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Association of Metabolic Surgery With Major Adverse Cardiovascular Outcomes in Patients With Type 2 Diabetes and Obesity
Open accessAbstract
IMPORTANCE: Although metabolic surgery (defined as procedures that influence metabolism by inducing weight loss and altering gastrointestinal physiology) significantly improves cardiometabolic risk factors, the effect on cardiovascular outcomes has been less well characterized. OBJECTIVE: To investigate the relationship between metabolic surgery and incident major adverse cardiovascular events (MACE) in patients with type 2 diabetes and obesity. DESIGN, SETTING, AND PARTICIPANTS: Of 287 438 adult patients with diabetes in the Cleveland Clinic Health System in the United States between 1998 and 2017, 2287 patients underwent metabolic surgery. In this retrospective cohort study, these patients were matched 1:5 to nonsurgical patients with diabetes and obesity (body mass index [BMI] ≥30), resulting in 11 435 control patients, with follow-up through December 2018. EXPOSURES: Metabolic gastrointestinal surgical procedures vs usual care for type 2 diabetes and obesity. MAIN OUTCOMES AND MEASURES: The primary outcome was the incidence of extended MACE (composite of 6 outcomes), defined as first occurrence of all-cause mortality, coronary artery events, cerebrovascular events, heart failure, nephropathy, and atrial fibrillation. Secondary end points included 3-component MACE (myocardial infarction, ischemic stroke, and mortality) and the 6 individual components of the primary end point. RESULTS: Among the 13 722 study participants, the distribution of baseline covariates was balanced between the surgical group and the nonsurgical group, including female sex (65.5% vs 64.2%), median age (52.5 vs 54.8 years), BMI (45.1 vs 42.6), and glycated hemoglobin level (7.1% vs 7.1%). The overall median follow-up duration was 3.9 years (interquartile range, 1.9-6.1 years). At the end of the study period, 385 patients in the surgical group and 3243 patients in the nonsurgical group experienced a primary end point (cumulative incidence at 8-years, 30.8% [95% CI, 27.6%-34.0%] in the surgical group and 47.7% [95% CI, 46.1%-49.2%] in the nonsurgical group [P < .001]; absolute 8-year risk difference [ARD], 16.9% [95% CI, 13.1%-20.4%]; adjusted hazard ratio [HR], 0.61 [95% CI, 0.55-0.69]). All 7 prespecified secondary outcomes showed statistically significant differences in favor of metabolic surgery, including mortality. All-cause mortality occurred in 112 patients in the metabolic surgery group and 1111 patients in the nonsurgical group (cumulative incidence at 8 years, 10.0% [95% CI, 7.8%-12.2%] and 17.8% [95% CI, 16.6%-19.0%]; ARD, 7.8% [95% CI, 5.1%-10.2%]; adjusted HR, 0.59 [95% CI, 0.48-0.72]). CONCLUSIONS AND RELEVANCE: Among patients with type 2 diabetes and obesity, metabolic surgery, compared with nonsurgical management, was associated with a significantly lower risk of incident MACE. The findings from this observational study must be confirmed in randomized clinical trials. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03955952.
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“After surgery, the significant improvement of metabolic disease, as well as the decrease in overall mortality, has been reported in multiple studies further supporting the importance of this treatment modality [15–19].”
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“After surgery, the significant improvement of metabolic disease, as well as the decrease in overall mortality, has been reported in multiple studies further supporting the importance of this treatment modality [15–19].”
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“Indeed, marked weight loss achieved through bariatric surgery is associated with improvements in glucose levels and cardiac structure and function in patients with obesity and T2DM.14, 15, 16”
From The cardioprotective effects of semaglutide exceed those of dietary weight loss in mice with HFpEF (2023) · cites this paper as [14]
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“In a recently published retrospective cohort study, a substantial reduction in all-cause mortality and incident cases of major adverse cardiovascular events such as coronary artery events, cerebrovascular events, nephropathy, heart failure and atrial fibrillation was noted in those who had bariatric surgery [62].”
