基于类固醇组学的原发性醛固酮增多症筛查：抗高血压药物的影响
Steroidomics-Based Screening for Primary Aldosteronism: Impact of antihypertensive Drugs.
作者信息
Constantinescu Georgiana, Gruber Sven, Fuld Sybille, Peitzsch Mirko, Schulze Manuel, Remde Hanna, Kürzinger Lydia, Yang Jun, Yen Tina, Williams Tracy Ann, Müller Lisa, Reincke Martin, Lenders Jacques W M, Beuschlein Felix, Pamporaki Christina, Eisenhofer Graeme F
机构信息
Department of Medicine III, University Hospital Carl Gustav Carus (G.C., S.F., C.P., G.F.E.).
Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital Zurich, University of Zurich, Switzerland (S.G., F.B.).
出版信息
Hypertension. 2024 Oct;81(10):2060-2071. doi: 10.1161/HYPERTENSIONAHA.124.23029. Epub 2024 Jul 31.
BACKGROUND
Diagnosis of primary aldosteronism (PA) is complicated by the need to withdraw antihypertensive medications that interfere with test results, particularly renin. This study examined whether machine learning-based steroid-probability scores offer a renin measurement-independent approach for testing less prone to interference than the aldosterone-to-renin ratio (ARR).
METHODS
This prospective multicenter cohort study involved the use of plasma steroidomics and the ARR in 839 patients tested for PA, including 190 with and 578 without PA (71 indeterminate). Receiver operating characteristic curves for steroid-probability scores and the ARR were examined with and without interfering medications. Impacts of individual medications on plasma aldosterone, 18-oxocortisol, 18-hydroxycortisol, steroid-probability scores, renin, and ARRs were examined by multivariable and paired analyses in patients with and without PA.
RESULTS
Receiver operating characteristic curves indicated a significant impact of interfering antihypertensive medications on the diagnostic performance of the ARR and minimal impact on steroid-probability scores. Mineralocorticoid receptor antagonists increased plasma aldosterone, 18-oxocortisol, and 18-hydroxycortisol in patients without PA and resulted in false-positive test results for steroid-probability scores and false-negative results for the ARR. Diuretics increased aldosterone, 18-oxocortisol, and steroid-probability scores in patients without PA, whereas angiotensin-converting enzyme inhibitors decreased aldosterone, steroid-probability scores, and ARRs. Beta-adrenoceptor blockers, dihydropyridine calcium channel blockers, and angiotensin receptor blockers had negligible impact on mineralocorticoids and steroid-probability scores.
CONCLUSIONS
Among antihypertensive drugs that impact plasma aldosterone, 18-oxocortisol, and 18-hydroxycortisol, mineralocorticoid receptor antagonists stood out as a cause of false-positive results for derived steroid-probability scores. Other antihypertensives have minimal or no impact, an advantage for use of steroid-probability scores over the ARR when those medications cannot be withdrawn.
REGISTRATION
URL: https://drks.de/search/en/trial/DRKS00017084; Unique identifier: DRKS00017084.
背景
原发性醛固酮增多症（PA）的诊断较为复杂，因为需要停用会干扰检测结果的抗高血压药物，尤其是肾素。本研究探讨基于机器学习的类固醇概率评分是否提供了一种独立于肾素测量的检测方法，该方法比醛固酮与肾素比值（ARR）更不易受干扰。
方法
这项前瞻性多中心队列研究纳入了839例接受PA检测的患者，使用了血浆类固醇组学和ARR，其中190例患有PA，578例未患PA（71例结果不确定）。在有和没有干扰药物的情况下，分别检查了类固醇概率评分和ARR的受试者工作特征曲线。通过多变量分析和配对分析，研究了个体药物对患有和未患PA患者的血浆醛固酮、18-氧皮质醇、18-羟皮质醇、类固醇概率评分、肾素和ARR的影响。
结果
受试者工作特征曲线表明，干扰性抗高血压药物对ARR的诊断性能有显著影响，而对类固醇概率评分的影响最小。盐皮质激素受体拮抗剂会使未患PA患者的血浆醛固酮、18-氧皮质醇和18-羟皮质醇升高，并导致类固醇概率评分出现假阳性检测结果，ARR出现假阴性结果。利尿剂会使未患PA患者的醛固酮、18-氧皮质醇和类固醇概率评分升高，而血管紧张素转换酶抑制剂会降低醛固酮、类固醇概率评分和ARR。β-肾上腺素能受体阻滞剂、二氢吡啶类钙通道阻滞剂和血管紧张素受体阻滞剂对盐皮质激素和类固醇概率评分的影响可忽略不计。
结论
在影响血浆醛固酮、18-氧皮质醇和18-羟皮质醇的抗高血压药物中，盐皮质激素受体拮抗剂是导致衍生类固醇概率评分出现假阳性结果的原因。其他抗高血压药物的影响极小或无影响，当无法停用这些药物时，使用类固醇概率评分比使用ARR更具优势。
注册
网址：https://drks.de/search/en/trial/DRKS00017084；唯一标识符：DRKS00017084。
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