Glycated Haemoglobin Levels and Its Effect on Outcomes in Cardiac Surgery

Ansari, Daniyal Matin; Harahwa, Tinotenda; Abuelgasim, Eyad; Harky, Amer

doi:10.21470/1678-9741-2020-0188

Daniyal Matin Ansari

St. George’s Hospital Medical School, London, United Kingdom.

Tinotenda Harahwa

BSc

St. George’s Hospital Medical School, London, United Kingdom.

Eyad Abuelgasim

BSc

Faculty of Medicine, Imperial College London, London, United Kingdom.

Amer Harky Correspondence Address: Amer Harky Department of Cardiothoracic Surgery, Liverpool Heart and Chest Hospital, Liverpool, United Kingdom - Zip code: L14 3PE. E-mail: amer.harky@lhch.nhs.uk

MRCS

MSc

Department of Cardiothoracic Surgery, Liverpool Heart and Chest Hospital, Liverpool, United Kingdom.

Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart and Chest Hospital, Liverpool, United Kingdom.

https://orcid.org/0000-0001-5507-5841

Correspondence Address: Amer Harky Department of Cardiothoracic Surgery, Liverpool Heart and Chest Hospital, Liverpool, United Kingdom - Zip code: L14 3PE. E-mail: amer.harky@lhch.nhs.uk

No conflicts of interest.

Tables (6)

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Abbreviations, acronyms & symbols ADA = American Diabetes Association LOS = Length of stay AF = Atrial fibrillation MI = Myocardial infarction AGEs = Advanced glycation end-products OCTOPUS = Optimising Cardiac Surgery outcomes in People with diabetes CABG = Coronary artery bypass grafting OPCAB = Off-pump coronary artery bypass CI = Confidence interval PCI = Percutaneous coronary intervention CMM = Composite morbidity-mortality TIA = Transient ischemic attack CVA = Cerebrovascular accident WHO = World Health Organization DM = Diabetes mellitus WMD = Weighted mean difference HbA1c = Glycated haemoglobin HR = Hazard ratio

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Table 1
Summary of clinical outcomes in included studies that showed that the HbA1c level is predictive of mortality.

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Table 2
Summary of clinical outcomes in included studies that showed that the HbA1c level had no effect on post-operative mortality.

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Table 3
Summary of clinical outcomes in included studies that showed that the HbA1c level had no effect on post-operative wound infection.

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Table 4
Summary of clinical outcomes in included studies that showed that the HbA1c level is predictive of post-operative wound infection.

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Authors' roles & responsibilities DMA Substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work; drafting the work or revising it critically for important intellectual content; final approval of the version to be published TH Substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work; drafting the work or revising it critically for important intellectual content; final approval of the version to be published EA Substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work; drafting the work or revising it critically for important intellectual content; final approval of the version to be published AH Substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work; drafting the work or revising it critically for important intellectual content; final approval of the version to be published

Abbreviations, acronyms & symbols
ADA	= American Diabetes Association	LOS	= Length of stay
AF	= Atrial fibrillation	MI	= Myocardial infarction
AGEs	= Advanced glycation end-products	OCTOPUS	= Optimising Cardiac Surgery outcomes in People with diabetes
CABG	= Coronary artery bypass grafting	OPCAB	= Off-pump coronary artery bypass
CI	= Confidence interval	PCI	= Percutaneous coronary intervention
CMM	= Composite morbidity-mortality	TIA	= Transient ischemic attack
CVA	= Cerebrovascular accident	WHO	= World Health Organization
DM	= Diabetes mellitus	WMD	= Weighted mean difference
HbA1c	= Glycated haemoglobin
HR	= Hazard ratio

