Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland, Kuopio, Finland.
Center for Medicine and Clinical Research, Kuopio University Hospital, Kuopio, Finland.
Ann Med. 2024 Dec;56(1):2419996. doi: 10.1080/07853890.2024.2419996. Epub 2024 Nov 26.
To investigate a comprehensive panel of biomarkers and risk of aortic stenosis (AS) in a prospective population-based study.
Anthropometric, metabolic, and inflammatory biomarkers were measured in the Metabolic Syndrome in the Men Study of 10,144 Finnish men without AS at baseline. Cases of AS were identified from the medical records. Cox regression analysis was used to identify variables predicting AS over a follow-up time of 10.8 years. Principal component (PC) analysis was applied to the biomarkers that predicted AS. Cox regression analysis was used to investigate the resulting PCs as AS predictors.
AS was diagnosed in 116 men (1.1%), with a median age of 62 years. In Cox regression analyses, fasting, 30 min, and 120 min plasma insulin, and proinsulin, with hazard ratios (HR) ranging from 1.38 (1.12-1.69, = 2.1E-3) to 1.44 (1.23-1.68, = 4.0E-6), Matsuda index [HR 0.68 (0.56-0.82, = 6.9E-5)], and serum C-peptide [HR 1.47 (1.22-1.77, = 5.0E-5)] were associated with incident AS, in addition to age, systolic blood pressure, BMI, waist circumference, waist/hip ratio, height, body fat mass, fat-free mass, and hs-CRP, and remained significant after adjustments, or if diabetic subjects were excluded. PC 1, consisting of fasting plasma insulin, C-peptide, Matsuda index, waist/hip ratio, and urine albumin excretion, and PC 2, consisting of age, body fat mass, and systolic blood pressure, were significantly associated with AS [HRs 1.37(1.09-1.73) and 1.77 (1.45-2.17), respectively].
Biomarkers reflecting insulin resistance are risk factors for AS, a novel finding indicating that insulin resistance is important in the pathogenesis of AS.
在一项前瞻性的基于人群的研究中，调查一组综合生物标志物与主动脉瓣狭窄（AS）的风险。
在基线时，对没有 AS 的 10144 名芬兰男性进行了代谢综合征男性研究中的人体测量、代谢和炎症生物标志物测量。从病历中确定 AS 病例。使用 Cox 回归分析确定在 10.8 年的随访期间预测 AS 的变量。应用主成分（PC）分析对预测 AS 的生物标志物进行分析。使用 Cox 回归分析研究得出的 PCs 作为 AS 预测因子。
在 116 名男性（1.1%）中诊断出 AS，中位年龄为 62 岁。在 Cox 回归分析中，空腹、30 分钟和 120 分钟的血浆胰岛素和前胰岛素，以及危险比（HR）范围为 1.38（1.12-1.69， = 2.1E-3）至 1.44（1.23-1.68， = 4.0E-6）、Matsuda 指数 [HR 0.68（0.56-0.82， = 6.9E-5）] 和血清 C 肽 [HR 1.47（1.22-1.77， = 5.0E-5）] 与 AS 相关，年龄、收缩压、BMI、腰围、腰臀比、身高、体脂肪量、无脂肪量和 hs-CRP 也是如此，并且在调整后或排除糖尿病患者后仍然具有统计学意义。由空腹血浆胰岛素、C 肽、Matsuda 指数、腰臀比和尿白蛋白排泄组成的 PC1，以及由年龄、体脂肪量和收缩压组成的 PC2，与 AS 显著相关 [HRs 1.37(1.09-1.73) 和 1.77 (1.45-2.17)]。
反映胰岛素抵抗的生物标志物是 AS 的危险因素，这一新发现表明胰岛素抵抗在 AS 的发病机制中很重要。
