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Background and objectives: Mortality may increase in hypouricemia as well as inhyperuricemia. We assessed the predictive value of low serum uric acid (SUA) levels on the risk of overall mortality or a composite endpoint of death and nonfatal events. Materials and Methods: In 1013 community-based middle-aged adults, free of uncontrolled diabetes and coronary heart disease at baseline, the association of sex-specific SUA tertiles with defined outcomes was evaluated prospectively by logistic regression, stratified to gender and presence of type-2 diabetes, using recent criteria. Results : Totally, 43 deaths and additional incident nonfatal events in 157 cases were recorded at a median 3.4 years' follow-up. Multivariable linear regression disclosed SUA to be significantly associated among non-diabetic individuals positively with creatinine, triglycerides, and body mass index in women further with fasted glucose. In multivariable-adjusted logistic regression analysis, sex-specifically dichotomized baseline uric acid (<5.1 and <4.1 mg/dL vs. higher values) significantly predicted the non-fatal events in the whole sample (relative risk (RR) 1.51 [95% confidence interval (CI) 1.02; 2.26]), as well as in men, while composite endpoint in the whole sample tended to rise (RR 1.38). Compared with the intermediate one, the top and bottom SUA tertiles combined tended to confer mortality risk (RR 2.40 [95% CI 0.89; 6.51]). Adverse outcomes in diabetic women were predicted by tertiles 2 and 3. Conclusions : Inverse association of SUA with adverse outcomes, especially in men, is consistent with the involvement of uric acid mass in autoimmune activation. The positive association of uric acid with adverse outcomes in diabetic women is likely mediated by concomitant high-density lipoprotein dysfunction.

Background: We aimed to identify the most suited anthropometric measure for the prediction of risk for incident coronary heart disease (CHD) among the Turkish population., Methods: We collected data on body mass index, waist circumference (WC), hip circumference, waist-to-hip ratio (WHR), waist-to-height ratio (WHtR) and a body shape index. We analysed these using both C-statistics and Cox regression models adjusted for age, systolic blood pressure, glucose and high-density lipoprotein (HDL)-cholesterol for assessing risk of incident CHD among 3203 Turkish Adult Risk Factor (TARF) study participants (mean [SD] age 48.5 [11] years)., Results: Over a mean follow-up of 9.93 years, new CHD developed in 573 individuals. Multi-adjusted C-statistics were highest for WHtR followed by WC, in both sexes. Except WHR, all measures were significantly associated with incident CHD in combined sexes in the full model. There was a sex difference, however, in the mediation of the three risk factors for adiposity; these attenuated hazard ratios (HRs) in males, whereas in females, significant prediction of incident CHD persisted for each measure. WC (HR 1.36 [95% CI 1.13; 1.64]), followed by WHtR (HR 1.24 [95% CI 1.10; 1.40]), were in combined sex, as in females, the most informative surrogates of adiposity. Hip circumference did not protect, but rather conferred modest CHD risk, especially in females, rendering a low utility of predictive value for WHR. The CHD risk curve did not have a J shape., Conclusions: WC is the most suitable of five adiposity surrogates for CHD risk among Turkish adults, while in males, unmediated adiposity risk was similarly identified by WHtR. Retention of the large part of CHD risk in females perhaps reflects the underlying autoimmune activation., Competing Interests: None

Objective: The associations of total testosterone (TT) and sex hormone-binding globulin (SHBG) with the hypertriglyceridemic waist (HtgW) phenotype and coronary heart disease (CHD) risk have scarcely been examined. We explored such cardiometabolic risk mediations in middle-aged adults., Methods: Participants (n = 1924) in a population-based study were studied by forming categories consisting of abdominal obesity, hypertriglyceridemia, both (HtgW), or none ('healthy'). Cardiometabolic risk was prospectively analyzed (mean follow-up 5.7 years)., Results: With reference to the healthy group, SHBG values in HtgW were significantly lower, alike serum HDL-cholesterol. ApolipoproteinB-containing lipoproteins, fasting glucose and complement C3 levels, inverse to lipoprotein[Lp](a) especially in female participants with HtgW phenotype compared with those in the 'healthy' category, suggested the operation of aggregation to Lp(a). Multivariable Cox regression analysis in a model comprising age, waist circumference and systolic blood pressure showed significant protection by SHBG against incident diabetes which tended to be so with TT in men. Sex hormones were not associated with risk of incident CHD or MetS. In another multivariable model, compared to the 'healthy' and the hypertriglyceridemia categories, dichotomized high and, in females, low SHBG values within the HtgW category, positively predicted CHD at significant over 2-fold relative risks., Conclusion: HtgW phenotype distinguishes itself from the (virtually neutral) simple abdominal obesity in independently conferring high CHD risk when elevated or reduced SHBG levels interact. Underlying operation of Lp(a) aggregation is suggested.

Aim: To assess the association of a surrogate of fatty liver disease (FLD) with incident type-2 diabetes, coronary heart disease, and all-cause mortality., Methods: In a prospective population-based study on 1822 middle-aged adults, stratified to gender, we used an algorithm of fatty liver index (FLI) to identify associations with outcomes. An index ≥ 60 indicated the presence of FLD. In Cox regression models, adjusted for age, smoking status, high-density lipoprotein cholesterol, and systolic blood pressure, we assessed the predictive value of FLI for incident diabetes, coronary heart disease (CHD), and all-cause mortality., Results: At a mean 8 year follow-up, 218 and 285 incident cases of diabetes and CHD, respectively, and 193 deaths were recorded. FLD was significantly associated in each gender with blood pressure, total cholesterol, apolipoprotein B, uric acid, and C-reactive protein; weakly with fasting glucose; and inversely with high-density lipoprotein-cholesterol and sex hormone-binding globulin. In adjusted Cox models, FLD was (with a 5-fold HR) the major determinant of diabetes development. Analyses further disclosed significant independent prediction of CHD by FLD in combined gender [hazard ratio (HR) = 1.72, 95% confidence interval (CI): 1.17-2.53] and men (HR = 2.35, 95%CI: 1.25-4.43). Similarly-adjusted models for all-cause mortality proved, however, not to confer risk, except for a tendency in prediabetics and diabetic women., Conclusion: A surrogate of FLD conferred significant high risk of diabetes and coronary heart disease, independent of some metabolic syndrome traits. All-cause mortality was not associated with FLD, except likely in the prediabetic state. Such a FLI may reliably be used in epidemiologic studies.

