Low Serum Uric Acid Predicts Risk of a Composite Disease Endpoint.

Background and objectives: Mortality may increase in hypouricemia as well as inhyperuricemia. We assessed the predictive value of low serum uric acid (SUA) levels on the risk of overall mortality or a composite endpoint of death and nonfatal events. Materials and Methods: In 1013 community-based middle-aged adults, free of uncontrolled diabetes and coronary heart disease at baseline, the association of sex-specific SUA tertiles with defined outcomes was evaluated prospectively by logistic regression, stratified to gender and presence of type-2 diabetes, using recent criteria. Results: Totally, 43 deaths and additional incident nonfatal events in 157 cases were recorded at a median 3.4 years' follow-up. Multivariable linear regression disclosed SUA to be significantly associated among non-diabetic individuals positively with creatinine, triglycerides, and body mass index in women further with fasted glucose. In multivariable-adjusted logistic regression analysis, sex-specifically dichotomized baseline uric acid (<5.1 and <4.1 mg/dL vs. higher values) significantly predicted the non-fatal events in the whole sample (relative risk (RR) 1.51 [95% confidence interval (CI) 1.02; 2.26]), as well as in men, while composite endpoint in the whole sample tended to rise (RR 1.38). Compared with the intermediate one, the top and bottom SUA tertiles combined tended to confer mortality risk (RR 2.40 [95% CI 0.89; 6.51]). Adverse outcomes in diabetic women were predicted by tertiles 2 and 3. Conclusions: Inverse association of SUA with adverse outcomes, especially in men, is consistent with the involvement of uric acid mass in autoimmune activation. The positive association of uric acid with adverse outcomes in diabetic women is likely mediated by concomitant high-density lipoprotein dysfunction.

Optimal anthropometric measures to predict incidence of coronary heart disease in adults in Turkey.

Background: We aimed to identify the most suited anthropometric measure for the prediction of risk for incident coronary heart disease (CHD) among the Turkish population. Methods: We collected data on body mass index, waist circumference (WC), hip circumference, waist-to-hip ratio (WHR), waist-to-height ratio (WHtR) and a body shape index. We analysed these using both C-statistics and Cox regression models adjusted for age, systolic blood pressure, glucose and high-density lipoprotein (HDL)-cholesterol for assessing risk of incident CHD among 3203 Turkish Adult Risk Factor (TARF) study participants (mean [SD] age 48.5 [11] years). Results: Over a mean follow-up of 9.93 years, new CHD developed in 573 individuals. Multi-adjusted C-statistics were highest for WHtR followed by WC, in both sexes. Except WHR, all measures were significantly associated with incident CHD in combined sexes in the full model. There was a sex difference, however, in the mediation of the three risk factors for adiposity; these attenuated hazard ratios (HRs) in males, whereas in females, significant prediction of incident CHD persisted for each measure. WC (HR 1.36 [95% CI 1.13; 1.64]), followed by WHtR (HR 1.24 [95% CI 1.10; 1.40]), were in combined sex, as in females, the most informative surrogates of adiposity. Hip circumference did not protect, but rather conferred modest CHD risk, especially in females, rendering a low utility of predictive value for WHR. The CHD risk curve did not have a J shape. Conclusions: WC is the most suitable of five adiposity surrogates for CHD risk among Turkish adults, while in males, unmediated adiposity risk was similarly identified by WHtR. Retention of the large part of CHD risk in females perhaps reflects the underlying autoimmune activation.

Use of Repeated Blood Pressure and Cholesterol Measurements to Improve Cardiovascular Disease Risk Prediction: An Individual-Participant-Data Meta-Analysis.

