ATS
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Personal Folders
Right arrow Download to citation manager
Right arrow Author home page(s):
Takeki Ohashi
Minoru Ono
Noboru Motomura
Shinichi Takamoto
Right arrow Permission Requests
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Ono, T.
Right arrow Articles by Takamoto, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ono, T.
Right arrow Articles by Takamoto, S.
Related Collections
Right arrow Coronary disease

Ann Thorac Surg 2006;81:608-612
© 2006 The Society of Thoracic Surgeons

Original article: Cardiovascular

Impact of Diabetic Retinopathy on Cardiac Outcome After Coronary Artery Bypass Graft Surgery: Prospective Observational Study

Takayuki Ono, MD a , * , Takeki Ohashi, MD c , Teiji Asakura, MD c , Nagara Ono, MD b , Minoru Ono, MD a , Noboru Motomura, MD a , Shinichi Takamoto, MD a

a Department of Cardiothoracic Surgery, The University of Tokyo Hospital, Tokyo, Japan
b Department of Anesthesiology, The University of Tokyo Hospital, Tokyo, Japan
c Department of Cardiovascular Surgery, Heart Center, Nagoya Tokushukai General Hospital, Aichi, Japan

Accepted for publication July 18, 2005.

* Address correspondence to Dr Takayuki Ono, Department of Cardiovascular Surgery, The University of Tokyo Hospital, 7-3-1, Hongo, Bunkyo-Ku, Tokyo, 113-8655, Japan (Email: takohno{at}hotmail.com).


   Abstract
Top
 Abstract
Introduction
 Patients and Methods
 Results
 Comment
 References
 
BACKGROUND: Diabetic retinopathy is a manifestation of more severe diabetes. We sought to assess the impact of diabetic retinopathy on cardiac outcome of coronary artery bypass graft surgery (CABG).

METHODS: We prospectively assessed the status of the retina of 74 consecutive diabetics who were referred for first-time CABG, and compared cardiac outcome of CABG in diabetics with retinopathy with that in those without retinopathy. Cardiac events included recurrent angina or congestive heart failure that needed admission to hospital, myocardial infarction, repeat revascularization, and cardiac death.

RESULTS: Twenty-six diabetics had retinopathy and 48 diabetics did not have retinopathy. Diabetics with retinopathy were likely to have higher hemoglobin A1c level (p = 0.048), and receive insulin treatment (p = 0.0065). In the 12 months of follow-up, 13 cardiac events occurred in diabetics with retinopathy and 7 in those without retinopathy (p = 0.0021). Among diabetics with retinopathy, heart failure or death due to heart failure accounted for 54% (7 of 13) of these cardiac events. Kaplan-Meier analysis showed significant difference in cardiac event-free survival between the two groups (p < 0.001). After adjustment for differences in patients' characteristics, diabetic retinopathy remained a predictor of cardiac event (adjusted relative risk = 4.2, 95% confidence interval, 1.5% to 11.9%; p = 0.0067).

CONCLUSIONS: After CABG, diabetics with retinopathy have a substantially increased risk of cardiac events, especially of congestive heart failure.


   Introduction
Top
 Abstract
 Introduction
Patients and Methods
 Results
 Comment
 References
 
Diabetic retinopathy is a frequent and early sign of microvascular complication. The risk of retinopathy is directly related to the degree and duration of hyperglycemia. Ophthalmologists all know that diabetics with advanced retinopathy are commonly in poor general health, and have a poor life expectancy. Epidemiologic evidence [1–9] demonstrated that diabetics with retinopathy have high mortality rates of heart disease. The Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR), which consists of a total of 2,366 diabetic patients who were followed up for 16 years, demonstrated that after controlling for age and sex, diabetics with poorer visual acuity and more severe retinopathy had a significant increased risk for death from coronary artery disease [8, 9].

Recently, my colleagues and I have shown [10] that the presence of retinopathy is a strong independent risk factor of all-cause mortality after coronary artery bypass graft surgery (CABG) in diabetics. The 12-year overall survival rate was 40% for diabetics with retinopathy, compared with 88% for those without retinopathy. Poor prognosis of diabetics with retinopathy might be contributed by the high prevalence of cardiac events after CABG. However, little is known about cardiac outcome of CABG in diabetics with retinopathy. In this study, therefore, we prospectively assessed 12-month cardiac outcome after CABG in diabetics with retinopathy, as compared with those without retinopathy.


