The Effect of Glycemic Control on Cardiac Outcomes in Saudi Diabetic Patients who Underwent Coronary Angiogram.

BACKGROUND: Diabetes mellitus is a metabolic disorder that causes impaired insulin secretion or cellular dysfunction. Glycated hemoglobin (HbA1c) indicates the long-term level of glucose. Diabetes can lead to cardiovascular complications such as acute coronary syndrome , which might require coronary intervention.
OBJECTIVES: The aim of this study was to estimate the effect of glycemic control measured by HbA1c levels on cardiac complications in Saudi diabetic patients who underwent percutaneous coronary intervention (PCI) or Coronary artery bypass graft (CABG).
METHODOLOGY: It was a cohort retrospective study conducted at King Abdulaziz Cardiac Center with a total sample size of 379 patients. The charts of all those diabetic patients were reviewed and their HbA1c level, type of intervention were compared to determine their effect on cardiac outcomes and complications. Inclusion criteria involved the age group 50-70 years within follow-up period of 3 years. Any patient known to have renal failure, liver dysfunction, type one diabetes, and cancer were excluded. The HbA1c level was divided into two groups (<7.5%, ≥7.5%).
RESULTS: Total sample size was 379, and the mean age was (60.33 ± 5.98) with male being (66.5%). HbA1c levels at admission were (mean 9.15 ± 2.03), whereas the mean after 3 years was (8.629 ± 1.518). The uncontrolled group was more likely to have PCI (n = 302), in comparison to the controlled group (n = 77) with a P value of 0.04. However, the controlled group was more likely to undergo medical treatment P value of 0.001. Patients with uncontrolled Hba1c after the intervention had a higher readmission rate with a P value of 0.018.
CONCLUSIONS: Patients with an elevated level of HbA1c were more likely to be managed with PCI. Furthermore, they are at a higher risk of multiple readmissions. Patients who had CABG were at a lower risk of cardiac complications. Further studies are required in our population to consider different approaches of diabetes control for preventing adverse outcomes. Copyright:

INTRODUCTION

Diabetes mellitus is a metabolic disorder resulting from the pancreas's inability to secrete enough of the hormone insulin or the body's inability to utilize it efficiently, leading to hyperglycemia. Statistically, 23.7% of the Saudi population has diabetes.[1] The diagnosis of diabetes depends on symptoms and laboratory findings. HbA1c (glycated hemoglobin) indicates the long-term level of glucose. An HbA1c level of ≥6.5% on two separate occasions indicates the presence of diabetes.[2] Diabetes can lead to cardiovascular complications and end-organ damage.

Diabetes is associated with cardiac complications. For instance, diabetes is a risk factor for the acute coronary syndrome (ACS).[1] ACS is a group of cardiac complications that occur when plaque within the arterial wall ruptures, causing partial or complete occlusion of the lumen. It can result in mortality and morbidities such as stroke, heart failure, and recurrent myocardial infarction (MI).[3] Some of these complications require admission for coronary interventions. For example, percutaneous coronary intervention (PCI) where the occluded artery is dilated and a stented. Another intervention is coronary artery bypass graft (CABG), in which a vessel is connected to the blocked coronary artery bypassing the blocked segment.[4]

Because of hyperglycemia in diabetics, some complications develop after they undergo these interventions. Recurrent MI, atrial fibrillation, and restenosis are examples.

It was observed in a study on diabetics who were undergoing PCI that patients without a good control of HbA1c had a higher mortality rate.[5] Moreover, another study suggested that there is a strong relationship between glucose level with short and long-term effects.[6] Furthermore, a prospective observational study on patients undergoing CABG with a follow-up of 3.5 years; reported that patients with HbA1c ≥6% had significantly greater mortality.[7] Furthermore, an observational cohort study was done on type 1 diabetic patients stated that poor glycemic control before CABG was linked with a higher risk of major cardiac events and higher mortality.[8] A study, however, reported that HbA1c level may not predict the long-term effects for diabetic patients who are undergoing off-pump CABG.[9] Another study concluded that short-term outcomes were not affected by different levels of HbA1c in diabetics who underwent CABG.[10]

The studies mentioned above show that more research about the relationship between glycemic control and cardiac complications after coronary intervention could be helpful. In addition, the information about the effect of glycemic control on Saudi diabetic patients was lacking. In this study, many different factors were included such as HbA1c level, coronary intervention type, and cardiac complications. The age range of Saudi diabetic patients was 50 and 70.

