This study provides evidence that retinal arteriolar tortuosity shows appreciable variation between individuals in childhood and is positively associated with established cardiovascular risk factors (including triglyceride, total and LDL cholesterol, systolic and diastolic blood pressure). These findings raise the possibility that early markers of cardiovascular disease, such as higher blood lipids (in particular triglyceride levels) and blood pressure, influence retinal arteriolar tortuosity during the first decade of life.
Cardiovascular disease has long been viewed as a disease originating in middle age. However, there is now substantial evidence from pathological studies,22-24
and combined pathological-epidemiological studies32;33
that CHD risk originates earlier in life and that abnormalities in arterial structure and function are apparent before adult life. Abnormalities of retinal microvasculature, particularly affecting the arterioles, are known to be related to cardiovascular disease and CHD in adult life.1-3;34;35
However, less is known about changes in the morphology of retinal vessels amongst populations without overt cardiometabolic disease. Studies that do exist have focused on the measurement of vessel width, both in adults 8;9
Measures of width are more difficult in children with prominent vessel reflexes (especially on arterioles), and in different ethnic groups with varying levels of refractive error (with higher levels of myopia amongst Asians)19;36;37
and background levels of retinal pigmentation (with higher levels amongst black African-Caribbeans – see ). Measuring vessel tortuosity offers another morphological characteristic of the vascular network, which we found was less sensitive to these difficulties.12
and is effectively independent of vessel width. The findings from this study are consistent with earlier studies that have shown a positive association between retinal vessel tortuosity (assessed subjectively) and hypertension, both in child and adult populations,4;5;38
and amongst those with severe coronary disease.39
However, not all studies have been consistent in their findings.40;41
This may reflect the unreliability of subjective assessment of tortuosity in many of these earlier studies. Objective measures of tortuosity will avoid measurement error inherent with subjective assessment (especially at lower levels of tortuosity).13
Strengths and limitations
We have used a novel measure of tortuosity based on a subdivided chord length method (chosen a priori) that has been validated against subjective assessment in this age group, which shows good agreement and repeatability across a broad range of vessel tortuosity,13
from smoothly curved to highly tortuous retinal vessels in infants with retinopathy of prematurity.20
Moreover, unlike dimensional measurements (such as width), we have also shown that the tortuosity measure is relatively unaffected by refractive error 13
and is therefore likely to be particularly valid in this multi-ethnic population with large differences in ametropia and ocular biometry.19
Other strengths of this study include the appreciable sample size and multi-ethnic population, designed to detect modest differences in risk markers between major ethnic groups (white European, South Asian, black African Caribbean).14
Overall response rates were high with little difference between ethnic groups. The slightly lower response rate in black African-Caribbeans is unlikely to invalidate the results as there was no strong evidence of ethnic difference in the pattern of association between tortuosity and cardiovascular risk factors (except perhaps for blood cholesterol). Response rates for blood sampling were slightly lower (as expected), but this is unlikely to have affected the associations observed, especially as those with extremes in arteriolar tortuosity are unlikely to know and choose not to participate. The cross sectional nature of the present study means that it cannot be assumed that cardiovascular risk factors caused increased retinal arteriolar tortuosity. Indeed, it is plausible that more tortuous microcirculation may lead to higher blood pressure.
We have observed appreciable variation in retinal arteriolar tortuosity and associations with established cardiovascular risk factors that were consistent in boys and girls and across ethnic groups. Our results suggest that unfavourable cardiovascular risk profiles in childhood may be having adverse effects on arteriolar structure and function in the first decade of life. The strength, consistency and graded associations observed between several established cardiovascular risk factors and retinal arteriolar tortuosity suggest that the associations, very unlikely to have occurred by chance, may be causal. However, biological mechanisms for the findings remain uncertain, especially the strong positive association with triglycerides. The mechanisms by which blood lipids influence the wall of larger arteries are not likely to apply to arterioles; blood pressure could be having a mechanical influence on arteriolar structure and function.42
Further research in population based studies is needed to clarify the associations between cardiovascular risk factors and retinal arteriolar tortuosity, and the relations between retinal arteriolar tortuosity and other markers of vascular structure and function. Prospective studies will also be useful in establishing the time sequence of these associations. In addition, more evidence on other potential determinants of retinal arteriolar tortuosity, including early life factors (such as birthweight and/or gestation),43;44
childhood lifestyle (including physical activity) and genetic predisposition41
may also be important in this context. We examined objective measures of physical activity in our study,45
but found no evidence of an association with arteriolar tortuosity (data not presented). The associations observed suggest that retinal arteriolar tortuosity may be influenced by cardiovascular risk factors in early life.