Association Of Chronic Subclinical Inflammation With Metabolic Syndrome

【Background】The metabolic syndrome is characterized as a group of cardiovascular risk factors including visceral obesity, hypertension, dyslipidemia, and impaired glucose tolerance.The pathogenesy of MS is not completely definite as yet. It is now realized that insulin resistance plays a principal role in initiating and perpetuating the pathologic manifestations of the metabolic syndrome. Some studies of epidemiology, clinic and basis showed that MS is a chronic,low-grade, systemic,inflammatory condition, of which inflammation maybe play a pivotal role from cell signal transduction mechanism. Chronic subclinical inflammation has been a hot spot of MS research and inflammation may become the effective therapy target point of MS.However,the association of chronic subclinical inflammation with metabolic syndrome has not been confirmed as yet.【Objective】To investigate the association of inflammatory markers high sensitivity C-reactive protein (hs-CRP), Interleukin-6 (IL-6), tumor necrosis factor-alpha(TNF-α),fibrinogen (Fg), plasminogen activator inhibitor-1(PAI-1),white blood cell (WBC) with metabolic syndrome (MS), and explore the role of chronic subclinical inflammation play in the development of metabolic syndrome.【Methods】160 subjects were enrolled, including 128 in-patients from Department of Cardiology and 32 health examinees. Baseline clinical measures included systolic blood pressure (SBP), diastolic pressure (DBP), waist circumference(WC), body mass index (BMI, kg/m2) was calculated based on weight and height. Plasma lipids, fasting blood glucose (FPG), fasting insulin, uric acid (UA), and the blood levels of hs-CRP, IL-6, TNF-α,Fg, PAI-1, WBC were also measured respectively. Association of the six inflammatory markers with MS components was analyzed.【Results】(1)The blood level of hs-CRP ( 3.69±0.80 vs 1.89±0.54 ,P<0.001),IL-6(135.40±64.20 vs 110.83±73.20 , P<0.001),TNF-α(25.42±9.20 vs 15.45±5.24,P<0.001),Fg(3.38±0.73 vs 3.13±0.48,P=0.025),PAI-1(53.89±7.92 vs 32.02±5.28,P<0.001),WBC(6.99±1.70 vs 6.53±1.71,P=0.034) in patients with MS were higher than that of subjects without MS.(2)The level of hs-CRP(1.69±0.62 vs 1.78±0.44 vs 2.09±0.52 vs 3.09±0.80 vs 3.49±0.74 vs 3.66±0.90 ,P=0.014),IL-6(98.83±83.22 vs 106.83±74.28 vs 118.83±68.26 vs 124.40±64.36 vs 130.40±55.40 vs 138.42±82.33 ,P=0.013),TNF-α(12.36±6.23 vs 14.27±7.34 vs 16.47±6.45 vs 23.45±7.24 vs 25.16±6.28 vs 26.42±10.22,P=0.022),Fg(3.02±0.57 vs 3.09±0.36 vs 3.14±0.58 vs 3.26±0.73 vs 3.30±0.64 vs 3.40±0.84 ,P=0.042),PAI-1(26.34±5.45 vs 30.12±6.38 vs 33.67±5.38 vs 48.23±7.28 vs 52.13±4.64 vs 56.23±5.92,P=0.045),WBC(6.55±1.72 vs 6.45±1.88 vs 6.58±1.71 vs 6.68±1.63 vs 6.96±1.74 vs 6.98±1.93,P=0.028) were elevated in accordance with the number of MS components coun(t0,1,2,3,4,5).(3) Spearman correlation analysis showed that hs-CRP was associated with WC(r=0.490,P<0.01),BMI(r=0.449,P<0.01),TG(r=0.351,P<0.01),FPG(r=0.237,P<0.01),SBP(r=0.393,P<0.01),DBP(r=0.222,P<0.01)positively;IL-6 was associated with WC(r=0.430,P<0.01),BMI(r=0.428,P<0.01),TG(r=0.378,P<0.01),FPG(r=0.231,P<0.01),SBP(r=0.388,P<0.01),DBP(r=0.230,P<0.01) positively;TNF-αwas associated with WC(r=0.432,P<0.01),BMI(r=0.434,P<0.01),TG(r=0.396,P<0.01),FPG(r=0.242,P<0.01),SBP(r=0.372,P<0.01),DBP(r=0.220,P<0.05)positively;PAI-1 was associated with WC(r=0.320,P<0.01),BMI(r=0.193,P<0.05),TG(r=0.326,P<0.01),FPG(r=0.231,P<0.01),SBP(r=0.188,P<0.05)positively;Fg was associated with WC(r=0.365,P<0.01),BMI(r=0.202,P<0.05),TG(r=0.324,P<0.01),FPG(r=0.224,P<0.01),SBP(r=0.272,P<0.05),DBP(r=0.290,P<0.01)positively;WBC was associated with WC(r=0.204,P<0.05),BMI(r=0.197,P<0.05),TG(r=0.229, P<0.01),FPG(r=0.210,P<0.01)positively.hs-CRP,IL-6,TNF-α,PAI-1,Fg,WBC were associated with HDL-C negatively.hs-CRP,IL-6 and TNF-αshowed a stronger association with MS components than other three inflammatory markers. (4)Logistic regression analysis showed that hs-CRP(OR=1.813,OR 95%CI:1.127-2.915,P=0.014),IL-6(OR=1.987,OR 95%CI:1.204-3.012,P=0.018), TNF-α(OR=2.151,OR 95%CI:1.274-3.302,P=0.003), Fg(OR=1.789,OR 95%CI:1.183-2.625,P=0.024), PAI-1(OR=1.736,OR 95%CI:1.125-2.432,P=0.032),WBC (OR=1.314,OR 95%CI: 1.097-1.574,P=0.008)were risk factors of MS, and hs-CRP,IL-6,TNF-αwere strong predictors who showed a stronger association with MS than other three inflammatory markers.(5) HOMA-IR was associated with hs-CRP ( r=0.260 ,P<0.01),IL-6(r=0.214,P<0.05),TNF-α(r=0.223,P<0.01),Fg (r=0.206,P<0.05),PAI-1(r=0.157,P<0.05)and WBC(r=0.147,P<0.05)positively.【Conclusions】1.The levels of inflammatory markers in patients with MS were higher than that of subjects without MS. Inflammatory markers were correlated to several components of MS.The level of inflammatory markers were elevated in accordance with the number of MS components count. It showed that chronic subclinical inflammation was associated with MS closely,and that may be the basis of generation and development about MS. 2. hs-CRP,IL-6,TNF-α,Fg,PAI-1,WBC were risk factors for MS and hs-CRP,IL-6,TNF-αwere strong predictors who showed a stronger association with MS than other three inflammatory markers. 3.Chronic subclinical inflammation may aggravate the development of MS through insulin resistance.