Pulse pressure variability and estimated pulse wave velocity predict structural glaucomatous damage in U.S. adults – the NHANES 2005–2008 cycle

Background Glaucoma is well-established as a disease that damages the optic nerve and causes loss of visual field. The association of chronic arterial stiffness and acute haemodynamic variability with glaucoma indices in adulthood remains unclear. Estimated pulse wave velocity (ePWV) is an established marker of vascular ageing, but recent evidence suggests that higher blood pressure variability may adversely affect the optic nerve head. Purpose We aimed to determine if arterial stiffness and pulse pressure (PP) variability are independently associated with structural optic nerve remodelling. Methods We conducted a cross-sectional analysis using the National Health and Nutrition Examination Survey (NHANES 2005-2008) data (N=5,078; aged ≥ 40 years with gradable image data). Primary exposures were standardised Z-scores of ePWV and the standard deviation of pulse pressure (variability). Structural changes were defined by the vertical cup-to-disc ratio (VCDR) using fundus photography. Multivariable survey-weighted linear regression was adjusted for sex, smoking, race, diabetes, heart disease, statin use and dyslipidaemia. We conducted sensitivity analysis for adults with VCDR < 0.6 (non-glaucoma suspect). Mediation analysis was performed to determine if type 2 diabetes mediates the pathway between arterial stiffness and total VCDR. Results In the adjusted model analysis, PP variability (β=0.004, 95% CI: 0.001–0.007; p=0.019) and ePWV (β=0.010, 95% CI: 0.007–0.014; p<0.001) were independently associated with VCDR. Among the participants with normal optic nerve morphology (VCDR < 0.6), the association between arterial stiffness and VCDR remained significant (β=0.005, 95% CI: 0.001–0.009; p=0.027), whereas it was insignificant for PP variability. In the causal mediation analysis, type 2 diabetes partially mediated the association between arterial stiffness (ePWV) and VCDR (β=3x10-4, 95% CI: 0.2x10-4–6x10-4; p=0.03), accounting for 2.9% of the total effect of ePWV on total defect count. Conclusions In the U.S. adult population, higher arterial stiffness and pulse pressure variability are independently associated with VCDR. Arterial stiffness may be a precursor to early visual damage, but longitudinal and temporal studies are warranted.