the control groups identified for our study were not perfect, this is a limitation endemic to studies using hospital-based controls and nonrandomized controls more generally. However, we used standard statistical methods for dealing with such circumstances and believe that our results, although imperfect, offer a reasonable approximation of the risk reduction associated with bariatric surgery in this population. This belief was further supported by the consistency of our results with most previously published data. Despite these limitations, our study had several key strengths. Before querying SCORS, a review of the Greenville Hospital System inpatient database was conducted, also under institutional review board approval. The purpose of the review was to identify morbidly obese patients to determine two general groupings of nonemergent procedures common among these patients and to verify that the prevalence of selected co-morbid conditions in these patient groups was reasonably comparable to that of our bariatric patient population. We used these two separate surgical control groups in an effort to eliminate the bias effect of a medical cohort in which some patients might have been deemed unfit for elective surgery. Furthermore, the use of two independent control groups should have helped to reconcile the biases unique to each control group. The attainment of similar results using different control groups lends additional support to the observation that bariatric surgery is associated with improved cardiovascular outcomes in morbidly obese adults healthy enough for elective surgery.
Although the risk reduction estimates of the two groups were not identical in magnitude (nor would we expect them to be), the direction of the reported effect was consistently in favor of bariatric surgery. Additionally, we conducted analyses using two different dates for censoring purposes. The first and most conservative method provided the basis of our results and used the last known discharge date from a South Carolina hospital. We would argue that if any bias were introduced using this method it would be in the direction of the null hypothesis, because patients without subsequent hospitalizations would contribute little to the overall follow-up data. Alternatively, using the end of study date (December 31, 2008) for censoring resulted in more profound differences among the groups (Fig. 3). However, the argument for the latter would be that the bias introduced by this method would favor the alternative hypothesis. As mentioned previously, the truth likely lies somewhere in the middle of these two estimates. Also, the use of an administrative database, in which large numbers of patients from a variety of settings and providers are studied, allows for increased study power and greater generalization of these results to the broader population. Unlike previous studies, our study population was limited to patients aged 40 –79 years, creating patient cohorts at high risk of the outcomes of interest. A cautious interpretation of the results supports the findings of similar studies: bariatric surgery reduces the overall risk of mortality, decreases the risk factors for CVD and cerebrovascular disease, and, ultimately, helps prevent MI and stroke. Although previous studies have indicated that cardiovascular mortality is affected by bariatric surgery, our results further demonstrate that nonfatal vascular morbidity is significantly lower in patients who have undergone bariatric surgery. Prospective studies are needed to confirm these findings and to better characterize the strength of association. Conclusion Bariatric surgery was significantly associated with a 25– 50% risk reduction in the composite index of postoperative MI, stroke, or death compared with other morbidly obese surgical patients in South Carolina. Acknowledgment The authors would like to thank Jonathan Lokey, Alfredo Carbonell, William Cobb, and Gregory Mancini for their help in the preparation of our report. Disclosures The authors have no commercial associations that might be a conflict of interest in relation to this article.
Bariatric Surgery and Risk of Major Cardiovascular Events / Surgery for Obesity and Related Diseases 9 (2013) 32– 41
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[9] Arteburn D, Schauer DP, Wise RE, et al. Change in predicted 10-year cardiovascular risk following laparoscopic Roux-en-Y gastric bypass surgery. Obes Surg 2009;19:184 –9. [10] Batsis JA, Sarr MG, Collazo-Clavell ML, et al. Cardiovascular risk after bariatric surgery for obesity. Am J Cardiol 2008;102:930 –7. [11] Adams TD, Pendleton RC, Strong MB, et al. Health outcomes of gastric bypass patients compared to nonsurgical, nonintervened severely obese. Obesity 2010;18:121–30. [12] Flum DR, Dellinger EP. Impact of gastric bypass operation on survival: a population-based analysis. J Am Coll Surg 2004;199:543–51. [13] Pontiroli AE, Morabito A. Long term mortality in morbid obesity through bariatric surgery: a systematic review and meta-analysis of trials with gastric banding and gastric bypass. Ann Surg 2011;253: 484 –7. [14] Flum DR. Editorial: Administrative data analyses in bariatric surgery—limits of the technique. Surg Obes Relat Dis 2006;2:78 – 81. [15] Svenson JE, Pollack SH, Fallat ME, Drapeau JL. Limitations of electronic databases: a caution. J Ky Med Assoc 2003;101:109 –12. [16] Guller U. Surgical outcomes research based on administrative data: inferior or complementary to prospective randomized clinical trials. World J Surg 2006;30:255– 66. [17] Christou NV, Sampalis JS, Liberman M, et al. Surgery decreases long-term mortality, morbidity, and health care use in morbidly obese patients. Ann Surg 2004;240:416 –24.
