Sex-dependent independent prediction of incident diabetes by depressive symptoms.

OBJECTIVE: To study the predictive value of depressive symptoms (DeprSs) in a general population of Turkey for type 2 diabetes. METHODS: Responses to three questions served to assess the sense of depression. Cox regression analyses were used regarding risk estimates for incident diabetes, after exclusion of prevalent cases of diabetes. Mean follow-up consisted of 5.15 (±1.4) years. RESULTS: Depressive symptoms were present at baseline in 16.2% of the whole study sample, threefold in women than men. Reduced physical activity grade was the only significant covariate at baseline in men, while younger age and lower blood pressure were significantly different in women compared with those without DeprS. In men, presence of DeprS predicted incident diabetes at a significant 2.58-fold relative risk (95% confidence interval 1.03; 6.44), after adjustment for age, systolic blood pressure, and antidepressant drug usage. When further covariates were added, waist circumference remained the only significant predictor, while DepS was attenuated to a relative risk of 2.12 (95% confidence interval 0.83; 5.40). DeprS was not associated with diabetes in women, whereas antidepressant drug usage only tended to be positively associated. CONCLUSION: Gender difference existed in the relationship between DeprS and incident diabetes. DeprS predicted subsequent development of diabetes in men alone, not in women. Copyright © 2016 John Wiley & Sons, Ltd.

Gender-modulated risk of coronary heart disease, diabetes and coronary mortality among Turks for three major risk factors, and residual adiposity risk.

BACKGROUND: We determined the proportion of the effects of body mass index (BMI) or its categories on cardiometabolic outcomes mediated through systolic blood pressure (SBP), total cholesterol and fasting glucose. METHODS: Cox regression analyses were performed for incident outcomes among Turkish Adult Risk Factor study participants in whom the three mediators had been determined (n = 2158, age 48.5 ± 11 years). Over a mean 10.2-years' follow-up, new coronary heart disease (CHD) developed in 406, diabetes in 284 individuals, and 149 CHD deaths occurred. RESULTS: Hazard ratios (HR) of BMI for incident diabetes were no more than marginally attenuated by the 3 mediators including glucose, irrespective of gender. Compared to "normal-weight", sex- and age-adjusted RRs for incident CHD of overweight and obesity were 1.40 and 2.24 (95 % CI 1.68; 2.99), respectively, in gender combined. Only three-tenths of the excess risk was retained by BMI in men, six-tenths in women. No mediation of glycemia was discerned in males, in contrast to greatest mediation in females. HR of age-adjusted continuous BMI was a significant but modest contributor to CHD mortality in each gender. While the BMI risk of CHD death was abolished by mediation of SBP in men, HR strengthened to over two-fold in women through mediation of fasting glucose. CONCLUSIONS: Mediation of adiposity by 3 traditional factors exhibited among Turkish adults strong gender dependence regarding its magnitude for CHD risk and the mediation by individual risk factors. Retention of the large part of risk for diabetes in each sex and for CHD in women likely reflects underlying autoimmune activation.

The relationship between aortic stiffness and serum hyaluronidase levels in patients with diabetes mellitus and hypertension.

The aim of this study was to investigate the association of serum hyaluronidase and nitric oxide (NO) levels with arterial stiffness in patients with hypertension (HT) and diabetes mellitus (DM). A total of 101 patients with diagnosis of DM and HT were enrolled in this study. The patients were divided into three groups as follows: only hypertensive (I), only diabetic (II) and both diabetic and hypertensive (III). Serum hyaluronidase levels were negatively correlated with aortic strain (AS) and aortic distensibility (AOD) in all groups, whereas a significant positive correlation was noted between serum hyaluronidase levels and aortic strain index (ASI) (all p-values < 0.05). There was a significant negative correlation between serum hyaluronidase and NO levels in all patients (p < 0.001). When the correlation between serum hyaluronidase and serum NO levels was investigated in the individual patient groups, a negative correlation was found in groups I, II and III (p = 0.017, p < 0.001 and p < 0.001, respectively). A significant relationship between plasma hyaluronidase level and parameters of aortic stiffness was found in patients with HT and/or DM. We suggest that the pathophysiological mechanisms responsible for the development of arterial stiffness in subjects with impaired endothelial function may involve pathological changes in the HA metabolism.

