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    Elevated serum uric acid in nondiabetic people mark pro-inflammatory state and HDL dysfunction and independently predicts coronary disease
    (Springer London Ltd, 2013) Onat, Altan; Can, Gunay; Ornek, Ender; Altay, Servet; Yuksel, Murat; Ademoglu, Evin
    We explored the association of serum uric acid (UA) concentrations with pro-inflammatory state and high-density lipoprotein (HDL) dysfunction. UA tertiles in tracked 1,508 nondiabetic participants were analyzed cross-sectionally for associations with inflammation biomarkers and protective proteins over a mean follow-up of 4.9 years for incident coronary heart disease (CHD) using Cox proportional hazards regression. In the absence of metabolic syndrome (MetS), UA tertiles significantly distinguished, in each sex, increasing categories of three MetS components (inflammation/oxidation markers, apolipoprotein (apo)B) and (inversely) current smoking (but not protective proteins such as HDL, apoA-I, and adiponectin). Distinctions attenuated in the presence of MetS. Linear regression model revealed fasting triglycerides (1.86 mg/dl variance), male sex, and gamma-glutamyl transferase and age as covariates of UA levels in women. In Cox analysis, incident CHD (n = 137) was predicted by mid and upper UA tertile in men alone at significant hazard ratios of 2.7, additively to conventional risk factors. Elevated serum UA levels, linked to triglycerides, mark in nondiabetic people pro-inflammatory state, and, notably, HDL dysfunction. CHD risk is independently predicted by elevated UA levels in nondiabetic men and is modulated by MetS and gender.
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    Impaired fasting glucose: Pro-diabetic, atheroprotective and modified by metabolic syndrome
    (Baishideng Publishing Group Inc, 2013) Onat, Altan; Aydin, Mesut; Can, Gunay; Cakmak, H. Altug; Koroglu, Bayram; Kaya, Aysem; Ademoglu, Evin
    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-III criteria modified for 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). (C) 2013 Baishideng. All rights reserved.
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    Lipoprotein(a)-activated immunity, insulin resistance and new-onset diabetes
    (Taylor & Francis Ltd, 2017) Kaya, Aysem; Onat, Altan; Yuksel, Husniye; Can, Gunay; Yuksel, Murat; Ademoglu, Evin
    Objectives: Some evidence suggests that serum lipoprotein[Lp](a) may be inversely linked to type-2 diabetes. We aimed to determine in nondiabetic people the relationship of serum [Lp](a) with insulin resistance and new-onset diabetes (NOD). Materials and methods: Population-based middle-aged adults (n = 1685) were categorized by fasting glucose and stratified to gender, having excluded prevalent diabetic subjects. NOD (n = 90) occurred over a median 5 years' follow-up. Results: Subjects that subsequently developed NOD, derived both from the normoglycemia and impaired fasting glucose (IFG) groups,were distinguished, among others, primarily by significantly elevated serum gamma glutamyltransferase, reduced Lp(a) (by 31%) and, compared to IFG, by low total cholesterol levels. Partial correlation of Lp(a) with homeostatic model assessment (HOMA) was inverse in normoglycemic men; such correlation, neutral in normoglycemic women, proved inverse in IFG (r = -0.17). Circulating Lp(a) in individuals with paired measures increased significantly (1.55-fold) in the period from baseline up to NOD. Multivariable-adjusted logistic regression analysis for NOD in combined sexes indicated independent and additive prediction by serum Lp(a), albeit inverse in direction (RR 0.84, [95%CI 0.72; 0.97]). Conclusion: Lp(a) is significantly reduced in the period preceding NOD and is inversely associated with HOMA index, observations consistent with underlying autoimmune activation.
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    Low acylation stimulating protein levels are associated with cardiometabolic disorders-secondary to autoimmune activation?
    (Turkish Soc Cardiology, 2017) Onat, Altan; Altay, Servet; Yuksel, Murat; Karadeniz, Yusuf; Can, Gunay; Yuksel, Husniye; Ademoglu, Evin
    Objective: We investigated the possible association of serum acylation stimulating protein (ASP) with cardiometabolic disorders and the evidence of autoimmune activation. Methods: Population-based randomly selected 1024 participants were cross-sectionally and prospectively analyzed. ASP concentrations were measured with a validated ELISA kit. Correlations were sought separately in subjects with no cardiometabolic disorders (n=427) designated as healthy. Results: ASP was positively correlated with total testosterone and inversely correlated with platelet activating factor (PAF), PAF-acetylhydrolase (AH), in each gender, and positively correlated in healthy men with lipoprotein [Lp](a) and apolipoprotein B. Correlations of ASP with PAF values =22 nmol/L were abolished, contrasted to a strongly inverse one in subjects with PAF Conclusion: Findings can be explained by the notion of operation of immune responses against both ASP and oxidized PAF-like lipids of Lp(a) to yield for reduced values and increased likelihood of cardiometabolic disorders.
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    Normal thyroid-stimulating hormone levels, autoimmune activation, and coronary heart disease risk
    (Springer, 2015) Onat, Altan; Aydin, Mesut; Can, Gunay; Celik, Etem; Altay, Servet; Karagoz, Ahmet; Ademoglu, Evin
    Whether euthyroid status affects cardiovascular disease risk is unclear. We aimed to investigate whether serum thyroid-stimulating hormone (TSH) levels within the normal range are related to the risk of coronary heart disease (CHD). In participants of the Turkish Adult Risk Factor Study (mean age 52.7 +/- A 11.5), in whom TSH was measured in the 2004/05 survey, cross-sectional and longitudinal analyses were performed. Subjects with TSH concentrations < 0.3 and > 4.2 mIU/L were excluded to ensure euthyroid status leaving 956 individuals as the study sample. Mean follow-up was 4.81 +/- A 1.3 years. Men had 18 % lower (p < 0.001) geometric mean TSH levels (1.10 mIU/L) than women (1.35 mIU/L). Correlations of TSH with risk variables were notably virtually absent except weakly positive ones in men with age and systolic blood pressure (SBP). The age-adjusted TSH mid-tertile in men was associated with lowest lipoprotein [Lp](a), apoB, and total cholesterol values. Incident CHD was predicted in Cox regression analyses in men [HR of 2.45 (95 %CI 1.05; 5.74] and in combined sexes by the lowest compared with the highest TSH tertile, after adjustment for age, smoking status, SBP, and LDL-cholesterol. Analysis for combined prevalent and incident CHD stratified by metabolic syndrome (MetS) confirmed the independent association with the lowest TSH tertile in men, specifically in men without MetS. TSH levels within normal range, low due to partial assay failure, may manifest as independent predictors of incident CHD, particularly in middle-aged men. Autoimmune responses involving serum Lp(a) under oxidative stress might be implicated mechanistically.