Differences in C-Reactive Protein Levels (CRP) Stratified by Sex in Geographic Atrophy (GA) vs Controls without Macular Degeneration

Abstract

Purpose : There is a consensus that chronic local inflammation plays a role in the pathogenesis of AMD. The role of systemic inflammation in GA is understudied. Some researchers have described a positive association between CRP, an established biomarker of systemic inflammation and activator of complement pathways, and AMD while others have not. There is a paucity of research on the contribution of sex to levels of CRP in patients with GA. The purpose of this study was to study CRP and to determine 1)Differences in the levels of CRP in a cohort of patients with GA compared with controls and 2)Sex-based differences in CRP levels in patients with GA compared with controls.

Methods : Patients with GA and controls were collected in a prospective AMD registry from Aug. 2014 to Jun. 2021. AMD was confirmed using multimodal imaging and the Beckman/Classification of Atrophy Meeting criteria for AMD. Serum CRP levels were measured using an automated nephelometer. A non-parametric linear regression model was fit to CRP with sex by AMD category interaction.

Results : We identified 96 GA cases and 128 controls; 52 (54%) and 83 (65%) were females in each group (Table 1). There was no significant difference in BMI between cases and controls, but the cohort was characterized by a low mean level of BMI (27.2(5.5)) and a low frequency of current cigarette smoking (1.3%). We found no statistically significant difference in levels of CRP between cases and controls, with a median of 1.2 (0.6 – 2.7) mg/L vs 1.5 (0.9-4.2) mg/L respectively, p = 0.26 (Fig.1). In cases and controls, CRP levels were not associated with age (p=0.59) or smoking (p=0.82) but were associated with sex (p=0.02) and BMI (p<0.01). Stratifying by sex, females had higher CRP levels compared to males. This difference was significant when cases and controls were combined but not significant between cases and controls of the same sex, although the magnitude of the difference was similar in both phenotypes (Fig.1).

Conclusions : We did not find a clinically significant difference in CRP levels between GA cases and controls. CRP was higher in females and associated with higher BMI levels. The Colorado cohort is distinguished by low rates of smoking and low mean BMI, which may contribute to the lack of association with GA. CRP may be an important marker in subjects with a higher frequency of smoking and higher levels of BMI.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.