Dual activity of serum lipoprotein-associated phospholipase A(2) yielding positive and inverse associations with cardiometabolic risk.

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.

Gender- and obesity-specific effect of apolipoprotein C3 gene (APOC3) -482C>T polymorphism on triglyceride concentration in Turkish adults.

BACKGROUND: Apolipoprotein C3 (APOC3) gene polymorphisms are associated with cardiometabolic risk factors, varying in ethnicities. This study aimed to investigate such association between the APOC3 -482C>T polymorphism and cardiometabolic risk factors in the turkish adult risk factor (TARF) study cohort, stratifying by gender and obesity. METHODS: Randomly selected 1548 individuals (757 male and 791 female, mean age 49.9±11.8 years) were genotyped for -482C>T polymorphism using hybridization probes in a Real-Time PCR LC480 device. RESULTS: The -482TT genotype prevailed 9.9% in men and 11.5% in women. Association between 482C>T polymorphism and dyslipidemia (p=0.036, OR=1.42, 95%Cl=1.02-1.97) was found only in men. Analysis of variance showed that anthropometric and metabolic variables were not differently distributed in APOC3 -482C>T genotypes in the study population. In relation to dyslipidemia and obesity, the -482C>T polymorphism showed significant gender-by-genotype interactions (p<0.01). When the study population was stratified according to gender and obesity, homozygotes for the T allele were associated strongly with (by 45%) elevated fasting triglyceride concentrations in obese men (p=0.009) and homeostatic model assessment (HOMA) index in non-obese women (p=0.013). Furthermore, in the same subgroups, the associations of the fasting triglyceride concentrations and HOMA index with the TT genotype remained after adjustment for risk factors (p<0.05). CONCLUSIONS: APOC3 -482TT genotype is independently associated with elevated fasting triglyceride concentrations in obese men. Presence of obesity seems to be required for this genotype to induce markedly elevated triglycerides. Furthermore, it is associated with the dyslipidemia in men, without requirement of obesity.

High absolute coronary disease risk among Turks: involvement of risk factors additional to conventional ones.

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 Framingham 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.

Impaired anti-inflammatory function of apolipoprotein A-II concentrations predicts metabolic syndrome and diabetes at 4 years follow-up in elderly Turks.

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.

[Major influence of dysfunctions of protective serum proteins on cardiometabolic risk among Turks and gender difference]. / Halkimizda koruyucu protein disfonksiyonlarinin kardiyometabolik risk üzerine büyük etkisi ve cinsiyet farki.

Knowledge obtained from the Turkish Adult Risk Factor (TARF) study on higher morbidity and mortality rates compared to other populations from coronary heart disease (CHD) among Turkish adults has been confirmed recently with greater power. This review provides insight that the dysfunctions of the protective serum proteins, attaining pro-inflammatory and atherogenic features, may be attributed to atherogenic dyslipidemia, oxidative stress, and systemic inflammation associated with the high prevalence of metabolic syndrome (MetS) among Turks. The mentioned protective protein dysfunctions, firstly described in a general population to date, are high-density lipoprotein (HDL), apolipoprotein (apo) A-I, A-II, and apoC-III, apart from adiponectin. Based on published findings of the TARF study, this review discusses the role of inflammatory mediators such as elevated C-reactive protein (CRP), apoB, apoC-III, fibrinogen, and low adiponectin serum levels in cardiometabolic risk comprising MetS, type 2 diabetes, and CHD, the degree of independence of these mediators from the ATP-III-defined MetS, and the influence of sex. Moreover, it is emphasized that dysfunctions of adiponectin and protective proteins related to HDL particles increase not only cardiometabolic risk significantly but also CHD risk among half of Turkish adults in a magnitude similar to or greater than that associated with traditional risk factors. Also underlined is the observation that cigarette smoking reduces the risk in Turkish women for the development of hypertension, MetS, and diabetes by mediation of positive effects on dysfunctional apoA-I, visceral fat accumulation and, above all, CRP levels. This knowledge is of utmost importance and sheds light to authorities and those concerned on the necessity of urgent and radical modifications regarding strategies in prevention and management of cardiovascular health of middle-aged Turks.

Moderate and heavy alcohol consumption among Turks: long-term impact on mortality and cardiometabolic risk.

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.

Predictive value of prehypertension for metabolic syndrome, diabetes, and coronary heart disease among Turks.

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.

Serum C-reactive protein is an independent risk factor predicting cardiometabolic risk.

