Renin Angiotensin system-modifying therapies are associated with improved pulmonary health
Tóm tắt
Pulmonary diseases are often complicated and have diverse etiologies. One common factor is the lack of therapeutics available for these diseases. The goal of this study was to investigate the impact of Renin-Angiotensin System (RAS)-modifying medications on incidence and time to pulmonary complications. A retrospective analysis was conducted using claims data from a US commercial insurance company (2007–2013). The study consisted of patients with an emerging hypertension (HTN) diagnosis. Cox analysis was used to look at the effect of angiotensin converting enzyme inhibitors (ACE-Is) and angiotensin receptor blockers (ARBs) in this population. The events included pneumonia and influenza (infectious), Chronic obstructive pulmonary disease (COPD) and allied conditions (inflammatory), and other diseases (structural). A total of 215,225 patients were followed in the study. These fell into three groups depending on the first prescribed anti-hypertension medication; ACE-Is (47.21%), ARBs (11.40%) and calcium channel blockers (CCBs)/Diuretics-Control (41.39%). The use of ACE-I as first treatment significantly reduced the incidence of infectious (Hazard Ratio (HR) 0.886, 95% Confidence Interval (95% CI) 0.859–0.886), inflammatory (HR 0.924, 95% CI 0.906–0.942) and structural outcomes (HR 0.865, 95% CI 0.847–0.885); it also increased the time (delayed) to diagnosis with prolonged treatment. Primary ARB use only significantly lowered the incidence of structural outcomes (HR 0.900, 95% CI 0.868–0.933); prolonged treatment did reduce incidence of all three diagnosis groups and significantly delayed disease onset. There is an association between the use of ACE-Is and ARBs and a delay in the progression of pulmonary complications in vulnerable populations. Research into the RAS may identify future therapies for patients with potential chronic pulmonary conditions.
Tài liệu tham khảo
Gattinoni L, Bombino M, Pelosi P, Lissoni A, Pesenti A, Fumagalli R, et al. Lung structure and function in different stages of severe adult respiratory distress syndrome. JAMA. 1994;271:1772–9.
Moore BB, Hogaboam CM. Murine models of pulmonary fibrosis. American Journal of Physiology- Lung Cellular and Molecular Physiology. 2008;294:L152–60.
Lyczak JB, Cannon CL, Pier GB. Lung infections associated with cystic fibrosis. Clin Microbiol Rev. 2002;15(2):194–222.
Song JW, Hong SB, Lim CM, Koh Y. Acute exacerbation of idiopathic pulmonary fibrosis: incidence, risk factors and outcome. Eur Respir J. 2011;37(2):356–63.
Saydain G, Islam A, Afessa B, Ryu JH. Outcome of patients with idiopathic pulmonary fibrosis admitted to the intensive care unit. Am J Respir Crit Care Med. 2002;11(2):117–22.
O'brien RJ, Nunn PP. The need for new drugs against tuberculosis: obstacles, opportunities, and next steps. Am J Respir Crit Care Med. 2001;163(5):1055–8.
Lythgoe MP, Rhodes CJ, Ghataorhe P, Attard M. Why drugs fail in clinical trials in pulmonary arterial hypertension, and strategies to succeed in the future. Pharmacol Ther. 2016;164:195–203.
Yamauchi Y, Nagase T. New anti-inflammatory drugs for COPD: is there a possibility of developing drugs that can fundamentally suppress inflammation? Chronic Obstructive Pulmonary Disease 2017:267-278.
Yang J, Tan Y, Zhao F, Ma Z, Wang Y, Zheng S, et al. Angiotensin II plays a critical role in diabetic pulmonary fibrosis most likely via activation of NADPH oxidase-mediated nitrosative damage. AJP: Endocrinology and Metabolism. 2011;301:E132–44.
Ogihara T, Asano T, Ando K, Chiba Y, Sakoda H. Angiotensin II–induced insulin resistance is associated with enhanced insulin signaling. Hypertension. 2002;40(6):872–9.
Wei Y, Sowers JR, Clark SE, Li W. Angiotensin II-induced skeletal muscle insulin resistance mediated by NF-κB activation via NADPH oxidase. Am J Physiol Endocrinol Metab. 2008;294(2):E345–51.
Ferder L, Inserra F, Martínez-Maldonado M. Inflammation and the metabolic syndrome: role of angiotensin II and oxidative stress. Curr Hypertens Rep. 2006;8(3):191–8.
White M, Lepage S, Lavoie J, De Denus S. Effects of combined candesartan and ACE inhibitors on BNP, markers of inflammation and oxidative stress, and glucose regulation in patients with symptomatic heart failure. J Card Fail. 2007;13(2):86–94.
Kurata A, Nishizawa H, Kihara S, Maeda N. Blockade of angiotensin II type-1 receptor reduces oxidative stress in adipose tissue and ameliorates adipocytokine dysregulation. Kidney Int. 2006;70(10):1717–24.
Dendorfer A, Dominiak P, Schunkert H. ACE inhibitors and angiotensin II receptor antagonists. Atherosclerosis: Diet and Drugs 2005:407-442.
Molloy DW, Standish TI, Zhou Q. A multicenter, blinded, randomized, factorial controlled trial of doxycycline and rifampin for treatment of Alzheimer's disease: the DARAD trial. International Journal of Geriatric Psychiatry. 2013;28(5):463–70.
Jain MK, Ridker PM. Anti-inflammatory effects of statins: clinical evidence and basic mechanisms. Nat Rev Drug Discov. 2005;4:977–87.
Merai R. CDC grand rounds: a public health approach to detect and control hypertension. MMWR Morb Mortal Wkly Rep. 2016;65(45):1261–4.
Cheung BMY, Li C. Diabetes and hypertension: is there a common metabolic pathway? Curr Atheroscler Rep. 2012;14:160–6.
Abernethy AD, Stackhouse K, Hart S. Impact of diabetes in patients with pulmonary hypertension. Pulmonary Circulation. 2015;5(1):117–23.
Ogawa S, Mori T, Nako K, Kato T, Takeuchi K, Ito S. Angiotensin II type 1 receptor blockers reduce urinary oxidative stress markers in hypertensive diabetic nephropathy. Hypertension. 2006;47:699–705.
Lindeman J. Ace inhibitors potently reduce vascular inflammation, results of an open proof-of-concept study in the abdominal aortic aneurysm. Atherosclerosis. 2014;9(12):e111952.
National High Blood Pressure Education Program. The seventh report of the joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure. 2004.
Papinska AM, Soto M, Meeks CJ, Rodgers KE. Long-term administration of angiotensin (1-7) prevents heart and lung dysfunction in a mouse model of type 2 diabetes (db/db) by reducing oxidative stress, inflammation and pathological remodeling. Pharmacol Res. 2016;107:372–80.