Abstract 15921: Antihypertensive Effects of Minocycline Are Associated With Improvement of Inflammatory Status in Patients With Treatment Resistant Hypertension
Background: Treatment resistant hypertension (TRH) is present in ~15% of hypertensive patients. It markedly increases mortality risk. Based on our previous studies and evidence from literature, we have proposed that systemic and neuro-inflammation is crucial in development and establishment of TRH. The objective of this study was to test the hypothesis that minocycline (Mino), an anti-inflammatory antibiotic, would reduce BP and inflammatory markers in patient with TRH. Mino was selected based on our preliminary studies showing that Mino can decrease systemic inflammation and cross the blood brain barrier to attenuate neuroinflammation in addition to its antibiotic effects.
Methods: A total of 29 subjects was recruited for this study. Exclusion and inclusion criteria are described at Clinicaltrials.gov (NCT02133872). Office and ambulatory BP measurements (ABPM) were used to confirm TRH diagnosis and subsequently measured 30d and 60 d after Mino administration (50mg/d). If BP failed to decline after 60 d Mino treatment (50mg/d), Mino was increased to 100mg/d and patients were monitored at 60 d. Circulating high-sensitivity C-reactive protein (hs-CRP), high-mobility group box 1 (HMGB1), and Th17 levels were measured.
Results: Average BP of TRH patients was 150/79mmHg, 67% responded to 50mg/d Mino and 33% to 100mg/d. ABPM 24h average BP for all m-TRH was less than 136/69mmHg at 60 d after Mino, and ABPM showed systolic and diastolic BP were significantly reduced by 14.5/10.5 mmHg. Plasma HMGB1 levels were 8- and 5-fold higher in TRH than normotensive (N) and controlled hypertensive (CH) patients, respectively (TRH: 45.2±25.10 vs N: 5.5±3.8 and CH: 8.9±10.2, ng/ml, p<0.05). Mino reduced HMGB1 level in TRH (m-TRH 3.0±0.7, ng/ml, p<0.05). Furthermore, there were 3-4-fold increases in Th17 cells and 67% increase in hs-CRP levels in TRH patients compared to N and CH. Mino treatment resulted in significant reduction in these parameters and did not change BMI in TRH patients.
Conclusions: This study demonstrates that Mino has a significant antihypertensive effect and decreases inflammatory markers in TRH patients. Thus, Mino could be considered a promising therapeutic option for TRH patients.
Author Disclosures: Y. Qi: None. S. Kim: None. D.D. Leach: None. S.J. Long: None. E.M. Handberg: None. V. Rodriguez: None. A. Mandloi: None. M.K. Raizada: Research Grant; Significant; R01 HL056921, R01 HL132448. C.J. Pepine: Research Grant; Significant; UL1 TR000064, 5UM1HL087366-09, 2 UM1 HL087366-06.
- © 2016 by American Heart Association, Inc.