ABSTRACT
BACKGROUND
DM is characterized by insulin resistance and dyslipidaemia, in particular, high levels of total cholesterol, triglycerides and LDL, and low levels of HDL-C, which confers increased risk for CAD that may manifest as life threatening ACS. We wanted to study the correlation between HbA1c & total cholesterol, low density lipoprotein (LDL), high density lipoprotein (HDL) in diabetic patients presenting with acute coronary syndrome and also their correlation with severity of ACS independently.

METHODS
Blood samples of 50 known diabetic patients presented to emergency with ACS were sent for HbA1c & lipid profile estimation. All patients underwent coronary angiography. Obtained results were statistically analysed & correlated.

RESULTS
Statistically significant direct co-relationship was found between HbA1c, LDL, Total cholesterol, ACS severity (SVD/MVD) & inverse co-relationship with HDL.

CONCLUSIONS
In our study we concluded that there is strong correlation between HbA1c and dyslipidaemia, with severity of coronary artery disease. HbA1c, total cholesterol, LDL cholesterol are directly proportional and HDL cholesterol is inversely proportional to the severity of coronary artery disease. Hence incidence of ACS can be minimized with adequate glycaemic control.

KEYWORDS
Diabetes, HbA1c, Lipid Profile, Coronary Artery Disease

BACKGROUND

Coronary artery disease (CAD) is a major cause of death as well as an economic burden to both developed and developing countries. The prevalence of CAD in urban areas of India is between 2.5%-12.6% and in rural areas, it is between 1.4%-4.6% and about 0.2% to 24% of CAD patients are having Diabetes Mellitus (DM).¹ Among several risk factors for coronary artery disease, the prevalence of high total cholesterol/high density lipoprotein ratio is around 45.6% among urban Indian population.² In addition low HDL cholesterol is an independent risk factor for CAD in general population.³ It is also observed that the prevalence of CAD in Diabetes mellitus patients is almost twice when compared to the prevalence in non-Diabetic patients and is applicable to acute ST segment elevation myocardial infarction (STEMI) as well, among Indian population.⁴

The term acute coronary syndrome (ACS) refers to any group of clinical symptoms compatible with myocardial ischemia and covers the spectrum of clinical conditions ranging from unstable angina, non ST segment elevated myocardial infarction (NSTEMI) and ST segment elevated MI (STEMI).⁵ Potentially modifiable risk factors for ACS - smoking, diabetes, hypertension, dyslipidaemia, obesity, psychosocial factors, lack of exercise, and a diet low in fruit and vegetables along with little or no alcohol consumption.⁶

Diabetes mellitus (DM), a well-known risk factor of atherosclerosis, is responsible for a three to four fold increase in cardiovascular events.⁷ It is known that hyperglycaemia stimulates the production of advanced glycosylated end products, activates protein kinase C, and enhances the polyol pathway leading to increased superoxide anion formation.⁸ Estimated risk of cardiovascular disease (CVD) has shown to be raised by 18% for every 1% rise in absolute HbA1c value in the diabetic population.⁹ HbA1c is a biomarker reflecting both fasting and PP plasma glucose concentration over preceding 3 months. HbA1c can be used to diagnose diabetes and the diagnosis can be made if HbA1c level is >6.5%.¹⁰ HbA1c just below 6.5% may indicate the presence of intermediate hyperglycaemia. ADA has suggested HbA1c between 5.7-6.4% as the high risk range and considered as prediabetic.¹¹ CAD in diabetic patient is mainly owing to dyslipidaemia (raised triglycerides, raised cholesterol and low HDL). Both persistent hyperglycaemia and dyslipidaemia, especially raised LDL and low HDL eventually causes endothelial cell dysfunction leading to atherosclerosis. Dyslipidemia is strongly associated with atherosclerosis which contributes to the risk of cardiovascular disease in diabetic patients.¹² Dyslipoproteinaemia with high levels of total cholesterol, triglycerides and LDL and low levels of HDL and family history of early CAD have been demonstrated to be predisposing factors of early CAD¹³ The atherogenic link between high triglycerides and HDL-c is due to the higher plasma concentration of triglyceride-rich, very low-density lipoprotein that generates small, dense LDL during lipid exchange and lipolysis. These LDL particles accumulate in the circulation and form small, dense HDL particles, which undergo accelerated catabolism, thus closing the atherogenic circle.¹⁴ LDLs modify the antithrombotic properties of the vascular endothelium and change vessel contractility by reducing the availability of endothelial nitric oxide and activating proinflammatory signalling pathways. LDL entering affected vessels undergo modifications including glycation and conversion to small dense form. These modifications potentiate its atherogenic properties.¹⁵ High plasma low-density lipoprotein cholesterol concentrations are directly correlated with the development of coronary artery disease¹⁶ and low high density lipoprotein cholesterol concentration have been pointed out as one of the strongest independent risk factor for CAD.¹⁷ LDL Cholesterol <100 - Optimal, 100-129 - Near or above optimal, 130-159 -Borderline high, 160-189 - High, >190 - Very high. Total cholesterol <200 - Desirable, 200-239 - Borderline high, >240 - High. HDL cholesterol <40 - Low >60 - High.¹⁸ Significantly increased levels of cholesterol and lipids are also seen in type 2 diabetic patients with CAD as compared to diabetic patients without CAD.

