Increased Risk of CHD in the Presence of rs7865618 (A allele): Tehran Lipid and Glucose Study.

Introduction: The scavenger receptor class B type I (SR-BI) is a key component in the reverse cholesterol transportation. The aim of this study was to assess the association between exon1 (G → A) polymorphism of SR-BI gene and lipid profiles among the Tehran Lipid and Glucose Study (TLGS) population.Materials and methods: This cross-sectional study included 774 adults (322 males and 452 females) aged 20–70 years who were randomly selected from among TLGS population. Anthropometrical and biochemical variables for participants were measured. Selected SR-BI gene polymorphism was determined with restriction fragment length polymorphism, via Alu restriction enzyme.Results: Minor allele frequency for SR-BI polymorphism in the selected population was 0.159. Allele frequencies were in conformity with Hardy–Weinberg equilibrium. Association between (G → A) SR-BI polymorphism and high density lipoprotein cholesterol (HDL-C) and HDL3 was significant only after adjustment for age as a potential covariate (p = 0.046, 0.041, respectively); however, the results did not improve after adjustment for sex.Discussion: The result of this study confirms the role of age as a potential confounder which could modify the association between the SR-BI single nucleotide polymorphism and HDL-C level.

ContextHypertension (HTN) is a well-known modifiable risk factor for cardiovascular disease (CVD), chronic kidney disease and mortality. Positive effects of blood pressure (BP) lowering for prevention of CVD and death have been documented in several meta-analyses of randomized controlled trials.Evidence AcquisitionThis review focuses on the key findings derived from the Tehran lipid and glucose study (TLGS) papers on different aspects of BP and HTN.ResultsA prevalence of 23% for HTN has been reported in the TLGS population, aged ≥ 20 years. Over a decade long follow-up, the crude incidence rate (95% CI) of new-onset HTN defined as systolic BP (SBP) ≥ 140 mmHg and/or diastolic BP (DBP) ≥ 90 mmHg, and not using antihypertensive medication was 33.63 (32.0 - 35.3) per 1000 person-years. Age, baseline SBP and body mass index were significant risk factors for development of isolated systolic HTN; regarding isolated diastolic HTN, baseline DBP and waist circumference were recognized as important risk factors whereas age, female gender and marriage were shown to be protective factors. SBP decreased significantly in both diabetic and non-diabetic participants; DBP showed a non-significant decrease in diabetic men and a statistically significant decrease in non-diabetic men. Among women, both those with and without diabetes (DM) generally experienced statistically significant decreases in DBP. Cox proportional hazard models showed that neither SBP nor DBP were associated with incident DM in the total population and in either gender, separately. All BP components were associated with CVD and all-cause mortality in the middle-aged population. Contribution of HTN to cerebrovascular events was also documented in the TLGS participants, aged ≥ 50 years.ConclusionsSeveral important findings regarding BP/HTN have been derived from the TLGS. According to data regarding the prevalence and incidence of preHTN and HTN and their contribution to cardiovascular morbidity and mortality in the TLGS population as a representative sample of Tehranian population, it is recommended that interventions be prioritized for lifestyle modifications for the prevention and appropriate management of preHTN/HTN.

To examine the performance of 'the Framingham's general CVD algorithm' in estimating 5-year risk of cardiovascular disease (CVD) and coronary heart disease (CHD) in an adult Middle Eastern community. In a population-based prospective cohort, the Tehran Lipid and Glucose Study (TLGS), CVD risk estimates were calculated for 3838 individuals (2183 women) free of CVD at baseline. Over 8.6 years, there were 119 CVD (106 CHD) events among women, and 164 (137) among men aged ≥ 30 years. Standard risk factors [age, systolic blood pressure (SBP), antihypertensive treatment, total and high-density lipoprotein cholesterol, smoking and diabetes mellitus], measured at baseline, were significantly related to the incidence of CVD. The only exception, lack of significance for coefficients of SBP among women, was attributable to collinearity between age and SBP. For most risk factors, hazard ratios (HRs) for CVD were similar for the TLGS and the Framingham cohorts' participants. Few exceptions were lower HR for SBP among TLGS' women and lower HR for age among TLGS' men. The Framingham equations quite correctly discriminated participants [C statistic: CVD, 0.818 (women) and 0.774 (men); CHD: 0.822 (women) and 0.751 (men)] with good calibration (all calibration χ(2) values < 15, ps > 0.1). The Framingham's CVD algorithm was effective at ranking individuals and could be used to quantify risk and to guide preventive care in Iranian adults. For regions without established cohort, recalibration using risk factors and CVD (CHD) rates may be an effective method to develop CVD (CHD) risk prediction algorithms for local practice.