Abdominal obesity with hypertriglyceridaemia, lipoprotein(a) and apolipoprotein A-I determine marked cardiometabolic risk.

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).

Chromosome 9p21 rs10757278 polymorphism is associated with the risk of metabolic syndrome.

Metabolic syndrome (MetS) is a common multifactorial disorder that involves abdominal obesity, dyslipidemia, hypertension, and hyperglycemia. Genome-wide association studies have identified a major risk locus for coronary artery disease and myocardial infarction on chromosome 9p21. Here, we examined the frequency of single nucleotide polymorphisms (SNPs) on chromosome 9p21 in a sample of Turkish patients with MetS and further investigated the correlation between regional SNPs, haplotypes, and MetS. The real-time polymerase chain reaction (RT-PCR) was used to analyze 4 SNPs (rs10757274 A/G, rs2383207 A/G, rs10757278 A/G, rs1333049 C/G) in 291 MetS patients and 247 controls. Analysis of 4 SNPs revealed a significant difference in the genotype distribution for rs2383207, rs10757278, and rs1333049 between MetS patients and controls (p = 0.041, p = 0.005, p = 0.023, respectively) but not for rs10757274 (p = 0.211). MetS and control allelic frequencies for rs2383207, rs10757278, and rs1333049 were statistically different (p < 0.05). The rs2383207 AG variant, was identified as a MetS risk factor (p = 0.012, OR = 33.271; 95 % CI: 2.193-504.805) and the AA haplotype in block 1 and the GC, AG haplotypes in block 2 were associated with MetS (χ(2) = 3.875, p = 0.049; χ(2) = 9.334, p = 0.0022; χ (2) = 9.134, p = 0.0025, respectively). In this study, we found that chromosome 9p21 SNP rs10757278 and related haplotypes correlate with MetS risk. This is the first report showing an association between a 9p21 variant and MetS and suggests that rs10757278 polymorphism may confer increased risk for disease.

Serum creatinine is associated with coronary disease risk even in the absence of metabolic disorders.

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.

Dysfunction of high-density lipoprotein and its apolipoproteins: new mechanisms underlying cardiometabolic risk in the population at large.

We review the metabolic and residual cardiovascular risk existing in populations with prevailing metabolic syndrome (MetS) or in people prone to impaired glucose tolerance. Evidence is presented that enhanced systemic inflammation, or oxidative stress associated with elevated plasma triglyceride-rich lipoproteins and their remnants, and excess oxidized lipoprotein(a) phospholipids underlie this risk. The adverse risk profile is augmented by loss of the anti-inflammatory, anti-oxidative and atheroprotective properties of high-density lipoprotein and its apolipoproteins (apo). Common clinical manifestations are atherogenic dyslipidemia and hypertriglyceridemia with elevated apoB or hypertriglyceridemic waist phenotype. These manifestations are often accompanied by such inflammatory mediators/markers as elevated serum apoE, C-reactive protein, complement C3, and uric acid levels. Compared with men, peri- and postmenopausal women are more commonly and more strongly affected by multiple inflammation mediators. The long-term effects of cigarette smoking are not adverse in such women, but instead, serve as protection against obesity and other health issues. ApoA-I may become dysfunctional in either gender, even in the absence of MetS and diabetes. The public health implications of this cardiometabolic risk are huge. Much research is needed on this topic to further clarify the impact of apoA-I dysfunction, to elucidate the underlying genetics and mechanisms, and to determine preventive measures and optimal management. Avoiding (abdominal) obesity via lifestyle modifications, including dietary changes, improving physical inactivity, and limiting smoking and alcohol consumption, are mainstay measures in the prevention and management of pro-inflammatory states and HDL dysfunction. Omega-3 fatty acids are a good adjunct to lower plasma triglycerides. When further treatment is needed, extended-release niacin or fibrates, with or without statins, are the best options.

