Heart Sci J 2020; 1(3): 1-3
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Heart Science Journal
Journal Homepage : www.heartscience.ub.ac.id

Editorial

The Importance of Managing HbA1c in Coronary Artery Disease:
Keep It Low
Djanggan Sargowo1,2
1
2

Brawijaya Cardiovascular Research Center, Department of Cardiology and Vascular Medicine, Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia.
Department of Cardiology and Vascular Medicine, Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia.

ARTI C LE I NFO

AB STR A C T

Keywords:
Coronary artery disease;
Diabetes mellitus;
HbA1c

Coronary Artery Disease (CAD) is the most prevalent cardiovascular disease, which remains the leading cause of
death worldwide. In Indonesia, it accounts for approximately 1.5% of the entire population. Diabetes mellitus
(DM) is taken into consideration as one of the most potent risk factors for cardiovascular diseases. HaemoglobinA1c (HbA1c) reflects a long-term glycemic control and is used as a valuable diabetes biomarker. High serum
glucose levels, expressed as glycated hemoglobin levels in diabetics or non-diabetics, are related to varying
degrees of systemic inflammation and promote the release of the proinflammatory cytokines. The association
between higher glycated serum HbA1c levels and the severity of the coronary disease is well known. The
predictive value of HbA1c for CAD severity, re-hospitalization, and the mortality of cardiovascular disease had
been studied extensively since 2004. Numerous previous trials discovered that severity of CAD correlated with the
elevation of HbA1c levels, suggesting it as a broad surrogate marker for CAD. Thus, HbA1c is currently considered
as an independent risk factor for CAD. A higher level of HbA1c and the presence of factors associated with
ongoing atherosclerosis and extensive CAD are concomitantly contributing to the higher major adverse cardiovascular events (MACEs) incidence and long-term mortality.

Coronary Artery Disease (CAD) is still the leading cause of
death of non-communicable diseases worldwide. CAD refers to the
pathologic process of atherosclerosis affecting the coronary arteries. It
remains predicted to be the leading cause of death globally within the
next 15 years, particularly in developing countries.1 Indonesia is one of
the developing countries with a high prevalence of CAD regarding data
from Riskesdas (2018), conducted by the Ministry of Health Republic of
Indonesia, with an estimation of 1.5% prevalence of the Indonesian
population.2

Hemoglobin A1c (HbA1c) indicates long-term glycemic
control, which also tracks well in individuals over time, in comparison
to fasting glucose specifically. In diabetics, HbA1c is associated with
microvascular disease development and is central to hyperglycemia's
clinical management. Even though there is evidence that HbA1c levels
are also related to macrovascular disease in people with diabetes, this
association remains controversial.5,6 Vascular complications can
develop in patients with HbA1c <7.0% and even in undiagnosed
patients because of a transient increase in plasma glucose concentration. Macrovascular complications may develop early and do not
linearly correlate to HbA1c, as well as microvascular complications. It
appears that chronic hyperglycemia is significant in CAD pathogenesis
and would extend to individuals with the elevation of HbA1c levels
even without a diabetes diagnosis.4

Diabetes mellitus (DM) is taken into consideration as one of
the major potential risk factors for cardiovascular disease. Compared to
non-diabetes of the same sex, age, and ethnicity, the excess risk for
cardiovascular disease was found to be two to eight times higher in
patients with diabetes mellitus.3 Glucotoxicity and lipotoxicity leading
to prolonged hyperglycemia and the dysfunction of beta-cell are reversible early pathophysiological events. This suggests that the course of
hyperglycemia and prevent or delay long-term complications can be
changed by proper management.4

HbA1c is a valuable diabetes biomarker used worldwide.
Mendel's randomization found genetic evidence that HbA1c is a risk
factor for CAD representing two different etiologic pathways, glycemic
and erythrocytic. The ability of HbA1c to predict CAD risk likely goes

*Corresponding author at: Brawijaya Cardiovascular Research Center, Department of Cardiology and Vascular Medicine, Faculty of Medicine,
Universitas Brawijaya, Malang, Indonesia
E-mail address: djanggan@yahoo.com (D. Sargowo).
https://doi.org/10.21776/ub.hsj.2020.001.03.1
Received 9 September 2020; Received in revised form 12 September 2020; Accepted 24 September 2020
Available online 21 October 2020