Editorial comment
Comment on: Does bariatric surgery reduce the risk of major cardiovascular events? A retrospective cohort study of morbidly obese surgical patients The prevalence of morbid obesity has been shown to be increasing at an even greater rate than general obesity in many developed countries and is likely to continue to increase [1,2]. The high risks of a range of chronic diseases associated with morbid obesity make this a critical healthcare challenge. Although comprehensive epidemiologic data are not yet available for all the health risks associated with morbid obesity, it is likely to be associated with very high risks of diseases with a large impact on the individual and the health system, including diabetes, cardiovascular disease, sleep apnea, cancer, osteoarthritis, infertility, depression, and mortality [3,4]. The prevention of these health sequelae will require a range of approaches, including addressing the obesogenic environment within which we live, encouraging individual level behaviour change and clinical intervention, with the goals of prevention of weight gain, but particularly focusing on weight loss [5]. Most clinical guidelines recommend bariatric surgery for morbidly obese patients for whom nonoperative measures of weight loss have failed. With the recent withdrawal of a prominent weight loss drug from the market, bariatric surgery is 1 of the few methods for achieving weight loss and 1 of the only methods to achieve substantial, sustained weight loss [6].
However, the evidence for the health benefits from bariatric surgery in the morbidly obese is still in its infancy. Recent reviews have described the demonstrable effectiveness of bariatric surgery in the morbidly obese in terms of weight loss but few have measured the health outcomes. There is good evidence that surgery results in diabetes remission and lower rates of metabolic syndrome, hypertension, and all-cause mortality [7–13]. The demonstrable effect of bariatric surgery on both cardiovascular risk factors and all-cause mortality make it likely that it has an effect on cardiovascular disease. The mortality analysis of the Swedish Obesity Study demonstrated an apparent reduction in myocardial infarction deaths; however, the numbers were too small to make a definitive conclusion [12]. The study by Adams et al. [10] demonstrated a 56% reduction in mortality from coronary artery disease. However, similar effectiveness has not yet been demonstrated for nonfatal cardiovascular disease. The study in this issue of the Journal by Scott et al. uses a detailed retrospective comparative cohort analysis to explore this issue. The authors use a large surgical cohort of all patients from all hospitals and outpatient surgical facilities in South Carolina treated from 1996 to 2008. The strengths of these data include the comprehensiveness, comparable data collection
Original article
Does bariatric surgery reduce the risk of major cardiovascular events? A retrospective cohort study of morbidly obese surgical patients John D. Scott, M.D., F.A.C.S., F.A.S.M.B.S.*, Brent L. Johnson, M.S., Dawn W. Blackhurst, Dr.P.H., Eric S. Bour, M.D., F.A.C.S., F.A.S.M.B.S. Greenville Hospital System University Medical Center, University of South Carolina School of Medicine, Greenville, Greenville, South Carolina Received May 1, 2011; accepted September 5, 2011
Abstract
Background: Morbid obesity is associated with the development of cardiovascular and cerebrovascular disease. Several studies have shown that bariatric surgery results in risk factor reduction; however, studies correlating bariatric surgery to the reduced rates of myocardial infarction, stroke, or death have been limited. Methods: We conducted a large retrospective cohort study of bariatric (BAR) surgical patients (n ⫽ 4747) and morbidly obese orthopedic (n ⫽ 3066) and gastrointestinal (n ⫽ 1327) surgical controls. Data were obtained for all patients aged 40 –79 years, from 1996 to 2008, with a diagnosis code of morbid obesity and a primary surgical procedure of interest. The data sources were the statewide South Carolina Universal Billing Code of 1992 inpatient hospitalization database and death records. The primary study outcome was the time-to-occurrence of the composite outcome of postoperative myocardial infarction, stroke, or death (all-cause). Results: The 5-year Kaplan-Meier life table estimate of the composite index of event-free survival in the BAR, orthopedic, and gastrointestinal cohorts was 84.8%, 72.8%, and 65.8%, respectively. After adjusting for baseline differences and potential confounders, the Cox proportional hazards ratio was .72 (95% confidence interval .58 –.89) for BAR versus orthopedic and .48 (95% confidence interval .39 –.61) for BAR versus gastrointestinal. Conclusion: Bariatric surgery was significantly associated with a 25–50% risk reduction in the composite index of postoperative myocardial infarction, stroke, or death compared with other morbidly obese surgical patients in South Carolina. (Surg Obes Relat Dis 2013;9:32– 41.) © 2013 American Society for Metabolic and Bariatric Surgery. All rights reserved.
