Perindopril treatment promote left ventricle remodeling in patients with heart failure screened positive for autoantibodies against angiotensin II type 1 receptor

BACKGROUND: Autoantibodies specific to the angiotensin II type I receptor (anti-AT(1)-AR) have been implicated in the pathology of congestive heart failure (CHF). Anti-AT(1)-AR may be associated with left ventricular function in CHF patients treated with perindopril. METHODS: Synthetic angiotensin II type 1 receptor (AT(1)-R) peptides served as the target antigen. ELISA was used to screen the sera of 156 CHF patients, which were divided into positive and negative groups based on their anti-AT(1)-AR reactivity. Echocardiography and a 6-minute walk test were performed at baseline and after one year of perindopril therapy. The end-point events were compared over a 5-year follow-up. RESULTS: Final analysis covered 138 patients, including 82 positive and 56 negative. The frequency and geometric mean titre of anti-AT(1)-AR were significantly lower in the positive group after one year of treatment (all P < 0.01, from 100% to 73.2% and from 1:125.3 ± 1.0 to 1:69.2 ± 1.1). Of these, 22 patients showed no antibodies. Both groups showed improvement in left ventricular end-diastole, end-systolic dimensions, ejection fraction, and a 6-minute walk test by perindopril in combination with standard treatment regime for one year (all P < 0.01). However, the 82 patients positive for anti-AT(1)-AR showed more pronounced improvement than the 56 negative patients (all P < 0.05). However, after 5 years of follow-up, the rate of all causes and cardiovascular mortality attributable to any cause and the re-hospitalisation rate showed no significant differences between the two groups (all P > 0.05). CONCLUSIONS: Perindopril treatment significantly decreased the frequency and geometric mean titre in patients positive for anti-AT(1)-AR, even to complete ablation. These patients showed greater improvement in left ventricular remodeling and heart function than negative that in patients after one year of perindopril treatment in combination with standard treatment, but no significant differences in endpoint events were observed in the following 5 years. Anti-AT(1)-AR might be a useful biomarker of over-activation of the renin-angiotensin-aldosterone system for clinical medication.