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Journal of Cardiovascular and Thoracic Research, 2012, 4(4), 113-117

doi: 10.5681/jcvtr.2012.027
http://jcvtr.tbzmed.ac.ir

Association between Diabetic Retinopathy and Left Ventricular
Dysfunction in Diabetic Patients with Unstable Angina
Ebadollah Heidari1, Sanaz Nematzadeh Pakdel2, Jahanbakhsh Samadikhah2, Rasoul Azarfarin2, Kamran
Shadvar2*
Department of Ophthalmology, Nikookari Hospital, Tabriz University of Medical Sciences, Tabriz, Iran
1

Cardiovascular Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
2

ARTICLE INFO ABSTRACT

Article Type: Introduction: Diabetes mellitus (DM) is associated with serious complications
Research Article including macro- and microvascular problems such as diabetic retinopathy. Coronary
involvement in diabetic patients is believed to be a consequence of microvascular
complications. However, the available data are inconclusive and scarce. This study
Article History: aimed to evaluate the probable association between diabetic retinopathy and left
Received: 10 July 2012
Accepted: 12 Oct 2012
ventricular dysfunction in diabetic patients with unstable angina (UA). Methods:
ePublished: 30 Oct 2012 In this cross-sectional study, 200 diabetic patients with UA (100 cases with diabetic
retinopathy and 100 cases without diabetic retinopathy) were enrolled in a teaching
hospital. Left ventricular ejection fraction (LVEF) as well as the frequency of cases with
left ventricular dysfunction (LVEF<50%) were compared between the two groups and
Keywords: different degrees of diabetic retinopathy (proliferative and non-proliferative). Results:
Unstable Angina
Diabetic Retinopathy
Patients’ demographic variables were comparable between the two groups. Mean
Left Ventricular Ejection Fraction diagnosis time of DM was significantly higher in the patients with diabetic retinopathy
(8.40±6.60 vs. 3.81±3.58 years; P<0.001). Mean LVEF was significantly lower in the
retinopathy group (50.50±6.91% vs. 53.07±4.87%; P=0.003). Frequency of cases with left
ventricular dysfunction was significantly higher in the group with diabetic retinopathy
(31% vs. 12%; P=0.001, OR=3.33, 95%CI: 1.58-7.14). The frequency of cases with left
ventricular dysfunction was significantly yet independently higher in patients with
proliferative vs. non-proliferative diabetic retinopathy. Conclusion: Left ventricular
dysfunction is more common in diabetic patients with unstable angina and diabetic
retinopathy compared with their counterparts without diabetic retinopathy.

Introduction by subsequent studies. In these studies, retinopathy signs
Diabetic retinopathy is one of the four leading causes of with T-wave changes in ECG, coronary artery stenosis in
blindness in 20 to 74 year-old adults and a major cause the angiographic and histologic evidence of myocardial
of blindness all over the world. Prevalence of diabetesis microvascular disease were associated.
up to 7% of the general population. It is estimated that Recent studies using photographic retinopathy grading
25% of the diabetic population has one form of diabetic have introduced stronger evidence on the relationship
retinopathy while 5% of the population suffers severe between this situation and cardiac dysfunction.10,11 It has
degrees of the disease. The prevalence of all types of been recognized that diabetic retinopathy increases the risk
diabetic retinopathy increases in the population parallel to of myocardial infarction, coronary artery disease and heart
the disease duration and onset age.1-4 On the other hand, failure.12-17 Due to the limitations and the importance of
heart disease in diabetic retinopathy has shown to occur the previously performed studies, we decided to study the
due to microvascular dysfunction. However, no simple relationship between diabetic retinopathy and its severity
and noninvasive evaluation of coronary microcirculation in patients with unstable angina with left ventricular
has been introduced and the existing studies suffer from dysfunction.
technical flaws.5-8
Two decades ago, Framingham suggested that retinopathy Materials and methods
symptoms may reflect a process of microangiopathy In this cross-sectional study after approval of the ethics
affecting the myocardium.9 This hypothesis was confirmed committee of Tabriz University of Medical Sciences

*Corresponding author: Kamran Shadvar , E-mail: k_shadvar@yahoo.com
Copyright © 2012 by Tabriz University of Medical Sciences