The added value of incorporating information from repeated blood pressure and cholesterol measurements to predict cardiovascular disease (CVD) risk has not been rigorously assessed. We used data on 191,445 adults from the Emerging Risk Factors Collaboration (38 cohorts from 17 countries with data encompassing 1962-2014) with more than 1 million measurements of systolic blood pressure, total cholesterol, and high-density lipoprotein cholesterol. Over a median 12 years of follow-up, 21,170 CVD events occurred. Risk prediction models using cumulative mean values of repeated measurements and summary measures from longitudinal modeling of the repeated measurements were compared with models using measurements from a single time point. Risk discrimination (C-index) and net reclassification were calculated, and changes in C-indices were meta-analyzed across studies. Compared with the single-time-point model, the cumulative means and longitudinal models increased the C-index by 0.0040 (95% confidence interval (CI): 0.0023, 0.0057) and 0.0023 (95% CI: 0.0005, 0.0042), respectively. Reclassification was also improved in both models; compared with the single-time-point model, overall net reclassification improvements were 0.0369 (95% CI: 0.0303, 0.0436) for the cumulative-means model and 0.0177 (95% CI: 0.0110, 0.0243) for the longitudinal model. In conclusion, incorporating repeated measurements of blood pressure and cholesterol into CVD risk prediction models slightly improves risk prediction.

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.

Risk of obesity and metabolic syndrome associated with FTO gene variants discloses clinically relevant gender difference among Turks.

Gene variations in the fat mass- and obesity-associated gene (FTO) have shown controversial associations with obesity and metabolic syndrome (MetS) in several populations. We explored the association of FTO gene with obesity, MetS, and insulin-related parameters separately in men and women. Two SNPs in the FTO, gene rs9939609 and rs1421085, were genotyped by the Taqman System in 1967 adults (mean age of the whole group 50.1 ± 12.0; 48.4 % male). A random sample of the Turkish Adult Risk Factor cohort was cross-sectionally analyzed. Both SNPs exhibited strong linkage disequilibrium (r(2) = 0.85) and minor alleles were associated with risk of obesity in women and of MetS in men. Carriers of the rs1421085 C-allele exhibited higher body mass index (BMI) in each gender. Adjusted fasting insulin and HOMA index were significantly higher in C-allele carriers in men alone. Logistic regression analysis demonstrated significantly increased likelihood for obesity in female C-risk allele carriers (OR 1.61; 95 % CI 1.19-2.18), after adjustment for age, smoking status, alcohol usage, physical activity grade and presence of diabetes mellitus. Male C-allele carriers were at increased risk for MetS (OR 1.44; 95 % CI 1.07-1.95), adjusted for age, smoking status, alcohol consumption, and physical activity. Further adjustment for BMI attenuated the MetS risk, indicating interaction between C-allele, gender and BMI. The FTO gene in Turkish adults contributes independently to obesity in women and-by interacting with BMI-to MetS and insulin resistance in men.

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.

Association of Cardiometabolic Multimorbidity With Mortality.

