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.

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.

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.

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.

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.

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.

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.

Lipoprotein(a) level and MIF gene variant predict incident metabolic syndrome and mortality.

Owing to the scarcity of available information, we aimed to assess the association of migration inhibitory factor (MIF)-173 G/C genotypes and serum lipoprotein(Lp)(a) with incident metabolic syndrome (MetS) and all-cause mortality, respectively. In population based, middle-aged adults (n=1297), stratified by gender and presence of MetS, we used Lp(a) quintiles to identify non-linear associations with outcomes using Cox regression models, adjusted for MIF genotype, age, smoking status, high density lipoprotein cholesterol, and systolic blood pressure. After 5.2 years of follow-up, 151 cases of incident MetS and 123 deaths were recorded. For incident MetS, adjusted HRs increased in each gender across four declining quintiles, starting from the highest quintile in men and from quintile 4 in women. The MIF CC-GC genotype appeared to contribute to the risk estimates in men. Similarly adjusted models in the whole sample disclosed that all-cause mortality tended to be inversely associated with Lp(a) quintiles and yielded an HR (2.42 (95% CI 1.03 to 5.81)) in men in quintile 2, whereas the MIF genotype additively predicted mortality (HR 1.79 (95% CI 1.01 to 3.18)) only in men. Excess risk of death was additively conferred on Turkish men by the MIF CC-GC genotype and by apparently reduced circulating Lp(a) assays, supporting the notion that 'low' serum Lp(a), mediating autoimmune activation, is a major determinant of metabolic disease risk and death. Damaged MIF protein and more complex autoimmune activation in women may be responsible from lack of relationship to MetS/mortality.

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.

The Trends in Utilizing Nonvitamin K Antagonist Oral Anticoagulants in Patients With Nonvalvular Atrial Fibrillation: A Real-Life Experience.

Dabigatran and rivaroxaban are novel nonvitamin K antagonist oral anticoagulants (NOACs) approved for thromboprophylaxis in atrial fibrillation (AF). In Turkey, like other countries, the efficacy of translation of the clinical trial results and current guideline recommendations into daily clinical practice is yet to be discovered. Using data from medical records of three tertiary care cardiology centers, we identified patients with nonvalvular AF on dabigatran or rivaroxaban treatment. Baseline characteristics and utilization trends were compared between dabigatran and rivaroxaban groups. Secondarily, clinical events including ischemic stroke and/or transient ischemic attack, systemic embolism, and bleeding were evaluated. Among 294 patients with AF included, dabigatran was utilized in 177 (60.2%) and rivaroxaban in 117 (39.8%). Overall, 76% of patients had received long-term warfarin therapy. The use of 110 mg twice a day (55.4%) was the prevailing strategy in dabigatran group, whereas in rivaroxaban group 20 mg every day (67.5%) was the preferred option. Of the patients, 37.3% had severe valvular disease in which mitral regurgitation was the predominant valve abnormality. Scores of CHADS2, CHA2DS2VASc, and HAS-BLED were similar in both the groups. Of the patients, 24% in dabigatran group and 13.7% in rivaroxaban group were prescribed the lower dose inappropriately. The two NOACs did not differ significantly in terms of clinical events. The results of this study indicate that in daily practice, the physicians' behavior in utilizing the NOACs is shaped by the clinical trials and the guideline recommendations. On the other hand, in dose selection, this adherence is not of high quality.

Sex-Specific Predictors of Metabolic Syndrome Independent of Its Components.

To what extent is the metabolic syndrome (MetS) determined beyond its recognized components? In 1702, middle-aged men and women without MetS at baseline, MetS development was identified in 546 participants at a mean of 10.1-year follow-up. Participants subsequently developing MetS had, beyond higher values of MetS traits, significantly higher total and low-density lipoprotein cholesterol, apolipoprotein B, C-reactive protein (CRP), γ-glutamyl transferase (GGT), and lower high-density lipoprotein cholesterol. Females were significantly more frequent never smokers and males had lower values of total testosterone. In logistic regression analyses, adjusted for sex, age, and smoking status, MetS was predicted disparately in the sexes, whereas males exhibited, beyond abdominal obesity, CRP, GGT, and sex hormone-binding globulin (SHBG) as independent predictors, abdominal obesity was not an independent predictor in females in whom other than age, CRP conferred MetS risk, whereas SHBG was and current smoking tended to be protective. A surrogate of hepatic steatosis proved a major mediator of abdominal obesity in determining incident MetS (relative risk, 5.6 [95% confidence interval, 3.4-9.3]) in each sex. We confirm that GGT and SHBG are novel independent MetS determinants. Hepatic steatosis is the major predictor of MetS mediating adiposity in each sex. Abdominal obesity is not an independent determinant in Turkish women in whom autoimmune activation seems to prevail before MetS development.