   Patients and Methods
Top
 Abstract
 Introduction
 Patients and Methods
Results
 Comment
 References
 
Patients referred to the Heart Center at Nagoya Tokushukai General Hospital, Japan for CABG between November 2001 and April 2003 were eligible for the study provided they had diabetes mellitus treated with hypoglycemic agents or insulin injection, and provided that they had stable angina or unstable angina. Patients were excluded if they required concomitant cardiac procedures, or they had previously undergone CABG, but there were no eligibility restrictions for ejection fraction, age, or urgency of surgery. All patients gave written informed consent (approved by our Institutional Ethics Committee), and completed ophthalmic examination for detection of diabetic retinopathy within one week prior to CABG by an ophthalmologist. According to a modification of the Diabetic Retinopathy Study and the Early Treatment Diabetic Retinopathy Study grading scale [10], the severity in the worst affected eye was used and the patients with retinopathy were grouped into three categories of retinopathy: those with mild-to-moderate nonproliferative retinopathy, those with severe stage of nonproliferative retinopathy, and those with proliferative retinopathy. Each patient underwent off-pump CABG performed by two surgeons experienced in the off-pump procedure, and the goal of surgery was to obtain complete revascularization [11, 12]. We have been performing off-pump CABG since February 1998. Before the study began, the off-pump procedure had been the routine procedure for all patients who need CABG. After CABG, antiplatelets were prescribed for all patients. Other routine medications included oral diuretics, cholesterol-lowering agents, nitrates, calcium-channel blocker, beta-blockers, and angiotensin-converting enzyme inhibitors as appropriate. After discharge from the hospital, medications were given as deemed appropriate by the responsible physicians.

Outcomes
All patients were followed for 12 months after the operation. The primary outcome variables were recurrent angina or congestive heart failure that needed admission to hospital, myocardial infarction, repeat revascularization (surgery or angioplasty), and death due to cardiac causes. Patients who died were classified according to their cause of death. The remaining patients who had had one or more nonfatal events were classified on the basis of their first event. Congestive heart failure was defined as paroxysmal nocturnal dyspnea or orthopnea, and evidence of radiographic pulmonary edema. Myocardial infarction was diagnosed based on typical symptoms, electrocardiographic changes, and cardiac enzyme elevations.

Statistical Analysis
Data were analyzed using SPSS for Windows (version 10.0, SPSS, Chicago, IL). Dichotomous data were compared by the {chi}2 test or Fisher's exact test for categorical variables. Descriptive data for continuous variables are presented as mean ± SD. The Student's t test was used for continuous variables. Cardiac event-free survival rates were estimated according to Kaplan-Meier methods and were compared using the log-rank test. We used a Cox proportional-hazards model to adjust for differences between patients' characteristics of the two groups. Two-sided p values of less than 0.05 were considered to indicate a statistically significant difference.


   Results
Top
 Abstract
 Introduction
 Patients and Methods
 Results
Comment
 References
 
Seventy-four diabetics were studied. Twenty-six (35.1%) diabetics have retinopathy and 48 (64.9%) did not have retinopathy. Baseline characteristics of the two groups are shown in Table 1. Of 26 diabetics with retinopathy, 11 patients were grouped as having mild-to-moderate nonproliferative retinopathy, seven as having severe nonproliferative retinopathy, and eight as having proliferative retinopathy. As compared with diabetics without retinopathy, diabetics with retinopathy were more likely to have higher hemoglobin A1c level (p = 0.048), and receive insulin treatment (p = 0.0065). Other patients' characteristics, including ejection fraction and serum creatinine level, did not differ significantly in the two groups. The mean number of grafts per patient was 2.9 among diabetics with retinopathy and 3.0 among diabetics without retinopathy. Complete revascularization was achieved in 92.3% of diabetics with retinopathy and 93.8% of diabetics without retinopathy. Follow-up angiography was performed in 21 diabetics with retinopathy (62 grafts) and 30 diabetics without retinopathy (94 grafts). The overall patency rates were 93.5% and 94.7%, respectively (p = 0.74). Twenty-three patients (31.1%) did not undergo follow-up angiography because they had no symptoms.


View this table:
[in this window]
[in a new window]
  		Table 1. Baseline Characteristics a
 
Cardiac events after CABG are summarized in Table 2. In the 12 months of follow-up, there were four cardiac deaths and 16 nonfatal cardiac events (total 20 patients [27% of study patients]). Most (80%) cardiac events occurred after discharge from the hospital. At 12 months, 13 of 26 (50%) diabetics with retinopathy had cardiac events, compared with 7 of 48 (15%) diabetics without retinopathy (p = 0.0021).