The aim of the study was to investigate the role of serum C-reactive protein (CRP) level as a risk factor in predicting metabolic syndrome (MS), hypertension, atherogenic dyslipidemia, type 2 diabetes mellitus, and coronary heart disease. We prospectively evaluated 1270 men and 1320 women, aged 30 to 89 years, who had serum CRP determinations and a mean 4.3 years' follow-up. The CRP values were log-transformed for calculations. Metabolic syndrome was defined by the Adult Treatment Panel III criteria modified for male abdominal obesity. Prediction of outcome was performed by excluding from analysis the particular outcome variable existing at baseline examination. Smoking men had higher age-adjusted estimated CRP concentrations (P < .001), whereas smoking women had lower CRP (P = .027) than never smokers. Risk of developing an elevated (> or =2 mg/L) CRP was predicted significantly by baseline CRP in both sexes and by apolipoprotein (apo B), current smoking, and family income in men, when adjusted for 5 further variables. Baseline CRP levels predicted atherogenic dyslipidemia when adjusted for age, baseline dyslipidemia values, and apo B tertiles and predicted incident hypertension independent of age, waist circumference, and smoking status. After adjustment for sex, age, and the 5 MS components, CRP predicted newly developing MS, with a hazard ratio (HR) of 1.16 (95% confidence interval, 1.02-1.32). When adjusted for sex, age, baseline glucose, waist circumference, and apo B tertiles, diabetes was significantly predicted by CRP in women (HR, 1.31) alone. Sex- and age-adjusted CRP level identified also those that progressed to diabetes independent of a fasting glucose >100 mg/dL (HR, 1.39; 95% confidence interval, 1.21-1.59), although not in men. In the prediction of incident coronary heart disease, CRP contributed to 7 established risk factors including waist circumference with a significant 1.18-fold HR. C-reactive protein is both an independent significant predictor and a risk factor of cardiometabolic risk among Turkish adults, additive to MS components, whereby risk is modulated by sex, smoking habit, and apo B.

Lipoprotein(a) is associated with coronary heart disease independent of metabolic syndrome.

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.

Serum total and high-density lipoprotein phospholipid levels in a population-based study and relationship to risk of metabolic syndrome and coronary disease.

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.

Serum asymmetric dimethylarginine levels among Turks: association with metabolic syndrome in women and tendency to decrease in smokers.

OBJECTIVES: We investigated serum asymmetric dimethylarginine (ADMA) levels and their association with smoking, metabolic syndrome (MS), and coronary heart disease (CHD) among Turkish adults. STUDY DESIGN: Serum ADMA concentrations were measured in a cross-sectional study by a validated ELISA kit in a random sample of 464 Turkish adults (222 men, 242 women; mean age 55+/-11 years; range 34-89). Metabolic syndrome was identified by the criteria of the Adult Treatment Panel-III modified for male abdominal obesity. RESULTS: The median serum ADMA concentration was 0.80 micromol/l, with the interquartile range of 0.57 to 1.13 micromol/l. Compared to nonsmokers, age-adjusted ADMA level was 20% lower in smoking men (p=0.057), and 6% lower in smoking women (p=0.6). Serum ADMA levels showed significant and positive correlations with age, testosterone, and fibrinogen concentrations in men, and a borderline significance with triglyceride, C-reactive protein, and sex hormone-binding globulin in women. No significant association was found with MS, hypertension, or CHD likelihood among men; but, after adjustment for age, smoking status, and systolic blood pressure, the odds ratio of doubling of ADMA for the likelihood of MS reached significance in women (OR 1.25; 95% CI 1.01; 1.53). Age- and smoking-adjusted ADMA in women tended to be associated also with hypertension (OR 2.55, p=0.07). CONCLUSION: Serum ADMA levels are significantly associated with MS likelihood in women alone, but not with the likelihood for CHD in either gender. Serum ADMA in middle-aged and elderly Turks is inversely associated with cigarette smoking, and thus possibly contributes to the smoking-related protection of Turkish women from MS.

Determinants and definition of abdominal obesity as related to risk of diabetes, metabolic syndrome and coronary disease in Turkish men: a prospective cohort study.

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.

Prospective epidemiologic evidence of a "protective" effect of smoking on metabolic syndrome and diabetes among Turkish women--without associated overall health benefit.

