Long-term Blood Pressure Variability Associated With Higher Risk of Advanced AMD

Local oxidative stress and choroidal ischemia are some of the main mechanisms of AMD’s pathophysiology, as it’s been shown to induce vasoconstriction of the choriocapillaris, which can lead to ischemia and thinning of the choroid and AMD onset. Photo: Mohammad Rafieetary, OD. Click image to enlarge. Although high blood pressure (BP) has long been known to be a risk factor for many diseases, an emerging area of study is the role of blood pressure variability (BPV), independent of BP levels. In a recent study, researchers aimed to assess associations between long-term BPV and the risk of age-related macular degeneration (AMD) and found that a 5mm Hg increase in diastolic BPV was associated with a 54% higher risk of advanced AMD, suggesting that one of the mechanisms is choroidal ischemia and inflammation leading to choroidal thinning and ultimately to AMD onset. The findings were reported in Ophthalmology Science.This was a prospective analysis of 14-year data from a French longitudinal population-based cohort study called ALIENOR that included 963 participants aged 73 years and older. All participants underwent blood pressure measurements (mm Hg) approximately every two to three years from baseline (1999 to 2000) to the seventh follow-up (2015 to 2017). During each visit, BP was measured twice (before and during the interview) in a seated position. BP values retained for a visit were the average of the two measurements. The device returned readings for systolic, diastolic and pulse blood pressure..Variability of blood pressure was determined from available BP measurements recorded between 1999 and 2017. AMD was assessed using retinal photos and OCT imaging every two years from 2006 to 2020. Analysis yielded the mean adjusted hazard ratio for AMD.Of 692 (median age: 79; 63.5% female) and 475 (median age: 78.5; 61.1% female) at-risk participants, 10% and 36% developed advanced and intermediate AMD, respectively. The hazard of advanced (but not intermediate) AMD increased by 54% for a 5mm Hg increase in diastolic BPV; statistical significance was not reached for a 5mm Hg increase in either systolic or pulse BPV.While the onset of AMD had not been documented and the underlying mechanisms remain unclear, the authors explained that given the systemic target-organ impact of BPV, they hypothesize that its role in AMD pathophysiology involves five independent mechanisms: BPV is associated with endothelial dysfunction, which impairs choroidal circulation and contributes to ischemia in the RPE.BPV-induced ischemia-reperfusion cycles may promote oxidative stress, characterized by increased production of reactive oxygen species, such as superoxide anions and hydrogen peroxide.BPV can compromise the integrity of the blood-retina barrier, increasing vascular permeability and promoting retinal edema.BPV may be associated with alterations in the local ocular reactive oxygen species, which plays a critical role in vascular homeostasis.BPV is often linked to autonomic dysfunction, which can lead to dysregulated retinal perfusion.In their paper, the researchers speculated that blood pressure variability affects choroidal thickness. A previous study observed that BPV was associated with an increased intima-media thickness, reducing the diameter of microvessels independent of BP levels, and another study found an association between BPV and decreased visual acuity. A third demonstrated an increased risk of AMD associated with orthostatic changes in BP levels.“It has been observed that, in the presence of continuous fluctuations in systemic BP, the choriocapillaris sympathetic system is overstimulated by, among others, local oxidative stress. This has been shown to induce vasoconstriction of the choriocapillaris, which can lead to ischemia and thinning of the choroid,” the authors explained in their article.One study observed a thinning of the choroid in hypertensive patients compared to a control group, particularly in the subfoveal region. The authors also showed that the longer the duration of hypertension, the thinner the choroidal layer. Another previous study consistently reported a decrease in choroidal thickness associated with vascular risk factors.“Choroidal ischemia and related local ‘microangiopathy’ has been put forward as one of the main mechanisms—along with inflammation—leading to choroidal thinning and ultimately to AMD onset,” they wrote.Understanding whether long-term BPV is an independent risk factor for AMD may provide new insights for clinical and public health recommendations aimed at preserving ocular health in aging populations, the authors wrote.“These findings underscore the need for further research to confirm this association, explore the underlying mechanisms and potential interventions that could mitigate this risk,” the researchers concluded.Click here for the journal source. Kayembe-Mulumba B, Leffondre K, Merle BMJ. Long-term blood pressure variability and risk of age-related macular degeneration in older adults: the ALIENOR study. Ophthalmol Sci. July 1, 2025. [Epub ahead of print.]