From Bariatric surgery: remission of inflammation, cardiometabolic benefits, and common adverse effects (2020) · cites this paper as [62]
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Biobaku, F., Ghanim, H., Monte, S. V., Caruana, J. A., & Dandona, P. (2020) · Journal of the Endocrine Society · doi:10.1210/jendso/bvaa049 · Cited by 68
“In a recently published retrospective cohort study, a substantial reduction in all-cause mortality and incident cases of major adverse cardiovascular events such as coronary artery events, cerebrovascular events, nephropathy, heart failure and atrial fibrillation was noted in those who had bariatric surgery [62].”
BackgroundAminian, A., Wilson, R. L., Zajichek, A., Tu, C., Wolski, K., Schauer, P. R., Kattan, M. W., Nissen, S. E., & Brethauer, S. A. (2021) · Diabetes Care · doi:10.2337/dc20-3023 · Cited by 70
“End Points As described in the original study (6), the primary end point was the incidence of”
BackgroundMethodInfluentialSelf-citationPatel, K. V., Bahnson, J. L., Gaussoin, S. A., Johnson, K. C., Pi-Sunyer, X., White, U., Olson, K. L., Bertoni, A. G., Kitzman, D. W., Berry, J. D., et al. (2020) · Circulation · doi:10.1161/circulationaha.120.050941 · Cited by 69
Prevention of cardiorenal complications in people with type 2 diabetes and obesity
Drucker, D. J. (2024) · Cell Metabolism · doi:10.1016/j.cmet.2023.12.018 · Cited by 68
Horne, B. D., Grajower, M. M., & Anderson, J. L. (2020) · JAMA · doi:10.1001/jama.2020.3908 · Cited by 68
Treating chronic diseases without tackling excess adiposity promotes multimorbidity
Sattar, N., McMurray, J. J. V., McInnes, I. B., Aroda, V. R., & Lean, M. E. J. (2023) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(22)00317-5 · Cited by 69
Näslund, E. B., Stenberg, E., Hofmann, R., Ottosson, J., Sundbom, M., Marsk, R., Svensson, P., Szummer, K. E., & Jernberg, T. (2020) · Circulation · doi:10.1161/circulationaha.120.048585 · Cited by 66
Donatelli, G., Spota, A., Cereatti, F., Granieri, S., Dagher, I., Chiche, R., Catheline, J.-M., Pourcher, G., Rebibo, L., Calabrese, D., et al. (2021) · Surgery for Obesity and Related Diseases · doi:10.1016/j.soard.2021.03.013 · Cited by 68
Diabetes Mellitus and Heart Failure
Triposkiadis, F. K., Xanthopoulos, A. V., Bargiota, Α., Kitai, T., Katsiki, N., Farmakis, D. T., Skoularigis, J. S., Starling, R. C., & Iliodromitis, E. K. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10163682 · Cited by 73
“Bariatric surgery significantly lowers HF risk in patients with DM and morbid obesity [88,89].”
BackgroundJirapinyo, P., Hadefi, A., Huberty, V., Sullivan, S. A., Thompson, C. C., Patai, Á. V., Pannala, R., Goelder, S. K., Kushnir, V. M., Barthet, M. A., et al. (2024) · Endoscopy · doi:10.1055/a-2292-2494 · Cited by 70
“The amount of weight loss is the most important predictor for improvement in obesity-related comorbidities such as cardio-vascular disease [27,28], metabolic disorders (T2DM) [29], metabolic dysfunction – associated steatotic liver disease [30], and cancer [31].”
Liakopoulos, V., Franzén, S., Svensson, J., Sattar, N. A., Miftaraj, M., Björck, S., Ottosson, J., Näslund, I., Guðbjörnsdóttir, S., & Eliasson, B. (2020) · Diabetes Care · doi:10.2337/dc19-1703 · Cited by 65
“A recent published retrospectivestudyshowedsimilar improvementsonmajorCVeventsaswell onheart failure, atrial fibrillation, and diabetic nephropathy (30).”