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.

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.

[Incidence, prevalence, and mortality estimates for chronic atrial fibrillation in Turkish adults]. / Türk halkinda kronik atriyal fibrilasyon insidansi, prevalansi ve mortalitesine iliskin tahminler.

OBJECTIVES: We investigated the incidence, prevalence, and mortality of chronic atrial fibrillation (AF) in Turkish adults. STUDY DESIGN: In a prospective and cross-sectional design, we analyzed 3,450 eligible participants (1707 men, 1743 women; mean age 52+/-13 years) of the Turkish Adult Risk Factor Study, who had been surveyed until 2006/07. Those who were dead and were found to have AF at baseline were excluded in the estimation of AF prevalence and incidence, respectively. RESULTS: Atrial fibrillation was determined in 67 participants. The total follow-up was 34,100 person-years (mean 9.9 years). There were 43 prevalent and 46 incident cases, which corresponded to 1.25% and 1.35 per 1000 person-years, respectively. For age brackets of 32-59, 60-69, and > or =70 years, the prevalence rates were 0.46%, 2.09%, and 2.49%, and the incidence rates were 0.31, 1.98, and 3.50 per 1000 person-years, respectively. Both were higher in women of all age groups, with female-to-male ratios for overall prevalence and incidence being 1.69 and 1.19, respectively. Survival after onset of AF was 5 to 9 years and overall mortality was 6.8 per 100 person-years. Hypertension was the most common cause of AF, followed by advanced age. Contrary to expectations, waist circumference of men with AF was smaller by 1.9 cm than that of women. Serum C-reactive protein levels in men with AF (mean 1.21 mg/l) were significantly lower than women with AF (mean 2.62 mg/l) and than males without AF (mean 1.78 mg/l). CONCLUSION: In Turkish adults, the current incidence and prevalence of chronic AF can be extrapolated to be 35,000 per year (22,000 in women) and 310,000 (200,000 in women), respectively. Considering the low incidence in males, it seems that inflammatory processes may play a minor role in the development of AF in Turkish men.

Lower circulating migration inhibitory factor protein is associated with metabolic syndrome and diabetes.

AIM: The controversial relationship between macrophage migration inhibitory factor (MIF) and the likelihood of cardiometabolic diseases was investigated. Results/methodology: Assayed MIF protein from 1225 adults was cross-sectionally analyzed. MIF was independently inversely associated with age, total testosterone and positively with high-density lipoprotein-cholesterol. In men MIF correlation with age, testosterone and waist circumference converted from inverse in the upper to positive in the bottom MIF third. Both metabolic syndrome and diabetes were significantly associated, in combined gender, with the intermediate (vs the highest) MIF tertile at an odds ratio 1.6. Coronary heart disease was not significantly related with MIF in either gender. DISCUSSION/CONCLUSION: Findings are consistent with oxidative damage to MIF protein and its involvement in autoimmune activation, likely more extensive in women.

Lipoprotein(a)-activated immunity, insulin resistance and new-onset diabetes.

OBJECTIVES: Some evidence suggests that serum lipoprotein[Lp](a) may be inversely linked to type-2 diabetes. We aimed to determine in nondiabetic people the relationship of serum [Lp](a) with insulin resistance and new-onset diabetes (NOD). MATERIALS AND METHODS: Population-based middle-aged adults (n = 1685) were categorized by fasting glucose and stratified to gender, having excluded prevalent diabetic subjects. NOD (n = 90) occurred over a median 5 years' follow-up. RESULTS: Subjects that subsequently developed NOD, derived both from the normoglycemia and impaired fasting glucose (IFG) groups,were distinguished, among others, primarily by significantly elevated serum gamma glutamyltransferase, reduced Lp(a) (by 31%) and, compared to IFG, by low total cholesterol levels. Partial correlation of Lp(a) with homeostatic model assessment (HOMA) was inverse in normoglycemic men; such correlation, neutral in normoglycemic women, proved inverse in IFG (r = -0.17). Circulating Lp(a) in individuals with paired measures increased significantly (1.55-fold) in the period from baseline up to NOD. Multivariable-adjusted logistic regression analysis for NOD in combined sexes indicated independent and additive prediction by serum Lp(a), albeit inverse in direction (RR 0.84, [95%CI 0.72; 0.97]). CONCLUSION: Lp(a) is significantly reduced in the period preceding NOD and is inversely associated with HOMA index, observations consistent with underlying autoimmune activation.

