Department of Cardiology and Transplant Institute, Sahlgrenska University Hospital, Gothenburg, Sweden.
Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Int J Obes (Lond). 2022 Dec;46(12):2088-2094. doi: 10.1038/s41366-022-01194-0. Epub 2022 Aug 9.
Obesity is associated with incident heart failure (HF), but the underlying mechanisms are unclear.
We performed a nested case-control study within the Swedish-Obese-Subjects study, by identifying 411 cases who developed HF and matched them with respect to age, sex, weight-loss-surgery and length of follow-up with 410 controls who did not develop HF. In analyses corrected for multiple testing, we studied 182 plasma proteins known to be related to cardiovascular disease to investigate whether they could add to the understanding of the processes underlying obesity-related HF.
A total of 821 subjects were followed for 16 ± 6 years. Multivariable analysis adjusted for matching variables revealed that 32 proteins were significantly associated with HF. Twelve proteins were related to HF ≥ 80% of the time using a bootstrap resampling approach (false-discovery-rate [FDR] < 0.05): 11 were associated with increased HF-risk: TNFRSF10A*, ST6GAL1, PRCP, MMP12, TIMP1, CCL3, QPCT, ANG, C1QTNF1, SERPINA5 and GAL-9; and one was related to reduced HF-risk: LPL. An further 20 proteins were associated with onset of HF 50-80% of the time using bootstrap resampling (FDR < 0.05). A pathway analysis including all significant 32 proteins suggested that these biomarkers were related to inflammation, matrix remodeling, cardiometabolic hormones and hemostasis. Three proteins, C1QTNF1, FGF-21 and CST3, reflecting dyslipidemia and kidney disease, displayed a higher association with HF in patients who did not undergo weight-loss-surgery and maintained with obesity.
Pathways associated with HF in obesity include inflammation, matrix remodeling, cardiometabolic hormones and hemostasis; three protein biomarkers predicting HF appeared to be obesity-specific.
肥胖与心力衰竭（HF）的发生有关，但潜在机制尚不清楚。
我们在瑞典肥胖受试者研究中进行了一项嵌套病例对照研究，通过确定 411 例发生 HF 的病例，并根据年龄、性别、减肥手术和随访时间与未发生 HF 的 410 例对照相匹配，对 182 种已知与心血管疾病相关的血浆蛋白进行了研究，以探讨它们是否有助于了解肥胖相关 HF 的潜在机制。
共有 821 例受试者接受了 16±6 年的随访。多变量分析调整了匹配变量后显示，有 32 种蛋白质与 HF 显著相关。采用自举重采样方法，有 12 种蛋白质与 HF 的相关性大于 80%（假发现率[FDR]＜0.05）：11 种与 HF 风险增加相关：TNFRSF10A*、ST6GAL1、PRCP、MMP12、TIMP1、CCL3、QPCT、ANG、C1QTNF1、SERPINA5 和 GAL-9；一种与 HF 风险降低相关：LPL。采用自举重采样，另外 20 种蛋白质与 HF 的发生时间相关性为 50-80%（FDR＜0.05）。包括所有显著的 32 种蛋白质的通路分析表明，这些生物标志物与炎症、基质重塑、心脏代谢激素和止血有关。C1QTNF1、FGF-21 和 CST3 三种反映血脂异常和肾脏疾病的蛋白质，与未接受减肥手术且肥胖的患者 HF 相关性更高。
肥胖相关 HF 的途径包括炎症、基质重塑、心脏代谢激素和止血；三种预测 HF 的蛋白质生物标志物似乎是肥胖特异性的。
