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 Table of Contents  
ORIGINAL ARTICLE
Year : 2021  |  Volume : 9  |  Issue : 3  |  Page : 184-187

Evaluation of the association between glycated hemoglobin levels and severity of coronary artery disease in nondiabetic patients


1 Department of Neurology, DMC, Ludhiana, Punjab, India
2 Department of Cardiology, MGMCH, Jaipur, Rajasthan, India
3 Department of Medicine, MGMCH, Jaipur, Rajasthan, India

Date of Submission29-Oct-2021
Date of Acceptance26-Nov-2021
Date of Web Publication22-Dec-2021

Correspondence Address:
Dr. Archit Dahiya
74-R Model Town, Rohtak - 124 001, Haryana
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/heartindia.heartindia_99_21

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  Abstract 


Introduction: Higher fasting blood glucose level plus raised glycated hemoglobin (HbA1c) levels is one of the major risk factors for cardiovascular (CV) events in nondiabetic population. HbA1c levels have low intra-individual variability especially in nondiabetic patients. Studies have shown that coronary artery disease (CAD) and HbA1c are predictors of CV mortality. In this study, we have evaluated the association between HbA1c and severity of CAD in nondiabetic patients.
Materials and Methods: This is a hospital-based observational study done on 300 patients in Department of Medicine and Department of Cardiology, Mahatma Gandhi Medical College and Hospital, Jaipur. Prior approval was taken before the start of study from the Institute Ethics Committee. Gensini score was used to estimate the CAD severity. This score is based on the sum of scores for all 3 coronary arteries to assess the entire extent of CAD. Data were analyzed and appropriate statistical tests were used. P < 0.05 were considered statistically significant.
Results: This study showed that the majority of cases (59.33%) were seen in 51–70 years of age group. The maximum number of patients (66.66%) had 5.6–6.5 HbA1c level and 29.36 ± 19.50 Gensini score in our study. Mean Gensini score showed a linear relationship with HbA1c.
Conclusion: HbA1c level has a prognostic value for predicting the severity of CAD among nondiabetic patients and can act as a useful marker in risk stratification of nondiabetic patients presenting with acute coronary syndrome and indicated for angiographic evaluation.

Keywords: Coronary artery disease, diabetes, Gensini score, glycated hemoglobin


How to cite this article:
Singh B, Agarwal D, Dahiya A, Saxena G N. Evaluation of the association between glycated hemoglobin levels and severity of coronary artery disease in nondiabetic patients. Heart India 2021;9:184-7

How to cite this URL:
Singh B, Agarwal D, Dahiya A, Saxena G N. Evaluation of the association between glycated hemoglobin levels and severity of coronary artery disease in nondiabetic patients. Heart India [serial online] 2021 [cited 2022 Aug 18];9:184-7. Available from: https://www.heartindia.net/text.asp?2021/9/3/184/333300




  Introduction Top


Diabetes mellitus (DM) has become a true pandemic of this century with an increasing prevalence and incidence in all the countries either poor or prosperous. It is expected that the total diabetic population in the world will be over 360 million people by 2030. DM is one of the most important risk factors for cardiovascular (CV) diseases. The risk of CV diseases is two to eight folds higher in patients with diabetes when compared to nondiabetics of similar age, sex, and ethnicity.[1]

The risk of developing coronary artery disease (CAD) and duration of diabetes have shown positive correlation in various studies.[2] CAD has become the most important cause of death all over the world including India. It resulted in 7.5 million deaths worldwide accounting for 13.3% of all deaths in 2013.[3]

Higher fasting blood glucose level plus raised glycated hemoglobin (HbA1c) levels is one of the major risk factors for CV events in nondiabetic population.[4] HbA1c levels have low intra-individual variability especially in nondiabetic patients.[5] Studies have shown that CAD and HbA1c are predictors of CV mortality.[6],[7],[8]

Many studies have reported about association between HbA1c levels and severity of CAD. Several scoring systems are being used to determine the severity of CAD. Gensini scoring system is one of these scoring systems, which is most commonly used for this purpose. The aim of this study was to evaluate the association between HbA1c levels and severity of CAD in nondiabetic patients.


  Materials And Methods Top


This study is done on 300 patients in Department of Medicine and Department of Cardiology, Mahatma Gandhi Medical College and Hospital, Jaipur, and is a hospital-based observational study. Prior approval was taken before the start of study from the Institute Ethics Committee.

