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Factors Associated with Changes in Retinal Microcirculation After Antihypertensive Treatment

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Factors Associated with Changes in Retinal Microcirculation After Antihypertensive Treatment Journal of Human Hypertension (2014) 28, 310–315 & 2014 Macmillan Publishers Limited All rights reserved 0950-9240/14 www.nature.com/jhh ORIGINAL ARTICLE Factors associated with changes in retinal microcirculation after antihypertensive treatment P-R Antonio1, P-S Marta1, DDJ Luı´s2, DPJ Antonio3, ST Manuel4, MS Rafael5, GV Sonia6, GP Manuel6, M-N Isabel7, ENJ Carlos7, C-d-T Gabriel8 and G-UI Francisco9 We report the results of hypertensive treatment over retinal arteriole narrowing in a group of 189 hypertensive patients during a 6-month treatment programme for hypertension. These patients were included in an observational study under clinical practice conditions and analysed using digital photographs of the eye fundus with a previously described semiautomatic snakes method. We analysed the relation between blood pressure control and retinal microcirculation changes during the treatment. We included 189 hypertensive patients; 74.0% of them had BP under control after 6 months of follow-up. The arteriovenous ratio (AVR), measured as the relation between the average retinal arteriole and venous diameter, significantly increased after 6 months of follow-up in both eyes (right eye AVR: 0.769±0.065 vs 0.799±0.066 (Po0.0001); left eye AVR: 0.770±0.065 vs 0.796±0.071 (Po0.0001)). AVR changes were caused by increases in arteriole diameter. No linear correlation was found between blood pressure- lowering levels and AVR increase, suggesting that other factors could be involved in the regression of retinal changes. We conclude that in our group of hypertensive patients it was possible to increase the retinal arteriole diameter, expressing an improvement in retinal microcirculation after 6 months of adequate BP control. Although there is an inverse tendency between blood pressure and arteriovenous ratio changes, we could not find a linear correlation between these changes. Journal of Human Hypertension (2014) 28, 310–315; doi:10.1038/jhh.2013.108; published online 21 November 2013 Keywords: arteriovenous ratio; blood pressure; retinal microcirculation INTRODUCTION locates the region of interest (ROI) – that is, the optic nerve. Second, the Early alterations in retinal microcirculation are observed in most system detects the vascular tree and measures the vessel calibre in several circumferences concentric to the optic disc. Then, the user selects the set hypertensive patients seen in daily practice (that is, retinal of vessels suitable for estimating the arteriovenous ratio and classifies arteriole narrowing or arteriovenous nicking without exudates or these vessels into arteries and veins. Finally, the system estimates the AVR haemorrhage causing damage to the retina itself), and these as the ratio between the average artery and vein vessel calibres. changes are subjective, imprecise and poorly reproducible. As per The snake-based method has high sensitivity and increases the hypertension guidelines, a method is necessary that objectively specificity of the previously described linear method. assesses these changes in hypertensive patients so that a valuable This is a post-authorisation, observational, prospective and multi-centre prognosis can be arrived at. study that was conducted under daily practice conditions at the We described elsewhere a semiautomatic computerised system Department of Internal Medicine of the Hospital de Conxo in Santiago for the evaluation of the calibre of retinal blood vessels that has de Compostela, Hospital Abente Lago and San Rafael de A Corun˜a, Hospital 1 de Barbanza, Hospital Xeral Calde in Lugo (Spain). Except for the shown very good reproducibility. In a later study, we described a photographs of the retina used as measurement instruments for the main semiautomatic method based on the snakes model that has better 2 objective of the study, the patients were not subjected to any diagnostic or reliability. follow-up procedure other than the usual in daily practice. Photographs Here we report the results of hypertensive treatment on retinal were taken at each hospital by an ophthalmologist and were analysed arteriole narrowing in a group of 189 hypertensive patients during both locally and centrally at Hospital de Conxo in Santiago de Compostela. a 6-month treatment programme with Telmisartan plus Hydro- Digital photographs were taken following pupillary dilatation with chlorothiazide under clinical practice conditions that were pilocarpine and phenylephrine using a TRC-50 IA camera connected to analysed with the previously described semiautomatic method. an Imagenet 1024 system (both from Topcon Instruments, Paramus, NJ, We analysed the relation between blood pressure control