BackgroundElsaid, M. I., Li, Y., Bridges, J. F. P., Brock, G., Minacapelli, C. D., & Rustgi, V. K. (2022) · JAMA Network Open · doi:10.1001/jamanetworkopen.2022.35003 · Cited by 63
Spearman, C. W., Afihene, M., Betiku, O., Bobat, B., Cunha, L., Kassianides, C., Katsidzira, L., Desalegn, H., Ocama, P., Ojo, O., et al. (2021) · The Lancet. Gastroenterology & hepatology · doi:10.1016/s2468-1253(21)00275-2 · Cited by 63
Obesity and Cardiovascular Disease: The Emerging Role of Inflammation
Khafagy, R. T. M., & Dash, S. (2021) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2021.768119 · Cited by 69
“To date, bariatric surgery remains the most efficacious weight loss treatment and improves multiple metabolic parameters, including adipose tissue and systemic inflammation (51, 70, 91, 92).”
BackgroundSutanto, A., Wungu, C. D. K., Susilo, H., & Sutanto, H. (2021) · Nutrients · doi:10.3390/nu13103568 · Cited by 58
“, 2019 [24] Each surgical patient was matched with a propensity score by the nearest-neighbor method to 5 nonsurgical patients from a logistic regression model with a logit link function based on 7 a priori–identified potential confounders including the index date, age at index date, sex, BMI at index date (categorize…”
BackgroundMethodResultInfluentialTreatment of Obesity in Mitigating Metabolic Risk
Heffron, S. P., Parham, J. S., Pendse, J., & Alemán, J. O. (2020) · Circulation Research · doi:10.1161/circresaha.119.315897 · Cited by 62
Bariatric Surgery as a Long-Term Treatment for Type 2 Diabetes/Metabolic Syndrome
Hanipah, Z. N., & Schauer, P. R. (2020) · Annual Review of Medicine · doi:10.1146/annurev-med-053117-123246 · Cited by 59
Self-citationChew, N., Pan, X. H., Chong, B., Chandramouli, C., Muthiah, M. D., & Lam, C. S. P. (2024) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2024.111652 · Cited by 63
Safety and Efficacy of Bariatric and Metabolic Surgery
Ghiassi, S., & Morton, J. M. (2020) · Current Obesity Reports · doi:10.1007/s13679-020-00377-y · Cited by 57
Roles of hepatic stellate cells in NAFLD: From the perspective of inflammation and fibrosis
Wang, M., Li, L., Xu, Y., Du, J., & Ling, C. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.958428 · Cited by 59
“Studies have showed that bariatric surgery can not only improve the histological features of NASH with fibrosis or compensated cirrhosis but also reduced the risk of cardiovascular events effectively (Maciejewski et al., 2016; Ikramuddin et al., 2018; Aminian et al., 2019).”
BackgroundAminian, A., Fathalizadeh, A., Tu, C., Butsch, W. S., Pantalone, K. M., Griebeler, M. L., Kashyap, S. R., Rosenthal, R. J., Burguera, B. G., & Nissen, S. E. (2020) · Surgery for Obesity and Related Diseases · doi:10.1016/j.soard.2020.10.026 · Cited by 56
Self-citationDoumouras, A. G., Lee, Y., Paterson, J. M., Gerstein, H. C., Shah, B. R., Sivapathasundaram, B., Tarride, J., Anvari, M., & Hong, D. (2021) · JAMA Network Open · doi:10.1001/jamanetworkopen.2021.6820 · Cited by 57
Dantas, W. S., Roschel, H., Murai, I. H., Gil, S., Davuluri, G., Axelrod, C. L., Ghosh, S., Newman, S. S., Zhang, H., Shinjo, S. K., et al. (2020) · Diabetes · doi:10.2337/db19-1180 · Cited by 54
“Bariatric surgery confers cardiometabolic protection to obese individuals, contributing to a reduced risk of allcause mortality (1,2).”