Objective: This study aimed to examine the overall and coronary mortality in the 2014 Turkish Adult Risk Factor Study survey, and the distribution of cumulative mortality and incident coronary heart disease (CHD) across 7 geographic regions., Methods: Information on mode of death was appropriately obtained. Information collected from survivors was based on history, examination of the cardiovascular system and the Minnesota coding of electrocardiograms. Cox regression analyses were performed., Results: Of the 1.323 participants to be surveyed, 87 were lost to follow-up, 753 examined, and 35 ascertained as deceased. In 448 subjects, verbal information alone was obtained regarding health status. Nineteen deaths were of coronary and cerebrovascular origin. Cumulative 24-year assessment of the entire cohort in the age bracket 45-74 years disclosed high coronary mortality, at 7.3 per 1000 person-years in men and 3.8 in women, and recorded a limited decline of 18% since the year 2000. Age-adjusted Cox regression analysis, comprising 614 deaths and 482 incident CHD over a follow-up of 9.6 years, revealed higher mortality rates in the Mediterranean region and in men in the Black Sea and Marmara regions. The age-adjusted CHD incidence was significantly higher in males of the Mediterranean and females of the Southeast regions. An estimated 400-420.000 incident CHD cases develop currently each year in Turkey., Conclusion: The generally high age-adjusted overall mortality in Turkey displays significant differences across geographic regions. Age-adjusted CHD incidence is not regressing sufficiently, and is especially high among men of the Mediterranean and women of the Southeast regions.

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±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±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.

Objective: We determined whether U-shaped relationships exist between serum lipoprotein[Lp](a) and cardiometabolic risk., Methods: In population-based nondiabetic and diabetic middle-aged adults (n=1 428 and 241, respectively) who had been genotyped for the LPA rs10455872 A>G polymorphism, we adjusted the Lp(a) concentration for the effects of genotype and other covariates. Via sex-specific equations we estimated expected Lp(a) concentration in each participant, and the quotient between observed to expected Lp(a) values was determined. Lp(a) and Lp(a) quotient tertiles served to identify non-linear associations with outcomes., Results: Incident 81 cases of diabetes and 128 of coronary heart disease (CHD) developed at 5.1 years' follow-up. Lp(a) concentration was linearly associated with the LPA genotype, gender, total cholesterol, (inversely) fasting insulin, which together with age formed the variables to derive the equations. In logistic regression for incident diabetes, the low Lp(a) quotient tertile was a predictor (RR 1.95 [95%CI 1.10; 3.47]) alike the low Lp(a) tertile, additively to major confounders. Cox regression models comprising sex, age, LPA genotype, smoking status, systolic pressure and serum HDL-cholesterol disclosed that, compared with the mid-tertile, both low (HR 1.77) and high Lp(a) quotient tertiles significantly predicted incident CHD, especially in women., Conclusion: Elevated cardiometabolic risk is conferred by apparently reduced circulating Lp(a) assays supporting the notion that "low" serum Lp(a), mediating autoimmune activation, is a major determinant of cardiometabolic risk., (© Georg Thieme Verlag KG Stuttgart · New York.)

Objective: We investigated the association of serum asymmetric dimethylarginine (ADMA) with metabolic syndrome (MetS), type-2 diabetes and coronary heart disease (CHD) in the general population., Methods: Cross-sectional and, at 2000 person-years' follow-up, prospective analysis. Adults with measured serum ADMA level (n=848) were analyzed using tertiles or dichotomized values. ADMA concentrations were measured by a validated commercial ELISA kit., Results: Dichotomized subjects of combined sexes with low (≤0.68 µmol/L) ADMA values had significantly higher fasting glucose, total cholesterol, apolipoprotein B and lower diastolic blood pressure. In linear regression analyses comprising age, smoking, triglyceride, HDL-cholesterol, C-reactive protein and waist circumference as well, creatinine was significantly and independently associated with ADMA, further in women glucose (inversely). In logistic regression analyses uniformly adjusted for age, smoking status and waist girth, prevalent MetS tended to positive independent association with ADMA tertiles only in men. Combined prevalent and incident diabetes weakly tended to be associated with the lowest (vs mid- and highest) ADMA tertiles in combined gender; and prevalent and incident CHD was not associated with ADMA tertiles in either sex., Conclusion: Apparently "low" circulating ADMA is independently associated with fasting glucose and tends to be so with type-2 diabetes. The lack of anticipated positive associations of ADMA with cardiometabolic disorders is likely due to autoimmune responses operating against serum ADMA under oxidative stress, rendering partial failure in immunoassay.

Insight is provided herein into the novel mechanisms of cardiometabolic risk. Previous reports, including the epidemiological work of the Turkish Adult Risk Factor study, indicated that proinflammatory state and oxidative stress are crucial for evaluating cardiometabolic risk. Autoimmune pathways in the course of oxidative stress are major determinants of cardiorenal and metabolic risk. The latter encompasses metabolic syndrome, type 2 diabetes, coronary heart disease, and chronic kidney disease (CKD). Along with platelet-activating factor acetylhydrolase, creatinine, thyroid stimulating hormone, acylation-stimulating protein, asymmetric dimethylarginine, and serum lipoprotein[Lp](a) are triggers of systemic low-grade inflammation and enhanced autoimmune reactions. Related studies are analyzed in the current review. Lp(a) plays a crucial role by taking part in the immune activation, thereby accelerating the course of diabetes, CKD, and other chronic disorders. Populations prone to impaired glucose tolerance, and particularly peri- and postmenopausal women, are at high risk of developing related vascular complications.