Risk Categories LDL Goal (mg/dl)

- CHD and Risk equivalents<100

- Multiple (2+) risk factors <130

0-1 risk factor <160

METHODS

This study is a cross-sectional study done from 1/1/2018 to 31/3/2019. Diabetic patients presented in cardiology unit of medicine at Karnataka institute of medical science, Hubli and were diagnosed to have acute coronary syndrome were taken for study.

Inclusion Criteria

Known patients of diabetes mellitus on treatment with either insulin or oral drugs or both, presenting with acute coronary syndrome, in emergency.

Exclusion Criteria

1. Patient already on hypolipidemic drugs.
2. Old case of coronary artery disease.
3. Newly diagnosed cases of diabetes mellitus.
4. Patients with conditions confounding lipid profile measurement such as hypothyroidism, obstructive liver disease, chronic renal disease, nephrotic syndrome.
5. Patients on medication such as oestrogen, progestin, anabolic steroids, corticosteroids, retinoid, cyclosporine & anti- retroviral medication.

Sample Size

50 Diabetic patients with acute coronary syndrome.

Methods of Data Collection

Diabetic patients presented in cardiology unit of medicine at KIMS, Hubballi with symptoms of myocardial ischemia or atypical symptoms of ACS were taken for study. Detailed history of present illness with past history, personal history, family history was taken. General and systemic examination was done. Following which written consent was taken and patient was investigated with ECG, 2D-ECHO, Glycosylated haemoglobin (HbA1c), Fasting lipid profile, Liver function tests, Kidney function tests, Complete blood count. Diagnosis of ACS was made on the basis of, clinical features, ECG, 2D-ECHO. All these patients undergone coronary angiography to find presence of whether single-vessel or multi-vessel disease.

Statistical Analysis

Data was entered in Microsoft Excel 2010 and statistical analysis was done using IBM SPSS V 20.00.

RESULTS

Among the 50 diabetic subjects studied, majority were in the age group of 51-60 years, 32 were males and 18 were females. 32 had hypertension, 17 were smokers, 13 were alcoholics, maximum patients had STEMI, majority were IWMI. And after CAG majority of the patients found to have double vessel disease. In the study among diabetics there was significant association between age and CAG. Among those with Single vessel disease, majority of subjects were in the age group 33.3%, among those with Multi vessel disease, majority of subjects were in the age group 51 to 60 years 34.2%. In the study there was significant association between HbA1c levels and CAG among diabetics. I.e. among those with single vessel disease, 91.7% had HbA1c 6.5 to 8.4 and among 8.3% had HbA1c >8.5. Among those with Multi vessel disease, 73.7% had HbA1c >8.5 and 26.3% had HbA1c of 6.5 to 8.4. In the study, there was significant correlation present between low level of HDL-c and number of vessel involved. Most of the patients with HDL-c <40 had Multi vessel disease. And mean HDLc in patients with SVD is 50.25, among those with multi vessel 31.24. LDLc also had significant correlation with severity of coronary artery disease. Most of the patients with LDLc >100 had Multi vessel disease (92.8%). and mean LDLc among those with SVD, is 108.75 and those with multi vessel involvement is 140.61.