View this table:
[in this window]
[in a new window]
  		Table 2. Cardiac Events After Coronary Artery Bypass Grafting
 
Cardiac events were categorized to two groups according to their cause. Twelve patients had coronary atherosclerotic events (recurrent angina, myocardial infarction, and repeat revascularization), and eight congestive heart failures occurred. In diabetics without retinopathy, most (6 out of 7) cardiac events were due to coronary atherosclerosis. In diabetics with retinopathy, congestive heart failure or death due to congestive heart failure accounted for 54% (7 out of 13) of cardiac events. It was diabetics with advanced retinopathy (4 of those with severe nonproliferative retinopathy, and 3 of those with proliferative retinopathy) who had congestive heart failure. A much larger proportion of diabetics with retinopathy had congestive heart failure during follow-up than did diabetics without retinopathy (p = 0.0022).

A 12-month cardiac event-free survival was 50.0% (95% confidence interval [CI], 41.2% to 59.8%) for diabetics with retinopathy, whereas 85.4% (95% CI, 80.3% to 90.5%) for diabetics without retinopathy. As shown in Figure 1, cardiac event-free survival curves differed significantly according to the presence or absence of retinopathy (p < 0.001). After adjustment for differences in patients' characteristics (hemoglobin A1c level and insulin treatment), the presence of retinopathy remained a predictor of cardiac event (adjusted relative risk, 4.2; 95% CI, 1.15 to 11.9; p < 0.0067).


Figure 1
View larger version (16K):
[in this window]
[in a new window]
  		Fig 1. Kaplan-Meier estimates of survival free from angina, congestive heart failure, myocardial infarction, repeat revascularization, and death due to cardiac causes, according to the presence or absence of diabetic retinopathy (DR). (CABG = coronary artery bypass graft surgery.)

 

   Comment
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
References
 
Diabetic retinopathy is a manifestation of more severe diabetes, which is known to be associated with a higher incidence of adverse cardiac events in any given time period. In this study, we have shown that diabetics with retinopathy had an unexpected increased risk of cardiac events even after CABG, as compared with diabetics without retinopathy. Especially, diabetics with advanced retinopathy are at a high risk of developing congestive heart failure.

Several epidemiologic studies demonstrated that the population with diabetic retinopathy have a high incidence of cardiac events in any given time period [13–16]. The Framingham Heart Study and the Framingham Eye Study examined the association between diabetic retinopathy and the occurrence of cardiovascular events including myocardial infarction, coronary insufficiency, angina, congestive heart failure, stroke, and intermittent claudication [13]. Among the 206 type 2 diabetics, the odds rates for diabetic retinopathy and cardiovascular events were 14.3, 2.0, and 0.3 for ages 52 to 64, 65 to 74, and 75 to 85 years, respectively. The Milan Study on Atherosclerosis and Diabetes [16] prospectively studied 735 patients with type 2 diabetes mellitus who were screened for unknown asymptomatic coronary artery disease. During 5-year follow-up a total of 42 ischemic heart events occurred: 3 fatal myocardial infarction, 20 nonfatal myocardial infarction, and 19 angina pectoris. Multivariate analysis demonstrated that diabetic retinopathy was an independent predictor of incidence of cardiac events (adjusted hazard rate = 2.37; p = 0.036; 1.06–5.31). In addition, Wong and colleagues [17] clearly demonstrated that the diabetics with retinopathy had an increased risk of developing congestive heart failure independent of coronary artery disease. However, there has been little study examining cardiovascular events of diabetics with retinopathy who undergo coronary revascularization. Kim and colleagues [18] studied 115 diabetics with retinopathy and 205 diabetics without retinopathy who underwent percutaneous coronary intervention (PCI), and assessed the association between the presence of retinopathy and the occurrence of major cardiovascular events including death, myocardial infarction, cerebrovascular event, and repeat revascularization. The 2-year survival rate was 96.3% for diabetics with retinopathy, as compared with 99.6% for diabetics without retinopathy (p = 0.02). However, the 2-year cardiovascular event-free survival rate was not statistically different between the two groups (67.7% and 73.8% in patients with retinopathy and without retinopathy, respectively, p = 0.17). A recent report [19] demonstrated that the severity of diabetic retinopathy correlates with the incidence of in-stent restenosis after PCI, especially for proliferative retinopathy.

It is generally accepted that hemoglobin A1c and treatment with insulin injection are markers of the severity of diabetes. However, hemoglobin A1c is a measure of short-term (3 or 4 months) glucose control. In diabetics who strictly treated with insulin therapy, glucose control would be good and the status of diabetes could be less severe. In contrast, among ophthalmologists diabetic retinopathy is used as a measure of how well glucose was controlled over time and therefore a precise measure of the severity of diabetes. Our study suggested that cardiac outcome after CABG is closely related to the status of diabetes mellitus independent of short-term glucose control.