Keywords:
Bariatric surgery; Myocardial infarction; Stroke; Cardiovascular events; Mortality
From 1986 to 2005, the prevalence of morbid obesity in the United States quintupled, with recent estimates suggesting nearly 1 in 17 U.S. adults is morbidly obese [1,2]. Bariatric surgery has been established as an efficacious treatment in this population, successfully resulting in reductions in body weight, resolution of type 2 diabetes mellitus and hypertension, and improvements in the lipid profile,
*Correspondence: John D. Scott, M.D., F.A.C.S., F.A.S.M.B.S., Department of Surgery, Greenville Hospital System University Medical Center, University of South Carolina School of Medicine, Greenville Campus, 2104 Woodruff Road, Greenville, SC 29607. E-mail: [email protected]
coronary heart disease risk score, and survival [3,4]. In 2007, two landmark studies explored the effect of bariatric surgery on mortality. The Swedish Obese Subjects study, a prospective controlled study, demonstrated that bariatric surgery is associated with decreased overall mortality [5]. A large retrospective cohort study by Adams et al. [6] also demonstrated that long-term mortality after gastric bypass surgery is significantly reduced. Although gastric bypass and adjustable gastric banding have shown strong evidence of risk factor reduction, evidence correlating the performance of bariatric surgery to a direct reduction in major adverse events, such as myocardial infarction (MI) and cerebrovascular accident, has been limited.
1550-7289/13/$ – see front matter © 2013 American Society for Metabolic and Bariatric Surgery. All rights reserved. doi:10.1016/j.soard.2011.09.002
Bariatric Surgery and Risk of Major Cardiovascular Events / Surgery for Obesity and Related Diseases 9 (2013) 32– 41
To date, we are unaware of any comparative studies examining cardiovascular event rates in patients undergoing bariatric surgery versus similar surgical controls. The purpose of our retrospective cohort study was to compare the incidence of major cardiovascular outcomes (i.e., MI, cerebrovascular accident, death) in bariatric surgical patients versus two surgical control groups.
Methods Data sources Administrative inpatient hospitalization data (i.e., Universal Billing Code of 1992) were obtained from the South Carolina Office of Research and Statistics (SCORS) for all patients from 1996 to 2008 who met the study inclusion criteria. The Universal Billing Code of 1992 data have been collected from all hospitals and outpatient surgical facilities by SCORS since 1995. Each patient is assigned a unique registry identification number that allows for linkage and tracking of all reported patient records across multiple hospital admissions and facilities. Death data were obtained from the South Carolina Department of Health and Environmental Control’s Office of Vital Statistics and linked to the SCORS data. Patients The Greenville Hospital System University Medical Center institutional review board approved our study. All patient linkages were performed by SCORS personnel, and all patient identifiers were removed from the final linked data set before the study analyses. The SCORS database was queried for all inpatients aged 40 –79 years who were discharged between January 1, 1996 and December 31, 2008, and who had a diagnosis of morbid obesity and a primary surgical procedure of interest. A detailed flow diagram of patient identification and cohort assignment is provided in Fig. 1. The final linked data set included all hospitalizations and death data available for the 3 cohorts of patients through December 31, 2008. All patients admitted nonemergently and having an “International Classification of Disease, 9th Revision, Clinical Modification” (ICD-9-CM) primary bariatric procedure code of 44.38, 44.39, or 44.95 were identified as the bariatric (BAR) cohort. Any patient not undergoing a bariatric procedure during the study period was then considered for inclusion in one of two surgical control groups. Patients undergoing the orthopedic procedures of joint replacement/ revision or spinal/vertebral/disc surgery were included in the orthopedic (ORT) cohort, and patients undergoing the gastrointestinal procedures of cholecystectomy, hernia repair, or lysis of adhesions were included in the gastrointestinal (GI) cohort. Patients were excluded if they had a documented history of MI or cerebrovascular accident, had
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a primary outcome within 30 days of the index procedure, or had missing or implausible data. Patient characteristics The demographic data were based on the index hospitalization used for cohort assignment. Co-morbid conditions were evaluated for each hospitalization, and a date of the first diagnosis was assigned for each condition. The following co-morbid conditions were assessed and defined using these ICD-9-CM diagnosis codes: morbid obesity (278.01), hypertension (401), diabetes (250), dyslipidemia (272), obstructive coronary artery disease (CAD, 414), sleep apnea (780.5), and a history of transient ischemic attack (TIA, 435). Any of these diagnoses, occurring before or concurrent with the index study procedure admission, were considered positive for that condition. Outcome assessment The primary study outcome was the time-to-occurrence of the composite outcome of MI (ICD-9-CM codes 410 – 413), stroke (434), or death from any cause. Beginning on the date of the index procedure, the patients were assessed for each subsequent hospitalization for a new diagnosis of MI or stroke or a discharge status of death. Patients not experiencing the outcome during the study period were censored on the date of last known hospitalization discharge date. The secondary outcomes were MI, stroke, and death assessed as individual outcomes. Previous definitions of MI and stroke were applied, with the addition of any cause of death consistent with MI (ICD9-CM codes 410 – 413; ICD-10-CM codes I20-I22, I24) or stroke (ICD-9-CM code 434; ICD-10-CM code I63) considered positive for the outcome. Statistical analysis Bivariate analyses were conducted using the Pearson chi-square test for categorical data and analysis of variance and the Kruskal-Wallis test for continuously distributed data. Two-group comparisons of continuous data were completed using the Wilcoxon rank-sum test. Kaplan-Meier life table analyses were used to estimate event-free survival, and the log-rank test was used to identify differences among the groups. Cox proportional hazards regression techniques were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). The models were fit with the type of surgery and adjusted for all demographic characteristics and co-morbid conditions measured. Statistical significance was assessed at ␣ ⫽ .05, except for the post hoc 2-group comparisons, which were assessed at P ⱕ .025. Results From 1996 to 2008, 43,104 patients aged 40 –79 years were hospitalized in South Carolina with a diagnosis of
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J. D. Scott et al. / Surgery for Obesity and Related Diseases 9 (2013) 32– 41
Fig. 1. Patient flow chart.