Inclusion criteria

  • All nondiabetic patients with HbA1c <6.5%
  • All patients with proven CAD by angiography.


Exclusion criteria

  • Patient with history of DM
  • HbA1c >6.5%
  • Previous history of coronary artery bypass grafting or percutaneous transluminal coronary angioplasty
  • Patient with ≤18 years of age.
  • Patient with comorbidities such as chronic kidney disease, sepsis, or hemoglobinopathy
  • Patient who did not give consent.


Gensini score was used to estimate the CAD severity. This score grades narrowing of the lumen of artery and give numerical values with the following system; for 1%–25% narrowing Score 1, for 26%–50% narrowing Score 2, for 51%–75% Score 4, for 76%–90% Score 8, for 91%–99% Score 16, and for a complete occlusion Score 32.[9]

Multiplier is used on these scores depending on the importance of lesion's location in the coronary artery system. The multiplying factor is of 5 points for the left main lesion; 2.5 for the proximal left anterior descending (LAD) or left circumflex (LCX) artery; 1.5 for the mid segment LAD and LCX; 1 for the distal segment of LAD and LCX artery, first diagonal branch, first obtuse marginal branch, right coronary artery, posterior descending artery, ramus intermedius artery; 0.5 for the second diagonal and second obtuse marginal branches. Gensini score is based on the sum of scores for all 3 coronary arteries to assess the entire extent of CAD.

Statistical analysis

Variables were compared and student paired t-test were used to find significant association. Spearman correlation was done in IBM SPSS Modeler 16.0. P < 0.05 were considered statistically significant.


  Results Top


The present study showed that the majority of cases (59.33%) were seen in 51–70 year of age group. The mean value of HbA1c was 5.766 ± 0.5131 in 51–70 years of age followed by 5.720 ± 0.5478 in 31–50 years of age and 4.955 ± 0.4172 in <30 years of age group [Table 1].
Table 1: Distribution of patients according to age group with glycated hemoglobin

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The mean value of Gensini score was 27.28 ± 20.44 in 51–70 years of age followed by 25.15 ± 20.18 in 31–50 years of age and 12.62 ± 10.24 in above 70 years of age group [Table 2].
Table 2: Age-wise distribution of Gensini score

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Maximum number of patients (66.66%) had 5.6–6.5 HbA1c level and 29.36 ± 19.50 Gensini score in our study. Mean Gensini score showed a linear relationship with HbA1c [Table 3].{Table 3]


  Discussion Top


In patients with DM, HbA1c is an established marker of long-term glycemic control. Elevated HbA1c levels in diabetics are strongly related with an increased risk of future macrovascular and microvascular disease.[10] HbA1c is a reflection of 2–3 months average endogenous exposure to blood glucose inclusive of postprandial spikes. It has a relatively low intra-individual variability especially in nondiabetic patients.[5] HbA1c level <7% was found beneficial in terms of reduction in vascular complications.[11]

Pani et al. reported that nonglycemic factors might contribute to the relationship of HbA1c with age.[12] Our study showed that the subjects with age <30 (1.33%) had a mean value of HbA1c 4.955 ± 0.4172, subjects in the age group 31–50 (30.66%) had a mean value of HbA1c 5.720 ± 0.5478, subjects in age group 51–70 (59.33%) had a mean value of HbA1c 5.766 ± 0.5131, and subjects >70 (8.66%) years had a mean value of HbA1c 5.675 ± 0.8193. Our study showed a linear relationship between age and HbA1c levels which was consistent with previous studies.

HbA1c levels showed significant correlation with Gensini score in premature CAD patients (age <40 years) in both diabetic and nondiabetics in the study by Ayhan et al.[13]

In the study by Ghaffari et al. in nondiabetics, patients with HbA1c >5.8% had two times higher risk of having triple-vessel diseases.[8] Kowalska et al. reported significant correlation between number of diseased vessels and increasing levels of HbAlc in a cohort of nondiabetic men referred for coronary angiography.[14] Complexity of coronary lesions in diabetic and nondiabetic adults was found to be significantly associated with increasing HbAlc levels in study by Ikeda et al.[15]

Kayali and Ozder demonstrated the use of HbA1c levels for determining the probability and severity of CAD in nondiabetic individuals and also as a strong marker in primary care predicting CAD.[16]

Our study showed that the mean value of Gensini score was 3.625 ± 3.311 in subjects with HbA1c <4.8%, 1.917 ± 1.625 in subjects with HbA1c 4.8%–5.1%, 24.20 ± 18.82 in subjects with HbA1c 5.1–5.6 and the maximum number of patients (66.66%) had 5.6–6.5 HbA1c level and 29.36 ± 19.50 Gensini score.

