Department of Public Health and Clinical Medicine, Section of Medicine, Umeå University, 901 87 Umeå, Sweden.
Department of Public Health and Clinical Medicine, Skellefteå Research Unit, Umeå University, 901 87 Umeå, Sweden.
Int J Mol Sci. 2022 Sep 6;23(18):10251. doi: 10.3390/ijms231810251.
Patients at a high risk for sudden cardiac death (SCD) without previous history of cardiovascular disease remain a challenge to identify. Atherosclerosis and prothrombotic states involve inflammation and non-cardiac tissue damage that may play active roles in SCD development. Therefore, we hypothesized that circulating proteins implicated in inflammation and tissue damage are linked to the future risk of SCD. We conducted a prospective nested case-control study of SCD cases with verified myocardial infarction (N = 224) and matched controls without myocardial infarction (N = 224), aged 60 ± 10 years time and median time to event was 8 years. Protein concentrations (N = 122) were measured using a proximity extension immunoassay. The analyses revealed 14 proteins significantly associated with an increased risk of SCD, from which two remained significant after adjusting for smoking status, systolic blood pressure, BMI, cholesterol, and glucose levels. We identified leukotriene A4 hydrolase (LTA4H, odds ratio 1.80, corrected confidence interval (CI) 1.02-3.17) and hepatocyte growth factor (HGF; odds ratio 1.81, CI 1.06-3.11) as independent risk markers of SCD. Elevated LTA4H may reflect increased systemic and pulmonary neutrophilic inflammatory processes that can contribute to atherosclerotic plaque instability. Increased HGF levels are linked to obesity-related metabolic disturbances that are more prevalent in SCD cases than the controls.
患有非心血管疾病的高危患者仍难以识别。动脉粥样硬化和血栓形成状态涉及炎症和非心脏组织损伤，这些可能在 SCD 发展中发挥积极作用。因此，我们假设涉及炎症和组织损伤的循环蛋白与 SCD 的未来风险有关。我们对患有已证实心肌梗死的 SCD 病例（N=224）和无心肌梗死的匹配对照（N=224）进行了前瞻性巢式病例对照研究，年龄 60±10 岁，中位随访时间为 8 年。使用邻近延伸免疫测定法测量蛋白质浓度（N=122）。分析显示 14 种蛋白质与 SCD 风险增加显著相关，其中两种蛋白质在调整吸烟状态、收缩压、BMI、胆固醇和血糖水平后仍然显著。我们确定了白三烯 A4 水解酶（LTA4H，比值比 1.80，校正置信区间（CI）1.02-3.17）和肝细胞生长因子（HGF；比值比 1.81，CI 1.06-3.11）是 SCD 的独立风险标志物。LTA4H 升高可能反映了全身性和肺部嗜中性粒细胞炎症过程的增加，这可能导致动脉粥样硬化斑块不稳定。HGF 水平升高与肥胖相关的代谢紊乱有关，这种紊乱在 SCD 病例中比对照组更为普遍。