morbid obesity. Of these 4747, 3066, and 1327 met the eligibility criteria and were included in the BAR, ORT, and GI cohorts, respectively (Fig. 1). The patients in the BAR cohort were, in general, younger, more frequently women and white, more likely to have been diagnosed with dyslipidemia and sleep apnea, and less likely to have been diagnosed with CAD or TIA than those in each control group (Table 1). The BAR cohort was more likely to have been diagnosed with hypertension than the ORT cohort but was similar to the GI cohort. The BAR group was significantly less likely to require additional hospitalizations during follow-up than were the ORT (P ⬍ .001) and GI (P ⬍ .001) groups, contributing to significant differences in the median follow-up (BAR ⬍1 mo versus ORT 10.4 mo, P ⬍ .001; versus GI 11.4 mo; P ⬍ .001).
Primary outcome Of the BAR cohort, 166 (3.5%) were identified as experiencing the composite index of MI, stroke, or death compared with 364 (11.9%) in the ORT cohort and 215 (16.2%) in the GI cohort. The life-table estimates demonstrated significantly improved event-free survival in the BAR cohort (1-, 3-, and 5-year survival rate 97.5% ⫾ .4%, 92.7% ⫾ .7%, and 84.8% ⫾ 1.4%, respectively) compared with the ORT (96.1% ⫾ .5%, 85.6% ⫾ 1.0%, and 72.8% ⫾ 1.5%, respectively; P ⬍ .001) and GI (93.4% ⫾ .9%, 79.9% ⫾ 1.7%, and 65.8% ⫾ 2.3%, respectively; P ⬍ .001) cohorts (Fig. 2). The adjusted HR estimates further supported a significant independent association of improved composite index event-free survival in the BAR cohort compared with the ORT (HR .72, 95% CI .58 –.89) and GI (HR .48, 95% CI .39 –.61) cohorts (Table 2).
Bariatric Surgery and Risk of Major Cardiovascular Events / Surgery for Obesity and Related Diseases 9 (2013) 32– 41
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Table 1 Patient characteristics by cohort Characteristic
Bariatric
Orthopedic
Gastrointestinal
P value
N Age in Years: N (%) 40–49 50–59 60–69 70–79 Mean ⫾ SD Male Gender: N (%) Race: N (%) Caucasian African-American Other Hypertension: N (%) Dyslipidemia: N (%) Diabetes: N (%) Coronary Artery Disease: N (%) Obstructive Sleep Apnea: N (%) History of TIA: N (%) Subsequent Hospitalization: N (%) Follow-up (Months) Mean ⫾ SD Follow-up (Months) Median (25th, 75th Percentiles)
4747
3066
1327
—
2315 (48.8) 1845 (38.9) 545 (11.5) 42 (0.9) 50.5 ⫾ 7.4 808 (17.0)
619 (20.2) 1095 (35.7) 962 (31.4) 390 (12.7) 58.1 ⫾ 9.3 733 (23.9)
501 (37.8) 498 (37.5) 230 (17.3) 98 (7.4) 53.7 ⫾ 9.3 287 (21.6)
⬍0.001*
3833 (80.8) 860 (18.1) 54 (1.1) 3372 (71.0) 1812 (38.2) 1936 (40.8) 249 (5.3) 1549 (32.6) 19 (0.4)
2060 (67.2) 981 (32.0) 25 (.8) 2372 (77.4) 991 (32.3) 1225 (40.0) 334 (10.9) 597 (19.5) 37 (1.2)
921 (69.4) 392 (29.5) 14 (1.1) 958 (72.2) 318 (24.0) 572 (43.1) 151 (11.4) 297 (22.4) 17 (1.3)
⬍0.001† ⬍0.001* 0.148‡ ⬍0.001* ⬍0.001* ⬍0.001*
2231 (47.0)
2144 (69.9)
847 (63.8)
⬍0.001*
13.7 ⫾ 21.9
25.3 ⫾ 32.5
25.8 ⫾ 32.0
⬍0.001*
0.2 (2 days, 21.7)
10.4 (5 days, 41.0)
11.4 (4 days, 44.5)
⬍0.001*
⬍0.001* ⬍0.001* ⬍0.001*
BAR ⫽ bariatric surgery; ORT ⫽ orthopedic surgery; GI ⫽ gastrointestinal surgery. * BAR vs. ORT P ⬍ 0.001 and BAR vs. GI P ⬍ 0.001. † BAR vs. ORT P ⬍ 0.001 and BAR vs. GI P ⬎ 0.05. ‡ BAR vs. ORT P ⬎ 0.05 and BAR vs. GI P ⬎ 0.05.
