Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Cardiovascular Diabetology
Published in: Cardiovascular Diabetology 1/2024

Open Access 01-12-2024 | Hyperglycemia | Research

Simultaneous assessment of stress hyperglycemia ratio and glycemic variability to predict mortality in patients with coronary artery disease: a retrospective cohort study from the MIMIC-IV database

Authors: Hao-ming He, Shu-wen Zheng, Ying-ying Xie, Zhe Wang, Si-qi Jiao, Fu-rong Yang, Xue-xi Li, Jie Li, Yi-hong Sun

Published in: Cardiovascular Diabetology | Issue 1/2024

Login to get access

Abstract

Background

Stress hyperglycemia and glycemic variability (GV) can reflect dramatic increases and acute fluctuations in blood glucose, which are associated with adverse cardiovascular events. This study aimed to explore whether the combined assessment of the stress hyperglycemia ratio (SHR) and GV provides additional information for prognostic prediction in patients with coronary artery disease (CAD) hospitalized in the intensive care unit (ICU).

Methods

Patients diagnosed with CAD from the Medical Information Mart for Intensive Care-IV database (version 2.2) between 2008 and 2019 were retrospectively included in the analysis. The primary endpoint was 1-year mortality, and the secondary endpoint was in-hospital mortality. Levels of SHR and GV were stratified into tertiles, with the highest tertile classified as high and the lower two tertiles classified as low. The associations of SHR, GV, and their combination with mortality were determined by logistic and Cox regression analyses.

Results

A total of 2789 patients were included, with a mean age of 69.6 years, and 30.1% were female. Overall, 138 (4.9%) patients died in the hospital, and 404 (14.5%) patients died at 1 year. The combination of SHR and GV was superior to SHR (in-hospital mortality: 0.710 vs. 0.689, p = 0.012; 1-year mortality: 0.644 vs. 0.615, p = 0.007) and GV (in-hospital mortality: 0.710 vs. 0.632, p = 0.004; 1-year mortality: 0.644 vs. 0.603, p < 0.001) alone for predicting mortality in the receiver operating characteristic analysis. In addition, nondiabetic patients with high SHR levels and high GV were associated with the greatest risk of both in-hospital mortality (odds ratio [OR] = 10.831, 95% confidence interval [CI] 4.494–26.105) and 1-year mortality (hazard ratio [HR] = 5.830, 95% CI 3.175–10.702). However, in the diabetic population, the highest risk of in-hospital mortality (OR = 4.221, 95% CI 1.542–11.558) and 1-year mortality (HR = 2.013, 95% CI 1.224–3.311) was observed in patients with high SHR levels but low GV.

