Abstract 9401: Relationship Between Circulating Levels of Angiotensinogen and Hypertension—The Multi-Ethnic Study of Atherosclerosis

Introduction: Angiotensinogen (AGT) is a critical component of the renin-angiotensin-aldosterone system (RAAS) that regulates blood pressure (BP), volume, and electrolyte levels. While physiological effects of AGT are primarily mediated by AGT-derived peptide hormones, effects of AGT independent of these peptides have been described recently in animal models. We sought to determine the relationship between AGT levels, sex, ethnicity, and hypertension (HTN). Methods: We measured baseline plasma AGT levels using an enzyme-linked immunoassay in 5,786 Multiethnic Study of Atherosclerosis (MESA) participants, aged 45 to 84 yrs. We determined the associations between AGT levels and clinical and demographic variables, medication usage, and BP at the first exam. The relationship between prevalent HTN was then determined using adjusted models. Results: Mean AGT levels (log-transformed) were significantly higher in females than males and differed across race/ethnicities with the ordering (from highest to lowest): White, Black, Hispanic, and Chinese adults. The difference between the sexes was greatest in White adults with females having 1.44 times greater levels than males (95% CI: 1.40, 1.48), and lowest in Chinese adults. In males not taking medications targeting RAAS, one SD higher log-AGT was associated with a 2.61 mmHg higher SBP (95% CI: 1.49, 3.80), in females it was associated with 0.97 mmHg higher SBP (95% CI: 0.30, 1.65). Use of RAAS-blocking medications attenuated these associations. In risk factor-adjusted models, higher levels of AGT were associated with higher odds of prevalent HTN. Conclusions: AGT levels differ between race/ethnicities and between the sexes. Higher levels of AGT are associated with higher BP and odds of prevalent HTN. Despite lower levels in males, the association between levels and BP was greater in males. Taken together, the difference in levels and in the association with BP suggests sex-specific regulation and effects of AGT.