In this population-based study of British people of African-Caribbean and European descent, we have demonstrated for the first time that specific quantitative measures of retinal microvascular structure differ by ethnicity and diabetes status.
Compared with Europeans, the relationship between arteriolar diameters at bifurcations was less optimal in African Caribbeans. We interpret the less optimal arteriolar bifurcations observed in African Caribbeans as indicative of impaired microvascular endothelial function in the cerebrovascular microcirculation [8, 9], and suggest that this might play a causal role in their elevated risk of stroke. Neither diabetes nor BP explained the ethnic difference in bifurcation optimality.
In contrast, arteriolar narrowing in African Caribbeans was explained by higher BPs. In our study, arteriolar narrowing was strongly associated with BP in people without diabetes in both ethnic groups, but this association was lost in people with diabetes. This is similar to the findings of the Cardiovascular Health Study, where relationships between BP and generalised arteriolar narrowing were weaker in diabetic than in non-diabetic individuals . Reasons for this attenuation of the relationship between LDR and BP in diabetes are not known. The reduction of arteriolar diameter increases resistance to blood flow but also serves to protect the capillary bed from the potentially damaging effects of elevated systemic BP. We hypothesise that the increase in arteriolar narrowing in response to elevated BP is impaired in insulin-resistant states, so that no association between LDR and BP is observed. Diabetes is well recognised to result in loss of autoregulation in the retinal circulation, and insulin resistance is also associated with altered cerebrovascular autoregulation. These observations provide a plausible mechanism for the greatly elevated stroke mortality rates in African Caribbeans with diabetes.
Limitations of the study include 28% and 16% of African Caribbeans and Europeans with unanalysable images. It is conceivable that people with more severe retinal disease would be more likely to have unanalysable images and that this might vary by ethnicity. However, there was nothing to suggest that this was the case and the baseline characteristics of the group with analysable images were similar to those of the whole study group; in any case such a scenario would tend to result in underestimation of between group differences.
We adjusted for the effects of antihypertensive medications by ranking people receiving treatment for hypertension as if they had the highest levels of BP; however, similar effects were observed when we adjusted our models for BP without taking medication use into account and when we excluded people receiving antihypertensive medications—this suggests that the effects of BP are independent of treatment.
Although we did not detect any significant interactions between ethnicity and other measured risk factors including sex, the study was not sufficiently powered to detect small interactions. However, effects of missed interactions are again likely to lead to underestimation of ethnic group differences.
Further limitations relate to the cross-sectional nature of the study. It is not possible to draw conclusions as to whether BP and glucose homeostasis are on the causal pathway to the observed retinal vascular findings, or whether suboptimal microvascular structure and function precede impaired glucose homeostasis and hypertension.
By focusing on two a priori primary outcome measures, we attempted to avoid multiple statistical testing in our main analyses, but acknowledge that the strength of associations between LDR, diabetes and ethnicity are relatively weak.
However, these associations offer a plausible explanation for at least part of the ethnic disparity in stroke risk and lead us to hypothesise that cerebral autoregulation and structural remodelling might be adversely affected in the presence of diabetes in both ethnic groups. Microvascular endothelial dysfunction, together with impaired arteriolar structure and function in association with diabetes, presents a possible explanation for the increased risk of stroke experienced by people of African-Caribbean origin. Prospective evidence is required to substantiate these hypotheses.