Results The average age (range) of patients in case group was 59. 2) Age of 40 years and older and 3) Willingness to participate in the study. Left ventricular function was assessed by a cardiology resident under attending supervision. ventricular dysfunction and smoking. Exclusion criteria were: 1) Patients with a history of valvular heart disease. Figure 1). Gender percentage of the patients with (case) and without SD. Figure 1. Age. Case group.06 (38-85) years and 59. hypertension.001.18 (42-79) years in the control group. history of alcohol consumption. duration of diabetes mellitus. 113-117 Copyright © 2012 by Tabriz University of Medical Sciences . frequency and percentage. presence of diabetic retinopathy and its relation with left ventricular dysfunction. Percentage consecutive patients with unstable angina referred to Of impaired left ventricular function was significantly Madani Heart Hospital were enrolled to investigate the higher in patients with retinopathy (P=0. 4) Patients with chronic heart arrhythmias and 5) Patients with bundle branch block in ECG. moderate and severe retinopathy and proliferative groups.79. Figure 3). dyslipidemia. hypertension and smoking history. Age distribution of the patients with (case) and without (control) Retinopathy detection was made by an ophthalmologist diabetic retinopathy and retina specialist who were unaware of the status of left ventricular function. dyslipidemia. Study variables by type of diabetic retinopathy Mean LVEF in case group (50. based on the grading & severity of retinopathy. 200 had left ventricular dysfunction respectively. SPSS statistical program (control) diabetic retinopathy version 15 was used. weight.46 ± 9. and 114 Journal of Cardiovascular and Thoracic Research. Quantitative variables were compared using Student T-test (Independent Samples). smoking and family history of heart disease were not significantly different (Figure 2). 4(4). body mass index (BMI).05 was considered statistically significant. Figure 6). The obtained information is presented as the mean ± Figure 2. left ventricular ejection fraction.31 and 12 patients diabetes mellitus.In two groups. and obtaining informed consent from all patients. demographic characteristics. history of hypertension.001.003. height. P≤0. diabetic retinopathy None of the patients had a history of alcohol consumption (Figure 4). It should be noted that these two individuals were also unaware of the patient's retinopathy status. sex.87%. There was no significant difference between two groups regarding patients’age (P= 0. 3) Patients with cardiomyopathy and congenital heart disease. Duration of diabet in the patients with (case) and without (control) significantly higher in case group (P<0. 2) A history of myocardial infarction.Heidari et al. sex. The average duration of diabetes mellitus was Figure 3. BMI.08 ± 10.P= 0. Qualitative variables (Categorical) were compared by Contingency tables using Chi-Squared test or Fisher's exact test.In case and control groups. (Figure 7): Mean age. and duration of diagnosed Figure 5).07 ±4.50± 6. was divided into four subgroups: Non-proliferative with mild.91%) was significantly Comparison between proliferative and non proliferative lower than the control group (53. 2012. Inclusion criteria were: 1) Type 2 diabetes mellitus patients with unstable angina. family history of heart disease and type and severity of diabetic retinopathy were studied. Patients were divided into two groups: 100 patients with retinopathy (case group) and 100 patients without retinopathy (control group). In this study. left ventricular dysfunction was defined as LVEF<50%.

