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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].”
In the citing paper
“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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“BS is also associated with a reduced risk of mortality and of some types of cancer [2].”
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“Additionally, when talking into account myocardial infraction, ischemic stroke and mortality as endpoints, patients in the surgical group realized a 41% risk reduction (65).”
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BackgroundResultThe cardiovascular effects of novel weight loss therapies
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“Consequently, the Kaplan-Meier curves tracked together for the first few months while the introduced immortal time bias counteracted the biases operating because of differential information and residual confounding, which, after 6 months, yielded the stark separation of the curves, including, most strikingly, for all-…”
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“However, long-term follow-up regarding weight-loss trajectories post-SG remains scarce and, when available, is often pooled with those post-RYGB (12).”
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“1 3 bariatric surgery, the surgical intervention was nearly 40% protective against a 6-component composite MACE outcome in patients with obesity and DM [10].”
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“A reduction in overall mortality of 30% to 80% has also been observed (123-126) in observational studies but has not yet been observed in prospective randomized trials.”
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“Larger-scale observational studies further showed that metabolic surgery, compared with nonsurgical management, is associated with a significantly lower risk of incident macrovascular and microvascular disease 4–7 .”
Self-citationInsulin resistance in bariatric surgery
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“Even so, data in the present study suggest that hypertensive patients in the surgery group experienced slightly lower reduction in the risk for an MACE as well as overall mortality compared to those with T2DM at baseline [20].”
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“This technique has been used previously in observational studies for these purposes.(11,12) A P value of <0.”
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“Bariatric surgery remains an effective long-term intervention for sustained weight loss in individuals with severe obesity and has demonstrated systemic benefits beyond weight reduction [149,150].”
Association between Drinking Patterns and Incident Hypertension in Southwest China
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“We calculated E-values to assess the sensitivity to nmeasured confounding factors [17].”
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“Besides favorable effects on body weight, it was shown that cardiovascular risk factors like type 2 diabetes mellitus, hypertension, dyslipidemia, and non-alcoholic fatty liver disease improve following surgery [1, 2], resulting in decreased all-cause mortality [3].”
BackgroundInfluentialSex and ethnic differences in the cardiovascular complications of type 2 diabetes
Yeo, J. L., Brady, E. M., McCann, G. P., & Gulsin, G. S. (2021) · Therapeutic Advances in Endocrinology and Metabolism · doi:10.1177/20420188211034297 · Cited by 19
Re-evaluating the concept of remission in type 2 diabetes: a call for patient-centric approaches
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Risk Factors for Kidney Stone Formation following Bariatric Surgery
Prochaska, M., & Worcester, E. M. (2020) · Kidney360 · doi:10.34067/kid.0004982020 · Cited by 18
Zaminpeyma, R., Claus, M., Paraskevas, S., Court, O., Tchervenkov, J., & Andalib, A. (2022) · Surgical Endoscopy · doi:10.1007/s00464-022-09552-9 · Cited by 18
“metabolic syndrome slowed after their metabolic/bariatric surgery which is clearly shown to provide protection against major adverse cardiovascular events including mortality among patients with obesity and metabolic syndrome [25, 26].”
BackgroundPharmacotherapy for obesity: recent evolution and implications for cardiovascular risk reduction
Maki, K. C., Kirkpatrick, C. F., Allison, D. B., & Gadde, K. M. (2023) · Expert Review of Endocrinology & Metabolism · doi:10.1080/17446651.2023.2209176 · Cited by 19
The Role of Obesity as a Cardiac Disease Risk Factor in Patients with Type 2 Diabetes
Koirala, S., Sunnaa, M., Bernier, T. D., & Oktay, A. A. (2024) · Current Cardiology Reports · doi:10.1007/s11886-024-02129-z · Cited by 17
“…with T2DM and obesity who underwent metabolic surgery and 11,435 matched controls showed that metabolic surgery was associated with a significantly lower risk of MACE (cumulative incidence of 30.8% in the surgery group and 47.7% in the nonsurgical group) during a median follow-up of 3.9 years [84].”
