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

• Published in: Circulation (New York, N.Y.) Vol. 135; no. 5; pp. 449 - 459
• Main Authors: Abadir, Peter M, Jain, Alka, Powell, Laura J, Xue, Qian-Li, Tian, Jing, Hamilton, Robert G, Bennett, David A, Finucane, Thomas, Walston, Jeremy D, Fedarko, Neal S
• Format: Journal Article
• Language: English
• Published: United States by the American College of Cardiology Foundation and the American Heart Association, Inc 31.01.2017
• Subjects: Adult; Aged; Aged, 80 and over; Angiotensin Receptor Antagonists - therapeutic use; Autoantibodies - therapeutic use; Biomarkers - blood; Female; Humans; Male; Middle Aged; Treatment Outcome; Young Adult; mortality; angiotensin receptor blockers; aging; inflammation; autoantibodies
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/CIRCULATIONAHA.116.022385

BACKGROUND—Agonistic angiotensin II type I receptor autoantibodies (AT1RaAbs) have not been associated with functional measures or risk for adverse health outcomes. AT1RaAbs could be utilized to stratify patient risk and to identify patients who can benefit from angiotensin receptor blocker (ARB) treatment. METHODS—Demographic and physiologic 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 ARB 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 BP (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% CI 1.38-11.0) times more likely to be at high risk after adjusting for age (P<0.05). Every 1 µg/ml increase in AT1RaAbs increased the odds of falling 30% after adjusting for age, gender, BMI and BP. 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 µg/ml increase in AT1RaAbs, decreased time to death by 9% after adjusting for age, gender, BMI and BP. Chronic treatment with ARBs was associated with better control of systolic BP 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. ARB treatment may blunt the harm associated with high levels of AT1RaAb.