Reduced circulating sTWEAK levels are associated with metabolic syndrome in elderly individuals at high cardiovascular risk

Andrés Díaz-López,Jordi Salas-Salvadó,Ramón Estruch,Joan Vendrell,Dolores Corella,Javier Díez-Espino,Matilde R Chacón,Montserrat Fitó,Mònica Bulló

doi:10.1186/1475-2840-13-51

Abstract

BackgroundThe circulating soluble TNF-like weak inducer of apoptosis (sTWEAK) is a cytokine that modulates inflammatory and atherogenic reactions related to cardiometabolic risk. We investigated the association between sTWEAK levels and metabolic syndrome (MetS) and its components in older subjects at high cardiovascular risk.MethodsCross-sectional analysis of 452 non-diabetic individuals (men and women aged 55–80 years) at high cardiovascular risk. MetS was defined by AHA/NHLBI and IDF criteria. Logistic regression analyses were used to estimate odds ratios (ORs) for MetS and its components by tertiles of serum sTWEAK concentrations measured by ELISA.ResultssTWEAK concentrations were lower in subjects with MetS than in those without. In gender- and age-adjusted analyses, subjects in the lowest sTWEAK tertile had higher ORs for overall MetS [1.71 (95% CI, 1.07-2.72)] and its components abdominal obesity [2.01 (1.15-3.52)], hyperglycemia [1.94 (1.20-3.11)], and hypertriglyceridemia [1.73 (1.05-2.82)] than those in the upper tertile. These associations persisted after controlling for family history of diabetes and premature coronary heart disease, lifestyle, kidney function and other MetS components. sTWEAK concentrations decreased as the number of MetS components increased. Individuals in the lowest vs the upper sTWEAK tertile had an increased risk of disclosing greater number of MetS features. Adjusted ORs for individuals with 2 vs ≤1, 3 vs ≤1, and ≥4 vs ≤ 1 MetS components were 2.60 (1.09-6.22), 2.83 (1.16-6.87) and 6.39 (2.42-16.85), respectively.ConclusionIn older subjects at high cardiovascular risk, reduced sTWEAK levels are associated with MetS: abdominal obesity, hypertriglyceridemia and hyperglycemia are the main contributors to this association.

Highlights

The circulating soluble TNF-like weak inducer of apoptosis is a cytokine that modulates inflammatory and atherogenic reactions related to cardiometabolic risk
Circulating soluble TNF-like weak inducer of apoptosis (sTWEAK) concentrations have been negatively correlated with such other laboratory and clinical parameters as fasting plasma glucose levels, insulin resistance assessed by homeostasis model assessment of insulin resistance (HOMA-IR) and systolic or diastolic blood pressure in patients with type 2 diabetes (T2D) and in chronic kidney disease [10,14]
We used the same partial correlation analysis to assess the relationship between sTWEAK concentrations and such markers of kidney function as urinary albumin (mg/L)-to-creatinine (mg/dL) ratio (ACR) (ACR data was available for only 246 participants) and eGFR

Summary

Introduction

The circulating soluble TNF-like weak inducer of apoptosis (sTWEAK) is a cytokine that modulates inflammatory and atherogenic reactions related to cardiometabolic risk. TWEAK is ubiquitously expressed in a variety of organs, tissues and cell types, with high levels in heart, brain, pancreas, In recent years, cross-sectional studies investigating the associations between sTWEAK and diseases and/or metabolic disorders have been widely reported. In this context, Blanco-Colio et al reported lower levels of sTWEAK in patients with atherosclerosis and a negative correlation between circulating TWEAK levels and the intima/media thickness in asymptomatic subjects [5]. Our group has demonstrated that patients with type 1 diabetes (T1D) had lower sTWEAK levels than healthy subjects [15], and a negative association between sTWEAK levels, glucose metabolism-related parameters and T2D incidence has been reported [16]

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Conclusion