Study	Study design	Single/ Multi-centre	Sample size	Main outcomes
Kuhl et al.[¹⁷17 Kuhl J, Sartipy U, Eliasson B, Nyström T, Holzmann MJ. Relationship between preoperative hemoglobin A1c levels and long-term mortality after coronary artery bypass grafting in patients with type 2 diabetes mellitus. Int J Cardiol. 2016;202:291-6. doi:10.1016/j.ijcard.2015.09.008. https://doi.org/10.1016/j.ijcard.2015.09... ], 2016	Retrospective	Multi-centre (across Sweden)	6,313 patients	•	HbA1c associated with increased risk of death in patients with HbA1c levels 9.1-10.0% (HR 1.26, 95% CI 1.04-1.53)
				•	HbA1c associated with increased risk of death in patients with HbA1c >10.0% (HR 1.33, 95% CI 1.05-1.69)
				•	Stepwise increased risk of death with increasing HbA1c: 8.1-9.0% (HR 1.17, 95% CI 1.04-1.33), 9.1-10.0% (HR 1.44, 95% CI 1.22-1.70) and >10.0% (HR 1.50, 95% CI 1.22-1.84)
Halkos et al.[¹⁸18 Halkos ME, Puskas JD, Lattouf OM, Kilgo P, Kerendi F, Song HK, et al. Elevated preoperative hemoglobin A1c level is predictive of adverse events after coronary artery bypass surgery. J Thorac Cardiovasc Surg. 2008;136(3):631-40. doi:10.1016/j.jtcvs.2008.02.091. https://doi.org/10.1016/j.jtcvs.2008.02.... ], 2008	Retrospective	Single centre (USA)	3,089 patients	•	Elevated HbA1c predicted in-hospital mortality after CABG (OR 1.40 per unit HbA1c increase, 95% CI 1.06-1.86, P=0.019)
	Retrospective	Single centre (USA)	3,089 patients	•	HbA1c >8.6% associated with a 4-fold increase in mortality
Kim et al.[¹⁹19 Kim HJ, Shim JK, Youn YN, Song JW, Lee H, Kwak YL. Influence of preoperative hemoglobin A1c on early outcomes in patients with diabetes mellitus undergoing off-pump coronary artery bypass surgery. J Thorac Cardiovasc Surg. 2020;159(2):568-76. doi:10.1016/j.jtcvs.2019.01.086. https://doi.org/10.1016/j.jtcvs.2019.01.... ], 2020	Retrospective	Single centre (South Korea)	703 patients	•	Incidence of the composite post-operative morbidity and mortality endpoint was greater in patients with HbA1c ≥7.0% when compared to HbA1c <7.0% (21% vs. 15%, P=0.041)
	Retrospective	Single centre (South Korea)	703 patients	•	·A greater pre-operative HbA1c ≥7.0% was independently associated with composite mortality and morbidity endpoints (OR 1.60, 95% CI 1.03-2.50, P=0.038)

