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Onat A.,Turkish Society of Cardiology | Can G.,Istanbul University | Hergenc G.,Yildiz Technical University | Kucukdurmaz Z.,Gaziantep Teaching Hospital | Ugur M.,sek Cardiovascular Surgery Center
Cardiology | Year: 2010

Objectives:To confirm previous findings on excess absolute coronary heart disease (CHD) risk among Turks. Methods: The observed incident CHD risk of a representative population sample was compared with that anticipated by Fra- mingham risk scores (FRS). At 7.4 years of follow-up of 3,027 participants free of CHD at baseline, risk estimation was contrasted in the 398 cases of newly developed fatal and nonfatal CHD. Results:CHD developed at a rate 2.2 times higher than the anticipated risk. In sex-specific quintiles of FRS, the 10-year incidence of CHD events in males in the 2 highest quintiles was 2 times the anticipated levels. In women, the 3 highest quintiles displayed an incidence 2.7 times the anticipated risk. Such individuals typically had abdominal obesity and evidence of dysfunctional apolipoprotein (apo) A-I. Men had high levels of non-high-density lipoprotein (HDL) cholesterol, total apoC-III, apoB and triglycerides. In Cox proportional hazard regression analyses, the 10-year probability of remaining free of CHD was low (81.1% in men, 84.2% in women). Women exhibited C-reactive protein as an independent predictor of CHD, lack of protection by HDL cholesterol and no conferred risk from current smoking. The observed excess CHD risk was primarily attributed to central obesity and related dysfunction of HDL, apoC-III and apoA-I. Conclusion: Dysfunction of protective serum proteins associated with metabolic syndrome impacts on CHD events, in addition to conventional risk factors. © 2010 S. Karger AG, Basel.


Ning F.,University of Helsinki | Tuomilehto J.,University of Helsinki | Tuomilehto J.,Finnish National Institute for Health and Welfare | Pyorala K.,University of Eastern Finland | And 6 more authors.
Diabetes Care | Year: 2010

OBJECTIVE - To study mortality in relation to fasting plasma glucose (FPG) and 2-h plasma glucose levels within the normoglycemic range. RESEARCH DESIGN AND METHODS - Data from 19 European cohorts comprising 12,566 men and 10,874 women who had FPG <6.1 mmol/l and 2-h plasma glucose <7.8 mmol/l at baseline examination were analyzed. Multivariate-adjusted hazard ratios (HRs) and 95% CIs for deaths from cardiovascular disease (CVD), non-CVD, and all causes were estimated for individuals whose 2-h plasma glucose > FPG (group II) compared with those whose 2-h plasma glucose ≤ FPG (group I). RESULTS - A total of 827 (246) CVD and 611 (351) non-CVD and 1,438 (597) all-cause deaths occurred in men (women). Group II was older and had higher BMI, blood pressure, and fasting insulin than group I. The multivariate-adjusted HRs (95% CIs) for CVD, non-CVD, and all-cause mortality were 1.22 (1.05-1.41), 1.09 (0.92-1.29), and 1.16 (1.04-1.30) in men and 1.40 (1.03-1.89), 0.99 (0.79-1.25), and 1.13 (0.94-1.35) in women, respectively, for group II as compared with group I. HRs were 1.25 (1.05-1.50), 1.09 (0.89-1.34), and 1.18 (1.03-1.35) in men and 1.60 (1.03-2.48), 1.05 (0.78-1.42), and 1.18 (0.93-1.51) in women, respectively, after additional adjustment for fasting insulin in a subgroup of individuals. CONCLUSIONS - In individuals with both FPG and 2-h plasma glucose within the normoglycemic range, high 2-h plasma glucose was associated with insulin resistance and increased CVD mortality. © 2010 by the American Diabetes Association.


Onat A.,Turkish Society of Cardiology | Can G.,Cerrahpasa Medical Faculty | Ademoglu E.,Istanbul University | Celik E.,Etlik Ihtisas Educational Hospital | And 2 more authors.
Journal of Investigative Medicine | Year: 2013