Diabetic Retinopathy and LV dysfunction family history of heart disease in the two groups were not Comparison between Proliferative and non-Proliferative statistically significant. Accordingly. The mean LVEF in the proliferative group was significantly less than severe non-proliferative groups. It has been Copyright © 2012 by Tabriz University of Medical Sciences Journal of Cardiovascular and Thoracic Research.9 This hypothesis was later approved by the future studies. Framingham Heart Study suggested that retinopathy symptoms may reflect a microangiopathic process in which the myocardium is also involved. Figure 4. duration of diagnosed diabetes mellitus was significantly cantly greater. Proliferative group than other groups. retinopathy signs were associated with T-wave changes in ECG. the underlying pathophysiology in coronary artery disease and diabetic retinopathy is the same.5-8 Two decades ago. The percentage of impaired left ventricular function in patients Figure 5. In other cases. Proliferative groups. Percentage of cases with a history of dyslipidemia in the proliferative group was significantly less than other groups. In these studies. Risk factors percentage in the patients with (case) and without (control) diabetic retinopathy Figure 7. the mean LVEF in patients with diabetic retinopathy was significantly lower than the group without diabetic retinopathy. 4(4). Percentage of impaired left ventricular function in 4 groups showed no significant difference. coronary artery stenosis in the angiographic and histologic evidence of myocardial microvascular disease. In other words. It has previously been shown that the heart disease in people with diabetes mellitus as retinopathy is caused by microvascular dysfunction. Type & severity of retinopathy in case group Discussion In this study. there was no statistically significant difference. 2012. Left ventricular ejection fraction in the patients with (case) and without (control) diabetic retinopathy with diabetic retinopathy was significantly higher. Percentage Of impaired left ventricu.11 Figure 6. Comparing the frequency of cases with smoking history was not possible.10. The mean LVEF in proliferative group was more in the proliferative group than the mild non- significantly low. Percentage of cases with a history lar function was significantly greater in the proliferative of hypertension was significantly higher in severe non- group. 113-117 115 . Percentage of non-proliferative with different degrees of severity (Table 1): The average cases with a history of dyslipidemia group was signifi. the relationship between diabetic retinopathy and left ventricular dysfunction in diabetic patients with unstable angina was evaluated. Left ventricular dysfunction in the patients with (case) and Recent studies using photographic retinopathy grading without (control) diabetic retinopathy have introduced stronger evidence on the relationship between retinopathy and cardiac dysfunction.

94±6.97 6.90 52.9± 9.08 0.18 In Fuller and colleagues study.33 31. proliferative retinopathy increased the risk studied. it diabetes were studied.00± 6.08 Duration Of Diabet(year) 7. independent of confounding ventricular dysfunction is associated with the duration of variables.5 to 2 times in diabetic retinopathy cases in patients with left ventricular patients with type 2 diabetes. Table 1.29 59. Accordingly.04± 4.5)20 (55)11 (93. coronary artery disease and heart heart failure.21± 4.Heidari et al. cardiovascular symptoms. a significant relationship between severity of diabetic retinopathy and duration of diabetes mellitus. After 12 years.6)17 (25)5 (31. Only in women Non. the percentage of impaired left of heart disease more than 2 times in these individuals ventricular function in patients with proliferative diabetic compared to the controls.14 this study it was demonstrated that increase in these verity Annonu et al. However. Non proliferative.01 Hypertension (57.55 Gender (male) (67.24 0.83 0. In this 2 times than those without retinopathy.04 Smoke (16.49 26.23± 5. after controlling for confounding factors. retinopathy was significantly higher than non-proliferative proliferative