IMPORTANCE: The prevalence of cardiometabolic multimorbidity is increasing. OBJECTIVE: To estimate reductions in life expectancy associated with cardiometabolic multimorbidity. DESIGN, SETTING, AND PARTICIPANTS: Age- and sex-adjusted mortality rates and hazard ratios (HRs) were calculated using individual participant data from the Emerging Risk Factors Collaboration (689,300 participants; 91 cohorts; years of baseline surveys: 1960-2007; latest mortality follow-up: April 2013; 128,843 deaths). The HRs from the Emerging Risk Factors Collaboration were compared with those from the UK Biobank (499,808 participants; years of baseline surveys: 2006-2010; latest mortality follow-up: November 2013; 7995 deaths). Cumulative survival was estimated by applying calculated age-specific HRs for mortality to contemporary US age-specific death rates. EXPOSURES: A history of 2 or more of the following: diabetes mellitus, stroke, myocardial infarction (MI). MAIN OUTCOMES AND MEASURES: All-cause mortality and estimated reductions in life expectancy. RESULTS: In participants in the Emerging Risk Factors Collaboration without a history of diabetes, stroke, or MI at baseline (reference group), the all-cause mortality rate adjusted to the age of 60 years was 6.8 per 1000 person-years. Mortality rates per 1000 person-years were 15.6 in participants with a history of diabetes, 16.1 in those with stroke, 16.8 in those with MI, 32.0 in those with both diabetes and MI, 32.5 in those with both diabetes and stroke, 32.8 in those with both stroke and MI, and 59.5 in those with diabetes, stroke, and MI. Compared with the reference group, the HRs for all-cause mortality were 1.9 (95% CI, 1.8-2.0) in participants with a history of diabetes, 2.1 (95% CI, 2.0-2.2) in those with stroke, 2.0 (95% CI, 1.9-2.2) in those with MI, 3.7 (95% CI, 3.3-4.1) in those with both diabetes and MI, 3.8 (95% CI, 3.5-4.2) in those with both diabetes and stroke, 3.5 (95% CI, 3.1-4.0) in those with both stroke and MI, and 6.9 (95% CI, 5.7-8.3) in those with diabetes, stroke, and MI. The HRs from the Emerging Risk Factors Collaboration were similar to those from the more recently recruited UK Biobank. The HRs were little changed after further adjustment for markers of established intermediate pathways (eg, levels of lipids and blood pressure) and lifestyle factors (eg, smoking, diet). At the age of 60 years, a history of any 2 of these conditions was associated with 12 years of reduced life expectancy and a history of all 3 of these conditions was associated with 15 years of reduced life expectancy. CONCLUSIONS AND RELEVANCE: Mortality associated with a history of diabetes, stroke, or MI was similar for each condition. Because any combination of these conditions was associated with multiplicative mortality risk, life expectancy was substantially lower in people with multimorbidity.

[Turkish Adult Risk Factor survey 2014: Overall mortality and coronary disease incidence in Turkey's geographic regions]. / TEKHARF 2014 taramasi ve Türkiye'de cografi bölgelere göre ölüm orani ile koroner hastalik insidansi.

OBJECTIVE: This study aimed to examine the overall and coronary mortality in the 2014 Turkish Adult Risk Factor Study survey, and the distribution of cumulative mortality and incident coronary heart disease (CHD) across 7 geographic regions. METHODS: Information on mode of death was appropriately obtained. Information collected from survivors was based on history, examination of the cardiovascular system and the Minnesota coding of electrocardiograms. Cox regression analyses were performed. RESULTS: Of the 1.323 participants to be surveyed, 87 were lost to follow-up, 753 examined, and 35 ascertained as deceased. In 448 subjects, verbal information alone was obtained regarding health status. Nineteen deaths were of coronary and cerebrovascular origin. Cumulative 24-year assessment of the entire cohort in the age bracket 45-74 years disclosed high coronary mortality, at 7.3 per 1000 person-years in men and 3.8 in women, and recorded a limited decline of 18% since the year 2000. Age-adjusted Cox regression analysis, comprising 614 deaths and 482 incident CHD over a follow-up of 9.6 years, revealed higher mortality rates in the Mediterranean region and in men in the Black Sea and Marmara regions. The age-adjusted CHD incidence was significantly higher in males of the Mediterranean and females of the Southeast regions. An estimated 400-420.000 incident CHD cases develop currently each year in Turkey. CONCLUSION: The generally high age-adjusted overall mortality in Turkey displays significant differences across geographic regions. Age-adjusted CHD incidence is not regressing sufficiently, and is especially high among men of the Mediterranean and women of the Southeast regions.

Obesity attenuates gender differences in cardiovascular mortality.

