|Year : 2019 | Volume
| Issue : 2 | Page : 83-87
The relation between retinopathy grade and coronary artery disease in acute coronary syndrome diabetics
Ahmed Shawky Shereef, Nader T Kandeel
Department of Cardiology, Faculty of Medicine, Zagazig University, Zagazig, Egypt
|Date of Web Publication||23-Sep-2019|
Dr. Ahmed Shawky Shereef
Department of Cardiology, Faculty of Medicine, Zagazig University, Zagazig
Source of Support: None, Conflict of Interest: None
Background: Diabetic retinopathy (DR) was found to be associated with an increased risk for coronary artery disease (CAD). However, there are less data about the relation between the degree of DR and the angiographic severity of CAD. Objective: The objective of the study is to examine the relation between the degree of DR and the angiographic severity of CAD in patients with acute coronary syndrome (ACS). Patients and Methods: Fifty diabetic patients with ACS were enrolled in this study. History, clinical examination, echocardiography, coronary angiography, and fundus examination were done to all patients. According to the degree of DR, patients were classified into two groups: Group I – patients with no or mild nonproliferative (NP) DR (n = 27) and Group II – patients with moderate or severe NP DR or with proliferative DR (n = 23). Results: Population characteristics, risk factors, diabetes duration, insulin use, and echocardiographic measures were comparable in the two groups. Patients in Group II had significantly more number of diseased vessels, more maximum stenosis, and higher Gensini score than those of Group I. There was a significant correlation between the degree of DR and the number of diseased vessels (r = 0.358, P =0.011) and highly significant correlation between the degree of DR and maximum stenosis (r = 0.452, P =0.001) and Gensini score (r = 0.706, P < 0.00001). Conclusion: There is an obvious relation between the degree of DR and angiographic severity of CAD in diabetic patients with ACS. Patients with a higher degree of DR had more severe CAD.
Keywords: Acute coronary syndrome, coronary angiography, diabetic retinopathy
|How to cite this article:|
Shereef AS, Kandeel NT. The relation between retinopathy grade and coronary artery disease in acute coronary syndrome diabetics. J Indian coll cardiol 2019;9:83-7
|How to cite this URL:|
Shereef AS, Kandeel NT. The relation between retinopathy grade and coronary artery disease in acute coronary syndrome diabetics. J Indian coll cardiol [serial online] 2019 [cited 2019 Dec 7];9:83-7. Available from: http://www.joicc.org/text.asp?2019/9/2/83/267491
| Introduction|| |
Coronary artery disease (CAD) is a leading cause of mortality in diabetics.,, Diabetes confers a risk equivalent to aging by 15 years, and more deaths from diabetes are directly due to CAD than to any other cause. The risk of a myocardial infarction in diabetic patients with no evidence of CAD matches that in patients without diabetes who have had a previous myocardial infarction, supporting the idea of diabetes as a coronary equivalent. While macrovascular disease is the primary pathogenic mechanism underlying CAD in the general population, microvascular disease may play a prominent role in CAD development in diabetics.,,,,, Diabetic retinopathy (DR) is a specific marker of microvascular disease in diabetics, and the presence of DR was found to be associated with an increased risk of CAD.,
Moreover, diabetic patients with CAD and retinopathy were found to be poorer outcome, with higher mortality when compared to those without retinopathy.
However, the relation between the degree of retinopathy and the severity of angiographically detected CAD was not fully investigated.
Our aim was to examine the relation between the degree of DR and the severity of CAD detected by coronary angiography in diabetic patients with acute coronary syndrome (ACS).
| Patients and Methods|| |
This study had been carried out in the Cardiology Department, Faculty of Medicine, Zagazig University, in the period between November 2016 and November 2017.
Fifty diabetic patients who were admitted to the Coronary Care Unit (CCU) of Zagazig University Hospitals with ACS were enrolled in the study. They included 24 males and 26 females, with a mean age of 55.1 ± 8.9 years, including 22 patients with unstable angina pectoris, 23 patients with non-ST-segment elevation myocardial infarction, and 5 patients with ST-segment elevation myocardial infarction.
Our Institutional Review Board had approved the study protocol. After obtaining a written informed consent from every patient, we made the following for them:
- Full history taking
- Thorough clinical examination
- Fundus examination.