Similar to previous studies, the results of our study showed that Gensini score is significantly higher in the high-risk group and demonstrated a linear relationship with HbA1c levels. HbA1c levels showed significant association with the severity of CAD (r = 0.35, P < 0.05).

In a study on nondiabetic patients with STEMI by Ghaffari et al., HbA1c >5.8% demonstrated correlation with severe CAD and multivessel involvement of the arteries. Furthermore, higher rates of 1-year mortality and hospital readmission was seen in HbA1c level >5.8% group.[8]

However, Habib et al. reported that in nondiabetic patients with acute coronary syndrome, HbA1c is not an independent predictor of the severity of CAD. This study included 119 nondiabetic adults ≥18 years who underwent coronary angiography.[17]

Ewid et al. enrolled 38 nondiabetic patients with no history of CAD in study and the coronary artery stenosis (CAS) assessment was seen by coronary computed tomography angiography. A strong correlation was seen between HbA1c and CAS percentages as well as between HbA1c levels and the number of affected arteries.[18]

Dutta et al. concluded that as HbA1c level increases, the mean number of diseased vessels also increases significantly (P < 0.001). Smoking was reported as an independent predictor of severity of CAD by SYNTAX score (P < 0.05). Other variables such as gender, age, hypertension, and dyslipidemia had no significant difference among quartiles.[19]

Ashraf et al. concluded that in nondiabetic patients, HbA1c may be use for risk stratification of CAD and its severity, independent of other CV risk factors, insulin resistance, and inflammatory markers.[20] Bastawesy et al. found that the HbA1c levels were positively associated with Gensini score (r = 0.35, P < 0.05).[21]


  Conclusion Top


Higher HbA1c is significantly correlated with the CAD severity among nondiabetic subjects in this study. HbA1c has a prognostic value in nondiabetic subjects for predicting the severity of CAD and it is an important marker for risk assessment in patients with ACS indicated for coronary angiography. Further research in the form of randomized controlled trials with larger patient population are needed to explore and give validation to this association.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

Ethical approval

This study was approved by Institutional Ethics Committee via letter MGMCH/IEC/JPR/2017/329 (Date- 06/04/2017).

Authors' contributions

All authors contributed to the study conception, design, material preparation, data collection and analysis. All authors have read and approved the final manuscript.



 
  References Top

1.
Klein R. Hyperglycemia and microvascular and macrovascular disease in diabetes. Diabetes Care 1995;18:258-68.  Back to cited text no. 1
    
2.
Barrett-Connor E. Does hyperglycemia really cause coronary heart disease? Diabetes Care 1997;20:1620-3.  Back to cited text no. 2
    
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GBD 2013 Mortality and Causes of Death Collaborators. Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: A systematic analysis for the Global Burden of Disease Study 2013. Lancet 2015;385:117-71.  Back to cited text no. 3
    
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Nasir K, Santos RD, Tufail K, Rivera J, Carvalho JA, Meneghello R, et al. High-normal fasting blood glucose in non-diabetic range is associated with increased coronary artery calcium burden in asymptomatic men. Atherosclerosis 2007;195:e155-60.  Back to cited text no. 4
    
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Selvin E, Crainiceanu CM, Brancati FL, Coresh J. Short-term variability in measures of glycemia and implications for the classification of diabetes. Arch Intern Med 2007;167:1545-51.  Back to cited text no. 5
    
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Rossing P, Hougaard P, Borch-Johnsen K, Parving HH. Predictors of mortality in insulin dependent diabetes: 10 year observational follow up study. BMJ 1996;313:779-84.  Back to cited text no. 6
    
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Gall MA, Borch-Johnsen K, Hougaard P, Nielsen FS, Parving HH. Albuminuria and poor glycemic control predict mortality in NIDDM. Diabetes 1995;44:1303-9.  Back to cited text no. 7
    
