Gülay Hergenç

Neck circumference as a measure of central obesity: Associations with metabolic syndrome and obstructive sleep apnea syndrome beyond waist circumference

BACKGROUND & AIMS To investigate the relationship of neck circumference (NC) to metabolic syndrome (MetS) and obstructive sleep apnea syndrome (OSAS) and whether it adds information to that provided by waist circumference. METHODS Cross-sectional analysis of a population sample of 1,912 men and women, aged 55.1 +/- 12 years, representative of Turkish adults. MetS was identified based on modified criteria of the ATP-III, OSAS when habitual snoring and episodes of apnea were combined with another relevant symptom. RESULTS NC measured 36.7 (+/- 3.5) cm in the total sample. It was significantly correlated with numerous risk factors, above all body mass index and waist girth (r > or = 0.6), homeostatic model-assessed insulin resistance, blood pressure and, inversely, with smoking status and sex hormone-binding globulin. Sex- and age-adjusted NC was associated significantly with MetS, at a 2-3-fold increased likelihood for 1 standard deviation (SD) increment. After further adjustment for waist circumference and smoking status, a significant residual odds ratio (OR, 1.13 [95% CI 1.08; 1.19]) persisted, corresponding to ORs of 1.53 and 1.27 in males and females, respectively, for 1 SD increment. Even when adjusted for all MetS components, a residual OR (1.08 [95% CI 1.000; 1.17]) remained. Sex- and age-adjusted NC was associated significantly also with OSAS in genders combined, independent of waist girth, yielding an added OR of 1.3 for 1 SD increment. CONCLUSIONS NC contributes to MetS likelihood beyond waist circumference and the MetS components. Regarding association with OSAS, NC is of greater value than WC among Turkish men, not women.

Apolipoprotein C-III, a strong discriminant of coronary risk in men and a determinant of the metabolic syndrome in both genders

AIMS Apolipoprotein C-III (apoC-III) has been recognized as a useful marker of triglyceride-rich lipoproteins (TRLs) metabolism and proposed as an indicator of prognosis for coronary risk in healthy subjects. We studied cross-sectionally in a population having low cholesterol levels, but a high prevalence of the metabolic syndrome, whether serum levels of total apoC-III or its sub-fractions were independent markers of prevalent coronary heart disease (CHD) or were related to variables reflecting the metabolic syndrome. METHODS AND RESULTS In 857 unselected participants of the representative population sample of the Turkish Adult Risk Factor Survey in 2001, apoC-III as well as other risk variables were evaluated, and CHD was diagnosed based on clinical findings and Minnesota coding of resting electrocardiograms. The sample consisted of men and women, aged 33-82 years, having a mean waist circumference of 89.4 and 92.9 cm, respectively, 42% of whom had the metabolic syndrome identified by criteria of the ATP III. ApoC-III values were measured by turbidimetric immunoassay. Mean concentrations for non-high-density lipoprotein (nonHDL) apoC-III in men and women were 6.4 and 6.2 mg/dl, respectively, and for apoC-III in HDL were 6.2 and 6.3 mg/dl, respectively. NonHDL apoC-III was similar to, and apoC-III in HDL was higher than that in Western populations. Both fractions of apoC-III were significantly correlated with lipids, lipoproteins, apoB, anthropometric measures, and blood pressures in both genders. Correlations for both were high with serum triglycerides (r(s)=around 0.70) and apoB (r(p)=around 0.37). Total apoC-III as well as both fractions were significantly correlated in women also with levels of inflammatory risk markers: strongly (r=0.40-0.45, P<0.001) with complement C3, and weakly (r(s)=around 0.20, P<0.001) with C-reactive protein. A cutoff of >7.0 mg/dl as opposed to lower levels of nonHDL apoC-III indicated the presence of hypertriglyceridemic hyperapo B with an age-adjusted odds ratio (OR) of 13.8; it indicated the presence of metabolic syndrome with 4.66-fold likelihood. Total apoC-III and nonHDL apoC-III proved to be significantly (P-trend <0.05 and 0.002) and strongly associated with prevalent CHD in men even after adjustment for age, low-density lipoprotein-cholesterol (LDL-C) and high-density lipoprotein-cholesterol (HDL-C): OR gradients across upper and lower quartiles were 3.88-fold (CI: 1.3; 11.4) and 8.8-fold (CI: 2.6; 29.8), respectively. CONCLUSIONS In a population among whom the metabolic syndrome prevails, total- and nonHDL apoC-III are each a determinant in both genders of the metabolic syndrome and of hypertriglyceridemic hyperapo B. Each is a powerful significant marker of prevalent CHD in men independent of LDL- and HDL-C levels. In women, despite being correlated with inflammatory risk markers, the significant association of elevated levels of apoC-III with CHD did not prove to be independent of age.