Secondary outcomes The BAR cohort experienced 81 MIs, 18 strokes, and 82 deaths during the follow-up period. The corresponding 5-year event-free survival estimates for MI, stroke, and
death were 92.4% ⫾ 1.0%, 98.1% ⫾ .5%, and 92.7% ⫾ 1.0%, respectively. The ORT cohort experienced 186 MIs, 48 strokes, and 215 deaths, with associated 5-year eventfree survival estimates of 85.6% ⫾ 1.2% (P ⬍ .001 versus BAR), 96.1% ⫾ .7% (P ⫽ .013), and 84.2% ⫾ 1.3% (P ⬍ .001). The GI cohort experienced 95 MIs, 21 strokes, and 143 deaths, with associated 5-year event-free survival estimates of 83.9% ⫾ 1.8% (P ⬍ .001 versus BAR), 96.1% ⫾ 1.0% (P ⫽ .022), and 77.8% ⫾ 2.0% (P ⬍ .001). Bariatric surgery remained significantly associated with improved MI-free survival on multivariate analysis compared with each control group (versus ORT, HR .59, 95% CI .44 –.79; and versus GI, HR .49, 95% CI .36 –.68). Associations with improved stroke-free survival and improved overall survival were seen among the BAR cohort versus the GI cohort (stroke, HR .49, 95% CI .24 –.98, death, HR .45, 95% CI .33–.60) but not the ORT cohort (stroke, HR .69, 95% CI .37–1.30; death, HR .81, 95% CI .60 –1.10). However, a general tendency toward improved event-free survival was noted in the BAR cohort (Fig. 3).
Discussion Fig. 2. Kaplan-Meier life table for cardiovascular outcomes in morbidly obese surgical patients undergoing bariatric surgery (BAR), orthopedic surgery (ORT), or gastrointestinal surgery (GI).
The results of the present study are consistent with a 25–50% relative risk reduction for a first MI, stroke, or
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Table 2 Cox proportional hazard ratios and 95% confidence intervals for primary and secondary outcomes stratified by cohort (full models) Factor BAR versus ORT Orthopedic surgery Bariatric surgery Age group 40–49 50–59 60–69 70–79 Race White Black Other Gender Female Male Hypertension Dyslipidemia Diabetes CAD OSA History of TIA BAR versus GI Orthopedic surgery Bariatric surgery Age group (yr) 40–49 50–59 60–69 70–79 Race White Black Other Gender Female Male Hypertension Dyslipidemia Diabetes CAD OSA History of TIA
Composite outcome
MI
Stroke
Death
Referent .72 (.6–.9)
Referent .59 (.4–.8)
Referent .69 (.4–1.3)
Referent .81 (.6–1.1)
Referent 1.30 (1.0–1.6) 1.62 (1.2–2.1) 1.94 (1.4–2.7)
Referent 1.05 (.8–1.5) 1.20 (.8–1.7) 1.10 (.7–1.7)
Referent 1.48 (.7–3.0) 2.00 (.9–4.4) 2.66 (1.1–6.5)
Referent 1.47 (1.0–2.1) 2.41 (1.7–3.5) 3.43 (2.3–5.2)
Referent .95 (.8–1.2) .98 (.2–3.9)
Referent .82 (.6–1.1) —
Referent 1.46 (.9–2.5) 10.3 (2.4–43.9)
Referent 1.07 (.8–1.4) 1.57 (.4–6.4)
Referent 1.57 (1.3–1.9) 1.08 (.9–1.4) 1.13 (.9–1.4) 1.41 (1.2–1.7) 1.52 (1.2–1.9) 1.01 (.8–1.2) .89 (.4–2.0)
Referent 1.55 (1.2–2.1) 1.19 (.9–1.7) 1.27 (1.0–1.7) 1.70 (1.3–2.2) 1.95 (1.4–2.7) .86 (.7–1.1) .49 (.1–2.0)
Referent 1.29 (.7–2.3) 1.20 (.6–2.4) 1.27 (.8–2.2) 1.41 (.9–2.3) 1.38 (.7–2.7) 1.41 (.8–2.4) 1.06 (.1–7.9)
Referent 1.45 (1.1–1.9) 1.02 (.8–1.4) .96 (.7–1.3) 1.14 (.9–1.5) 1.08 (.8–1.5) 1.15 (.9–1.5) 1.11 (.4–3.0)
Referent .48 (.4–.6)
Referent .49 (.4–.7)
Referent .49 (.2–.9)
Referent .45 (.3–.6)
Referent 1.21 (.9–1.5) 1.83 (1.4–2.5) 2.86 (1.9–4.4)
Referent .84 (.6–1.2) 1.19 (.8–1.8) 1.29 (.6–2.7)
Referent 2.29 (1.0–5.2) 4.64 (1.9–11.2) —
Referent 1.49 (1.1–2.1) 2.37 (1.6–3.5) 5.10 (3.1–8.5)
Referent 1.07 (.8–1.4) .91 (.2–3.7)
Referent 1.04 (.7–1.5) 1.96 (.5–8.0)
Referent 1.46 (.7–2.9) —
Referent 1.19 (.9–1.6) 1.13 (.3–4.6)
Referent 1.33 (1.0–1.7) 1.00 (.8–1.3) 1.28 (1.0–1.6) 1.54 (1.2–1.9) 1.37 (1.0–1.8) 1.16 (.9–1.5) .85 (.3–2.1)
Referent 1.40 (1.0–2.0) 1.05 (.7–1.5) 1.67 (1.2–2.3) 1.85 (1.3–2.6) 1.91 (1.3–2.8) 1.08 (.8–1.5) 1.60 (.6–4.5)
Referent .82 (.3–2.0) 3.08 (1.1–9.0) 1.24 (.6–2.5) 1.14 (.6–2.2) .56 (.2–1.9) 1.31 (.7–2.6) —
