Discovery and Validation of Agonistic Angiotensin Receptor Autoantibodies as Biomarkers of Adverse Outcomes

BACKGROUND: Agonistic angiotensin II type 1 receptor autoantibodies (AT1RaAbs) have not been associated with functional measures or risk for adverse health outcomes. AT1RaAbs could be used to stratify patient risk and to identify patients who can benefit from angiotensin receptor blocker treatment. METHODS: Demographic and physiological covariates were measured in a discovery set of community-dwelling adults from Baltimore (N= 255) and AT1RaAb associations with physical function tests and outcomes assessed. A group from Chicago (N= 60) was used for validation of associations and to explore the impact of angiotensin receptor blocker treatment. RESULTS: The Baltimore group had 28 subjects with falls, 32 frail subjects, and 5 deaths. Higher AT1RaAbs correlated significantly with interleukin-6 (Spearman r= 0.33, P< 0.0001), systolic blood pressure (Spearman r= 0.28, P< 0.0001), body mass index (Spearman r= 0.28, P< 0.0001), weaker grip strength (Spearman r=-0.34, P< 0.01), and slower walking speed (Spearman r=-0.30, P< 0.05). Individuals with high AT1RaAbs were 3.9 (95% confidence interval, 1.38-11.0) times more likely to be at high risk after adjusting for age (P< 0.05). Every 1 mu g/mL increase in AT1RaAbs increased the odds of falling 30% after adjusting for age, sex, body mass index, and blood pressure. The Chicago group had 46 subjects with falls and 60 deaths. Serum AT1RaAb levels were significantly correlated with grip strength (Spearman r=-0.57, P< 0.005), walking speed (Spearman r=-0.47, P< 0.005), and falls (Spearman r= 0.30, P< 0.05). Every 1 mu g/mL increase in AT1RaAbs, decreased time to death by 9% after adjusting for age, sex, body mass index, and blood pressure. Chronic treatment with angiotensin receptor blockers was associated with better control of systolic blood pressure and attenuation of decline in both grip strength and time to death. CONCLUSIONS: In older individuals, higher AT1RaAb levels were associated with inflammation, hypertension, and adverse outcomes. Angiotensin receptor blocker treatment may blunt the harm associated with high levels of AT1RaAb.