Study	Study design	Single/ Multi-centre	Sample size	Main outcomes
Narayan et al.[²⁰20 Narayan P, Kshirsagar SN, Mandal CK, Ghorai PA, Rao YM, Das D, et al. Preoperative glycosylated hemoglobin: a risk factor for patients undergoing coronary artery bypass. Ann Thorac Surg. 2017;104(2):606-12. doi:10.1016/j.athoracsur.2016.12.020. https://doi.org/10.1016/j.athoracsur.201... ], 2017	Retrospective	Single centre (India)	4,678 patients	•	30-day mortality was significantly higher in patients with HbA1c ≥6.5% when compared to those with HbA1c <6.5% (4.22% vs. 3.07%, P=0.0035), but in the multivariable analysis there was no significant difference in mortality (OR 1.36, 95%, CI 0.95-1.953, P=0.08)
van den Boom et al.[²¹21 van den Boom W, Schroeder RA, Manning MW, Setji TL, Fiestan GO, Dunson DB. Effect of A1C and glucose on postoperative mortality in noncardiac and cardiac surgeries. Diabetes Care. 2018;41(4):782-8. doi:10.2337/dc17-2232. https://doi.org/10.2337/dc17-2232... ], 2018	Retrospective	Single centre (USA)	6,393 patients	•	HbA1c was found to not be a significant predictor of post-operative mortality in cardiac surgery (P=0.88)
Tsuruta et al.[²²22 Tsuruta R, Miyauchi K, Yamamoto T, Dohi S, Tambara K, Dohi T, et al. Effect of preoperative hemoglobin A1c levels on long-term outcomes for diabetic patients after off-pump coronary artery bypass grafting. J Cardiol. 2011;57(2):181-6. doi:10.1016/j.jjcc.2010.11.003. https://doi.org/10.1016/j.jjcc.2010.11.0... ], 2011	Prospective	Single centre (Japan)	306 patients	•	No significant difference in all-cause mortality or cardiac mortality between patients with HbA1c <6.5%, 6.5-7.5% and ≥7.5% (HR 0.80, 95% CI 0.49-1.23, P=0.26 and P=0.17, respectively)
	Prospective	Single centre (Japan)	306 patients	•	Multivariate analysis showed that HbA1c did not predict mortality
Ramadan et al.[²³23 Ramadan M, Abdelgawad A, Elshemy A, Sarawy E, Emad A, Mazen M, et al. Impact of elevated glycosylated hemoglobin on hospital outcome and 1 year survival of primary isolated coronary artery bypass grafting patients. Egypt Heart J. 2018;70(2):113-8. doi:10.1016/j.ehj.2017.09.002. https://doi.org/10.1016/j.ehj.2017.09.00... ], 2018	Prospective	Single centre (Egypt)	80 patients	•	There was no statistically significant difference for in-hospital mortality between patients with HbA1c ≤7.0% and HbA1c >7.0% (2.5% vs. 7.5%, P=0.608)
	Prospective	Single centre (Egypt)	80 patients	•	There was no statistically significant difference for one-year mortality between patients with HbA1c ≤7.0% and HbA1c >7.0% (5.13% vs. 8.11%, P=0.600)
Subramaniam et al.[²⁴24 Subramaniam B, Lerner A, Novack V, Khabbaz K, Paryente-Wiesmann M, Hess P, et al. Increased glycemic variability in patients with elevated preoperative HbA1C predicts adverse outcomes following coronary artery bypass grafting surgery. Anesth Analg. 2014;118(2):277-87. doi:10.1213/ANE.0000000000000100.n.24 https://doi.org/10.1213/ANE.000000000000... ], 2014	Prospective	Single centre (Israel)	1,461 patients	•	No statistically significant difference in the incidence of death between patients with HbA1c <6.5% and with HbA1c ≥6.5% (3% vs. 2.6%, P=0.90)
Biskupski et al.[²⁸28 Biskupski A, Waligórski S, Kowalik B, Żych A, Sielicki P, Mirecki O, et al. Glycated hemoglobin HbA1c - a new risk marker for the outcome of cardiac surgery? Kardiochir Torakochirurgia Pol. 2014;11(1):7-11. doi:10.5114/kitp.2014.41922. n.28 https://doi.org/10.5114/kitp.2014.41922... ], 2014	Retrospective	Single centre (Poland)	350 patients	•	There was no significant difference in the incidence of death between patients with HbA1c <7.0% compared to HbA1c 7.0-8.0% (1.02% vs. 2.27%, P=0.78)
	Retrospective	Single centre (Poland)	350 patients	•	There was no significant difference in the incidence of death between patients with HbA1c <7.0% and with HbA1c >8.0% (1.02% vs. 4.74%, P=0.20)
Finger et al.[³⁰30 Finger B, Brase J, He J, Gibson WJ, Wirtz K, Flynn BC. Elevated hemoglobin A1c is associated with lower socioeconomic position and increased postoperative infections and longer hospital stay after cardiac surgical procedures. Ann Thorac Surg. 2017;103(1):145-51. doi:10.1016/j.athoracsur.2016.05.092. https://doi.org/10.1016/j.athoracsur.201... ], 2017	Retrospective	Single centre (USA)	531 patients+D21:D24D19:D24	•	There was no statistically significant difference in 30-day mortality between patients with HbA1c ≤7.0% or with HbA1c >7.0% (2.74% vs. 3.51%, P=0.670)

Study	Study design	Single/ Multi-centre	Sample size	Main outcomes
Biskupski et al.[²⁸28 Biskupski A, Waligórski S, Kowalik B, Żych A, Sielicki P, Mirecki O, et al. Glycated hemoglobin HbA1c - a new risk marker for the outcome of cardiac surgery? Kardiochir Torakochirurgia Pol. 2014;11(1):7-11. doi:10.5114/kitp.2014.41922. n.28 https://doi.org/10.5114/kitp.2014.41922... ], 2014	Retrospective	Single centre (Poland)	350 patients	•	There was no significant difference in the incidence of wound infection between patients with HbA1c <7.0% compared to HbA1c 7.0-8.0% (1.53% vs. 3.40%, P=0.57)
	Retrospective	Single centre (Poland)	350 patients	•	There was no significant difference in the incidence of wound infection between patients with HbA1c <7.0% and with HbA1c >8.0% (1.53% vs. 5.97%, P=0.13)
Tsuruta et al.[²²22 Tsuruta R, Miyauchi K, Yamamoto T, Dohi S, Tambara K, Dohi T, et al. Effect of preoperative hemoglobin A1c levels on long-term outcomes for diabetic patients after off-pump coronary artery bypass grafting. J Cardiol. 2011;57(2):181-6. doi:10.1016/j.jjcc.2010.11.003. https://doi.org/10.1016/j.jjcc.2010.11.0... ], 2011	Prospective	Single centre (Japan)	306 patients	•	There was no significant difference in the frequency of mediastinitis between patients with HbA1c <6.5%, HbA1c 6.5-7.5% and HbA1c ≥7.5% (P=0.11)
Ramadan et al.[²³23 Ramadan M, Abdelgawad A, Elshemy A, Sarawy E, Emad A, Mazen M, et al. Impact of elevated glycosylated hemoglobin on hospital outcome and 1 year survival of primary isolated coronary artery bypass grafting patients. Egypt Heart J. 2018;70(2):113-8. doi:10.1016/j.ehj.2017.09.002. https://doi.org/10.1016/j.ehj.2017.09.00... ], 2018	Prospective	Single centre (Egypt)	80 patients	•	There was no statistically significant difference in the incidence of deep sternal wound infection between patients with HbA1c ≤7.0% and >7.0% (0 vs. 5%, P=0.152)
Göksedef et al.[²⁹29 Strahan S, Harvey RM, Campbell-Lloyd A, Beller E, Mundy J, Shah P. Diabetic control and coronary artery bypass: effect on short-term outcomes. Asian Cardiovasc Thorac Ann. 2013;21(3):281-7. doi:10.1177/0218492312451983. https://doi.org/10.1177/0218492312451983... ], 2018	Prospective	Single centre (Turkey)	150 patients	•	HbA1c level was found to not affect the short-term infectious complication rates
	Prospective	Single centre (Turkey)	150 patients	•	There were no statistical differences between patients with HbA1c <7.0% and HbA1c >7.0% for non-sternal infection (2.1% vs. 3.5%, P=0.744) and for deep sternal wound infection (P=0.431)

