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Diabetic Retinopathy as a Predictor of Late Clinical Events Following Percutaneous Coronary Intervention<br />
October 2002
Coronary artery disease is frequently encountered in diabetic patients.1 Previous reports showed that 15–25% of patients undergoing coronary revascularization had diabetes mellitus (DM).2–4 Although the initial success and in-hospital complication rates in diabetic patients after percutaneous coronary intervention (PCI) were similar to those in nondiabetic patients, diabetic patients had less favorable long-term clinical outcomes.2,5 Large randomized trials showed that the 5-year mortality rate in diabetic patients who had undergone PCI was 15–25%.4,6
Recent data suggested that proteinuria and poor glycemic control reflected by HbA1c level might be associated with the poor long-term prognosis in diabetic patients after PCI.7–9 The recent prospective study revealed that hyperglycemia was shown to be associated with an increased risk of diabetic retinopathy.10 Therefore, it has been suggested that retinopathy, albuminuria and cardiovascular disease are the consequences of similar widespread vascular damage.11
Several physiologic stimuli incite acute and chronic inflammation in the vessel wall, which induces multiple signaling pathways to activate migration and proliferation of smooth muscle cells.12–14 This process has a pivotal role in restenosis after PCI. Diabetic retinopathy can be recognized as another example of vascular proliferation.15 Therefore, we hypothesized that the presence of diabetic retinopathy is related to the development of adverse cardiovascular events after PCI.
Methods
Subjects. From January 1998 to February 2001, a total of 365 non-insulin dependent DM patients, who had undergone ophthalmologic evaluation of fundi by an experienced ophthalmologist before or immediately after PCI, were selected from 613 consecutive diabetic patients who had undergone PCI in our hospital. We excluded 13 insulin-dependent DM patients and 235 non-insulin dependent DM patients who had not had fundoscopic examinations. There were no statistically significant differences of baseline clinical characteristics between the 365 enrolled patients who had fundoscopic examinations and the 235 excluded patients who did not have fundoscopic examinations. Diagnosis of non-insulin dependent DM was based on onset age, presence of insulin dependency and level of fasting C-peptide by experienced diabetologists.16
Ophthalmologic evaluation. Ophthalmologic examination of fundi was performed by experienced ophthalmologists. Fundoscopic findings were classified into 3 categories according to the status of the worse eye: no retinopathic changes, background retinopathy (microaneurysm, cotton or hard exudates or hemorrhages), and proliferative retinopathy (neovascularization or previous laser coagulation therapy).17
Angiographic analysis. Coronary angiograms were analyzed by 2 experienced angiographers not involved in the procedure. The diameter of the reference vessel and the minimal luminal diameter using an online quantitative coronary angiography system (ANCOR V2.0, Siemens) were determined at baseline and after the procedure. Angiographic measurements were made during diastole after intracoronary nitroglycerin administration using the guiding catheter for magnification calibration. The lesions were characterized by the modified ACC/AHA (American College of Cardiology/American Heart Association) classification scores.18 Procedure success required all treated sites to have less than 50% residual stenosis after PCI.
Clinical follow-up. All patients were clinically evaluated by office visits at 3-month intervals for 1 year after PCI. Thereafter, patients were contacted at 6-month intervals. The predetermined primary endpoint of this study was freedom from all-cause mortality. The secondary endpoint was the freedom from major adverse cardiac or cerebrovascular events (MACCE) including death, myocardial infarction (MI), cerebrovascular event and target lesion revascularization (TLR). Cerebrovascular events were defined as stroke, transient ischemic attacks and reversible neurologic deficits.
Statistical analysis. Data are listed as means ± standard deviation. Statistical analysis was conducted using SPSS statistical software. The student’s t-test was used for continuous variables and the Chi-square test for categorical variables. The endpoint is presented as Kaplan-Meier event-free survival curves. A probability value Study limitations. The main limitation of our study is that all diabetic patients who underwent PCI were not included due to the retrospective study design. Fundoscopic examinations were performed in only two-thirds of diabetic patients recorded in our interventional registry. Prospective analyses comparing the association of diabetic complications and long-term prognosis after PCI are warranted. In addition, due to the relatively short follow-up duration, the number of cardiac and cerebrovascular events was too small to compare the frank difference between the 2 groups. A larger number of subjects and longer follow-up might provide more insight to the most powerful predictor of the long-term prognosis of diabetic patients following PCI.
