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The metabolic syndrome is a general term given to a clustering of cardiometabolic risk factors that may consist of different phenotype combinations. The purpose of this study was to determine the prevalence of the different combinations of factors that make up the metabolic syndrome as defined by the National Cholesterol Education Program and to examine their association with all-cause mortality in younger and older men and women.A total of 2,784 men and 3,240 women from the Third National Health and Nutrition Examination Survey with public-access mortality data linkage (follow-up = 14.2 ± 0.2 years) were studied.Metabolic syndrome was present in 26% of younger (aged ≤65 years) and 55.0% of older (aged >65 years) participants. The most prevalent metabolic syndrome combination was the clustering of high triglycerides, low HDL cholesterol, and elevated blood pressure in younger men (4.8%) and triglycerides, HDL cholesterol, and elevated waist circumference in younger women (4.2%). The presence of all five metabolic syndrome factors was the most common metabolic syndrome combination in both older men (8.0%) and women (9.2%). Variation existed in how metabolic syndrome combinations were associated with mortality. In younger adults, having all five metabolic syndrome factors was most strongly associated with mortality risk, whereas in older men, none of metabolic syndrome combinations were associated with mortality. In older women, having elevated glucose or low HDL as one of the metabolic syndrome components was most strongly associated with mortality risk.Metabolic syndrome is a heterogeneous entity with age and sex variation in component clusters that may have important implications for interpreting the association between metabolic syndrome and mortality risk. Thus, metabolic syndrome used as a whole may mask important differences in assessing health and mortality risk.