Rheumatoid factor mediates excess serum lipoprotein(a) for independent association with type 2 diabetes in men.

OBJECTIVE: The potential association of rheumatoid factor (RF) and lipoprotein (Lp)(a) levels, as well as with the likelihood of type 2 diabetes and hypertension, needs exploring. METHODS: Cross-sectional associations were sought in this unselected and population-based 1539-adult cohort (age 58.8±10.6 years). RF was assayed nephelometrically. Multiple logistic regression analyses were used for covariates of RF positivity and for the latter's association with diabetes and hypertension. RESULTS: RF-positive individuals were older, fewer current smokers, had significantly lower fasting triglycerides (by 13%), higher fibrinogen, and tended to higher sex hormone-binding globulin (SHBG) levels. Whereas, women had a similar risk profile irrespective of RF status, RF-positive men had significantly higher Lp(a). In contrast to Lp(a) being positively correlated with SHBG in RF-negative subjects (r=0.08; p=0.007), an inverse correlation existed in seropositive individuals (r=-0.32, p=0.011), suggesting the interplay of an immune complex. In regression analyses, RF positivity was associated with Lp(a) in men but not in women, [OR 1.53 (1.19; 1.96)], independent of age, SHBG, and C-reactive protein (CRP). RF positivity was further associated with diabetes [OR 1.98 (95% CI 1.11; 3.52)] in the whole sample, additively to waist circumference and CRP, major determinants of diabetes. RF-positive subjects were not significantly associated independently with hypertension. CONCLUSION: Autoimmune activation linked to Lp(a) is mediated by the autoantibody RF in contributing to the development of type 2 diabetes.

Fatty liver disease: Disparate predictive ability for cardiometabolic risk and all-cause mortality.

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

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.

Evaluation of association between common genetic variants on chromosome 9p21 and coronary artery disease in Turkish population.

OBJECTIVE: Coronary artery disease (CAD), which develops from complex interactions between genetic and enviromental factors, is a leading cause of death worldwide. Based on genome-wide association studies (GWAS), the chromosomal region 9p21 has been identified as the most relevant locus presenting a strong association with CAD in different populations. The aim of the present study was to investigate the association of two SNPs on chromosome 9p21 on susceptibility to CAD and the effect of these SNPs along with cardiovascular risk factors on the severity of CAD in the Turkish population. METHODS: This study had an observational case-control design. We genotyped 460 subjects, aged 30-65 years, to investigate the association of 2 SNPs (rs1333049, rs2383207) on chromosome 9p21 and CAD risk in Turkish population. Real-time polymerase chain reaction (RT-PCR) was used to analyze the 2 SNPs in CAD patients and healthy controls. The genotype and allelic variations of these SNPs with the severity of CAD was also assessed using semi-quantitative methods such as the Gensini score. Student's t test and multiple regression analysis were used for statistical analysis. RESULTS: The SNPs rs1333049 and rs2383207 were found to be associated with CAD with an adjusted OR of 1.81 (95% Cl 1.05-3.12) and 2.12 (95% CI 1.19-4.10) respectively. After adjustment of CAD risk factors such as smoking, family history of CAD and diabetes, the homozygous AA genotype for rs2383207 increased the CAD risk with an OR 3.69. Also a very strong association was found between rs1333049 and rs2383207 and Gensini scores representing the severity of CAD (p<0.001). CONCLUSION: The rs2383207 and rs1333049 SNPs on 9p21 chromosome were significantly associated with the risk and severity of CAD in the Turkish population.