Hypertension Research (2009) 32, 975–982 & 2009 The Japanese Society of Hypertension All rights reserved 0916-9636/09 $32.00 www.nature.com/hr ORIGINAL ARTICLE Effect of blood pressure on the retinal vasculature in a multi-ethnic Asian population V Swetha E Jeganathan1,2, Charumathi Sabanayagam2,3, E Shyong Tai4, Jeannette Lee3, Cong Sun1, Ryo Kawasaki1, Sangeetha Nagarajan2, Maisie Ho Huey-Shi2, Mya Sandar2 and Tien Yin Wong1,2 Blood pressure has a significant effect on retinal arterioles. There are few data on whether this effect varies by race/ethnicity. We examined the relationship of blood pressure and retinal vascular caliber in a multi-ethnic Asian population. The study is population-based and cross sectional in design. A total of 3749 Chinese, Malay and Indian participants aged X24 years residing in Singapore were included in the study. Retinal vascular caliber was measured using a computer program from digital retinal photographs. The associations of retinal vascular caliber with blood pressure and hypertension in each racial/ethnic group were analyzed. The main outcome measures are retinal arteriolar caliber and venular caliber. The results show that retinal arterioles were narrower in persons with uncontrolled/untreated hypertension (140.0 lm) as compared with persons with controlled hypertension (142.1 lm, P¼0.0001) and those with no hypertension (146.0 lm, Po0.0001). On controlling for age, gender, body mass index, lipids and smoking, each 10 mm Hg increase in mean arterial blood pressure was associated with a 3.1 lm decrease in arteriolar caliber (Po0.0001), with a similar magnitude seen in all three racial/ethnic groups: 3.1 lmin Chinese, 2.8 lm in Malays and 3.2 lm in Indians (Po0.0001 for all). Each 10 mm Hg increase in mean arterial blood pressure was associated with a 1.8 lm increase in venular caliber (Po0.0001); furthermore, the magnitude of this effect was similar across the three racial/ethnic groups. The effect of blood pressure on the retinal vasculature was similar across three major racial/ethnic groups in Asia. Hypertension Research (2009) 32, 975–982; doi:10.1038/hr.2009.130; published online 28 August 2009 Keywords: arteriolar narrowing; blood pressure; epidemiology; retinal arteriolar caliber; retinal venular caliber INTRODUCTION in the development of new treatment strategies targeted at Hypertension affects multiple organs in the body, including the retinal microcirculation.16 vasculature. Retinal arteriolar narrowing is a marker of the early However, whether the effects of BP on the retinal microvasculature are structural microvascular damage associated with chronic hyperten- similar across different racial/ethnic groups remains unclear. There are sion.1–3 Recent population-based studies using computer-based meth- well-recognized racial/ethnic differences in the association between BP ods to measure retinal vascular caliber from fundus photographs have and other markers of end-organ damage, including subclinical and now established the strong linear relationship between elevated blood clinical coronary artery disease,17 left ventricular hypertrophy,18 kidney pressure (BP) and the severity of retinal arteriolar narrowing.4–6 Newer disease19 and cerebrovascular disease.20 Previous studies on the relation- analyses suggest that elevated BP may also have a weaker effect on ship of BP on the retinal vasculature have been conducted in predomi- retinal venules.7–9 Prospective studies have further shown that retinal nantly Caucasian populations,7,9,21,22 with few studies in Asians,23,24 and arteriolar narrowing predicts the incidence of hypertension10–12 and even fewer directly comparing racial/ethnic differences.22 clinical cardiovascular events, such as stroke and coronary heart disease, The purpose of this study is to examine the relationship between independent of traditional risk factors.13–15 As such, an assessment of BP and retinal vascular caliber in a multi-ethnic Asian population of retinal vascular caliber may provide insights into early microvascular Chinese, Malays and Indians in Singapore. These three racial/ethnic effects before the onset of clinical hypertension, and may help groups in Asia represent more than two-third of the world’s population. 1Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, Melbourne, Victoria, Australia; 2Singapore Eye Research Institute, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; 3Department of Community, Occupational and Family Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore and 4Department of Endocrinology, Singapore General Hospital, Singapore Correspondence: Dr TY Wong, Singapore Eye Research Institute, Yong Loo Lin School of Medicine, Royal Victorian Eye and Ear Hospital, National University of Singapore, 11 Third Hospital Avenue, 168751, Singapore. E-mail: [email protected] Meeting Presentation: Royal Australian and New Zealand College of Ophthalmologists Congress, Melbourne, Australia, November 2008. Received 31 March 2009; revised 20 July 2009; accepted 20 July 2009; published online 28 August 2009 Retinal vascular caliber and blood pressure VSE Jeganathan et al 976 METHODS clinic, and 6 had left the country. Participants were contacted first through Study population mail, then by phone and if there was no response or no available phone This study used data from the Singapore Prospective Study Program and number, interviewers visited the home; three different home visits were made Singapore Cardiovascular Cohort Study 2, which included participants from before participants were deemed non-contactable (2292 individuals). Another one of four previous cross-sectional studies: Thyroid and Heart Study 1982– 30 contacted participants refused to participate, leaving 7742 who were 1984,25 National Health Survey 1992,26 National University of Singapore Heart interviewed at their homes. The interviewer-administered questionnaire Study 1993–199527 or National Health Survey 1998.28 All studies involved a included data on demographic and lifestyle (alcohol intake, smoking) factors random sample of individuals from the Singapore population, aged 24–95 as well as medical history. years, with disproportionate sampling stratified by ethnicity to increase the All 7742 participants were then invited for a clinical examination that number of minority ethnic groups (Malays and Indians). The Ministry of included systemic and ocular examination, retinal photography and laboratory Health, Singapore, selected the study population. investigations, of which 5157 attended. Logistic constraints, due to availability Figure 1 shows a flow diagram of subjects that were considered for inclusion of one retinal camera, resulted in only 1 in 2 Chinese participants (the group in the study. From 2003 to 2007, all 10 747 participants were invited to with the largest sample size) who were asked to undergo retinal photography participate in this study by linking their unique national identification numbers between 19 March 2005 and 20 February 2006. Consequently, 1020 (of 5517) with national registries; 85 individuals had errors in their identification Chinese participants did not undergo retinal photography. Out of the remain- (national registration identity card) number (preventing linkage to national ing 4137 participants, retinal photographs were obtained for virtually all those registries), 555 had died before contact was made, 37 died before attending the who underwent the procedure (4098 or 99.1% of 4137). Participants with Thyroid Heart National University of National Health National Health Study Singapore Heart Study (NUH) Survey 1992 Survey 1998 (THS) [1982-1984] [1993-1995] N=982 (NHS92) (NHS98) 10747 Subjects Qualify 592 Die 6 Emigrate 85 Errors in NRIC 10064 Subjects Qualify 2292 Subjects Not Available 7772 Subjects Contacted 30 Subjects Refused 7742 Subjects Complete Questionnaire 2585 Subjects Decline Health Screening 5157 Subjects Complete Health Screening 1020 Subjects with No Retinal Photography 4137 Subjects with Retinal Photography 29 Subjects 297 Subjects 3748 Subjects with 20 Missing 43 Other with Available Unavailable Glucose Missing Ungradable for Retinal Variables Variables Photography Photography Final Analysis Figure 1 Flow diagram of subjects that were considered for inclusion in the study. Hypertension Research Retinal vascular caliber and blood pressure VSE Jeganathan et al 977 ungradable retinal photographs (n¼297),missinginformationonBPorother the fovea, identical to the Early Treatment for Diabetic Retinopathy Study relevant variables (n¼52) were then excluded, leaving 3749 for the final analysis standard fields 1 and 2.30 (48.4% of 7742 eligible participants). Excluded participants were found to be Retinal vascular caliber was measured at the Retinal Vascular Imaging older and had higher high-density lipoprotein cholesterol, systolic BP and Centre, University of Melbourne using a computer-assisted software (IVAN, lower low-density lipoprotein cholesterol (all significant at Po0.05) than University of Wisconsin, Madison, WI, USA) according to the standardized included participants. The Code of Ethics of the World Medical Association protocol used in other population-based studies.22,23,31 A trained grader, (the Declaration of Helsinki Principles, 1964 and Declaration of Tokyo, 1975, as masked to participant characteristics, carried out the vessel measurements on revised in 1983) was followed, and institutional review board approval was the