BACKGROUND: To estimate cardiovascular disease (CVD) mortality in relation to obesity and gender. METHODS: Data from 11 prospective cohorts from four European countries including 23 629 men and 21 965 women, aged 24 to 99 years, with a median follow-up of 7.9 years were analyzed. Hazards ratios (HR) for CVD mortality in relation to baseline body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR) and waist-to-height ratio (WHtR) were estimated using Cox proportional hazards models with age as the timescale. RESULTS: Men had higher CVD mortality than women in all four BMI categories (<25.0, 25.0-29.9, 30.0-34.9 and ≥35.0 kg/m(2)). Compared with the lowest BMI category in women, multivariable adjusted HRs (95% confidence intervals) for higher BMI categories are 1.0 (0.8-1.4), 1.6 (1.1-2.1) and 2.8 (2.0-3.8) in women and 2.8 (2.2-3.6), 3.1 (2.5-3.9), 3.8 (2.9-4.9) and 5.4 (3.8-7.7) in men, respectively. Similar findings were observed for abdominal obesity defined by WC, WHR or WHtR. The gender difference was slightly smaller in obese than in non-obese individuals; but the interaction was statistically significant only between gender and WC (p = 0.02), and WHtR (p = 0.01). None of the interaction terms was significant among non-diabetic individuals. CONCLUSIONS: Men had higher CVD mortality than women across categories of anthropometric measures of obesity. The gender difference was attenuated in obese individuals, which warrants further investigation.

Renal "hyperfiltrators" are at elevated risk of death and chronic diseases.

BACKGROUND: The definition of glomerular hyperfiltration has not been agreed upon and the pathophysiological mechanisms have not been well explored. Low serum creatinine concentrations may be associated with increased risk of coronary heart disease (CHD) or cardiopulmonary events the impact of which needs further study. METHODS: Consecutive applicants to a cardiovascular hospital free of moderate/severe chronic kidney disease (age 55.6 ± 8.2 years) were grouped into those without ("healthy", n = 469) and with CHD (320 stable and acute coronary syndrome cases) at baseline and into sex-specific quartiles of CKD-EPI equation-estimated glomerular filtration rate (eGFR). New or recurrent cardiovascular (myocardial infarction, stroke, heart failure [HF]) events, obstructive pulmonary disease (COPD) and death were determined during 3-years' follow-up. RESULTS: Among 25 deaths and 75 cardiopulmonary events, HF was the leading nonfatal event. Age, serum uric acid and left ventricular ejection fraction proved the best independent inverse covariates of eGFR in the "healthy" sample. The highest eGFR quartile ("hyperfiltrators"), exhibiting significantly lower serum LDL-cholesterol levels, significantly predicted the combined outcome (at a RR of 6) in "healthy" subjects, after adjustment for sex, age, body mass index, smoking status and presence of hypertension. This finding was paralleled by the highest eGFR quartile calculated also by the MDRD equation, replicating this also in the CHD group. CONCLUSION: Renal "hyperfiltrators" represent individuals with autoimmune activation (involving serum creatinine, partly escaping assay), are misclassified into optimal renal function and actually are at significantly higher risk of death, HF or cardiopulmonary events. Low serum creatinine levels may represent a clue to the existence of autoimmune activation.

Glycated hemoglobin measurement and prediction of cardiovascular disease.