Conclusions

The simultaneous evaluation of SHR and GV provides more information for risk stratification and prognostic prediction than SHR and GV alone, contributing to developing individualized strategies for glucose management in patients with CAD admitted to the ICU.
Appendix
Available only for authorised users
Literature
1.
Tsao CW, Aday AW, Almarzooq ZI, Anderson CAM, Arora P, Avery CL, Baker-Smith CM, Beaton AZ, Boehme AK, Buxton AE, et al. Heart Disease and Stroke Statistics-2023 update: a Report from the American Heart Association. Circulation. 2023;147(8):e93–e621.PubMedCrossRef
2.
Shin SH, Claggett B, Pfeffer MA, Skali H, Liu J, Aguilar D, Diaz R, Dickstein K, Gerstein HC, Køber LV, et al. Hyperglycaemia, ejection fraction and the risk of heart failure or cardiovascular death in patients with type 2 diabetes and a recent acute coronary syndrome. Eur J Heart Fail. 2020;22(7):1133–43.PubMedCrossRef
3.
Xu W, Song Q, Wang X, Zhao Z, Meng X, Xia C, Xie Y, Yang C, Guo Y, Zhang Y, et al. Association of stress hyperglycemia ratio and in-hospital mortality in patients with coronary artery disease: insights from a large cohort study. Cardiovasc Diabetol. 2022;21(1):217.PubMedPubMedCentralCrossRef
4.
Rizas KD, Nieminen T, Barthel P, Zürn CS, Kähönen M, Viik J, Lehtimäki T, Nikus K, Eick C, Greiner TO, et al. Sympathetic activity-associated periodic repolarization dynamics predict mortality following myocardial infarction. J Clin Investig. 2014;124(4):1770–80.PubMedPubMedCentralCrossRef
5.
Bartnik M, Malmberg K, Hamsten A, Efendic S, Norhammar A, Silveira A, Tenerz A, Ohrvik J, Rydén L. Abnormal glucose tolerance–a common risk factor in patients with acute myocardial infarction in comparison with population-based controls. J Intern Med. 2004;256(4):288–97.PubMedCrossRef
6.
Wallander M, Bartnik M, Efendic S, Hamsten A, Malmberg K, Ohrvik J, Rydén L, Silveira A, Norhammar A. Beta cell dysfunction in patients with acute myocardial infarction but without previously known type 2 diabetes: a report from the GAMI study. Diabetologia. 2005;48(11):2229–35.PubMedCrossRef
7.
Shamoon H, Hendler R, Sherwin RS. Synergistic interactions among antiinsulin hormones in the pathogenesis of stress hyperglycemia in humans. J Clin Endocrinol Metab. 1981;52(6):1235–41.PubMedCrossRef
8.
Roberts GW, Quinn SJ, Valentine N, Alhawassi T, O’Dea H, Stranks SN, Burt MG, Doogue MP. Relative hyperglycemia, a marker of critical illness: introducing the stress hyperglycemia ratio. J Clin Endocrinol Metab. 2015;100(12):4490–7.PubMedCrossRef
9.
Marenzi G, Cosentino N, Milazzo V, De Metrio M, Cecere M, Mosca S, Rubino M, Campodonico J, Moltrasio M, Marana I, et al. Prognostic value of the Acute-to-chronic glycemic ratio at Admission in Acute myocardial infarction: a prospective study. Diabetes Care. 2018;41(4):847–53.PubMedCrossRef
10.
Shimabukuro M, Tanaka A, Sata M, Dai K, Shibata Y, Inoue Y, Ikenaga H, Kishimoto S, Ogasawara K, Takashima A, et al. α-Glucosidase inhibitor miglitol attenuates glucose fluctuation, heart rate variability and sympathetic activity in patients with type 2 diabetes and acute coronary syndrome: a multicenter randomized controlled (MACS) study. Cardiovasc Diabetol. 2017;16(1):86.PubMedPubMedCentralCrossRef
11.
Gerbaud E, Darier R, Montaudon M, Beauvieux MC, Coffin-Boutreux C, Coste P, Douard H, Ouattara A, Catargi B. Glycemic variability is a powerful independent predictive factor of Midterm Major adverse cardiac events in patients with diabetes with Acute Coronary Syndrome. Diabetes Care. 2019;42(4):674–81.PubMedCrossRef
12.
Chun KH, Oh J, Lee CJ, Park JJ, Lee SE, Kim MS, Cho HJ, Choi JO, Lee HY, Hwang KK, et al. In-hospital glycemic variability and all-cause mortality among patients hospitalized for acute heart failure. Cardiovasc Diabetol. 2022;21(1):291.PubMedPubMedCentralCrossRef