retinopathy was reported as a risk factor for cases. severities of Non proliferative recognized that the diabetic retinopathy increases the risk retinopathy.13 Juutilainen and study.01 0. In than 2 times. decreased.21 9. Some (12.8%) of these patients had diabetic relationship became insignificant after controlling for 116 Journal of Cardiovascular and Thoracic Research. CVD: Cardio vascular diseases.17 diabetes and diabetic retinopathy. After controlling other risk factors.20 Aguilar and with type 1 diabetes. After 9 years. This study demonstrated that left atrial dimension and LVEF. significant association was present between later.5)54 (70. this evaluated.12% vs. 10.37 26.77 53.5)31 (75)15 (50)8 (70)14 0.01 Hyperlipedemia (33.3)13 (18.16 ventricular dysfunction independent of this parameter was Wong and colleagues.84± 5. the risk of heart disease was more colleagues studied 531 patients with type 2 diabetes.5)2 (15)3 (0)0 (5)1 0.1% of the patients developed of myocardial infarction.16 0. Echocardiographic systolic patients with type 1 diabetes and 3179 patients with type 2 and diastolic function was assessed separately.8)15 (40)8 0.01 0.4±9.03 LV.2)8 (15)3 (12. *Proliferative vs.73± 7. cardiovascular events in proliferative diabetic retinopathy Retinopathy severity and the incidence of heart failure and is about 4 times higher than patients suffering from mortality associated with the severity of retinopathy were non-proliferative diabetic retinopathy. heart disease.65 - LVEF(%) 51.39 BMI 27.04 0. diabetic retinopathy was shown that there was significantly higher number of increased the risk of heart disease to 1.23 0. This study demonstrated that diabetic retinopathy increased the risk of heart failure by left ventricular dysfunction has a significant relation with 2. this status was significantly observed in women with type 1 diabetes while in men associated with duration of diabetes mellitus. LV: Left ventricle. Variables were compared according to the type and severity of diabetic retinopathy Non proliferative Proliferative P* P** (n=20) Total Mild Mod Sever (n=80) (n=44) (n=20) (n=16) Age (year) 60.15 10.11 - Positive Family History CVD (6. in a similar study. evaluated the diabetic patients without of 6.5)2 (50)10 0.96 57.65± 2.16± 4. BMI: Body mass index. 5.19 Klein and colleagues As can be seen. Finally.94 0.46 0. the risk of To the best of our knowledge. Frati et al.3)5 (5)1 0. Twenty years In our study.3)5 (4.06± 8.31 10. Cheung and colleagues studied 1021 middle-aged patients Van Hecke et al.27 0. retinopathy was significantly higher (cumulative incidence In a study.44± 4.65± 8. 1126 symptoms of heart disease. left retinopathy and heart disease was reported. studied 66 type 1 diabetes patients without of retinopathy increased left ventricular mass and left cardiovascular diseases.8)27 (38.43 0. patients with type 2 diabetes. in their study on 2237 patients with with type2 diabetes with normal renal function and no type 1 diabetes mellitus showed that mortality from symptoms of coronary artery disease and heart failure. studied 627 significantly higher in the group with diabetic retinopathy.99 50.09 27. **Proliferative vs.5)2 (35)7 0.69 59. our results are in line with existing reports. However.97 61.5 times.73 47. Dysfunction (26. 2012. studied 996 patients with type 1 diabetes.31± 5. The incidence of heart failure in people with failure. the correlation between left ventricular dysfunction colleagues studied 824 patients with type 2 diabetes.16± 10.71± 8.09 Data are demonstrated as mean±SD or number (%).15 this significance disappeared.3)21 (31. After 7 years. The increased risk was also dysfunction. 4(4).12 duration of diabetes and microvascular disease including Mishra and colleagues studied 73 diabetic patients without diabetic retinopathy. 113-117 Copyright © 2012 by Tabriz University of Medical Sciences . Additionally. LVEF: Left ventricular ejection fraction.5)46 (45. no similar study on patients heart failure in people with retinopathy was more than with unstable angina has been conducted so far.8%).8)14 (25)5 (12.35± 7.25±9. and the type and severity of diabetic retinopathy was After 18 years.26± 7.