BackgroundMethodKrishnan, A., Hadi, Y. B., Alqahtani, S. A., Woreta, T. A., Fang, W., Abunnaja, S., Szoka, N. L., Tabone, L. E., Thakkar, S. J., & Singh, S. (2023) · JAMA Network Open · doi:10.1001/jamanetworkopen.2023.7188 · Cited by 54
Aminian, A., Zajichek, A., Tu, C., Wolski, K. E., Brethauer, S. A., Schauer, P. R., Kattan, M. W., & Nissen, S. E. (2020) · Annals of Surgery · doi:10.1097/sla.0000000000004369 · Cited by 52
“Although not tested in the setting of RCT, numerous observational studies have shown that substantial and durable weight loss after metabolic surgery is associated with lower risk of mortality.(11,12,18,19) Our findings indicated that >5% to 10% of surgically induced weight loss is associated with improved CV and mort…”
BackgroundMethodInfluentialSelf-citationAminian, A., Kashyap, S. R., Wolski, K. E., Brethauer, S. A., Kirwan, J. P., Nissen, S. E., Bhatt, D. L., & Schauer, P. R. (2021) · Annals of Surgery · doi:10.1097/sla.0000000000005003 · Cited by 50
Self-citationCosentino, F., Verma, S., Ambery, P., Treppendahl, M. B., van Eickels, M., Anker, S. D., Cecchini, M., Fioretto, P., Groop, P., Hess, D. A., et al. (2023) · European Heart Journal · doi:10.1093/eurheartj/ehad445 · Cited by 66
Cresci, B., Cosentino, C., Monami, M., & Mannucci, E. (2020) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.14045 · Cited by 46
Aminian, A., Tu, C., Milinovich, A., Wolski, K., Kattan, M. W., & Nissen, S. E. (2021) · JAMA Surgery · doi:10.1001/jamasurg.2021.6496 · Cited by 42
Self-citationLong‐term all‐cause and cause‐specific mortality for four bariatric surgery procedures
Adams, T. D., Meeks, H., Fraser, A. M., Davidson, L. E., Holmen, J. R., Newman, M. G., Ibele, A. R., Richards, N. G., Hunt, S. C., & Kim, J. (2023) · Obesity · doi:10.1002/oby.23646 · Cited by 47
Lam, C. S. P., Rodríguez, Á., Aminian, A., Ferrannini, E., Heerspink, H. J. L., Jastreboff, A. M., Laffin, L. J., Pandey, A., Ray, K. K., Ridker, P. M., et al. (2025) · Obesity · doi:10.1002/oby.24332 · Cited by 51
“Weight reduction with metabolic surgery is associated with improved renal outcomes [ 10, 45].”
InfluentialSelf-citationMetabolic surgery: A clinical update
Wilson, R. L., Aminian, A., & Tahrani, A. A. (2021) · Diabetes Obesity and Metabolism · doi:10.1111/dom.14235 · Cited by 42
“Data consistently show that metabolic surgery offers a survival benefit.(77,78) Long-term survival is undoubtedly a key outcome of metabolic surgery that supports”
BackgroundMethodResultInfluentialSelf-citationJirapinyo, P., Hadefi, A., Thompson, C. C., Patai, Á. V., Pannala, R., Goelder, S. K., Kushnir, V. M., Barthet, M. A., Apovian, C. M., Boškoski, I., et al. (2024) · Gastrointestinal Endoscopy · doi:10.1016/j.gie.2023.12.004 · Cited by 43
“The amount of weight loss is the most important predictor for improvement in obesity-related comorbidities such as cardio-vascular disease [27,28], metabolic disorders (T2DM) [29], metabolic dysfunction – associated steatotic liver disease [30], and cancer [31].”