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.

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.)

Background: In view of recent evidence that serum creatinine and dysfunctional apolipoprotein (apo)A-I may serve as inflammation mediators in people with enhanced inflammation, we studied whether or not these molecules were interrelated and associated with coronary heart disease (CHD) likelihood even in subjects without metabolic syndrome (MetS) or type-2 diabetes., Methods: Among unselected middle-aged Turkish adults with available serum apo A-I, lipoprotein(a) and creatinine measurements, 697 participants (designated as 'healthy') were enrolled, after exclusion of the stated metabolic disorders. CHD was identified in 87 subjects, roughly half during 3.1 years' follow-up., Results: 'Healthy' individuals were overweight and had partly impaired fasting glucose but otherwise normal serum creatinine and other biochemical measurements. Being consistent with lacking anti-inflammatory activity, apoA-I was linearly and positively associated with apoB, in women further with creatinine. Logistic regression analyses showed that, beyond age, not non-HDL-cholesterol, systolic blood pressure and smoking status, but serum creatinine in each sex (OR in men 1.63 [95% CI 1.14; 2.31]) and CRP in women were significantly associated with CHD likelihood. The combined highest and lowest creatinine quartiles in women displayed an OR 2.14 (1.02; 4.51) compared with the intermediate quartiles, after similar adjustments., Conclusion: Elevated creatinine levels within normal range, linked to apoA-I dysfunctionality, are independently associated with CHD likelihood even in non-diabetic subjects without MetS. In such women the lowest creatinine quartile is also linked to CHD risk.

We determined in non-diabetic persons the risk of fasting and non-fasting glucose levels for pre-diabetes, diabetes, and coronary heart disease (CHD), including the roles of serum C-reactive protein (CRP) and HDL cholesterol, and delineated risk profiles of the pre-diabetic states. Over 7¼ years, 2,619 middle-aged Turkish adults free of diabetes and CHD were studied prospectively. Using different serum glucose categories including impaired fasting glucose (IFG, 6.1-6.97 mmol/L) and impaired glucose tolerance (IGT), outcomes were analyzed by Cox regression. IFG was identified at baseline in 112 and IGT in 33 participants. Metabolic syndrome components distinguished individuals with IFG from those with normoglycemia. Participants with IGT tended to differ from adults in normal postprandial glucose categories in regard to high levels of triglycerides, apoA-I, and CRP. Diabetes risk, adjusted for sex, age, waist circumference, CRP, and HDL cholesterol, commenced at a fasting 5.6-6.1 mmol/L threshold, was fourfold at levels 6.1-6.97 mmol/L. Optimal glucose values regarding CHD risk were 5.0-6.1 mmol/L. Fasting and postprandial glucose values were not related to CHD risk in men; IGT alone predicted risk in women (HR 3.74 [1.16;12.0]), independent of age, systolic blood pressure, non-HDL cholesterol, waist circumference, smoking status, and CRP. HDL cholesterol was unrelated to the development of IFG, IGT, and diabetes, while CRP elevation independently predicted the development of diabetes. IGT independently predicts CHD risk, especially in women. HDL dysfunction associated with low-grade inflammation is a co-determinant of pre-diabetic states and their progression to diabetes.

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.

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.

Objective: Impaired function of high-density lipoprotein (HDL) particles generates cardiometabolic disorders in people prone to impaired glucose tolerance for which clinical biomarkers need delineation., Study Design: Prospective population-based study., Methods: Totally, data of 2725 adults followed-up over 7.3 ± 3.0 years were analyzed by Cox regression analysis. C-reactive protein (CRP), complement C3 (C3), triglycerides (Trg) and HDL-cholesterol were tested to predict risk for incident diabetes or coronary heart disease (CHD)., Results: Beyond atherogenic dyslipidemia, high-Trg/normal HDL-cholesterol category was associated with elevated CRP and diabetes risk in women. Normotriglyceridemic men with normal HDL-cholesterol showed higher apolipoprotein A-I levels and higher diabetes risk than men having low HDL-cholesterol. Diabetes risk doubled in hypertriglyceridemic women regardless of HDL-cholesterol. Trg/HDL-C>2 in men and Trg>1.7 mmol/L in women were best predictors of diabetes. C3>1.3 g/L served additively in women alone. Regarding CHD risk, not CRP, but C3 contributed independently to Trg/HDL>2 in men [RR 2.46 (95% CI 1.33; 4.53)]; a high ratio was merely additive to elevated CRP in women. Among five cut-off values, predictive values for diabetes were highest for CRP >2.5 mg/L in men, Trg>1.7 mmol/L and C3>1.3 g/dL in women., Conclusion: Trg/HDL-C ratio >2 and/or CRP >2.5 mg/L in men and Trg>1.7 mmol/L+C3>1.3 g/dL in women are most appropriate markers regarding impaired antiinflammatory or atheroprotective HDL function. In normotriglyceridemic men with normal HDL-cholesterol levels, diabetes risk may be elevated due to presumably dysfunctional apolipoprotein A-I.

