Age- and sex- specific all-cause mortality risk greatest in metabolic syndrome combinations with elevated blood pressure from 7 U.S. cohorts

Background: The association between metabolic syndrome (MetS) and all-cause mortality is well established but it is unclear if there are differences in mortality risk among the 32 possible MetS combinations. Hence, the purpose of this study is to evaluate the associations between different MetS combinations and its individual components with all-cause mortality, and to examine differences in the association by age and sex. Methods: A merged sample of 82,717 adults from 7 U.S. cohorts was used. Results: In our sample, MetS was present in 32% of men, 34% of women, 28% of younger adults (18–65 years) and 62% of older adults (>65 years) with 14,989 deaths over 14.6 ± 7.4 years of follow-up. Risk of all-cause mortality was higher in younger individuals with a greater number of MetS factors present, but in older adults having all 5 MetS factors was the only combination significantly associated with mortality. Regardless of age or sex, elevated blood pressure was the MetS factor most consistently present in MetS combinations that were significantly and most strongly associated with mortality. In fact, elevated blood pressure in the absence of other risk factors was significantly associated with mortality in men (HR, 95% CI = 1.56, 1.33–1.84), women (HR = 1.62, 1.44–1.81) and younger adults (HR = 1.61, 1.45–1.79). Conversely, waist circumference, glucose and triglycerides in isolation were not associated with mortality (p>0.05). Conclusion: In a large U.S. population, different combinations of MetS components vary substantially in their associations with all-cause mortality. Men, women and younger individuals with MetS combinations including elevated blood pressure had stronger associations with greater mortality risk, with minimal associations between MetS and mortality risk in older adults. Thus, we suggest that future algorithms may wish to consider differential weighting of these common metabolic risk factors, particularly in younger populations.