Elevated plasma hepcidin concentrations are associated with an increased risk of mortality and nonfatal cardiovascular events in patients with type 2 diabetes: a prospective study.

IF 8.5 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Cardiovascular Diabetology Pub Date : 2024-08-17 DOI:10.1186/s12933-024-02377-x

Alessandro Mantovani, Fabiana Busti, Nicolò Borella, Enrico Scoccia, Barbara Pecoraro, Elena Sani, Riccardo Morandin, Alessandro Csermely, Daniele Piasentin, Elisabetta Grespan, Annalisa Castagna, Josh Bilson, Christopher D Byrne, Luca Valenti, Domenico Girelli, Giovanni Targher

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Abstract

Background: The effect of plasma hepcidin concentrations on the long-term risk of developing adverse cardiovascular outcomes in people with type 2 diabetes mellitus (T2DM) is unclear.

Methods: We followed for a median of 55.6 months 213 outpatients with established T2DM (45.5% women, mean age 69 ± 10 years; BMI 28.7 ± 4.7 kg/m²; median diabetes duration 11 years). Baseline plasma ferritin and hepcidin concentrations were measured with an electrochemiluminescence immunoassay and mass spectrometry-based assay, respectively. The primary study outcome was a composite of all-cause mortality or incident nonfatal cardiovascular events (inclusive of myocardial infarction, permanent atrial fibrillation, ischemic stroke, or new hospitalization for heart failure).

Results: 42 patients developed the primary composite outcome over a median follow-up of 55.6 months. After stratifying patients by baseline hepcidin tertiles [1st tertile: median hepcidin 1.04 (IQR 0.50-1.95) nmol/L, 2nd tertile: 3.81 (IQR 3.01-4-42) nmol/L and 3rd tertile: 7.72 (IQR 6.37-10.4) nmol/L], the risk of developing the primary composite outcome in patients in the 3rd tertile was double that of patients in the 1st and 2nd tertile combined (unadjusted hazard ratio [HR] 2.32, 95%CI 1.27-4.26; p = 0.007). This risk was not attenuated after adjustment for age, sex, adiposity measures, smoking, hypertension, statin use, antiplatelet medication use, plasma hs-C-reactive protein and ferritin concentrations (adjusted HR 2.53, 95%CI 1.27-5.03; p = 0.008).

Conclusions: In outpatients with T2DM, higher baseline hepcidin concentrations were strongly associated with an increased long-term risk of overall mortality or nonfatal cardiovascular events, even after adjustment for established cardiovascular risk factors, plasma ferritin concentrations, medication use, and other potential confounders.

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血浆血钙素浓度升高与 2 型糖尿病患者死亡和非致死性心血管事件风险增加有关：一项前瞻性研究。

背景：血浆血钙素浓度对 2 型糖尿病（T2DM）患者长期心血管不良后果风险的影响尚不清楚：我们对 213 名已确诊的 T2DM 门诊患者（45.5% 为女性，平均年龄为 69 ± 10 岁；体重指数为 28.7 ± 4.7 kg/m2；中位糖尿病病程为 11 年）进行了中位 55.6 个月的随访。血浆铁蛋白和肝素的基线浓度分别用电化学发光免疫测定法和质谱分析法测量。主要研究结果是全因死亡率或非致死性心血管事件（包括心肌梗死、永久性心房颤动、缺血性中风或因心力衰竭再次住院）的复合结果：42名患者在55.6个月的中位随访期间出现了主要的综合结果。按基线血红素三等分对患者进行分层后[第一等分：血红素中位数为1.04（IQR 0.50-1.95) nmol/L，第二等分：3.81（IQR 3.01-4-42) nmol/L，第三等分：7.72（IQR 6.37-10.4) nmol/L]，第 3 三分位数患者发生主要复合结局的风险是第 1 和第 2 三分位数患者总和的两倍（未调整危险比 [HR] 2.32，95%CI 1.27-4.26；P = 0.007）。在对年龄、性别、脂肪含量、吸烟、高血压、他汀类药物的使用、抗血小板药物的使用、血浆 hs-C 反应蛋白和铁蛋白浓度进行调整后，这一风险并未降低（调整后的危险比为 2.53，95%CI 为 1.27-5.03；P = 0.008）：在T2DM门诊患者中，即使调整了既定的心血管风险因素、血浆铁蛋白浓度、药物使用和其他潜在的混杂因素，较高的基线血红素浓度与总体死亡率或非致死性心血管事件的长期风险增加密切相关。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cardiovascular Diabetology 医学-内分泌学与代谢

CiteScore

12.30

自引率

15.10%

发文量

240

审稿时长

1 months

期刊介绍： Cardiovascular Diabetology is a journal that welcomes manuscripts exploring various aspects of the relationship between diabetes, cardiovascular health, and the metabolic syndrome. We invite submissions related to clinical studies, genetic investigations, experimental research, pharmacological studies, epidemiological analyses, and molecular biology research in this field.