Abstract
BACKGROUND: Metabolic syndrome (MetS) encompasses a collection of metabolic abnormalities. This study aims to determine which combination of MetS components has the highest mortality risk, and to investigate the causal relationships between MetS components and longevity. METHODS: Prospective analyses were conducted on 340,196 participants from the MJ cohort at baseline, and 121,936 participants had follow-up MetS information. We defined MetS according to the NCEP ATP III criteria. The study's outcomes included mortality from cardiovascular disease (CVD), cancer, and all causes combined. We employed Cox proportional hazard models to calculate hazard ratios (HRs) and 95% confidence intervals. Multivariable Mendelian randomization (MVMR) was employed to infer causality using the genetic data of MetS components and longevity. RESULTS: Elevated blood pressure (BP) was the initial split for all-cause mortality, cancer mortality, and CVD mortality. Participants with MetS, especially those with elevated BP and elevated fasting plasma glucose (FPG), had higher mortality risks than those with other types of MetS. In the MJ cohort, participants with elevated BP and FPG (BG-type MetS) had a 44% (HR = 1.44, 95% CI = 1.37-1.51), 73% (HR = 1.73, 95% CI = 1.62-1.84), and 34% (HR = 1.34, 95% CI = 1.27-1.42) increased risk of all-cause mortality, cancer mortality, and CVD mortality, respectively, compared with non-BG-type MetS (12%, 24%, 5%). The highest mortality rate and mortality risk were observed in participants with BG-type MetS at baseline and follow-up (mortality rate/1000 person years = 9.73, 95% CI = 8.81-10.74; HR = 1.52, 95% CI = 1.35-1.72). SBP and FPG increases that were genetically proxied to a 1-standard deviation higher level decreased the probabilities of living to the 90th percentile age by 41% (OR = 0.59, 95% CI = 0.40-0.86) and 32% (OR = 0.68, 95% CI = 0.48-0.98) in MVMR, respectively. CONCLUSIONS: Individuals with BG-type MetS are at a higher risk of death than those with other types of MetS. Therefore, these individuals should be targeted to improve MetS outcomes.