The aim of this study is to identify and estimate the effect of glycemic control (HbA1c) on cardiac complications in Saudi diabetic patients who underwent PCI or CABG.

Specific objectives

The aim of this study was to estimate the effect of glycemic control measured by HbA1c levels on cardiac complications in Saudi diabetic patients who underwent PCI or coronary artery bypass grafting (CABG).

METHODOLOGY

Study setting and study design

This study was a retrospective cohort study that was conducted at King Abdulaziz Cardiac Center (KACC) in which consecutive charts of Saudi diabetic patients admitted between 2008 and 2012 were reviewed. Their HbA1c level and type of intervention was compared to determine their effect on developing cardiac complications. Grouping of the patients was as follows: Patients with glycemic control (Group A; HbA1c below 7.5%; n = 77) and patients with poor glycemic control (Group B, HbA1c above or equal 7.5%; n = 302).

The study was conducted at KACC, which is located at King Abdelaziz Medical City in Riyadh, Saudi Arabia, where male patients represent 65% of admissions, while females represent 35%. Moreover, 60% of admissions were usually from the emergency room. The majority of patients were Saudis with a high number of ACS cases.

Data collection method, sampling technique, and instruments

This study included Saudi diabetic patients. Inclusion criteria: Diabetic patients who were admitted to KACC in Riyadh, patients admitted in the period 2008–2012, and patients between 50 and 70 years old. The follow-up of outcomes in these patients was for a period of 3 years. Exclusion criteria were any patients diagnosed with renal failure, liver dysfunction, Type 1 one diabetes, cancer and incomplete data. Consecutive sampling was the sampling technique by reviewing all the charts that were available. Data collection started in December 2017, and chart review was the method in which the data were collected by the research team from of KACC and clinical records were reviewed using a data collection form. Background variables were age, gender, and body mass index (BMI).

The grouping variables used for comparison were HbA1c level (≥7.5%, <7.5%) and type of intervention (medication, PCI, and CABG). Heart failure, ACS, and mortality were the outcome variables. Furthermore, the cardiac center provided us with a list of patients diagnosed with ACS. We organized the data immediately and coded the patients' records to ensure the privacy of the record. After that, we were assigned to get access for the computer systems at the cardiac center. We organized the records and started the data collection.

At first, we had 397 records and 18 patients were excluded due to loss of follow-up. By November 2019, data collection was completed, and data was transferred to an Excel sheet. Then we coded the variables and transferred the data into SPSS.

Statistical analysis

In November 2019, data collection was completed, and data were transferred to an Excel sheet. Then, we coded the variables and transferred the data into SPSS. Data were managed using Excel 2016 and analyzed by using (SPSS software (v.20) in August 2018.

Numerical data such as HbA1c level and age were calculated by mean and standard deviation and presented by boxplot. Percentages and frequencies were measured for categorical data such as ejection fracture and BMI. For bivariate analysis, the Chi-square test was used to assess the effect of risk factors individually on the outcomes. If the P < 0.05, the test is considered significant.

RESULTS

The total sample size is 379 and the mean age is (60.33 ± 5.98 years) with males being (66.5%). Patients who were managed by diet only were 3.7%, oral medications were 54.1% and insulin injections were 42.2. Most of the patients are overweight 39% and obese 43%. Furthermore, HbA1c levels at admission are (mean 9.15 ± 2.03), whereas the mean after 3 years is (8.629 ± 1.518).