UNLABELLED: Sex-specific effects of cigarette smoking on the development of metabolic syndrome (MS) and diabetes (DM), concomitant with its clinical impact on CHD, were prospectively evaluated in a cohort of 3385 participants (mean age 48 years), representative of Turks. Heavy smoking denoted smoking 11 or more cigarettes daily. During a mean 5.9-year follow-up, 485 incident cases of MS and 216 of DM were diagnosed. Among women, baseline characteristics as a whole were similar. Smoking status was inversely associated with waist circumference (p=0.004) and predicted in women hyperinsulinemia (p=0.045) after adjustment for age and body mass index. In the prediction of MS, heavy smoking was significantly "protective" (RR 0.50 [95% CI 0.26; 0.94]) in women and in both genders combined, after adjustment for age, baseline family income bracket and physical activity grade. As predictor of new DM, heavy smoking was significantly "protective" (RR 0.54 [95% CI 0.35; 0.83]) in all adults and in women (RR 0.13 [95% CI 0.02; 0.97]), after similar adjustment. Additional adjustment for insulin and CRP levels hardly modified in women the RRs, though attenuated to borderline significance risk for MS and DM due to smaller sample size. Risks of incident CHD and overall mortality were significantly elevated in smoking men, but not in women, when adjusted for age, serum total cholesterol, elevated BP, DM and physical activity grade. CONCLUSIONS: Heavy cigarette smoking is "protective" of future MS and DM in Turkish women, mainly via protection from obesity. A separate modest effect on central obesity appeared independent of plasma insulin concentrations. Evidence of a translated beneficial effect on subsequent CHD or all-cause mortality did not emerge.

Serum sex hormone-binding globulin, a determinant of cardiometabolic disorders independent of abdominal obesity and insulin resistance in elderly men and women.

Serum sex hormone-binding globulin (SHBG) is related to cardiometabolic disorders; but whether or not this relationship is purely secondary to hyperinsulinemia and/or obesity, which down-regulates SHBG, is unknown. The aim of the study was to investigate the association of SHBG and total testosterone with atherogenic dyslipidemias, metabolic syndrome (MS), and diabetes among predominantly elderly Turkish adults. After appropriate exclusions, 777 randomly selected male and female subjects with available measurements of both variables were eligible and were analyzed cross-sectionally, with diabetic subjects analyzed separately. Free testosterone was calculated. Metabolic syndrome was identified by the modified criteria of the Adult Treatment Panel III. Metabolic syndrome was identified in half the sample, which had a median age of 58 years. The odds of low SHBG concentrations (<45 nmol/L in men, <55 nmol/L in women) for the likelihood of 2 types of dyslipidemias, MS, and diabetes were examined by regression analyses in standard models including age, smoking status, presence of abdominal obesity, and insulin resistance (homeostasis model assessment of insulin resistance). In both sexes, low SHBG was associated independently with high triglyceride/low high-density lipoprotein dyslipidemia and with MS, at significant 2.2- to 4.5-fold odds ratios, independent of waist circumference or homeostasis model assessment of insulin resistance index. Low SHBG among women was additionally associated with the likelihood of hypertriglyceridemia with elevated apolipoprotein B and-at borderline significance-with that of diabetes, again when adjusted for the same confounders. In an elderly population with prevalent MS, low SHBG levels significantly associate with high triglyceride/low high-density lipoprotein dyslipidemia, MS, and, in women alone, diabetes and a dyslipidemia marking small dense low-density lipoprotein particles, all independent of abdominal obesity and insulin resistance. Low SHBG may be an important independent factor for cardiometabolic risk, particularly in women.

Predictors of abdominal obesity and high susceptibility of cardiometabolic risk to its increments among Turkish women: a prospective population-based study.

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.

The S447X variant of lipoprotein lipase gene is associated with metabolic syndrome and lipid levels among Turks.

BACKGROUND: We evaluated the relationship of the lipoprotein lipase (LPL) S447X variant with serum lipid levels and the metabolic syndrome (MS) in the Turkish Adult Risk Factor (TARF) study. This is the first study examining this LPL variant in the Turkish population. METHODS: The sample comprised 1586 Turkish adults. Genotyping was performed using the Taqman allelic discrimination assay. RESULTS: The X447 allele frequency was 0.11 (95% CI: 0.10-0.12). X447 allele carriers had significantly higher levels of HDL-C, LDL-C and total cholesterol; and lower fasting glucose, when compared with the SS genotype in females. In men, no significant association with any parameters was seen. The genotypic impact of the S447X variant on lipid levels appears to be modulated by environmental factors, such as cigarette smoking in women. Logistic regression analysis demonstrated a significantly reduced likelihood for metabolic syndrome in female X447 allele carriers (p=0.04), after adjustment for age, cigarette smoking, alcohol usage and physical activity grade. CONCLUSIONS: In especially Turkish women, compared to non-carriers, carriers of the LPL X447 allele have higher levels of HDL-C, LDL-C and total cholesterol, and show a degree of protection against developing the metabolic syndrome.