Metabolic syndrome (MetS) is a multi-factorial disorder with five important components. A high triglyceride level combined with low HDL cholesterol has been reported to be associated with Apolipoprotein A5 (APOA5) gene variations. In this study, we aimed to determine the association of single nucleotide polymorphisms including: rs662799, rs3135506 and rs2075291 in the apolipoprotein A-V (APOA5) gene in relation to MetS component like triglyceride and HDL-C level in Tehran Lipid and Glucose Study (TLGS). Metabolic syndrome was defined according to ATPIII and phenotypes were defined by the National Cholesterol Education Program (NCEP) criteria for MetS. Demographic, biochemical parameters and anthropometric variables were measured. Selected APOA5 gene polymorphisms were genotyped using PCR-RFLP method. From TLGS population, 947 adults, aged 19 - 70 years, were randomly selected and recruited into the study. Mean age, triglyceride and WC were higher and mean HDL was lower in MetS vs. non-MetS group. C allele in rs2075291 showed a significant association with MetS (OR: 2.38, 95% CI; 1.11 - 5.08, P = 1.5 ×10(-2)). The association was shown between higher serum triglyceride and the presence of T allele (P = 4.5 × 10(-4)) and also lower serum HDL-C and the presence of T allele (P = 1.6 × 10(-3)) in rs2075291. Also this association showed between raised waist circumference and C allele in rs3135506 (P = 3.5 × 10(-2) ) and raised systolic and diastolic blood pressure level and C allele of rs662799 (P = 4.5 × 10(-2)). According to the results, there is a relationship between lipid profile and studied polymorphism in the presence of metabolic syndrome. It seems that APOA5 rs2075291 could play an important role in triglyceride and HDL-C level in metabolic syndrome affected, while the association of APOA5 rs662799 polymorphism is still under debate.

ContextDyslipidemia, including elevated serum total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), and triglycerides (TG), and low high density lipoprotein cholesterol (HDL-C) is a major modifiable risk factor for non-communicable diseases (NCDs). This review summarizes many of the key findings on lipid measures in the Tehran lipid and glucose study (TLGS), a large scale community-based study with an approximately two decade follow-up.Evidence AcquisitionA systematic literature search was conducted using PubMed, Scopus, Web of Science databases, and the library of the Research Institute for Endocrine Sciences, using the following keywords: Lipid measures, lipid ratios, lipid profile, dyslipidemia, and “Tehran lipid and glucose study”. Articles were categorized based on fields of prevalence, trends, and impact of lipid profile on incident NCDs and mortality.ResultsBetween 1999 - 2001, the prevalence of high risk lipids ranged from 14% (low HDL-C) to 17% (high LDL-C) among adolescents, although among adults the lowest and highest prevalence were observed for low HDL-C (19%) and high TG (28%). Despite favorable trends for lipid parameters among adolescents, adults, and the elderly population, a considerable number of diabetic individuals, failed to achieve the optimum level of serum lipids. During follow-up, consumption of lipid-lowering drugs increased from 1.5 to 9.0% and 3.7 to 11.4% among adult men and women, respectively. The association between different lipid parameters and related ratios for incident type 2 diabetes (T2D), hypertension, metabolic syndrome and cardiovascular diseases differed between genders. Interestingly, each 1-unit increase in TC/HDL-C increased risk of hypertension among women (odds ratio (OR): 1.19, 95% confidence interval (CI): 1.00 - 1.27) and T2D among men (OR: 1.27, 95% CI: 1.06 - 1.51). Moreover, TC, LDL-C, non-HDL-C, Ln-TG, TC/HDL-C, and Ln-TG/HDL were inversely associated with non-cardiovascular mortality.ConclusionsDespite high prevalence of high risk lipid profiles among the TLGS population at baseline, favorable trends were observed in levels of all lipid components, which might be attributable to increased consumption of lipid-lowering medications and improvement in the general knowledge of Iranians regarding limited consumption of hydrogenated oil. Considering the impact of lipid profiles on incident NCDs, more attention should be paid to at-risk groups for screening and treatment purposes.