Objectives: The highest levels of glomerular filtration rate are associated with increased coronary heart disease (CHD) risk, an issue we investigated in separate sexes in a population prone to metabolic syndrome. Research Methods and Procedures: In total, 1948 participants of the Turkish Adult Risk Factor study with available creatinine determinations were studied at a mean 3.4 years' follow-up. Using quartiles of creatinine, risk in Cox models of incident CHD or the likelihood of combined prevalent and incident CHD was assessed. Results: Women in the lowest creatinine quartile demonstrated the lowest risk profile across diverse variables, except showing low high-density lipoprotein cholesterol and average apolipoprotein A-I and lipoprotein (a) concentrations implicating impaired atheroprotective properties. Whereas serum creatinine in men was not significantly associated with 6 proinflammatory variables comprised in linear regression analysis, apolipoprotein A-I and lipoprotein (a) were significant positive covariates in women, the latter tending to negative association in women without metabolic syndrome. In men, the highest (>1.10 mg/dL), compared with the lowest, creatinine quartile significantly predicted CHD risk, at 1.85-fold relative risks, after adjustment for established risk factors. The risk curve in women was U-shaped, the top and bottom quartiles tending to display higher risk (odds ratio, 1.28 [95% confidence interval, 0.91-1.80]) compared with the 2 intermediate quartiles. Conclusions: Increasing serum creatinine values are associated strongly and independently with CHD risk in men but not in women in whom the risk curve is U-shaped. The phenomenon of low creatinine levels underlies some hitherto unexplained relevant observations, and low measurements may be attributed to inassayability secondary to involvement in autoimmune activation. Copyright © 2013 by The American Federation for Medical Research.


Onat A.,Turkish Society of Cardiology | Onat A.,Istanbul University | Can G.,Istanbul University | Ornek E.,Etlik Ihtisas Educ Hospital | And 3 more authors.
European Journal of Clinical Investigation | Year: 2013

Background: Risks for coronary heart disease (CHD) and diabetes (T2DM) of the 'hypertriglyceridemic waist' phenotype (HtgW) warrant further investigation. We studied this issue and whether partial proinflammatory conversion of apolipoprotein (apo) A-I by lipoprotein(a) [Lp(a)] is a codeterminant. Materials and Methods: In a population-based prospective study, 1328 Turkish adults were analysed in four groups by the presence of abdominal obesity and elevated triglycerides (Htg). Results: LDL-cholesterol levels, significantly elevated in isolated Htg, were lower in HtgW, yet significantly higher apoB and complement C3 values existed in women with HtgW in whom also the lowest Lp(a) values prevailed. Lp(a) was linearly associated, more strongly in HtgW than in the remaining groups, with apoB and, in women inversely, with gamma-glutamyltransferase. Incident HtgW was predicted, not in men, but in women inversely by Lp(a) (OR 0·80 [95%CI 0·65; 0·97]), regardless of adjustment for relevant confounders. After adjustment for conventional risk factors, HtgW (OR 2·84) and high apoA-I/HDL-C ratio (OR 1·50) were significantly and additively associated with combined prevalent and incident CHD risk. High apoA-I and low HDL-cholesterol levels interacted therein in women. Type-2 diabetes was strongly predicted by HtgW, mediated in men by high apoA-I/HDL-C ratio. Conclusion: HtgW is associated with excess inflammatory markers, is predicted in women paradoxically by lower circulating Lp(a) and is associated in both sexes with marked excess cardiometabolic risk to which high apoA-I/HDL-C ratio contributes additively. These findings are consistent in women with apoA-I being oxidized via aggregation to Lp(a). © 2013 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.


Onat A.,Turkish Society of Cardiology | Can G.,Istanbul University | Murat S.,Etlik Ihtisas Education Hospital | Cicek G.,Siyami Ersek Center for Cardiovascular Surgery | And 2 more authors.
Anadolu Kardiyoloji Dergisi | Year: 2013

Objective: Dysfunction of high-density lipoprotein (HDL) may contribute to coronary heart disease (CHD) risk. We determined whether aggregation to lipoprotein (Lp)(a) of apolipoprotein (apo) A-I underlies HDL dysfunction conferring incident CHD risk. Methods: A representative sample of 1509 middle-aged Turkish adults was studied at 4.9-years' follow-up yielding 198 incident CHD cases. Statistical analysis was performed using multiple linear regression and Cox proportional regression analyses. Results: In women, not age or apoA-I, rather complement C3, apoE levels and statin use were linearly related to log-Lp(a). Individuals in the low Lp(a) tertile (<6.4 mg/dL) displayed high mean triglyceride and apoE values, and geometric mean Lp(a) values increased moderately in subjects having low and mid tertiles of apoE or triglycerides, only to be lower in the high tertiles (p≤0.002). These two findings indicated the unexpected fall in Lp(a) under circumstances of high apo E (>4.5 mg/dL) and/or triglycerides (>2.0 mmol/L). Levels actually represent aggregation of Lp(a) to apoA-I in an immune complex, rendering apoA-I atherogenic. Lp(a) did not, but apoA-I did significantly predict incident CHD (HR 1.21 [95%CI 1.07; 1.37]) in Cox regression analyses after adjustment for conventional risk factors and statin use. This adverse action of apoA-I was independent of prevalent metabolic syndrome (MetS), existed in individuals in whom ATPIII-defined MetS was not identified, and was similar in magnitude to that of conventional risk factors. Conclusion: Beyond being atherogenic, Lp(a) may aggregate in a pro-inflammatory milieu to apoA-I, rendering apoA-I atherogenic. This process is independent of ATPIII-defined MetS and exhibits risk magnitude similar to that of conventional risk factors. © 2013 by AVES Yayi{dotless}nci{dotless}li{dotless}k Ltd.