Background and Aim: An algorithm is needed for predicting coronary heart disease (CHD) risk in Turkish adults who have a high prevalence of metabolic syndrome (MetS)., Methods and Results: Ten-year risk of CHD was estimated in 2232 middle-aged adults free of CHD at baseline, followed over 7.6-years. Cox proportional hazard regression was used to predict CHD. Discrimination was assessed with area under receiver operating characteristics curve (AROC). CHD developed in 302 subjects. In multivariable analysis, high-density lipoprotein (HDL)-cholesterol levels were borderline predictive in men; smoking status and HDL-and low-density lipoprotein (LDL)-cholesterol levels were not predictive in women. Age, presence of diabetes, systolic blood pressure and C-reactive protein (CRP) were predictors in both sexes, while smoking status and LDL-cholesterol were so in men only. AROC of the model was 0.789 in men, and 0.806 in women (p < 0.001 each). An algorithm using the stated seven variables was derived separately for each sex. After age adjustment, men and women in the highest quintile of risk score were significantly and 20-27-fold more likely to develop CHD than those in the lowest quintile., Conclusions: In a population with prevalent MetS, low-grade inflammation is independently relevant for CHD, as are serum lipoproteins and smoking status. The derived algorithm is effective in estimating CHD risk among Turkish adults., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Objective: We evaluated the associations of short stature with coronary heart disease (CHD) risk or overall mortality, which vary with sex and ethnicity/race., Methods: Such associations were studied prospectively at a mean 13.5-years' follow-up in a population-based sample of 3394 Turkish adults (mean age 44±11 years) using Cox proportional hazards models. Covariates of height were sought in sex-specific tertiles., Results: Height averaged 162.7±6.5 cm. Age-adjusted estimated marginal means for serum triglycerides, C-reactive protein and complement C3 in women (but not men) were significantly higher with decreasing height tertiles. In sex- and age-adjusted models, height was associated in men with neither incident CHD, nor death. In women, 1-SD increment (6.5 cm) in height only tended to marginal inverse association with CHD, but predicted significantly all-cause death (HR 0.83, 95% CI 0.59-0.98); HR attenuated only marginally after further adjustment for family income bracket, smoking status, alcohol usage, systolic blood pressure, serum high-density lipoprotein (HDL)- and non HDL-cholesterol. A threshold below 160 cm of female height doubled the adjusted risk of death compared to taller women., Conclusion: In contrast to men, short stature in Turkish women tends to be an independent risk marker for CHD, and height below 160 cm is a strong marker of death. Gender-specific early-life influences enhancing pro-inflammatory state may affect death and future CHD.

Serum γ-glutamyltransferase (GGT) is associated with oxidative stress and hepatic steatosis. The extent to which its value in determining incident cardiometabolic risk (coronary heart disease (CHD), metabolic syndrome (MetS), hypertension and type 2 diabetes) is independent of obesity needs to be further explored in ethnicities. After appropriate exclusions, a cohort of 1,667 adults of a general population (age 52 ±11 years) was evaluated prospectively at 4 year's follow-up using partly Cox proportional hazard regressions. GGT activity was measured kinetically, and values were log-transformed for analyses. MetS was identified by Adult Treatment Panel-III criteria modified for male abdominal obesity. Median (interquartile range) GGT activity was 24.9 (17.0; 35.05) U/l in men, 17.0 (12.3; 24.0) U/l in women. In linear regression analysis, while smoking status was not associated, (male) sex, sex-dependent age, alcohol usage, BMI, fasting triglycerides and C-reactive protein (CRP) were significant independent determinants of circulating GGT. Each 1-s.d. increment in (= 0.53 ln GGT) GGT activity significantly predicted in each sex incident hypertension (hazard ratio (HR) 1.20 (95% confidence interval (CI) 1.10; 1.31)), and similarly MetS, after adjustment for age, alcohol usage, smoking status, BMI and menopause. Strongest independent association existed with diabetes (HR 1.3 (95% CI 1.1; 1.5)) whereas GGT activity tended to marginally predict CHD independent of total bilirubin but not of BMI. Higher serum total bilirubin levels were protective against CHD risk in women. We conclude that elevated serum GGT confers, additively to BMI, risk of hypertension, MetS, and type 2 diabetes but only mediates adiposity against CHD risk.

We addressed whether or not the risk of coronary heart disease (CHD) in non-diabetic persons is linear at the lower end of fasting glucose levels. Middle-aged Turkish adults (n=2893) free from diabetes and CHD at baseline were studied prospectively over a 7.6-year follow-up. Participants with fasting glucose measurements were analyzed in 3 groups separated by 90 mg/dl and 110 mg/dl limits. Outcomes were analyzed by Cox regression. Cox regression for CHD incidence (n=374) showed an increased age-adjusted risk in the <90 mg/dl fasting glucose group (n=788) [HR 1.32 (1.03; 1.68)], compared with the 90-110 mg/dl group after adjustment for sex, age and the glucose groups. Further adjustment for waist circumference, C-reactive protein and conventional risk factors attenuated the HR to 1.27 (p=0.077). The risk profile in the low-glucose group could not be accounted for by age, smoking status, systolic blood pressure or fasting insulin levels but tended to show higher levels of circulating C-reactive protein. The increased CHD risk observed in individuals with lower compared with higher normal glucose concentrations is likely to be related to an associated pro-inflammatory state., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Objectives: We determined the independent predictive value of serum apolipoprotein (apo) B/LDL-cholesterol ratio for the risk of diabetes, metabolic syndrome (MetS) and coronary heart disease (CHD)., Design and Methods: Prediction of incident cases was assessed in 2466 adults at 7 years' follow-up., Results: ApoB/LDL ratio was independently associated log-linearly with waist circumference, and, only in men, with HDL-cholesterol in a multivariable regression model. Positive partial correlations existed with fasting insulin, fibrinogen and apo A-I and, only in women, with CRP. Cox regression analyses revealed the two highest apoB/LDL quartiles to be significant determinants of diabetes, at 2-fold RRs, independently of waist circumference, fasting glucose and other confounders. However, apoB/LDL quartiles were not independently associated with CHD in either gender. Only the highest apoB/LDL quartile was associated (RR 1.46) with the development of MetS. Serum apoB/LDL-cholesterol ratio, determined by insulin resistance and in women additionally by pro-inflammatory state, is of independent predictive value for incident diabetes and weakly for MetS, but not for CHD., (Copyright © 2010 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

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.