Determinants of obstructive sleep apnea syndrome: Pro-inflammatory state and dysfunction of high-density lipoprotein.

OBJECTIVE: The goal of this study was to determine variables preceding and predicting incident obstructive sleep apnea syndrome (OSAS) in the population at large. METHODS: Anthropometric, lipid, and non-lipid variables in participants with newly developing OSAS (n = 131) were compared with those of a cohort sample (n = 2615) of the Turkish Adult Risk Factor study. Available values preceding (by a median of 32 mo) the development of OSAS were used in multivariable Cox regression models. RESULTS: Significant determinants of OSAS assessed by group differences were waist/neck circumference and fibrinogen. Fasting triacylglycerols, systolic blood pressure, and C-reactive protein in men and low sex hormone-binding globulin and elevated homeostatic model assessment in women were further significant covariates. Cox regression analysis for the risk of incident OSAS confirmed the independent predictive value of central obesity measures, especially neck circumference (having a twofold hazard ratio) and younger age. Age-adjusted former smoking status and-compared with the lowest tertile-the upper two tertiles of fibrinogen (relative risk = 1.66, 95% confidence interval: 1.05-2.63) were significant predictors. Elevated triacylglycerols in males and high apolipoprotein B and lowest high-density lipoprotein cholesterol tertile in females also predicted subsequent OSAS. Systolic blood pressure and total cholesterol did not prove to be independent predictors in multivariable adjusted Cox models in which partial sex-dependent independence of obesity measures of the previously stated five variables was essentially retained. CONCLUSIONS: An enhanced pro-inflammatory state appeared to be the underlying pathophysiologic mechanism for OSAS, whereas in men, the added factor of high-density lipoprotein dysfunction was suggested. Because it contributes to the pro-inflammatory state, discontinuance of smoking was another further significant predictor of OSAS.

Low acylation stimulating protein levels are associated with cardiometabolic disorders-secondary to autoimmune activation?

OBJECTIVE: We investigated the possible association of serum acylation stimulating protein (ASP) with cardiometabolic disorders and the evidence of autoimmune activation. METHODS: Population-based randomly selected 1024 participants were cross-sectionally and prospectively analyzed. ASP concentrations were measured with a validated ELISA kit. Correlations were sought separately in subjects with no cardiometabolic disorders (n=427) designated as "healthy." RESULTS: ASP was positively correlated with total testosterone and inversely correlated with platelet activating factor (PAF), PAF-acetylhydrolase (AH), in each gender, and positively correlated in "healthy" men with lipoprotein [Lp](a) and apolipoprotein B. Correlations of ASP with PAF values ≥22 nmol/L were abolished, contrasted to a strongly inverse one in subjects with PAF <22 nmol/L. In linear regression analyses in the whole sample, ASP was inversely associated independently with PAF and PAF-AH and, in men, positively with Lp(a) and sex hormone-binding globulin. Prevalent and (at 2.0 years' follow-up) incident metabolic syndrome (MetS, n=393), diabetes (n=154), and coronary heart disease (CHD, n=171) were analyzed by sex-, age-, and Lp(a)-adjusted logistic regression, using tertiles of ASP and PAF. The lower two (<42 nmol/L) ASP tertiles were a risk factor in combined sexes for MetS and diabetes. In women, incident CHD was predicted by either reduced or elevated ASP tertiles. CONCLUSION: Findings can be explained by the notion of operation of immune responses against both ASP and oxidized PAF-like lipids of Lp(a) to yield for "reduced" values and increased likelihood of cardiometabolic disorders.