BackgroundAlthough current data shows a positive association between obesity and development of coronary heart disease (CHD) in general population, there is limited data on the important protective role of central or general obesity in patients with prevalent CHD or the “obesity paradox”, from this region.ObjectivesThe objective of the present investigation was to describe the relationship between BMI categories and the recurrence of CHD in patients with a history of CHD using data from a large population-based study, the Tehran lipid and glucose study (TLGS).Patients and MethodsThe study was conducted on 440 adults, aged ≥ 30 years, with a history of CHD at baseline who attended the first (1999 - 2001) or second (2001 - 2003) phases of the Tehran Lipid and Glucose Study and had at least one year of follow-up until March 31, 2010. Cox proportional hazard models were used to evaluate the association among various BMI groups and recurrent CHD incidence.ResultsDuring a median follow-up of 8.44 years, 169 new cases of CHD occurred (incidence density of: 54.53 per 1000 person-years). The incidence of recurrent CHD was higher in the normal BMI compared with overweight and obese categories (68.71, 47.56 and 54.46 per 1000 person-years, respectively). In multivariable models, using the forward stepwise selection approach, compared to the overweight group (0.48 95% CI, 0.30-0.80), the obese group (0.55 95% CI, 0.28-1.06) lost its significant protective effect.ConclusionsResults of this study demonstrated an apparently protective effect for overweight in comparison with normal weight against long-term recurrent CHD in patients with history of CHD.

背景与目的肺癌驱动基因检测具有重要意义，目前检测方法多样，临床适用性有差异。本研究旨在比较基于扩增阻碍突变系统-聚合酶链反应(Amplification Refractory Mutation System-polymerase chain reaction, ARMS-PCR)技术的试剂盒与一代测序及ARMS-qPCR检测肺癌突变基因的敏感性和特异性，探究突变位点特异扩增法(Amplification Mutation Specific System, AMSS)-PCR技术在肺癌突变基因检测中的应用价值。方法对前期已行ARMS-PCR检测的肿瘤标本进行一代测序及试剂盒检测，比较各种方法的检测结果，并对检测结果进行统计学分析。结果本研究共收集了309例肺癌标本。试剂盒与一代测序符合率97.41%，ARMS-PCR的符合率97.73%。试剂盒与一代测序、试剂盒与实时定量聚合酶链反应(quantitative real-time polymerase chain reaction, qPCR)、qPCR与一代测序一致性检验的Kappa值分别为0.946、0.953、0.913。试剂盒以一代测序为参照的受试者工作特征曲线(receiver operating characteristic curve, ROC)曲线下面积为0.976，以qPCR为参照的ROC曲线下面积为0.975。结论AMSS-qPCR技术能够有效检测肺癌突变基因，具有较好的临床应用价值。

Comparative Analysis Between Molecular Techniques Used for the Detection of JAK2V617F Mutation in Patients with Chronic Myeloproliferative Disorders

We validated the transportability of the updated diabetes prediction model from Atherosclerosis Risk in Communities (ARIC) Study, to a Middle Eastern population. We investigated 3,721 participants of the Tehran Lipid and Glucose Study (TLGS) aged ≥20years, free of diabetes at baseline. They underwent a standard 75gr 2-h post-challenge plasma glucose test that was repeated every 3years using the same protocol. All the models were tested with respect to discrimination and calibration. We confirm the findings of Kahn et al. (Ann Intern Med 150(11):741-751, 2009) in a middle-aged, Middle Eastern population. We obtained the same predictive discrimination for the ARIC model (C statistic: men 0.790 and women 0.829) as for the TLGS' own model (men 0.824 and women 0.847) and validated a good calibration for the updated ARIC diabetes prediction model in the TLGS sample. Among men, optimal cut-point was set to the score of 31 where the maximum value of sensitivity (71.6%) plus specificity (75.3%) was achieved. Among women, the optimal point was set to the score of 38 with sensitivity of 67.1% and specificity of 85.0%. The updated ARIC model predicted the individual diabetes risk with a high level of sensitivity and specificity in the TLGS population, which was comparable with that of original sample. More parsimonious model incorporating age, family history of diabetes, waist circumference, pulse rate, and fasting plasma glucose, which were significantly associated with the risk of incident diabetes in the TLGS population, could be equally effective in predicting diabetes.