[Prospective validation in identical Turkish cohort of two metabolic syndrome definitions for predicting cardiometabolic risk and selection of most appropriate definition]. / Iki metabolik sendrom taniminin kardiyometabolik risk öngörüsünün ayni kohortta prospektif yolla degerlendirilmesi ve halkimiz için en uygun tanimin seçilmesi.

OBJECTIVES: To investigate the relative values in the prediction of type 2 diabetes and coronary heart disease (CHD) by the metabolic syndrome (MS) as defined by the ATPIII and by its modification of the Turkish Adult Risk Factor Study (TEKHARF-def) and selection of most appropriate definition. METHODS: Prospective evaluation of 1683 men and 1718 women, aged > or =28 years participating in the TEKHARF study surveys 1997/98 and 2002/03 with a mean follow-up of 5.9 years. The modification involved especially abdominal obesity (> or =95 cm in men, > or =91 cm in women). RESULTS: After exclusion of participants with diabetes at baseline and adjustment for sex and age, both MS definitions predicted the development of diabetes with virtually identical relative risks (RR) (ATPIII 2.85 [95%CI 2.14; 3.80]; TEKHARF 2.84 [95%CI 2.13; 3.81]. After similar exclusion and adjustments, both MS definitions predicted significantly the development of CHD with similar RRs (ATPIII 2.10 [95%CI 1.64; 2.68] in 36% of the cohort; TEKHARF-def 1.90 [95%CI 1.49; 2.43] in 39.6% of the cohort. For both outcomes, the TEKHARF-def provided higher predictive values in men, and (because of the high density lipoprotein (HDL)-cholesterol cutoff) the ATPIII definition in women. Absolute annual CHD risk in individuals with MS exceeded on average 2%, while age > or =50 years constituted the most appropriate indicator of further elevated risk in both genders. Most suitable modifications of the ATPIII definition are proved to be impaired fasting glucose (IFG) > or =100 mg/dl and in men > or =95 cm of waist circumference. Most CHD cases afflicting Turkish adults (namely 61% in men and 69% in women) originated from the latter definition of MS. CONCLUSIONS: In predicting diabetes and CHD risk, the TEKHARF-def MS is more valuable in men; the ATPIII definition modified for IFG (> or =100 mg/dl) should be adopted in women. In 2 out of every 3 cases, CHD originates from MS among Turks, and age > or =50 years is a good indicator of higher risk in both genders.

[Serum apolipoprotein B is superior to LDL-cholesterol level in predicting incident coronary disease among Turks]. / Türk halkinda yeni gelisen koroner hastalik öngördürücüsü olarak serum apolipoprotein B düzeyi LDL-kolesterolden üstün.

OBJECTIVE: To investigate the relative roles of serum apolipoprotein (apo) B and low density lipoprotein (LDL)-cholesterol levels in predicting incident coronary heart disease (CHD). Whether apo B/apo A-I ratio has advantage over apo B in this prediction constitutes a secondary aim. METHODS: Prospective evaluation of 1138 men and 1210 women, aged 28-74 years participating in the TEKHARF survey 1997/98 with a mean 5.9-years' follow-up in whom serum apo B was determined. Tertiles of LDL-cholesterol were formed by cut points of 130 and 100 mg/dl, and of apo B by 120 and 95 mg/dl. Metabolic syndrome was defined by modified ATPIII criteria. Nonfatal CHD diagnosis was based on history of angina and myocardial revascularization, physical examination of the cardiovascular system and Minnesota coding of resting electrocardiograms. RESULTS: Apolipoprotein B showed significant correlations with a greater number of parameters than did LDL-cholesterol. Incident CHD was not significantly predicted in age-adjusted logistic regression by LDL-cholesterol but by apo B concentrations in men with a relative risk (RR) 1.005. Apolipoprotein B level >120 vs <95 mg/dl retained significance in both genders combined, even after adjustment for waist girth and log C-reactive protein. The top (>1.02) compared with the bottom bracket of apo B/A-I ratio, though not reaching significantly predictive values among women, did significantly predict in men incident CHD with a RR 1.89. CONCLUSIONS: Apolipoprotein B, which marks small, dense LDL particles in plasma, is a better predictor of incident CHD than LDL-cholesterol among Turkish adults. While in the prediction of CHD apo B level should be preferred in women, an apo B/A-I ratio >1.02 has advantages over the latter in men. It is time to create the environment (at least in our cities) for measuring in equipped laboratories apo B, which has advantages over measurements that permit calculation of LDL-cholesterol.

