Greater plasma factor D significantly associated with cardiovascular disease, inflammation

Netherlands: A recent study published in Atherosclerosis by Shunxin Jin and colleagues has revealed a potential association between factor D plasma concentration and cardiovascular disease (CVD), specifically in relation to low-grade inflammation (LGI) and endothelial dysfunction (ED).

Factor D is an essential protease involved in the activation of the alternative complement pathway, which has been implicated in vascular damage and the development of CVD. The findings of this study shed light on the potential role of factor D in CVD and its related complications.

The study included 2,947 participants, with a slight majority being men, and the average age of participants being 59.9 years. Among the participants, 26.5% had type 2 diabetes (T2D), which was oversampled for analysis. Various markers were measured, including LGI, ED, carotid intima-media thickness (cIMT), ankle-brachial index (ABI), and the presence of CVD. Plasma concentrations of factor D were also assessed. The associations between factor D and these markers were evaluated while adjusting for demographic, lifestyle, and dietary factors.

In the study, it was observed that factor D showed a significant association with various cardiovascular parameters. Specifically, per standard deviation (SD) increase in factor D, there was a positive association with low-grade inflammation (LGI) of 0.171 SD, endothelial dysfunction (ED) of 0.158 SD, and cardiovascular disease (CVD) with an odds ratio (OR) of 1.15.

There was no significant association between factor D and carotid intima-media thickness (cIMT) with a decrease of -6.62 μm or ankle-brachial index (ABI) with a decrease of -0.003.

Further analysis revealed that the association between factor D and endothelial dysfunction (ED) was stronger in individuals without type 2 diabetes (T2D), showing an increase of 0.237 SD compared to those with T2D who showed an increase of 0.095 SD.

These interaction analyses were statistically significant (pinteraction <0.05). Additional analyses conducted with complement components C3 and C3a largely supported these findings.

In participants without diabetes, factor D demonstrated an inverse association with carotid intima-media thickness (cIMT), showing a decrease of -13.37 μm.

However, this inverse association was not observed in individuals with type 2 diabetes (T2D), where a slight increase of 4.49 μm was observed. This interaction effect was also statistically significant.

These findings suggest that factor D may play a role in the development and progression of CVD, specifically through its association with LGI and ED. The results were largely corroborated by analyses involving other complement system components, such as C3 and C3a. It is worth noting that the association between factor D and cIMT differed in individuals with and without diabetes, with a potential protective effect observed in non-diabetic participants.

The study highlights the importance of factor D in CVD and its potential contribution to disease progression through complement activation, inflammation, and endothelial dysfunction. Future research is warranted to further investigate the mechanisms underlying these associations and to explore potential therapeutic interventions targeting the complement system for CVD prevention and management.

Understanding the role of factor D in CVD may have significant clinical implications, including the identification of new biomarkers and therapeutic targets for patients at risk of developing CVD. Moreover, these findings may help inform the development of personalized treatment strategies for individuals with specific risk profiles related to factor D plasma concentration.

Reference:

Jin, S., Eussen, S. J. P. M., Schalkwijk, C. G., Stehouwer, C. D. A., & van Greevenbroek, M. M. J. (2023). Plasma factor D is cross-sectionally associated with low-grade inflammation, endothelial dysfunction and cardiovascular disease: The Maastricht study. Atherosclerosis, 377, 60–67. https://doi.org/10.1016/j.atherosclerosis.2023.06.079