Figure 1 shows diabetes in years before the admission of the first ACS, and it shows that the mean is around 10 years. The ejection fraction of the heart is presented in Figure 2, where it shows that 39% of patients were considered as having normal ejection fraction of the heart at admission. The type of ACS is shown in the bar chart Figure 3 in which patients who were diagnosed with ST-segment elevation myocardial infarction (STEMI) are (n = 95), non-STEMI (n = 148), and unstable angina (n = 136).

Figure 1

The graph, shows diabetes in years since diagnosis, and it also shows that the mean is 10 years

Figure 2

The graph shows, levels of ejection fraction among diabetic patients at admission

Figure 3

The graph shows, incidence of acute coronary syndrome among HbA1C grouping at admission. Blue color controlled group HA1C <7.5, red uncontrolled HA1C >7.5

Table 1 shows risk factors and HbA1c level grouping (controlled level of HbA1c <7.5% vs. uncontrolled level of HbA1c ≥7.5). The history of peripheral vascular disease was only shown in the uncontrolled group, with a P value of 0.015. Moreover, the controlled group was more likely to be managed with oral hypoglycemic while the uncontrolled group by insulin therapy with a P value of (0.045 and 0.005, respectively). Other risk factors did not show any statistical significance.

Table 1

Grouping of glycated hemoglobin and sociodemographics variables

Demographics	HbA1c grouping		Total	Chi-square tests, P
	Controlled (HbA1c <7.5%) number of patients=77, n (%)	Uncontrolled (HbA1c =7.5% or above) number of patients=302, n (%)
Male	50 (64.9)	202 (66.9)	252	0.745
Female	27 (35.1)	100 (33.1)	127
Diet only	7 (30.4)	7 (10.6)	14	0.024
Diabetics oral medication	52 (91.2)	153 (79.7)	205	0.045
Insulin therapy	18 (62.2)	141 (84.4)	159	0.005
Hypertension	64 (83.1)	238 (78.8)	302	0.409
Dyslipidemia	61 (79.2)	240 (79.5)	301	0.961
Peripheral vascular disease	0	22 (7.3)	22	0.015
Chronic obstructive pulmonary disease	2 (2.6)	16 (5.3)	18	0.320
Cerebrovascular accident	8 (10.4)	18 (6)	26	0.170
Smoker	17 (22.1)	59 (19.5)	76	0.619
History of obesity	30 (39)	128 (42.4)	158	0.587
Heart failure	26 (34.7)	77 (25.5)	103	0.111

HbA1c: Glycated hemoglobin

The number of patients who underwent diagnostic coronary angiogram 233 (controlled 23% n = 55, uncontrolled 77% n = 178), and the number pf patients who underwent PCI using stents was 146 (controlled 28.6% n = 22, Uncontrolled 41.1%, n = 124).

Table 2 grouping ofHbA1c and outcomes. It shows that patients with uncontrolled HbA1c after the intervention had a higher readmission rate within 36 months when compared with the controlled group with a P value of 0.018. On the other hand, the mortality rate was 4.7% (4 patients for controlled) and (14 patients for uncontrolled) with no statistical significance P = 0.836. In addition, no significance was found when comparing the other cardiac outcomes (cardiac re-hospitalization P = 0.283, restenosis 0.284, stent thrombosis 0.986, target vessels revascularization 0.325, recurrent ACS 0.786, and heart failure 0.518).