InfluentialA New Endemic of Concomitant Nonalcoholic Fatty Liver Disease and Chronic Hepatitis B
Hanif, H., Khan, M. M., Ali, M. J., Shah, P. A., Satiya, J., Lau, D., & Aslam, A. (2020) · Microorganisms · doi:10.3390/microorganisms8101526 · Cited by 17
“For selective patients, bariatric surgery leads to improve co-morbidities, decreased cardiovascular-related deaths, and all-cause mortality in addition to weight loss [130].”
BackgroundAtherosclerotic disease burden after bariatric surgery in patients with obesity and type 2 diabetes
Ardissino, M., Watson, F., Amin, R., Collins, P. D., Moussa, O., Purkayastha, S., & Imperial Obesity Study Group (2020) · Journal of Diabetes · doi:10.1111/1753-0407.13151 · Cited by 16
“In patients with T2DM, it improves glycemic control, improves rates of T2DM remission, and has been associated with lower rates of cardiovascular events in one previous study.(18) These promising results, combined with the rapid reduction in perioperative risk that has resulted from the advancement of minimally invasi…”
ResultBariatric Surgery Outcomes in Patients with Chronic Kidney Disease
Pané, A., Claro, M. I., Andújar, A. M., Olbeyra, R. P., Romano‐Andrioni, B., Boswell, L., Montagud‐Marrahí, E., Jiménez, A., Ibarzábal, A., Viaplana, J., et al. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm12186095 · Cited by 17
Metabolic endoscopy: Today’s science—tomorrow’s treatment
Hadefi, A., Arvanitakis, M., Huberty, V., & Deviere, J. M. E. (2020) · United European Gastroenterology Journal · doi:10.1177/2050640620926837 · Cited by 16
Huang, S., Lan, Y., Zhang, C., Zhang, J., & Zhou, Z. (2022) · Obesity Surgery · doi:10.1007/s11695-022-06366-5 · Cited by 15
“The following seven criteria were used to determine the risk of bias: [1] confounding, [2] selection of participants into the study, [3] classification of exposures, [4] departures from intended exposures, [5] missing data, [6] measurement of outcomes, and [7] selection of the reported results.”
BackgroundMethodGrieco, A., Huffman, K. M., Cohen, M. E., Hall, B. L., Morton, J. M., & Ko, C. Y. (2022) · Surgery for Obesity and Related Diseases · doi:10.1016/j.soard.2022.12.028 · Cited by 15
Luo, Y., Haddad, R. A., Öntan, M. S., Eldin, A. W. J., Abu-Rumaileh, M. A., Yosef, M., Khalatbari, S. H., Varban, O. A., Kraftson, A. T., Esfandiari, N. H., et al. (2023) · Clinical Endocrinology · doi:10.1111/cen.14922 · Cited by 15
A Contemporary Approach to Hypertensive Cardiomyopathy: Reversing Left Ventricular Hypertrophy
Bourdillon, M. T., & Vasan, R. S. (2020) · Current Hypertension Reports · doi:10.1007/s11906-020-01092-8 · Cited by 16
Fischer, H. J., Weiss, R. E., Friedman, A. N., Imam, T. H., & Coleman, K. J. (2020) · Surgery for Obesity and Related Diseases · doi:10.1016/j.soard.2020.11.010 · Cited by 17
“(34) While previous observational studies have demonstrated an association between bariatric surgery and a slowing in the decline of kidney function or kidney risk indices post-surgery(4,12-17), this study provides additional insight by comparing patient post-surgical weight and eGFR trajectories with their own pre-su…”
BackgroundResultBecker, A., Gaballa, D., Roslin, M., Gianos, E., & Kane, J. (2021) · Current Cardiology Reports · doi:10.1007/s11886-021-01515-1 · Cited by 14
Jia, X., Rifai, M. A., Gluckman, T. J., Birnbaum, Y., & Virani, S. S. (2019) · Current Atherosclerosis Reports · doi:10.1007/s11883-019-0813-7 · Cited by 14
Mabeza, R. M., Vadlakonda, A., Chervu, N. L., Ebrahimian, S., Sakowitz, S., Yetasook, A. K., & Benharash, P. (2023) · Surgery for Obesity and Related Diseases · doi:10.1016/j.soard.2023.10.006 · Cited by 14
Clinical Update in Heart Failure with Preserved Ejection Fraction
Krittanawong, C., Britt, W., Rizwan, A. M., Siddiqui, R., Khawaja, M., Khan, R., Joolharzadeh, P., Newman, N. A., Rivera, M. R. R., & Tang, W. H. W. (2024) · Current Heart Failure Reports · doi:10.1007/s11897-024-00679-5 · Cited by 17
“Significant weight loss has also been shown to improve exercise capacity and quality of life and reduce rates of incidence of HFpEF and AF [169, 179].”
