German Cancer Research Center (DKFZ), Division of Cancer Epidemiology, Im Neuenheimer Feld 581, 69120 Heidelberg, Germany.
Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany.
Am J Clin Nutr. 2018 Jan 1;107(1):113-119. doi: 10.1093/ajcn/nqx014.
High iron load and red meat consumption could increase the risk of cardiovascular diseases (CVDs). As red meat is the main source of heme iron, which is in turn a major determinant of increased iron load, adverse cardiometabolic effects of meat consumption could be mediated by increased iron load.
The object of the study was to assess whether associations between red meat consumption and CVD risk are mediated by iron load in a population-based human study.
We evaluated relations between red meat consumption, iron load (plasma ferritin), and risk of CVD in the prospective EPIC-Heidelberg Study using a case-cohort sample including a random subcohort (n = 2738) and incident cases of myocardial infarction (MI, n = 555), stroke (n = 513), and CVD mortality (n = 381). Following a 4-step mediation analysis, associations between red meat consumption and iron load, red meat consumption and CVD risk, and iron load and CVD risk were assessed by multivariable regression models before finally testing to which degree associations between red meat consumption and CVD risk were attenuated by adjustment for iron status.
Red meat consumption was significantly positively associated with ferritin concentrations and MI risk [HR per 50 g daily intake: 1.18 (95% CI: 1.05, 1.33)], but no significant associations with stroke risk and CVD mortality were observed. While direct associations between ferritin concentrations and MI risk as well as CVD mortality were significant in age- and sex-adjusted Cox regression models, these associations were substantially attenuated and no longer significant after multivariable adjustment for classical CVD risk factors. Strikingly, ferritin concentrations were positively associated with a majority of classical CVD risk factors (age, male sex, alcohol intake, obesity, inflammation, and lower education).
Increased ferritin concentrations may be a marker of an overall unfavorable risk factor profile rather than a mediator of greater CVD risk due to meat consumption.
高铁负荷和食用红肉可能会增加心血管疾病(CVD)的风险。由于红肉是血红素铁的主要来源,而血红素铁又是增加铁负荷的主要决定因素,因此肉类消费对心脏代谢的不良影响可能是通过增加铁负荷来介导的。
本研究旨在通过一项基于人群的人类研究来评估红肉摄入与 CVD 风险之间的关联是否通过铁负荷来介导。
我们使用前瞻性 EPIC-Heidelberg 研究中的病例-队列样本(包括一个随机亚队列(n=2738)和心肌梗死(MI,n=555)、中风(n=513)和 CVD 死亡率(n=381)的病例),评估了红肉摄入、铁负荷(血浆铁蛋白)与 CVD 风险之间的关系。在进行多变量回归模型评估铁负荷与 CVD 风险之间的关联之前,首先进行了 4 步中介分析,以评估红肉摄入与铁负荷、红肉摄入与 CVD 风险以及铁负荷与 CVD 风险之间的关联,最后检验通过调整铁状态,红肉摄入与 CVD 风险之间的关联在多大程度上减弱。
红肉摄入与铁蛋白浓度呈显著正相关,与 MI 风险呈正相关[每 50g 每日摄入量的 HR:1.18(95%CI:1.05,1.33)],但与中风风险和 CVD 死亡率无显著关联。虽然在年龄和性别调整的 Cox 回归模型中,铁蛋白浓度与 MI 风险和 CVD 死亡率之间的直接关联具有统计学意义,但在对经典 CVD 危险因素进行多变量调整后,这些关联显著减弱且不再具有统计学意义。引人注目的是,铁蛋白浓度与大多数经典 CVD 危险因素(年龄、男性、饮酒、肥胖、炎症和低教育水平)呈正相关。
铁蛋白浓度升高可能是整体不良危险因素谱的标志物,而不是由于肉类摄入导致 CVD 风险增加的中介物。