Table 2

Outcomes among two groups of glycated hemoglobin level

Outcomes	HbA1c grouping		Total (n=379)	Chi-square tests, P
	Controlled (HbA1c <7.5%) number of patients=77, n (%)	Uncontrolled (HbA1c =7.5% or above) number of patients=302, n (%)
Readmission within 36 months	22 (24.7)	105 (38.5)	127	0.018
Mortality	4 (5.2)	14 (4.6)	18	0.836
Cardiac rehospitalization	11 (14.3)	61 (20.9)	72	0.238
Restenosis	4 (5.2)	27 (8.9)	31	0.284
Stent thrombosis	1 (1.3)	4 (1.3)	5	0.986
Target vessels revascularization	3 (3.9)	21 (7)	24	0.325
Recurrent ACS	13 (16.9)	55 (18.2)	68	0.786
Heart failure	11 (14.3)	35 (11.6)	103	0.518
Peripheral vascular disease	2 (2.6)	11 (3.6)	13	0.653
Atrial fibrillation	2 (2.6)	5 (1.7)	7	0.584

ACS: Acute coronary syndrome, HbA1c: Glycated haemoglobin

DISCUSSION

This study emphasizes on the effects of glycemic control and the type of cardiac intervention on cardiac complications in Saudi diabetic patients. By dividing the patients into controlled and uncontrolled groups, it was easy to follow them up and to compare their outcomes for common cardiac complications in an organized way.

No studies have been done in Saudi Arabia to compare the results after the cardiac intervention. Therefore, some of the comparisons might not reflect the actual results when comparing several populations with different demographic variables.

In our study, most of the patients were overweight or obese, while a minority of the patients were underweight or normal. This reflects the need of increasing awareness regarding diet modification and the importance of healthy life styles.

In this study, it was found out that most of the patients were on oral hypoglycemic medications 54.1% and insulin injections 42.2%. For instance, the only significance that has been found that is the uncontrolled group (HbA1c ≥7.5) are more likely to be treated by either oral hypoglycemic agent or insulin therapy, which was predicted due to their higher level of HbA1c over the years. Although a study from Ramadan et al. considered not involving the effect of medical therapy on cardiac outcomes as one of their study's limitations, examining the relationship between the type of medical treatment and its impact on cardiac complication may not be important since the majority of the patient presented with previous macrovascular complications of diabetes.[11]

When it comes to the type of intervention, patients who only underwent a diagnostic coronary angiography had either normal coronary artery; or, they had a diffuse three vessels disease. These patients were treated medically and those with severe stenosis were planned to get CABG.

The uncontrolled group were less likely to be treated with medical therapy for their ACS. In fact, most of the patients underwent PCI. The reason might be that those with a higher level of HgbA1c at admission possibly had a different treatment plan to control for the other risk factors.

Although a study conducted by Nusca et al. had mentioned that there is a strong relationship between the glucose level and short- and long-term effects, the readmission rate was the only significant factor found in our study when evaluating the effect of the HbA1c on the outcomes.[6] For instance, the uncontrolled group after intervention are more likely to be readmitted to the cardiac center. It is probably a result from their other comorbidities and the number of lesions affecting the coronary vessels. Another reason might also be due to other risk factors that have a role in developing cardiac complications and not only the HbA1c level. Another explanation might be that those patients who had a higher level of HbA1c at admission had becoming relatively controlled, as shown in our study.

Alserius et al. and Nyström et al. reported that poor glycemic control is associated with a higher mortality rate. However, in our study, mortality rate was not significant in either group.[78] The reason might be that they included different age groups and different levels of grouping.

Limitation

Our study has some limitations. The data are only from a single cardiac center, and 18 patients were excluded due to their loss of follow-up. Only the Saudi population was included, and this is considered as one of the limitations since the genetic predisposition tends to be one of the risk factors. Furthermore, there are no other studies with similar demographics within the region to compare with. Nevertheless, when compared to international studies, we found similar results.

CONCLUSIONS

Patients with an elevated level of Hba1c ≥7.5 are more likely to be managed with PCI. Also, they are at a higher risk of having multiple readmissions within 3 years of follow-up. Patients with an HbA1c level <7.5 are more likely to be managed with conservative treatment. Patients who had CABG are at a lower risk of having cardiac complications.

Further studies need to be done in our population to consider different approaches of diabetic's control to prevent the development of complications.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.