Onat A.,Turkish Society of Cardiology | Onat A.,Istanbul University | Ugur M.,Siyami Ersek Center for Cardiovascular Surgery | Can G.,Istanbul University | And 2 more authors.
Nutrition | Year: 2010

Objective: We investigated the predictive values of visceral adipose tissue area (VAT) and body fat mass for a composite endpoint consisting of type 2 diabetes and coronary heart disease and for incident metabolic syndrome. Methods: We analyzed at 4-y follow-up 157 middle-aged men and women in whom body composition analyzer and single-scan computerized tomography had been used. Results: Sex- and age-adjusted mean areas of visceral fat were 1.5-fold greater in individuals with than without the composite endpoint (P < 0.001), whereas abdominal subcutaneous fat was similar. Analysis of receiver operating characteristics for the optimal criterion regarding the composite endpoint (in 37 participants) indicated a VAT of 130 cm2 and accuracies of 60% in men and 85% in women. Whereas age-adjusted VAT alone significantly predicted the composite endpoint in men, body fat mass or VAT predicted it in women (with 2.2- to 2.6-fold relative risks for 1-SD increment). Age-adjusted incident metabolic syndrome was significantly predicted by each parameter in men but only by fat mass in women. Conclusion: Visceral adiposity in men and body fat mass in women seem to be of greater relevance in cardiometabolic risk for the prediction of which 130 cm2 of VAT in both sexes and/or 27 kg of fat mass in women are useful cutoffs. Sex differences may reflect the predominating role of visceral adiposity in men and of insulin resistance in women in this risk. © 2010.


Onat A.,Turkish Society of Cardiology | Onat A.,Istanbul University | Hergenc G.,Yildiz Technical University | Can G.,Istanbul University | And 2 more authors.
Clinical Chemistry and Laboratory Medicine | Year: 2011

Background: The clinical relevance of serum lipoprotein-associated phospholipase A 2 (Lp-PLA 2) in populations prone to cardiometabolic risk needs exploration. We determined major covariates of Lp-PLA 2 mass, and its associations with cardiometabolic disorders. Methods: In 736 Turkish adults, serum total Lp-PLA 2 mass was determined by immunoassay. Its association with cardiometabolic risk was assessed in three categories. In a second sample of 98 subjects, enzyme protein in high-density lipoprotein (HDL) was also assayed after precipitation. Results: Significant inverse correlation existed with high triglyceride/low HDL cholesterol dyslipidemia, waist girth, apolipoprotein C-III, homeostatic model assessment, and linear inverse associations in women with lipoprotein (a) and fibrinogen, suggesting that Lp-PLA 2 mass reflected insulin sensitivity and that HDL bound enzyme mass dominated the associations. Among men, positive linear association with total cholesterol suggested additional association with low-density lipoprotein (LDL)-bound enzyme. High (>450 ng/mL) opposed to low (<210 ng/mL) circulating Lp-PLA 2 mass was associated with prevalent and incident coronary heart disease (CHD) in men. One SD increment in Lp-PLA 2 was associated with a 1.64-fold (95% CI 1.00; 2.70) likelihood of CHD, after adjustment for potential confounders. Furthermore, Lp-PLA 2 categories were significantly, independently and inversely associated in men with diabetes only (OR 0.61) and in women with metabolic syndrome only (OR 0.68), for a 1-SD increment. Conclusions: Serum total Lp-PLA 2 mass may indicate either elevated or diminished cardiometabolic risk, specific for gender, depending on its partitioning in lipoprotein groups. © 2011 by Walter de Gruyter Berlin Boston.


Onat A.,Turkish Society of Cardiology | Onat A.,Istanbul University | Hergenc G.,Yildiz Technical University | Can G.,Istanbul University | And 3 more authors.
Metabolism: Clinical and Experimental | Year: 2010

