Retinal Vessel Calibers in Predicting Long-Term Cardiovascular Outcomes: The Atherosclerosis Risk in Communities Study

Abstract

Background: Narrower retinal arterioles and wider retinal venules have been associated with negative cardiovascular outcomes. We investigated whether retinal vessel calibers are associated with cardiovascular outcomes in long-term follow-up and provide incremental value over the 2013 American College of Cardiology/American Heart Association Pooled Cohort Equations in predicting atherosclerotic cardiovascular disease events.

Methods: A total of 10 470 men and women without prior atherosclerotic cardiovascular disease events or heart failure in the ARIC Study (Atherosclerosis Risk in Communities) underwent retinal photography at visit 3 (1993-1995).

Results: During a mean follow-up of 16 years, there were 1779 incident coronary heart disease events, 548 ischemic strokes, 1395 heart failure events, and 2793 deaths. Rates of all outcomes were higher in those with wider retinal venules and narrower retinal arterioles. Subjects with wider retinal venules (hazard ratio [HR], 1.13; 95% confidence interval [CI], 1.08-1.18; HR, 1.18; 95% CI, 1.07-1.31; and HR, 1.10; 95% CI, 1.00-1.20 per 1-SD increase) and narrower retinal arterioles (HR, 1.06; 95% CI, 1.01-1.11; HR, 1.14; 95% CI, 1.03-1.26; and HR, 1.13; 95% CI, 1.03-1.24 per 1-SD decrease) had a higher risk of death and stroke in both sexes and incident coronary heart disease in women but not men (interaction P=0.02) after adjustment for the Pooled Cohort Equations risk score variables. The association between retinal vessel caliber and heart failure was nonsignificant after adjustment for systolic blood pressure. Among women with Pooled Cohort Equations-predicted 10-year atherosclerotic cardiovascular disease event risk <5% (overall risk, 3.9%), women in the narrowest arteriolar quartile had a 10-year event rate of 5.6% compared with 2.8% for women in the widest quartile (5.0% versus 3.4% for wider versus narrower venules). Retinal vessel caliber reclassified 21% of low-risk women (11% of all women) as intermediate risk (>5%).

Conclusions: Narrower retinal arterioles and wider retinal venules conferred long-term risk of mortality and ischemic stroke in both sexes and coronary heart disease in women. These measures serve as an inexpensive, reproducible biomarker that added incremental value to current practice guidelines in atherosclerotic cardiovascular disease event risk prediction in low-risk women.

Keywords: cardiovascular diseases; death; stroke; women.

Figure 1

Risk of Death and Atherosclerotic Cardiovascular Events per 1 Standard Deviation widening of the retinal vein or narrowing in the retinal artery in the Atherosclerosis Risk in Communities Study cohort (N=10,470) assessed by fundus photography following multivariate adjustment for the components of the Pooled Cohort Equations Risk Score (age, gender, race, systolic blood pressure, TChol, HDL, HTN, DM, cigarette use). CHD and ASCVE represents incident Coronary Heart Disease risk in women only (N=5952).

Figure 2

Kaplan Meier failure curves of Atherosclerotic Cardiovascular Event (ASCVE) Risk by Central Retinal Arteriolar Equivalent (CRAE) or Central Retinal Venular Equivalent (CRVE) quartiles in women with predicted 10-year ASCVE risk <5% according to the ACC/AHA pooled cohort equation (PCE) risk score (low-risk, N=3,277) in the Atherosclerosis Risk in Communities Study cohort. The first quartile represents the most narrow arterioles and venules and the fourth quartile represents the least narrow arterioles and widest venules. For CRAE quartiles the log rank p-value=0.0001; for CRVE quartiles the log-rank p=0.004.