For DNA-based tests that assess genetic predisposition to coronary heart disease (CHD) to be of clinical value, they need to provide information over and above conventional risk factors (CRFs) currently used in risk algorithms, such as the Framingham Risk Score,1 which incorporates CRFs such as age, gender, blood lipid concentrations, blood pressure, body mass index, family history, and smoking habit. To achieve this, several hurdles must be passed. The first challenge is to identify a set of common single-nucleotide polymorphisms (SNPs) at loci associated with CHD risk. Over the last 10 to 15 years, this has been done by use of a “candidate gene” approach through association studies in prospective analysis or case-control studies, ie, comparing SNP genotype or allele frequency between groups of individuals with CHD and healthy subjects. Several of the genes, chosen because of their key role in processes that predispose to atherosclerosis, have meta-analysis–confirmed effects on risk of CHD,2 the best example of which is the APOE gene, which encodes apolipoprotein E, with 3 common isoforms that are associated with strong effects on plasma lipids and more modest effects on risk of CHD.3 This “hypothesis-driven” search for useful genetic variants provides the foundation for the development of genetic CHD risk profiles, and in the last 2 years, it has been enhanced by technical advances that have allowed “hypothesis-free” genome-wide association studies (GWASs), primarily in a case-control setting. Although the list of identified CHD-risk loci and SNPs will clearly grow, we have at least the basis to start the examination of their potential clinical utility. The second set of challenges is to obtain a robust estimate of the size of the risk effects associated with these SNPs. This requires population-based prospective studies to avoid bias, because estimates in the case-control setting, although efficient for …

Usefulness of Ventricular Premature Complexes to Predict Coronary Heart Disease Events and Mortality (from the Atherosclerosis Risk In Communities Cohort)

BackgroundHealth-related quality of life (HRQOL) is a multi-dimensional concept that is affected by different variables. A large body of evidence shows that socio-demographic factors have a significant influence on HRQOL. When considering differences in cultural contexts and social values of various countries and the lack of evidence regarding socio-demographic determinants of HRQOL among the Iranian general population, it is important to verify the main socio-demographic determinants of HRQOL in an urban Iranian population.ObjectivesThis study aimed to explore socio-demographic factors associated with HRQOL and to ascertain the determinants of poor HRQOL in participants of the Tehran lipid and glucose study (TLGS).MethodsThe participants included 3491 adults, aged ≥ 20 years, who had participated in the TLGS. To obtain socio-demographic and HRQOL information, participants were interviewed by trained interviewers. Mean HRQOL scores were compared using the student’s t test and analysis of variance (ANOVA). To determine significant determinants of poor HRQOL, multivariate logistic regression analysis was performed.ResultsMean ages of males and females were 47.7 ± 15.6 and 47.8 ± 14.2 years, respectively and 58.6% of participants were male. Males had significantly higher scores compared to females in both the physical and mental domains of HRQOL (P < 0.001). In males, significant determinants of poor physical HRQOL were older age, being married, being unemployed yet having other sources of income, having literacy levels below high school diploma, and having chronic diseases (P < 0.05). In females, however older age and being housewives were significant determinants of poor physical HRQOL (P < 0.05). In addition, significant determinants of poor mental HRQOL were younger age and being single or divorced/widowed in males and younger age and being illiterate as well as having literacy levels below high school diploma in females (P < 0.05).ConclusionsCurrent findings highlight the importance of socio-demographic determinants of HRQOL in both genders, specifically in the physical domain, and demonstrate their roles to be more prominent in males. These findings highlight gender-specific associations between socio-demographic factors and various aspects of HRQOL among the TLGS population, which could be applied in future research focusing on non-communicable diseases and planning health promotion programs.