This study carries the clinical implications for diabetics who undergo CABG. In the present study, in the 12 months of follow-up after CABG, adverse cardiac events occurred in as many as 50% of diabetics with retinopathy. This high prevalence of cardiac events might contribute to poor prognosis in diabetics with retinopathy undergoing CABG. Nowhere is this more "visible" than in the eye, where the retinal circulation represents the cerebrovascular microcirculation [20], and the status of the retina is a good predictor of cardiac events in diabetics. As a result, pre-CABG retinal examination in diabetics has become part of our practice guidelines. Diabetics with retinopathy would be a target for more aggressive management after CABG to improve cardiac outcome of the diabetic population. A better knowledge of the relationship between diabetic retinopathy and cardiac outcome after CABG would be useful for developing a future therapeutic strategy for diabetics requiring CABG.

Study Limitations
Limitations of this study include, first, that the effects of postoperative medication on cardiac events were not examined because medications were given as deemed appropriate by the responsible physicians after hospital discharge. Second, diabetic retinopathy was assessed only within one week prior to CABG, and we do not have information about progression of retinopathy during the year of follow-up. Third, our patient sample was small. A larger sample and longer follow-up would be needed to assess influences of the severity of retinopathy on cardiac outcome.


   References
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
 References
 

  1. Davis MD, Hiller R, Magli YLM, et al. Prognosis for life in patients with diabetesrelation to severity of retinopathy. Trans Am Ophthalmol Soc 1979;77:144-170.[Medline]
  2. Sullivan P, Caldwell G, Alexander N, et al. Long-term outcome after photocoagulation for proliferative diabetic retinopathy Diabet Med 1990;7:788-794.[Medline]
  3. Neil A, Hawkins M, Potok M, et al. A retrospective population-based study of microalbuminuria as a predictor of mortality in NIDDM Diabetes Care 1993;16:996-1003.[Abstract]
  4. Sasaki A, Uehara M, Horiuchi N, et al. A 15-year follow-up study of patients with non-insulin-dependent diabetes mellitus (NIDDM) in Osaka, Japan. Factors predictive of the prognosis of diabetic patients Diabetes Res Clin Pract 1997;36:41-47.[Medline]
  5. Helbig H, Kellner U, Bornfeld N, et al. Life expectancy of diabetic patients undergoing vitreous surgery Br J Ophthalmol 1996;80:640-643.[Abstract/Free Full Text]
  6. Rajala U, Pajunpaa H, Koskela P, et al. High cardiovascular disease mortality in subjects with visual impairment caused by diabetic retinopathy Diabetes Care 2000;23:957-961.[Abstract]
  7. Henricsson M, Nilsson A, Heiji A, et al. Mortality in diabetic patients participating in an ophthalmological control and screening programme Diabet Med 1997;14:576-583.[Medline]
  8. Klein R, Moss SE, DeMets DL. Relation of ocular and systemic factors to survival in diabetes Arch Intern Med 1989;149:266-272.[Abstract/Free Full Text]
  9. Klein R, Klein BE, Moss SE, et al. Association of ocular disease and mortality in a diabetic population Arch Ophthalmol 1999;117:1487-1495.[Abstract/Free Full Text]
  10. Ono T, Kobayashi J, Sasako Y, et al. The impact of diabetic retinopathy on long-term outcome following coronary artery bypass graft surgery J Am Coll Cardiol 2002;40:428-436.[Abstract/Free Full Text]
  11. Ono T, Asakura T, Ohashi T, et al. A simple method of triggering balloon counterpulsation accurately during off-pump coronary artery bypass surgery Ann Thorac Surg 2005;79:723-725.[Abstract/Free Full Text]
  12. Ono N, Ono T, Asakura T, et al. Usefulness of unipolar epicardial ventricular electrogram for triggering of IABP during off-pump coronary artery bypass surgery in patients with hemodynamic instability complicating acute coronary syndrome Anesth Analg 2005;100:937-941.[Abstract/Free Full Text]
  13. Hiller R, Sperduto RD, Podgor MJ, et al. Diabetic retinopathy and cardiovascular disease in type II diabetics. The Framingham Heart Study and the Framingham Eye Study Am J Epidemiol 1988;128:402-409.[Abstract/Free Full Text]
  14. Mittinen H, Haffner SM, Lehto S, et al. Retinopathy predicts coronary heart disease events in NIDDM patients Diabetes Care 1996;19:1445-1448.[Abstract]
  15. Diglas J, Willinger C, Neu U, et al. Morbidity and mortality in type 1 and 2 diabetes mellitus after the diagnosis of diabetic retinopathy Dtsch Med Wochenschr 1992;117:1703-1708.[Medline]
  16. Fagila E, Favales F, Paleari F, et al. Cardiac events in 735 type 2 diabetic patients who underwent screening for unknown asymptomatic coronary heart disease5-year follow-up report from the Milan study on atherosclerosis and diabetes (MiSAD). Diabetes Care 2002;25:2032-2036.[Abstract/Free Full Text]
  17. Wong TY, Rosamond W, Chang PP, et al. Retinopathy and risk of congestive heart failure JAMA 2005;293:63-69.[Abstract/Free Full Text]
  18. Kim YH, Hong MK, Song JM, et al. Diabetic retinopathy as a predictor of late clinical events following percutaneous coronary intervention J Invasive Cardiol 2002;14:599-602.[Medline]
  19. Kim SH, Han JG, Oh BH, et al. Grade of diabetic retinopathy has a powerful predictive relevance of in-stent restenosis after percutaneous coronary intervention Circulation 2004;110(suppl 3)III–482.
  20. Ono T, Okita Y, Ando M, et al. Retrograde cerebral perfusion in human brains Lancet 2000;356:1323.[Medline]



