Homocysteine Facilitates the Formation of Carotid Atherosclerotic Plaque Through Inflammatory and Noninflammatory Mechanisms.

Abstract

Background: Elevated homocysteine (Hcy) was considered a significant risk factor in the development and progression of carotid atherosclerosis (CAS), which involves a combination of inflammatory and noninflammatory mechanisms. However, epidemiological surveys have presented conflicting results. In this study, we aim to offer an epidemiological viewpoint on how elevated Hcy impacts CAS and its potential mechanisms. Methods: Levels of high-sensitivity C-reactive protein (hsCRP) were measured to assess the inflammatory status. The estimation of CAS events was performed by assessing carotid intima-media thickness using Doppler ultrasonography. Univariate analysis was conducted to investigate the variations in biochemical parameters among three groups: normal, carotid atherosclerotic thickening (CAT), and carotid atherosclerotic plaque (CAP) formation. Logistic regression analysis was conducted to identify the risk factors associated with the progression of CAT and CAP. In addition, multivariate linear regression analysis was conducted to identify the independent factors that correlated with hsCRP levels. Results: The study encompassed 3897 participants, with 2992 (76.8%) being males and 905 (23.2%) being females. The incidence of CAT and CAP rose with higher Hcy levels, with an overall odds ratio (OR) of 2.04 [95% confidence intervals (CI) 1.69-2.40] for CAT and 2.68 (95% CI 2.32-3.05) for CAP. After adjusting for gender, age, and blood markers, the OR for CAT and CAP decreased, with an overall OR of 1.05 (95% CI 0.81-1.28) and OR of 1.24 (95% CI 1.02-1.46), respectively. CAP risk independently increased when Hcy level exceeded 19.7 μmol/L (P = 0.030), but not CAT risk (P = 0.299). The impact of hsCRP on CAS events is similar to that of Hcy, and a multiple linear analysis found a significant independent correlation between hsCRP and Hcy (P = 0.001). Conclusions: Elevated Hcy levels can facilitate the formation of CAP through both inflammatory and noninflammatory processes, but it does not independently influence CAT.