Algorithm for predicting CHD death risk in Turkish adults: conventional factors contribute only moderately in women.

OBJECTIVE: To assist the management strategy of individuals, we determined an algorithm for predicting the risk of coronary heart disease (CHD) death in Turkish adults with a high prevalence of metabolic syndrome (MetS). METHODS: The risk of CHD death was estimated in 3054 middle-aged adults, followed over 9.08±4.2 years. Cox proportional hazard regression was used to predict risk. Discrimination was assessed using C-statistics. RESULTS: CHD death was identified in 233 subjects. In multivariable analysis, the serum high-density lipoprotein-cholesterol (HDL-C) level was not predictive in men and the non-HDL-C level was not predictive in women. Age, presence of diabetes, systolic blood pressure ≥160 mm Hg, smoking habit, and low physical activity were predictors in both sexes. The exclusion of coronary disease at baseline did not change the risk estimates materially. Using an algorithm of the 7 stated variables, individuals in the highest category of risk score showed a 19- to 50-fold higher spread in the absolute risk of death from CHD than those in the second lowest category. C-index of the model using age alone was as high as 0.774 in men and 0.836 in women (p<0.001 each), while the incorporation of 6 conventional risk factors contributed to a C-index of 0.058 in males and 0.042 in females. CONCLUSION: In a middle-aged population with prevalent MetS, men disclosed anticipated risk parameters (except for high HDL-C levels) as determinants of the risk of CHD death. On the other hand, serum non-HDL-C levels and moderate systolic hypertension were not relevant in women. The moderate contribution of conventional risk factors (beyond age) to the estimation of the risk of CHD death in women is consistent with the operation of autoimmune activation.

Fasting glycemia and glycated hemoglobin categories: Relationship to serum lipoprotein(a) level and disparity in 2 geographic regional groups of Turkey.

OBJECTIVE: The goal of the present study was to determine covariates of serum lipoprotein (Lp) (a) within fasting glucose and glycated hemoglobin (HbA1c) categories, and to detect features that were different among covariates based on residence in Marmara and Central Anatolia (Marm-CA) regions or remaining 5 geographic regions of Turkey. METHODS: Data of randomly-selected group of 1167 men and women (mean age 61 years) who participated in biennial surveys of 2013 and 2015 were cross-sectionally analyzed in 6 categories. RESULTS: In multiple linear regression analysis of nondiabetic women, homeostatic model assessment (HOMA) index score was inversely associated with Lp(a) (ß coefficient 0.49; p=0.001); this was not true for men. In the whole sample, Lp(a) was significantly positively associated with female sex and with serum creatinine, and inversely in each sex with HOMA index (ß coefficient 0.63; p<0.001). Linear models within separate categories showed significant associations of Lp(a) only in individuals with no evidence of diabetes other than HbA1c >6.5%: in women, positive association with total cholesterol and inverse relationship with creatinine were found, and in men, positive association with apolipoprotein (apo) B was determined. Similar age, diastolic blood pressure, fasting glucose, triglyceride, uric acid, and C-reactive protein values were obtained from participants of 2 regional groups. Residents of the Marm-CA region who were nondiabetic exhibited significantly (by 23%) lower serum Lp(a) among individuals with HbA1c ≥5.7%, significantly higher HOMA index score, concentrations of apoB, and low-density lipoprotein cholesterol. CONCLUSION: Hallmark of prediabetic and diabetic glycemia/HbA1c categories seems to be an independent inverse association between Lp(a) protein (yet not of apoB) and HOMA score, this being primarily so in residents of Marm-CA region.

Tenth categories of total and HDL cholesterol fail to independently predict death risk in middle-aged Turkish adults.