1. Hambly RI, Sherman L, Mehta J, Aintablian A. Reappraisal of the role of the diabetic state in coronary artery disease. Chest 1976;70:251–257.
2. Kip KE, Faxon DP, Detre KM, et al. Coronary angioplasty in diabetic patients: The National Heart, Lung and Blood Institute percutaneous transluminal coronary angioplasty registry. Circulation 1996;94:1818–1825.
3. Barsness GW, Peterson ED, Ohman EM, et al. Relationship between diabetes and long-term survival after coronary bypass and angioplasty. Circulation 1997;96:2551–2556.
4. The BARI Investigators. Comparison of coronary bypass surgery with angioplasty in patients with multivessel disease. N Engl J Med 1996;335:217–215.
5. Stein B, Weintraub WS, Gebhart SP, et al. Influence of diabetes mellitus on early and late outcome after percutaneous transluminal coronary angioplasty. Circulation 1995;91:979–989.
6. Ellis SG, Narins CR. Problem of angioplasty in diabetes. Circulation 1997;96:1707–1710.
7. Marso SP, Ellis SG, Tuzcu M, et al. The importance of mortality following percutaneous coronary revascularization in diabetics. J Am Coll Cardiol 1999;33:1269–1277.
8. Dinneen SF, Gerstein HC. The association of microalbuminuria and mortality in non-insulin dependent diabetes mellitus. Arch Intern Med 1997;157:1413–1418.
9. Hasdai D, Rizza RA, Grill DE, et al. Glycemic control and outcome of diabetic patients after percutaneous coronary revascularization. Am Heart J 2001;141:117–123.
10. Klein R, Klein BE, Moss SE, et al. Glycosylated hemoglobin predicts the incidence and progression of diabetic retinopathy. JAMA 1988;260:2864–2871.
11. Deckert T, Feldt-Rasmussen B, Borch-Johnsen K, et al. Albuminuria reflects widespread vascular damage: The Steno hypothesis. Diabetologia 1989;32:219–226.
12. Farb A, Sangiorgi G, Carter AJ, et al. Pathology of acute and chronic coronary stenting in humans. Circulation 1999;99:44–52.
13. Grewe P, Deneke T, Machraoui A. Acute and chronic tissue response to coronary stent implantation: Pathologic findings in human specimen. J Am Coll Cardiol 2000;35:157–163.
14. Kornowski R, Hong MK, Tio FO, et al. In-stent restenosis: Contributions of inflammatory responses and arterial injury to neointimal hyperplasia. J Am Coll Cardiol 1998;31:224–230.
15. Nguyen LL, D’amore PA. Cellular interactions in vascular growth and differentiation. Int Rev Cytol 2001;204:1–48.
16. Gavin JR III, Alberti KGMM, Davidson MB, et al. Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care 1997;20:1183–1197.
17. Aiello LP, Gardner TW, King GL, et al. Diabetic retinopathy. Diabetes Care 1998;21:143–156.
18. Ryan TJ, Faxon DP, Gunnar RM, et al. Guidelines for percutaneous transluminal coronary angioplasty. A report of the American College of Cardiology/American Heart Association Task Force on Assessment of Diagnostic and Therapeutic Cardiovascular Procedures (Subcommittee on Percutaneous Transluminal Coronary Angioplasty). Circulation 1988;78:486–502.
19. Klein R, Moss SE, Klein BE, DeMets DL. Relation of ocular and systemic factors to survival. Arch Int Med 1989;149:266–272.
20. Miettinen H, Haffner SM, Lehto S, et al. Retinopathy predicts coronary heart disease events in NIDDM patients. Diabetes Care 1996;19:1445–1448.
21. Abizaid A, Kornowski R, Mintz GS, et al. The influence of diabetes mellitus on acute and late clinical outcomes following coronary stent implantation. J Am Coll Cardiol 1998;32:584–589.
22. United Kingdom Prospective Diabetes Study (UKPDS) Group. The UKPDS risk engine: A model for the risk of coronary heart disease in type II diabetes (UKPDS 56). Clin Sci 2001;101:671–679.