Referent 1.27 (.9–1.8) .79 (.6–1.1) 1.07 (.8–1.5) 1.49 (1.1–2.0) 1.17 (.8–1.7) 1.22 (.9–1.6) .84 (.3–2.7)
BAR ⫽ bariatric surgery; ORT ⫽ orthopedic surgery; GI ⫽ gastrointestinal surgery; CAD ⫽ coronary artery disease; OSA ⫽ obstructive sleep apnea; TIA ⫽ transient ischemic attack.
death associated with bariatric surgery and a 20 –50% relative risk reduction for each component considered individually. Although the risks of stroke and death were not statistically significantly reduced in the BAR cohort compared with the ORT cohort, other factors might have influenced this result. We used the last discharge date from a South Carolina hospital as the censor date for patients not experiencing the primary outcome. This practice, although statistically conservative, might have artificially influenced our results because patients not requiring subsequent hospitalizations (i.e., the healthiest patients after surgery) were censored at the discharge date of the index procedure hospitalization. If one is willing to assume that patients not
included in the death index and not requiring hospital readmission remained event free to the end of the study period, our results are more marked (Fig. 3). Most likely, the true estimate lies somewhere in the middle of these two approaches. Several previous studies have evaluated changes in the Framingham risk score after bariatric surgery, with most estimates proposing a relative Framingham risk score reduction of 20 – 60% achieved at 1 year [7–10]. The 40 –50% relative risk reduction for a first MI we have reported appears consistent with these prediction models. In the only known controlled study reporting on incident stroke and MI, Adams et al. [11] reported exceedingly low rates of MI and
Bariatric Surgery and Risk of Major Cardiovascular Events / Surgery for Obesity and Related Diseases 9 (2013) 32– 41
Fig. 3. Estimated HRs and 95% CIs for cardiovascular outcomes in morbidly obese surgical patients undergoing bariatric surgery, orthopedic surgery, or gastrointestinal surgery.
stroke within two years across bariatric and nonsurgical control groups and, thus, was severely underpowered to adequately address this question. Mortality data are both more readily available and have been more rigorously studied than the Framingham risk score and cardiovascular event data. The Swedish Obesity Subjects study, a prospective, controlled observational study of 4047 obese subjects (mean follow-up 10.9 yr) reported a significant relative mortality risk reduction of 29% among patients undergoing bariatric surgery compared with matched nonsurgical controls [5]. In a similar study of statewide administrative data, Flum et al. [12] reported a 33% risk reduction among bariatric patients versus nonsurgical controls when examining those patients who had survived ⱖ1 year. A recent meta-analysis of 8 controlled clinical trials, including 44,022 patients, reported a 45% relative risk reduction for mortality in patients undergoing bariatric surgery; the effect was stronger for cardiovascular causes (HR .58) than for noncardiovascular causes (HR .70) [13]. Again, our results (19 –55% relative risk reduction) are consistent with those from previous reports. We selected a composite primary outcome measure because it is an accepted and frequently used outcome in epidemiologic cohort studies. All-cause mortality, instead of cardiovascular mortality, was selected, because it is an accepted outcome measure and the data are more reliable. The cause-of-death information on death certificates is often inconsistent and subjective. Thus, because we had no ability to review the medical records and verify the cause of death, we chose the more reliable measure.
