Patients With Retinal Vein Occlusion May Have Increased CVD Risk

A population-based cohort study found that patients with retinal vein occlusion (RVO) 40 years and older had increased risk of cardiovascular disease CVD compared with patients who did not have RVO.

Patients with retinal vein occlusion (RVO) were shown to have a greater risk of incident cardiovascular disease (CVD) vs unexposed patients, according to a new study published in British Journal of Ophthalmology that was conducted in Denmark.

The study was based on data from the Danish National Patient Registry, which contains information on all hospitalizations in Denmark since 1977. Patients who were alive and living in Denmark aged 40 years and older between January 1, 1998, and December 31, 2017, were identified for this study and included at the date they were aged 40 years after the initial cohort entry date. Patients were excluded if they had a history of CVD and all-cause mortality, which were the primary study outcomes. The researchers also implemented a 90-day lag-time period between RVO exposure and incident CVD to account for undetected CVD.

There were 4,194,781 patients included in this study; the median follow-up was 15.5 years; and the median age at time of exposure was 71.8 years. Patients exposed to RVO were older at entry and more likely to have arterial hypertension, dyslipidemia, diabetes, and smoking-related disorders compared with patients without RVO exposure.

The mean number of registered patients per year with RVO almost doubled after 2011, when vascular endothelial growth factor inhibition for macular edema in RVO was approved in Europe.

RVO exposure was identified having a 13% greater risk of incident CVD (adjusted HR [aHR], 1.13; 95% CI, 1.09-1.17). Risk of ischemic CVD and nonischemic CVD also was higher in patients exposed to RVO, at 23% (aHR, 1.23; 95% CI, 1.15-1.33).

Patients with branch retinal vein occlusion (BRVO) were younger, more likely to be women, and less likely to have a diagnosis of smoking-related disorders than patients with central retinal vein occlusion (CRVO). The median ages at exposure to BRVO and CRVO were 71.1 and 73.0 years, respectively.

Patients with BRVO had an increased risk of CVD (aHR, 1.14; 95% CI, 1.03-1.25), ischemic CVD (aHR, 1.18; 95% CI, 1.05-1.33), and nonischemic CVD (aHR, 1.22; 95% CI, 1.07-1.38).

Patients with CRVO had an increased risk of CVD (aHR, 1.12; 95% CI, 1.00-1.25), ischemic CVD (aHR, 1.12; 95% CI, 0.99-1.28), nonischemic CVD (aHR, 1.16; 95% CI, 1.00-1.35), and all-cause mortality (aHR, 1.18; 95% CI, 1.11-1.26).

Risk of CVD, ischemic CVD, and nonischemic CVD increased after 2011, especially in CVD and nonischemic CVD:

  • CVD:
    • Before 2011: 10% (aHR, 1.10; 95% CI, 1.06-1.15)
    • After 2011: 19% (aHR, 1.19; 95% CI, 1.11-1.28)
  • Ischemic CVD:
    • Before 2011: 15% (aHR, 1.15; 95% CI, 1.10-1.21)
    • After 2011: 17% (aHR, 1.17; 95% CI, 1.07-1.27)
  • Nonischemic CVD:
    • Before 2011: 6% (aHR, 1.06; 95% CI, 1.01-1.12)
    • After 2011: 24% (aHR, 1.24; 95% CI, 1.15-1.33)

There was also an increased risk of all-cause mortality in patients referred after 2011 (before 2011: aHR, 0.97; 95% CI, 0.94-1.00, after 2011: aHR, 1.11; 95% CI, 1.06-1.16).

The study used RVO and CVD in patients 40 years and older, so the findings might not apply outside of this setting, marking a limitation. Lifestyle, socioeconomic, and genetic factors also were not included in the registers used for this study, which meant that those factors could not be evaluated.

The researchers concluded that patients with RVO had an overall increased risk of developing CVD compared with non-RVO controls. Patients with diagnosed RVO when angiostatic treatment was introduced in 2011 were also more likely to have a risk of all-cause mortality, which was not an issue prior to 2011.


Frederiksen KH, Stokholm L, Frederiksen PH, et al. Cardiovascular morbidity and all-cause mortality in patients with retinal vein occlusion: a Danish nationwide cohort study. Br J Ophthalmol. Published online May 10, 2022. doi:10.1136/bjophthalmol-2022-321225

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