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Heart Sci J 2020; 1(3): 1-3

beyond its reflection of ambient glycemia and suggests the importance
of further research into the biology underlying the HbA1c-CAD association.6 High serum glucose levels expressed in glycated hemoglobin
levels in diabetic or non-diabetic individuals are related with varying
degrees of systemic inflammation and promotes the release of the
proinflammatory cytokines. The relation between higher glycated
hemoglobin levels in the blood with coronary disease severity and
hospital admission was associated with low-grade vascular inflammation and long-term promotion of atherogenesis.7
Selvin et al. (2005) showed that the elevation of HbA1c
levels was an independent risk factor for CAD in people with and
without diabetes.5 Glycosylated HbA1c is an important biomarker that
considers fasting and postprandial plasma glucose concentrations over
the previous 2-3 months.3,8 HbA1c has been taken into consideration as
the standard criterion for monitoring and diagnosing diabetes mellitus
(DM) for many years. It has several advantages over oral glucose
tolerance tests and fasting plasma glucose, including greater comfort,
greater pre-analysis stability, and less daily distraction during stress
and illness. HbA1c has been recommended by The American Diabetes
Association (2019) as the most effective diagnostic and prognostic tool
for DM and its complications.9 Selvin et al. (2005) shows that even CAD
risk could start at HbA1c less than 7%, the usual target for good
glycemic control. Thus, well into the "normal” range (i.e., between
4.6% and 6.0%), HbA1c values relate to CAD. The current study
provides guidance on the informative range of HbA1c for CAD risk and
suggests that future studies of HbA1c and cardiovascular risk in non-diabetic individuals should be considered.5 Since 2004, the predictive
value of HbA1c for the severity of CAD and cardiovascular mortality in
non-diabetes has been extensively studied. Elevation of HbA1c levels
was found in many trials to be related with CAD severity, indicating it
as an extensive marker of CAD.3

Figure 1. Forest Plot For Long-Term Mortality.10

Based on research by Timmer and Pai on non-diabetic adults,
the Atherosclerosis Risk In Communities (ARIC) study (2015), a higher
HbA1c level was related to higher cardiovascular disease and mortality.6,9 Ghaffari et al. (2015), which evaluate the correlation of HbA1c
with CAD severity using the Califf scoring system in STEMI patients,
demonstrated similar results as well. Levels of HbA1c on admission
correlated with short-term and in-hospital outcomes of non-diabetic
patients presenting with STEMI. This study showed HbA1c level >
5.8% in non-diabetic patients with STEMI was related to severe CAD
and the involvement of coronary artery multivessel as well. Although
the same complications and mortality occurred during the hospitalization period, the significant decrease of 1 year survival in patients with
HbA1c level > 5.8% was observed. Among these cases, the percentage
of cardiovascular disease-related re-hospitalization was also higher
than the HbA1c percentage below the median value.7

Figure 2. Forest Plot For Re-infarction During Follow-Up.10
In conclusion, many data support the involvement of HbA1c
as an independent risk factor for CAD. A significant correlation was
shown between HbA1c, admission to hospital, coronary artery severity,
and adverse cardiovascular events, which could act as a surrogate for
worse long-term outcomes. Therefore, it is recommended that HbA1c
levels be maintained within normal limits (below 5.7%). Higher HbA1c
levels and the presence of factors such as changes in blood glucose
levels can be associated with ongoing atherosclerosis and extensive
CAD, and together can lead to higher long-term mortality.

A meta-analysis conducted by Geng et al. (2017) demonstrated an association between elevated HbA1c level and higher
long-term mortality (shown in Figure 1) and higher re-infarction
incidence (shown in Figure 2). HbA1c 5.7% to 6.5% is considered
prediabetes, according to the most recent guidelines for the diagnosis of
diabetes mellitus. In this meta-analysis, eight studies presented the
HbA1c threshold of 5.7%, and subgroup analysis of HbA1c levels
showed a significant association between prediabetes and long-term
mortality. (OR 1.31, 95% CI 1.10–1.55).10

Conflict of interest
There is no conflict of interest.
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