OBJECTIVE: The aim of this study was to delineate in detail the longitudinal association of total cholesterol (TC) and highdensity lipoprotein cholesterol (HDL-C) levels with overall mortality in middle-aged participants of the biennial Turkish Adult Risk Factor study. METHODS: Baseline lipid variables were analyzed in sex-specific deciles. A baseline age of 45 to 84 years as an inclusion criterion led to the enrollment of 2121 men and women. Cox regression analyses were performed. RESULTS: Deaths were recorded in 237 and 306 women and men, respectively, during a mean 8.85±4.4 years of follow-up. After adjustment for age, smoking status, lipid-lowering and antihypertensive drug usage, prevalent diabetes, and coronary heart disease, and using the lowest decile as referent, neither TC (p trend=0.94 and 0.96, respectively), nor HDL-C categories (p trend=0.20 and 0.31, respectively) were significantly predictive of mortality in either gender. TC deciles exhibited a gender difference insofar as hazard ratios in females tended to be reciprocal to those in males in deciles 2 through 5. CONCLUSION: The findings on TC deciles may be attributed to a comparatively higher death rate in the female (compared with male) bottom decile, reflecting the autoimmune process-induced elevated risk in the lowest decile. Observations on HDLC confirmed presumed pro-inflammatory conversion in levels >50 mg/dL. These results have important clinical implications.

Advances in understanding gender difference in cardiometabolic disease risk.

Gender differences exist in cardiovascular or metabolic disease risk, beyond the protective effect of estrogens, mostly burdening the postmenopausal female. We aimed to review herein sex differences in pro-inflammatory states, the independence of inflammation from insulin resistance, differences in high-density lipoprotein dysfunction, in gene-environment interactions, and in the influence of current and former smoking on cardiometabolic risk. Sex differences in absorption of long-chain fatty acids are highlighted. Differences exist in the first manifestation of cardiovascular disease, men being more likely to develop coronary heart disease as a first event, compared to women who have cerebrovascular disease or heart failure as a first event. Autoimmune activation resulting from pro-inflammatory states, a fundamental mechanism for numerous chronic diseases in people prone to metabolic syndrome, is much more common in women, and these constitute major determinants. Therapeutic approaches to aspects related to sex difference are briefly reviewed.

Polymorphisms in the long non-coding RNA CDKN2B-AS1 may contribute to higher systolic blood pressure levels in hypertensive patients.

OBJECTIVES: Hypertension (HT) is a complex disorder influenced by both genetic and environmental factors. Recent genome-wide association studies have identified a major risk locus for atherosclerosis on chromosome 9p21.3. SNPs within the coding sequences of CDKN2A/B and the long non-coding RNA CDKN2B-AS1 could potentially contribute to HT development. Thus, this study aimed to investigate whether the frequency of four SNPs on chromosome 9p21.3 affects blood pressure (BP) levels in Turkish HT patients, and to examine correlations between these SNPs, specific SNP haplotypes, and HT. DESIGN AND METHODS: This is a case-control study comparing HT patients and healthy controls. Real-time polymerase chain reaction (RT-PCR) analysis was utilized to detect SNPs rs10757274, rs2383207, rs10757278, and rs1333049 in 170 HT patients and 180 healthy controls. RESULTS: Each SNP was detected at significantly higher frequencies in HT patients than in controls (p values 0.001); however, there was no significant link between rs10757274, rs2383207, rs10757278, and rs1333049 SNPs and HT grades. Furthermore, there was a significant association between elevated systolic BP levels and rs1333049 GG genotype (p=0.047), while weight gain and increased fasting glucose levels were significantly associated with rs2383207 AA genotype (p=0.020 and p=0.009, respectively). Lastly, we detected a correlation between GG, GA, and AG haplotypes in block 1 (rs10757274, rs2383207) and GC and AG haplotypes in block 2 (rs10757278, rs1333049) and HT. CONCLUSIONS: Our findings suggest that SNPs rs10757274, rs2383207, rs10757278, and rs1333049, particularly those within the CDKN2B-AS1 gene, and related haplotypes may confer increased susceptibility to HT development.