BackgroundLorkowski, S. W., Brubaker, G., Rotroff, D. M., Kashyap, S. R., Bhatt, D. L., Nissen, S. E., Schauer, P. R., Aminian, A., & Smith, J. D. (2020) · Biomolecules · doi:10.3390/biom10040551 · Cited by 45
“A recent large matched cohort study further supports the superiority of this treatment showing that metabolic surgery, compared with nonsurgical management, decreases major adverse cardiovascular outcomes in patients with type 2 diabetes and obesity [6].”
ResultSelf-citationMitochondrial Lipid Homeostasis at the Crossroads of Liver and Heart Diseases
Dabravolski, S. A., Bezsonov, E. E., Baig, M. S., Попкова, Т. В., & Orekhov, A. N. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22136949 · Cited by 44
“Bariatric surgery also reduced the risk of CVD events among T2D and obese patients; thus, a similar effect would be also expected in the case of NASH patients [202].”
BackgroundAdvances in Phenotyping Obesity and in Its Dietary and Pharmacological Treatment: A Narrative Review
Pujia, R., Tarsitano, M. G., Arturi, F., LORENZO, A. D., Lenzi, A., Pujia, A., & Montalcini, T. (2022) · Frontiers in Nutrition · doi:10.3389/fnut.2022.804719 · Cited by 42
“In addition, among patients with T2DM and a BMI of 30 or greater, compared with usual care, metabolic surgery (which included Roux-en-Y gastric bypass, sleeve gastrectomy, adjustable gastric banding, and duodenal switch) was associated with a significantly lower risk of major adverse cardiac events (MACE) and diabetic…”
BackgroundIncretin-based investigational therapies for the treatment of MASLD/MASH
Brouwers, B., Rao, G., Tang, Y., Rodríguez, Á., Glass, L. C., & Hartman, M. L. (2024) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2024.111675 · Cited by 40
Courcoulas, A. P., Johnson, E., Arterburn, D. E., Haneuse, S., Herrinton, L. J., Fisher, D. P., Li, R. A., Theis, M. K., Liu, L., Taylor, B., et al. (2023) · Annals of Surgery · doi:10.1097/sla.0000000000005155 · Cited by 41
Self-citationMentias, A., Desai, M. Y., Aminian, A., Patel, K. V., Keshvani, N., Verma, S., Cho, L., Jacob, M., Alvarez, P., Lincoff, A. M., et al. (2024) · Circulation: Heart Failure · doi:10.1161/circheartfailure.122.010453 · Cited by 40
“While the observed magnitude of association is consistent with the prior reports, 11,12,52 large treatment effects for mortality outcomes in favor of intervention in retrospective analyses may be related to several potential biases.”
ResultSelf-citation
Metadata
- Authors
- Aminian, A., Zajichek, A., Arterburn, D. E., Wolski, K. E., Brethauer, S. A., Schauer, P. R., Kattan, M. W., & Nissen, S. E.
- Affiliations
- Cleveland Clinic (US)
- Kaiser Permanente Washington Health Research Institute (US)
- Corresponding author
- Nissen, Steven E.
- ORCID
- Venue
- JAMA
- Publisher
- American Medical Association (AMA)
- Published
- 2019-10-01
- Volume
- 322
- Issue
- 13
- Pages
- 1271
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- PMC
- PMC6724187
- OpenAlex
- W2970007463
- Cited by
- 505
- References
- 32
- Citations by year
- 2026: 61 · 2025: 71 · 2024: 68 · 2023: 73 · 2022: 66 · 2021: 83 · 2020: 73 · 2019: 9
- FWCI
- 55.12
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- JAMA (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Bariatric Surgery and Outcomes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac, Anesthesia and Surgical Outcomes
- Keywords
- metabolic surgery, type 2 diabetes, obesity, major adverse cardiovascular events, cardiovascular outcomes, bariatric surgery, weight loss, myocardial infarction, ischemic stroke, heart failure, atrial fibrillation, kidney disease, mortality, cardiometabolic risk factors
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