Correlation of systemic arterial stiffness with changes in retinal and choroidal microvasculature in type 2 diabetes

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Abstract

This study was conducted to assess whether systemic arterial stiffness, indicated by cardio-ankle vascular index (CAVI), is related to changes in the microvasculature of the retina and choroid in diabetes mellitus (DM). This study included 113 patients with a confirmed diagnosis of type-2 DM. Among them, 18 patients did not have diabetic retinopathy (DR), 71 had non-proliferative DR (NPDR), and 24 had proliferative DR (PDR). The mean CAVI was 7.58 ± 1.41 in no DR, 8.72 ± 1.47 in NPDR, and 8.43 ± 1.25 in PDR group. Of the 113 eyes, 42 (37.2%) were classified as abnormal CAVI group (CAVI ≥ 9). This group had significantly higher cardiac autonomic neuropathy risk index score, decreased central choroidal thickness, and decreased choroidal vascularity index (CVI). Deep foveal avascular zone area was higher in the abnormal CAVI group. After adjustment for possible confounding factors, CAVI showed negative correlation with the CVI (r = −0.247, P = 0.013). In conclusion, there was a significant correlation between arteriosclerosis and choroidal vascular changes in DR. We suggest prompt ophthalmic evaluation in patients with systemic arteriosclerosis. If the ophthalmologist notes advanced DR, the patient should be referred to a cardiovascular clinic for detailed evaluation of systemic arteriosclerosis.

Introduction

Arterial stiffness is a term used to describe the degree of vascular rigidity due to reduced elasticity of the artery. Many studies have demonstrated the predictive value of arterial stiffness on systemic cardiovascular diseases1,2,3,4,5. The most important factor determining arterial stiffness is age; the elasticity of the arterial wall decreases with age and arterial stiffness increases. In addition, increased arterial stiffness can occur as a result of elevated blood pressure, smoking, obesity, and other systemic vascular diseases including diabetes mellitus (DM)6.

Arterial stiffness, termed arteriosclerosis, can be assessed noninvasively by measuring the pulse wave velocity (PWV)1, central blood pressure (CBP)7, or cardio-ankle vascular index (CAVI)8. Among these, CAVI is superior to PWV because it is not affected by blood pressure at the time of measurement8,9. CAVI increases with age. It is high in many arteriosclerotic diseases, such as cerebrovascular diseases, chronic kidney disease, carotid arteriosclerosis, and coronary artery disease; it is also related to many coronary risk factors including smoking, DM, hypertension, and dyslipidemia8.

Atherosclerosis is a narrowing of the arteries caused by a buildup of plaque, and the term is sometimes used as a specific subtype of arteriosclerosis. Atherosclerosis can be assessed by measuring the ankle-brachial index (ABI) or intima-media thickness of the common carotid artery. Studies on the association between arterial stiffness and atherosclerosis showed conflicting results10,11.

Recent advances in multimodal imaging have facilitated many studies on microvascular changes in diabetic retinopathy12,13,14,15. Further, attempts have been made to quantitatively analyze diabetic microvascular changes of the retina and choroid. In patients with DM, increased foveal avascular zone area12, decreased retinal perfusion density12,14, and decreased choroidal vascularity index (CVI)15 were associated with worsening diabetic retinopathy (DR). Moreover, in patients with DM, these microvascular changes were evident even without DR.

Generally, DR is a metabolic disorder caused by hyperglycemia, and it shares common risk factors with other diabetic microvascular complications including diabetic nephropathy and neuropathy. Some previous studies identified a relationship between diabetic retinopathy and systemic endothelial dysfunction with peripheral arterial stiffness16,17,18. However, these studies evaluated only the presence of DR18 or the grade of severity of DR16,17. To date, the association between arterial stiffness and diabetic ocular microvascular changes using quantitative vascular parameters has not been explored. Further, the underlying mechanism and the association between large-artery stiffness and diabetic ocular microvascular changes remain unclear.

In this study, we evaluated the CAVI and the quantitative vascular parameters of the retina and choroid in patients with type 2 DM. The aim of the current study was to assess whether systemic arterial stiffness, as indicated by CAVI, has an association with changes in the microvasculature of the retina and choroid in type 2 DM.

Results

In total, 113 eyes of patients with diabetes were included in this study. We have summarized the demographic, ocular, and systemic characteristics of the subjects according to the severity of diabetic retinopathy in Table 1. Of the 113 eyes, 18 (15.9%) were classified as no DR, 71 (62.8%) as non-proliferative DR (NPDR), and 24 (21.2%) as proliferative diabetic retinopathy (PDR). There were no significant differences with regard to age, sex, blood pressure, visual acuity, intraocular pressure, or refractive error among the 3 groups. Disease duration (P < 0.001), glycated hemoglobin (HbA1c) (P < 0.001), and glycoalbumin level (P = 0.030) differed significantly between each DR group. The mean CAVI was 7.58 ± 1.41 in the no DR, 8.72 ± 1.47 in NPDR, and 8.43 ± 1.25 in the PDR group (P = 0.012). If the ABI was set into ordinal variables (as normal versus abnormal ABI), advanced DR severity and abnormal ABI showed a significant correlation (P = 0.042, linear-by-linear association test). However, the mean ABI was 1.06 ± 0.14 in the no DR, 1.05 ± 0.10 in NPDR, and 1.10 ± 0.10 in the PDR group; the differences were not statistically significant (P = 0.162).Tables 2 and 3 display comparisons of demographic and clinical data according to CAVI and ABI values. Of the 113 eyes, 42 (37.2%) were classified as abnormal CAVI group (CAVI ≥ 9). cardiac autonomic neuropathy (CAN) risk index score was significantly higher in the abnormal CAVI group (62.54 ± 20.23 and 71.15 ± 14.33, for CAVI < 9 and CAVI ≥ 9, respectively, P = 0.018). We noted decreased central choroidal thickness (P = 0.002) and decreased CVI (P = 0.041) in the abnormal CAVI group. Deep foveal avascular zone (FAZ) area was higher in the abnormal CAVI group (0.62 ± 0.28 and 0.79 ± 0.36, for CAVI < 9 and CAVI ≥ 9, respectively, P = 0.005). However, retinal microvascular parameters including superficial FAZ area, superficial and deep FAZ circulatory index, and superficial and deep capillary vessel density showed no significant differences between the two CAVI groups (all P values > 0.05). Of the 113 eyes, 34 (30.1%) were classified as abnormally low or high ABI (ABI < 0.9 or ≥1.3). There were no significant differences in terms of ocular microvascular parameters between the two ABI groups (all P values > 0.05).

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