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Retinal vascular caliber and the development of hypertension: a meta-analysis of individual participant data

Ding, Jiea,b; Wai, Khin Layc; McGeechan, Kevind; Ikram, M. Kamrana,b,e; Kawasaki, Ryof; Xie, Jingf; Klein, Ronaldg; Klein, Barbara B.K.g; Cotch, Mary Francesh; Wang, Jie Jinf,i; Mitchell, Pauli; Shaw, Jonathan E.j; Takamasa, Kayamak; Sharrett, A. Richeyl; Wong, Tien Y.a,b,efor the Meta-Eye Study Group

doi: 10.1097/HJH.0b013e32836586f4

Objective: Microvascular dysfunction has been suggested to be a major pathogenic factor for the development of hypertension. We examined the association between retinal vascular caliber, a marker of systemic microvascular dysfunction, and incident hypertension on a meta-analysis of individual participant data.

Methods: We performed a systematic review with relevant studies identified through a search of electronic databases, a review of reference lists, and correspondence with experts. Studies were included if participants were selected from a general population, retinal vascular caliber was measured from photographs using computer-assisted methods at baseline, and individuals were followed up to ascertain the incidence of hypertension. Prespecified individual recorded data from six population-based prospective cohort studies were included. Discrete time proportional odds models were constructed for each study with adjustment for hypertension risk factors. Log odds ratios (ORs) per 20-μm difference were pooled using random-effects meta-analysis.

Results: Among 10 229 participants without prevalent hypertension, diabetes, or cardiovascular disease, 2599 developed new-onset hypertension during median follow-up periods ranging from 2.9 to 10 years. Both narrower retinal arterioles [pooled multivariate-adjusted OR per 20-μm difference 1.29, 95% confidence interval (CI) 1.20–1.39] and wider venules (OR per 20-μm difference 1.14, 95% CI 1.06–1.23) were associated with an increased risk of hypertension. Each 20 μm narrower arterioles at baseline were associated with a 1.12 mmHg (95% CI 0.25–1.99) greater increase in SBP over 5 years.

Conclusions: Retinal arteriolar narrowing and venular widening were independently associated with an increased risk of hypertension. These findings underscore the importance of microvascular remodeling in the pathogenesis of hypertension.

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aSingapore Eye Research Institute, Singapore National Eye Centre

bDepartment of Ophthalmology

cInvestigational Medicine Unit, National University of Singapore, Singapore

dSydney School of Public Health, University of Sydney, Australia

eEye Academic Clinical Program, Duke-NUS Graduate Medical School, Singapore

fCentre for Eye Research Australia, University of Melbourne, Australia

gDepartment of Ophthalmology & Visual Sciences, School of Medicine & Public Health, University of Wisconsin, Madison

hDivision of Epidemiology and Clinical Applications, National Eye Institute, National Institutes of Health, Bethesda, Maryland, USA

iDepartment of Ophthalmology and Westmead Millennium Institute, Centre for Vision Research, University of Sydney, Sydney

jBaker IDI Heart and Diabetes Institute, Melbourne, Australia

kThe Global COE Investigators, Yamagata University, Yamagata, Japan

lDepartment of Epidemiology, John Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA

Correspondence to Tien Y. Wong, MD, PhD, Singapore Eye Research Institute, National Eye Centre, 11 Third Hospital Avenue, Singapore 168751, SingaporeTel: +65 63224571; fax: +65 63231903; e-mail:

Abbreviations: ARIC, Atherosclerosis Risk in Communities; AusDiab, Australian Diabetes Obesity and Lifestyle; AVR, arteriolar-to-venular diameter ratio; BDES, Beaver Dam Eye Study; BMES, Blue Mountains Eye Study; CRAE, central retinal arteriolar equivalent; CRVE, central retinal venular equivalent; CVD, cardiovascular disease; IQR, interquartile range; MABP, mean arterial blood pressure; MESA, Multi-Ethnic Study of Atherosclerosis; OR, odds ratio

Received 14 May, 2013

Revised 16 July, 2013

Accepted 1 August, 2013

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