13.
Esposito K, Nappo F, Marfella R, Giugliano G, Giugliano F, Ciotola M, Quagliaro L, Ceriello A, Giugliano D. Inflammatory cytokine concentrations are acutely increased by hyperglycemia in humans: role of oxidative stress. Circulation. 2002;106(16):2067–72.PubMedCrossRef
14.
Worthley MI, Holmes AS, Willoughby SR, Kucia AM, Heresztyn T, Stewart S, Chirkov YY, Zeitz CJ, Horowitz JD. The deleterious effects of hyperglycemia on platelet function in diabetic patients with acute coronary syndromes mediation by superoxide production, resolution with intensive insulin administration. J Am Coll Cardiol. 2007;49(3):304–10.PubMedCrossRef
15.
Stegenga ME, van der Crabben SN, Blümer RM, Levi M, Meijers JC, Serlie MJ, Tanck MW, Sauerwein HP, van der Poll T. Hyperglycemia enhances coagulation and reduces neutrophil degranulation, whereas hyperinsulinemia inhibits fibrinolysis during human endotoxemia. Blood. 2008;112(1):82–9.PubMedPubMedCentralCrossRef
16.
Piconi L, Quagliaro L, Da Ros R, Assaloni R, Giugliano D, Esposito K, Szabó C, Ceriello A. Intermittent high glucose enhances ICAM-1, VCAM-1, E-selectin and interleukin-6 expression in human umbilical endothelial cells in culture: the role of poly(ADP-ribose) polymerase. J Thromb Haemostasis: JTH. 2004;2(8):1453–9.CrossRef
17.
Monnier L, Mas E, Ginet C, Michel F, Villon L, Cristol JP, Colette C. Activation of oxidative stress by acute glucose fluctuations compared with sustained chronic hyperglycemia in patients with type 2 diabetes. JAMA. 2006;295(14):1681–7.PubMedCrossRef
18.
Cooper ME, El-Osta A. Epigenetics: mechanisms and implications for diabetic complications. Circul Res. 2010;107(12):1403–13.CrossRef
19.
Johnson AEW, Bulgarelli L, Shen L, Gayles A, Shammout A, Horng S, Pollard TJ, Hao S, Moody B, Gow B, et al. MIMIC-IV, a freely accessible electronic health record dataset. Sci data. 2023;10(1):1.PubMedPubMedCentralCrossRef
20.
21.
Su Y, Fan W, Liu Y, Hong K. Glycemic variability and in-hospital death of critically ill patients and the role of ventricular arrhythmias. Cardiovasc Diabetol. 2023;22(1):134.PubMedPubMedCentralCrossRef
22.
Levey AS, Coresh J, Balk E, Kausz AT, Levin A, Steffes MW, Hogg RJ, Perrone RD, Lau J, Eknoyan G. National Kidney Foundation practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Ann Intern Med. 2003;139(2):137–47.PubMedCrossRef
23.
Brunner R, Adelsmayr G, Herkner H, Madl C, Holzinger U. Glycemic variability and glucose complexity in critically ill patients: a retrospective analysis of continuous glucose monitoring data. Crit Care (London England). 2012;16(5):R175.CrossRef
24.
Xu F, Zhao LH, Su JB, Chen T, Wang XQ, Chen JF, Wu G, Jin Y, Wang XH. The relationship between glycemic variability and diabetic peripheral neuropathy in type 2 diabetes with well-controlled HbA1c. Diabetol Metab Syndr. 2014;6(1):139.PubMedPubMedCentralCrossRef
25.
Luo M, Kong X, Wang H, Zhai X, Cai T, Ding B, Hu Y, Jing T, Su X, Li H et al. Effect of Dapagliflozin on Glycemic Variability in Patients with Type 2 Diabetes under Insulin Glargine Combined with Other Oral Hypoglycemic Drugs. Journal of diabetes research 2020, 2020:6666403.
26.
Lanspa MJ, Dickerson J, Morris AH, Orme JF, Holmen J, Hirshberg EL. Coefficient of glucose variation is independently associated with mortality in critically ill patients receiving intravenous insulin. Crit Care (London England). 2014;18(2):R86.CrossRef
27.
Shen Y, Fan X, Zhang L, Wang Y, Li C, Lu J, Zha B, Wu Y, Chen X, Zhou J, et al. Thresholds of Glycemia and the outcomes of COVID-19 complicated with diabetes: a retrospective exploratory study using continuous glucose monitoring. Diabetes Care. 2021;44(4):976–82.PubMedPubMedCentralCrossRef
28.