 DISCUSSION

Our study showed direct correlation of HbA1c with severity of coronary artery disease in ACS patients. Similar type of relation was also observed in study “Co-relation Between Total Cholesterol, High Density Lipoprotein, Low Density Lipoprotein and Glycosylated Haemoglobin (HbA1c) in Diabetic Patients with Acute Coronary Syndrome (ACS)” conducted by D C Pant et al1 in 2016 on 50 diabetic patients presented with ACS. Coronary angiography was performed on all patients. Patients were divided as having: 1) HDL <40, >40; 2) LDL <100, >100; 3) Total cholesterol <200, >200; 4) HbA1c 6.5-8.4, >8.4; 5) Single vessel disease (SVD) / multi vessel disease (MVD). Statistically significant direct co-relationship was found between HbA1c, LDL, Total cholesterol, ACS severity (SVD/MVD) & inverse co-relationship with HDL.

In our study significant inverse relationship was found between HDL-cholesterol and ACS. In the study “Prevalence of conventional risk factors and lipid profiles in with ACS and significant coronary disease” by Gonzalez-Pacheco H et al15 in 2014 on 3,447 patients with a diagnosis of ACS and significant CAD with stenosis > or =50%, as shown in CAG. The lipid profile analysis revealed that 85.1% of patients had some type of dyslipidaemia, and most frequent was low level of HDL-cholesterol.¹⁹ Our study also showed significant co-relationship between LDL-cholesterol level and ACS. In a study conducted by n. Bouzidi et al, “lipid profile variables and prediction of the severity of coronary artery disease in Tunisian type 2 diabetic patients” elevated plasma LDL-c and triacylglycerol, and reduced HDL-cholesterol contribute to accelerate atherogenesis in T2DM.

Our study also found significant relationship between total cholesterol and ACS, probably attributable to high LDL-C and low HDL-C. Results of our study showed mean cholesterol of >200 mg/dl in patients with multi-vessel disease which was considered high and risk factor for CAD.

Our study showed significant co-relationship between HbA1c levels and LDL, total cholesterol and also significant inverse relationship with HDL. Similar type of co-relation has also been found in study conducted by Cho SW et al in 2016 on 708 patients who visited OPD and followed for a mean period of 28.5 months.²⁰ Patients were divided in two groups, patients without major adverse cardiovascular event and patients with major adverse cardiovascular event, which included cardiac death, acute MI and newly diagnosed coronary heart disease. HbA1c and lipid profiles between the groups were compared. It was found that patients with major adverse cardiovascular events had significantly higher HbA1c, lower HDL when compared with patients with no adverse events.

CONCLUSIONS

Severity of ACS, as depicted in the form of single or multi-vessel disease in coronary angiography, directly correlates with poor glycaemic control in form of raised HbA1c. Severity of ACS also correlates directly with deranged lipid profile like raised LDL, triglyceride/HDL ratio, total cholesterol and decreased HDL. Elevation in LDLc was the single most powerful predictor of extensive coronary heart disease among all the lipid variables examined in T2DM. There is also significant relationship between poor glycaemic control and deranged lipid profile. Patients with raised HbA1c were also found to have deranged lipid profile and results in more severe ACS. Thus, we conclude that early therapeutic interventions, aiming to stabilize blood glucose levels along with reduction of HbA1c and appropriate measures to prevent or treat dyslipidemia, significantly reduce cardiovascular events and mortality in patients with diabetes.

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