Serum uric acid is a determinant of metabolic syndrome in a population-based study.

BACKGROUND: Determination of serum uric acid concentrations and role in risk of metabolic syndrome (MS) were investigated in 1877 participants in a cross-sectional population-based study including a brief follow-up. METHODS: The MS was identified by modified criteria of the Adult Treatment Panel III, and coronary heart disease (CHD) by clinical findings and Minnesota coding of resting electrocardiograms. Uric acid concentrations were measured by the uricase method. RESULTS: Metabolic syndrome was present in 39.1% of the cohort. Linear regression analysis of uric acid levels in a model comprising 13 variables identified gender, waist girth, total cholesterol (TC), alcohol usage, triglycerides, log C-reactive protein (CRP), and log gamma-glutamyl transferase (GGT), and in women diuretic use and elevated blood pressure (BP), as significant independent covariates whereby the largest contribution (1.6 mg/dL) was generated by waist girth. Logistic regression analysis of serum uric acid for MS disclosed for the top versus the bottom tertile an odds ratio (OR) of 1.89 (95% confidence interval [CI]: 1.45-2.46) in men and women combined, after adjustment for sex, age, TC, log CRP, log GGT, alcohol, and diuretic drug use, presence of diabetes/impaired fasting glucose, elevated BP, and smoking status. This corresponded to an increase by 35% in MS likelihood for each 1 SD uric acid increment. This rate declined to a significant 15% by inclusion of waist girth into the model. The OR of uric acid concentrations for prevalent and incident CHD, adjusted for age, MS, smoking, and diuretic use, was not significant among women and only tended toward significance in men. CONCLUSIONS: Abdominal obesity is the main determinant of uric acid variance. An increment of 1 SD in serum uric acid levels are associated in both sexes with a 35% higher MS likelihood, independent of 10 risk factors related to MS. After adjustment for waist girth, a more modest but significant likelihood persists, which suggests that serum uric acid is a determinant of MS.

Discordance between insulin resistance and metabolic syndrome: features and associated cardiovascular risk in adults with normal glucose regulation.

The aims of this study were to investigate the extent of concordance between metabolic syndrome (MS) and insulin resistance (IR), the features of discordance, and the magnitude of their independent association with cardiovascular disease (CVD) risk. After exclusion of individuals with diabetes and impaired fasting glucose, the population sample of 1534 men and women, representative of Turkish adults (mean age, 52.2 years), were evaluated cross-sectionally and at a mean 2 years' follow-up. Metabolic syndrome was identified by criteria of the Adult Treatment Panel III, except for male waist circumference (>94 cm). Insulin resistance was defined by the upper quartile in the sample (>2.245) of the homeostatic model assessment (HOMA) index. Clinical fatal and nonfatal CVD existed or developed in 165 subjects. Waist circumference proved to be by far the strongest significant determinant of HOMA in both sexes, followed by triglycerides. The cohort was categorized into 4 by the presence or absence of MS and IR. Each of the latter represented 34% and 25%, but together constituted 45% of the sample, thus disclosing concordance in a third of the conditions combined. The nonconcordant IR/NoMS group was less common than the MS/NoIR group and was distinct from the latter in having significantly lower waist girth, blood pressure, apolipoprotein B and triglyceride levels, and higher high-density lipoprotein cholesterol, glucose, and insulin levels and physical activity in both sexes. When adjusted for 5 important risk factors, although the excess risk in men with MS failed to attain significance, men with IR were associated with a significant 1.9-fold CVD risk. The IR/NoMS group had a 2.2-fold (95% confidence interval, 0.97-5.11) CVD likelihood compared with the large insulin-sensitive group, after adjustment for age, sex, log C-reactive protein, low-density lipoprotein cholesterol, smoking status, physical activity, and the 2 groups of MS with or without IR. Overlapping between MS and IR is limited in either sex, and MS/NoIR is more common than IR/NoMS. Overall, IR is more significantly associated with CVD risk than MS in men and in both sexes after adjustment for important confounders. Insulin resistance without MS tends to implicate in middle-aged and elderly Turkish men roughly a 2-fold CVD risk, corresponding to 50% excess risk per 1 SD in HOMA index, independent of MS and important covariates.