'Retinal Age Gap' Linked to Arterial Stiffness and CVD Risk

Yasser Heakal, PhD, for Medscape

January 26, 2022

The study covered in this summary was published in medRxiv.org as a preprint and has not yet been peer reviewed.

Key Takeaways

  • A 1-year increase in the retinal age gap, defined as fundus image predicted age minus chronologic age, is associated with a significant increase in arterial stiffness index (ASI), an early indicator of atherosclerosis and a predictor of future cardiovascular disease (CVD) events.

  • The retinal age gap is a potential novel independent biomarker for future incident CVD events.

Why This Matters

  • Prevention and early detection of CVD are needed to minimize CVD morbidity and mortality.

  • Previously developed CVD risk calculators, such as the Cardiovascular Risk Score (QRISK), the Systemic Coronary Risk Evaluation (SCORE), and the Framingham risk score, are limited by lack of precision, information bias for questionnaire-based models, and the need for invasive procedures.

  • The retina, highly vascular and readily accessible to noninvasive imaging and evaluations, offers a surrogate noninvasive tool to assess systemic vasculature.

  • This study used a deep learning algorithm to examine retinal images and investigate the association of retinal age gap with ASI for the noninvasive evaluation of cardiovascular health and to predict subclinical CVD.

Study Design

  • The study was based on the UK Biobank, a large-scale prospective study with more than 500,000 patients aged 40–69 years recruited between 2006 and 2010.

  • The ASI was derived from the analysis of the digital volume pulse, an indirect method to assess AS peripherally.

  • CVD events were identified based on the first known myocardial infarction or stroke date derived from the hospital admission data in England, Scotland, and Wales; the national death register data; and self-reporting.

  • A total of 19,200 fundus images from 11,052 participants with no medical history at baseline were used to generate the deep learning model for age prediction.

  • A total of 33,817 participants who had no history of CVD events at baseline were included to investigate the effects of the retinal age gap on the risk of future CVD events.

  • Descriptive statistics were used to assess baseline characteristics of study participants, and linear regression models considering the retinal age gap as a continuous linear term were used to investigate the association between a 1-year increase in retinal age gap and ASI.

  • Cox proportional hazards regression models were used to assess the relationship between retinal age gap (continuous or quintiles) and incident CVD.

Key Results

  • A 1-year increase in the retinal age gap was associated with a significant rise in ASI, with a beta-coefficient of 0.002 (95% CI, 0.001 – 0.003; P < .001) after adjusting for all included confounders.

  • A total of 675 (2.00%) participants had incident CVD events. After adjustment for confounders, each 1-year increase in retinal age gap was associated with a 3% increase in the risk of incident CVD (hazard ratio [HR], 1.03; 95% CI, 1.01 – 1.06, P = .012).

  • This independent predictive value remained significant when ASI was incorporated into the fully adjusted model (HR, 1.03; 95% CI, 1.01 – 1.06, P = .009).


  • The calculation of the retinal age gap was based on fundus images captured at specific time points and did not account for the dynamic nature of aging of the retina.

  • The possibility of residual confounding effects could not be excluded.


  • This study was supported by the NHMRC Investigator Grant; Fundamental Research Funds of the State Key Laboratory of Ophthalmology, National Natural Science Foundation of China; Project of Investigation on Health Status of Employees in Financial Industry in Guangzhou, China; and the Science and Technology Program of Guangzhou, China. He receives support from the University of Melbourne through its Research Accelerator Program and the CERA Foundation. The Centre for Eye Research Australia receives operational infrastructure support from the Victorian State Government.

This is a summary of a preprint research study, "Association of Retinal Age Gap with Arterial Stiffness and Incident Cardiovascular Disease," written by Zhuoting Zhu, MD, PhD, of the Centre for Eye Research Australia and the University of Melbourne and colleagues, on medRxiv provided to you by Medscape. This study has not yet been peer reviewed. The full text of the study can be found on medRxiv.org.

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