Role of Renin-Angiotensin-Aldosterone System Activation in Promoting Cardiovascular Fibrosis and Stiffness.
Role of Renin-Angiotensin-Aldosterone System Activation in Promoting Cardiovascular Fibrosis and Stiffness.
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DOI：
10.1161/hypertensionaha.118.11065
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发表时间：
2018-09
期刊：
影响因子：
--
通讯作者：
Sowers JR
中科院分区：
文献类型：
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作者：
Jia G;Aroor AR;Hill MA;Sowers JR
538高血压2018年9月或接近正常LV射血分数，与HFpEF的临床表现一致。在涉及4128例患者的I-PRESERVE研究（厄贝沙坦治疗射血分数保留的心力衰竭）中，在大多数HFpEF患者中发现LV肥大或向心性重构和舒张功能障碍。14同时，LV质量与CVD发病率和死亡率的增加风险独立相关。14 RAAS激活在心脏舒张功能障碍和心力衰竭发展中的重要作用在使用各种RAAS抑制剂的临床试验中得到支持，包括血管紧张素转换酶（ACE）抑制剂、Ang II受体1（AT-1 R）阻断剂以及盐皮质激素受体（MR）拮抗剂。在8152例HFpEF患者中进行的RAAS阻断的荟萃分析显示，ACE抑制或AT-1 R拮抗剂显著降低了心力衰竭住院和心血管死亡的风险。3此外，阿利吉仑治疗6个月可降低老年高血压伴HFPEF患者的颈动脉僵硬度，改善左室收缩末期弹性，维持心室-动脉耦联，对舒张期充盈无任何影响。15一项随机双盲试验，对患有慢性心力衰竭的老年人给予培哚普利（PEP-CHF [慢性心力衰竭老年人培哚普利]），结果显示治疗1年可改善心功能，减少主要CVD结局，并减少心力衰竭住院治疗。16此外，大型随机临床试验，如RALES（随机安体舒通评价研究）、EMPHASIS（依普利酮治疗轻度心力衰竭患者住院和生存研究）和EPHESUS（依普利酮治疗急性心肌梗死后心力衰竭疗效和生存研究）表明，使用MR拮抗剂治疗可降低心力衰竭患者的CVD发病率和死亡率。在心脏舒张功能障碍和HFpEF患者中进行的17项随机对照临床试验显示，MR拮抗剂可减少心脏纤维化并改善心功能。这些结果表明，激活的RAAS信号是动脉和心脏僵硬和心力衰竭的发病机制中的重要贡献者。18
538 Hypertension September 2018 or near normal LV ejection fractions, consistent with the clinical picture of HFpEF. In the I-PRESERVE study (Irbesartan in Heart Failure With Preserved Ejection Fraction) involving 4128 patients, LV hypertrophy or concentric remodeling and diastolic dysfunction were found in the majority of patients with HFpEF. 14 Meanwhile, LV mass was independently associated with an increased risk of CVD morbidity and mortality. 14 The important role of RAAS activation in the development of cardiac diastolic dysfunction and heart failure is supported in clinical trials using various RAAS inhibitors, including angiotensin-converting enzyme (ACE) inhibitors, Ang II receptor 1 (AT-1R) blockers, as well as mineralocorticoid receptor (MR) antagonists. Meta-analysis of RAAS blockade in 8152 patients with HFpEF showed that either ACE inhibition or AT-1R antagonism significantly lowered risks for heart failure hospitalization and cardiovascular mortality. 3 Furthermore, 6 months of aliskiren treatment decreased the stiffness of carotid arteries and improved LV end-systolic elasticity with maintenance of ventricular-arterial coupling without any effects on diastolic filling in elderly hypertensive patients with HFPEF. 15 A randomized double-blind trial where perindopril was administered to elderly people with chronic heart failure (PEP-CHF [Perindopril in Elderly People With Chronic Heart Failure]) showed that 1 year of treatment improved cardiac function, reduced the primary CVD outcome, and hospitalization for heart failure. 16 Furthermore, large randomized clinical trials, such as RALES (Randomized Aldactone Evaluation Study), EMPHASIS (Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure), and EPHESUS (Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study), have suggested that treatment with an MR antagonist decreases CVD morbidity and mortality in patients with heart failure. 17 Randomized controlled clinical trials in patients with cardiac diastolic dysfunction and HFpEF showed that MR antagonists reduced cardiac fibrosis and improved cardiac function. These results implicate that an activated RAAS signaling is an important contributor in the pathogenesis of arterial and cardiac stiffness and heart failure. 18