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 cm(2) 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 cm(2) 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., (Copyright 2010. Published by Elsevier Inc.)

The issue of whether or not incident type 2 diabetes mellitus and coronary heart disease (CHD) can be predicted by high-density lipoprotein (HDL) cholesterol in both sexes needs investigation. A representative sample of 3035 middle-aged Turkish adults free of CHD at baseline was studied with this purpose prospectively over a mean of 7.8 years. High-density lipoprotein cholesterol levels were found to be correlated in women positively with plasma fibrinogen and weakly with waist girth and C-reactive protein, and to be not correlated with fasting insulin. High-density lipoprotein cholesterol protected men against future CHD risk (for a 12-mg/dL increment: relative risk = 0.80 [95% confidence interval, 0.69-0.95]) after multivariable adjustment in logistic regression analyses for age, smoking status, physical activity grade, hypertension, abdominal obesity, diabetes, and lipid-lowering drugs. However, men were not protected against risk of diabetes. In women, HDL cholesterol was not associated with risk for CHD, whereas intermediate (40-60 mg/dL) compared with lower HDL cholesterol levels proved protective against risk of diabetes (relative risk = 0.57 [95% confidence interval, 0.36-0.90]) after adjustments that included apolipoprotein A-I tertiles. Yet higher serum concentrations failed to yield protection against diabetes. It was concluded that HDL particles confer partially lacking protection against cardiometabolic risk among Turks, and this impairment is modulated by sex. This highly important observation may result from a setting of prevailing chronic subclinical inflammation.

Objectives: The impact of alcohol consumption on various outcomes was prospectively evaluated in the participants of the Turkish Adult Risk Factor Study., Study Design: A total of 3,443 men and women (mean age 47.6+/-12 years) were included at baseline and followed-up for a mean of 7.4 years (range 5 to 9 years). Alcohol drinking status was assessed as abstention and brackets of moderate and heavy intake. Only 19.5% of adults (35% of men and 4.2% of women) reported consumption of alcohol. In each multivariate analysis, individuals with the examined endpoint at baseline were excluded, and alcohol drinking status was adjusted for age, sex, smoking status, and physical activity., Results: Alcohol intake increased overall mortality (by 2-fold) in men drinking heavily, but not in men drinking moderately, nor in women. Heavy drinking in combined sexes predicted the risk for incident coronary heart disease (CHD) (RR 2.3; 95% CI 1.30; 4.05), while moderate drinking tended to be protective (RR 0.72; 95% CI 0.50; 1.035). Heavy intake predicted incident diabetes risk (RR 2.13) and tended to be so for new metabolic syndrome (MetS) in men (RR 1.71), whereas moderate alcohol intake was not significantly associated with subsequent development of diabetes or MetS and the risk for MetS was reduced in women (p=0.10)., Conclusion: Risk of alcohol intake depends on the amount used: heavy intake raising the risk for diabetes and CHD in combined sexes, and overall mortality in men, contrasted to moderate intake reducing (borderline) the CHD risk and marginally reducing all-cause mortality. Risk for MetS tends to be reduced in women alone.

Background: We evaluated prospectively the predictive value of serum apolipoprotein (apo) A-II, the second major apolipoprotein of high-density lipoprotein (HDL), for cardiometabolic risk in Turkish adults showing abnormalities in other proteins that normally confer protection., Methods: Determinants of apoA-II and its associations with coronary heart disease (CHD), metabolic syndrome (MetS) and diabetes were investigated at 4 years follow-up in 193 elderly men and women., Results: ApoA-II concentrations at baseline, in addition to being significantly related to HDL-cholesterol, were directly associated with complement C3 in multivariate linear regression analyses comprising nine variables. Following adjustment for gender, age and HDL-cholesterol (>30/>33 g/L, in men and women, respectively), low serum apoA-II concentrations predicted incident MetS [relative risk (RR) 3.5 (95% CI 1.4; 8.6)] and type 2 diabetes [RR 4.5 (95% CI 1.3; 15.6)] in both genders at an increment of 1 SD. Increased apoA-II values were not associated with prevalent or incident CHD, and tended to be marginally atheroprotective only in males., Conclusions: Serum apoA-II concentrations confer risk for MetS and diabetes and exhibit evidence of anti-inflammatory properties among Turks. These findings support the effects seen for several other HDL protein constituents. This finding may explain the increased cardiometabolic risk among Turks.

Objectives: The significance of T-wave negativity in lead V1 in adults and its relationship with cardiovascular risk factors have not been clarified. This study was designed to determine the prevalence of negative T waves in chest lead V1 in an adult cohort., Study Design: The study included 508 adults (278 males, mean age 51.5+/-9.7 years; 230 females, mean age 51.2+/-10.0 years) enrolled in the longitudinal Turkish Adult Risk Factor survey from all geographical regions of Turkey, whose prospective data on the prevalence of coronary heart disease and its risk factors were available for comparative assessment of T-wave groups. Associations of negative T waves were sought in relation to age, sex, cardiovascular risk factors, and coronary heart disease., Results: The prevalence of T-wave negativity in women was significantly higher than that of men (38.3% vs 7.2%; p<0.001). No age-related differences were found between the two sexes with respect to the presence or absence of negative T waves (p>0.05). Cardiovascular risk factors and cardiometabolic conditions did not differ among men with respect to the T-wave pattern. However, women presenting negative T waves in lead V1 had significantly lower systolic blood pressure (p=0.007) and HDL-cholesterol (p=0.034) values, and a higher incidence of type 2 diabetes (p=0.048) than women with positive T waves., Conclusion: No convincing explanation could be offered for the significantly higher female predilection for the presence of negative T-waves in lead V1. Negative T waves in lead V1 were not associated with adverse cardiometabolic risks.