The COVID-19 Pandemic Did Not Affect Target Weight Loss 1 Year Post Bariatric Surgery
Pereira, X., Romero-Vélez, G., Skendelas, J. P., Rodríguez-Quintero, J. H., Grosser, R., Lima, D. J. M., Moran-Atkin, E., Choi, J., & Camacho, D. R. (2021) · Obesity Surgery · doi:10.1007/s11695-021-05672-8 · Cited by 14
Adekunle, O. A., Le, P., Gupta, D. Y., Rothberg, M. B., Tran, H. T., Yue, Y., & Gasoyan, H. (2025) · Diabetes Obesity and Metabolism · doi:10.1111/dom.16544 · Cited by 12
Pontiroli, A., Centofanti, L., Le Roux, C., Magnani, S., Tagliabue, E., & Folli, F. (2023) · Nutrients · doi:10.3390/nu15040940 · Cited by 13
“Aminian 2019 [27] 1 1 1 1 0 1 1 0 0 6 Intermediate”
BackgroundObesity, Challenges, and Weight-Loss Strategies for Patients With Ventricular Assist Devices
daSilva‐deAbreu, A., Rodgers, J. E., Seltz, J., Mandras, S. A., Lavie, C. J., Loro-Ferrer, J. F., Ventura, H. O., Schauer, P. R., & Vest, A. R. (2024) · JACC Heart Failure · doi:10.1016/j.jchf.2024.04.006 · Cited by 14
Self-citationAssessing the state of obesity care: Quality, access, guidelines, and standards
Kaplan, L. M., Apovian, C. M., Ard, J. D., Allison, D. B., Aronne, L. J., Batterham, R. L., Busetto, L., Dicker, D., Horn, D. B., Kelly, A. S., et al. (2024) · Obesity Science & Practice · doi:10.1002/osp4.765 · Cited by 15
“65,80 Limitations of these approaches Current treatment guidelines seem less directive for treatment when patients with obesity are seen in a primary care provider's office as compared to guidelines for other diseases.”
BackgroundMaan, M. S. A., Sohail, A. H., Sulaiman, S. A., Mansoor, L., Cohen, E. M., Adekolu, A. A., Abunnaja, S., Szoka, N. L., Tabone, L. E., Thakkar, S. J., et al. (2025) · The American Journal of Surgery · doi:10.1016/j.amjsurg.2025.116242 · Cited by 13
Update on Metabolic Bariatric Surgery for Morbidly Obese Adolescents
Till, H., Mann, O., Singer, G., & Blüher, S. (2021) · Children · doi:10.3390/children8050372 · Cited by 14
Long-term outcomes of bariatric surgery in patients with diabetes
Sudlow, A. C., le Roux, C. W., & Pournaras, D. J. (2020) · Expert Review of Endocrinology & Metabolism · doi:10.1080/17446651.2020.1754191 · Cited by 13
“These findings were echoed by a recent retrospective cohort study of nearly 14,000 patients with diabetes and obesity which found a significant reduction in the risk of major cardiovascular endpoints in surgical patients as compared to those managed medically [31].”