Associations of obesity markers, insulin, and sex hormones with HDL-cholesterol levels in Turkish and German individuals

Turkish men and women have about 20% lower mean levels of HDL-C and apoA-I than German individuals. To obtain some information on the metabolic basis of this difference, we compared anthropometric data as well as serum levels of leptin, insulin, testosterone (T), estradiol (E2), and sex hormone binding globuline (SHBG) in 289 German and 120 Turkish men as well as in 108 German and 182 Turkish women aged 20-60. Individuals who smoke, take hormones, have overt diabetes mellitus, BMI > 30 kg/m2, triglycerides > 400 mg/dl, or LDL-cholesterol > 200 mg/dl were excluded. In both sexes, Turks had significantly lower levels of HDL-C, apoA-I, Lp(a), and SHBG than Germans. Moreover, German men had a larger waist circumference, lower levels of E2 and a lower ratio of T/SHBG. German women also had a lower BMI, smaller waist circumference, lower insulin levels and higher T levels. Mean values of age, waist-hip-ratio (WHR), leptin, triglycerides, LDL-C, and apoB did not differ significantly among Germans and Turks. Upon univariate analysis HDL-C had inverse correlations with BMI, waist circumference, WHR, leptin, and insulin as well as positive correlations with SHBG in both sexes. Upon multivariate analysis, most of the different levels of HDL-C and apoA-I between Germans and Turks were explained by ethnicity, independently of obesity markers, insulin, and sex hormones.

Low-grade inflammation, and dysfunction of high-density lipoprotein and its apolipoproteins as a major driver of cardiometabolic risk

Dysfunction of high-density lipoprotein (HDL) particles that even become proinflammatory or lose atheroprotective properties is known through analyses of HDL isolated from diabetic subjects. Recently, high concentrations of HDL or apolipoprotein (apo) A-I in individuals with diabetes or coronary heart disease were found to reveal dysfunction in some population-based studies. Such dysfunction of HDL and its apos A-I, A-II, and C-III has been observed in a general population for the first time among Turkish adults. Functional defectiveness manifested itself by unexpected correlations with inflammatory biomarkers and, in long-term follow-up, by lack of protection against diabetes and coronary heart disease, accounting for the excess incidences in Turks. Female sex was more pronouncedly affected by this process that presumably exists in other ethnicities in South Asia, East Europe, and the Middle East. In contradistinction, in Western and East Asian population, only individuals with glucose intolerance or those at risk for cardiometabolic disease are considered to be or were documented in a review of clinical trials to have been affected by impaired function of HDL. High-density lipoprotein dysfunctionality is closely linked to obesity and low-grade inflammation yet seems to act partly independently of them. Cigarette smoking in overweight women with low-grade inflammation appears to offer limited protection against cardiometabolic risk. The great impact in public health of the dysfunction of protective serum proteins requires individual clinical recognition, appropriate preventive measures, and delineation of management, including with anti-inflammatory drugs.

Impaired protection against diabetes and coronary heart disease by high-density lipoproteins in Turks

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.

Cross-sectional study of complement C3 as a coronary risk factor among men and women.

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 paradox of high apolipoprotein A-I levels independently predicting incident type-2 diabetes among Turks

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.

C-reactive protein and coronary heart disease in Western Turkey ☆

C-reactive protein (CRP) has been recognized as a useful marker for coronary or cardiovascular risk in healthy subjects or patients with coronary heart disease (CHD) in industrialized societies. We assessed whether CRP could serve as a marker of prevalent CHD risk in a cross-sectional study of a population with low cholesterol levels (4.61 mmol/L in men and 4.82 mmol/L in women) but higher prevalence of other risk factors. In 1,046 participants of the Turkish Adult Risk Factor Survey in 2000, high-sensitivity CRP as well as other risk variables were evaluated, and CHD was diagnosed, based on clinical findings and Minnesota coding of electrocardiograms at rest. Almost an equal number of men and women > or = 30 years of age constituted the population sample of the western regions of Turkey. Geometric mean value of CRP was 1.9 mg/L (interquartile range 0.8 to 4.3), without revealing a significant difference in gender. CRP was correlated with many variables, notably those involving central obesity, fibrinogen, and apolipoprotein-B, but not with smoking status (regardless of age adjustment). In multiple regression models, blood fibrinogen, waist circumference, total cholesterol, and physical activity grade were independently associated with log CRP concentrations. Among many risk variables, CRP quartiles and systolic blood pressure were, besides age and gender, the only significant independent determinants of CHD. The age-adjusted odds ratio for CHD in the highest as opposed to the lowest quartile was 4.48 (p < 0.001). Even after adjustment for the 5 previously mentioned determinants of CRP, a 4.2-fold increased risk of CHD still persisted between the highest and lowest quartiles. Thus, the observed increased risk was not in large part due to the intermediary effects of fibrinogen, nor were some indicators of insulin resistance, but interaction appeared to be independent of these effects. Thus, CRP values serve as a marker of prevalent CHD risk in populations with low cholesterol levels. This association is independent of, or in addition to, the effects of conventional risk factors, suggesting that the contribution of chronic low-grade inflammation to the atherothrombotic process is present even in the setting of low cholesterol levels.

Serum complement C3: a determinant of cardiometabolic risk, additive to the metabolic syndrome, in middle-aged population

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.

Serum apolipoprotein C‐III in high‐density lipoprotein: a key diabetogenic risk factor in Turks

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).