Background & Aims: Whether serum homocysteine levels are associated with coronary heart disease (CHD) and the metabolic syndrome (MS) needs investigation in different ethnic groups. These associations and the influence of serum folate and vitamin B(12) thereupon were addressed separately in genders., Methods: A random sample of Turkish adults was studied cross-sectionally., Results: Median age of 338 men and 342 women was 55 years. Geometric mean serum homocysteine concentrations were 12.7+/-1.5 micromol/l in men and 9.6+/-1.4 micromol/l in women (p<0.001). Linear regression analysis among 11 variables revealed male sex, reduced estimated glomerular filtration rate (eGFR) and vitamin B(12), (in men) reduced folate as significant independent covariates of higher homocysteine levels. Logistic regression analysis disclosed that (sex-specific) top versus bottom homocysteine tertile was borderline significantly and independently associated with CHD in men and both genders combined, after adjustment for gender, age, smoking status, systolic blood pressure, eGFR, folate and vit B(12). Folate revealed significant inverse association with CHD likelihood in men and combined genders (OR 0.73 for doubling [95%CI 0.56; 0.94]), independently of homocysteine levels and even of presence of type-2 diabetes. Serum vit B(12) concentrations were significantly associated with MS likelihood in women alone after adjustment for sex, age, smoking status, folate and antidiabetic medication., Conclusion: High serum homocysteine and low folate levels are associated in Turkish men independently with CHD, which needs confirmation in a larger sample. In women, vitamin B(12) concentrations are significantly associated with MS likelihood.

Background: Predictors of prehypertension and the latter's significance in predicting metabolic syndrome (MetS), type 2 diabetes (DM), and incident coronary heart disease (CHD) need further exploration., Methods: Individuals with or without prehypertension (blood pressure (BP) 120-139 systolic or 80-89 mm Hg diastolic) were studied prospectively in a representative sample of Turkish adults., Results: Mean age of 1,501 men and 1,533 women was 48 +/- 12 years at baseline. Prehypertension, identified in 32.8% of the sample, differed from the normotensive group mainly by age-adjusted obesity measures and C-reactive protein (CRP) and progressed to hypertension at more than twofold annual incidence as normotension did. In logistic regression analysis, adjusted for sex, age, heart rate, and smoking status, prehypertension was predictive for risk of MetS in both genders (relative risk (RR) 1.55 (95% confidence interval (CI) 1.21; 1.99)) compared with normotensives. However, DM and CHD were significantly predicted by prehypertension only in women (RR 2.06 and 1.98, respectively, for outcomes). Cardiometabolic risks in women were largely independent of obesity. Body mass index (BMI) at baseline predicted significantly subsequent development of new prehypertension in both genders (hazard ratio 1.39 (95% CI 1.17; 1.65)) and CRP tended to contribute to this risk., Conclusions: Prehypertension, compared with normotension, approximately doubles the risk for DM, MetS, and CHD in women without conferring substantial risk in Turkish men, except toward MetS. Excess cardiometabolic risk of prehypertension in women is independent of obesity. BMI is a determinant of prehypertension.

Aim: To assess (i) the association between lipoprotein(a) [Lp(a)] with the likelihood of coronary heart disease and metabolic syndrome (MS) and (ii) its covariates in Turkish adults., Methods: Cross-sectional evaluation of 1309 adults, who had serum Lp(a) determinations by Behring nephelometry, and followed for a mean 1.0 year. MS was defined by ATPIII criteria modified for male abdominal obesity., Results: Mean age of the sample was 56.8+/-11.3 years. After adjustment for sex, age, and smoking status, log-transformed Lp(a) levels were associated significantly with coronary heart disease likelihood in both sexes combined [odds ratio: 1.53 (95% confidence interval: 1.06; 2.20)]. This association persisted after additional adjustment for MS [odds ratio: 1.57 (95% confidence interval: 1.09; 2.26)]. The Lp(a) mid-tertile (5-17 mg/dl), accompanied by significantly lower serum triglycerides than the two remaining tertiles, was inversely associated significantly with MS in either sex; in women, this association was independent of waist circumference. In a linear regression comprising seven variables, excepting total cholesterol, only gamma-glutamyltransferase in women (P=0.002) and waist circumference (P=0.057) in men were inverse covariates of modest magnitude of Lp(a)., Conclusion: Coronary heart disease likelihood, significantly associated with Lp(a) concentrations, is independent of MS and insulin resistance. Suggestive evidence was provided that intermediary Lp(a) concentrations, when accompanied by the presence of MS, could accelerate progression of vascular disease, especially in women.

