Coronary disease risk prediction algorithm warranting incorporation of C-reactive protein in Turkish adults, manifesting sex difference.

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.

An algorithm to predict risk of type 2 diabetes in Turkish adults: contribution of C-reactive protein.

BACKGROUND AND AIM: An algorithm for predicting Type 2 diabetes (DM) risk in a population with prevalent metabolic syndrome (MetS) is needed since ethnicity influences the pathogenesis of DM. MATERIAL AND METHODS: The 8- yr risk of DM was estimated in 2261 middle-aged Turkish adults free of DM at baseline who were followed for over 7.6 yr. DM newly developed in 212 subjects. Cox proportional hazard regression and 15 variables were used to predict DM. Discrimination was assessed with area under receiver operating characteristics curve (AROC). RESULTS: In multivariable analysis, height, family income brackets, systolic blood pressure, smoking status, alcohol usage, and HDL-cholesterol levels were not predictive in either sex. In addition to sex, family history of DM, fasting glucose, and waist circumference were predictors, in men, age and non-HDL-cholesterol, while in women physical inactivity and serum C-reactive protein were so. AROC of the final model was 0.783 in men, 0.772 in women (p<0.001 each). An algorithm using the stated 7 variables was developed separately for each sex. Men and women in the top quintile of risk score were, respectively, 20 and 50 times and significantly more likely to develop DM than those in the bottom quintile. The predictive value of the algorithm was validated in 2 split samples. CONCLUSIONS: A marker of low grade inflammation provides useful predictive ability beyond other simple predictors in a female population with MetS prevailing. The derived simple algorithm may be useful in estimating the 8-yr risk of DM among middle-aged Turkish men and women.

Obstructive sleep apnea and type 2 diabetes.

Type 2 diabetes and obstructive sleep apnea (OSA) are diseases with high prevalence and major public health impact. There is evidence that regular snoring and OSA are independently associated with alterations in glucose metabolism. Thus, OSA might be a risk factor for the development of type 2 diabetes. Possible causes might be intermittent hypoxia and sleep fragmentation, which are typical features of OSA. OSA might also be a reason of ineffective treatment of type 2 diabetes. There is further evidence that the treatment of OSA by continuous positive airway pressure (CPAP) therapy might correct metabolic abnormalities in glucose metabolism. It is assumed that this depends on therapy compliance to CPAP. On the other hand, there are also hints in the literature that type 2 diabetes per se might induce sleep apnea, especially in patients with autonomic neuropathy. Pathophysiological considerations open up new insights into that problem. Based on the current scientific data, clinicians have to be aware of the relations between the two diseases, both from the sleep medical and the diabetological point of view. The paper summarizes the most important issues concerning the different associations of OSA and type 2 diabetes.

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.

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). 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.

Association of C-reactive protein (CRP) gene allelic variants with serum CRP levels and hypertension in Turkish adults.

OBJECTIVE: Serum C-reactive protein (CRP) is an independent risk factor for cardiovascular disease and metabolic syndrome (MetS). The aim of this study was to analyze the CRP gene allelic variations in the Turkish adult risk factor (TARF) study and relate them with serum CRP levels as well as MetS and its components. METHODS: We analyzed CRP gene polymorphisms (-286C>T>A [rs3091244], +1444C>T [rs1130864], +1059G>C [rs1800947], and +1846G>A [rs1205]) as well as their haplotypes, in addition to measuring CRP levels (n=1138) and collecting risk factor data from 1987 adults (mean age 54.3+/-11.9 years, 51.3% women) participating in the TARF Study. MetS was defined by using the criteria of the National Cholesterol Education Program modified for pre-diabetes and in men for abdominal obesity. RESULTS: After adjustment for the major cardiovascular risk factors, four CRP SNPs (-286C>T>A, +1059G>C, +1444C>T, and +1846G>A) were significantly associated with serum CRP levels in women (p<0.05), whereas the -286C>T>A and +1444C>T polymorphisms were associated with CRP levels in men (p<0.05). The haplotype analyses revealed four common CRP haplotypes. The haplotype 1 (CGCA) in women and the haplotype 3 (TGTG) in men were associated with serum CRP levels and hypertension (p<0.05). However, no haplotype association was observed for MetS or its components. CONCLUSION: CRP gene allelic variation is associated with serum CRP levels as well as hypertension in Turkish adults.

Serum apolipoprotein B predicts dyslipidemia, metabolic syndrome and, in women, hypertension and diabetes, independent of markers of central obesity and inflammation.

OBJECTIVES: To investigate the role of serum apolipoprotein (apo) B levels in predicting metabolic syndrome (MS), hypertension, atherogenic dyslipidemia and type II diabetes. METHODS: Prospective evaluation of 1125 men and 1223 women, aged 28-74 years, participating in the survey 1997/1998 who had serum apo B determinations and were followed-up for a mean 5.9 years. Tertiles of apo B were formed by cut points by 120 and 95 mg/dl. MS was defined by modified ATPIII criteria. RESULTS: Apo B values exhibited no significant difference among sexes. Low-density lipoprotein (LDL)-cholesterol and triglycerides were their leading determinants on linear regression analysis. By logistic regression analyses, the top versus bottom apo B tertile predicted significantly newly developing MS in both sexes separately with two-fold relative risks (RRs) (P<0.02) and the development of high triglyceride/low high-density lipoprotein-cholesterol dyslipidemia with nearly threefold RRs (P=0.001), after adjustment for waist circumference, C-reactive protein (CRP), physical activity grade and family income category. Development of hypertension was predicted only in women by the apo B top tertile (fully adjusted RR 1.71 [95% CI 1.001; 2.92]), while the significance of the prediction regarding age-adjusted diabetes in women (RR 1.86 [95% CI 1.04; 3.36]) attenuated after adjustment for the stated confounding factors. CONCLUSIONS: Apo B concentrations, which reflect the number of small, dense LDL particles in plasma, are a significant predictor of cardiometabolic risk among adults with a high prevalence of MS, independent of waist circumference and CRP.

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.

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.

Apolipoprotein E Genotyping in Turkish Myocardial Infarction Survivors and Healthy Controls.

The apolipoprotein (Apo) E gene is known to be polymorphic. Three common alleles determine six phenotypes which can easily be detected by restriction fragment length polymorphism. We performed apo E genotyping in myocardial infarction survivors and healthy controls for the first time in the Turkish population. DNA was amplified by polymerase chain reaction (PCR) and the PCR product was digested with restriction enzymes HhaI to detect apo E2, E3, E4 and with TaqI to detect apo E1. Relative allele frequency for the patient group was found to be 0.91 for E3, 0.07 for E2, 0.02 for E4 and for the control group 0.875 for E3, 0.067 for E2, 0.058 for E4. Copyright 1995 S. Karger AG, Basel