Metabolic syndrome and subsequent risk of type 2 diabetes and cardiovascular disease in elderly women: Challenging the current definition

Abstract

The prognostic value of the metabolic syndrome (MetS) is believed to vary with age. With an elderly population expecting to triple by 2060, it is important to evaluate the validity of MetS in this age group. We examined the association of MetS risk factors with later risk of type 2 diabetes (T2DM) and cardiovascular disease (CVD) in elderly Caucasian women. We further investigated if stratification of individuals not defined with MetS would add predictive power in defining future disease prevalence of individuals with MetS.The Prospective Epidemiological Risk Factor Study, a community-based cohort study, followed 3905 Danish women since 2000 (age: 70.1 ± 6.5) with no previous diagnosis of T2DM or CVD, holding all measurements used for MetS definition; central obesity, hypertension, hyperlipidemia, and hyperglycemia combined with register-based follow-up information.Elderly women with defined MetS presented a 6.3-fold increased risk of T2DM (95% confidence interval: [3.74-10.50]) and 1.7-fold increased risk of CVD (1.44-2.05) compared to women with no MetS risk factors. Subdividing the control group without defined MetS revealed that both centrally obese controls and controls holding other MetS risk factors also had increased risk of T2DM (hazard ratio (HR) = 2.21 [1.25-3.93] and HR = 1.75 [1.04-2.96]) and CVD (HR = 1.51 [1.25-1.83] and HR = 1.36 [1.15-1.60]) when compared to controls with no MetS risk factors.MetS in elderly Caucasian women increased risk of future T2DM and CVD. While not defined with MetS, women holding only some risk factors for MetS were also at increased risk of T2DM or CVD compared to women with no MetS risk factors.

Figure 1

Definition of the study population. CVD = cardiovascular disease, MetS = metabolic syndrome, IDF = International Diabetes Federation, PERF = Prospective Epidemiological Risk Factor study.

Figure 2

Risk associated with the 5 metabolic risk factors used to define the metabolic syndrome showed central obesity to be the only risk factor contributing to increased risk of both T2DM and CVD outcome. Multivariate Cox regression analysis for the risk of developing T2DM and CVD based on individual metabolic risk factors; central obesity, high blood pressure, elevated fasting glucose, decreased HDL cholesterol, and increased triglyceride levels. Values were adjusted for age, smoking, alcohol consumption, and physical activity. CVD = cardiovascular disease, T2DM = type 2 diabetes mellitus. Data represent hazard ratio with 95% confidence interval.

Figure 3

A heterogeneous metabolic risk profile within the control group. (A) Principal component analysis score plot colored by group: reference group subjects with no metabolic risk factors (green), subjects with risk factors for MetS but no central obesity (gray), subjects with central obesity and up to 1 other MetS risk factor (purple), and subjects with defined MetS (orange). The ellipses cover 68% of the subjects belonging to a given subgroup. Loadings for the included parameters are shown with arrows. ALAT = alanine-aminotransferase, ASAT = aspartate-aminotransferase, C/P ratio = central/peripheral fat mass ratio, cholesterol = total cholesterol, glucose = fasting glucose, WBC = white blood cell count. Exercise: physical activity. (B) Distribution of the principal component 1 scores for the 4 subgroups. Boxes represent the upper quartile, the mean, and the lower quartile of the data. Whiskers designate the Tukey interval with outliers shown as staggered dots. ^∗∗∗P < 0.001. MetS = metabolic syndrome, non-CO = non-central obese.

Figure 4

Stratification of the heterogeneous control group in identified intermediate subgroups with increased risk for later T2DM and CVD. (A) Multivariate Cox regression analysis for the risk of developing T2DM and CVD based on control group stratification. Subgroups represent reference group with no risk factors for MetS, subjects with risk factors for MetS but no central obesity, subjects with central obesity and up to one additional MetS risk factor, and subjects with defined MetS. Values are adjusted for age, smoking, alcohol consumption, and physical activity. CVD = cardiovascular disease, MetS = metabolic syndrome, non-CO = non-central obesity, T2DM = type 2 diabetes mellitus. (B) Risk of developing T2DM and CVD for subjects with 1 to 5 risk factors for MetS as compared to the reference group with no MetS risk factors. 0: n = 432; 1: n = 1404; 2: n = 1083; 3: n = 647; 4: n = 271; and 5: n = 68. Values are adjusted for age, smoking, alcohol, and physical activity. Data represent hazard ratio with 95% confidence interval.