This article has been cited by other articles:


Home page
 J Am Coll CardiolHome page
N. Cheung, J. J. Wang, S. L. Rogers, F. Brancati, R. Klein, A. R. Sharrett, T. Y. Wong, and for the ARIC (Atherosclerosis Risk In Communities)
Diabetic retinopathy and risk of heart failure.
J. Am. Coll. Cardiol., April 22, 2008; 51(16): 1573 - 1578.
[Abstract] [Full Text] [PDF]

Home page
 J Am Coll CardiolHome page
H. O. Ventura and M. Reddy
The eye as an indicator of heart failure in diabetic patients.
J. Am. Coll. Cardiol., April 22, 2008; 51(16): 1579 - 1580.
[Full Text] [PDF]

Home page
 Ann. Thorac. Surg.Home page
T. Ohno, S. Takamoto, and N. Motomura
Diabetic Retinopathy and Coronary Artery Disease From the Cardiac Surgeon's Perspective
Ann. Thorac. Surg., February 1, 2008; 85(2): 681 - 689.
[Abstract] [Full Text] [PDF]

Home page
 Ann. Thorac. Surg.Home page
T. Ohno, S. Takamoto, N. Motomura, M. Ono, J. Ando, T. Morita, H. Fujita, Y. Hirata, R. Nagai, T. Shigeeda, et al.
Coronary Artery Bypass Grafting Versus Coronary Implantation of Sirolimus-Eluting Stents in Patients with Diabetic Retinopathy
Ann. Thorac. Surg., November 1, 2007; 84(5): 1474 - 1478.
[Abstract] [Full Text] [PDF]

Home page
 J Am Coll CardiolHome page
N. Cheung, D. A. Bluemke, R. Klein, A. R. Sharrett, F.M. A. Islam, M. F. Cotch, B. E.K. Klein, M. H. Criqui, and T. Y. Wong
Retinal Arteriolar Narrowing and Left Ventricular Remodeling: The Multi-Ethnic Study of Atherosclerosis
J. Am. Coll. Cardiol., July 3, 2007; 50(1): 48 - 55.
[Abstract] [Full Text] [PDF]

Home page
 Eur. J. Cardiothorac. Surg.Home page
T. Ohno, J. Ando, M. Ono, T. Morita, N. Motomura, Y. Hirata, and S. Takamoto
The beneficial effect of coronary-artery-bypass surgery on survival in patients with diabetic retinopathy
Eur. J. Cardiothorac. Surg., December 1, 2006; 30(6): 881 - 886.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Personal Folders
Right arrow Download to citation manager
Right arrow Author home page(s):
Takeki Ohashi
Minoru Ono
Noboru Motomura
Shinichi Takamoto
Right arrow Permission Requests
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Ono, T.
Right arrow Articles by Takamoto, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ono, T.
Right arrow Articles by Takamoto, S.
Related Collections
Right arrow Coronary disease

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
ANN THORAC SURG ASIAN CARDIOVASC THORAC ANN EUR J CARDIOTHORAC SURG
J THORAC CARDIOVASC SURG ICVTS ALL CTSNet JOURNALS