The aim of study was to investigate the role of serum total (TPL) and high-density lipoprotein phospholipids (HDL-pl) as a risk factor in coronary heart disease (CHD) and metabolic syndrome (MS). In a random sample, total and HDL-pl were measured in 1088 and 642 adults from Turkey, respectively, who have a high prevalence of MS; this was done with an enzymatic method that measures total phosphatidylcholine, sphingomyelin, and lysophosphatidylcholine. Serum TPL and HDL-pl levels were significantly higher in women (TPL, 2.8 mmol/L; HDL-pl, 1.21 mmol/L) than in men. Strong correlations existed between serum TPL levels and non-HDL cholesterol (HDL-C), triglycerides, apolipoprotein (apo) B, complement C3, and gamma-glutamyltransferase. Non-HDL-C, HDL triglyceride, and apo A-I were strongly correlated with HDL-pl. Linear regression analyses revealed HDL-C, apo B, triglycerides, diabetes, and female gender as independent significant determinants of TPL levels in adults. HDL-C and impaired glucose regulation were sole significant variables, together contributing one-quarter of serum HDL-pl. Individuals with MS or diabetes had significantly higher TPL concentrations. The gender- and age-adjusted odds ratio (OR) of TPL for MS was 1.73 (95% confidence interval, 1.35-2.21), whereas the multiadjusted OR of HDL-pl per 1 SD increment corresponded to a significantly reduced independent MS likelihood by 26% in women (and 18% in the entire group). The multiadjusted OR of HDL-pl for CHD in men and women combined was 0.32 (P = .057) corresponding to a reduced CHD likelihood by 32% per 1 SD increment of HDL-pl. Plasma TPL levels point to an adverse relationship to MS, whereas their role in CHD risk needs further investigation. HDL-pls, in contrast, mark substantial protection from MS as well as from CHD.

To investigate determinants of abdominal obesity and its metabolic and clinical consequences relative to its degree in women, a prospective evaluation of 1682 female participants (aged 28-79 years at baseline), representative of Turkey's women, was performed. For components of metabolic syndrome (MS), criteria of National Cholesterol Education Program guidelines were adopted, modified for cut point of 91 cm or greater for abdominal obesity and less than 45 mg/dL for low high-density lipoprotein (HDL) cholesterol. Fasting insulin and C-reactive protein concentrations and (inversely) smoking more than 10 cigarettes daily were significant predictors of newly developed abdominal obesity at a follow-up of mean 5.9 years. In the prediction of high triglyceride-low HDL dyslipidemia, elevated blood pressure (BP) or MS and doubling of baseline fasting insulin level contributed approximately 25% to the hazard ratio (HR), whereas waist circumference exhibited independent HRs of 1.30, 1.62, and 2.22, respectively. Waist girth (or body mass index) quartiles was the major predictor (HR, 1.72) of diabetes mellitus (DM), followed by physical inactivity and total cholesterol and insulin levels, all independent of each other. Waist girth quartiles in women conferred excess risk of incident coronary heart disease from quartile II onward, independent of age, DM, and elevated BP. Fasting insulin and C-reactive protein levels and (inversely) heavy smoking are main predictors in Turkish women of abdominal obesity. Across waist girth quartiles, multiadjusted relative risks for dyslipidemia, elevated BP, MS, and coronary heart disease rise sharply and asymptotically from quartile II (> or = 83 cm) onward, whereas risk of DM emerges in the top quartile. A waist girth of 83 cm or greater should be regarded as abdominal obesity among Turkish women.

Unlabelled: We aimed to investigate determinants of abdominal obesity and its clinical impact on metabolic syndrome (MS), diabetes (DM) and coronary heart disease (CHD) in men., Methods: Prospective evaluation of 1638 male participants (aged 48.5+/-12.3), representative of Turkey's men who have a high prevalence of MS. For components of MS, criteria of NCEP guidelines were adopted, modified for abdominal obesity. Follow-up constituted 9650 person-years., Results: Insulin level (relative risk [RR] 1.40 for doubling), C-reactive protein (CRP) and heavy smoking (protective) were independent predictors of newly developing abdominal obesity. High triglyceride and low HDL-cholesterol were significantly associated already with waist girth quartile II, apolipoprotein B with quartile III. Waist girth significantly predicted future MS from quartile II on, independent of insulin resistance (IR) by homeostatic model assessment, whereby its hazard ratio (HR, 2.6) exceeded double that of HOMA. CRP independently predicted MS. Age-adjusted HR of waist girth (1.59) was significant in predicting DM. Age- and smoking-adjusted top waist quartile conferred significant risk for incident CHD (RR 1.71) but not for overall mortality. As judged by sensitivity and specificity rates for future CHD, DM and MS, abdominal obesity was most appropriately defined with a waist girth of >or=95 cm, and an action level 1 of >or=87 cm was proposed for MS in this population., Conclusions: Serum insulin, CRP levels and (inversely) heavy smoking are predictors for abdominal obesity in Turkish men. Atherogenic dyslipidemia and elevated blood pressure are associated significantly already with modest rises in waist girth adjusted for age and smoking. Abdominal obesity shows substantial independence of IR in the development of MS. Increasing waist girth was predictive of MS, more strongly than of DM. Risk for CHD imparted by abdominal obesity is essentially mediated by risk factors it induces.

In the present study, we examined (i) whether C3 (complement C3) was an independent marker of prevalent CHD (coronary heart disease), and (ii) which preferential associations existed between C3 and some cardiovascular risk factors when jointly analysed with CRP (C-reactive protein) and fibrinogen. In a cohort of 756 unselected adults, 39% of whom had the metabolic syndrome, C3 and other risk variables were evaluated in a cross-sectional manner. In a logistic regression model for the likelihood of CHD, a significant OR (odds ratio) of 3.5 [95% CI (confidence intervals), 1.27 and 9.62)] for C3 was obtained after adjustment for smoking status, TC (total cholesterol) and usage of statins. A similar model, also comprising systolic blood pressure, with a cut-off point of >or=1.6 g/l C3 exhibited a 1.9-fold risk (95% CI, 1.01 and 3.58) compared with individuals below the cut-off point. Both analyses displayed an adjusted OR of 1.37 for each S.D. increment in C3. The significant relationship of C3 with a likelihood of CHD also proved to be independent of CRP. In multiple linear regression models, associations were tested for each acute-phase protein with measures of obesity, fasting insulin, triacylglycerols (triglycerides), TC, HDL (high-density lipoprotein)-cholesterol, physical activity, smoking status, diagnosis of metabolic syndrome and family income. When both genders were combined, C3 was independently associated with serum triacylglycerols, waist circumference, BMI (body mass index) and TC. CRP was independently associated with waist circumference, TC, family income (inversely) and physical activity, and fibrinogen with BMI, TC, smoking status and metabolic syndrome. In summary, elevated levels of complement C3 are associated with an increased likelihood of CHD independent of standard risk factors and regardless of the presence of acute coronary events, suggesting that C3 might be actively involved in coronary atherothrombosis. Unlike CRP and fibrinogen, C3 was preferentially associated with waist girth and serum triacylglycerols.