Marfella R, Siniscalchi M, Esposito K, Sellitto A, De Fanis U, Romano C, Portoghese M, Siciliano S, Nappo F, Sasso FC, et al. Effects of stress hyperglycemia on acute myocardial infarction: role of inflammatory immune process in functional cardiac outcome. Diabetes Care. 2003;26(11):3129–35.PubMedCrossRef
29.
Esposito K, Marfella R, Giugliano D. Stress hyperglycemia, inflammation, and cardiovascular events. Diabetes Care. 2003;26(5):1650–1.PubMedCrossRef
30.
Paolisso P, Foà A, Bergamaschi L, Angeli F, Fabrizio M, Donati F, Toniolo S, Chiti C, Rinaldi A, Stefanizzi A, et al. Impact of admission hyperglycemia on short and long-term prognosis in acute myocardial infarction: MINOCA versus MIOCA. Cardiovasc Diabetol. 2021;20(1):192.PubMedPubMedCentralCrossRef
31.
Kuroda M, Shinke T, Sakaguchi K, Otake H, Takaya T, Hirota Y, Sugiyama D, Nakagawa M, Hariki H, Inoue T, et al. Effect of daily glucose fluctuation on coronary plaque vulnerability in patients pre-treated with lipid-lowering therapy: a prospective observational study. JACC Cardiovasc Interventions. 2015;8(6):800–11.CrossRef
32.
Saito S, Teshima Y, Fukui A, Kondo H, Nishio S, Nakagawa M, Saikawa T, Takahashi N. Glucose fluctuations increase the incidence of atrial fibrillation in diabetic rats. Cardiovascular Res. 2014;104(1):5–14.CrossRef
33.
Gohbara M, Iwahashi N, Kataoka S, Hayakawa Y, Sakamaki K, Akiyama E, Maejima N, Tsukahara K, Hibi K, Kosuge M, et al. Glycemic variability determined by continuous glucose monitoring system predicts left ventricular remodeling in patients with a First ST-Segment Elevation myocardial infarction. Circulation Journal: Official Journal of the Japanese Circulation Society. 2015;79(5):1092–9.PubMedCrossRef
34.
Gómez AM, Henao DC, Imitola Madero A, Taboada LB, Cruz V, Robledo Gómez MA, Rondón M, Muñoz-Velandia O, García-Jaramillo M. León Vargas FM: defining high glycemic variability in type 1 diabetes: comparison of multiple indexes to identify patients at risk of Hypoglycemia. Diabetes Technol Ther. 2019;21(8):430–9.PubMedCrossRef
35.
Rama Chandran S, Tay WL, Lye WK, Lim LL, Ratnasingam J, Tan ATB, Gardner DSL. Beyond HbA1c: comparing Glycemic Variability and Glycemic indices in Predicting Hypoglycemia in Type 1 and type 2 diabetes. Diabetes Technol Ther. 2018;20(5):353–62.PubMedCrossRef
36.
Desouza C, Salazar H, Cheong B, Murgo J, Fonseca V. Association of hypoglycemia and cardiac ischemia: a study based on continuous monitoring. Diabetes Care. 2003;26(5):1485–9.PubMedCrossRef
37.
Reno CM, Daphna-Iken D, Chen YS, VanderWeele J, Jethi K, Fisher SJ. Severe hypoglycemia-induced lethal cardiac arrhythmias are mediated by sympathoadrenal activation. Diabetes. 2013;62(10):3570–81.PubMedPubMedCentralCrossRef
38.
Ceriello A, Monnier L, Owens D. Glycaemic variability in diabetes: clinical and therapeutic implications. The Lancet Diabetes & Endocrinology. 2019;7(3):221–30.CrossRef
39.
Sechterberger MK, Bosman RJ, Oudemans-van Straaten HM, Siegelaar SE, Hermanides J, Hoekstra JB, De Vries JH. The effect of diabetes mellitus on the association between measures of glycaemic control and ICU mortality: a retrospective cohort study. Crit Care (London England). 2013;17(2):R52.CrossRef
40.
Krinsley JS, Rule P, Pappy L, Ahmed A, Huley-Rodrigues C, Prevedello D, Preiser JC. The Interaction of Acute and Chronic Glycemia on the relationship of hyperglycemia, hypoglycemia, and glucose variability to Mortality in the critically ill. Crit Care Med. 2020;48(12):1744–51.PubMedCrossRef
41.
Kosiborod M, Rathore SS, Inzucchi SE, Masoudi FA, Wang Y, Havranek EP, Krumholz HM. Admission glucose and mortality in elderly patients hospitalized with acute myocardial infarction: implications for patients with and without recognized diabetes. Circulation. 2005;111(23):3078–86.PubMedCrossRef
42.
Yao Y, Song Q, Hu C, Da X, Yu Y, He Z, Xu C, Chen Q, Wang QK. Endothelial cell metabolic memory causes cardiovascular dysfunction in diabetes. Cardiovascular Res. 2022;118(1):196–211.CrossRef
