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Retinal Arteriolar Narrowing and Risk of Coronary Heart Disease Correction Correction Error in Accompanying Abstract. In the Commentary by Bressler titled “Retinal Arteriolar Narrowing and Risk of Coronary Heart Disease,” published in the January issue of the ARCHIVES (2003;121:113-114), the accompanying abstract on page 113, on which Bressler’s article was commenting, was incorrect. The abstract should have been taken from “Retinal Arteriolar Nar- rowing and Risk of Coronary Heart Disease in Men and Women: The Atherosclerosis Risk in Communities Study” by Wong et al (JAMA. 2002;287:1153-1159). The Commentary, with the correct abstract, is reprinted here. The journal regrets this error. COMMENTARY JAMA Retinal Arteriolar Narrowing and Risk of Coronary Heart Disease in Men and Women: The Atherosclerosis Risk in Communities Study Tien Yin Wong, MD, MPH; Ronald Klein, MD, MPH; A. Richey Sharrett, MD, DrPH; Bruce B. Duncan, MD, PhD; David J. Couper, PhD; James M. Tielsch, PhD; Barbara E. K. Klein, MD, MPH; Larry D. Hubbard, MAT Context: Microvascular processes have been hypothesized to play a greater role in the development of coronary heart dis- ease (CHD) in women than in men; however, prospective clinical data are limited. Objective: To examine the association between retinal arteriolar narrowing, a marker of microvascular damage from hyper- tension and inflammation, and incident CHD in healthy middle-aged women and men. Design, Setting, and Participants: The Atherosclerosis Risk in Communities Study, an ongoing prospective, population- based cohort study in 4 US communities initiated in 1987-1989. Retinal photographs were taken in 9648 women and men aged 51 to 72 years without CHD at the third examination (1993-1995). To quantify retinal arteriolar narrowing, the pho- tographs were digitized, individual arteriolar and venular diameters were measured, and a summary arteriole-to-venule ra- tio (AVR) was calculated. Main Outcome Measure: Risk of CHD associated with retinal arteriolar narrowing. Results: During an average 3.5 years of follow-up, 84 women and 187 men experienced incident CHD events. In women, after controlling for mean arterial blood pressure averaged over the previous 6 years, diabetes, cigarette smoking, plasma lipid levels, and other risk factors, each SD decrease in the AVR was associated with an increased risk of any incident CHD (relative risk [RR], 1.37; 95% confidence interval [CI], 1.08-1.72) and of acute myocardial infarction (RR, 1.50; 95% CI, 1.10-2.04). In contrast, AVR was unrelated to any incident CHD in men (RR, 1.00; 95% CI, 0.84-1.18) or to acute myocar- dial infarction (RR, 1.08; 95% CI, 0.85-1.38). Conclusion: Retinal arteriolar narrowing is related to risk of CHD in women but not in men, supporting a more prominent microvascular role in the development of CHD in women than in men. Future work is needed to confirm these findings. Author Affiliations: Department of Ophthalmology, University of Wisconsin-Madison (Drs Wong, R. Klein, B. Klein, and Mr Hub- bard); Department of Ophthalmology, National University of Singapore (Dr Wong); National Heart, Lung, and Blood Institute, Bethesda, Md (Dr Sharrett); Social Medicine Department, School of Medicine, Federal University of Rio Grande do Sul, Porto Alegre, RS Brazil (Dr Duncan); Department of Biostatistics, University of North Carolina, Chapel Hill (Dr Couper); Department of International Health, Johns Hopkins University, Baltimore, Md (Dr Tielsch). Corresponding Author and Reprints: Tien Yin Wong, MD, MPH, Department of Ophthalmology, National University of Singapore, 10 Kent Ridge Crescent, Singapore 119260 (e-mail: [email protected]). Retinal Arteriolar Narrowing and Risk of Coronary Heart Disease ICROVASCULAR PROCESSES, such as nar- more prominent role than macrovascular disease in CHD rowing of small coronary arteries, and in women2 and may explain observations such as women macrovascular processes, such as ath- having poorer outcomes than men after coronary artery erosclerosis of large coronary arter- bypass graft surgery.3 To explore this hypothesis, one ies, are believed to contribute to the planned analysis of the Atherosclerosis Risk in Commu- Mrisk of coronary heart disease (CHD),1 a major public nities (ARIC) Study examined the association between health problem with respect to morbidity and mortality retinal arteriolar narrowing, a marker of microvascular in the United States and elsewhere. The cardiology lit- damage from hypertension and inflammation,4 and in- erature suggests that microvascular disease may play a cident CHD.5 (REPRINTED) ARCH OPHTHALMOL / VOL 121, MAY 2003 WWW.ARCHOPHTHALMOL.COM 738 ©2003 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/25/2021 