ContextChronic kidney disease (CKD), is correlated with a substantial upsurge in mortality and morbidity worldwide. In this review, we aimed to review the 20-year-findings on CKD of the Tehran lipid and glucose study (TLGS).Evidence AcquisitionWe conducted a systematic review of all studies on CKD that had been performed in the context of TLGS.ResultsAge adjusted prevalence of CKD, according to estimated glomerular filtration rate (eGFR) assessed with the two abbreviated equations of the modification of diet in renal disease (MDRD) and the CKD epidemiology collaboration (CKD-EPI) were 11.3% (95% confidence interval (CI): 10.7, 12.0) and 8.5% (95% CI: 7.9, 9.1), respectively. Using MDRD equation, over a mean follow up of 9.9 years, the incidence density rates of CKD were 285.3 person years in women and 132.6 per 10000 person-years in men. Studies on the TLGS population documented that abdominal adiposity defined as waist circumference (WC) categories (P for trend < 0.02) and waist gain in men (hazard ratio (HR) = 1.7, CI: 1.3, 2.2) significantly affected CKD development. Also, CKD had a significant effect on coronary heart disease (CHD) only in participants with low body mass index (HR = 2.06; CI: 1.28, 3.31 and HR = 2.56; CI: 1.04, 6.31 in men and women, respectively). Moreover, CKD was among the strongest independent predictors of stroke (HR = 2.01, CI: 1.22, 3.33). Also, compared to diabetic patients, an abnormal ECG was more prevalent in moderate CKD (P = 0.02).ConclusionsIncreased waist circumference and waist gain (only in men) were associated with developing CKD in the TLGS population. CKD was an independent predictor of CHD (in lean individuals) and stroke.

ContextTehran Lipid and Glucose Study (TLGS), a longitudinal family based cohort study, is the oldest and largest longitudinal family based study in Iran, aimed at investigating effects of environmental, social and biological factors on the health of Tehranians over time. Considering the importance of genetic studies in this aspect, here we present a summary of the important genetic findings, and the potentiality of their contributions to future related projects.Evidence AcquisitionFor all related studies during the past 20 years the search sources were all prominent search engines such as PubMed, Scopus, and Google Scholar with the most proper Medical Subject Headings (MeSH).ResultsThis review summarizes associations of 6 binary phenotypes and 17 quantitative traits with genetic markers in 26 genes. Of the 47 genetic markers, studied most were related to cardio metabolic risk factors. Results of heritability and linkage analysis were also collected and the highest heritability was found to be related to HDL-C (0.5).ConclusionConsidering the opportunity provided by large-scale cohort studies to investigate molecular effects of genetic variants on causality and different omics’ data, genetic studies conducted on TLGS population have had a remarkable success in identifying genetic variants that facilitating a unique genetic database on Iranian populations. The results of genome wide association studies in this population are currently facilitating investigations to define the Iranian genetic differences with other population.

Objectives: The menopause is associated with an increased incidence of coronary heart disease (CHD). Assessing CHD risk factors in menopausal women can shed more light on the pathogenesis of acceleratedatherosclerosis after the cessation of ovarian function.Design: In this study, 1980 women aged 44-69 years were selected from among 15 005 participants in the Tehran Lipid and Glucose Study(TLGS) and assessed for CHD risk factors. They were classified into three groups: premenopausal women (n = 483), aged between 44 and 50 years, without any history of menstrual irregularities; menopausalwomen (n = 310), with permanent cessation of menses for at least 12 months and a duration of less than 3 years; and postmenopausal women (n = 1187), with at least a 3-year history of cessationof menses. Demographic information including waist size, height, weight and systolic and diastolic blood pressures was recorded, and body mass index, low-density lipoprotein/high-density lipoprotein ratio(LDL/HDL) and waist/hip ratio were calculated. Serum total cholesterol, triglycerides and HDL were measured and an oral glucose tolerance test was performed. The LDL level was calculated using the Friedwaldformula.Results: Mean systolic blood pressures were 121 ± 18, 125 ± 20 and 136 ± 23 mmHg (p< 0.001) and mean diastolic blood pressures were 80 ± 10, 81± 11 and 82 ± 11 mmHg (p< 0.001) in premenopausal, menopausal and postmenopausal women, respectively. For premenopausal, menopausal and postmenopausal women, mean cholesterol levelswere 215 ± 42, 238 ± 45 and 245 ± 46 mg/dl (p< 0.001), respectively. HDL and LDL levels were 44 ± 11, 48 ± 12 and 47 ± 11 mg/dl and 138 ± 38, 156± 41 and 161 ± 42 mg/dl (p< 0.001) for premenopausal, menopausal and postmenopausal women, respectively. Mean LDL/HDL ratios were 3.4 ± 1.4, 3.5 ± 1.3 and 3.6 ±1.2 (p< 0.01) and mean waist measurements were 92 ± 11, 93 ± 12 and 95 ± 12 cm (p< 0.001) for the same groups of women, respectively. However, body mass index, waist/hipratio and triglycerides showed no significant differences between the three groups.Conclusion: These data demonstrate an increase in CHD risk factors in a group of Tehranian women after themenopause.