IMPORTANCE: The value of measuring levels of glycated hemoglobin (HbA1c) for the prediction of first cardiovascular events is uncertain. OBJECTIVE: To determine whether adding information on HbA1c values to conventional cardiovascular risk factors is associated with improvement in prediction of cardiovascular disease (CVD) risk. DESIGN, SETTING, AND PARTICIPANTS: Analysis of individual-participant data available from 73 prospective studies involving 294,998 participants without a known history of diabetes mellitus or CVD at the baseline assessment. MAIN OUTCOMES AND MEASURES: Measures of risk discrimination for CVD outcomes (eg, C-index) and reclassification (eg, net reclassification improvement) of participants across predicted 10-year risk categories of low (<5%), intermediate (5% to <7.5%), and high (≥ 7.5%) risk. RESULTS: During a median follow-up of 9.9 (interquartile range, 7.6-13.2) years, 20,840 incident fatal and nonfatal CVD outcomes (13,237 coronary heart disease and 7603 stroke outcomes) were recorded. In analyses adjusted for several conventional cardiovascular risk factors, there was an approximately J-shaped association between HbA1c values and CVD risk. The association between HbA1c values and CVD risk changed only slightly after adjustment for total cholesterol and triglyceride concentrations or estimated glomerular filtration rate, but this association attenuated somewhat after adjustment for concentrations of high-density lipoprotein cholesterol and C-reactive protein. The C-index for a CVD risk prediction model containing conventional cardiovascular risk factors alone was 0.7434 (95% CI, 0.7350 to 0.7517). The addition of information on HbA1c was associated with a C-index change of 0.0018 (0.0003 to 0.0033) and a net reclassification improvement of 0.42 (-0.63 to 1.48) for the categories of predicted 10-year CVD risk. The improvement provided by HbA1c assessment in prediction of CVD risk was equal to or better than estimated improvements for measurement of fasting, random, or postload plasma glucose levels. CONCLUSIONS AND RELEVANCE: In a study of individuals without known CVD or diabetes, additional assessment of HbA1c values in the context of CVD risk assessment provided little incremental benefit for prediction of CVD risk.

[Cardiovascular publications in 2013 in Turkey advanced in quantity alone]. / Kardiyovasküler tip yayinlarinda 2013 yilinda yalniz nicelikte artis

Turkey's institutions in cardiovascular medicine were evaluated regarding publication output in 2013 based on data available in the Web of Science. Only articles in full-text and reviews appearing in source publications covered by the Science Citation Index proper were included. A fractional count system was used for items published jointly with a foreign or a non-cardiological Turkish institution. Turkey's publications increased numerically to 268, and its global share from 4.3 to 6.0 per mille, yet only to the level of 2001. Articles originating from adult cardiology numbered 188 (70%), while cardiovascular surgery and pediatric cardiology contributed 15% each. Three hospitals affiliated with the Ministry of Health (Kartal Kosuyolu, M. Akif Ersoy and Türkiye Yüksek Ihtisas Hastanesi) and the cardiology departments of the medical faculties of Baskent, Hacettepe and Ege Universities ranked highest, each generating 7-15 papers. The median impact factor remained similar to the preceding year, at 1.52 (interquartile range 1.20-2.31). The undertaking of promotional and supportive measures by the central authorities regarding the conspicuous decline in Turkey's medical research output is long overdue.

Negative results in screening for possible new sequence variations on ATP-binding cassette transporter A1 gene in Turkish adults with metabolic syndrome.

OBJECTIVES: ATP binding cassette transporter A1 (ABCA1) plays a pivotal role in the reverse cholesterol transport. Some mutations in the ABCA1 gene have correlation with changes in serum high-density lipoprotein-cholesterol (HDL-C) and other lipids concentrations. The role of genetic factors in susceptibility to metabolic syndrome (MetS) is not clear. The aim of this study was to explore the relationship between ABCA1 gene and the MetS. STUDY DESIGN: Therefore, to investigate probable new mutations in the functional regions of the ABCA1 gene, 14th, 19th and 49th exons were analyzed using single strand conformational polymorphism method in 220 subjects, 110 of whom had MetS, selected from the Turkish Adults Risk Factor study. RESULTS: No significant relationship was found between the functional region of ABCA1 and MetS. The risk for low HDL-C-high triglyceride levels and MetS are not associated with selected functional regions of the gene, 14th, 19th and 49th exons, which code for the first extracellular loop, the nucleotide binding domain and the C-terminal region, respectively. CONCLUSION: These data indicate that the mutations and polymorphisms in ABCA1 gene are not associated with MetS in Turks.

