Retinal Vasculometry Associations with Cardiometabolic Risk Factors in the European Prospective Investigation of Cancer-Norfolk Study

Abstract

Purpose: To examine associations between retinal vessel morphometry and cardiometabolic risk factors in older British men and women.

Design: Retinal imaging examination as part of the European Prospective Investigation into Cancer-Norfolk Eye Study.

Participants: Retinal imaging and clinical assessments were carried out in 7411 participants. Retinal images were analyzed using a fully automated validated computerized system that provides novel measures of vessel morphometry.

Methods: Associations between cardiometabolic risk factors, chronic disease, and retinal markers were analyzed using multilevel linear regression, adjusted for age, gender, and within-person clustering, to provide percentage differences in tortuosity and absolute differences in width.

Main outcomes measures: Retinal arteriolar and venular tortuosity and width.

Results: In all, 279 802 arterioles and 285 791 venules from 5947 participants (mean age, 67.6 years; standard deviation [SD], 7.6 years; 57% female) were analyzed. Increased venular tortuosity was associated with higher body mass index (BMI; 2.5%; 95% confidence interval [CI], 1.7%-3.3% per 5 kg/m²), hemoglobin A1c (HbA1c) level (2.2%; 95% CI, 1.0%-3.5% per 1%), and prevalent type 2 diabetes (6.5%; 95% CI, 2.8%-10.4%); wider venules were associated with older age (2.6 μm; 95% CI, 2.2-2.9 μm per decade), higher triglyceride levels (0.6 μm; 95% CI, 0.3-0.9 μm per 1 mmol/l), BMI (0.7 μm; 95% CI, 0.4-1.0 per 5 kg/m²), HbA1c level (0.4 μm; 95% CI, -0.1 to 0.9 per 1%), and being a current smoker (3.0 μm; 95% CI, 1.7-4.3 μm); smoking also was associated with wider arterioles (2.1 μm; 95% CI, 1.3-2.9 μm). Thinner venules were associated with high-density lipoprotein (HDL) (1.4 μm; 95% CI, 0.7-2.2 per 1 mmol/l). Arteriolar tortuosity increased with age (5.4%; 95% CI, 3.8%-7.1% per decade), higher systolic blood pressure (1.2%; 95% CI, 0.5%-1.9% per 10 mmHg), in females (3.8%; 95% CI, 1.4%-6.4%), and in those with prevalent stroke (8.3%; 95% CI, -0.6% to 18%); no association was observed with prevalent myocardial infarction. Narrower arterioles were associated with age (0.8 μm; 95% CI, 0.6-1.0 μm per decade), higher systolic blood pressure (0.5 μm; 95% CI, 0.4-0.6 μm per 10 mmHg), total cholesterol level (0.2 μm; 95% CI, 0.0-0.3 μm per 1 mmol/l), and HDL (1.2 μm; 95% CI, 0.7-1.6 μm per 1 mmol/l).

Conclusions: Metabolic risk factors showed a graded association with both tortuosity and width of retinal venules, even among people without clinical diabetes, whereas atherosclerotic risk factors correlated more closely with arteriolar width, even excluding those with hypertension and cardiovascular disease. These noninvasive microvasculature measures should be evaluated further as predictors of future cardiometabolic disease.