High adiponectin levels fail to protect against the risk of hypertension and,in women,against coronary disease:involvement in autoimmunity?

AIM:To investigate whether serum adiponectin protects against cardiometabolic risk in a population sample with prevailing metabolic syndrome.METHODS:Middle-aged adults representative of a general population with baseline circulating adiponectin measurements(n=1224)were analyzed prospectively at a mean of 3.8 years’follow-up,using continuous values or sex-specific tertiles.Total adiponectin was assayed by an ELISA kit.Type-2 diabetes was identified by criteria of the American Diabetes Association.Hypertension was defined as a blood pressure≥140 mmHg and/or≥90 mmHg and/or use of antihypertensive medication.Outcomes were predicted using Cox proportional hazards regression analysis in models that were controlled for potential confounders.RESULTS:In models of multiple linear regression,sex hormone-binding globulin,fasting insulin(inverse)and,in men,age were significant independent covariates of serum adiponectin which further tended in women to be positively associated with serum creatinine.Cox regression analyses for incident coronary heart disease(CHD),adjusted for sex,age,non-HDL cholesterol,waist circumference and C-reactive protein,revealed significant inverse association with adiponectin tertiles in men but not women(HR=0.66;95%CI:0.32-1.38 for highest tertile).Cox regression for type-2 diabetes in a similar model(wherein glucose replaced non-HDL cholesterol),adiponectin tertiles appeared to protect in each gender.HR for incident hypertension roughly displayed unity in each of the adiponectin tertiles(P-trend=0.67).CONCLUSION:High adiponectin levels failed to protect against the development of hypertension and,in women,against CHD,presumably paralleling impairment in renal function as well.Involvement of adiponectin in autoimmune complex with loss of antioxidative-antiatherogenic properties may be underlying.

Impaired fasting glucose:Pro-diabetic,“atheroprotective”and modified by metabolic syndrome

AIM:To investigate whether impaired fasting glucose(IFG)confers cardiovascular risk.METHODS:A non-diabetic population-based sample representative of middle-aged and elderly Turks was studied at 8.5 years’follow-up for incident diabetes and coronary heart disease(CHD).Metabolic syndrome(MetS)was defined by ATP-Ⅲcriteria modifiedfor male abdominal obesity,and IFG and type 2 diabetes were identified by criteria of the American Diabetes Association.Stratification by presence of MetS was used.Outcomes were predicted providing estimates for hazard ratio(HR)obtained by use of Cox proportional hazards regression analysis in models that controlled for potential confounders.RESULTS:In 3181 adults(aged 52±11.5 years at baseline),analysis stratified by MetS,gender and IFG status distinguished normoglycemic subjects by a"hypertriglyceridemic waist"phenotype consisting of significantly higher waist circumference,fasting triglyceride and lower high-density lipoprotein-cholesterol,regardless of gender and MetS.Additionally,lipoprotein(Lp)(a)tended to be lower in(especially female)participants with MetS.Multivariable linear regression in a subset of the sample demonstrated decreased Lp(a)levels to be associated with increased fasting glucose and insulin concentrations,again particularly in women.In Cox regression analysis,compared with normoglycemia,baseline IFG adjusted for major confounders significantly predicted incident diabetes at a 3-fold HR in men and only women with MetS.Cox models for developing CHD in 339 individuals,adjusted for conventional risk factors,revealed that IFG status protected against CHD risk[HR=0.37(95%CI:0.14-0.998)]in subjects free of MetS,a protection that attenuated partly in male and fully in female participants with MetS.CONCLUSION:IFG status in non-diabetic people without MetS displays reduced future CHD risk,yet is modulated by MetS,likely due to autoimmune activation linked to serum Lp(a).