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The results of our study must be considered in the context of several strengths and limitations of our study design. The limitations of administrative billing data are well-documented [14 –16]. These data are subject to significant misclassification and omission, identify only the 15 leading ICD-9 diagnoses at each hospitalization, and might be highly variable from coder to coder. This limited our ability to successfully adjust for key risk factors, such as smoking, and could not rule out significant residual confounding due to misclassification for those risk factors we were able to assess. Furthermore, the placement of the morbid obesity diagnosis code in the diagnostic hierarchy is predominantly attributable to reimbursement directives, resulting in a primary diagnosis of morbid obesity in nearly 100% of the BAR cohort and a secondary diagnosis in the ORT and GI cohorts. Thus, we could not compare the ranking of this code across groups as an assessment of the baseline health status. In reviewing our own institutional data for placement of the morbid obesity code in patients undergoing ORT or GI procedures, 65% of patients had code 278.01 located within the top five diagnoses and 84% and 94% had this code in the top 10 and 15 codes, respectively. Patients with morbid obesity codes outside the top 15 codes are likely very ill patients, and the exclusion of these patients from the control groups prevented inclusion of the sickest ORT and GI patients. Additionally, administrative data often lack key diagnostic and empirical data. In our study, the lack of body mass index or weight data are a valid criticism. The absence of data supporting the proposed mechanism of risk reduction limits any assessment of a causal relationship. The SCORS registry passively follows patients, recording events only if they occur within the confines of a South Carolina healthcare institution. If an index procedure was performed in South Carolina, but the patient relocated to another state and had a composite outcome event, this would not be reflected in our data. We believe that the rate of relocation of bariatric patients is at least similar, if not lower, than that of orthopedic or general surgical patients. Additionally, if a patient assumes a normal healthy life after surgery and requires no additional hospitalizations, this patient would have been censored at the date of discharge of the index hospitalization, limiting the contribution of this healthiest group of patients to the overall results. Our results reflect that the BAR cohort was significantly less likely to require subsequent hospitalizations than the ORT and GI cohorts This might indicate differences in the baseline health status. It could also be a direct result of bariatric surgery, because the myriad health benefits of surgically induced weight loss have been shown to be significantly associated with fewer hospitalizations. A number of specific diseases or conditions, including cardiovascular and circulatory diseases, cancers, endocrine conditions, infections, and musculoskeletal conditions, have been shown to decrease during the first five years after surgery [17]. Most
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importantly, despite a median follow-up among the BAR cohort consistent with the discharge date of the index procedure hospitalization, statistically significant differences were still present. Long-term outcomes were not captured well in our study and would likely require active follow-up and a longer study duration. Bariatric surgical patients are a truly unique population. The lower prevalence of diagnosed CAD and history of TIA at baseline were likely consistent with the younger age of the BAR cohort compared with the two control groups. We made our best attempt at choosing two separate control groups with a reasonably comparable baseline health status. Although these two groups were a perfect match the BAR group, it is unlikely that such a group exists outside of randomization. One might propose matching patients for CAD and a history of TIA as an alternative approach. However, given the longitudinal nature of the study with substantial known losses to follow-up occurring in each patient cohort, it is unlikely that matching would offer any benefit because the composition of the cohorts was altered substantially within a short period after the index procedure. Thus, one would still need to rely on the use of regression techniques to account for differences in CAD, a history of TIA, age, and any other confounding variables, just as we have done. Furthermore, the penalties for such a design strategy would include the loss of data and preclude any analysis of matched variables. Although the control groups identified for our study were not perfect, this is a limitation endemic to studies using hospital-based controls and nonrandomized controls more generally. However, we used standard statistical methods for dealing with such circumstances and believe that our results, although imperfect, offer a reasonable approximation of the risk reduction associated with bariatric surgery in this population. This belief was further supported by the consistency of our results with most previously published data. Despite these limitations, our study had several key strengths. Before querying SCORS, a review of the Greenville Hospital System inpatient database was conducted, also under institutional review board approval. The purpose of the review was to identify morbidly obese patients to determine two general groupings of nonemergent procedures common among these patients and to verify that the prevalence of selected co-morbid conditions in these patient groups was reasonably comparable to that of our bariatric patient population. We used these two separate surgical control groups in an effort to eliminate the bias effect of a medical cohort in which some patients might have been deemed unfit for elective surgery. Furthermore, the use of two independent control groups should have helped to reconcile the biases unique to each control group. The attainment of similar results using different control groups lends additional support to the observation that bariatric surgery is associated with improved cardiovascular outcomes in morbidly obese adults healthy enough for elective surgery.