and USA). Photographs were taken with a 1280 Â 1024 pixel resolution for an adequate contrast for vessel differentiation. This study was approved by retinal microcirculation changes during the treatment. the authonomic, ethical and clinical investigation committee. Patients in the study were both male and female and were aged 18 or older with grade 1 or grade 2 essential hypertension with novo or previous MATERIALS AND METHODS diagnosis of hypertension, who had uncontrolled BP regardless of whether The semiautomatic snakes method was developed to evaluate retinal they had other vascular risk factors and/or lesions in the target organ and blood vessel calibre, and it is composed of four main steps. First, the user were treated with telmisartan as monotherapy or in combination with a 1Department of Internal Medicine, Hospital de Conxo Medicine Deparment, Complexo Hospitalario Universitario de Santiago de Compostela, Spain; 2Department of Internal Medicine, Hospital Abente y Lago, ACorun˜a, Spain; 3Department of Internal Medicine, Hospital Barbanza, Ribeira, Spain; 4Department of Internal Medicine, Hospital San Rafael, A Corun˜a, Spain; 5Department of Internal Medicine, Hospital Lucus Augusti, Lugo, Spain; 6Department of Electronics and Computation (Artificial Vision Group) University of A Corun˜a, A Corun˜ a, Spain; 7Department of Econometrics, University of Santiago de Compostela, Santiago de Compostela, Spain; 8Assistance Healthcare Institute Angle`s, Girona, Spain and 9Department of Ophthalmology, Hospital de Conxo, Complexo Hospitalario Universitario de Santiago de Compostela, Santiago de Compostela, Spain. Correspondence: Professor P-R Antonio, Department of Internal Medicine, Hospital de Conxo, Complexo Hospitalario Universitario de Santiago de Compostela, Ru´a Ramo´n Baltar s/n, Santiago de Compostela 15706, Spain. E-mail: [email protected] Received 21 June 2013; revised 31 July 2013; accepted 19 August 2013; published online 21 November 2013 Factors associated with changes in retinal microcirculation P-R Antonio et al 311 diuretic following daily standard practice. All patients gave their written in retinal microcirculation was considered to exist when the arteriovenous informed consent. ratio had increased between the final visit and the baseline visit). Patients whose participation was not recommended in the opinion of Every eye fundus photograph was taken by a local researcher from the the physician investigator or for whom it was not possible to take a digital hospital where the patient was being treated and was analysed by local photograph of the eye fundus were excluded from the study. Also research and by an expert from the main research centre. Concordance excluded were those for whom the treatment was contraindicated in the between the two evaluators regarding the arteriovenous ratio and the data sheet—namely, diabetic patients with advanced diabetic retinopathy. artery and venous diameters was assessed using the Bland–Altman The observation period of the patients was 6 months. Recommendations method, along with a histogram of the difference between measurement in the Telmisartan’s data sheet were observed, and dosage was adjusted to and the Spearman correlation coefficient between measurements. the requirements of each patient and as per medical opinion. If the patient Statistical analyses were carried out using the SAS version 9.2 statistical did not reach target values for BP control, the dose of Telmisartan was package. titrated each month during the study period and if necessary thiazide was added. The decision to prescribe the study drug must have been taken earlier and before suggesting to the patient the possibility of participating in the RESULTS study and must not have been influenced by the patient’s potential A total of 189 patients were included. Table 1 shows the participation in the study. anthropometric characteristics of the sample. Not considered in our study was a washout period in patients who had Of the patients, 53% were male; at baseline, 114 (52.5%) undergone previous antihypertensive treatment because this is a prospective observational study conducted under conditions of routine patients were seen to suffer from dyslipidaemia, 58 (26.7%) were clinical practice. smokers and 32 (14.7%) were diabetic. In 28 patients, a digital Calculation of the sample size was established on the basis of both the photograph of the eye fundus could not be taken, as there was no main objective and the main variable of the study. On the basis of previous adequate fundus camera available. studies3 from a binomial distribution, an estimation was made of the In all, 66.8% of patients received a dose of 80 mg on completion proportion of hypertensive patients treated with telmisartan where the of the study and 27.9% received a dose of 160 mg; 60.9% of retinal arteriovenous ratio increased after 6 months of treatment
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