Cardiovascular Risk Factors and Retinal Vessel Calibre. What is the Longitudinal Relationship?

Abstract

Background: Cardiovascular disease is a leading cause of death worldwide. Retinal vessel calibre is a non-invasive in vivo marker of cardiovascular disease and is linked to cardiovascular risk factors. However, the longitudinal impact of cardiovascular risk factors on retinal vessel calibre is unknown.

Hypothesis: Retinal vessel calibre at early middle age is influenced by longitudinally measured cardiovascular risk factors from early childhood.

Method: Simple and multiple linear regression analysis of longitudinal data from the Dunedin Study (n=1037 at birth) was performed with age and sex stratification and adjustment for cardiovascular risk factors and socioeconomic status. The dependent variable was retinal vessel calibre (arterioles and venules) at age 38 and the independent variables were blood pressure (ages 7, 9, 11, 13, 15, 18, 26, 32 and 38), body mass index (all phases), glycated haemoglobin, lipids, inflammatory markers, smoking, endothelial function and cardiorespiratory fitness variably assessed between ages 3, 5, 7, 9, 11, 13, 15, 18, 21, 26, 32 and 38. A group based trajectory model for systolic blood pressure was also used as an independent variable.

Results: Elevated blood pressure from ages 7 through to 38 was consistently and significantly associated with narrower arterioles and wider venules at age 38. At age 7 every 10 mmHg rise in systolic blood pressure was associated with age 38 arteriolar narrowing of 1.42 µm in females and 1.38 µm in males; and age 38 venular widening of 1.81 µm in females and 1.66 µm in males, p < 0.05, after adjusting for covariates. Trajectory modelling showed the highest blood pressures at ages 7 and 11 continued to age 32 and 38 as hypertensives with significant arteriolar narrowing at age 38 (15.20 µm narrower in females and 6.64 µm narrower in males (p<0.05) compared with normotensives) in a clinically meaningful manner with evidence of a dose response in multiple linear regression analysis.

Novel findings in this study includes statistically significant associations between greater cardiorespiratory fitness and wider arterioles (females: β = 0.337, p < 0.001, males: β = 0.321, p <0.001) and narrower venules (females: β = - 0.311, p = 0.004, males: β = - 0.351, p < 0.001) with adjustment for fellow retinal vessel calibre. This significance was lost when adjusted for other covariates. Better level of endothelial function was significantly associated with wider venules in multiple linear regression analysis for males (β = 4.403, p = 0.006).

Many of the other variables either had no statistically significant association or non-consistent statistically significant association with retinal vessel calibre in multiple linear regression analysis.

Conclusion: The major finding of this study is that childhood through early mid-life blood pressure and the trajectories of blood pressure from childhood to early mid-life predict retinal vessel calibre in early midlife which is a predictor of cardiovascular events and mortality. These data suggest the effects of elevated blood pressure manifest early in life and are sustained into adulthood.