The aim of the present study was to examine possible pathophysiological relationships among a wide array of proatherogenic risk factors in postmenopausal women. Fasting lipids, apoB (apolipoprotein B), BMI (body mass index) and waist circumference were measured in 178 women (59.4+/-7.2 years) from the Turkish Adult Risk Factor Study. Fasting levels of complement C3, insulin, SHBG (sex hormone-binding globulin), cortisol, oestradiol, testosterone and DHEA-S (dehydroepiandrosterone sulphate) were also determined. This is the first study to examine the relationships of all these variables with apoB. In the first of two different approaches, three groups of obese women were compared. Group 1 comprised women who were normolipidaemic with normal apoB; group 2, women who were hypertriglyceridaemic, but with normal apoB; and group 3, women who were hypertriglyceridaemic with elevated apoB. Complement C3, fasting insulin and glucose were significantly higher and HDL-C (high-density lipoprotein-cholesterol) and SHBG levels were significantly lower in group 3 than in group 1. In the former group, the testosterone/SHBG ratio tended to be higher, indicating more free testosterone, than in group 1. The mean risk score in group 3 and the odds ratio for coronary disease by logistic regression analysis were significantly higher, 2.56 (confidence intervals, 1.12-5.85; P=0.026), compared with the two other groups combined. In examining the whole group, apoB levels correlated significantly with a wider array of pro-atherogenic risk factors than did LDL-C (low-density lipoprotein-cholesterol), particularly being linked to complement C3 and glucose, as well as the risk score. Complement C3 demonstrated the widest associations and was significantly linked with BMI, waist circumference, insulin, glucose, fibrinogen, triacylglycerols (triglycerides) and apoB and was inversely correlated with HDL-C and SHBG. SHBG was also correlated inversely with a wide spectrum of risk variables. In summary, in Turkish women, apoB was linked with a complex array of proatherogenic risk factors, and hypertriglyceridaemia with elevated apoB was associated with a higher risk of coronary disease.

Aims We studied determinants of serum apolipoprotein C-III (apoC-III) and whether levels of apoC-III or its fractions predict metabolic syndrome (MetS), Type 2 diabetes and coronary heart disease (CHD). Methods The predictive value of apoC-III, measured by immunoturbimetric immunoassay in 802 tracked individuals of a Turkish general population in determining cardiometabolic risk was assessed over 4.4 ± 1.2 years’ follow-up. Patients with MetS, Type 2 diabetes and CHD at baseline were excluded. Results Total apoC-III, as well as both fractions, was significantly, linearly and inversely related to smoking status, positively to alcohol usage and to levels of complement C3. Mid and high tertiles of total or non-high density lipoprotein (HDL) apoC-III predicted significantly and independently incident MetS; they predicted CHD with risk ratios of 1.6 [95% confidence intervals (CI) 1.02–2.5], for 1 sd increment, after adjustments that included HDL cholesterol and body mass index (BMI). The highest tertile of HDL apoC-III was a major independent predictor of new-onset diabetes with a 2.5-fold risk ratio for 1 sd increment (95% CI 1.5–4.0) in combined sexes, after adjustment for waist circumference, HDL cholesterol and other confounders and was a better predictor than waist girth. Conclusions Serum total apoC-III or its fractions are linearly and inversely associated with smoking, positively with alcohol usage and serum complement C3. The presumably dysfunctional HDL apoC-III is a stronger predictor of Type 2 diabetes than waist girth in Turks. Non-HDL apoC-III predicts strongly the development of MetS as well as incident CHD, independent of HDL cholesterol, BMI and non-lipid factors. The atherogenicity of apoC-III and dysfunctionality of HDL apoC-III carry huge public health implications in Turks. [ABSTRACT FROM AUTHOR]

Abstract: Background: Predictive value of apolipoprotein (apo) A-I for incident hypertension, metabolic syndrome (MetS), type 2 diabetes (DM) and coronary heart disease (CHD) needs further exploration. Methods: A representative sample of Turkish adults was studied with this purpose prospectively. Sex-specific apoA-I tertiles were examined regarding cardiometabolic risk. Results and conclusions: A total of 1044 men and 1067 women (aged 49±12 years at baseline) were followed up over 7.4 years. High serum apoA-I levels were significantly associated in multivariable analysis with female sex, aging, alcohol intake, (inversely) cigarette smoking and, in women, with systolic blood pressure. Risk of diabetes was predicted in logistic regression in both genders by top versus bottom apoA-I tertile (RR 1.98; [95%CI 1.31; 3.0]), additive to age, body mass index (BMI), C-reactive protein (CRP), HDL-cholesterol and lipid lowering drugs. By adding sex hormone-binding globulin to the model in a subset of the sample, the association between high apoA-I and incident diabetes was attenuated only in women. ApoA-I tertiles tended to be positively associated also with hypertension and CHD only in women but this did not reach significance. High compared with low serum apoA-I levels nearly double the risk for incident diabetes, additively to age, BMI, CRP, HDL-cholesterol among Turks. Systemic inflammation concomitant with prevailing MetS might turn apoA-I into proinflammatory particles. [Copyright &y& Elsevier]