[Turkish Adult Risk Factor survey 2013: rapid rise in the prevalence of diabetes]. / TEKHARF 2013 taramasi ve diyabet prevalansinda hizli artis

OBJECTIVES: To analyze (1) the sex-specific and age-bracket defined all-cause and coronary mortality in the 23-years' follow-up of the Turkish Adult Risk Factor Study, and (2) to determine the nation-wide prevalence of Type-2 diabetes and its recent trend. STUDY DESIGN: Information on the mode of death was obtained from first-degree relatives and/or health personnel of local heath office. Information collected in survivors was based on history, physical examination of the cardiovascular system and Minnesota coding of resting electrocardiograms. Diabetes was defined by criteria of the American Diabetes Association without the use of glycated hemoglobin. RESULTS: Of the 1370 participants to be surveyed, 768 were examined, in 452 subjects information was gathered, and 29 men, 18 women were ascertained to have died. Cumulative assessment of the entire cohort in the age bracket 45-74 years disclosed coronary mortality to be 7.5/1000 person-years in men and 3.74 in women, persisting to be high among the European countries. The recent decline observed in overall mortality seemed to halt as well. Of greatest concern was the finding in the past 12 years that the rate of rise in the age-controlled prevalence of Type-2 diabetes was as high as 5% annually. CONCLUSION: Overall and coronary mortality in Turkish adults continue to be high, while an elicited annual increase of 5% in the age-controlled prevalence of diabetes is virtually alarming and requires new public health policies.

Interleukin-6 receptor pathways in coronary heart disease: a collaborative meta-analysis of 82 studies.

BACKGROUND: Persistent inflammation has been proposed to contribute to various stages in the pathogenesis of cardiovascular disease. Interleukin-6 receptor (IL6R) signalling propagates downstream inflammation cascades. To assess whether this pathway is causally relevant to coronary heart disease, we studied a functional genetic variant known to affect IL6R signalling. METHODS: In a collaborative meta-analysis, we studied Asp358Ala (rs2228145) in IL6R in relation to a panel of conventional risk factors and inflammation biomarkers in 125,222 participants. We also compared the frequency of Asp358Ala in 51,441 patients with coronary heart disease and in 136,226 controls. To gain insight into possible mechanisms, we assessed Asp358Ala in relation to localised gene expression and to postlipopolysaccharide stimulation of interleukin 6. FINDINGS: The minor allele frequency of Asp358Ala was 39%. Asp358Ala was not associated with lipid concentrations, blood pressure, adiposity, dysglycaemia, or smoking (p value for association per minor allele ≥0·04 for each). By contrast, for every copy of 358Ala inherited, mean concentration of IL6R increased by 34·3% (95% CI 30·4-38·2) and of interleukin 6 by 14·6% (10·7-18·4), and mean concentration of C-reactive protein was reduced by 7·5% (5·9-9·1) and of fibrinogen by 1·0% (0·7-1·3). For every copy of 358Ala inherited, risk of coronary heart disease was reduced by 3·4% (1·8-5·0). Asp358Ala was not related to IL6R mRNA levels or interleukin-6 production in monocytes. INTERPRETATION: Large-scale human genetic and biomarker data are consistent with a causal association between IL6R-related pathways and coronary heart disease. FUNDING: British Heart Foundation; UK Medical Research Council; UK National Institute of Health Research, Cambridge Biomedical Research Centre; BUPA Foundation.

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).

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.

Turkey's contribution to medicine: Main institutions, fields and publications.

OBJECTIVE: To identify and disclose publications from Turkey with the greatest "genuine" contributons to medicine in the past 50 years. MATERIAL AND METHODS: Based on the data of Web of Science, publications originating from Turkey's institutions that were received by May, 2013, ≥72 citations were identified, after excluding papers having more than a minor share by international authors. RESULTS: Primary authors numbering 223 generated 271 medical papers, each receiving ≥72 (95% CI 72; 263) citations. The articles cited herein were of a level of top global 8-10% papers. Half of the articles were published in 1997-2004. Compared with about 25-28 papers annually 10 years previously, it is estimated that currently only 20 papers are generated in Turkey annually, representing a global share of only 1.5 per thousand. The rate of rise registered in the period 1995-2004 may be anticipated to attenuate. Internal medicine, led by rheumatology, cardiology and hematology, and neurosciences were represented at 1.8-fold odds higher than the overall average. Led by Behçet's disease, health issues encountered more widely than in other populations, formed frequent topics of contribution. Led by the Medical Faculties of Istanbul, Hacettepe, Ankara Universities and the Military Medical Academy, only 33 medical faculties and 14 public and private hospitals constituted sources. CONCLUSION: Since the elicited results are unsatisfactory, compared with Turkey's potential, much more concerted efforts should be directed to rebuild a milieu favorable to promote research likely to contribute to medicine.