Retinal Arteriolar Narrowing and Risk of CHD: decreased retinal arteriole-to-venule ratio was not asso- What Did the ARIC Study Find? ciated with incident CHD in men; the inconsistency sug- gests that additional confirmatory investigations are In a prospective, population-based cohort study in 4 com- needed to be more sure about the association. munities in the United States, retinal photographs were Why should ophthalmologists not refer people taken in 9648 men and women aged 51 to 72 years who with low arteriole-to-venule ratios for further cardiac did not have CHD at the time of examination between evaluations in case the association is real? After all, oph- 1993 and 1995. The photographs were digitized, and the thalmologists are more likely than their primary care phy- diameters of individual arterioles and venules coursing sician counterparts to identify such a finding on oph- through a zone located one-half to 1 disc diameter from thalmoscopy as part of an annual eye examination in the optic disc margin were measured and summarized people older than 50 years. If the association is not truly as an arteriole-venule ratio.6 During an average fol- a cause-and-effect relationship, then people referred for low-up of 31⁄2 years, 84 women and 187 men had an in- investigations or management of CHD on the basis of reti- cident CHD event.5 After controlling for other known risk nal arteriole-to-venule ratio findings may have unnec- factors for CHD, each 1-SD decrease in the arteriole-to- essary tests or treatments (and their associated risks) for venule ratio was associated with an increased risk of any CHD. Ophthalmologists should look at the solid inves- incident CHD (relative risk, 1.37; 95% confidence inter- tigations reported by the ARIC Study authors as provid- val, 1.08-1.72) and of acute myocardial infarction (rela- ing support to the hypothesis that microvascular dis- tive risk, 1.50; 95% confidence interval, 1.10-2.04) in ease plays a more prominent role in the development of women but not in men. myocardial ischemia and CHD in women, but not as pro- viding support to refer patients with low retinal arteriole- How Might These ARIC Study Results to-venule ratios for care beyond the current standard care Impact on Ophthalmologists? for cardiovascular disease. Do these results imply that routine care of patients by Neil M. Bressler, MD ophthalmologists should now include evaluating reti- Baltimore, Md nal arteriole-to-venule ratio (in women but not in men) and refer those patients for evaluation of CHD? Not yet. Accepted for publication September 18, 2002. As the authors of the ARIC Study of retinal arteriolar nar- Reprints not available from the author. rowing and risk of CHD conclude, these results support “... amore prominent microvascular role in the de- REFERENCES velopment of CHD in women than in men. Future work is needed to confirm these findings.”5(p1153) These asso- 1. Chilian WM. Coronary microcirculation in health and disease: summary of an NHLBI workshop. Circulation. 1990;82:1-7. ciations offer insights that support the hypothesis that 2. Cannon RO III, Balaban FS. Chest pain in women with normal coronary angio- microvascular disease may play a more prominent role grams. N Engl J Med. 2000;342:885-887. in the development of myocardial ischemia and CHD in 3. Vaccarino V, Parsons L, Every NR, Barron HV, Krumholz HM, for the National women. The study is limited from making a more de- Registry of Myocardial Infarction 2 Participants. Sex-based differences in early mortality after myocardial infarction. N Engl J Med. 1999;341:217-225. finitive conclusion since the retinal microvasculature, not 4. Tso MOM, Jampol LM. Pathophysiology of hypertensive retinopathy. Ophthal- the coronary microcirculation, was assessed directly. Fur- mology. 1982;89:1132-1145. thermore, these associations do not necessarily imply a 5. Wong TY, Klein R, Sharrett AR, et al. Retinal arteriolar narrowing and risk of coro- cause (decreased retinal arteriole-to-venule ratio) and nary heart disease in men and women: the Atherosclerosis Risk in Communities effect (incident CHD) relationship. Other unmeasured Study. JAMA. 2002;287:1153-1159. 6. Hubbard LD, Brothers RJ, King WN, et al. Methods for evaluation of retinal mi- factors associated with a decreased retinal arteriole-to- crovascular abnormalities associated with hypertension/sclerosis in the Athero- venule ratio might have been the true cause of the inci- sclerosis Risk in Communities (ARIC) Study. Ophthalmology. 1999;106:2269- dent CHD. Also, it is unclear why the association of a 2280. (REPRINTED) ARCH OPHTHALMOL / VOL 121, MAY 2003 WWW.ARCHOPHTHALMOL.COM 739 ©2003 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/25/2021.
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