We studied whether serum complement C3 (C3) is an independent determinant of incident cardiometabolic risk (coronary heart disease [CHD], metabolic syndrome [MetS], and type 2 diabetes mellitus). A cohort of 1220 adults of a general population (age, 53 ± 10.5 years) was evaluated prospectively at 3.3 years follow-up using Cox proportional hazard regressions. Cardiometabolic risk factors were measured. Metabolic syndrome was identified by Adult Treatment Panel III criteria modified for male abdominal obesity. The C3 levels were associated significantly and linearly with serum triglycerides, waist circumference, and C-reactive protein (CRP), and inversely with current smoking but not with the marker of insulin resistance. In regression models for incident MetS, increasing C3 quartiles strongly predicted MetS in women and in both sexes combined after adjusting for all 5 MetS components and other confounders. Circulating C3 significantly predicted in each sex incident CHD independent of age, smoking status, and presence of MetS. Even after entering CRP, C3 predicted CHD with a relative risk of 1.35 (95% confidence interval, 1.09-1.67) for 1-SD increment of C3 in the total sample. Complement C3 tended to contribute, additively to MetS, to the association with diabetes with a relative risk of 1.36 in women alone, not in men. In conclusion, elevated serum complement C3 is part of the MetS cluster and confers CHD risk, additively to MetS components and CRP, in a population in which MetS prevails. Levels contribute, additively to MetS, to the diabetes risk in women alone. © 2010 Elsevier Inc. All rights reserved.


PubMed | Turkish Society of Cardiology
Type: Journal Article | Journal: Lipids | Year: 2013

The relevance of serum apolipoprotein E (apoE) levels to two hypertriglyceridemic dyslipidemias has not been clarified. We explored, in a cross-sectional (and short-term prospective) evaluation, the independent relationship of serum apoE to the atherogenic dyslipidemia, hypertriglyceridemia with elevated apoB (HtgB) and to apoA-I dysfunctionality, previously shown in Turkish adults to be independent of apoE genotype. Serum apoE concentrations were measured by immunonephelometry in 1,127 middle-aged adults. In multivariable regression analysis, apoE concentrations showed log-linear associations with apoB and apoA-I levels, waist circumference, independent of C-reactive protein (CRP), homeostatic model assessment (HOMA) index and other confounders. The likelihood of atherogenic dyslipidemia and of HtgB roughly tripled per 1-SD increment in apoE concentrations, additively to apoE genotype, HOMA, apoA-I, CRP concentrations and waist circumference; yet apoA-I, protective against atherogenic dyslipidemia, appeared to promote HtgB, a finding consistent with apoA-I dysfunctionality in this setting. Each 1-SD increment in the apoE level was moreover, associated in both genders with MetS (at OR 1.5), after adjustment for sex, age, apoB, apoA-I and CRP, or for apoE genotypes. Circulating apoE predicted in both genders age-adjusted prevalent and incident coronary heart disease (CHD), independent of apoE genotype and CRP (OR 1.32 [95 % CI 1.11; 1.58]). To conclude, in a general population prone to MetS, elevated apoE concentrations are strongly linked to HtgB and atherogenic dyslipidemia, irrespective of apoE genotype, are associated with MetS and CHD. Excess apoE reflects pro-inflammatory state and likely autoimmune activation.


PubMed | Turkish Society of Cardiology
Type: Journal Article | Journal: Anadolu kardiyoloji dergisi : AKD = the Anatolian journal of cardiology | Year: 2013

Dysfunction of high-density lipoprotein (HDL) may contribute to coronary heart disease (CHD) risk. We determined whether aggregation to lipoprotein (Lp)(a) of apolipoprotein (apo) A-I underlies HDL dysfunction conferring incident CHD risk.A representative sample of 1509 middle-aged Turkish adults was studied at 4.9-years follow-up yielding 198 incident CHD cases. Statistical analysis was performed using multiple linear regression and Cox proportional regression analyses.In women, not age or apoA-I, rather complement C3, apoE levels and statin use were linearly related to log-Lp(a). Individuals in the low Lp(a) tertile (<6.4 mg/dL) displayed high mean triglyceride and apoE values, and geometric mean Lp(a) values increased moderately in subjects having low and mid tertiles of apoE or triglycerides, only to be lower in the high tertiles (p0.002). These two findings indicated the unexpected fall in Lp(a) under circumstances of high apo E (>4.5 mg/dL) and/or triglycerides (>2.0 mmol/L). Levels actually represent aggregation of Lp(a) to apoA-I in an immune complex, rendering apoA-I atherogenic. Lp(a) did not, but apoA-I did significantly predict incident CHD (HR 1.21 [95%CI 1.07; 1.37]) in Cox regression analyses after adjustment for conventional risk factors and statin use. This adverse action of apoA-I was independent of prevalent metabolic syndrome (MetS), existed in individuals in whom ATPIII-defined MetS was not identified, and was similar in magnitude to that of conventional risk factors.Beyond being atherogenic, Lp(a) may aggregate in a pro-inflammatory milieu to apoA-I, rendering apoA-I atherogenic. This process is independent of ATPIII-defined MetS and exhibits risk magnitude similar to that of conventional risk factors.

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