This is a rare study in the literature that aimed
to determine the correlation between coronary artery
lesion severity determined by coronary CTA and
HbA1c value in nondiabetic patients. In our study, the
median HbA1c levels were significantly higher in the
patient group with significant coronary artery stenosis
compared to the group with nonsignificant coronary
artery stenosis (p<0.001), and there was a strong
correlation between coronary artery lesion severity and
the HbA1c value in nondiabetic patients with CCS.
One of the confounding factors affecting HbA1c
is the hemoglobin value, as it changes HbA1c. A
low hemoglobin value may lower the HbA1c level.
Therefore, low hemoglobin status may show an
inaccurate relationship between CAD severity and low
HbA1c levels.[9] One of the advantages of our study
is that the median hemoglobin values were within
normal limits in both groups.
Garg et al.,[10] Ayhan et al.,[11] and Kis and
Guzel[12] found the cut-off values of HbA1c as 5.7,
6.52, and 5.5, respectively, and concluded that it
was an independent predictor of the severity of CAD in nondiabetic patients. In our study, the
HbA1c cut-off value was determined as 5.66 as
a predictor of a severe coronary artery lesion in
coronary CTA.
Hemoglobin A1c is a parameter that is used in the
diagnosis and follow-up of DM and quantitatively
shows the three-month glycemic control. It is possible
to establish a relationship between HbA1c and
coronary atherosclerosis, considering that exposure
to high blood sugar causes vascular complications.
Unregulated blood sugar induces oxidative stress,
and the developing glycation end products and lipid
peroxidation products initiate endothelial damage.
As a result, an inflammatory process develops, and
atherogenesis becomes active.[13] Hemoglobin A1c is
also an advanced glycation end product.
In a study by Haring et al.[14] in 1798 nondiabetic
patients, it was shown that the carotid intimamedia
diameter increased by 0.02 mm for each
1% increase in HbA1c. The study of Kayalı and
Ozder[15] hypothesized that HbA1c predicts CAD in
nondiabetic patients. In the study, 247 patients were
recruited and classified according to the coronary
arteries lesion severity, and a close relationship was
found between HbA1c and coronary stenosis. When
the recent prospective studies were examined, it was
observed that although some claimed the opposite
between HbA1c and CAD, most of them contributed
to the literature. It has been shown that each
percentage increase in HbA1c in nondiabetic patients
increases the risk of CAD 1.2 times.[16] In a study that
included 93 patients investigating the relationship
between the severity of coronary atherosclerosis and
HbA1c, HbA1c values were found to be higher in the
group with severe atherosclerosis.[17] In the study of
Dutta et al.,[18] it was concluded that as the HbA1c
level increased, the number of affected vessels in the
coronary arteries also significantly increased.
Ashraf et al.[19] investigated whether HbA1c was
an independent predictor of CAD in their study
of 382 patients with suspected coronary ischemia
without a known history of DM. However, while age
and sex were statistically significantly higher at first,
among the cardiovascular risk factors (for example,
sex, hypertension, dyslipidemia, and smoking), no
statistically significant difference was observed after
additional analysis. We can believe that these risk
factors that may cause CAD may have affected the
outcome of the current study. However, a significant difference was found between the two groups only in
terms of hypertension, which is one of the etiological
factors that may cause coronary atherosclerosis. In this
study, LVEF was found to be lower in the group with
more severe coronary lesions. This result was thought
to be due to the negative effect of coronary ischemia
on left ventricular systolic function. In our study, the
hypertension rate was higher and the median LVEF
value was lower in the group with higher coronary
lesion severity.
There are several limitations to this study. First,
the HbA1c values of the patients were calculated
when the patients were admitted to the hospital.
The HbA1c value is based on a single measurement;
thus, it may underestimate any relationship between
HbA1c and coronary artery lesion severity. Second,
coronary CTA calcium score was not included in the
analysis as the selected patient population differed
according to whether severe lesions were detected.
Although the study population was relatively small,
the patient group was found to be sufficient in the
power analysis performed before the study. However,
studies involving more patients are needed, and
we believe that our study may be a pioneer for
further studies on this subject. Since we do not
have long-term follow-up results, we do not know
the prognostic value of HbA1c in the long-term
follow-up of patients with CCS.
In conclusion, in nondiabetic patients with CCS,
HbA1c, which shows the long-term glycemic index, is
associated with severe coronary artery lesions detected
in CTA. Controlling the HbA1c values of patients
while planning diagnostic coronary CTA may be a
guide in patients with suspected nondiabetic CAD.
Ethics Committee Approval: The study protocol was
approved by the Bakırçay University Medicine Faculty Ethics
Committee (date: 03.08.2022, no: 684). The study was
conducted in accordance with the principles of the Declaration
of Helsinki.
Patient Consent for Publication: A written informed
consent was obtained from each patient.
Data Sharing Statement: The data that support the
findings of this study are available from the corresponding
author upon reasonable request.
Author Contributions: Idea/concept, design, control/
supervision, critical review: M.K., Data collection and/or
processing, analysis and/or interpretation, references and
fundings, materials: F.S.Y.; Literature review, writing the
article: F.S.Y., M.K.
Conflict of Interest: The authors declared no conflicts
of interest with respect to the authorship and/or publication
of this article.
Funding: The authors received no financial support for
the research and/or authorship of this article.