43.
Ceriello A, Lucisano G, Prattichizzo F, La Grotta R, Frigé C, De Cosmo S, Di Bartolo P, Di Cianni G, Fioretto P, Giorda CB, et al. The legacy effect of hyperglycemia and early use of SGLT-2 inhibitors: a cohort study with newly-diagnosed people with type 2 diabetes. Lancet Reg Health Europe. 2023;31:100666.PubMedCrossRef
44.
Lu Z, Tao G, Sun X, Zhang Y, Jiang M, Liu Y, Ling M, Zhang J, Xiao W, Hua T, et al. Association of Blood Glucose Level and glycemic variability with mortality in Sepsis patients during ICU hospitalization. Front Public Health. 2022;10:857368.PubMedPubMedCentralCrossRef
45.
Krinsley JS, Egi M, Kiss A, Devendra AN, Schuetz P, Maurer PM, Schultz MJ, van Hooijdonk RT, Kiyoshi M, Mackenzie IM, et al. Diabetic status and the relation of the three domains of glycemic control to mortality in critically ill patients: an international multicenter cohort study. Crit Care (London England). 2013;17(2):R37.CrossRef
46.
Engerman RL, Kern TS. Progression of incipient diabetic retinopathy during good glycemic control. Diabetes. 1987;36(7):808–12.PubMedCrossRef
47.
Bajaj HS, Venn K, Ye C, Patrick A, Kalra S, Khandwala H, Aslam N, Twum-Barima D, Aronson R. Lowest glucose variability and hypoglycemia are observed with the combination of a GLP-1 receptor agonist and basal insulin (VARIATION Study). Diabetes Care. 2017;40(2):194–200.PubMedCrossRef
48.
Marfella R, Di Filippo C, Portoghese M, Ferraraccio F, Rizzo MR, Siniscalchi M, Musacchio E, D’Amico M, Rossi F, Paolisso G. Tight glycemic control reduces heart inflammation and remodeling during acute myocardial infarction in hyperglycemic patients. J Am Coll Cardiol. 2009;53(16):1425–36.PubMedCrossRef
49.
Paolisso P, Bergamaschi L, Santulli G, Gallinoro E, Cesaro A, Gragnano F, Sardu C, Mileva N, Foà A, Armillotta M, et al. Infarct size, inflammatory burden, and admission hyperglycemia in diabetic patients with acute myocardial infarction treated with SGLT2-inhibitors: a multicenter international registry. Cardiovasc Diabetol. 2022;21(1):77.PubMedPubMedCentralCrossRef
Metadata
Title
Simultaneous assessment of stress hyperglycemia ratio and glycemic variability to predict mortality in patients with coronary artery disease: a retrospective cohort study from the MIMIC-IV database
Authors
Hao-ming He
Shu-wen Zheng
Ying-ying Xie
Zhe Wang
Si-qi Jiao
Fu-rong Yang
Xue-xi Li
Jie Li
Yi-hong Sun
Publication date
01-12-2024
Publisher
BioMed Central
Published in
Cardiovascular Diabetology / Issue 1/2024
Electronic ISSN: 1475-2840
DOI
https://doi.org/10.1186/s12933-024-02146-w

Other articles of this Issue 1/2024

Cardiovascular Diabetology 1/2024 Go to the issue

Research

Liraglutide and not lifestyle intervention reduces soluble CD163 after comparable weight loss in obese participants with prediabetes or type 2 diabetes mellitus

Research

Persistent epigenetic signals propel a senescence-associated secretory phenotype and trained innate immunity in CD34+ hematopoietic stem cells from diabetic patients

Research

Effect of physical activity on incident atrial fibrillation in individuals with varying duration of diabetes: a nationwide population study

Research

Risk factors for and risk of all-cause and atherosclerotic cardiovascular disease mortality in people with type 2 diabetes and peripheral artery disease: an observational, register-based cohort study

Research

The impact of type 2 diabetes mellitus on the clinical profile, myocardial fibrosis, and prognosis in non-ischemic dilated cardiomyopathy: a prospective cohort study

Research

Contributions of elevated CRP, hyperglycaemia, and type 2 diabetes to cardiovascular risk in the general population: observational and Mendelian randomization studies
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits