越来越多的证据表明代谢综合征（MetS）与死亡的风险之间存在密切关联。然而，MetS及其组分的动态变化是否会影响特定原因的死亡风险，以及这种关系如何受性别影响，尚有待澄清。在这个长期队列研究中，我们纳入了4904名30岁以上的伊朗成年人（其中2820名女性），从1999年3月开始追踪至2018年12月。我们使用联合过渡期协会（JIS）的标准确定了MetS的诊断标准。由于MetS状态在三年内的变化，我们将个体划分为无MetS、MetS恢复、MetS发展和MetS持续四组。MetS的每个组分也定义了相同的分类。采用多变量Cox回归模型计算了校正后的危险比（HRs）和女性对男性的相对危险比（F/M-RHRs）以评估总因死亡、心血管（CV）、非CV和癌症的风险。为了排除逆向因果关系，我们排除了追踪期的前三年内的死亡事件。对于非糖尿病和非高血压患者进行了亚组分析。在12.5年的追踪中，共发生了357例总因死亡，112例心血管病因死亡和79例癌症死亡。与无MetS相比，MetS持续组的男女都增加了总因死亡和心血管病因死亡的风险。对于无糖尿病（HR = 1.66（1.03-3.00））或无高血压（HR = 1.89（1.09-3.64））的女性，也发现了同样的关联。此外，既无高血压也无糖尿病的MetS持续女性的总因死亡风险增加了88%（F/M-RHR = 3.99（1.53-5.58））。稳定的MetS状态使女性癌症死亡风险增加了40%（F/M-RHR = 1.63（1.02-5.06））。总的来说，无论男女，从MetS中恢复能降低死亡风险。关于MetS组分，持续升高的空腹血糖（FPG）与男女的总因死亡相关，但在女性中的关联更强（F/M-RHR = 1.41（1.11-2.49）），并且仅与女性的心血管病因死亡有关（F/M-RHR = 3.04（1.02-5.96））。高血压的发展或稳定状态仅增加了女性的心血管病因死亡风险（F/M-RHR = 3.10（0.60-6.87）和F/M-RHR = 3.24（1.26-6.11），分别）。每个甘油三酯、高密度脂蛋白胆固醇和腰围变量的发展或恢复并不能单独影响男女死亡风险。稳定的MetS状态可能会增加风险，而在女性中的关联较强。尽管高血压和高血糖是死亡风险的主要驱动因素，但即使没有高血压和糖尿病，女性的MetS也可能具有相应的效应。© 2023 The Italian Diabetes Society、意大利动脉粥样硬化研究学会、意大利人类营养学学会和罗马费德里科二世大学临床医学和外科学系。由Elsevier B.V.出版。版权所有。

Accumulating evidence suggests a close association between metabolic syndrome (MetS) and excess risk of mortality. However, whether the dynamic change of MetS and its components could affect cause-specific mortalities and how this relation could be influenced by gender is yet to be clarified.In this longitudinal cohort, we entered 4904 Iranian adults>30 years (2820 women) from March-1999 and followed up until December-2018. MetS was determined using the joint interim societies (JIS) criteria. Due to change in MetS status over three years, we divided individuals into MetS-free, MetS-recovery, MetS-developed, and MetS-persistent groups. The same categories were defined for each MetS component. Multivariate Cox regression models were employed to compute the adjusted hazard ratios (HRs) and female-to-male relative HRs (F/M-RHRs) for risk of all-cause, cardiovascular (CV), non-CV, and cancer mortalities. To resolve reverse causation, mortalities during the first three years of follow-up were excluded. Subgroup analysis was conducted for non-diabetic and non-hypertensive participants. During 12.5 years of follow-up, 357 all-cause, 112 CV-, and 79 cancer-mortalities occurred. Compared to MetS-free, MetS-persistent raised all-cause- and CV-mortalities in both genders. Same association was found for non-diabetic (HR = 1.66 (1.03-3.00)) or non-hypertensive (HR = 1.89 (1.09-3.64)) women. Moreover, MetS-persistent women with neither hypertension nor diabetes had increased all-cause mortality risk by 88% (F/M-RHR = 3.99 (1.53-5.58)). Women with stable MetS had excess risk of cancer-mortality by 40% (F/M-RHR = 1.63 (1.02-5.06)). Generally, among both genders, recovery from MetS declined risk of mortality events. Regarding MetS components, persistent elevated fasting plasma glucose (FPG) was related to all-cause mortality in both genders, but with stronger association in women (F/M-RHR = 1.41 (1.11-2.49), and CV-mortality only in women (F/M-RHR = 3.04 (1.02-5.96). Both development and stable status of high blood pressure (BP) increased the risk of CV-mortality merely in women (F/M-RHR = 3.10 (0.60-6.87) and F/M-RHR = 3.24 (1.26-6.11), respectively). Development or recovery from each Triglyceride, HDL-C, and waist circumference variables did not solely affect risk of mortality events in both genders.Stable status of MetS could increase risk of mortalities with an overall stronger association in women. Although elevated BP and FPG are the main drivers for mortality risk, MetS among women could carry the corresponding effect even in absence of hypertension and diabetes.Copyright © 2023 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.