Adrenal aldosterone synthase (CYP11B2) histopathology and its association with disease-induced sudden death: a cross-sectional study

IF 13.6 Q1 HEALTH CARE SCIENCES & SERVICES

Lancet Regional Health-Europe Pub Date : 2025-02-06 DOI:10.1016/j.lanepe.2025.101226

Antero Ylänen , Juhani Isojärvi , Antti Virtanen , Helena Leijon , Tiina Vesterinen , Aapo L. Aro , Heini Huhtala , Eeva Kokko , Ilkka Pörsti , Marianna Viukari , Pasi I. Nevalainen , Niina Matikainen

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引用次数: 0

Abstract

Background

Unidentified cardiovascular risk factors may account for approximately half of sudden deaths, a devastating event with limited preventive tools. We investigated whether adrenal histopathology suggestive of primary aldosteronism, pheochromocytoma, or adrenal masses could explain part of the risk for disease-induced sudden death (DSD).

Methods

In this study, autopsies and histopathological analyses, including aldosterone synthase staining of adrenal glands, were performed on 403 consecutive individuals who experienced sudden death. These individuals were classified into 258 cases of DSD and 144 deaths caused by trauma, suicide, or intoxication, i.e., non-disease-induced sudden death (nDSD). This trial was registered at ClinicalTrials.gov (NCT05446779).

Findings

Adrenal histopathology revealed changes in 31 (7.7%) subjects of the cohort. Of these, the most prevalent findings [25 (6.2%)] were aldosterone-producing adenomas (APA) or nodules (APN), which were associated with myocardial infarction and atherosclerosis at autopsy. Individuals in the DSD group and the subgroup with sudden cardiac death (SCD) were more likely to have APA or APN than individuals in the nDSD group [23 (8.9%) vs. 2 (1.4%), p = 0.002; 16 (8.8%) vs. 2 (1.4%), p = 0.003, respectively]. APA or APN were explanatory factors for DSD (odds ratio [OR] 6.47, 95% confidence interval [CI] 1.40–29.88, p = 0.017) and SCD (OR 10.68, 95% CI 2.02–56.43, p = 0.005). Other findings included two pheochromocytomas, one bilateral adrenal metastasis, and two unilateral adrenal metastases.

Interpretation

In this exploratory study, APA or APN were more frequently seen in DSD and SCD than nDSD cases. Whether primary aldosteronism constitutes a novel risk factor for sudden death warrants further study.

Funding

Finnish State Research funds and independent research foundations: Aarne Koskelo Foundation, the Finnish Kidney Foundation, and the Finnish Foundation for Cardiovascular Research.

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肾上腺醛固酮合成酶（CYP11B2）组织病理学及其与疾病性猝死的关系：一项横断面研究

背景未确定的心血管危险因素可能占突然死亡的大约一半，这是一种具有有限预防工具的破坏性事件。我们研究了原发性醛固酮增多症、嗜铬细胞瘤或肾上腺肿块的肾上腺组织病理学是否可以部分解释疾病性猝死（DSD）的风险。方法对403例猝死患者进行尸检和组织病理学分析，包括肾上腺醛固酮合成酶染色。这些个体被分类为258例猝死，144例死于创伤、自杀或中毒，即非疾病引起的猝死（nDSD）。该试验已在ClinicalTrials.gov注册（NCT05446779）。研究结果：队列中31例（7.7%）患者肾组织病理学改变。其中，最常见的发现[25例（6.2%）]是醛固酮生成腺瘤（APA）或结节（APN），尸检时发现与心肌梗死和动脉粥样硬化相关。与nDSD组相比，DSD组和心源性猝死亚组更容易发生APA或APN [23 (8.9%) vs. 2 (1.4%), p = 0.002；16(8.8%)和2(1.4%),分别为p = 0.003)。APA或APN是DSD（比值比[or] 6.47, 95%可信区间[CI] 1.40 ~ 29.88, p = 0.017）和SCD（比值比[or] 10.68, 95% CI 2.02 ~ 56.43, p = 0.005）的解释因素。其他发现包括两个嗜铬细胞瘤，一个双侧肾上腺转移，和两个单侧肾上腺转移。在本探索性研究中，APA或APN在DSD和SCD中比在nDSD中更常见。原发性醛固酮增多症是否构成猝死的新危险因素有待进一步研究。芬兰国家研究基金和独立研究基金会：Aarne Koskelo基金会、芬兰肾脏基金会和芬兰心血管研究基金会。

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来源期刊

Lancet Regional Health-Europe Multiple-

CiteScore

19.90

自引率

1.40%

发文量

260

审稿时长

9 weeks

期刊介绍： The Lancet Regional Health – Europe, a gold open access journal, is part of The Lancet's global effort to promote healthcare quality and accessibility worldwide. It focuses on advancing clinical practice and health policy in the European region to enhance health outcomes. The journal publishes high-quality original research advocating changes in clinical practice and health policy. It also includes reviews, commentaries, and opinion pieces on regional health topics, such as infection and disease prevention, healthy aging, and reducing health disparities.