Study	Study design	Single/ Multi-centre	Sample size	Main outcomes
Narayan et al.[20], 2017	Retrospective	Single centre (India)	4,678 patients	•	HbA1c ≥6.5% was found to be associated with a higher rate of sternal dehiscence (0.44% vs. 1.27%, P=0.002) and deep sternal wound infection (0.53% vs. 1.32%, P=0.004) compared to HbA1c <6.5%
Narayan et al.[20], 2017	Retrospective	Single centre (India)	4,678 patients	•	Multivariable analysis found that HbA1c ≥6.5% is an independent risk factor for sternal dehiscence (OR 2.161, 95% CI 1.008-4.630, P=0.04)
Subramaniam et al. [24], 2014	Prospective	Single centre (Israel)	1,461 patients	•	Rate of deep sternal wound infection was significantly higher in patients with HbA1c ≥6.5% than <6.5% (2.2% vs. 0.5%, P=0.008)
Finger et al.[30], 2017	Retrospective	Single centre (USA)	531 patients	•	HbA1c >7.0% was associated with increased risk of infection compared to patients with HbA1c ≤7.0% (10.76% vs. 31.58%, P<0.001)
Finger et al.[30], 2017	Retrospective	Single centre (USA)	531 patients	•	HbA1c >7.0% was associated with increased risk of sternal wound infection (0.84% vs. 5.26%, P=0.030)
Gatti et al.[25], 2016	Prospective	Multi-centre (16 centres across France, Italy, Germany, UK, Finland and Sweden)	114 patients	•	Baseline HbA1c was found to be significantly higher in patients who developed sternal wound infection than those who did not (mean 54±17 vs. 45±13 mmol/mol, P<0.0001)
				•	Logistic regression analysis showed that HbA1c was an independent risk factor for sternal wound infection (OR 1.04, 95% CI 1.02-1.05, P<0.0001)
				•	HbA1c >8.6% was associated with the highest risk of sternal wound infection (adjusted OR 5.01, 95% CI 2.47-10.15)
				•	HbA1c >7.0% was found to be associated with increased incidence for superficial wound infection (7.2% vs. 1.6%), deep wound infection (2.4% vs. 1.7%) and mediastinitis (1.1% vs. 0.6%) when compared to HbA1c ≤7.0% (P<0.0001)
				•	HbA1c >7.0% was associated with an increased risk of sternal wound infection (OR 2.15, 95% CI 1.28-1.96, P=0.004)

Authors' roles & responsibilities
DMA	Substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work; drafting the work or revising it critically for important intellectual content; final approval of the version to be published
TH	Substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work; drafting the work or revising it critically for important intellectual content; final approval of the version to be published
EA	Substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work; drafting the work or revising it critically for important intellectual content; final approval of the version to be published
AH	Substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work; drafting the work or revising it critically for important intellectual content; final approval of the version to be published

[1] Correspondence Address: Amer Harky Department of Cardiothoracic Surgery, Liverpool Heart and Chest Hospital, Liverpool, United Kingdom - Zip code: L14 3PE. E-mail: amer.harky@lhch.nhs.uk

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Glycated Haemoglobin Levels and Its Effect on Outcomes in Cardiac Surgery

Abstract