Fundus examination was done to all patients by an experienced ophthalmologist, unaware to the patients' conditions. The presence of DR and its degree was detected and was graded according to the American Academy of Ophthalmology, as follows:
- Grade 0: No retinopathy
- Grade I: Mild nonproliferative (NP) DR
- Grade II: Moderate NP-DR
- Grade III: Severe NP-DR
- Grade IV: Patients with proliferative DR.
According to the degree of DR, patients were divided into two groups:
- Group I: Patients with Group 0 or Group I DR. This group included 27 patients, 12 males and 15 females; their mean age was 54 ± 7.3 years
- Group II: Patients with Group II, Group III, or Group IV DR. This group included 23 patients, 12 males and 11 females; their mean age was 56.4 ± 10.48 years.
Standard echocardiographic study was done to every patient. The following measures were taken:
- Left ventricular end-diastolic dimension (LVEDD)
- Left ventricular end-systolic dimension (LVESD)
- Fraction of shortening
- Ejection fraction (EF)
- Mitral valve E-wave velocity
- Mitral valve A-wave velocity
- E/A ratio
Coronary angiography was done to all patients using retrograde, transfemoral technique. Coronary angiography was done and reviewed by an experienced angiographer, unaware by patients' conditions.
The following were stressed upon:
- Number of diseased vessels
- Site of lesions
- Severity of stenosis percentage.
Gensini score was calculated for every patient to determine the angiographic severity of CAD. In this score, we give 1 for 25% stenosis, 2 for 50%, 4 for 75%, 8 for 90%, 16 for 99%, and 32 for total occlusion. The score is then multiplied by a factor according to the site of the lesion [Figure 1].
|Figure 1: (a-c) Correlation of diabetic retinopathy grade with number of diseased vessels, maximum coronary, and Gensini scores|
Click here to view
All data were analyzed using the SPSS for Windows package program (Version 20.0, IBM Corp.; Armonk, NY, USA). Differences between patients' group and control group were analyzed using Chi-square test and Student's t-test. Correlations between different variables were investigated by Pearson correlation analysis. P < 0.05 was regarded as being statistically significant.
| Results|| |
We enrolled 50 diabetic patients (24 males and 26 females) in the study. All patients were admitted to the CCU of Zagazig university hospitals with ACS; among them, 27 patients were with Group 0–Group I DR (Group I) and 23 patients were with Group II–Group IV DR (Group II).
As shown in [Table 1], there was no significant difference between the two groups regarding population characteristics, risk factors for CAD, duration of diabetes, or number of patients using insulin.
|Table 1: Risk factors, clinical, echocardiographic, and angiographic data of study groups|
Click here to view
Furthermore, there was no significant difference between the two groups regarding echocardiographic parameters (LVEDD, LVESD, EF, E-wave, A-wave, or E/A ratio).
Coronary angiographic results showed no significant difference regarding affected vessels or number of diseased vessels.
Maximum coronary stenosis was significantly higher in Group II (84% ±12.56% in Group I, 95.6% ±7.8% in Group II, P = 0.000231). Gensini score was significantly higher in Group II [19 ± 12.97 in Group I, 51 ± 27.98 in Group II, P = 0.0000069, [Table 1].
As shown in [Figure 1]a, there was a significant positive correlation between the grade of DR and number of diseased vessels (r = 0.358, P = 0.011).
There was a highly significant positive correlation between the grade of DR and maximum coronary score [r = 0.452, P = 0.00098, [Figure 1]b and Gensini score [r = 0.706, P < 0.000001, [Figure 1]c.
| Discussion|| |
CAD is the leading cause of death among adult diabetics and accounts for about 3 times as many deaths among diabetic as among nondiabetics. Data of the Framingham Heart Study have shown an increased risk of CAD in diabetics as well as the poor outcome of diabetic CAD patients than nondiabetics.
DR is a common vascular complication in diabetic patients. It occurs in about 19%–30% of adult diabetic patients.,
DR was found to be associated with increased risk of CAD and to have a predictive value for CAD events in diabetic patients. Furthermore, CAD patients with DR have poorer outcome, with increased mortality and morbidity.,,,,,,,,,,
Diabetic patients with CAD and DR tend to have a poorer prognosis after coronary artery bypass grafting, or after percutaneous coronary intervention with insertion of drug eluting stents, or bare-metal stents.
However, none of these studies evaluated the severity of CAD by coronary angiography, which is the gold standard of the diagnosis of CAD, and its relation to the degree of DR.
In our study, we examined the relation between the degree of DR and the severity of CAD. We used Gensini score to measure CAD severity. Patients with advanced DR had more severe CAD, more stenosis, and higher Gensini score than those with mild or no DR. We also found significant correlations between the degree of DR and number of diseased vessels and maximum stenosis and Gensini score.
