Gender differences in change of metabolic syndrome status and its components on all-cause and cause-specific mortalities: Over a decade follow-up study

Background: 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.Methods and results: 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.Conclusion: 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.

Automated summary

The stable state of metabolic syndrome may increase the risk of mortality, with a stronger association in women. Even in the absence of hypertension and diabetes, metabolic syndrome in women may still carry a corresponding effect, increasing the risk of all-cause mortality.