Mitigating Cardiovascular and Renal Risk in Primary Aldosteronism

项目摘要 原发性醛固酮增多症(PA)占所有高血压患者的10%，占顽固性高血压患者的20% 案子。PA显著增加心血管和肾脏疾病的风险，与血压无关。 尽管使用盐皮质激素受体(MR)拮抗剂的药物治疗被广泛推荐为一线药物 对于大多数PA病例的治疗，几乎没有关于MR有效性的长期数据 在改善健康结果方面的拮抗者。MR拮抗剂可能不够充分或没有积极使用 在实践中足够有效地阻止病理性的醛固酮过剩，就像大多数手术治疗的PA病例一样 治愈高血压，而绝大多数使用MR拮抗剂治疗的PA患者需要额外的 控制血压的降压药。此外，没有基于证据的 建议如何最好地开出和监测MR拮抗剂，以最大限度地提高长期健康效益。 我们建议前瞻性地研究PA中MR拮抗剂治疗与 心血管和肾脏结果，并探讨最佳医疗和监测策略 在这些病人身上。使用合作伙伴研究患者数据注册中心，这是一个集中的临床数据存储库 ~来自马萨诸塞州总医院布里格姆妇女医院的1000万名患者和他们的 联合医院，我们将收集3500例使用MR拮抗剂(暴露)治疗的PA病例 1,500例接受手术治疗的PA患者(对照1组)，以及10,000名年龄、性别、种族和血液 血压匹配的高血压病患者(对照组2)。在目标1中，我们将研究MR拮抗剂在 PA和突发心血管疾病。我们假设发生事故的风险会更高 接受MR拮抗剂治疗的PA患者的心血管疾病，不受血压影响，与：a) 手术治疗的PA和b)治疗原发性高血压。在目标2中，我们将研究MR拮抗剂在PA中的使用 估计肾小球滤过率(EGFR)下降率。我们假设会有一个更快的EGFR 与a)手术治疗相比，使用MR拮抗剂治疗的PA患者的血压下降与血压无关 PA和B)治疗原发性高血压。在目标3中，我们将评估肾素活性是否可以作为一种 指导PA中MR拮抗剂治疗滴定的临床信息生物标志物。我们假设PA 服用MR拮抗剂时肾素活性较高的患者需要较少的降压药物和 与肾素活性较低的PA患者相比，发生心血管疾病的风险较低 关于对抗者先生。这项研究可能会对PA的管理产生直接和直接的影响：a) 阐明MR拮抗剂是否足以有效阻断病理性的醛固酮过剩和 降低不良健康后果的风险以及b)评估肾素活性是否可作为生物标记物 在临床实践中指导MR拮抗剂滴定。

Project Summary Primary aldosteronism (PA) accounts for >10% of all hypertensive cases and >20% of resistant hypertensive cases. PA substantially increases the risk of cardiovascular and renal disease, independent of blood pressure. Although medical therapy with mineralocorticoid receptor (MR) antagonists is widely recommended as first-line treatment for the majority of cases of PA, almost no long-term data exists on the effectiveness of MR antagonists in improving health outcomes. MR antagonists may be inadequate or not used aggressively enough in practice to effectively block pathologic aldosterone excess as most surgically treated PA cases are cured of hypertension while the vast majority of PA cases treated with MR antagonists require additional antihypertensive medications for blood pressure control. Further, there are no evidence-based recommendations on how best to prescribe and monitor MR antagonists to maximize long-term health benefits. We propose to prospectively examine the associations between MR antagonist therapy in PA and cardiovascular and renal outcomes and to investigate the optimal medical treatment and surveillance strategy in these patients. Using the Partners Research Patient Data Registry, a centralized clinical data repository of ~10 million patients from Brigham and Women's Hospital, Massachusetts General Hospital, and their associated hospitals, we will assemble a cohort of 3,500 cases of PA treated with MR antagonists (exposed group), 1,500 cases of surgically treated PA (comparison group 1), and 10,000 age-, sex-, race-, and blood pressure-matched essential hypertensives (comparison group 2). In Aim 1, we will study MR antagonist use in PA and incident cardiovascular disease. We hypothesize that there will be a higher risk of incident cardiovascular disease, independent of blood pressure, in PA treated with MR antagonists compared with: a) surgically treated PA and b) treated essential hypertension. In Aim 2, we will study MR antagonist use in PA and rate of estimated glomerular filtration rate (eGFR) decline. We hypothesize that there will be a faster eGFR decline, independent of blood pressure, in PA treated with MR antagonists compared with: a) surgically treated PA and b) treated essential hypertension. In Aim 3, we will evaluate whether renin activity can serve as a clinically informative biomarker to guide titration of MR antagonist therapy in PA. We hypothesize that PA patients with higher renin activity while on MR antagonists will require fewer antihypertensive medications and have a lower risk of incident cardiovascular disease compared with PA patients with lower renin activity while on MR antagonists. This study may have immediate and direct implications on the management of PA by: a) elucidating whether MR antagonists are adequate at effectively blocking pathologic aldosterone excess and reducing the risk of adverse health outcomes and b) evaluating whether renin activity can serve as a biomarker in clinical practice to guide MR antagonist titration.