Similar results to our study were found by Norgaz et al. However, they did not include patients with ACS, in spite of the great importance of detecting CAD severity in this subset of patients for early risk stratification and plan of management.
However, in our study, there was no significant difference between the two groups regarding the duration of diabetes, blood glucose level, or number of patients using insulin.
Klein et al. reported an association between DR and carotid artery intima-media wall thickness in a cross-sectional study from a population-based cohort of diabetic adults, but they found no association between the severity of DR and atherosclerotic risk factors. We similarly did not observe any relation between the DR and risk factors for CAD.
In a study by Yamamoto et al., they focused on the nonenzymatic glycation reaction under prolonged hyperglycemia, which results in the formation and accumulation of advanced glycation end-products (AGEs). The interaction of AGEs with the receptor for AGEs (RAGEs) has been implicated in the development of vascular complications.
AGEs play an important role in the accelerated course of atherosclerosis in diabetes mellitus (DM). Wang et al. have demonstrated that the AGEs-RAGEs interaction in vascular smooth muscle cells, in addition to growth factors induced by AGEs, contributes to the stimulatory effect of diabetes on vascular smooth muscle cell proliferation which can accelerate atherosclerosis.
Aso et al. measured the serum concentrations of AGEs in type 2 DM patients and proposed that they were associated with the development of CAD as well as DR and nephropathy.
Therefore, it is reasonable to speculate that there is at least one common pathway in the development of DR and diabetic atherosclerotic lesions.
Limitations of the study
We have evaluated the severity of coronary atherosclerosis by lumen irregularities detected on coronary angiographic images. However, the growth of atherosclerotic plaque that does not protrude into the lumen may result in an underestimation of the CAD severity, which could have been recognized by the use of intravascular ultrasound. However, even by using coronary angiography, the relation with CAD severity and DR was significant.
According to the results of the present study, the presence of DR, especially if more than Group I, in patients with DM presenting with ACS, was associated with more diffuse and severe CAD. Meanwhile, a fundus examination is a simple, noninvasive, and routinely employed technique used in the follow-up of diabetic patients and may add a role for early risk stratification and management of this, frequently seen, subset of patients.
| Conclusion|| |
Among diabetics with ACS, those with more than mild DR have more diffuse and severe coronary atherosclerosis, compared with diabetics without retinopathy, which cannot be explained by the longer duration or inferior control of the disease. Further studies focusing on the mechanisms of this situation are needed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Gu K, Cowie CC, Harris MI. Diabetes and decline in heart disease mortality in US adults. JAMA 1999;281:1291-7.
Kannel WB, McGee DL. Diabetes and cardiovascular disease. The Framingham study. JAMA 1979;241:2035-8.
Grundy SM, Benjamin IJ, Burke GL, Chait A, Eckel RH, Howard BV, et al.
Diabetes and cardiovascular disease: A statement for healthcare professionals from the American Heart Association. Circulation 1999;100:1134-46.
Booth GL, Kapral MK, Fung K, Tu JV. Relation between age and cardiovascular disease in men and women with diabetes compared with non-diabetic people: A population-based retrospective cohort study. Lancet 2006;368:29-36.
Haffner SM, Lehto S, Rönnemaa T, Pyörälä K, Laakso M. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N
Engl J Med 1998;339:229-34.
Factor SM, Okun EM, Minase T. Capillary microaneurysms in the human diabetic heart. N
Engl J Med 1980;302:384-8.
Di Carli MF, Janisse J, Grunberger G, Ager J. Role of chronic hyperglycemia in the pathogenesis of coronary microvascular dysfunction in diabetes. J Am Coll Cardiol 2003;41:1387-93.
Miura H, Wachtel RE, Loberiza FR Jr., Saito T, Miura M, Nicolosi AC, et al.
Diabetes mellitus impairs vasodilation to hypoxia in human coronary arterioles: Reduced activity of ATP-sensitive potassium channels. Circ Res 2003;92:151-8.
Li H, Gutterman DD, Rusch NJ, Bubolz A, Liu Y. Nitration and functional loss of voltage-gated K+ channels in rat coronary microvessels exposed to high glucose. Diabetes 2004;53:2436-42.
Pitkänen OP, Nuutila P, Raitakari OT, Rönnemaa T, Koskinen PJ, Iida H, et al.