Coronary microvascular dysfunction. 30: 292-9. 4(4). Sharrett carefully. 31:952-7. Reaven PD. Cheung N. 9. Laakso M. 195: 335-8. Stehouwer CD. Piller LB. Pyörälä K. Diabetic retinopathy and cardiovascular disease in type II diabetics. Klein R. Tyroler HA. Wong TY. the results of our study are in line with high risk men. Annonu AK. 2012. larger sample size are recommended. References 20. Moss SE. in patients with unstable angina and a sign of retinopathy 15. Duran JR 3rd. Benson WE. Retinopathy in persons with impaired glucose metabolism: In our study. Graef A. Kerrison JB. J Am Coll Cardiol 2003. JAMA 1966. 1st ed. to evaluate more 12. Rönnemaa T. Klein BE. Diabetologia 2001. Curr Diabetes Rev 2009. Breslin DJ. K. Barr EL. in RB. Hurtado R. in asymptomatic patients with non-insulin-dependent diabetes mellitus. et al. Polak BC. Am J Ophthalmol 2005. and severity of diabetic retinopathy 16. Di Carli MF. dysfunction. 113-117 117 . Changes in ventricular function in diabetes mellitus. 51: 1573-8. Zimmet PZ. Yannuzzi LA. Podgor MJ. Grunberger G. type. van Hecke MV. Camici PG.356:2324-5. microvascular complications in normotensive. previous reports in this field. Lehto S. 128: 402-9. Klein BE. Role of chronic hyperglycemia in the pathogenesis of coronary microvascular dysfunction in diabetes. 25th ed. Mohanty NK. Ronnemaa T. Relation Acknowledgment to the duration of the diabetes and its complications. Aiello LP. USA: Saunders. Skuta GL. has a direct relationship with diabetic retinopathy. Pitkänen OP. 5. Raitakari OT. Retinopathy predicts cardiovascular mortality in type 2 diabetic There was no association between left ventricular men and women. Klein R. Trial (VADT). Ghareeb S. Sperduto RD. Wilson PW. Duane TD. Stevens LK.22 Hypertensive retinopathy and incident coronary heart disease in As can be seen. Barjau R. Cantor LB. Fuller JH. et al. Conclusion et al. Dekker JM. 41:1387-93. in diabetic patients without retinopathy and with unstable 14. New York: McGraw Hill. 7.1999. N related to coronary artery calcium in the Veterans Affairs Diabetes Engl J Med. Left ventricular 1. 44: S54-64. Br J Ophthalmol 2002. 28: 1383- retinopathy and angiogenesis. Cavallerano JD. Fuchs FD. Rogers SL. et al. In: Guyer DR. Harper CA. 2004. Emanuele N. Duane’s Clinical JH. Coronary microvascular dysfunction. J Am Soc Echocardiogr 2001.21 Study. Tasman W. Diabetes Care 2008. Mishra SK. Diabetes Care 1992. Fattah AA. Rivera C. Rath PK. Nuutila P. Juutilainen A. Iida H. Mishra TK. Liesegang TJ. 13. Glander Engl J Med 2007. are significantly higher than the group without retinopathy. 18. Bursell SE. Ferris 3rd FL. et al. Ager J. Kearns TP. Prognostic importance of ophthalmoscopic findings in essential This relationship in patients with proliferative diabetic hypertension.Diabetic Retinopathy and LV dysfunction other risk factors for cardiovascular disease. 86: 1002-6. 21. Chang S. 1: 563-8. Coronary flow reserve is reduced in young men with IDDM. Proliferative diabetic retinopathy in type 2 diabetes is 6. Am J Epidemiol 1988. J Am Coll required. Wang JJ. retinopathy was significantly higher than patients with 11. Moritz T. further studies with larger sample size are AR. Sjolie AK. 60: retinopathy. Mokhtar MS. Koskinen PJ. Davis CE. Retina & Vitreous. Retina 548-53. Klein R. Wong TY. Although the risk of diabetic retinopathy. Diabetic retinopathy and risk of heart failure. Tabriz University of Medical Sciences. Diabetic prospective complications study. Diabetic patients with type 2 diabetes mellitus. Indian Heart J 2008. Diabetes Care 2005. However. Left ventricular systolic and diastolic functional abnormalities Conflict of interests: The authors declare no conflicts of interest. et al. Diabetes Care 2007. Epidemiology of proliferative in patients with unstable angina. Aiello LM. Duncan BB. 47:248-54. Devereux diabetic retinopathy is more than non-proliferative. Janisse J.356:830-40. Elhendy A.5:8-13. Crawford TN. Taylor HR. Adverse association between diabetic retinopathy and order to reach conclusive results. Am Heart J 2009. While. editors. Risk factors for cardiovascular angina. mortality and cardiovascular disease incidence: the EURODIAB 4. 8. Fuller 3. 140: 1157-9. unstable angina had left ventricular dysfunction. asymptomatic 2. Alfaro DV 3rd. 19. Wang SL. Ariza CR. Crea F. Aguilar D. 2007. Diabetic retinopathy is associated with Ophthalmology. non-proliferative diabetic retinopathy. systolic and diastolic dysfunction and their relationship with USA: LEO Publication. 31% of diabetic patients with retinopathy and the Australian Diabetes Obesity and Lifestyle (AusDiab) study. 6th ed. Tapp RJ. Gifford RW Jr. Arch Inst This research project was funded by Cardiovascular Cardiol Mex 1985. 15: 1875-91. Hallman DM. further studies with cardiac structure and function. Cardiol 2008. Fairbairn JF 2nd. Frati AC. 9. Jablon EP. 14: 885-91. Diabetes 1998. Hiller R. Taffet G. Vitreous Macula. Research Center. The Framingham Heart Study and the Framingham Eye Copyright © 2012 by Tabriz University of Medical Sciences Journal of Cardiovascular and Thoracic Research. Davis M. et al. 55: 133-9. Brancati F.1994. left ventricular dysfunction was seen in only 12% mortality and morbidity: the WHO Mutinational Study of Vascular of cases. left ventricular dysfunction in patients with proliferative 17. N 22. Percentage of impaired left ventricular function Disease in Diabetes. Reaven and colleagues showed that coronary calcium 10. Klein R.