Although the risk reduction estimates of the two groups were not identical in magnitude (nor would we expect them to be), the direction of the reported effect was consistently in favor of bariatric surgery. Additionally, we conducted analyses using two different dates for censoring purposes. The first and most conservative method provided the basis of our results and used the last known discharge date from a South Carolina hospital. We would argue that if any bias were introduced using this method it would be in the direction of the null hypothesis, because patients without subsequent hospitalizations would contribute little to the overall follow-up data. Alternatively, using the end of study date (December 31, 2008) for censoring resulted in more profound differences among the groups (Fig. 3). However, the argument for the latter would be that the bias introduced by this method would favor the alternative hypothesis. As mentioned previously, the truth likely lies somewhere in the middle of these two estimates. Also, the use of an administrative database, in which large numbers of patients from a variety of settings and providers are studied, allows for increased study power and greater generalization of these results to the broader population. Unlike previous studies, our study population was limited to patients aged 40 –79 years, creating patient cohorts at high risk of the outcomes of interest. A cautious interpretation of the results supports the findings of similar studies: bariatric surgery reduces the overall risk of mortality, decreases the risk factors for CVD and cerebrovascular disease, and, ultimately, helps prevent MI and stroke. Although previous studies have indicated that cardiovascular mortality is affected by bariatric surgery, our results further demonstrate that nonfatal vascular morbidity is significantly lower in patients who have undergone bariatric surgery. Prospective studies are needed to confirm these findings and to better characterize the strength of association. Conclusion Bariatric surgery was significantly associated with a 25– 50% risk reduction in the composite index of postoperative MI, stroke, or death compared with other morbidly obese surgical patients in South Carolina. Acknowledgment The authors would like to thank Jonathan Lokey, Alfredo Carbonell, William Cobb, and Gregory Mancini for their help in the preparation of our report. Disclosures The authors have no commercial associations that might be a conflict of interest in relation to this article.
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[9] Arteburn D, Schauer DP, Wise RE, et al. Change in predicted 10-year cardiovascular risk following laparoscopic Roux-en-Y gastric bypass surgery. Obes Surg 2009;19:184 –9. [10] Batsis JA, Sarr MG, Collazo-Clavell ML, et al. Cardiovascular risk after bariatric surgery for obesity. Am J Cardiol 2008;102:930 –7. [11] Adams TD, Pendleton RC, Strong MB, et al. Health outcomes of gastric bypass patients compared to nonsurgical, nonintervened severely obese. Obesity 2010;18:121–30. [12] Flum DR, Dellinger EP. Impact of gastric bypass operation on survival: a population-based analysis. J Am Coll Surg 2004;199:543–51. [13] Pontiroli AE, Morabito A. Long term mortality in morbid obesity through bariatric surgery: a systematic review and meta-analysis of trials with gastric banding and gastric bypass. Ann Surg 2011;253: 484 –7. [14] Flum DR. Editorial: Administrative data analyses in bariatric surgery—limits of the technique. Surg Obes Relat Dis 2006;2:78 – 81. [15] Svenson JE, Pollack SH, Fallat ME, Drapeau JL. Limitations of electronic databases: a caution. J Ky Med Assoc 2003;101:109 –12. [16] Guller U. Surgical outcomes research based on administrative data: inferior or complementary to prospective randomized clinical trials. World J Surg 2006;30:255– 66. [17] Christou NV, Sampalis JS, Liberman M, et al. Surgery decreases long-term mortality, morbidity, and health care use in morbidly obese patients. Ann Surg 2004;240:416 –24.
Editorial comment
Comment on: Does bariatric surgery reduce the risk of major cardiovascular events? A retrospective cohort study of morbidly obese surgical patients The prevalence of morbid obesity has been shown to be increasing at an even greater rate than general obesity in many developed countries and is likely to continue to increase [1,2]. The high risks of a range of chronic diseases associated with morbid obesity make this a critical healthcare challenge. Although comprehensive epidemiologic data are not yet available for all the health risks associated with morbid obesity, it is likely to be associated with very high risks of diseases with a large impact on the individual and the health system, including diabetes, cardiovascular disease, sleep apnea, cancer, osteoarthritis, infertility, depression, and mortality [3,4]. The prevention of these health sequelae will require a range of approaches, including addressing the obesogenic environment within which we live, encouraging individual level behaviour change and clinical intervention, with the goals of prevention of weight gain, but particularly focusing on weight loss [5]. Most clinical guidelines recommend bariatric surgery for morbidly obese patients for whom nonoperative measures of weight loss have failed. With the recent withdrawal of a prominent weight loss drug from the market, bariatric surgery is 1 of the few methods for achieving weight loss and 1 of the only methods to achieve substantial, sustained weight loss [6].
However, the evidence for the health benefits from bariatric surgery in the morbidly obese is still in its infancy. Recent reviews have described the demonstrable effectiveness of bariatric surgery in the morbidly obese in terms of weight loss but few have measured the health outcomes. There is good evidence that surgery results in diabetes remission and lower rates of metabolic syndrome, hypertension, and all-cause mortality [7–13]. The demonstrable effect of bariatric surgery on both cardiovascular risk factors and all-cause mortality make it likely that it has an effect on cardiovascular disease. The mortality analysis of the Swedish Obesity Study demonstrated an apparent reduction in myocardial infarction deaths; however, the numbers were too small to make a definitive conclusion [12]. The study by Adams et al. [10] demonstrated a 56% reduction in mortality from coronary artery disease. However, similar effectiveness has not yet been demonstrated for nonfatal cardiovascular disease. The study in this issue of the Journal by Scott et al. uses a detailed retrospective comparative cohort analysis to explore this issue. The authors use a large surgical cohort of all patients from all hospitals and outpatient surgical facilities in South Carolina treated from 1996 to 2008. The strengths of these data include the comprehensiveness, comparable data collection