[Turkish Adult Risk Factor Study survey 2012: overall and coronary mortality and trends in the prevalence of metabolic syndrome]. / TEKHARF 2012: Genel ve koroner mortalite ile metabolik sendrom prevalansi egilimleri.

OBJECTIVES: We aimed to analyze 1) overall and coronary mortality findings in the Turkish Adult Risk Factor (TARF) study survey 2012 and 2) the temporal trends in prevalence of metabolic syndrome (MetS) and its distribution across seven geographic regions. STUDY DESIGN: Information on the mode of death was obtained from first-degree relatives and/or health personnel of a local health office. Information collected in survivors was based on history, physical examination of the cardiovascular system and Minnesota coding of resting electrocardiograms. RESULTS: Of 1527 participants to be surveyed, 796 were examined; information was obtained on the health status in 502 subjects, and death was ascertained in 56 participants. Thirty deaths were attributed to coronary and cerebrovascular disease. Cumulative 22-year evaluation of participants in the age bracket 45-74 years revealed coronary mortality to be high, with 7.6 per 1000 person-years in men and 3.8 in women. Data used from 1754 identical subjects (median age 46 years initially), and examined in two periods 12 years apart, indicated an increase in the prevalence of MetS by 1.3% per aging of 1 year. Analysis across geographic regions showed a rise in the prevalence in the Mediterranean region, already having highest prevalence along with Southeast Anatolia, while the prevalence declined in the Marmara region and persisted to be lowest in the Aegean region. CONCLUSION: The prevalence of MetS in Turkish adults aged 40 years or over, currently standing at 53%, shows significant differences across geographic regions, being highest in the two southern regions and lowest in the Aegean region.

Development of coronary heart disease and ischemic stroke in relation to fasting and 2-hour plasma glucose levels in the normal range.

BACKGROUND: Individuals who had normoglycemia but whose 2-hour plasma glucose (2hPG) concentrations did not return to the fasting plasma glucose (FPG) levels during an oral glucose tolerance test (OGTT) have been shown to have increased cardiovascular mortality. This is further investigated regarding to the first events of coronary heart disease (CHD) and ischemic stroke (IS). METHOD: Data from 9 Finnish and Swedish cohorts comprising 3743 men and 3916 women aged 25 to 90 years who had FPG < 6.1 mmol/l and 2hPG < 7.8 mmol/l and free of CVD at enrollment were analyzed. Hazard ratios (HRs) for first CHD and IS events were estimated for the individuals with 2hPG > FPG (Group II) compared with those having 2hPG ≤ FPG (Group I). RESULTS: A total of 466 (115) CHD and 235 (106) IS events occurred in men (women) during a median follow-up of 16.4 years. Individuals in Group II were older and had greater body mass index, blood pressure, 2hPG and fasting insulin than those in Group I in both sexes. Multivariate adjusted HRs (95% confidence intervals) for incidence of CHD, IS, and composite CVD events (CHD + IS) in men were 1.13 (0.93-1.37), 1.40 (1.06-1.85) and 1.20 (1.01-1.42) in the Group II as compared with those in the Group I. The corresponding HRs in women were 1.33 (0.83-2.13), 0.94 (0.59-1.51) and 1.11 (0.79-1.54), respectively. CONCLUSION: Within normoglycemic range individuals whose 2hPG did not return to their FPG levels during an OGTT had increased risk of CHD and IS.