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Ghaffari S, Niafar F, Separham A, Niafar M, Pourafkari L, Nader ND. Association between HbA1c levels with severity of coronary artery disease and short-term outcomes of acute ST-elevation myocardial infarction in nondiabetic patients. Ther Adv Cardiovasc Dis 2015;9:305-13.  Back to cited text no. 8
    
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Selvin E, Steffes MW, Zhu H, Matsushita K, Wagenknecht L, Pankow J, et al. Glycated hemoglobin, diabetes, and cardiovascular risk in nondiabetic adults. N Engl J Med 2010;362:800-11.  Back to cited text no. 9
    
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Malmberg K, Rydén L, Wedel H, Birkeland K, Bootsma A, Dickstein K, et al. Intense metabolic control by means of insulin in patients with diabetes mellitus and acute myocardial infarction (DIGAMI 2): Effects on mortality and morbidity. Eur Heart J 2005;26:650-61.  Back to cited text no. 10
    
11.
Selvin E, Coresh J, Shahar E, Zhang L, Steffes M, Sharrett AR. Glycemia (haemoglobin A1c) and incident of ischemic stroke: The atherosclerosis risk in communities (ARIC) study. Lancet Neurol 2015;4:821-6.  Back to cited text no. 11
    
12.
Pani LN, Korenda L, Meigs JB, Driver C, Chamany S, Fox CS, et al. Effect of aging on A1C levels in individuals without diabetes: Evidence from the Framingham offspring study and the national health and nutrition examination survey 2001-2004. Diabetes Care 2008;31:1991-6.  Back to cited text no. 12
    
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Ayhan SS, Tosun M, Ozturk S, Alcelik A, Ozlu MF, Erdem A, et al. Glycated haemoglobin is correlated with the severity of coronary artery disease independently of traditional risk factors in young patients. Endokrynol Pol 2012;63:367-71.  Back to cited text no. 13
    
14.
Kowalska I, Prokop J, Bachórzewska-Gajewska H, Telejko B, Kinalskal I, Kochman W, et al. Disturbances of glucose metabolism in men referred for coronary arteriography. Postload glycemia as predictor for coronary atherosclerosis. Diabetes Care 2001;24:897-901.  Back to cited text no. 14
    
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Ikeda N, Iijima R, Hara H, Moroi M, Nakamura M, Sugi K. Glycated hemoglobin is associated with the complexity of coronary artery disease, even in non-diabetic adults. J Atheroscler Thromb 2012;19:1066-72.  Back to cited text no. 15
    
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Kayali Y, Ozder A. Glycosylated hemoglobin A1c predicts coronary artery disease in non-diabetic patients. J Clin Lab Anal 2021;35:e23612.  Back to cited text no. 16
    
17.
Habib S, Ullah SZ, Saghir T, Syed Muhammad A, Ud Deen Z, Naseeb K, et al. The association between hemoglobin A1c and the severity of coronary artery disease in non-diabetic patients with acute coronary syndrome. Cureus 2020;12:e6631.  Back to cited text no. 17
    
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Ewid M, Sherif H, Billah SM, Saquib N, AlEnazy W, Ragab O, et al. Glycated hemoglobin predicts coronary artery disease in non-diabetic adults. BMC Cardiovasc Disord 2019;19:309.  Back to cited text no. 18
    
19.
Dutta B, Neginhal M, Iqbal F. Glycated hemoglobin (HbA1c) correlation with severity of coronary artery disease in non-diabetic patients – A hospital based study from North-Eastern India. J Clin Diagn Res 2016;10:C20-3.  Back to cited text no. 19
    
20.
Ashraf H, Boroumand MA, Amirzadegan A, Talesh SA, Davoodi G. Hemoglobin A1C in non-diabetic patients: An independent predictor of coronary artery disease and its severity. Diabetes Res Clin Pract 2013;102:225-32.  Back to cited text no. 20
    
21.
Bastawesy RB, Abdelmoniem A, Abdelkader M, Ismaiel R. The relation between glycated hemoglobin and severity of coronary artery disease in non-diabetic patients with acute coronary syndrome. Int J Adv Res 2016;4:2393-9.  Back to cited text no. 21
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

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