ResultBariatric surgery to aLleviate OCcurrence of Atrial Fibrillation Hospitalization—BLOC-AF
Srivatsa, U. N., Malhotra, P., Zhang, X. J., Beri, N., Xing, G., Brunson, A. M., Ali, M., Fan, D., Pezeshkian, N. G., Chiamvimonvat, N., et al. (2020) · Heart Rhythm O2 · doi:10.1016/j.hroo.2020.04.004 · Cited by 13
“9% absolute 8-year risk reduction for combined cardiovascular endpoints.(29) In contrast to the medically managed control groups in both of those studies, all of our controls had undergone another abdominal surgery, so such comparison eliminates confounding early clinical outcomes related to postoperative state.”
ResultThe role of bariatric surgery in the management of nonalcoholic steatohepatitis
Seymour, K. A., & Abdelmalek, M. F. (2021) · Current Opinion in Gastroenterology · doi:10.1097/mog.0000000000000721 · Cited by 13
Chindamporn, P., Wang, L., Bena, J., Zajichek, A., Milinovich, A., Kaw, R. K., Kashyap, S. R., Cetin, D. C., Aminian, A., Kempke, N., et al. (2022) · Journal of Clinical Sleep Medicine · doi:10.5664/jcsm.10216 · Cited by 12
Self-citationUnveiling the cost-effectiveness of bariatric surgery: insights from a matched cohort study
Lloyd, S. J.-A., Wall-Wieler, E., Liu, Y., Zheng, F., & LaMasters, T. (2025) · Surgery for Obesity and Related Diseases · doi:10.1016/j.soard.2025.04.004 · Cited by 12
Advances in Clinical Cardiology 2019: A Summary of Key Clinical Trials
Linden, K., Mailey, J. A., Kearney, A., & Menown, I. B. A. (2020) · Advances in Therapy · doi:10.1007/s12325-020-01355-5 · Cited by 13
“In an observational study of patients with T2D and body mass index (BMI) C 30, 2287 patients who underwent bariatric surgery in the Cleveland Clinic were compared with 11,435 controls receiving usual care [40].”
MethodMorey-Vargas, O. L., Aminian, A., Steckner, K., Zhou, K.-R., Kashyap, S., Cetin, D., Pantalone, K., Daigle, C. R., Griebeler, M. L., Butsch, W. S., et al. (2022) · Surgery for Obesity and Related Diseases · doi:10.1016/j.soard.2022.05.008 · Cited by 9
Self-citationWeight loss trend after bariatric surgery in a population of obese patients
Palumbo, P., Banchelli, F., Miloro, C., Toschi, P. F., Mécheri, F., Gabriele, S., Pantaleoni, M., D’Amico, R., & Menozzi, R. (2023) · Clinical Nutrition ESPEN · doi:10.1016/j.clnesp.2023.06.015 · Cited by 12
A Structured Approach for Safely Reintroducing Bariatric Surgery in a COVID-19 Environment
Daigle, C. R., Augustin, T., Wilson, R. L., Schulz, K., Fathalizadeh, A., Laktash, A., Bauman, M. D., Bencsath, K. P., Cha, W., Rodriguez, J. H., et al. (2020) · Obesity Surgery · doi:10.1007/s11695-020-04733-8 · Cited by 12
“The profoundmetabolic effects of bariatric surgery are well known [16].”
BackgroundSelf-citationGoldberg, I., Nie, L., Yang, J., Docimo, S., Obici, S., Talamini, M. A., Pryor, A. D., & Spaniolas, K. (2020) · Surgical Endoscopy · doi:10.1007/s00464-020-07848-2 · Cited by 12
Selby, L. V., Ejaz, A. M., Brethauer, S. A., & Pawlik, T. M. (2020) · Expert Opinion on Investigational Drugs · doi:10.1080/13543784.2020.1721457 · Cited by 12
Self-citationZhang, S., Jiang, J., Luo, Y., Liu, G., Hu, S., Wan, S., Luo, C., Li, H., Li, N., Vasconcelos, J. D. G. E. S., et al. (2025) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2025.1613900 · Cited by 11
Migliore, E., Brunani, A., Ciccone, G., Pagano, E., Arolfo, S., Rosso, T., Pellegrini, M., Capodaglio, P., Morino, M., Ghigo, E., et al. (2021) · Nutrients · doi:10.3390/nu13093150 · Cited by 11
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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