Coronary flow reserve is reduced in young men with IDDM. Diabetes 1998;47:248-54.
Di Carli MF, Bianco-Batlles D, Landa ME, Kazmers A, Groehn H, Muzik O, et al.
Effects of autonomic neuropathy on coronary blood flow in patients with diabetes mellitus. Circulation 1999;100:813-9.
Cheung N, Wang JJ, Klein R, Couper DJ, Sharrett AR, Wong TY, et al.
Diabetic retinopathy and the risk of coronary heart disease: The atherosclerosis risk in communities study. Diabetes Care 2007;30:1742-6.
Ohno T, Takamoto S, Motomura N. Diabetic retinopathy and coronary artery disease from the cardiac surgeon's perspective. Ann Thorac Surg 2008;85:681-9.
Klein R, Klein BE, Moss SE, Cruickshanks KJ. Association of ocular disease and mortality in a diabetic population. Arch Ophthalmol 1999;117:1487-95.
Wilkinson CP, Ferris FL 3rd
, Klein RE, Lee PP, Agardh CD, Davis M, et al.
Proposed international clinical diabetic retinopathy and diabetic macular edema disease severity scales. Ophthalmology 2003;110:1677-82.
Hoel B, Eie H, Semb G, Sivertssen E. Selective coronary arteriography. Acta Med Scand 1975;197:377-82.
Gensini GG. A more meaningful scoring system for determining the severity of coronary heart disease. Am J Cardiol 1983;51:606.
Kannel WB. Lipids, diabetes, and coronary heart disease: Insights from the Framingham study. Am Heart J 1985;110:1100-7.
Klein R, Klein BE, Moss SE. The Wisconsin epidemiological study of diabetic retinopathy: A review. Diabetes Metab Rev 1989;5:559-70.
Al-Maskari F, El-Sadig M. Prevalence of diabetic retinopathy in the United Arab Emirates: A cross-sectional survey. BMC Ophthalmol 2008;7:1186-90.
Miettinen H, Haffner SM, Lehto S, Rönnemaa T, Pyörälä K, Laakso M, et al.
Retinopathy predicts coronary heart disease events in NIDDM patients. Diabetes Care 1996;19:1445-8.
Pambianco G, Costacou T, Ellis D, Becker DJ, Klein R, Orchard TJ, et al.
The 30-year natural history of type 1 diabetes complications: The Pittsburgh epidemiology of diabetes complications study experience. Diabetes 2006;55:1463-9.
Ono T, Kobayashi J, Sasako Y, Bando Ko, Tagusari O, Niwaya K, et al.
The impact of diabetic retinopathy on long-term outcome following coronary artery bypass graft surgery. J Am Coll Cardiol 2002;40:428-36.
Ohno T, Takamoto S, Ando J, Morita T, Fujita H, Hirata Y, et al.
Diabetic retinopathy and coronary implantation of sirolimus-eluting stents. J Interv Cardiol 2007;20:122-31.
Briguori C, Condorelli G, Airoldi F, Manganelli F, Violante A, Focaccio A, et al.
Impact of microvascular complications on outcome after coronary stent implantations in patients with diabetes. J Am Coll Cardiol 2005;45:464-6.
Norgaz T, Hobikoglu G, Aksu H, Guveli A, Aksoy S, Ozer O, et al.
Retinopathy is related to the angiographically detected severity and extent of coronary artery disease in patients with type 2 diabetes mellitus. Int Heart J 2005;46:639-46.
Aso Y, Inukai T, Tayama K, Takemura Y. Serum concentrations of advanced glycation endproducts are associated with the development of atherosclerosis as well as diabetic microangiopathy in patients with type 2 diabetes. Acta Diabetol 2000;37:87-92.
Klein R, Sharrett AR, Klein BE, Moss SE, Folsom AR, Wong TY, et al.
The association of atherosclerosis, vascular risk factors, and retinopathy in adults with diabetes: The atherosclerosis risk in communities study. Ophthalmology 2002;109:1225-34.
Yamamoto Y, Sakurai S, Watanabe T, Yonekura H, Yamamoto H. Possible participation of advanced glycation endproducts and their receptor system in the development of diabetic vascular complications. Nihon Yakurigaku Zasshi 2003;121:49-55.
Wang R, Kudo M, Yokoyama M, Asano G. Roles of advanced glycation endproducts (AGE) and receptor for AGE on vascular smooth muscle cell growth. J Nippon Med Sch 2001;68:472-81.